Πέμπτη, 19 Οκτωβρίου 2017

Reappraisal of systemic venous chemoreceptors: might they explain the matching of breathing to metabolic rate in humans?

New Findings

  • What is the topic of this review?

    One of the major unanswered questions in physiology is that of how breathing matches metabolic rate. Venous chemoreceptors seem to have been dismissed since the 1960s.

  • What advances does it highlight?

    New evidence shows that their apparent dismissal needs reappraisal.

    • The paper on which this depends has more than one interpretation, and another paper obtained the opposite result.
    • Previous search ignored all locations between skeletal muscle and the right heart.
    • Oxygen sensors other than the arterial chemoreceptors do exist. Heymans and colleagues originally demonstrated some residual breathing response to hypoxia in sino-aortically denervated animals. Similar results occur in humans.

One of the major unanswered questions in physiology is that of how breathing matches metabolic rate. The existence in humans of venous chemoreceptors that might control breathing seems to have been dismissed since the 1960s. New evidence has emerged showing that this apparent dismissal needs reappraisal. Firstly, the paper in humans on which this depends has more than one interpretation. Moreover, a previous paper obtained the opposite result and is not cited. Secondly, previous search for venous chemoreceptors failed to examine all venous locations between skeletal muscle and the right heart and lungs. Thirdly, oxygen sensors other than the arterial chemoreceptors do exist. Heymans himself originally demonstrated some residual breathing response to hypoxia in sino-aortically denervated animals. Others confirm a residual breathing response to hypoxia in mammals, including humans. There is now considerable interest in the importance of afferent feedback in controlling the cardiovascular and respiratory systems. Moreover, it is now clear that arterial, aortic and central chemoreceptors have no role in explaining how breathing matches metabolic rate. These together provide a timely reminder that venous chemoreceptors remain ideal candidates still to be considered as metabolic rate sensors to explain matching in humans. Firstly, this is because venous inline image and inline image values do change appropriately in proportion to metabolic rate, so a metabolic rate signal sufficient to drive breathing might already exist. Secondly, chemoreceptor-like anatomical structures are present in the systemic venous system but remain unexplored. Finally, no extant experimental evidence precludes their existence.

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The comings and goings of the vagus and the need to know your neural fulcrum



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Single-incision laparoscopic cholecystectomy for gallbladder torsion: A case report and literature review

Abstract

We present a case of preoperatively diagnosed gallbladder torsion (GT) that was successfully treated by single-incision laparoscopic cholecystectomy. An 80-year-old woman presented with sudden pain and a palpable mass in the right upper quadrant. Contrast-enhanced CT revealed ischemic changes, a swollen gallbladder with a V-shaped distortion of the extrahepatic ducts, and the gallbladder in an abnormal anatomical position; clinical findings indicated GT. We performed single-incision laparoscopic cholecystectomy and intraoperatively found that the floating gallbladder was twisted counterclockwise by 180° around the cystic duct. After an uneventful postoperative course, the patient was discharged on postoperative day 7. Laparoscopic cholecystectomy for a GT was first performed in 1994, and since then, 28 cases, including ours, have been treated laparoscopically. Laparoscopic cholecystectomy for GT could be the standard treatment for this condition, and single-incision laparoscopic cholecystectomy may be a good surgical option for patients with GT because of its anatomical characteristics.



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Laparoscopic transabdominal preperitoneal repair for strangulated inguinal hernia

Abstract

Introduction

Laparoscopic transabdominal preperitoneal repair (TAPP) is widely accepted in elective inguinal hernioplasty. However, given the scarcity of data, the feasibility and safety of TAPP in strangulated hernia cases have not yet been determined.

Methods

We retrospectively evaluated the data from a consecutive series of 33 patients who had undergone surgery for acute strangulated inguinal hernia associated with suspected visceral ischemic damage by either TAPP (TAPP group, n = 11) or conventional open hernioplasty via the anterior approach (anterior group, n = 22).

Results

The TAPP group had a significant longer surgical duration than the anterior group (147 vs 84 min) and relatively less blood loss. Incision and enlargement of the hernial orifice, which enables easy reduction of the strangulated organ, was performed in the last 7 of 11 cases in the TAPP group. The morbidity was lower in the TAPP group, but the difference was not statistically significant (18% vs 23%). The TAPP group had a significantly shorter postoperative hospital stay than the anterior group (7 vs 10 days).

Conclusion

For surgeons with sufficient knowledge of the anatomy and expertise in reducing the strangulated organ, TAPP for strangulated inguinal hernia is at least comparable to open hernioplasty via the anterior approach in short-term outcomes.



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Correlation between the pain numeric rating scale and the 12-item WHO Disability Assessment Schedule 2.0 in patients with musculoskeletal pain.

Objective: The aim of this study was to assess the correlation between pain severity measured on a numeric rating scale and restrictions of functioning measured with the WHO Disability Assessment Schedule (WHODAS 2.0). Patients and methods: This was a cross-sectional study of 1207 patients with musculoskeletal pain conditions. Correlation was assessed using Spearman's and Pearson tests. Results: Although all the Spearman's rank correlations between WHODAS 2.0 items and pain severity were statistically significant, they were mostly weak, with only a few moderate associations for 'S2 household responsibilities', 'S8 washing', 'S9 dressing', and 'S12 day-to-day work'. The correlation between the WHODAS 2.0 total score and pain severity was also moderate: 0.41 [95% confidence interval (CI): 0.36-0.45] for average pain and 0.42 (95% CI: 0.37-0.46) for worst pain. The correlation between the WHODAS 2.0 total score and pain level was also assessed using Pearson's product-moment correlation, yielding figures that were similar to Spearman's correlation: 0.42 (P

