Τετάρτη 1 Ιουνίου 2016

Construct Validity of the Four Square Step Test in Multiple Sclerosis

Publication date: Available online 1 June 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Alon Kalron, Uri Givon
ObjectiveTo expand the construct validity of the Four Square Step Test (FSST) in people with multiple sclerosis (PwMS).DesignCross-sectional study.SettingMultiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, Israel.Participants218 PwMS (133 women, 85 men), mean age 43.2 (S.D=13.5) and mean disease duration of 7.5 (SD=7.7) years since diagnosis were enrolled in the study. The expanded disability status scale (EDSS) score was 3.1 (SD=1.3) indicating minimal-moderate neurological disability.InterventionsNot applicable.Main Outcome MeasuresFour Square Step Test (FSST), posturography measures, 2-Minute Walk test (2mWT), Timed Up and Go test (TUG), Timed 25-Foot Walk test (T25FW), Fall status, Falls Efficacy Scale International (FES-I), Modified Fatigue Impact Scale (MFIS), instrumented cognitive assessment and the Multiple Sclerosis Walking Scale self-reported questionnaire (MSWS-12).ResultsThe FSST score of the total sample was 11.0 (SD=4.9). Significant differences were observed between the very mild, mild and moderate disability groups; 8.8 (SD=3.4), 11.1 (SD=4.9), 14.1 (SD=5.3), respectively. In terms of fall status, the MS fallers demonstrated a significant slower FSST compared to the MS non-fallers; 12.5 (SD=5.7) vs. 9.0 (SD=2.6). Modest significant correlation scores were found between the FSST and the TUG and 2MWT; Pearson's rho=0.652, -0.575, respectively. In terms of posturography, all measures were significantly associated with the FSST scores. A significant positive relationship was observed with the visual spatial cognitive domain (Pearson's rho=-0.207).ConclusionsThe current study supports and broadens the construct validity of the FSST in PwMS.



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The relationship between intracranial pressure and obesity: an ultrasonographic evaluation of the optic nerve

Abstract

Background

Measurements of optic nerve sheath diameter (ONSD) with noninvasive ocular ultrasonography have been shown to be accurate in determining increased intracranial pressure. Obesity is associated with chronic increases in intraabdominal pressure that could consequently result in intracranial hypertension. By utilizing ONSD ultrasonographic measurements, we compare the difference that may exist between obese and non-obese patients.

Study Design

We prospectively collected data from patients who underwent laparoscopic procedures in the supine position between July 2013 and March 2014. Ophthalmic pathology was not present in any patient. Ultrasonographic measurement of the ONSD was obtained sagittally with a 12-MHz transducer 3 mm from its origin. The measurements were taken at 0, 15, and 30 min, and at the end of surgery.

Results

There were 62 subjects, 28 females (45.2 %) and 34 males (54.8 %), with a mean age of 44.22 ± 10.44 years (range 23–66). Forty-eight percent of patients were non-obese, and 52 % of patients were obese. The mean body mass index was 30.70 ± 7.61 kg/m2 (range 20.0–59.5). The mean ONSD of non-obese and obese patients was 4.7 and 5.5 mm at baseline (p = 0.01), 5.4 and 6.2 mm at 15 min (p = 0.01), 5.8 and 6.6 mm at 30 min (p = 0.01), and 5.1 and 5.7 mm after deflation of pneumoperitoneum (p = 0.03), respectively.

Conclusions

Utilizing a noninvasive method to measure the ONSD, a chronic increase in intracranial pressure in obese patients was demonstrated. The increase in the ONSD during laparoscopic procedures reflects a temporary increase in the intracranial pressure from baseline.



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Laparoscopic right hemicolectomy for a patient with idiopathic retroperitoneal fibrosis: A case report

Abstract

A 62-year-old man with abdominal pain and lumbago was admitted to our hospital. Blood examination revealed renal insufficiency, and CT revealed retroperitoneal fibrosis causing bilateral hydrocele and ureteral compression. A colonoscopy was performed to rule out secondary retroperitoneal fibrosis due to malignancies, and this imaging revealed an ascending colon cancer. Laparoscopic right hemicolectomy with lymphadenectomy and retroperitoneal biopsy were performed. The retroperitoneum was filled with hard, white fibrous tissue, which made it difficult to mobilize the right mesocolon from the retroperitoneum. Devascularization performed before mobilization allowed for a safe and oncologically feasible procedure. Histologically, there were no malignant cells in the retroperitoneal tissue. The patient has been without colon cancer reoccurrence for 4 years. When the surgical challenges that distinguish these patients from ordinary cases are recognized preoperatively, laparoscopic colectomy may be a feasible option for patients with colorectal cancer with idiopathic retroperitoneal fibrosis.



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Femoral arterial cannulation performed by residents: a comparison between ultrasound-guided and palpation technique in infants and children undergoing cardiac surgery

Summary

Background

Percutaneous cannulation of the femoral artery in the pediatric age group can be technically challenging, especially when performed by residents in training.

Objective

We examined whether the use of real-time ultrasound guidance is superior to a palpation landmark technique for femoral artery catheterization in children undergoing heart surgery.

Methods

Patients were prospectively randomized into two groups. In the palpation group, the femoral artery was cannulated using the traditional landmark method of palpation of arterial pulse. In the ultrasound group, cannulation was guided by real-time scanning with an ultrasound probe. Ten minutes were set as time limit for the resident's trials during which the time taken for attempted cannulation (primary outcome), number of attempts, number of successful cannulations on first attempt, and success rate were compared between the two groups. Adverse events were monitored on postoperative days 1 and 3.

Results

A total of 106 patients were included in the study. The time taken for attempted femoral artery cannulation was shorter (301 ± 234 vs 420 ± 248 s; difference in mean: 119; 95% confidence interval (CI) of difference: 26–212; P = 0.012) and the number of attempts was lower [1 (1–10) vs 2 (1–5); difference in median: 1, 95% CI of difference: 0.28–1.72; P = 0.003] in the ultrasound group compared with the palpation group. The number of successful cannulations on first attempt was higher in the ultrasound group compared with palpation group [24/53 (45%) vs 13/53 (25%); odds ratio (OR): 2.54, 95% CI: 1.11–5.82; P = 0.025]. The number of patients who had successful cannulation was 31 of 55 (58%) in the palpation group and 40 of 53 (75%) in the ultrasound group (OR: 2.18, 95% CI: 0.95–5.01; P = 0.06). None of the patients had adverse events at days 1 and 3.

Conclusions

Ultrasound-guided femoral arterial cannulation in children when performed by anesthesia residents is superior to the palpation technique based on the reduction of the time taken for attempted cannulation and the number of attempts, and improvement in first attempt success.

