Pancreatic Leaks and Fistulae: An Endoscopy-Oriented Classification

Abstract

Background

Pancreatic leaks occur as a complication of upper gastrointestinal surgery, acute pancreatitis, or abdominal trauma. Pancreatic fistulas and leaks are primarily managed conservatively. Overall, conservative measures are successful in more than half of cases. Whenever conservative treatment is not efficient, surgery is usually considered the treatment of choice. Nowadays however, endoscopic treatment is being increasingly considered and employed in many cases, as a surgery sparing intervention.

Aim

To introduce a classification of pancreatic fistulas according to the location of the leak and ductal anatomy and finally propose the best suited endoscopic method to treat the leak according to current literature.

Methods

We performed an extensive review of the literature on pancreatic fistulae and leaks.

Results

In this paper, we review the various types of leaks and propose a novel endoscopic classification of pancreatic fistulas in order to standardize and improve endoscopic treatment.

Conclusions

A proper and precise diagnosis should be made before embarking on endoscopic treatment for pancreatic leaks in order to obtain prime therapeutic results. A multidisciplinary team of interventional endoscopists, pancreatic surgeons, and interventional radiologists is best suited to care for these patients.

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SX-Ella Stent Danis Effectively Controls Refractory Variceal Bleed in Patients with Acute-on-Chronic Liver Failure

Abstract

Background and Aims

Almost 10% of bleeding episodes are refractory to combination of vasoactive agent and endotherapy, and are associated with a mortality up to 50%. Severity of liver disease and high portal pressure are mainly responsible for it. TIPS cannot be used in these patients due to high MELD score. We aimed to evaluate the efficacy of self-expandable DE stents for control of refractory variceal bleeds in patients with ACLF.

Methods

Acute-on-chronic liver failure patients (n = 88, mean age 47.3 ± 10.9 years) with refractory variceal bleeds received either DE stent (Gr. A, n = 35) or continued with repeat endotherapy and vasoactive drug (Gr.B, n = 53). Matching by propensity risk score (PRS) was done to avoid selection bias. Competing risk Cox regression analysis was done to identify event-specific, i.e., gastrointestinal bleed-related death.

Results

Majority (78.4%) of patients were alcoholic with MELD score of 45.9 ± 20.1. Control of initial bleeding was significantly more in the DE stent group as compared to controls in both pre-match (89 vs. 37%; p < 0.001) and PRS-matched cohorts (73 vs. 32%; 0.007). Further, bleed-related death was also significantly lower in DE group as compared to controls in both pre-match (14 vs. 64%; p = 0.001) and PRS-matched cohorts (6 vs. 56%; p = 0.001). In a multivariate competing risk Cox model, patients who underwent DE stenting had reduced mortality in both pre-match (p = 0.04, HR 0.36, 95% CI 0.13–0.96) and PRS-matched cohorts (p < 0.001, HR 0.21, 95% CI 0.08–0.51).

Conclusions

Self-expandable DE stents are very effective in control of refractory variceal bleeding and reduced mortality in patients with severe liver failure.

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Unstable Housing Still a Barrier to Receiving HCV Treatment in France (ANRS CO13 HEPAVIH Cohort)

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Strategies to Identify and Reduce Opioid Misuse Among Patients with Gastrointestinal Disorders: A Systematic Scoping Review

Abstract

Background

Scoping reviews are preliminary assessments intended to characterize the extent and nature of emerging research evidence, identify literature gaps, and offer directions for future research. We conducted a systematic scoping review to describe published scientific literature on strategies to identify and reduce opioid misuse among patients with gastrointestinal (GI) symptoms and disorders.

Methods

We performed structured keyword searches to identify manuscripts published through June 2016 in the PubMed MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science databases to extract original research articles that described healthcare practices, tools, or interventions to identify and reduce opioid misuse among GI patients. The Chronic Care Model (CCM) was used to classify the strategies presented.

Results

Twelve articles met the inclusion criteria. A majority of studies used quasi-experimental or retrospective cohort study designs. Most studies addressed the CCM's clinical information systems element. Seven studies involved identification of opioid misuse through prescription drug monitoring and opioid misuse screening tools. Four studies discussed reductions in opioid use by harnessing drug monitoring data and individual care plans, and implementing self-management and opioid detoxification interventions. One study described drug monitoring and an audit-and-feedback intervention to both identify and reduce opioid misuse. Greatest reductions in opioid misuse were observed when drug monitoring, self-management, or audit-and-feedback interventions were used.

Conclusion

Prescription drug monitoring and self-management interventions may be promising strategies to identify and reduce opioid misuse in GI care. Rigorous, empirical research is needed to evaluate the longer-term impact of these strategies.

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Therapeutic Potential of the Gabaergic System in Ulcerative Colitis: Current Status and Perspectives

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Barriers to implementation of the FUSE program

Abstract

Introduction

The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) developed The Fundamental Use of Surgical Energy (FUSE) Program to promote safe use of energy devices in the operating room and endoscopy suite. Utilization of the program has been slower than anticipated. This study aims to determine the barriers to implementing FUSE.

Methods

An anonymous survey was distributed to a surgery department at an academic teaching hospital (n = 256). Participants indicated their level of training. Answers were measured using a 5-point Likert scale.

Results

There were 94 (36.7%) respondents to the survey from September 7 to 20, 2016. Fifteen surveys were incomplete, leaving 79 responses for analysis. Most respondents were at the faculty level (45/79, 57.0%). The majority had heard of FUSE (62/79, 78.5%), but only 19 had completed the certification (19/62, 32.3%). There was no difference in the completion rate between faculty and trainees (26.7 vs. 20.6%, OR 1.4, 95% CI 0.49–4.06, p = 0.53). The most common reasons for not taking the exam were lack of time to study (26/43, 60.5%) and lack of time to take the exam (28/43, 62.1%); however, cost was not a barrier (12/43, 27.9%). The majority identified a personal learning gap regarding the safe use of surgical energy (30/43, 69.7%). Of the 19 FUSE-certified respondents, reasons cited for completing the exam included wanting to prevent adverse events to patients and in the operating room (17/19, 89.5% and 17/19, 89.5%), and the belief that the course would make them a safer surgeon (16/19, 84.2%).

Conclusions

FUSE teaches the proper use of radiofrequency energy, how to prevent unnecessary injury, and promotes safe practice. Close to three out of every four surgeons self-identified a personal knowledge gap regarding the safe use of surgical energy. Time restraints were cited most commonly as the barrier to starting and completing FUSE. Integrating the FUSE program into resident educational conferences, faculty grand rounds, or national conferences may help improve participation and drive adoption of FUSE certification.

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Three decades later: investigating the rate of and risks for conversion from laparoscopic to open cholecystectomy

Abstract

Introduction

Recent data suggest a wide range of conversion (4.9–20%) from laparoscopic (LC) to open cholecystectomy (OC) despite increasing surgeon familiarity and superior equipment. Previously identified risk factors for conversion include increased age, male gender, diabetes, and emergent surgeries. Recent studies also suggest that formal minimally invasive surgical training (MIST) reduces conversion rates. We sought to determine conversion rates in our population, a rural academic medical center, and identify any significant risks for conversion.

Methods

We conducted a single-center retrospective review of 2810 cholecystectomies performed over a seven-year period (2009–2016).

Results

Our study included 837 (29.8%) males and 1973 (70.2%) females with a mean age of 49.2 years. Forty-two percent of cases were done by surgeons with MIST. A total of 139 (4.95%) cases were converted to OC. Univariate predictors of conversion to OC included male gender, age ≥65, urgent and emergent admissions, and MIST of the surgeon. In multivariate modeling, which included significant univariate predictors of conversion, independent predictors of conversion to OC included urgent or emergent admission, male gender, and age ≥65. MIST status was no longer a significant predictor.

Conclusion

Our conversion rate from LC to OC falls within the lower range of recently published rates. This is likely multifactorial, and reflects increasing familiarity of the laparoscopic technique, improved quality of laparoscopic equipment, and/or prior knowledge of preoperative risk factors for conversion. Our results, consistent with previous literature, show a reduced conversion rate among surgeons with MIST. This finding, albeit not significant on multivariate analysis, may offer insight into a potential alterable preoperative risk factor for conversion and warrants further research. Further knowledge about the impact MIST has on conversion may provide a feasible preoperative approach to reducing conversion to OC, thereby reducing costs and overall patient morbidity.

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Efficacy of endoscopic self-expandable metal stent placement versus surgical bypass for inoperable pancreatic cancer-related malignant biliary obstruction: a propensity score-matched analysis

Abstract

Background and aims

We explored the difference in treatment efficacy of endoscopic self-expendable metal stent (SEMS) and surgical bypass (SB) in the management of malignant biliary obstruction (MBO) secondary to pancreatic cancer.

Method

A retrospective analysis was conducted using consecutive patients who were admitted from 2008 to 2016 receiving either endoscopic SEMS or SB. Diagnosis other than pancreatic cancer and SEMS placement as a pre-operative drainage before Whipple's operation was excluded. Propensity score (PS) matching was performed to eliminate the confounding effect of heterogeneity between patients from two treatment groups. The rate of early, late treatment-related events, readmission and re-intervention, the duration of hospitalization, and the cost of treatment were compared.

Results

There were 98 patients undergoing endoscopic SEMS or SB in the study period. The median age was 68.5 years and 52% of the patients had metastatic disease with median survival of 6 months. After 1:1 PS matching, 30 patients from each group were analyzed. The hospital stay was significantly longer in the SB group (13 vs. 5 days, P < 0.001) with a trend of higher rate of early treatment-related events (24.1 vs. 6.7%, P = 0.113). None of the patients in SB group developed recurrent biliary obstruction. Higher readmission rate (36.7 vs. 3.3%, P = 0.004) and re-intervention rate (36.7 vs. 10%, P = 0.033) were found in the SEMS group. The 3-, 6-, and 9-month re-intervention rates for endoscopic SEMS and SB group were 24.9, 29.4, 45.7, and 11.2, 11.2, and 11.2%, respectively (P = 0.03). When all subsequent readmissions were taken into account, there was no significant difference in hospital stay in both groups (7.5 vs. 14 days, P = 0.359); however, the total cost of treatment in SB group was significantly higher than that in the SEMS group (13,307 vs. 7113 USD, P = 0.035).