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New evidence for association of recessive IARS gene mutations with hepatopathy, hypotonia, intellectual disability and growth retardation

Thumbnail image of graphical abstract

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Coronary Capillary Blood Flow in a Rat Model of Congestive Heart Failure

The aim of this study is to explore the role of abnormal coronary microvasculature morphology and hemodynamics in the development of congestive heart failure (CHF). Methods: CHF was induced in rats by aortic banding, followed by ischemia/reperfusion and later aortic debanding. Polymerized casts of coronary vasculature were imaged under a Scanning Electron Microscope (SEM). Matrix Laboratory (MATLAB) software was used to calculate Capillary Structure Index (CSI), a measure of structural alignment also called Mean Vector Length (MVL), for 93 SEM images of coronary capillaries (CSI-> 1 perfect linearity, CSI-> 0 circular disarray). CSI was incorporated as a constant to represent tortuosity and non-laminar flow in Poiseuille's equation in order to estimate the differences in capillary blood flow rate, velocity, and resistance for CHF versus control. Results: The morphology of congestive heart failure capillaries is significantly disordered and tortuous compared to control (CSI 0.35 ± 0.02 for 61 images from 7 CHF rats, 0.58 ± 0.02 for 32 images from 7 control rats. p<0.01). Estimated capillary resistance in congestive heart failure is elevated by 173% relative to control, while blood flow rate and blood velocity are 56% and 43% slower than control. Capillary resistance increased 67% due to the significantly narrower capillary diameter in congestive heart failure, while it increased an additional 105% due to tortuosity. Conclusions: The significant structural abnormalities of CHF coronary capillaries may drastically stagnatehemodynamics in myocardium and increase resistance to blood flow. This could play a role in the development of CHF.



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Gravity outweighs the contribution of structure to passive ventilation-perfusion matching in the supine adult human lung

Gravity and matched airway/vascular tree geometries are both hypothesized to be key contributors to ventilation-perfusion (V/Q) matching in the lung, but their relative contributions are challenging to quantify experimentally. We used a structure-based model to conduct an analysis of the relative contributions of tissue deformation (the 'Slinky' effect), other gravitational mechanisms (weight of blood and gravitational gradient in tissue elastic recoil), and matched airway and arterial tree geometry to V/Q matching and therefore to total lung oxygen exchange. Our results showed that the heterogeneity in V and Q were lowest and the correlation between V and Q was highest when the only mechanism for V/Q matching was either tissue deformation or matched geometry. Heterogeneity in V and Q was highest and their correlation was poorest when all mechanisms were active (that is, at baseline). Eliminating the contribution of matched geometry did not change the correlation between V and Q at baseline. Despite the much larger heterogeneities in V and Q at baseline, the contribution of in-common (to V and Q) gravitational mechanisms provided sufficient compensatory V/Q matching to minimize the impact on oxygen transfer. In summary, this model predicts that during supine normal breathing under gravitational loading, passive V/Q matching is predominantly determined by shared gravitationally-induced tissue deformation, compliance distribution, and the effect of the hydrostatic pressure gradient on vessel and capillary size and blood pressures. Contribution from the matching airway and arterial tree geometries in this model is minor under normal gravity in the supine adult human lung.



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Pre-load Corrected Dynamic Starling Mechanism in Patients with Heart Failure with Preserved Ejection Fraction

The beat-to-beat dynamic Starling mechanism (DSM), the dynamic modulation of stroke volume (SV) due to breath-to-breath changes in left ventricular end-diastolic pressure (LVEDP), reflects ventricular-arterial coupling. The purpose of this study was to test whether LVEDP-SV relationship remained impaired in HFpEF patients after normalization of LVEDP. Right heart catheterization and model-flow analysis of the arterial pressure waveform were performed while preload was manipulated using lower body negative pressure to alter LVEDP. The DSM was compared at similar levels of LVEDP between HFpEF patients (N=10) and age-matched healthy controls (N=12): (HFpEF vs. controls: 10.9±3.8 vs. 11.2±1.3 mmHg, P=0.72). Transfer function analysis between diastolic pulmonary artery pressure (PAD) representing dynamic changes in LVEDP versus SV-index was applied to obtain gain and coherence of the DSM. The DSM gain was significantly lower in HFpEF patients than in the controls, even at a similar level of LVEDP (0.46±0.19 vs. 0.99±0.39 ml/m2/mmHg, P=0.0011). Moreover, the power spectral density of PAD, the input variability, was greater in the HFpEF group than the controls (0.75±0.38 vs. 0.28±0.26 mmHg2, P=0.003). Conversely, the power spectral density of SV-index, the output variability, was not different between the groups (P=0.77). There was no difference in the coherence, which confirms the reliability of the linear transfer function between the 2-groups (0.71±0.13 vs. 0.77±0.19, P=0.34). The DSM gain in HFpEF patients is impaired compared to age-matched controls even at a similar level of LVEDP, which may reflect intrinsic LV diastolic dysfunction and incompetence of ventricular-arterial coupling.