Thumbnail image of graphical abstract

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Predictors of unanticipated admission following ambulatory surgery in the pediatric population: a retrospective case–control study

Summary

Background

Ambulatory surgery plays an important role in pediatric anesthesia. However, it is difficult to predict which patients will experience complications. Age >80, ASA class 3 or 4, duration of surgery >3 h, and BMI 30–35 are independent predictors of unanticipated admission in adults. In this study, we retrospectively evaluate risk factors for unanticipated admission, following ambulatory surgery in children.

Methods

All ambulatory patients requiring unanticipated admission between 2005 and 2013 were compared to a random sample of patients not requiring admission in this case–control study. Demographic data, surgical information, medications, intraoperative events, and patient comorbidities were collected from both groups. The reason for admission was classified according to five subtypes. Multiple conditional logistic regression was used to assess factors associated with unanticipated admissions.

Results

The incidence of unanticipated admission was 0.97% (213). Of these, 47% (98) was anesthesia related. Age <2 years (odds ratio [OR] 4.26 95% CI 1.19–15.25), ASA 3 class (OR 3.77 95% CI 1.46–9.71), duration of surgery >1 h (OR 6.54 95% CI 3.47–12.33), completion of surgery >3 pm (OR 2.17 95% CI 1.05–4.51), orthopedic (OR 2.52 95% CI 1.03–6.20), dental (OR 0.21 95% CI 0.06–0.81), ENT (OR 6.47 95% CI 2.99–14.03) surgery, intraoperative events (OR 4.45 95% CI 1.35–18.12), and OSA (OR 6.32 95% CI 1.54–25.94) were factors associated with unanticipated admission.

Conclusion

The incidence of unanticipated admission in children following ambulatory surgery is low. Age, ASA class, duration, and time of completion of surgery are predictors common to pediatrics and adults. Interestingly, intraoperative complications, OSA, and type of surgery (ENT, orthopedic, dental) are specific to pediatrics.

Thumbnail image of graphical abstract

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A comparison of hand-assisted laparoscopic surgery and conventional laparoscopic surgery in rectal cancer: a propensity score analysis

Abstract

Purpose

The aim of this study was to compare oncologic outcomes and perioperative variables following conventional laparoscopic surgery (LAP) versus hand-assisted laparoscopic surgery (HALS) for rectal cancer.

Methods

Between January 2008 and December 2012, 2680 consecutive patients who underwent curative resection for rectal cancer were analyzed. We used 1:1 propensity score matching to adjust for potential baseline confounders between groups including age, sex, body mass index, American Society of Anesthesiologists score, tumor distance from the anal verge, clinical T and N categories, pathologic T and N categories, preoperative carcinoembryonic antigen level, and the status of preoperative concurrent chemoradiotherapy. After matching, we analyzed 278 patients in each group (n = 556).

Results

The median follow-up period was 36.2 and 37.4 months in the HALS group and the conventional LAP group, respectively. Postoperative complications were not significantly different between the two groups (P = 0.531). The 5-year overall survival rate was 88.8 % in the HALS group and 91.2 % in the conventional LAP group (P = 0.329). The 5-year disease-free survival rate was 77.0 % in the HALS group and 79.7 % in the conventional LAP group (P = 0.591).

Conclusions

HALS is considered a safe and feasible approach for rectal cancer treatment that enables the preservation of the advantages of conventional laparoscopic surgery.



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Endoscopic mucosal resection of early oesophageal neoplasia in patients requiring anticoagulation: is it safe?

Abstract

Background and aim

Endoscopic mucosal resection (EMR) has become the standard treatment for early oesophageal neoplasia. The mucosal defect caused by EMR usually takes several weeks to heal. Despite guidelines on high-risk endoscopic procedures in patients on anticoagulation, evidence is lacking whether EMR is safe in such patients. We investigated the immediate and delayed bleeding risk in patients undergoing diagnostic or therapeutic oesophageal EMR comparing patients requiring warfarin anticoagulation with a control group.

Methods

Warfarin was stopped 5 days before the planned EMR and restarted on the evening following the procedure. Patients with high-risk conditions, such as recent pulmonary thromboemboli, received bridging with low molecular weight heparin. All EMRs were performed when the INR was <1.5. Bleeding events on the day of the EMR and within 3 months post-procedure were documented.

Results

One hundred and seventeen consecutive patients with early oesophageal neoplasia were included. Sixty-eight EMRs were performed in 15 patients requiring anticoagulation. One patient on warfarin was readmitted 10 days after EMR with haematemesis and melaena. Out of 400 EMRs in 102 controls, 26 immediate bleeding events occurred requiring endoscopic intervention. One delayed bleeding event (melaena) occurred in the control group. The number of bleeding events did not differ between groups [p = 0.99; odds ratio 1.01 (0.30–3.44)], neither for acute (p = 0.76) nor delayed bleeding (p = 0.24).

Conclusion

EMR of early oesophageal neoplasia can be safely performed in patients requiring anticoagulation when warfarin is discontinued 5 days before the endoscopic intervention and reinstituted on the evening of the procedure day.



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Single-stage revision from gastric band to gastric bypass or sleeve gastrectomy: 6- and 12-month outcomes

Abstract

Background

Laparoscopic adjustable gastric banding (LAGB) is increasingly requiring revisional surgery for complications and failures. Removal of the band and conversion to either laparoscopic Roux-en-y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) is feasible as a single-stage procedure. The objective of this study is to compare the safety and efficacy of single-stage revision from LAGB to either LRYGB or LSG at 6 and 12 months postoperatively.

Methods

Retrospective analysis was performed on patients undergoing single-stage revision between 2009 and 2014 at a single academic medical center. Patients were reassessed for weight loss and complications at 6 and 12 months postoperatively.

Results

Thirty-two patients underwent single-stage revision to LRYGB, and 72 to LSG. Preoperative BMIs were similar between the two groups (p = 0.27). Median length of stay for LRYGB was 3 days versus 2 for LSG (p = 0.14). Four patients in the LRYGB group required reoperation within 30 days, and two patients in the LSG group required reoperation within 30 days (p = 0.15). There was no difference in ER visits (p = 0.24) or readmission rates (p = 0.80) within 30 days of operation. Six delayed complications were seen in the LSG group with three requiring intervention. At 6 months postoperatively, percent excess weight loss (%EWL) was 50.20 for LRYGB and 30.64 for LSG (p = 0.056). At 12 months, %EWL was 51.19 for LRYGB and 34.89 for LSG (p = 0.31). There was no difference in diabetes or hypertension medication reduction at 12 months between LRYGB and LSG (p > 0.07).