Conclusion

Despite being more invasive and expensive, surgical bypass provides durable relief of biliary obstruction. Endoscopic SEMS is associated with minimal procedural risks and low re-intervention rate, which are important considerations for frail patients with limited life expectancy.

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Same day discharge for benign laparoscopic hiatal surgery: a feasibility analysis

Abstract

Background

Advances in minimally invasive surgery and the development of enhanced recovery pathways have favored the spread of day-surgery programs. Despite laparoscopic approaches being accepted as the standard of care for benign hiatal diseases, safety and feasibility of same day discharges for laparoscopic hiatal surgeries other than fundoplication has yet to be established.

Objective

This study aimed to assess the feasibility of same day discharge for primary and revisional laparoscopic hiatal surgeries including paraesophageal hernia repairs (PEHR), fundoplication for reflux, and Heller myotomy (±diverticulectomy).

Methods

A retrospective cohort study including all patients undergoing elective laparoscopic hiatal procedures in the division of Thoracic surgery between 2011 and 2016 at McGill University Health Centre was performed. Planned day-surgery (DAYCASE) was compared to planned inpatient (INPATIENT) cohorts with respect to operative and postoperative outcomes, length of stay, readmission, and emergency room visits.

Results

A total of 261 patients were identified, 161 female (62%); median age 62 (20). The case distribution was: PEHR (123; 47.1%), Heller myotomy (94;36%, 7 diverticulectomy), and fundoplication (44; 16.9%). Twenty patients had revisional procedures (7.7%). Same day discharge was planned in 98 cases (38%) and was successful in 80 (81.6%). Proportion of DAYCASE increased form 12% prior to 2013 to 67% in 2016. INPATIENTs were older (median 66 vs. 60 years), and had a higher proportion of PEHR (55 vs. 34%), p < 0.05. Both cohorts were comparable in gender proportion, ASA classification, and length of surgery. Complications, readmission, and emergency visits did not differ between the two cohorts. On multivariate analysis, female gender (OR 37, 95% CI 1.46–936, p = 0.028), surgery beginning after noon (OR 5.4, 95% CI 1.1–26.9, p = 0.038), intraoperative complications (OR 20.4 95% CI 1.5–286, p = 0.025), and postoperative complications (OR 52.1, 95% CI 4.5–602, p = 0.002) were independently associated with unplanned admission.

Conclusions

Day-case surgery for complex laparoscopic hiatal procedures is feasible and can be achieved in a significant number of patients without compromising safety.

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Barrett’s esophagus before and after Roux-en-Y gastric bypass for severe obesity

Abstract

Introduction

Barrett's esophagus (BE) has been associated with obesity and metabolic syndrome. Laparoscopic Roux-en-Y gastric bypass (LRYGB) may represent a surgical approach which addresses both severe obesity and BE. LRYGB diverts bile away from the gastric pouch and esophagus due to the long Roux limb, and very little acid is produced in the cardia-based gastric pouch. Furthermore, surgically induced weight loss may diminish systemic inflammation, which may contribute to metaplastic changes in the esophagus. Moreover, improved compliance with proton-pump inhibitor therapy, as a consequence of enrolling in a bariatric program, will decrease acid production further. Decreased duodeno-gastro-esophageal reflux should lead to decreased BE. In this study we examine the effect of LRYGB on regression of BE.

Methods and procedures

We performed a review of all patients with biopsy proven BE, who underwent LRYGB at our institution. A total of 19 patients were identified. A subset of those patients was identified who had at least 1 year of clinical, endoscopic, or histological data, comprising a total of 14 patients. Seven of these patients had symptoms of gastroesophageal reflux. All 19 patients had short-segment BE. One patient had low-grade dysplasia.

Results

Post-LRYGB, 6 of 14 (42.9%) patients had histologic regression of BE to normal esophageal mucosa, with no evidence of ongoing BE. 13 of 14 patients (92.8%) reported compliance with continuing PPI therapy for at least the first year after surgery. Body mass index for the group of 14 patients improved from 46.6 to 30.3 kg/m².

Conclusions

We recommend LRYGB as an effective combined bariatric and anti-reflux surgical procedure for patients with severe obesity and BE. In short-term follow-up, LRYGB achieved endoscopic and histologic regression to normal mucosa in a substantial number of the patients in our series. Long-term follow-up for patients with BE according to standard surveillance protocols is still recommended.

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Tailored approach to gastroparesis significantly improves symptoms

Abstract

Background

Gastroparesis is difficult to treat and many patients do not report relief of symptoms with medical therapy alone. Several operative approaches have been described. This study shows the results of our selective surgical approach for patients with gastroparesis.

Materials and methods

This is a retrospective study of prospective data from our electronic medical record and data symptom sheet. All patients had a pre-operative gastric emptying study showing gastroparesis, an esophagogastroduodenoscopy, and either a CT or an upper GI series with small bowel follow-through. All patients had pre- and post-operative symptom sheets where seven symptoms were scored for severity and frequency on a scale of 0–4. The scores were analyzed by a professional statistician using paired sample t test.

Results

58 patients met inclusion criteria. 33 had gastric stimulator (GES), 7 pyloroplasty (PP), 16 with both gastric stimulator and pyloroplasty (GSP), and 2 sleeve gastrectomy. For patients in the GSP group, the second procedure was performed if there was inadequate improvement with the first procedure. There was no mortality. The follow-up period was 6–316 weeks (mean 66.107, SD 69.42). GES significantly improved frequency and severity for all symptoms except frequency of bloating and postprandial fullness. PP significantly improved nausea and vomiting severity, frequency of nausea, and early satiety. Symptom improvement for GSP was measured from after the first to after the second procedure. GSP significantly improved all but vomiting severity and frequency of early satiety, postprandial fullness, and epigastric pain.

Conclusion

All procedures significantly improved symptoms, although numbers are small in the PP group. GES demonstrates more improvement than PP, and if PP or GES does not adequately improve symptoms GSP is appropriate. In our practice, gastrectomy was reserved as a last resort.

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Laparoscopic sleeve gastrectomy in a patient with situs viscerum inversus totalis: is the life easy upside-down?

Abstract

Introduction

Obesity is an epidemic on the rise [1]. The number of bariatric procedures has increased worldwide. Laparoscopic sleeve gastrectomy (LSG) is a valid therapeutic option, leading to a sustained weight loss with a low complication rate [2]. Situs viscerum inversus totalis (SIT) is the complete transposition of all the abdominal organs, occurring in about 1 in 10,000 people [3]. Laparoscopic approach in SIT is challenging due to the mirror image anatomy.

Materials and methods

We present the case of a 41-year-old man with a body mass index of 46.4 kg/m² (131 kg; 1.68 m) previously diagnosed with SIT who has undergone LSG.

Results

In this video, we show a LSG performed in a patient with SIT. There were no changes in the technique compared to the "standard anatomy." The patient was placed on the operative table in anti-trendelenburg position with legs abducted. The surgeon stood between the legs while the assistant was on the right side of the patient and the scrub nurse on the opposite side. A 12-mm trocar was inserted with a direct technique in the right lateral flank. Carbon dioxide insufflation was done under vision. Other three trocars (12, 10, and 5 mm) were positioned in the left lateral flank, supraumbilical, and subxiphoid areas, respectively. Gastroepiploic dissection started at 5 cm from the pylorus up to the right crus. After the insertion of a 36-Fr boogie, an accurate stapling of the stomach was performed. The proximal side of the sleeve was reinforced with a non-absorbable suture. Titanium clips were placed leading to a complete haemostasis. The procedure lasted 45 min. The patient followed a "fast-track" protocol afterwards, with no changes in the perioperative workup compared to "standard anatomy" patients. He was discharged on day 2 postoperatively and no complication occured in the perioperative period.

Conclusion

SIT is a rare condition leading to a mirror image that can be challenging for a laparoscopic surgeon. LSG is feasible and safe also for morbidly obese patients with SIT, not requiring any change in the surgical technique and perioperative management, as long as the surgeon is well beyond the learning curve.

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Impedance-pH monitoring on medications does not reliably confirm the presence of gastroesophageal reflux disease in patients referred for antireflux surgery

Abstract

Introduction

The gold standard for the objective diagnosis of gastroesophageal reflux disease (GERD) is ambulatory-pH monitoring off medications. Increasingly, impedance-pH (MII-pH) monitoring on medications is being used to evaluate refractory symptoms. The aim of this study was to determine whether an MII-pH test on medications can reliably detect the presence of GERD.

Methods

Patients referred for persistent reflux symptoms despite pH confirmed adequate acid suppression (DeMeester score ≤14.7) were reviewed retrospectively. All patients who originally had MII-pH testing on medications were re-evaluated with an off medication Bravo-pH study. Acid exposure results (defined by off medication Bravo) were compared to the original on medication MII-pH.

Results

There were 49 patients who met study criteria (median age 51). Patients had normal acid exposure during their MII-pH test on medications (average DMS 4.35). Impedance was abnormal (normal ≤47) in 25 of the 49 patients (51%). On subsequent Bravo-pH off medications, 37 patients (75.7%) showed increased esophageal acid exposure (average DMS 36.4). Bravo-pH testing was abnormal in 84% of patients with abnormal MII testing and in 67% with normal MII testing. The sensitivity and specificity of an abnormal MII-pH on medications for increased esophageal acid exposure off medications was 56.8 and 66.7%, respectively. The positive predictive value of confirming GERD from an abnormal MII-pH on medications is 84%, while the negative predictive value is 33.3%. A receiver operating characteristic (ROC) curve was generated and the area under the curve was 0.71, indicating that MII-pH on medications is a fair test (0.7–0.8) in diagnosing pathologic GERD.