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Exercise Limitations in Heart Failure with Reduced and Preserved Ejection Fraction

The hallmark symptom of chronic heart failure (CHF) syndrome is severe exercise intolerance. Impaired perfusive and diffusive O2 transport are two of the major determinants of reduced physical capacity and lowered maximal O2 uptake (VO2max) in CHF patients. It has now become evident that this syndrome manifests two different phenotypic variations: heart failure with preserved or reduced ejection fraction (HFpEF and HFrEF, respectively). Unlike HFrEF, however, there is currently limited understanding of HFpEF pathophysiology leading to a lack of effective pharmacological treatments for this subpopulation. This brief review focuses on the disturbances within the O2 transport pathway resulting in limited exercise capacity in both HFpEF and HFrEF. Evidence from human and animal research reveals CHF-induced impairments in both perfusive and diffusive O2 conductances identifying potential targets for clinical intervention. Specifically, utilization of different experimental approaches in humans (e.g., small vs. large muscle mass exercise) and animals (e.g., intravital microscopy and phosphorescence quenching) has provided important clues to elucidating these pathophysiological mechanisms. Adaptations within the skeletal muscle O2 delivery-utilization system following established and emerging therapies (e.g., exercise training and inorganic nitrate supplementation, respectively) are discussed. Clarifying the underlying mechanisms of skeletal muscle dysfunction and exercise intolerance is necessary for the development and refinement of treatments for CHF patients.



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Case studies in physiology: The biomechanics of the fastest sprinter with a unilateral transtibial amputation

People have debated whether athletes with transtibial amputations should compete with non-amputees in track events despite insufficient information regarding how the use of running-specific prostheses affects athletic performance. Thus, we sought to quantify the spatio-temporal variables, ground reaction forces, and spring-mass mechanics of the fastest athlete with a unilateral transtibial amputation using an RSP to reveal how he adapts his biomechanics to achieve elite running speeds. Accordingly, we measured ground reaction forces during treadmill running trials spanning 2.87 to 11.55 m/s of the current male International Paralympic Committee T44 100 m and 200 m world record holder. To achieve faster running speeds, the present study's athlete increased his affected leg (AL) step lengths (p<0.001) through longer contact lengths (p<0.001), and his unaffected leg (UL) step lengths (p<0.001) through longer contact lengths (p<0.001) and greater stance average vertical ground reaction forces (p<0.001). Across running speeds, step time decreased for both legs (p<0.001) through shorter ground contact and aerial times (p<0.001). Unlike previous athletes with unilateral transtibial amputations, this athlete maintained constant AL and UL stiffness across running speeds (p≥0.569). Across speeds, AL step lengths were 8% longer (p<0.001) despite 16% lower AL stance average vertical ground reaction forces compared to the UL (p<0.001). The present study's athlete exhibited biomechanics that differed from those of athletes with bilateral and without transtibial amputations. Overall, we present the biomechanics of fastest athlete with a unilateral transtibial amputation across running speeds, providing insight into the functional abilities of athletes with transtibial amputations using running-specific prostheses.



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Parenchymal Strain Heterogeneity During Oscillatory Ventilation: Why Two Frequencies are Better than One

High frequency oscillatory ventilation (HFOV) relies on low tidal volumes cycled at supraphysiologic rates, producing fundamentally different mechanisms for gas transport and exchange compared with conventional mechanical ventilation. Despite the appeal of using low tidal volumes to mitigate the risks of ventilator-induced lung injury (VILI), HFOV has not improved mortality for most clinical indications. This may be due to non-uniform and frequency-dependent distribution of flow throughout the lung. The goal of this study was to compare parenchymal strain heterogeneity during eucapnic HFOV when using oscillatory waveforms that consisted of either a single discrete frequency or two simultaneous frequencies. We utilized on a three-dimensional, anatomically-structured canine lung model for simulating frequency-dependent ventilation distribution. Gas transport was simulated via direct alveolar ventilation, advective mixing at bifurcations, turbulent and oscillatory dispersion, and molecular diffusion. Volume amplitudes at each oscillatory frequency were iteratively optimized to attain eucapnia. Ventilation using single-frequency HFOV demonstrated increasing heterogeneity of acinar flow and CO2 elimination with frequency, for frequencies greater than the resonant frequency. For certain pairs of frequencies, a linear combination of the two corresponding ventilation distributions yielded reduced acinar strain heterogeneity compared to either frequency alone. Our model demonstrates that superposition of two simultaneous oscillatory frequencies can achieve more uniform ventilation distribution, and therefore lessen the potential for ventilator-induced lung injury, compared to traditional single-frequency HFOV.



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The occurrence of cardiac output decrease (via stroke volume) is more pronounced in women than in men during prolonged dry static apnoea.

Little is known on gender differences in autonomic cardiovascular regulation of diving response (DR) and the few available studies into these differences were conducted on subjects with limited or no diving experience. We examined gender influence on hemodynamics during dry-static apnoea (SA) in 8 male and 8 female elite divers matched for their breath-hold (BH) ability. Hemodynamics was assessed by means of simultaneous echocardiography and impedance cardiography measurements and arterial pressure and oxygen saturation (SaO2) were also collected. In the first quarter (AP25%) and half (AP50%) of apnoea duration cardiac output (CO) showed a more rapid and intense decrease in females than males (-43% vs. -17% during AP25% and -40% vs. -19% during AP50% respectively, P<0.05). At the same time, points systemic vascular resistance (SVR) increased more in women than in men (+22% vs. +100% at AP25% and +48% vs. +107% at AP50% respectively, P<0.05). SaO2 progressively declined in both groups but males showed a more pronounced decrease than females at the end of apnoeas (-13% vs. -5% respectively, P<0.05). In men, the higher the BSA values the longer the apnoeas, whilst in women, the higher the SVR response the longer the apnoea. In elite female divers, the magnitude of CO decrease during dry static apnoea was larger than in males. Both the capacity to store oxygen and to reduce O2 consumption play a pivotal role in BH performance but their extent seems to be different in genders.