Conclusion

Single-stage revision from LAGB to LRYGB or LSG is technically feasible, but not without complications. The complications in the bypass group were more severe. There was no difference in readmission or reoperation rates, weight loss or comorbidity reduction. Revision to LRYGB trended toward higher rate and greater severity of complications with equivalent weight loss and comorbidity reduction.



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The role of flexible endotherapy for the treatment of recurrent Zenker’s diverticula after surgery and endoscopic stapling

Abstract

Background

Currently there are three main treatment options for Zenker's diverticulum (ZD): surgery, rigid endoscopy and flexible endoscopy. After primary success, recurrence can be as high as 19 % for surgery, 12.8 % for rigid endoscopy and 20 % for flexible endoscopy. Flexible endoscopy may represent an ideal treatment option for recurring ZD. The aims of this paper are to evaluate the efficacy and safety of flexible endotherapy for recurring ZD after surgery and/or endoscopic stapling and to compare the treatment outcome between naive and recurring patients.

Methods

Data on patients that underwent flexible endotherapy for ZD between January 2010 and January 2015 were collected. Patients were divided into those with recurrences after surgery and/or endoscopic stapling and those who did not have previous treatments. Dysphagia, regurgitation, and respiratory symptom severity before the procedure were graded. The outcome parameters were: complications, symptom improvement after the first treatment, number of treatment sessions, rate of complete remission and relapses. These parameters were then compared between patients groups.

Results

Twenty-five recurring patients were included. Treatment was carried out successfully in all patients. Two adverse events occurred; they were successfully managed conservatively. After the first treatment, there was a significant reduction in dysphagia, regurgitation and respiratory symptoms scores. The median number of treatments was 1 (IQR 0.25, range 1–3): symptom remission was achieved in 84 % patients and partial improvement in 16 %. Relapsing symptoms occurred in 20 % patients; they were successfully managed with an additional treatment session. Results were compared with data on 34 consecutive naive patients treated within the same time span; no differences of the outcome parameters were revealed.

Conclusions

Flexible endotherapy for ZD recurrences after surgery and endoscopic stapling appears to be safe and effective, and its efficacy and safety profile seems to be comparable between recurring and naive patients.



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Laparoscopic transhiatal esophagectomy improves hospital outcomes and reduces cost: a single-institution analysis of laparoscopic-assisted and open techniques

Abstract

Background

Several case series have demonstrated that laparoscopic transhiatal esophagectomy (LTHE) is associated with favorable perioperative outcomes compared to historical data for open transhiatal esophagectomy (OTHE). Contemporaneous evaluation of open and laparoscopic THE is rare, limiting meaningful comparison of techniques.

Methods

All patients who underwent OTHE (n = 32) and LTHE (n = 41) during the introduction of the latter procedure at our institution (1/2012–4/2014) were identified, and patient charts were retrospectively reviewed.

Results

Indications for operation included 69 patients with esophageal malignancy (adenocarcinoma: 64; squamous cell carcinoma: 4; melanoma: 1) and 4 patients with benign disease. There were no significant differences in clinicopathologic variables between OTHE and LTHE cohorts, except for an increased rate of cardiovascular disease in the LTHE cohort (p = 0.04). There was no significant difference in median operative time or operative complications, yet LTHE was associated with a lower incidence of intraoperative blood transfusion (p < 0.01). There were no 30-day mortalities. LTHE was associated with a reduced time to reach 24-h tube feeding goals (p = 0.02), shorter length of hospital stay (p = 0.01), and 6 % reduced median direct cost (p = 0.04). There were no significant differences in rates of major perioperative morbidities. Patients were followed for a median of 11.0 months during which there were no significant differences between cohorts in disease-free survival or overall survival.

Conclusion

When compared to OTHE, LTHE improves surgical outcomes and decreases hospital costs; short-term oncologic outcomes are similar. LTHE is preferable to OTHE in patients requiring transhiatal esophagectomy.



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Weight loss outcomes and complications from bariatric surgery in the super super obese

Abstract

Background

Bariatric surgery has been established as the most effective long-term treatment for morbid obesity.

Methods

We performed a retrospective review of SSO patients treated at our institute between 2008 and 2013 who underwent a laparoscopic gastric bypass (LGBP) or sleeve gastrectomy (LSG). The primary end point for this study was excess weight loss (EWL) at 1, 3, 6, and 12 months. Secondary end points included procedure length (PL), length of stay (LOS), diabetes management and postoperative complications.

Results

We identified 135 SSO patients who underwent bariatric surgery (93 LGBP, 42 LSG) at our institute from 2008 to 2013 with a median follow-up of 49 months. The incidence of EWL > 30 % for patients in the LGBP group was 3.9, 29.0, 72.2 and 94.6 % at 1, 3, 6 and 12 months, respectively, while the incidence of EWL > 30 % in patients in the LSG group was 4.2, 25.0, 59.1 and 100 % at 1, 3, 6 and 12 months, respectively. PL was 124 ± 49 min for the LGBP group and 98 + 51 min for the LSG group (p < 0.005). LOS was on average 3.0 days (range 1–21) for the LGBP group and 3.4 days (range 1–13) for the LSG group (p = 0.41). Patients experienced a decrease in their hemoglobin A1C level by 10 % for the LGBP group and 9 % for the LSG group at 1 year (p = 0.89). Postoperative complications were seen in 15.1 % of LGBP patients and 4.8 % of LSG patients.

Conclusions

Bariatric surgery is feasible in the SSO patients with comparable EWL outcomes and postoperative complications to historical non-SSO patients.



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Laparoscopic common bile duct exploration using V-Loc suture with insertion of endobiliary stent

Abstract

Background

The treatment of concomitant gallbladder (GB) and common bile duct (CBD) stones is still variable, without a standard treatment protocol. Endoscopic retrograde cholangiopancreatography followed by laparoscopic cholecystectomy is widely being used, but laparoscopic common bile duct exploration (LCBDE) is also being widely performed. We present our method of LCBDE, with anterograde insertion of an endobiliary stent and primary closure of the CBD using unidirectional barbed suture.

Methods

From November 2013 to March 2015, LCBDE was performed on 15 consecutive patients. Chart review was performed to analyze demographic data and perioperative data. After dissection of the GB from the liver bed, the CBD is dissected and a choledochotomy is made. A choledochoscope is inserted in the CBD, and using various methods, CBD stones are extracted. An endobiliary stent is inserted, and the CBD is closed using unidirectional barbed sutures.