Conclusion

Compared to the gold standard, MII-pH on medications does not reliably confirm the presence of GERD. Excellent outcomes with antireflux surgery are dependent on the presence of GERD; thus, patients should not be offered antireflux surgery until GERD is confirmed with pH testing off medications.

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Advanced Roux-en-Y hepaticojejunostomy with magnetic compressive anastomats in obstructive jaundice dog models

Abstract

Background

Although commonly used procedure, Roux-en-Y hepaticojejunostomy (RYHJ) remains to be complicated, time consuming, and has a relatively poor prognosis. We designed the magnetic compressive anastomats (MCAs) to perform RYHJ more efficiently and safely.

Materials and methods

36 dogs were divided into two groups randomly. After obstructive jaundice model construction, RYHJ was performed with MCAs in study group or by hand-sewn in control group. Both groups were followed for 1, 3, and 6 months after RYHJ. The liver function and postoperative complications were recorded throughout the follow-up. At the end of each time point, dogs were sent for magnetic resonance imaging (MRI) and sacrificed. Anastomotic samples were taken for anastomotic narrowing rate calculation, histological analyses, tensile strength testing, and hydroxyproline content testing.

Results

The anastomotic construction times were 44.20 ± 23.02 min in study group, compared of 60.53 ± 11.89 min in control group (p < 0.05). The liver function recovered gradually after RYHJ in both groups (p > 0.05). All anastomats were expelled out of the body in 8.81 ± 2.01 days. The gross incidence of morbidity and mortality was 33.3% (6/18) and 16.7% (3/18) in study group compared with 38.9% (7/18) and 22.2% (4/18) in control group (p > 0.05), and there is no single case of anastomotic-specific complications happened in study group. The narrowing rates of anastomosis were 14.6, 18.5, and 18.7% in study group compared with 35.4, 36.9, and 34% in control group at 1st, 3rd, and 6th month after RYHJ (p < 0.05). In study group, preciser alignment of tissue layers and milder inflammatory reaction contributed to the fast and better wound healing process.

Conclusion

Perform RYHJ with MCAs is safer, more efficient than by hand-sewn method in obstructive jaundice dog models.

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EMS/Paramedic - Tri-Lakes Monument Fire Protection District

Position Title: EMS/Paramedic Agency Division: Operations Pay Grade: 3P-5P (non-exempt) Employment Status: At-Will Reports to: Shift Officer Job Summary: Paramedics respond to emergency calls as a member of the Fire Department's emergency response team to perform first aid and transport services. Additionally, they assist the public with non-emergency requests or complaints, emergency medical ...

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Newly discovered Neanderthal remains from Shanidar Cave, Iraqi Kurdistan, and their attribution to Shanidar 5

Publication date: October 2017
Source:Journal of Human Evolution, Volume 111
Author(s): Emma Pomeroy, Marta Mirazón Lahr, Federica Crivellaro, Lucy Farr, Tim Reynolds, Chris O. Hunt, Graeme Barker
The Neanderthal remains from Shanidar Cave, excavated between 1951 and 1960, have played a central role in debates concerning diverse aspects of Neanderthal morphology and behavior. In 2015 and 2016, renewed excavations at the site uncovered hominin remains from the immediate area where the partial skeleton of Shanidar 5 was found in 1960. Shanidar 5 was a robust adult male estimated to have been aged over 40 years at the time of death. Comparisons of photographs from the previous and recent excavations indicate that the old and new remains were directly adjacent to one another, while the disturbed arrangement and partial crushing of the new fossils is consistent with descriptions and photographs of the older discoveries. The newly discovered bones include fragments of several vertebrae, a left hamate, part of the proximal left femur, a heavily crushed partial pelvis, and the distal half of the right tibia and fibula and associated talus and navicular. All these elements were previously missing from Shanidar 5, and morphological and metric data are consistent with the new elements belonging to this individual. A newly discovered partial left pubic symphysis indicates an age at death of 40–50 years, also consistent with the age of Shanidar 5 estimated previously. Thus, the combined evidence strongly suggests that the new finds can be attributed to Shanidar 5. Ongoing analyses of associated samples, including for sediment morphology, palynology, and dating, will therefore offer new evidence as to how this individual was deposited in the cave and permit new analyses of the skeleton itself and broader discussion of Neanderthal morphology and variation.



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Optimization of liposomal indocyanine green for imaging of the urinary pathways and a proof of concept in a pig model

Abstract

Background

Iatrogenic ureteral injury is an increasing concern in the laparoscopic era, affecting both patient morbidity and costs. Current techniques enabling intraoperative ureteral identification require invasive procedures or radiations. Our aim was to develop a real-time, non-invasive, radiation-free method to visualize ureters, based on near-infrared (NIR) imaging. For this purpose, we interfered with the biliary excretion pathway of the indocyanine green (ICG) fluorophore by loading it into liposomes, enabling renal excretion. In this work, we studied various parameters influencing ureteral imaging.

Methods

Fluorescence intensity (FI) of various liposomal ICG sizes and doses were characterized in vitro and subsequently tested in vivo in mice and pigs. Quantification was performed by measuring FI in multiple points and applying the ureteral/retroperitoneum ratio (U/R).

Results

The optimal liposomal ICG loading dose was 20%, for the different liposomes' sizes tested (30, 60, 100 nm). Higher concentration of ICG decreased FI. In vivo, the optimal liposome size for ureteral imaging was 60 nm, which yielded a U/R of 5.2 ± 1.7 (p < 0.001 vs. free ICG). The optimal ICG dose was 8 mg/kg (U/R = 2.1 ± 0.4, p < 0.05 vs. 4 mg/kg). Only urine after liposomal ICG injection had a measurable FI, and not after free ICG injection. Using a NIR-optimized laparoscopic camera, ureters could be effectively imaged in pigs, from 10 min after injection and persisting for at least 90 min. Ureteral peristaltic waves could be clearly identified only after liposomal ICG injection.

Conclusions

Optimization of liposomal ICG allowed to visualize enhanced ureters in animal models and seems a promising fluorophore engineering, which calls for further developments.

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Quality of life after laparoscopic totally extraperitoneal repair of an asymptomatic inguinal hernia

Abstract

Background

When considering an asymptomatic inguinal hernia, surgeons must weigh the risks of watchful waiting against the risk of operative complications. Laparoscopy offers the benefit of reduced postoperative pain, which, for appropriate surgical candidates, may strengthen the case for repair. This study compares general and disease-specific quality of life following totally extraperitoneal (TEP) laparoscopic inguinal hernia repair (LIHR) of asymptomatic and symptomatic hernias.

Methods

We summarize prospective data from 387 patients who underwent TEP LIHR between 2009 and 2015 by four surgeons at a single institution. Asymptomatic individuals were identified by pain scores of zero at preoperative clinic visits. Validated quality of life (QOL) measurements were administered preoperatively and at 3 weeks, 6 months, and 1-year postop. Comparisons were made using Chi-square test, t test, or Mann–Whitney U test. Changes over time were assessed using longitudinal mixed effects models.

Results

A cohort of 79 asymptomatic cases were compared to 308 symptomatic individuals. The asymptomatic cohort had larger median hernia defects (2.5 vs 2 cm, p < 0.01), was older (mean 63.0 vs 58.9 years, p = 0.03), included fewer indirect hernias (57.7 vs 74.9%, p < 0.01), took pain medication for fewer days (mean 1.2 ± 1.5 vs 2.2 ± 3.0 days, p = 0.02), returned to baseline activities of daily living earlier (median 3 vs 5 days, p < 0.01), and reported decreased postoperative pain (p = 0.02). There was no significant difference in general QOL. There was one recurrence in the asymptomatic group and were two in the symptomatic cohort.

Conclusions

Asymptomatic individuals undergoing TEP LIHR reported less postoperative pain, returned to baseline activities, and discontinued pain medication sooner than symptomatic patients. These results are encouraging and may inform patient-centered discussions about asymptomatic hernia repair.

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Approach to asymptomatic paraesophageal hernia: watchful waiting or elective laparoscopic hernia repair?

Abstract

Background

There is no consensus on whether asymptomatic paraesophageal hernia (PEH) should be operated. Some argue that surgery is necessary prophylaxis against potentially catastrophic consequences of acute complications in untreated PEH. Others reason that the acute complications are rare and emergent operations have relatively low mortality. In the laparoscopic era, elective operations have become safer and less morbid. However, recent studies report high incidence of recurrent hernia, some of which affect quality of life and require further interventions. In light of these new findings, we investigated whether asymptomatic PEH should receive elective laparoscopic hernia repair (ELHR) or watchful waiting (WW).

Methods

A Markov Monte Carlo microsimulation decision analysis model followed a hypothetical cohort of asymptomatic PEH patients who have predominantly female gender and normally distributed mean age of 62.5 years for the lifetime. Accrued health benefits expressed in quality-adjusted life months (QALM) were compared between two strategies: WW and ELHR. Two-dimensional simulations were performed to account for uncertainties in the model. Deterministic sensitivity analyses were performed to test key assumptions.

Results

After considering both individual- and parameter-level uncertainties in the two-dimensional simulations, WW was the superior strategy in 82% of the simulations, accumulating mean 5 QALM more than ELHR (168 vs. 163). Our model was robust to deterministic sensitivity analyses and was internally validated, which supported the validity of our results.

Conclusions

Patients with asymptomatic PEH are more likely to achieve greater health outcomes if they undergo WW as initial treatment than ELHR.

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Laparoscopic resection for gastrointestinal stromal tumors in esophagogastric junction (EGJ): how to protect the EGJ

Abstract

Background

Laparoscopic surgery for gastric gastrointestinal stromal tumors (GISTs) is now widely performed. However, laparoscopic resection of GIST in the esophagogastric junction (EGJ) is technically difficult and rarely reported. Herein, we introduce four fashions of laparoscopic resection for EGJ-GIST.