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Molecular Basis of Overdominance at a Flower Color Locus

Single-gene overdominance is one of the major mechanisms proposed to explain heterosis (i.e., hybrid vigor), the phenomenon that hybrid offspring between two inbred lines or varieties show superior phenotypes to both parents. Although sporadic examples of single-gene overdominance have been reported over the decades, the molecular nature of this phenomenon remains poorly understood and it is unclear whether any generalizable principle underlies the various cases. Through bulk segregant analysis, chemical profiling, and transgenic experiments, we show that loss-of-function alleles of the FLAVONE SYNTHASE (FNS) gene cause overdominance in anthocyanin-based flower color intensity in the monkeyflower species Mimulus lewisii. FNS negatively affects flower color intensity by competing with the anthocyanin biosynthetic enzymes for the same substrates, yet positively affects flower color intensity by producing flavones, the colorless co-pigments required for anthocyanin stabilization, leading to enhanced pigmentation in the heterozyote (FNS/fns) relative to both homozygotes (FNS/FNS and fns/fns). We suggest that this type of antagonistic pleiotropy (i.e., alleles with opposing effects on different components of the phenotypic output) might be a general principle underlying single-gene overdominance.



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The Effect of Tackler Technique on Head Injury Assessment Risk in Elite Rugby Union.

Purpose: To use match video evidence of tackles in elite level rugby union in order to identify tackler proficiency characteristics, for both Lower Body and Upper Body Tackles, that result in Head Injury Assessments (HIA) for the tackler. Methods: A review of international rugby union matches (2013-2016) and Pro 12/ERC Champions Cup matches (2014-2016) from a professional rugby union club was conducted. HIA (n=53) and non-HIA tackles (n=233) were categorised as either front-on or side-on Upper Body or Lower Body Tackles and scored for tackling proficiency characteristics. A Chi-Square test (p

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Sensitive Timing for Risk of Overweight Among Infants of Low-Income Hispanic Immigrants

This study examined the association between early weight gain (0–6 months) and risk for overweight, as defined by the Institute of Medicine, at 1 year among infants of low-income Hispanic immigrant mothers.

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Sleep Characteristics in Mothers of Children With Developmental Disabilities

Impaired sleep can contribute to conditions such as cardiometabolic disorders, depression, and decreased immune function. Mothers of children with developmental disabilities (DDs) may be at greater risk for impaired sleep due to the sleep problems of their children. This cross-sectional study described the self-reported sleep characteristics of mothers of children (ages 6-12) with DDs by using a sleep diary and the Pittsburgh Sleep Quality Index (PSQI) as quantitative and qualitative measures of sleep in these mothers.

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Factors associated with post-stroke physical activity: a systematic review and meta-analysis

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Publication date: Available online 19 October 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Shamala Thilarajah, Benjamin F. Mentiplay, Kelly J. Bower, Dawn Tan, Pua Yong Hao, Gavin Williams, Gerald Koh, Ross A. Clark
ObjectiveTo integrate the literature investigating factors associated with post-stroke physical activity.Data SourcesA search was conducted from database inception to June 2016 across nine databases: Cochrane, Medline, ProQuest, Web of Science ISI, PsycInfo, Scopus, Embase, CINAHL and AMED. The reference lists of included articles were screened for secondary literature.Study selectionCohort and cross-sectional studies were included if they recruited community-dwelling stroke survivors and measured factors associated with physical activity.Data ExtractionRisk of bias was evaluated using the Quality in Prognosis Studies checklist. A meta-analysis was conducted for correlates where there were at least two studies that reported a correlation value. Correlation values were used in an effect size measure and converted to a standardised unit with Fisher r to z transformation and conversion back to r method. Results were described qualitatively for studies that could not be pooled.Data Synthesis2161 studies were screened and 26 studies were included. Age (meta r=-0.17; p=<0.001) and gender (meta r=-0.01; p=0.02) were the non-modifiable factors that were found to be associated with post-stroke physical activity. The modifiable factors were physical function (meta r=0.68-0.73; p<0.001), cardiorespiratory fitness (meta r=0.35; p=<0.001), fatigue (meta r=-0.22; p=0.01), falls self-efficacy (meta r=-0.33; p<0.001), balance self-efficacy (meta r=0.37; p<0.001), depression (meta r=-0.58-0.48; p<0.001) and health-related quality of life (meta r=0.38-0.43; p<0.001). The impact of side of infarct, neglect and cognition on post-stroke physical activity were inconclusive.ConclusionsAge, gender, physical function, depression, fatigue, self-efficacy and quality of life were factors associated with post-stroke physical activity. The cause and effect of these relationships are unclear and the possibility of reverse causality needs to be addressed.



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Long-term outcomes of endoscopic submucosal dissection in comparison to surgery in undifferentiated-type intramucosal gastric cancer using propensity score analysis

Abstract

Background

The treatment of intramucosal early gastric cancer with undifferentiated-type histologies (UD-EGCs) using endoscopic submucosal dissection (ESD) is controversial. This study aimed to compare the clinical and oncologic long-term outcomes of ESD and surgery for UD-EGCs.

Methods

A prospectively collected database of patients who underwent ESD or surgery between January 2006 and December 2012 was established. Patients who diagnosed with UD-EGC and satisfied the expanded indications of ESD were included. Clinical data from 111 patients treated with ESD and 382 patients underwent surgery were analyzed, and 1–1 propensity score-matched 81 pairs of patients were also compared.