Results

Mean age of the patients was 64.7 ± 12.5 years. Of the 15 patients, six patients (40 %) were male and nine patients (60 %) were female. The average operation time and postoperative stay were 90.7 ± 32.5 min and 4.3 ± 1.2 days, respectively. There were no significant complications such as postoperative bleeding, bile leakage, or biliary stricture.

Conclusions

LCBDE using barbed V-Loc suture with insertion of endobiliary stent is a safe, feasible treatment modality that is easily reproducible. Our preliminary results show a zero complication rate, with an acceptable operation time.



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A prospective analysis of GERD after POEM on anterior myotomy

Abstract

Background

Peroral endoscopic myotomy (POEM) is an emerging, minimally invasive procedure capable of overcoming limitations of achalasia treatments, but gastroesophageal reflux disease (GERD) after POEM is of concern and its risk factors have not been evaluated. This prospective study examined GERD and the association of POEM with reflux esophagitis.

Methods

Achalasia patients were recruited from a single center. The pre- and postoperative assessments included Eckardt scores, manometry, endoscopy, and pH monitoring.

Results

Between September 2011 and November 2014, 105 patients underwent POEM; 70 patients were followed up 3 months after POEM. Postoperatively, significant reductions were observed in lower esophageal sphincter (LES) pressure [from 40.0 ± 22.8 to 20.7 ± 14.0 mmHg (P < 0.05)], LES residual pressure [from 22.1 ± 13.3 to 11.4 ± 6.6 mmHg (P < 0.05)], and Eckardt scores [from 5.7 ± 2.5 to 0.7 ± 0.8 (P < 0.05)]. Symptomatic GERD and moderate reflux esophagitis developed in 5 and 11 patients (grade B, n = 8; grade C, n = 3), respectively, and were well controlled with proton pump inhibitors. Univariate logistic regression analysis revealed integrated relaxation pressure was a predictor of ≥grade B reflux esophagitis. No POEM factors were found to be associated with reflux esophagitis.

Conclusion

POEM is effective and safe in treating achalasia, with no occurrence of clinically significant refractory GERD. Myotomy during POEM, especially of the gastric side, was not associated with ≥grade B (requiring medical intervention) reflux esophagitis. Extended gastric myotomy (2–3 cm) during POEM is recommended to improve outcomes.



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The use of endoluminal vacuum (E-Vac) therapy in the management of upper gastrointestinal leaks and perforations

Abstract

Introduction

Upper intestinal leaks and perforations are associated with high morbidity and mortality rates. Despite the growing experience using endoscopically placed stents, the treatment of these leaks and perforations remain a challenge. Endoluminal vacuum (E-Vac) therapy is a novel treatment that has been successfully used in Germany to treat upper gastrointestinal leaks and perforations. There currently are no reports on its use in the USA.

Methods

E-Vac therapy was used to treat 11 patients with upper gastrointestinal leaks and perforations from September 2013 to September 2014. Five patients with leaks following sleeve gastrectomy were excluded from this study. A total of six patients were treated with E-Vac therapy; these included: (n = 2) iatrogenic esophageal perforations, (n = 1) iatrogenic esophageal and gastric perforations, (n = 1) iatrogenic gastric perforation, (n = 1) gastric staple line leak following a surgical repair of a traumatic gastric perforation, and (n = 1) esophageal perforation due to an invasive fungal infection. Four patients had failed an initial surgical repair prior to starting E-Vac therapy.

Results

All six patients (100 %) had complete closure of their perforation or leak after an average of 35.8 days of E-Vac therapy requiring 7.2 different E-Vac changes. No deaths occurred in the 30 days following E-Vac therapy. One patient died following complete closure of his perforation and transfer to an acute care facility due to an unrelated complication. There were no complications directly related to the use of E-Vac therapy. Only one patient had any symptoms of dysphagia. This patient had severe dysphagia from an esophagogastric anastomotic stricture prior to her iatrogenic perforations. Following E-Vac therapy, her dysphagia had actually improved and she could now tolerate a soft diet.

Conclusions

E-Vac therapy is a promising new method in the treatment of upper gastrointestinal leaks and perforations. Current successes need to be validated through future prospective controlled studies.



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Multiplanar MDCT measurement of esophageal hiatus surface area: association with hiatal hernia and GERD

Abstract

Background

Accurate measurement of esophageal hiatus size is clinically important, especially when antireflux surgery is planned. We present a novel method for in vivo measurement of esophageal hiatal surface area using MDCT multiplanar reconstruction. We aimed to determine whether large hiatal area is associated with hiatal hernia and gastroesophageal reflux disease.

Methods

We retrospectively analyzed subjects prospectively enrolled in the COPDGene® project. We created two test groups, one with hiatal hernia on chest CT and one with GERD on medical treatment identified by history without hernia. Matched control groups were formed. We performed CT postprocessing to define the double-oblique plane of the esophageal hiatus, on which the hiatal surface area is manually traced.

Results

Subjects with hernia (n = 48) had larger mean hiatus areas than matched controls (6.9 vs. 2.5 cm2, p < 0.0001), and were more likely to have GERD (42 vs. 10 %, p < 0.0005). Subjects with mixed (type III) hernias had larger hiatuses compared to subjects with sliding (type I) hernias, who, in turn, had larger hiatuses than subjects without hernia (p < 0.0001). Hernia-negative subjects with GERD (n = 55) did not have significantly larger mean hiatal areas compared to matched controls (3.0 vs. 2.5 cm2, p = 0.12). Twenty measurements obtained by two radiologists showed correlation of 0.93, with mean difference of 0.5 cm2 (p = 0.20).

Conclusions

We devised a method to measure in vivo esophageal hiatal surface area using MDCT reconstruction and established the normal size range for the first time. This methodology has the potential to guide decision-making in antireflux surgery technique preoperatively, and assess surgical result postoperatively. The presence of hernia correlated with large hiatuses and GERD. However, hiatal area failed to identify those with GERD in the absence of hiatal hernia.



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Randomized controlled trial comparing laparoscopic greater curvature plication versus laparoscopic sleeve gastrectomy

Abstract

Background

Laparoscopic greater curvature plication (LGCP) is a new restrictive bariatric procedure, which has a similar restrictive mechanism like laparoscopic sleeve gastrectomy (LSG) without potential risk of leak. Aim of the study was to compare 2-year outcomes of LSG and LGCP.