Methods

A retrospective review of 42 consecutive patients with EGJ-GIST who underwent attempted laparoscopic surgery was conducted. EGJ-GIST was defined as GIST with an upper border of less than 5 cm from the esophagogastric line. Four fashions of laparoscopic resection were performed: fashion A, laparoscopic wedge resection using linear stapler; fashion B, laparoscopic complete resection by opening the stomach wall and closing with suture or linear stapler; fashion C, laparoscopic mucosa-preserving resection; and fashion D, laparoscopic proximal gastrectomy with pyloroplasty and gastric plication. Clinicopathologic characteristics, operative course, and short-term and long-term outcomes were analyzed.

Results

All procedures were completed successfully without operative complications. In 24 of 42 (57.1%) patients, tumors were located in the fundus or greater curvature. Out of those, 70.8% (17/24) received fashion A and 29.2% (7/24) received fashion B. Tumors in 16 of 42 (38.1%) patients were located in the lesser curvature. Of those, 81.3% (13/16) underwent fashion B and 18.7% (3/16) underwent fashion D. One tumor in the anterior stomach wall and one in the posterior wall received fashion C. The mean operative time was 103.8 ± 22.1 min and the mean estimated blood loss was 22.4 ± 13.5 ml. The mean time to flatus was 40.3 ± 12.9 h and the time to fluid intake was 43.2 ± 14.3 h. The mean hospital stay was 4.8 ± 2.1 days.

Conclusions

Laparoscopic surgery for EGJ-GIST is safe and feasible. The selection of various laparoscopic resection fashions should be chosen based on tumor location and the surgeon's experience.

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Increased glycine-amidated hyocholic acid correlates to improved early weight loss after sleeve gastrectomy

Abstract

Background

Bile acids (BAs) are post-prandial hormones that play an important role in glucose and lipid homeostasis as well as energy expenditure. Total and glycine-amidated BAs increase after sleeve gastrectomy (SG) and correlate to improved metabolic disease. No specific bile acid subtype has been shown conclusively to mediate the weight loss effect. Therefore, the objective of this study was to prospectively evaluate the comprehensive changes in meal-stimulated BAs after SG and determine if a specific change in the BA profile correlates to the early weight loss response.

Methods

Patients were prospectively enrolled at the University of Nebraska Medical Center who were undergoing a SG for treatment of morbid obesity. Primary and secondary plasma bile acids and their amidated (glycine, G-, or taurine, T-) subtypes were measured at fasting, 30 and 60 min after a liquid meal performed pre-op, and at 6 and 12 weeks post-op. Area under the curve (AUC) was calculated for the hour meal test for each bile acid subtype. BAs that were significantly increased post-op were correlated to body mass index (BMI) loss.

Results

Total BA AUC was significantly increased at 6 (p < 0.01) and 12 weeks post-op (p < 0.01) compared to pre-operative values. The increase in total BA AUC was due to a statistically significant increase in G-BAs. Nine different BA AUC subtypes were significantly increased at both 6 and 12 weeks post-op. Increased total and G-chenodeoxycholic acid AUC was significantly correlated to the 6 week BMI loss (p = 0.03). Increased G-hyocholic acid was significantly correlated to increased weight loss at both 6 (p = 0.05) and 12 weeks (p = 0.006).

Conclusions

SG induced an early and persistent post-prandial surge in multiple bile acid subtypes. Increased G-hyocholic consistently correlated with greater early BMI loss. This study provides evidence for a role of BAs in the surgical weight loss response after SG.

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First case of complete full robotic surgical resection of leiomyosarcoma of the right renal vein

Abstract

Background

Leiomyosarcomas present high postoperative morbidity and poor prognosis [1]. In the literature, only few cases of localized small leiomyosarcoma have been described [2, 3]. These cases might benefit from a minimally invasive approach. Robotic surgery has been claimed to have several advantages over laparoscopy such as enhanced vision and instruments movements which might make more feasible the execution of this type of surgery where partial renal resection is required.

Methods

A 53-year-old female with a medical history of myeloid leukemia and with chronic renal failure (creatinine: 2.6) was referred to our hospital for an incidental finding of right perirenal tumor of almost 3 cm compatible with leiomyosarcoma arising from the right renal vein.

Results

The operation was performed using a Da Vinci Robotic Surgical System model Si (Intuitive Surgical, Sunnyvale, CA, USA).Robotic ports were placed in a standard configuration for minimally invasive right nephrectomy. The dissection started with the partial mobilization of the right liver and Kocher maneuver. After the identification of the inferior vena cava the tumor was finally localized and dissected. Resection ended with a partial right vein resection and suture. Pathological final exam confirmed the diagnosis with margins free from tumor.

Conclusions

In selected cases, robotic resection of leiomyosarcoma might be a safe and feasible procedure in experienced hands.

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Laparoscopic resection of multiple aneurysms of the gastroepiploic arterial arcade

Abstract

Background

Gastroepiploic arterial aneurysms (GEAA) represent a very rare disorder [1, 2]. The risk of GEAA rupture is high, and it is associated with a high mortality rate [3]. GEAAs are usually identified following rupture or are incidentally diagnosed. In emergency, an open surgical approach to treat GEAAs has been most frequently reported [4]. Alternatively, if the patient is hemodynamically stable, an angiography and embolization can be attempted. Herein we report the case of a patient presenting with two fissurated GEAAs that were successfully excised laparoscopically after failure of the endovascular approach.

Materials and methods

A 83-year-old lady was admitted for acute epigastric pain. Upon admission, her general status was stable. The abdomen was soft and slightly painful at deep palpation in epigastrium, with no sign of peritonism. In her past medical history, she had a transient ischemic attack and atrial fibrillation episodes for which a pacemaker had been placed. Her blood examinations showed a slight anemia (hemoglobin 10.5 g/dl). An abdominal ultrasonography identified two solid, circular, nodules next to the gastric anterior wall that, in a following angio-TC, were diagnosed as two aneurysms of the gastro-epiploic arterial arcade (GEA), one measuring 17 mm × 13 mm, the other 39 mm × 33 mm. Both showed X-ray signs of impending rupture and intraluminal "thrombization". The patient underwent selective angiography, during which, after an attempt of common hepatic artery catheterism, a dissection and, consequently, an occlusion of the hepatic artery and the celiac trunk unfortunately occurred. Therefore, after a catetherism of the superior mesenteric artery, only a partial and incomplete embolization procedure was possible. As a matter, at the end of the angiographic procedure, reperfusion of the GEA coming from the splenic and hepatic artery was recognized. After 24 h, repeated abdominal CT scan with contrast showed the persistence of the aneurysms with no dimensional changes and the presence of a small active extravasation of contrast from the lateral aneurysm.

Results

Laparoscopic surgical exploration was then warranted. Two voluminous GEA arcade aneurysms, very close to greater curvature of the stomach, were identified. After a cautious visceral dissection, the right and left gastroepiploic arteries were clipped and sectioned. Due to the presence of strength adhesions between the aneurysms and the greater curvature of the stomach, we decided to perform double aneurismectomy "en bloc" with the excision of the adjacent greater gastric curve by using an articulated laparoscopic stapler (Endo GIA™ 60 mm Articulating Medium/Thick Reload with Tri-Staple™ Technology, MEDTRONIC, Minneapolis, US). No intraoperative complications were reported. The patient was discharged in fifth post-operative day.

Conclusions

In case of failure of a non-surgical management of ruptured GEA aneurysms, the laparoscopic resection is a safe and effective procedure.

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Pure laparoscopic radical resection for type IIIa hilar cholangiocarcinoma

Abstract

Background

Pure laparoscopic radical resection of hilar cholangiocarcinoma is still a challenging procedure, in which laparoscopic lymphadenectomy, hemihepatectomy with caudate lobectomy, and hepaticojejunostomy were included [1–4]. Relative report is rare in the world up to now. Hilar cholangiocarcinoma has a poor prognosis, especially when it occurs with lymph node metastasis or vessel invasion [5, 6]. We recently had a patient who underwent a pure laparoscopic extended right hepatectomy and lymph node dissection and hepaticojejunostomy for a type IIIa hilar cholangiocarcinoma.

Methods

The tumor was 20 × 15 × 12 mm in diameter and located in the right bile duct and common hepatic duct. Radiological examination showed that hepatic artery and portal vein was not invaded. After the division and mutilation of the right hepatic artery and the right portal vein, short hepatic veins were divided and cut off with clip and ultrasound knife from the anterior face of the vena cava. Mobilization was performed after the devascularization of the right liver, followed by the transection of liver parenchymal with CUSA and ultrasound knife. Finally, left hepatic bile duct jejunum Roux-en-Y reconstruction was performed.

Results

This patient underwent successfully with a totally laparoscopic procedure. An extended right hepatectomy (right hemihepatectomy combined with caudate lobectomy) and complete lymph node dissection and hepaticojejunostomy were performed in this operation. The operation time was nearly 590 min, and the intraoperative blood loss was about 300 ml. No obvious complication was observed and the postoperative hospital stay was 11 days. The final diagnosis of the hilar cholangiocarcinoma with no lymph node metastasis was pT2bN0M0 stage II (American Joint Committee on Cancer, AJCC).

Conclusions

Pure laparoscopic resection for hilar cholangiocarcinoma was proved safe and feasible, which enabled the patient to recover early and have an opportunity to receive chemotherapy as soon as possible. We present a video of the described procedure.

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Laparoscopic pancreaticoduodenectomy: changing the management of ampullary neoplasms

Abstract

Background

The purpose of this study is to present the largest reported series comparing open pancreaticoduodenectomy (OPD) to total laparoscopic pancreaticoduodenectomy (TLPD) in patients with ampullary neoplasms.

Methods

Patients undergoing OPD or TLPD for ampullary neoplasms from June 2012 to August 2016 were retrospectively identified. Perioperative outcomes were compared using a Wilcoxon rank-sum test, Student's t test, and Chi square analysis where appropriate. Kaplan–Meier estimates for progression-free survival (PFS) and overall survival (OS) were compared between the groups using the log-rank test.