Results

In both groups, two-thirds of the UD-EGCs had signet ring cell (SRC)-type histology and about 90% of UD-EGCs were flat or depressed types. The mean size of tumors was smaller in ESD group (9.7 vs. 13.2 mm; P < 0.001). After propensity score-matched, case-matching covariates were not significantly different between the groups. Disease-free survival (DFS) was significantly shorter in the ESD group, but overall survival (OS) was not different between the two groups both in overall comparison (DFS; P < 0.001 and OS; P = 0.078) and propensity score-matched analysis (DFS; P < 0.001 and OS; P = 0.850). According to histologic type, OS of SRC histology was not different between the group, both in overall comparison and propensity score-matched analysis (P = 0.286 and P = 0.210). On the other hands, OS of poorly differentiated adenocarcinoma was significantly shorter in ESD group in overall comparison (P = 0.007), but was not as so in propensity score-matched analysis (P = 0.088).

Conclusions

ESD might be a complementary option for the treatment of UD-EGCs, especially in those with SRC-type histology based on strict expanded indications. Nonetheless, close endoscopic surveillance is required because of a high incidence of intragastric recurrence.



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Validation of the VBLaST pattern cutting task: a learning curve study

Abstract

Background

Mastery of laparoscopic skills is essential in surgical practice and requires considerable time and effort to achieve. The Virtual Basic Laparoscopic Skill Trainer (VBLaST-PC©) is a virtual simulator that was developed as a computerized version of the pattern cutting (PC) task in the Fundamentals of Laparoscopic Surgery (FLS) system. To establish convergent validity for the VBLaST-PC©, we assessed trainees' learning curves using the cumulative summation (CUSUM) method and compared them with those on the FLS.

Methods

Twenty-four medical students were randomly assigned to an FLS training group, a VBLaST training group, or a control group. Fifteen training sessions, 30 min in duration per session per day, were conducted over 3 weeks. All subjects completed pretest, posttest, and retention test (2 weeks after posttest) on both the FLS and VBLaST© simulators. Performance data, including time, error, FLS score, learning rate, learning plateau, and CUSUM score, were analyzed.

Results

The learning curve for all trained subjects demonstrated increasing performance and a performance plateau. CUSUM analyses showed that five of the seven subjects reached the intermediate proficiency level but none reached the expert proficiency level after 150 practice trials. Performance was significantly improved after simulation training, but only in the assigned simulator. No significant decay of skills after 2 weeks of disuse was observed. Control subjects did not show any learning on the FLS simulator, but improved continually in the VBLaST simulator.

Conclusions

Although VBLaST©- and FLS-trained subjects demonstrated similar learning rates and plateaus, the majority of subjects required more than 150 trials to achieve proficiency. Trained subjects demonstrated improved performance in only the assigned simulator, indicating specificity of training. The virtual simulator may provide better opportunities for learning, especially with limited training exposure.



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Robotic ventral hernia repair is not superior to laparoscopic: a national database review

Abstract

Background

Minimally invasive surgery (MIS) use for ventral hernia repair has increased over the last decade. Whether outcomes are improved by robotic assistance remains a subject of debate. The aim of this study is to evaluate outcomes (including cost, complications, length of stay (LOS), and pain medication utilization) in patients who underwent an open (OVHR), laparoscopic (LVHR), or robotic (RVHR) ventral hernia repair (VHR).

Methods

The Vizient database was queried using ICD-9 procedure and diagnosis codes for patients who underwent VHR from January 2013 to September 2015. Complications, 30-day readmission, mortality, LOS, cost, and intra-hospital opiate utilization were analyzed using IBM SPSS v.23.0.0.0. Median tests with post hoc pairwise comparisons, Fischer's exact, and Pearson's chi-squared test with Bonferroni correction were applied where appropriate, with α = 0.05.

Results

46,799 patients (OVHR: N = 39,505, LVHR: N = 6829, RVHR: N = 465) met the criteria and patients in each group had similar demographics (Table 1). OVHR was associated with significant increased overall complications, 30-day readmission, LOS, and postoperative pain use compared to RVHR or LVHR. OVHR had higher mortality and postoperative infection rates than LVHR. RVHR had significantly higher rates of complications and postoperative infections compared to LVHR, although there was no difference in mortality, 30-day readmission, LOS, and postoperative pain medication use. Mean direct cost of surgery was significantly higher for RVHR, followed by OVHR and LVHR.

Conclusions

Overall patient outcomes were improved in the LVHR and RVHR groups compared to the open approach. However, RVHR patients did not have significant improvement compared with the LVHR group in either short-term outcomes or opiate medication used. While RVHR surgery was the most expensive modality, OVHR was also significantly costlier than LVHR, which was the least expensive. Long-term data on recurrence could not be evaluated and should be studied to determine the role of robotic surgery in VHR and recurrence rates.



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Long-term clinical outcomes after intrathoracic stomach surgery: a decade of longitudinal follow-up

Abstract

Background

A subset of patients with large paraesophageal hernias have more than 75% of the stomach herniated above the diaphragm; such cases are referred to as intrathoracic stomach (ITS). Herein, we report longitudinal symptomatic outcomes over a decade after surgical ITS repair in a large patient cohort.

Methods

Patients who underwent surgical treatment for ITS from 01/2004 to 05/2016 were studied. Preoperative and follow-up data were prospectively collected. Patients completed a standardized symptom questionnaire 1 year postoperatively and at 2-year intervals thereafter.

Results

In total, 235 patients were reviewed. The mean age was 70.0 ± 11.6 years; 174 patients (74.0%) were women. Surgical procedures included 7 transthoracic repairs and 228 transabdominal repairs (222 laparoscopic, 2 open, 4 laparoscopic-to-open conversions). Anti-reflux procedures were performed in 173 patients (73.6%). 33 patients (14.0%) had mesh reinforcement of hiatal closure; 11 (4.7%) underwent Collis gastroplasty. Follow-up symptom questionnaires at 1, 3, 5, 7, 9, and 11 years were available for 81, 48, 47, 30, 33, and 38% of patients, respectively. Significant and lasting symptom improvement was reported at all follow-up time points. Mean satisfaction scores of 9.3, 9.1, 9.3, 9.0, 9.5, and 9.8 on a 1–10 scale were recorded at the aforementioned intervals.