Methods

Multicenter prospective randomized trial was started in 2010. A total of 54 patients with morbid obesity were allocated either to LGCP group (n = 25) or LSG group (n = 27). Main exclusion criteria were: ASA > III, age > 75 and BMI > 65 kg/m2. There were 40 women and 12 men, and the mean age was 42.6 ± 6.8 years (range 35–62). Data on the operation time, complications, hospital stay, body mass index loss, percentage of excess weight loss (%EWL), loss of appetite and improvement in comorbidities were collected during the follow-up examinations.

Results

All procedures were completed laparoscopically. The mean operative time was 92.0 ± 15 min for LSG and 73 ± 19 min for LGCP (p > 0.05). The mean hospital stay was 4.0 ± 1.9 days in the LSG group and 3.8 ± 1.7 days in LGCP group (p > 0.05). One year after surgery, the mean %EWL was 59.5 ± 15.4 % in LSG group and 45.8 ± 17 % in LGCP group (p > 0.05). After 2 years, mean %EWL was 78.9 ± 20 % in the LSG group and 42.4 ± 18 % in the LGCP group (p < 0.01). After 3 years, mean %EWL was 72.8 ± 22 in the LSG group and only 20.5 ± 23.9 in the LGCP group (p < 0.01). Loss of feeling of hunger after 2 years was 25 % in LGCP group and 76.9 % in the LSG group (p < 0.05). The comorbidities including diabetes, sleep apnea and hypertension were markedly improved in the both groups after surgery.

Conclusion

The short-term outcomes demonstrated equal effectiveness of the both procedures, but 2-year follow-up showed that LGCP is worse than LSG as a restrictive procedure for weight loss.



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A comparison of robotic single-incision and traditional single-incision laparoscopic cholecystectomy

Abstract

Background

Surgeons continually strive to improve technology and patient care. One remarkable demonstration of this is the development of laparoscopic surgery. Once this proved to be a safe and reliable surgical approach, robotics seemed a logical progression of surgical technology. The aim of this project was to evaluate the utility of robotics in the context of single-incision laparoscopic cholecystectomy (SILC).

Methods

A retrospective review of a prospectively maintained database of robotic single-incision laparoscopic cholecystectomy (RSILC) and traditional SILC performed by a single surgeon at our institution from July 2010 to August 2013 was queried. All consecutive patients undergoing RSILC and SILC during this time period were included. Primary outcomes include conversion rate and operative time. Secondary outcomes include length of stay, duration of narcotic use, time to independent performance of daily activities and cost. Categorical variables were evaluated using Chi-square analysis and continuous variables using t test or Wilcoxon's rank test.

Results

Thirty-eight patients underwent RSILC and 44 underwent SILC. BMI was higher in the RSILC group, and the number of patients with prior abdominal surgeries was higher in the SILC group. Otherwise, demographics were similar between the two groups. There was no difference in conversion rate between RSILC and SILC (8 vs 11 %, p = 0.60). Mean operative time for RSILC was significantly greater compared with SILC (98 vs 68 min, p < 0.0001). RSILC was associated with a longer duration of narcotic use (2.3 vs 1.7 days, p = 0.0019) and time to independent performance of daily activities (4 vs 2.3 days, p < 0.0001). Total cost is greater in RSILC ($8961 vs $5379, p < 0.0001).

Conclusion

While RSILC can be safely performed, it is associated with longer operative times and greater cost.



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Exercise duration-matched interval and continuous sprint cycling induce similar increases in AMPK phosphorylation, PGC-1α and VEGF mRNA expression in trained individuals

Abstract

Purpose

The effects of low-volume interval and continuous 'all-out' cycling, matched for total exercise duration, on mitochondrial and angiogenic cell signalling was investigated in trained individuals.

Methods

In a repeated measures design, 8 trained males ( \(\dot{V}{\text{O}}_}}\) , 57 ± 7 ml kg−1 min−1) performed two cycling exercise protocols; interval (INT, 4 × 30 s maximal sprints interspersed by 4 min passive recovery) or continuous (CON, 2 min continuous maximal sprint). Muscle biopsies were obtained before, immediately after and 3 h post-exercise.

Results

Total work was 53 % greater (P = 0.01) in INT compared to CON (71.2 ± 7.3 vs. 46.3 ± 2.7 kJ, respectively). Phosphorylation of AMPKThr172 increased by a similar magnitude (P = 0.347) immediately post INT and CON (1.6 ± 0.2 and 1.3 ± 0.3 fold, respectively; P = 0.011), before returning to resting values at 3 h post-exercise. mRNA expression of PGC-1α (7.1 ± 2.1 vs. 5.5 ± 1.8 fold; P = 0.007), VEGF (3.5 ± 1.2 vs. 4.3 ± 1.8 fold; P = 0.02) and HIF-1α (2.0 ± 0.5 vs. 1.5 ± 0.3 fold; P = 0.04) increased at 3 h post-exercise in response to INT and CON, respectively; the magnitude of which were not different between protocols.

Conclusions

Despite differences in total work done, low-volume INT and CON 'all-out' cycling, matched for exercise duration, provides a similar stimulus for the induction of mitochondrial and angiogenic cell signalling pathways in trained skeletal muscle.



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Laparoscopic splenic hilar lymph node dissection for proximal gastric cancer using integrated three-dimensional anatomic simulation software

Abstract

Background

Laparoscopic lymph node (LN) dissection along the distal splenic artery (Station No. 11d) and around the splenic hilum (Station No. 10) remains challenging even for skilled surgeons. The major reason for the difficulty is the complex, multifarious anatomy of the splenic vessels. The latest integrated three-dimensional (3D) simulations may facilitate this procedure.

Methods

Usefulness of 3D simulation was investigated during 20 laparoscopic total gastrectomies with splenic hilar LN dissection while preserving the spleen and pancreas (LTG + PSP) or with splenectomy (LTG + S). Clinical information acquired by 3D simulation and the consistency of the virtual and real images were evaluated. Furthermore, clinical data of these patients were compared with that of the patients who underwent the same surgery before the introduction of 3D simulation (n = 10), to clarify its efficacy.

Results

The vascular architecture and morphologic characteristics were clearly demonstrated in 3D simulation, with sufficient consistency. The median durations of 14 LTG + PSP and 6 LTG + S operations were 318 and 322 min, respectively. The estimated blood losses were 18 and 38 g, respectively. There were no deaths. One postoperative peritoneal abscess (grade II according to Clavien–Dindo) was recorded. A comparison of clinical parameters between surgeries without or with 3D simulation showed no differences in operation time, blood loss, or complication rate; however, the number of retrieved No. 10 LNs has significantly increased in cases with the use of 3D simulation (p = 0.006).

Conclusions

This kind of surgery is not easy to perform, but the latest 3D computed tomography simulation technology has made it possible to reduce the degree of difficulty and also to enhance the quality of surgery, potentially leading to widespread use of these techniques.