Results

We identified 47 patients with ampullary neoplasms (adenocarcinoma n = 36, neuroendocrine tumor n = 7, undifferentiated n = 1, adenoma n = 3) undergoing OPD (n = 25) and TLPD (n = 22). The proportion of patients being offered TLPD has progressively increased every year over 5 years: 0% (2012) to 50% (2015). There were no differences in baseline variables between the two groups. TLPD was associated with less blood loss (300 vs. 500 mL, p < 0.001) and shorter operative times (314 vs. 359 min, p = 0.024). No patient required conversion to an open procedure and there were no perioperative deaths in either group. TLPD was associated with lower rates of intra-abdominal abscess (0 vs. 16.0%, p = 0.049), but there were no differences in rates of pancreatic fistula, bile leak, delayed gastric emptying, wound infection, length of stay, and readmission (all p > 0.05). Among patients with adenocarcinoma, there was no difference in pathological features between the two groups (p > 0.05) and all patients had negative margins. At a median follow up of 25 months, there was no difference in PFS or OS between the two groups.

Conclusions

TLPD in patients with ampullary neoplasms results in improved perioperative outcomes while having equivalent short and long-term oncologic outcomes compared to the traditional open approach.

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Closure of a direct inguinal hernia defect in laparoscopic repair with barbed suture: a simple method to prevent seroma formation?

Abstract

Purpose

Seroma is a frequent postoperative complication after laparoscopic direct inguinal hernia repair (both in TAPP and TEP). There are several methods to address this problem; however, these techniques are not without problems. The purpose of this study was to introduce and evaluate a new technique to address this problem.

Methods

This is a prospective study of consecutive patients. All patients diagnosed with direct inguinal hernias eligible for laparoscopic repair were included. A single surgeon performed all the included operations. During laparoscopic inguinal hernia repair (TAPP or TEP), we closed the direct hernia defect with barbed sutures around the transversalis fascia, inverted the apex of the attenuated transversalis fascia, and sutured it at the base to completely eradicate the defect cavity. Prosthetic mesh was not additionally fixed in all patients. The primary postoperative outcome parameter was seroma formation, and secondary outcome parameters included groin pain, surgical complications, and hernia recurrence.

Results

Twenty-five male patients with 36 sides of direct hernias were included in this study, and all procedures were carried out laparoscopically and successfully. Only one patient developed significant seroma, which resolved 1 month later. The early postoperative pain was minimal, and no recurrence and chronic pain occurred during the follow-up period (4–13 months).

Conclusions

The present direct inguinal hernia defect closing technique with barbed suture is a simple, easily reproducible, and effective method for the prevention of seroma formation.

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Impact of laparoscopy on the prevention of pulmonary complications after thoracoscopic esophagectomy using data from JCOG0502: a prospective multicenter study

Abstract

Background

Postoperative pulmonary complications (PPCs) are the most common causes of serious morbidity after esophagectomy, which involves both thoracic and abdominal incisions. Although the thoracoscopic approach decreases PPC frequency after esophagectomy, it remains unclear whether the frequency is further decreased by combining it with laparoscopic gastric mobilization. This study aimed to determine the impact of laparoscopy on the prevention of PPCs after thoracoscopic esophagectomy using data from the Japan Clinical Oncology Group Study 0502 (JCOG0502).

Methods

JCOG0502 is a four-arm prospective study comparing esophagectomy with definitive chemo-radiotherapy. The use of thoracoscopy and/or laparoscopy was decided at the surgeon's discretion. PPCs were defined as one or more of the following postoperative morbidities grade ≥2 (as per Common Terminology Criteria for Adverse Events v3.0): pneumonia, atelectasis, and acute respiratory distress syndrome.

Results

A total of 379 patients were enrolled in JCOG0502. Of these, 210 patients underwent esophagectomy via thoracotomy with laparotomy (n = 102), thoracotomy with laparoscopy (n = 7), thoracoscopy with laparotomy (n = 43), and thoracoscopy with laparoscopy (n = 58). PPC frequency was reduced to a greater extent by thoracoscopy than by thoracotomy (thoracoscopy 15.8%, thoracotomy 30.3%; p = 0.015). However, following thoracoscopic esophagectomy, laparoscopy failed to further decrease the PPC frequency compared with laparotomy (laparoscopy 15.5%, laparotomy 16.3%; p = 1.00). Univariable analysis showed that thoracoscopy (shown above) and less blood loss (<350 mL 16.3%, ≥350 mL 30.2%; p = 0.022) were associated with PPC prevention, whereas laparoscopy showed a borderline significant association (laparoscopy 15.4%, laparotomy 26.9%; p = 0.079). Multivariable analysis also showed that thoracoscopy and less blood loss were associated with PPC prevention.

Conclusion

Thoracoscopic approach to esophagectomy significantly reduced PPC frequency with minimal additional effect from laparoscopic gastric mobilization.

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Health Services Research in Rehabilitation and Disability – The Time is Now

Publication date: Available online 4 August 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): James E. Graham, Addie Middleton, Janet Prvu Bettger, Trudy Mallinson, Pamela Roberts
Policy drives practice, and health services research (HSR) is at the intersection of policy, practice and patient outcomes. HSR specific to rehabilitation and disability is particularly needed. As rehabilitation researchers and providers, we are uniquely positioned to provide the evidence that guides reforms targeting rehabilitative care. We have the expertise to define the value of rehabilitation in a policy-relevant context. HSR is a powerful tool for providing this evidence. We need to continue building capacity for conducting rigorous, timely rehabilitation-related HSR. Fostering stakeholder engagement in these research efforts will ensure we maintain a patient-centered focus as we address the "Triple Aim" of better care, better health, and better value. In this Special Communication we discuss the role of rehabilitation researchers in HSR. We also provide information on current resources available in our field for conducting HSR and identify gaps for capacity-building and future research. Healthcare reforms are a reality, and through HSR we can give rehabilitation a strong voice during these transformative times.



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Supported Employment for Veterans with Traumatic Brain Injury: Patient Perspectives

Publication date: Available online 4 August 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Kathleen F. Carlson, Terri K. Pogoda, Tess Gilbert, Sandra G. Resnick, Elizabeth Twamley, Maya E. O'Neil, Nina A. Sayer
ObjectiveTo quantify the need for, and interest in, Supported Employment (SE) among recent military Veterans with traumatic brain injury (TBI), and to examine characteristics associated with Veterans' interest in SE.DesignStratified random sample of Iraq and Afghanistan War Veterans confirmed to have TBI through the Veterans Health Administration (VHA) screening and evaluation system.SettingCommunity-based via mailed survey.ParticipantsWe recruited 1,800 Veterans with clinician-confirmed TBI (1,080 mild TBI; 720 moderate/severe TBI) through multiple mailings. Among 1,451 whose surveys were not returned undeliverable, 616 (42%) responded.InterventionsNot applicable.Main Outcome MeasuresVeterans rated their interest in SE after reading a script describing the program. Additional measures assessed mental health and pain-related comorbidities, employment, financial/housing difficulties, demographics, and military service characteristics. Estimates were weighted to represent the population of Veterans with VHA clinician-confirmed TBI.ResultsUnemployment was reported by 45% (95% confidence interval [CI]: 43, 47) of Veterans with TBI. Although 42% (95% CI: 40, 44) reported they would be interested in using SE if it were offered to them, only 12% had heard of SE (95% CI: 11, 14) and <1% had used it. TBI severity and comorbidities were not associated with Veterans' interest in SE. However, those who were unemployed, looking for work, experiencing financial strain, or at risk for homelessness were more likely to be interested in SE.ConclusionsOur research highlights an important gap between Veterans' vocational needs and interests and their use of SE. Systematically identifying and referring those with employment and financial/housing difficulties may help close this gap.



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Off-duty paramedic saves man’s life at gym

Stephen Harris was touring the gym with his son when a man on an exercise machine collapsed

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Spinal cord injury following a mild trauma in homocystinuria-related bone frailty: neurorehabilitation and education on bone health management.

Homocystinuria (HCU) is a rare autosomal recessive disease characterized by the deficiency of cystathionine [beta]-synthetase, presenting with variable clinical features including micronutrient deficiency-related osteoporosis. Early-onset osteoporosis results in increased bone fragility, which is associated with low-impact fractures. To date, no traumatic myelopathy has ever been described in patients with HCU. This case report describes a 30-year-old male patient with HCU who was not aware that he was at high risk of sustaining debilitating bone fractures. After a mild trauma, he reported a T12 compression fracture with spinal cord injury. The patient underwent a tailored rehabilitation program, on the basis of multidisciplinary approach, and was educated about the increased risk of fractures, maintaining adherence to treatment and diet, having an active lifestyle, avoiding excessive weight loss, and preventing falls or other traumatic injury. To reduce the risk of fractures - with possible catastrophic consequences - patients with HCU, and their caregivers, should be educated about prevention of fractures. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Antivertiginous drug therapy does not hinder the efficacy of individualized vibrotactile neurofeedback training for vestibular rehabilitation - a randomized trial.