Conclusions

Long-term clinical outcomes confirm that laparoscopic ITS repair is safe and durable, and is associated with a high degree of patient satisfaction and symptom resolution.



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A Systematic review and meta-analysis of the efficacy and safety of video-assisted anal fistula treatment (VAAFT)

Abstract

Background

Video-assisted anal fistula treatment (VAAFT) is a novel, minimally invasive technique for the treatment of fistula-in-ano (FIA). This review aimed to search the literature for the outcome of VAAFT regarding the recurrence and complication rates of the technique.

Methods

A systematic literature search was conducted in compliance with the PRISMA screening guidelines. PubMed/MEDLINE and Scopus were searched for articles reporting the outcomes of VAAFT procedure from inception through April 2017. The main outcomes were patients' characteristics, technical aspects, operation time, recurrence, and complication rates.

Results

Eleven studies (n = 788 patients) were included. The mean age of the patients was 39.5 years. 66.5% of patients had high or complex FIA and 18.4% underwent previous fistula surgery. The internal opening of the fistula was detected in 85.7% of patients. The mean operation time was 42 ± 14.2 min. The weighed mean rate of detection of internal opening was 93.3%. Recurrence occurred in 112 (14.2%) patients after a median follow-up of 9 months. Recurrence rates varied according to method of closure of internal opening from 15.3% after using staplers, 17.7% after suturing, to 25% after advancement flap. The weighted mean recurrence rate across the studies was 17.7%. The weighted mean complication rate was 4.8%.

Conclusion

VAAFT may be considered an effective diagnostic tool and a safe method for the treatment of complex and high FIA attaining satisfactory outcome and acceptably low complications. Recurrence after VAAFT may be related to previous fistula surgery and the method of closure of the internal opening.



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Determinants of variability in management of acute calculous cholecystitis

Abstract

Background

While evidence supports early compared to delayed cholecystectomy as optimal management of acute calculous cholecystitis (ACC), significant variability in practice remains. The purpose of this study was to identify variables associated with early cholecystectomy, to target opportunities to improve adherence to best practices.

Methods

Adult patients admitted to surgical units with ACC at two hospitals in a university hospital network between June 2010 and January 2015 were reviewed. Patients with concurrent pancreatitis, cholangitis or severe ACC (with organ system failure) were excluded. Early cholecystectomy was defined as surgery performed during same admission and within 7 days of presentation. Non-operative management was defined as admission for ACC treated conservatively, with or without eventual delayed cholecystectomy. The primary outcome was early cholecystectomy versus initial non-operative management; secondary outcomes included time to cholecystectomy, complications, and total hospital length of stay (LOS).

Results

A total of 374 patients were included. Two hundred and forty six patients (66%) underwent early cholecystectomy, 60 (16%) were treated non-operatively and had delayed cholecystectomy, and 68 (18%) were only treated non-operatively. Median time to OR from initial presentation was 38 h [22–63] for early cholecystectomy patients and 69 days [29–116] for the non-operative patients who had delayed cholecystectomy. When comparing both groups, early cholecystectomy patients were younger and were treated more often at site 1. There were no differences in complications during hospitalization, but early cholecystectomy patients had a lower median total LOS (3 [2–5] vs. 5 [4–9], p < 0.001), and they had fewer gallstone-related events after discharge (1 vs. 18%, p < 0.001). On multiple logistic regression analysis, lower age, hospital site and lower risk of concurrent choledocholithiasis were all significantly associated with early cholecystectomy (p < 0.05).

Conclusion

Our data supports early cholecystectomy as best practice in management of ACC with no differences in complications during hospitalization, shorter median LOS and fewer gallstone-related events compared to non-operative management. We identified patient and institutional factors associated with early cholecystectomy. This suggests that multiple strategies will be necessary to promote adherence to best practices in the management of ACC within our institution.



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The feasibility of laparoscopic rectal resection in patients undergoing reoperation after transanal endoscopic microsurgery (TEM)

Abstract

Background

The success of transanal endoscopic microsurgery (TEM) for early rectal cancer depends on proper indications and strict patient selection. When unfavorable pathologic features are identified after TEM operation, total mesorectal excision is recommended to minimize the risk of recurrence. In this study, data were collected in a retrospective series of patients to determine the results of laparoscopic reoperation after TEM.

Methods

All patients underwent an accurate rectal-digital examination and clinical tumor staging by transanal endosonography, CT, and/or MRI. The histologic examination included an evaluation of the free margins, depth of tumor infiltration according to International Union Against Cancer guidelines, degree of tumor differentiation, and the presence of lymphovascular and perineural invasion. When a high-risk tumor was identified, reoperation was performed within 6 weeks from TEM. The patients were divided into two groups according to the procedure performed: laparoscopic anterior resection (LAR) or laparoscopic abdominal perineal amputation (LAPR).

Results

Sixty-eight patients (5.3%) underwent reoperation: 38 underwent LAR and 30 underwent LAPR. The mean operative time was 148.24 min (± 35.8, p = 0.62). Meanwhile, the mean distance of the TEM scar from the anal verge differed statistically between the two groups (p = 0.003) and was statistically correlated with abdominal perineal amputation (p = 0.0001) in multivariate analysis. Conversion to open surgery was required in 6 patients (15.7%) in the LAR group and 3 patients (10%) in the LAPR group (p = 0.38). The histologic examination revealed residual cancer cells in 3 cases (3 pT2N0) and 1 case (1 pT3N0), respectively, and lymph node metastases in 4 cases. No residual neoplasms were detected in the remaining 60 cases (88.3%). After a mean follow-up of 108 months, the overall disease-free survival was 98% (95% CI 88–99%).