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Efficacy and safety of a resorbable collagen membrane COVA+™ for the prevention of postoperative adhesions in abdominal surgery

Abstract

Background

This clinical study was designed to assess the efficacy and safety of COVA+™, a collagen membrane (CM), for the prevention of postoperative adhesions in abdominal surgery.

Methods

This prospective multicenter study concerned one hundred and thirteen patients undergoing two-stage abdominal surgeries between 2011 and 2014: either bariatric surgery (BS) or reversal of a diverting stoma (DS). They were divided into two groups, according to whether a CM was placed at the end of the first procedure or not. The primary endpoint was the evaluation of adhesions (incidence, severity, and extent) on the operative site during the second surgery using standard grading scales and a combined adhesion score. Secondary endpoints were the duration of reoperation and the overall postoperative morbidity.

Results

Sixty-five patients were included in the BS group, and forty-eight patients in the DS group. Mean time interval between surgeries was 33.2 ± 51.1 weeks for BS and 14.1 ± 10 weeks for DS. In both indications, results in the CM group were better compared to the control group regarding incidence, severity, and extent of adhesions. Mean combined adhesion scores were lower in the CM group: respectively, 2.1 ± 1.6 versus 3.6 ± 1.7 (p < 0.001) for BS and 1.1 ± 1.7 versus 3.1 ± 2.2 (p < 0.005) for DS. In BS group, the operative duration at reoperation was significantly shorter if a CM was used: 56 ± 34 versus 77 ± 47 min (p < 0.03). No adverse events related to the use of the CM were observed. Overall complication rate was 13.5 % in the CM group versus 27.9 % in the control group. Ease of handling and application of the CM were rated as satisfying or very satisfying in the great majority of cases.

Conclusions

In abdominal surgery, COVA+™ acts efficiently on the prevention of postoperative adhesions with lower incidence, severity, and extent levels. The CM can be used safely and might render reoperations less difficult.



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Simple versus reinforced cruroplasty in patients submitted to concomitant laparoscopic sleeve gastrectomy: prospective evaluation in a bariatric center of excellence

Abstract

Background

Crural closure in addition to laparoscopic sleeve gastrectomy (LSG) represents a valuable option for the synchronous management of morbid obesity and hiatal defects, providing good outcomes in terms of weight loss and gastroesophageal reflux disease (GERD) symptoms control. The aim of this prospective study was to evaluate the safety and effectiveness of the reinforced cruroplasty during LSG compared with a concurrent group of simple cruroplasty.

Methods

The study groups included 96 morbidly obese patients who underwent simultaneous LSG and cruroplasty. Group A: 48 patients with hiatal areal defect <4 cm2 and normal pillars (simple posterior cruroplasty); group B: 48 patients with hiatal areal defect >4 and <8 cm2 with weakness of the right pillar (on-lay synthetic absorbable mesh-reinforced cruroplasty). Upper GI symptoms were assessed by Roma III standard questionnaire. Endoscopy, imaging, esophageal 24-h pH monitoring and HR manometry were performed in cases of persistent or recurrent symptoms after surgery.

Results

Mortality rate was nil. The conversion rate to open was 1 %. Intra-operative diagnosis of hiatal hernia occured in 41 patients (42.7 %). Mesh-related complications were none. Perioperative complications occurred in four patients (4.1 %). After 19- to 21-month follow-up, GERD symptom remission occurred in 89 % of patients. GERD symptoms were detected postoperatively in eight patients: six in group A (five symptomatic and radiological recurrences and one persistent) and two in group B (one persistent and one de novo GERD) (P < 0.05).

Conclusions

The synthetic absorbable mesh offers an effective option for crural repair during LSG with no clinical recurrences at 19 months. The midterm results of this prospective comparative study evaluating two different technical options for cruroplasty confirm that the simultaneous procedures are safe and cruroplasty is effective in mild-to-moderate GERD control .



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Transanal Hartmann reversal: a new technique

Abstract

Background

Hartmann procedure consists in a sigmoidectomy followed by a terminal colostomy. However, the stoma is associated with complications and suboptimal quality of life, so the restoration of colonic continuity should be, at least, considered in any case. Open restoration has been associated with significant morbidity and mortality; therefore, many authors have described the advantages of laparoscopic Hartmann reversal. We want to go a step further showing our experience using a combined laparoscopic and transanal approach in an attempt to improve the surgical technique.

Methods

Patients with an end colostomy due to an emergency Hartmann procedure are selected for this intervention. This approach is performed simultaneously laparoscopically and transanally, with single-port devices, through the colostomy wound in the first case and trough anal canal in the second one. The previous stapler line is resected transanally and the proximal rectum and mesorectum are dissected until the peritoneal reflexion, where both teams work together to complete the adhesiolysis. Finally an end-to-end anastomosis is performed under laparoscopic control.

Results

As in patients with rectal cancer, dissection of the stump in Hartmann reversal procedure may be better and associated with shorter operative time.

Conclusions

As with any new surgical procedure, it is probably too early to draw conclusions, but nowadays transanal combined with laparoscopic approach seems to be a safe and feasible technique to perform a Hartmann reversal.



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Stent-in-stent technique for removal of embedded partially covered self-expanding metal stents

Abstract

Background

Removal of embedded partially covered self-expanding metal stents (PCSEMS) is associated with an increased risk of adverse events compared with removal of fully covered self-expanding stents (FCSES) due to tissue ingrowth. Successful removal of embedded PCSEMS has been described by the stent-in-stent (SIS) technique.

Aims

To report the first US experience from three high-volume quaternary care centers on the safety and efficacy of the SIS technique for removal of embedded PCSEMS.

Methods

Retrospective study of outcomes for consecutive patients who underwent the SIS for removal of embedded PCSEMS over a 5-year period.

Results

Twenty-seven embedded PCSEMS were successfully removed using the SIS technique (100 %) from 25 patients (11 males), median age 65 (range 37–80). All stents were successfully removed in one endoscopic session (no repeat SIS procedures were required for persistently embedded stents). The embedded PCSEMS had been in situ for a median of 76 days (range 26–501). Median SIS dwell time (FCSES in situ of PCSEMS) was 13 days (interquartile range 8–16 days; range 4–212 days). One adverse event (self-limited bleeding) occurred during a median follow-up period of 3 months (range 1–32). No patients died, required surgery, or had long-term disability due to adverse events attributed to the SIS technique. Twelve patients required additional interventions following SIS procedure for persistence or recurrence of the underlying pathology.