Vestibular rehabilitation using individualized vibrotactile neurofeedback training (IVNT) can lead to significant improvement in the postural stability of patients with vestibular symptoms of different origins. However, some of these patients have complex, severe dizziness, meaning that a pharmacological pretreatment or parallel (to vestibular rehabilitation) treatment can help them perform the rehabilitation exercises. Hence, the present study investigated the influence of a pharmacological treatment on the efficacy of vibrotactile neurofeedback training in patients with chronic, noncompensated vestibulopathies. All participants performed IVNT for ~10 min each day for 2 weeks. In addition, every second participant was selected randomly to receive oral medication (20 mg cinnarizine and 40 mg dimenhydrinate per tablet), taking three tables per day. Trunk and ankle sway and postural stability were measured. In addition, the dizziness handicap inventory was evaluated immediately before training on the last day of training and 6 months after training. After the 10-day period of IVNT, both groups showed a statistically significant improvement in all parameters tested. A follow-up analysis after 6 months showed a long-term efficacy for the IVNT, that is, the patients remained significantly improved in their postural stability. The antivertiginous therapy did not hinder the efficacy of the IVNT. The present results indicate that IVNT even in combination with an antivertiginous drug therapy is an effective treatment regime for patients with disabling vertigo of different origins. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Wakefulness suppresses retinal wave-related neural activity in visual cortex

In the developing visual system before eye opening, spontaneous retinal waves trigger bursts of neural activity in downstream structures, including visual cortex. At the same ages when retinal waves provide the predominant input to the visual system, sleep is the predominant behavioral state. However, the interactions between behavioral state and retinal wave-driven activity have never been explicitly examined. Here we characterized unit activity in visual cortex during spontaneous sleep-wake cycles in 9- and 12-day-old rats. At both ages, cortical activity occurred in discrete rhythmic bursts, ~30–60 s apart, mirroring the timing of retinal waves. Interestingly, when pups spontaneously woke up and moved their limbs in the midst of a cortical burst, the activity was suppressed. Finally, experimentally evoked arousals also suppressed intraburst cortical activity. All together, these results indicate that active wake interferes with the activation of the developing visual cortex by retinal waves. They also suggest that sleep-wake processes can modulate visual cortical plasticity at earlier ages than has been previously considered.

NEW & NOTEWORTHY By recording in visual cortex in unanesthetized infant rats, we show that neural activity attributable to retinal waves is specifically suppressed when pups spontaneously awaken or are experimentally aroused. These findings suggest that the relatively abundant sleep of early development plays a permissive functional role for the visual system. It follows, then, that biological or environmental factors that disrupt sleep may interfere with the development of these neural networks.

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Control of the strength of visual-motor transmission as the mechanism of rapid adaptation of priors for Bayesian inference in smooth pursuit eye movements

Bayesian inference provides a cogent account of how the brain combines sensory information with "priors" based on past experience to guide many behaviors, including smooth pursuit eye movements. We now demonstrate very rapid adaptation of the pursuit system's priors for target direction and speed. We go on to leverage that adaptation to outline possible neural mechanisms that could cause pursuit to show features consistent with Bayesian inference. Adaptation of the prior causes changes in the eye speed and direction at the initiation of pursuit. The adaptation appears after a single trial and accumulates over repeated exposure to a given history of target speeds and directions. The influence of the priors depends on the reliability of visual motion signals: priors are more effective against the visual motion signals provided by low-contrast vs. high-contrast targets. Adaptation of the direction prior generalizes to eye speed and vice versa, suggesting that both priors could be controlled by a single neural mechanism. We conclude that the pursuit system can learn the statistics of visual motion rapidly and use those statistics to guide future behavior. Furthermore, a model that adjusts the gain of visual-motor transmission predicts the effects of recent experience on pursuit direction and speed, as well as the specifics of the generalization between the priors for speed and direction. We suggest that Bayesian inference in pursuit behavior is implemented by distinctly non-Bayesian internal mechanisms that use the smooth eye movement region of the frontal eye fields to control of the gain of visual-motor transmission.

NEW & NOTEWORTHY Bayesian inference can account for the interaction between sensory data and past experience in many behaviors. Here, we show, using smooth pursuit eye movements, that the priors based on past experience can be adapted over a very short time frame. We also show that a single model based on direction-specific adaptation of the strength of visual-motor transmission can explain the implementation and adaptation of priors for both target direction and target speed.

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Efferent inhibition strength is a physiological correlate of hyperacusis in children with autism spectrum disorder

Autism spectrum disorder (ASD) is a developmental disability that is poorly understood. ASD can influence communication, social interaction, and behavior. Children with ASD often have sensory hypersensitivities, including auditory hypersensitivity (hyperacusis). In adults with hyperacusis who are otherwise neurotypical, the medial olivocochlear (MOC) efferent reflex is stronger than usual. In children with ASD, the MOC reflex has been measured, but without also assessing hyperacusis. We assessed the MOC reflex in children with ASD by measuring the strength of MOC-induced inhibition of transient-evoked otoacoustic emissions (TEOAEs), a noninvasive physiological measure that reflects cochlear amplification. MOC activity was evoked by contralateral noise. Hyperacusis was assessed subjectively on the basis of the children's symptoms. We found a significant correlation between hyperacusis scores and MOC strength in children with ASD. When children were divided into ASD-with-severe-hyperacusis (ASDs), ASD-with-not-severe-hyperacusis (ASDns), and neurotypical (NT) groups, the last two groups had similar hyperacusis and MOC reflexes, whereas the ASDs group, on average, had hyperacusis and MOC reflexes that were approximately twice as strong. The MOC inhibition of TEOAEs averaged larger at all frequencies in the ASDs compared with ASDns and NT groups. The results suggest that the MOC reflex can be used to estimate hyperacusis in children with ASD and might be used to validate future questionnaires to assess hyperacusis. Our results also provide evidence that strong MOC reflexes in children with ASD are associated with hyperacusis and that hyperacusis is a comorbid condition and is not a necessary, integral part of the abnormal neural processing associated with ASD.

NEW & NOTEWORTHY Children with autism spectrum disorder (ASD) are a heterogeneous group, some with hyperacusis and some without. Our research shows that hyperacusis can be estimated in children with ASD by using medial olivocochlear (MOC) reflex measurements. By establishing that an objective measure correlates with attributes of hyperacusis, our results enable future work to enable subtyping of children with ASD to provide improved individualized treatments to at-risk children and those without adequate language to describe their hyperacusis symptoms.

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A balance of outward and linear inward ionic currents is required for generation of slow-wave oscillations

Regenerative inward currents help produce slow oscillations through a negative-slope conductance region of their current-voltage relationship that is well approximated by a linear negative conductance. We used dynamic-clamp injections of a linear current with such conductance, I_NL, to explore why some neurons can generate intrinsic slow oscillations whereas others cannot. We addressed this question in synaptically isolated neurons of the crab Cancer borealis after blocking action potentials. The pyloric network consists of a distinct pacemaker and follower neurons, all of which express the same complement of ionic currents. When the pyloric dilator (PD) neuron, a member of the pacemaker group, was injected with I_NL with dynamic clamp, it consistently produced slow oscillations. In contrast, all follower neurons failed to oscillate with I_NL. To understand these distinct behaviors, we compared outward current levels of PD with those of follower lateral pyloric (LP) and ventral pyloric (VD) neurons. We found that LP and VD neurons had significantly larger high-threshold potassium currents (I_HTK) than PD and LP had lower-transient potassium current (I_A). Reducing I_HTK pharmacologically enabled both LP and VD neurons to produce I_NL-induced oscillations, whereas modifying I_A levels did not affect I_NL-induced oscillations. Using phase-plane and bifurcation analysis of a simplified model cell, we demonstrate that large levels of I_HTK can block I_NL-induced oscillatory activity whereas generation of oscillations is almost independent of I_A levels. These results demonstrate the general importance of a balance between inward pacemaking currents and high-threshold K⁺ current levels in determining slow oscillatory activity.

NEW & NOTEWORTHY Pacemaker neuron-generated rhythmic activity requires the activation of at least one inward and one outward current. We have previously shown that the inward current can be a linear current (with negative conductance). Using this simple mechanism, here we demonstrate that the inward current conductance must be in relative balance with the outward current conductances to generate oscillatory activity. Surprisingly, an excess of outward conductances completely precludes the possibility of achieving such a balance.

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Reevaluation of reflex responses of the human masseter muscle to electrical lip stimulation

We examined the reflex response of the human masseter muscle to electrical stimulation of the lip using both single motor unit and surface electromyogram based methods. Using the classical analysis methods, reflex response to mild electrical stimuli generated two distinct short-lasting inhibitions. This pattern may reflect the development of combinations of short- and long-latency inhibitory postsynaptic potentials as a result of the mildly painful electrical lip stimulation. However, this pattern appearing in the classical analysis methods may have developed as a consequence of earlier responses and may not be genuine. This study examined the genuineness of these responses using both the classical analysis methods and the discharge rate method to uncover the realistic postsynaptic potentials in human trigeminal motor nucleus. Using the discharge rate method, we found that the electrical lip stimulation only generated a long-lasting single or compound inhibitory response that is followed by late, long-lasting excitation. These findings have important implications on the redrawing of the neuronal pathways of the trigeminal nerve that are frequently used to judge neuromuscular disorders of the trigeminal region.

NEW & NOTEWORTHY We examined the human masseter reflex response to electrical stimulation of lower lip to uncover realistic postsynaptic potentials in the trigeminal motor nucleus. We found that the stimulation generates a long-lasting single or compound inhibitory response that is followed by a late, long-lasting excitation. These findings have important implications on the redrawing of the neuronal pathways of the trigeminal nerve that are frequently used to judge neuromuscular disorders of the trigeminal region.

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Sodium pump regulation of locomotor control circuits

Sodium pumps are ubiquitously expressed membrane proteins that extrude three Na⁺ ions in exchange for two K⁺ ions, using ATP as an energy source. Recent studies have illuminated additional, dynamic roles for sodium pumps in regulating the excitability of neuronal networks in an activity-dependent fashion. We review their role in a novel form of short-term memory within rhythmic locomotor networks. The data we review derives mainly from recent studies on Xenopus tadpoles and neonatal mice. The role and underlying mechanisms of pump action broadly match previously published data from an invertebrate, the Drosophila larva. We therefore propose a highly conserved mechanism by which sodium pump activity increases following a bout of locomotion. This results in an ultraslow afterhyperpolarization (usAHP) of the membrane potential that lasts around 1 min, but which only occurs in around half the network neurons. This usAHP in turn alters network excitability so that network output is reduced in a locomotor interval-dependent manner. The pumps therefore confer on spinal locomotor networks a temporary memory trace of recent network performance.