Conclusions

In our experience, reoperation after TEM using a laparoscopic approach is feasible and safe, with low conversion rates and optimal postoperative results.



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Endoscopic treatment of leaks after laparoscopic sleeve gastrectomy using MEGA esophageal covered stents

Abstract

Background

Sleeve gastrectomy has become one of the main bariatric procedures over the last few years. This can be explained by the relative simplicity and high effectiveness of this method. Yet, it causes complications as any other method. Staple line leaks are the most frequent ones. According to different sources, this complication may occur with 0–7% frequency. Until 2013, surgery was the only effective treatment method for this complication. However, reoperations considerably increased treatment cost and patient morbidity. The aim of this study is to present the possibilities of endoscopic treatment of leaks after laparoscopic sleeve gastrectomy.

Methods

From 2014 to 2016 14, cases of leaks following sleeve gastrectomy were diagnosed in our Department in Łódź. All of them were treated with MEGA stent in order to cover the leak site. Due to severe peritonitis, 3 patients had to undergo surgery prior to implantation of the prosthesis. Another patient underwent an unsuccessful attempt of leak closing via OTSC method prior to implantation of the prosthesis. Patients were nourished from the 3rd day after the surgery. On average, prostheses were removed on the 34th day after the implantation.

Results

The leak was fully sealed in 13 out of 14 cases. In 10 cases the leak was fully healed. There were 2 cases of patients' deaths: the result of a multi-organ failure in one case and early esophageal perforation in the other one. The overall success rate was 90.9%.

Conclusion

Sealing leaks occurring after sleeve gastrectomy with MEGA stents represent an effective method and should become the technique of choice.



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Comparison of two new techniques for the management of malignant central airway obstruction: argon plasma coagulation with mechanical tumor resection versus cryorecanalization

Abstract

Background

The development of central airway obstruction during malignant diseases is an important cause of morbidity and mortality. Endobronchial therapies can decrease the patient's symptoms and improve quality of life. Here, we compare airway recanalization methods: argon plasma coagulation with mechanical tumor resection (APC + MTR) and cryorecanalization (CR efficiency, complications, restenosis rate, and time to restenosis) in patients with malignant exophytic endobronchial airway obstruction.

Methods

A total of 89 patients were included who were admitted to our hospital between 2005 and 2012. The data were analyzed retrospectively. Initially, a CR procedure was performed in 52 patients using rigid bronchoscopy under general anesthesia; the APC + MTR procedure was performed in 37 patients with malignant airway obstruction.

Results

The airway patency rate with APC + MTR was 97.3% (n = 36) and CR was 80.8% (n = 42). The APC + MTR procedure was more effective than CR for recanalization of malignant endobronchial exophytic airway obstruction. Additionally, the achievement rate of airway patency with APC + MTR was significantly higher in tumors with distal bronchial involvement. There was no statistically significant difference between groups in terms of complications, restenosis rate, and time to restenosis.

Conclusions

The APC + MTR procedure is preferred over CR to introduce and maintain airway patency in patients with malignancy-related endobronchial exophytic airway obstruction.



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Robotic single-site versus multiport laparoscopic cholecystectomy: a case-matched analysis of short- and long-term costs

Abstract

Background

Multiport laparoscopy is the gold-standard approach for cholecystectomy, and single-port laparoscopy has been developed to further reduce its invasiveness. A specific robotic single-port platform (da Vinci single-site, Intuitive Surgical Inc., Sunnyvale, CA, USA) has been released in 2011, which could technically facilitate single-site cholecystectomy. Current data show its feasibility; however, detailed short- and long-term analyses of costs and comparisons relative to multiport laparoscopy are not available to date.

Methods

Patients who underwent robotic single-site cholecystectomy for benign, clinically noninflammatory disease between 2011 and 2015 were matched for disease, age, gender, BMI, ASA classification, diagnosis, and elapsed year of surgery to a cohort of multiport cholecystectomies. Demographic, perioperative, and long-term data were collected retrospectively and analyzed. Perioperative and long-term costs including re-operations due to the primary procedure until February 2017 were compared across both cohorts.

Results

99 patients who underwent robotic single-site cholecystectomy were matched to 99 patients with multiport cholecystectomy. A higher rate of outpatient procedures in the robotic cohort (31.3 vs. 17.2%, p = 0.0305) was found, and demographic parameters and perioperative clinical outcomes were similar. Perioperative costs were significantly higher for the robotic single-site patients (6158.0 vs. 4288.0 USD, p < 0.0001). With similar follow-up times of 59.0 and 58.9 months, respectively (p = 0.9552), significantly more patients of the robotic Single-Site cohort underwent follow-up surgery (7.1 vs. 0.0%, p = 0.0140), and follow-up costs were significantly higher for the robotic cohort (694.7 vs. 0.0 USD, p = 0.0145).

Conclusion

With similar early postoperative clinical results and a higher rate of re-operations, perioperative and long-term costs are significantly higher with robotic Single-Site cholecystectomy compared with multiport cholecystectomy. Considering the unclear clinical value of robotic single-site cholecystectomy and the significant short- and long-term costs, a call for further research and a debate as to who should bear the costs beyond the ones of the gold-standard treatment appear reasonable.