Conclusion

When performed by experienced endoscopists, safe and effective removal of embedded PCSEMS can be achieved via the SIS technique.



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Laparoscopic common bile duct exploration: 15-year experience in a district general hospital

Abstract

Introduction

The treatment of common bile duct (CBD) stones remains controversial with debate between endoscopic cholangiopancreatography (ERCP) and CBD exploration. A recent meta-analysis has shown no significant difference between these approaches; however, there is a trend in the literature to favour a single-stage procedure in the form of laparoscopic CBD exploration. We report our experience over a 15-year period.

Methods

All cases of CBD exploration were identified from 2000 to 2015 and analysed retrospectively from a large NHS Foundation Trust in Northumbria. There were no exclusions. The mean clinical follow-up was 6 months (range 3–36 months).

Results

A total of 296 patients were included who underwent laparoscopic CBD exploration: 203 were female and 93 were male. The mean age was 60 years (range 16–84 years). A total of 231 procedures were performed electively and 65 as an emergency. Ten procedures were successfully performed as day cases. Eleven procedures were converted to an open procedure due to adhesions or a difficult dissection (4 %). Sixty-three procedures were performed with a transcystic approach with a mean post-op stay of 2 days (range 0–7). A total of 233 procedures were performed with a choledocotomy with a mean post-op stay of 6 days (range 3–14 days). Stone clearance was successful in 255 patients (86 %). Three patients died over the study period. Two were for medical complications and one for abdominal sepsis. Three patients returned to theatre for early post-operative bleeding (1 %). Sixteen patients had persistent bile leaks following a choledocotomy (6.8 %). No patients had a bile leak following transcystic exploration. Fourteen patients were followed up following failed stone removal. Nine had a successful ERCP, three had no stone seen on MRCP, and one patient required re-operation following a failed ERCP.

Conclusions

Laparoscopic bile duct exploration can be performed successfully in both the emergency and elective settings. Day-case surgery is feasible in selected patients. A transcystic approach should be favoured where possible.



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Totally laparoscopic versus laparoscopic-assisted left colectomy for cancer: a retrospective review

Abstract

Background

Laparoscopic left colectomy (LLC) became the standard of care for treating distal transverse and descending colon cancer in many centers. Most centers use laparoscopic-assisted colectomy with extracorporeal anastomosis (LAC/EA). A totally laparoscopic colectomy with intracorporeal anastomosis (TLC/IA) has been proposed. The purpose of our study is to compare these two techniques.

Methods

A series of 52 patients undergoing LLC for left-sided colon cancer was retrospectively evaluated. Thirty-three patients underwent TLC/IA, and 19 underwent LAC/EA. The following data were collected: gender, age, body mass index, American Society of Anesthesiologists risk class, operation duration, conversion to laparotomy, intraoperative complications, postoperative complications, postoperative course (duration of stay, time to first flatus), number of excised lymph nodes, readmission, and reoperation rates. Data were prospectively recorded in a colorectal cancer database and retrospectively analyzed.

Results

The only demographic parameter that differed significantly between the groups was age (64.2 ± 12.4 years for the TLC/IA group, vs. 72.7 ± 2.1 years for LAC/EA, p = 0.0116). The mini-laparotomy incision was significantly shorter in the TLC/IA than in the LAC/EA group (5.8 ± 0.9 vs. 8.2 ± 0.9 cm, respectively, p < 0.00001). Hospital stay duration was shorter in the TLC/IA group (4.2 ± 1.2 vs. 6.3 ± 1.9, p = 0.0001). The average number of harvested lymph nodes did not differ significantly between the groups (12.9 ± 5.7 in TLC/IA vs. 11.2 ± 4.2 in LAC/EA, p = 0.2546). No significant differences between the groups were observed in any other perioperative or surgical outcome parameters.

Conclusions

TLC/IA in LLC for the treatment of left colon cancer is technically feasible and can be performed with a low complication rate, favorable cosmetics, and possibly shorter hospital stay, without significantly lengthening operative duration or compromising oncologic radicality principles. Although further prospective randomized studies are needed to determine its role and limitations, we encourage using it as an alternative to LAC/EA in LLC.



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Characterization of SPATA5-related encephalopathy in early childhood

Abstract

Mutations in SPATA5 have recently been shown to result in a phenotype of microcephaly, intellectual disability, seizures, and hearing loss in childhood. Our aim in this report is to delineate the SPATA5 syndrome as a clinical entity, including the facial appearance, neurophysiological, and neuroimaging findings. Using whole exome sequencing and Sanger sequencing, we identified three children with SPATA5 mutations from two families. Two siblings carried compound heterozygous mutations, c.989_991del (p.Thr330del) and c.2130_2133del (p.Glu711Profs*21), and the third child had c.967T>A (p.Phe323Ile) and c.2146G>C (p.Ala716Pro) mutations. The three patients manifested microcephaly, psychomotor retardation, hypotonus or hypertonus, and bilateral hearing loss from early infancy. Common facies were a depressed nasal bridge/ridge, broad eyebrows, and retrognathia. Epileptic spasms or tonic seizures emerged at 6–12 months of age. Interictal electroencephalography showed multifocal spikes and bursts of asynchronous diffuse spike-wave complexes. Augmented amplitudes of visually evoked potentials were detected in two patients. Magnetic resonance imaging revealed hypomyelination, thin corpus callosum, and progressive cerebral atrophy. Blood copper levels were also elevated or close to the upper normal levels in these children.

Clinical delineation of the SPATA5-related encephalopathy should improve diagnosis, facilitating further clinical and molecular investigation.

Thumbnail image of graphical abstract

Absence of brainstem auditory evoked potentials and augmented visually evoked potentials, hypomyelination and progressive cerebral atrophy observed in STATA5- related encephalopathy



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Expanding the clinical picture of the MECP2 Duplication Syndrome

ABSTRACT

Individuals with two or more copies of the MECP2 gene, located at Xq28, share clinical features and a distinct facial phenotype known as MECP2 Duplication syndrome. We have examined perinatal characteristics, early childhood development and medical co-morbidities in this disorder. The International Rett Syndrome Phenotype Database (InterRett), which collects information from caregivers and clinicians on individuals with Rett syndrome and MECP2 associated disorders, was used as the data source. Data were available on 56 cases (49 males and 7 females) with MECP2 Duplication syndrome. Median age at ascertainment was 7.9 yrs (range 1.2-37.6 yrs) and at diagnosis 3.0 yrs (range 3wks-37 yrs). Less than a third (29%) learned to walk. Speech deterioration was reported in 34% and only 20% used word approximations or better at ascertainment. Over half (55%) had been hospitalised for respiratory infections in the first two years of life. Just under half (44%) had seizures, occurring daily in nearly half of this group. The majority (89%) had gastrointestinal problems and a third had a gastrostomy. Following the recent demonstration of phenotype reversal in a mouse model of MECP2 Duplication, a clear understanding of the natural history is crucial to the design and implementation of future therapeutic strategies.