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Inferring neuronal network functional connectivity with directed information

A major challenge in neuroscience is to develop effective tools that infer the circuit connectivity from large-scale recordings of neuronal activity patterns. In this study, context tree maximizing (CTM) was used to estimate directed information (DI), which measures causal influences among neural spike trains in order to infer putative synaptic connections. In contrast to existing methods, the method presented here is data driven and can readily identify both linear and nonlinear relations between neurons. This CTM-DI method reliably identified circuit structures underlying simulations of realistic conductance-based networks. It also inferred circuit properties from voltage-sensitive dye recordings of the buccal ganglion of Aplysia. This method can be applied to other large-scale recordings as well. It offers a systematic tool to map network connectivity and to track changes in network structure such as synaptic strengths as well as the degrees of connectivity of individual neurons, which in turn could provide insights into how modifications produced by learning are distributed in a neural network.

NEW & NOTEWORTHY This study brings together the techniques of voltage-sensitive dye recording and information theory to infer the functional connectome of the feeding central pattern generating network of Aplysia. In contrast to current statistical approaches, the inference method developed in this study is data driven and validated by conductance-based model circuits, can distinguish excitatory and inhibitory connections, is robust against synaptic plasticity, and is capable of detecting network structures that mediate motor patterns.

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Background noise exerts diverse effects on the cortical encoding of foreground sounds

In natural listening conditions, many sounds must be detected and identified in the context of competing sound sources, which function as background noise. Traditionally, noise is thought to degrade the cortical representation of sounds by suppressing responses and increasing response variability. However, recent studies of neural network models and brain slices have shown that background synaptic noise can improve the detection of signals. Because acoustic noise affects the synaptic background activity of cortical networks, it may improve the cortical responses to signals. We used spike train decoding techniques to determine the functional effects of a continuous white noise background on the responses of clusters of neurons in auditory cortex to foreground signals, specifically frequency-modulated sweeps (FMs) of different velocities, directions, and amplitudes. Whereas the addition of noise progressively suppressed the FM responses of some cortical sites in the core fields with decreasing signal-to-noise ratios (SNRs), the stimulus representation remained robust or was even significantly enhanced at specific SNRs in many others. Even though the background noise level was typically not explicitly encoded in cortical responses, significant information about noise context could be decoded from cortical responses on the basis of how the neural representation of the foreground sweeps was affected. These findings demonstrate significant diversity in signal in noise processing even within the core auditory fields that could support noise-robust hearing across a wide range of listening conditions.

NEW & NOTEWORTHY The ability to detect and discriminate sounds in background noise is critical for our ability to communicate. The neural basis of robust perceptual performance in noise is not well understood. We identified neuronal populations in core auditory cortex of squirrel monkeys that differ in how they process foreground signals in background noise and that may contribute to robust signal representation and discrimination in acoustic environments with prominent background noise.

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Split-arm swinging: the effect of arm swinging manipulation on interlimb coordination during walking

Human locomotion is defined by bilateral coordination of gait (BCG) and shared features with the fore-hindlimb coordination of quadrupeds. The objective of the present study is to explore the influence of arm swinging (AS) on BCG. Sixteen young, healthy individuals (eight women; eight right motor-dominant, eight left-motor dominant) participated. Participants performed 10 walking trials (2 min). In each of the trials AS was unilaterally manipulated (e.g., arm restriction, weight on the wrist), bilaterally manipulated, or not manipulated. The order of trials was random. Walking trials were performed on a treadmill. Gait kinematics were recorded by a motion capture system. Using feedback-controlled belt speed allowed the participants to walk at a self-determined gait speed. Effects of the manipulations were assessed by AS amplitudes and the phase coordination index (PCI), which quantifies the left-right anti-phased stepping pattern. Most of the AS manipulations caused an increase in PCI values (i.e., reduced lower limb coordination). Unilateral AS manipulation had a reciprocal effect on the AS amplitude of the other arm such that, for example, over-swinging of the right arm led to a decrease in the AS amplitude of the left arm. Side of motor dominance was not found to have a significant impact on PCI and AS amplitude. The present findings suggest that lower limb BCG is markedly influenced by the rhythmic AS during walking. It may thus be important for gait rehabilitation programs targeting BCG to take AS into account.

NEW & NOTEWORTHY Control mechanisms for four-limb coordination in human locomotion are not fully known. To study the influence of arm swinging (AS) on bilateral coordination of the lower limbs during walking, we introduced a split-AS paradigm in young, healthy adults. AS manipulations caused deterioration in the anti-phased stepping pattern and impacted the AS amplitudes for the contralateral arm, suggesting that lower limb coordination is markedly influenced by the rhythmic AS during walking.

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Auditory fear conditioning modifies steady-state evoked potentials in the rat inferior colliculus

The rat inferior colliculus (IC) is a major midbrain relay for ascending inputs from the auditory brain stem and has been suggested to play a key role in the processing of aversive sounds. Previous studies have demonstrated that auditory fear conditioning (AFC) potentiates transient responses to brief tones in the IC, but it remains unexplored whether AFC modifies responses to sustained periodic acoustic stimulation—a type of response called the steady-state evoked potential (SSEP). Here we used an amplitude-modulated tone—a 10-kHz tone with a sinusoidal amplitude modulation of 53.7 Hz—as the conditioning stimulus (CS) in an AFC protocol (5 CSs per day in 3 consecutive days) while recording local field potentials (LFPs) from the IC. In the preconditioning session (day 1), the CS elicited prominent 53.7-Hz SSEPs. In the training session (day 2), foot shocks occurred at the end of each CS (paired group) or randomized in the inter-CS interval (unpaired group). In the test session (day 3), SSEPs markedly differed from preconditioning in the paired group: in the first two trials the phase to which the SSEP coupled to the CS amplitude envelope shifted ~90°; in the last two trials the SSEP power and the coherence of SSEP with the CS amplitude envelope increased. LFP power decreased in frequency bands other than 53.7 Hz. In the unpaired group, SSEPs did not change in the test compared with preconditioning. Our results show that AFC causes dissociated changes in the phase and power of SSEP in the IC.

NEW & NOTEWORTHY Local field potential oscillations in the inferior colliculus follow the amplitude envelope of an amplitude-modulated tone, originating a neural response called the steady-state evoked potential. We show that auditory fear conditioning of an amplitude-modulated tone modifies two parameters of the steady-state evoked potentials in the inferior colliculus: first the phase to which the evoked oscillation couples to the amplitude-modulated tone shifts; subsequently, the evoked oscillation power increases along with its coherence with the amplitude-modulated tone.

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Automatic and intentional influences on saccade landing

Saccadic eye movements enable us to rapidly direct our high-resolution fovea onto relevant parts of the visual world. However, while we can intentionally select a location as a saccade target, the wider visual scene also influences our executed movements. In the presence of multiple objects, eye movements may be "captured" to the location of a distractor object, or be biased toward the intermediate position between objects (the "global effect"). Here we examined how the relative strengths of the global effect and visual object capture changed with saccade latency, the separation between visual items and stimulus contrast. Importantly, while many previous studies have omitted giving observers explicit instructions, we instructed participants to either saccade to a specified target object or to the midpoint between two stimuli. This allowed us to examine how their explicit movement goal influenced the likelihood that their saccades terminated at either the target, distractor, or intermediate locations. Using a probabilistic mixture model, we found evidence that both visual object capture and the global effect co-occurred at short latencies and declined as latency increased. As object separation increased, capture came to dominate the landing positions of fast saccades, with reduced global effect. Using the mixture model fits, we dissociated the proportion of unavoidably captured saccades to each location from those intentionally directed to the task goal. From this we could extract the time course of competition between automatic capture and intentional targeting. We show that task instructions substantially altered the distribution of saccade landing points, even at the shortest latencies.

NEW & NOTEWORTHY When making an eye movement to a target location, the presence of a nearby distractor can cause the saccade to unintentionally terminate at the distractor itself or the average position in between stimuli. With probabilistic mixture models, we quantified how both unavoidable capture and goal-directed targeting were influenced by changing the task and the target-distractor separation. Using this novel technique, we could extract the time course over which automatic and intentional processes compete for control of saccades.

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Variations on a theme: species differences in synaptic connectivity do not predict central pattern generator activity

A fundamental question in comparative neuroethology is the extent to which synaptic wiring determines behavior vs. the extent to which it is constrained by phylogeny. We investigated this by examining the connectivity and activity of homologous neurons in different species. Melibe leonina and Dendronotus iris (Mollusca, Gastropoda, Nudibranchia) have homologous neurons and exhibit homologous swimming behaviors consisting of alternating left-right (LR) whole body flexions. Yet, a homologous interneuron (Si1) differs between the two species in its participation in the swim motor pattern (SMP) and synaptic connectivity. In this study we examined Si1 homologs in two additional nudibranchs: Flabellina iodinea, which evolved LR swimming independently of Melibe and Dendronotus, and Tritonia diomedea, which swims with dorsal-ventral (DV) body flexions. In Flabellina, the contralateral Si1s exhibit alternating rhythmic bursting activity during the SMP and are members of the swim central pattern generator (CPG), as in Melibe. The Si1 homologs in Tritonia do not burst rhythmically during the DV SMP but are inhibited and receive bilaterally synchronous synaptic input. In both Flabellina and Tritonia, the Si1 homologs exhibit reciprocal inhibition, as in Melibe. However, in Flabellina the inhibition is polysynaptic, whereas in Tritonia it is monosynaptic, as in Melibe. In all species, the contralateral Si1s are electrically coupled. These results suggest that Flabellina and Melibe convergently evolved a swim CPG that contains Si1; however, they differ in monosynaptic connections. Connectivity is more similar between Tritonia and Melibe, which exhibit different swimming behaviors. Thus connectivity between homologous neurons varies independently of both behavior and phylogeny.

NEW & NOTEWORTHY This research shows that the synaptic connectivity between homologous neurons exhibits species-specific variations on a basic theme. The neurons vary in the extent of electrical coupling and reciprocal inhibition. They also exhibit different patterns of activity during rhythmic motor behaviors that are not predicted by their circuitry. The circuitry does not map onto the phylogeny in a predictable fashion either. Thus neither neuronal homology nor species behavior is predictive of neural circuit connectivity.