Thumbnail image of graphical abstract

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Use of genome-editing tools to treat sickle cell disease

Abstract

Recent advances in genome-editing techniques have made it possible to modify any desired DNA sequence by employing programmable nucleases. These next-generation genome-modifying tools are the ideal candidates for therapeutic applications, especially for the treatment of genetic disorders like sickle cell disease (SCD). SCD is an inheritable monogenic disorder which is caused by a point mutation in the β-globin gene. Substantial success has been achieved in the development of supportive therapeutic strategies for SCD, but unfortunately there is still a lack of long-term universal cure. The only existing curative treatment is based on allogeneic stem cell transplantation from healthy donors; however, this treatment is applicable to a limited number of patients only. Hence, a universally applicable therapy is highly desirable. In this review, we will discuss the three programmable nucleases that are commonly used for genome-editing purposes: zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9). We will continue by exemplifying uses of these methods to correct the sickle cell mutation. Additionally, we will present induction of fetal globin expression as an alternative approach to cure sickle cell disease. We will conclude by comparing the three methods and explaining the concerns about their use in therapy.



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Identification of a homozygous nonsense mutation in KIAA0556 in a consanguineous family displaying Joubert syndrome

Abstract

Joubert Syndrome (JS) is an inherited ciliopathy associated with mutations in genes essential in primary cilium function. Whole exome sequencing in a multiplex consanguineous family from India revealed a KIAA0556 homozygous single base pair deletion mutation (c.4420del; p.Met1474Cysfs*11). Knockdown of the gene in zebrafish resulted in a ciliopathy phenotype, rescued by co-injection of wildtype cDNA. Affected siblings present a mild and classical form of Joubert syndrome allowing for further delineation of the JS associated genotypic spectrum.



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Advances in intracellular Ca2+ signalling



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Extracellular vesicles in cardiovascular disease: focus on vascular calcification



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Investigating the effect of exercise duration on functional and biochemical perturbations in the human heart: total work or ‘isoeffort’ matching?



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Issue Information



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Strict glucose control and artificial regulation of the NO–ADMA–DDAH system in order to prevent endothelial dysfunction



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Balancing SR Ca2+ uptake and release in the cycle of heart rhythm



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TMEM16F: function from (iso)form



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Reply from Glenn M. Stewart, Justin J. Kavanagh, Luke J. Haseler and Surendran Sabapathy



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Extracellular vesicles in cardiovascular calcification: expanding current paradigms

Abstract

Vascular calcification is a major contributor to the progression of cardiovascular disease, one of the leading causes of death in industrialized countries. New evidence on the mechanisms of mineralization identified calcification-competent extracellular vesicles (EVs) derived from smooth muscle cells, valvular interstitial cells and macrophages as the mediators of calcification in diseased heart valves and atherosclerotic plaques. However, the regulation of EV release and the mechanisms of interaction between EVs and the extracellular matrix leading to the formation of destabilizing microcalcifications remain unclear. This review focuses on current limits in our understanding of EVs in cardiovascular disease and opens up new perspectives on calcific EV biogenesis, release and functions within and beyond vascular calcification. We propose that, unlike bone-derived matrix vesicles, a large population of EVs implicated in cardiovascular calcification are of exosomal origin. Moreover, the milieu-dependent loading of EVs with microRNA and calcification inhibitors fetuin-A and matrix Gla protein suggests a novel role for EVs in intercellular communication, adding a new mechanism to the pathogenesis of vascular mineralization. Similarly, the cell type-dependent enrichment of annexins 2, 5 or 6 in calcifying EVs posits one of several emerging factors implicated in the regulation of EV release and calcifying potential. This review aims to emphasize the role of EVs as essential mediators of calcification, a major determinant of cardiovascular mortality. Based on recent findings, we pinpoint potential targets for novel therapies to slow down the progression and promote the stability of atherosclerotic plaques.

Thumbnail image of graphical abstract

 Vessel wall-derived extracellular vesicles (EVs) are selectively loaded with calcification inhibitors fetuin-A, matrix Gla protein (MGP) and anti-osteogenic microRNA (miRNA) (green box) or pro-calcific annexins, alkaline phosphatase (ALP), calcium (Ca2+) and inorganic phosphate (Pi) (red box). Calcifying conditions (e.g. culture in osteogenic media, OM) increase absolute EV release and EV calcific potential by shifting the balance towards increased expression of pro-calcific factors and suppression of calcification inhibitors in EVs. EVs may originate from the exosomal pathway (1), as multivesicular bodies (MVB; observed but not confirmed in smooth muscle cells, SMCs) (2), or by budding off the cell membrane (not confirmed in SMCs) (3). While the exocytosis pathway is an established mechanism in SMC-mediated calcific EV release, the exact conditions and potential context specificity of these pathways of EV biogenesis are still unclear. Under physiological conditions, non-calcifying EVs transfer inhibitory factors and regulatory miRNA as a form of paracrine signalling, preventing osteogenic differentiation of adjacent cells. Under calcifying conditions, however, calcification-competent EVs are sequestered in the fibrillar matrix, nucleating calcium phosphate mineral. Dysregulated paracrine signalling resulting in an imbalance of calcification inhibitors and miRNA leads to increased osteogenic differentiation of vessel wall cells, expediting vascular calcification.



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Reply from Elizabeth Schroder, Brian Hodge, Lance Riley, Xiping Zhang and Karyn Esser



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Inactivation of the intrinsic muscle clock does not cause sarcopenia



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The plateau phase is a slippery slope: raising blood pressure may lower brain perfusion



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Exercise-induced cardiac fatigue: the need for speed



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Understanding complexity of physiology by combined molecular simulations and experiments: anion channels as a proof of concept



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Targeted genomic enrichment and massively parallel sequencing identifies novel nonsyndromic hearing impairment pathogenic variants in Cameroonian families

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In sub-Saharan Africa GJB2-related nonsyndromic hearing impairment (NSHI) is rare. Ten Cameroonian families was studied using a platform (OtoSCOPE®) with 116 genes. In seven of 10 families (70%), 12 pathogenic variants were identified in six genes. Five of the 12 (41.6%) variants are novel. These results confirm the efficiency of comprehensive genetic testing in defining the causes of NSHI in sub-Saharan Africa.



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