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Development and aging of human spinal cord circuitries

The neural motor circuitries in the spinal cord receive information from our senses and the rest of the nervous system and translate it into purposeful movements, which allow us to interact with the rest of the world. In this review, we discuss how these circuitries are established during early development and the extent to which they are shaped according to the demands of the body that they control and the environment with which the body has to interact. We also discuss how aging processes and physiological changes in our body are reflected in adaptations of activity in the spinal cord motor circuitries. The complex, multifaceted connectivity of the spinal cord motor circuitries allows them to generate vastly different movements and to adapt their activity to meet new challenges imposed by bodily changes or a changing environment. There are thus plenty of possibilities for adaptive changes in the spinal motor circuitries both early and late in life.

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Robotic navigation to subcortical neural tissue for intracellular electrophysiology in vivo

In vivo studies of neurophysiology using the whole cell patch-clamp technique enable exquisite access to both intracellular dynamics and cytosol of cells in the living brain but are underrepresented in deep subcortical nuclei because of fouling of the sensitive electrode tip. We have developed an autonomous method to navigate electrodes around obstacles such as blood vessels after identifying them as a source of contamination during regional pipette localization (RPL) in vivo. In mice, robotic navigation prevented fouling of the electrode tip, increasing RPL success probability 3 mm below the pial surface to 82% (n = 72/88) over traditional, linear localization (25%, n = 24/95), and resulted in high-quality thalamic whole cell recordings with average access resistance (32.0 M) and resting membrane potential (–62.9 mV) similar to cortical recordings in isoflurane-anesthetized mice. Whole cell yield improved from 1% (n = 1/95) to 10% (n = 9/88) when robotic navigation was used during RPL. This method opens the door to whole cell studies in deep subcortical nuclei, including multimodal cell typing and studies of long-range circuits.

NEW & NOTEWORTHY This work represents an automated method for accessing subcortical neural tissue for intracellular electrophysiology in vivo. We have implemented a novel algorithm to detect obstructions during regional pipette localization and move around them while minimizing lateral displacement within brain tissue. This approach leverages computer control of pressure, manipulator position, and impedance measurements to create a closed-loop platform for pipette navigation in vivo. This technique enables whole cell patching studies to be performed throughout the living brain.

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Separable systems for recovery of finger strength and control after stroke

Impaired hand function after stroke is a major cause of long-term disability. We developed a novel paradigm that quantifies two critical aspects of hand function, strength, and independent control of fingers (individuation), and also removes any obligatory dependence between them. Hand recovery was tracked in 54 patients with hemiparesis over the first year after stroke. Most recovery of strength and individuation occurred within the first 3 mo. A novel time-invariant recovery function was identified: recovery of strength and individuation were tightly correlated up to a strength level of ~60% of estimated premorbid strength; beyond this threshold, strength improvement was not accompanied by further improvement in individuation. Any additional improvement in individuation was attributable instead to a second process that superimposed on the recovery function. We conclude that two separate systems are responsible for poststroke hand recovery: one contributes almost all of strength and some individuation; the other contributes additional individuation.

NEW & NOTEWORTHY We tracked recovery of the hand over a 1-yr period after stroke in a large cohort of patients, using a novel paradigm that enabled independent measurement of finger strength and control. Most recovery of strength and control occurs in the first 3 mo after stroke. We found that two separable systems are responsible for motor recovery of hand: one contributes strength and some dexterity, whereas a second contributes additional dexterity.

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Wake County EMS driver training

Operating an ambulance on the highway is usually fairly straight forward. But navigating tight neighborhoods while patients are being cared for in the back can be a little tricky. Academy members spend time exercising vehicle operations drills.

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Identification of STAC3 variants in non-Native American families with overlapping features of Carey–Fineman–Ziter syndrome and Moebius syndrome

Horstick et al. (2013) previously reported a homozygous p.Trp284Ser variant in STAC3 as the cause of Native American myopathy (NAM) in 5 Lumbee Native American families with congenital hypotonia and weakness, cleft palate, short stature, ptosis, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia (MH). Here we present two non-Native American families, who were found to have STAC3 pathogenic variants. The first proband and her affected older sister are from a consanguineous Qatari family with a suspected clinical diagnosis of Carey–Fineman–Ziter syndrome (CFZS) based on features of hypotonia, myopathic facies with generalized weakness, ptosis, normal extraocular movements, cleft palate, growth delay, and kyphoscoliosis. We identified the homozygous c.851G>C;p.Trp284Ser variant in STAC3 in both sisters. The second proband and his affected sister are from a non-consanguineous, Puerto Rican family who was evaluated for a possible diagnosis of Moebius syndrome (MBS). His features included facial and generalized weakness, minimal limitation of horizontal gaze, cleft palate, and hypotonia, and he has a history of MH. The siblings were identified to be compound heterozygous for STAC3 variants c.851G>C;p.Trp284Ser and c.763_766delCTCT;p.Leu255IlefsX58. Given the phenotypic overlap of individuals with CFZS, MBS, and NAM, we screened STAC3 in 12 individuals diagnosed with CFZS and in 50 individuals diagnosed with MBS or a congenital facial weakness disorder. We did not identify any rare coding variants in STAC3. NAM should be considered in patients presenting with facial and generalized weakness, normal or mildly abnormal extraocular movement, hypotonia, cleft palate, and scoliosis, particularly if there is a history of MH.

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Skewed X-inactivation in a family with DLG3-associated X-linked intellectual disability

Mutations in DLG3 are a rare cause of non-syndromic X-linked intellectual disability (XLID) (MRX90, OMIM *300189). Only ten DLG3 mutations have been reported to date. The majority of female heterozygous mutation carriers was healthy and had random X-inactivation patterns. We report on an XLID family with a novel DLG3 mutation. The 12-year-old male index patient had moderate intellectual disability (ID) and dysmorphic features. The mutation was also present in four female relatives. A maternal aunt had moderate ID and significantly skewed X-inactivation favorably inactivating the normal DLG3 allele. The proband's healthy mother also had skewed X-inactivation but in the opposite direction (i.e., inactivation of the mutated allele). Two other female relatives had intermediate cognitive phenotypes and random X-inactivation. This family broadens the mutational and phenotypical spectrum of DLG3-associated XLID and demonstrates that heterozygous female mutation carriers can be as severely affected as males. Reports of additional families will be needed to elucidate the causes of unfavorable skewing in female XLID patients.

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A human case of SLC35A3-related skeletal dysplasia

Researchers have identified a subset of Holstein having a range of skeletal deformities, including vertebral anomalies, referred to as complex vertebral malformation due to mutations in the SLC35A3 gene. Here, we report the first case in humans of SLC35A3-related vertebral anomalies. Our patient had prenatally diagnosed anomalous vertebrae, including butterfly, and hemivertebrae throughout the spine, as well as cleft palate, micrognathia, patent foramen ovale, patent ductus arteriosus, posterior embryotoxon, short limbs, camptodactyly, talipes valgus, rocker bottom feet, and facial dysmorphism including proptosis, nevus flammeus, and a cupped left ear. Clinical exome sequencing revealed a novel missense homozygous mutation in SLC35A3. Follow-up biochemical analysis confirmed abnormal protein glycosylation, consistent with a defective Golgi UDP-GlcNAc transporter, validating the mutations. Congenital disorders of glycosylation, including SLC35A3-CDG, can present as a wide phenotypic spectrum, including skeletal dysplasia. Previously reported patients with SLC35A3-CDG have been described with syndromic autism, epilepsy, and arthrogryposis.

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A novel genetic syndrome with STARD9 mutation and abnormal spindle morphology

Intellectual disability (ID) is one of neurodevelopmental disorders characterized by serious defects in both intelligence and adaptive behavior. Although it has been suggested that genetic aberrations associated with the process of cell division underlie ID, the cytological evidence for mitotic defects in actual patient's cells is rarely reported. Here, we report a novel mutation in the STARD9 (also known as KIF16A) gene found in a patient with severe ID, characteristic features, epilepsy, acquired microcephaly, and blindness. Using whole-exome sequence analysis, we sequenced potential candidate genes in the patient. We identified a homozygous single-nucleotide deletion creating a premature stop codon in the STARD9 gene. STARD9 encodes a 4,700 amino acid protein belonging to the kinesin superfamily. Depletion of STARD9 or overexpression of C-terminally truncated STARD9 mutants were known to induce spindle assembly defects in human culture cells. To determine cytological features in the patient cells, we isolated lymphoblast cells from the patient, and performed immunofluorescence analysis. Remarkably, mitotic defects, including multipolar spindle formation, fragmentation of pericentriolar materials and centrosome amplification, were observed in the cells. Taken together, our findings raise the possibility that controlled expression of full-length STARD9 is necessary for proper spindle assembly in cell division during human development. We propose that mutations in STARD9 result in abnormal spindle morphology and cause a novel genetic syndrome with ID.

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ALG13-CDG in a male with seizures, normal cognitive development, and normal transferrin isoelectric focusing

ALG13-CDG has been recently discovered as a disorder of severe developmental, intellectual and speech disability, microcephaly, visual abnormalities, seizures, hepatomegaly, coagulation abnormalities, and abnormal serumtransferrin isoelectric focusing in serum. A male with seizures, delayed motor, and speech development, but normal cognition carried a hemizygous, predicted pathogenic ALG13 variant (p.E463G). N-glycosylation studies in plasma were normal. ICAM-1 expression was decreased in patient fibroblasts, supporting the variant's pathogenicity. Adding D-galactose to the patient's fibroblast culture increased ICAM-1 expression in vitro, offering a potential treatment option in ALG13-CDG. The present report is a new example for an N-glycosylation disorder, that may present with normal transferrin isoform analysis, and also demonstrates, that CDG type I patients can have normal cognitive development.

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Wake County EMS driver training

Operating an ambulance on the highway is usually fairly straight forward. But navigating tight neighborhoods while patients are being cared for in the back can be a little tricky. Academy members spend time exercising vehicle operations drills.

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