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Concomitant open ventral hernia repair: what is the financial impact of performing open ventral hernia with other abdominal procedures concomitantly?

Abstract

Background

Open ventral hernia repair (VHR) is often performed in conjunction with other abdominal procedures. Clinical outcomes and financial implications of VHR are becoming better understood; however, financial implications of concomitant VHR during other abdominal procedures are unknown. This study aimed to evaluate the financial implications of adding VHR to open abdominal procedures.

Methods

This IRB-approved study retrospectively reviewed hospital costs to 180-day post-discharge of standalone VHRs, isolated open abdominal surgeries (bowel resection or stoma closure, removal of infected mesh, hysterectomy or oophorectomy, panniculectomy or abdominoplasty, open appendectomy or cholecystectomy), performed at our institution from October 1, 2011 to September 30, 2014. The perioperative risk data were obtained from the local National Surgery Quality Improvement Program (NSQIP) database, and resource utilization data were obtained from the hospital cost accounting system.

Results

345 VHRs, 1389 open abdominal procedures as described, and 104 concomitant open abdominal and VHR cases were analyzed. The VHR-only group had lower ASA Class, shorter operative duration, and a higher percentage of hernias repaired via separation of components than the concomitant group (p < 0.001). The median hospital cost for VHR-alone was $12,900 (IQR: $9500–$20,700). There were significant increases to in-hospital costs when VHR was combined with removing an infected mesh (63%) or with bowel resections or stoma closures (0.7%). The addition of VHR did not cause a significant change in 180-day post-discharge costs for any of the procedures.

Conclusions

This study noted decreased costs when combining VHR with panniculectomy or abdominoplasty and hysterectomy or oophorectomy. For removal of infected mesh and bowel resection or stoma closure, waiting, when feasible, is recommended. Given the impending changes in financial reimbursements in healthcare in the United States, it is prudent that future studies evaluate further the clinical and fiscal benefit of concomitant procedures.



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Laparoscopy for primary cytoreduction with multivisceral resections in advanced ovarian cancer: prospective validation. “The times they are a-changin”?

Abstract

Background

Primary cytoreduction is the mainstay of treatment for advanced ovarian cancer (AOC). We developed and prospectively evaluated an algorithm to investigate the possible role of laparoscopic primary cytoreduction (LPC) in carefully selected patients, with AOC.

Methods

From June 2007 to July 2015, all patients with stage III–IV ovarian cancer and clinical conditions allowing aggressive surgery were candidate to primary cytoreduction with the aim of achieving residual tumor (RT) = 0. The possibility of attempting laparoscopic cytoreduction was carefully evaluated using strict selection criteria. The other patients were approached by abdominal primary cytoreduction (APC). At the end of LPC, an ultra-low pubic mini-laparotomy was performed to extract surgical specimens and to accomplish a laparoscopic hand-assisted exploration of the abdominal organs, in order to confirm complete excision of the disease.

Results

Of the included 66 patients, 21 were considered eligible for LPC; the remaining 45 underwent APC. Optimal cytoreduction (i.e., RT = 0) was obtained in 95 and 88.4% in the LPC and APC groups, respectively. No intra-operative complication and 4 (19%) early post-operative complications were observed among patients who received LPC. Patients who underwent APC had 17.8 and 46.7% intra- and early post-operative complications, respectively. Median time to initiation of chemotherapy was 15 (range, 10–30) days in the LPC group and 28 (20–35) days in the APC group. After a median follow-up of 51 months, 2-year disease-free survival was 76.2% in the LPC group and 73.4% in the APC group.

Conclusions

After strict selection, a group of patients with AOC may undergo LPC with extremely high rates of optimal cytoreduction, satisfactory perioperative morbidity, a short interval to chemotherapy, and encouraging survival outcomes.

Clinical trial registration NCT02980185



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How much pain relief do patients expect after cholecystectomy?

Abstract

Background

Cholecystectomy is a common operation, increasingly performed, in the USA, for "functional gall bladder disorder" (FGBD). Outcomes of these surgeries are uncertain. In planning a study of FGBD, we needed to define the best outcome measures.

Methods

We sought the opinions of patients (52 with FGBD and 100 with stones for comparison) coming to cholecystectomy. They were asked to respond in four ways about the minimum benefit they would count as "success."

Results

We found that most patients do not expect cholecystectomy to relieve their pain-related disability completely, regardless of the presence or absence of stones.

Conclusions

Future studies of the success of surgery should use patient-centered outcome assessments, such as PGIC (patient's global impression of change), in addition to objective measures of the impact of treatment on key symptoms, such as pain.



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Endoscopic biliary stenting for unresectable malignant hilar obstruction

Abstract

Palliative drainage is the primary treatment option for unresectable malignant hilar biliary obstruction (UMHBO) to improve the prognosis and quality of life. Currently, endoscopic biliary drainage is considered as a first-line treatment for UMHBO as well as for distal biliary obstruction. Self-expanding metal stents (SEMSs) are preferred over plastic stents (PSs) in patients with life expectancy of >3 months. However, endoscopic treatment of UMHBO is often more challenging and complex than that of distal biliary obstruction. Although no consensus exists on the optimal method for biliary drainage because of the lack of well-designed, large-scale randomized control trials, several essential aspects of various optimal methods have been studied. Presently, technological developments in this field are under way and newly designed or modified stenting devices for UMHBO are being developed. In this review, we assess the optimal stenting strategy for UMHBO based on the previous literature, focusing on the stent type (PS vs SEMS), the liver volume to be drained, unilateral (single) vs bilateral (multiple) stent deployment, and bilateral stenting method (stent-in-stent vs side-by-side).



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A reliability and validity study for different coronal angles using ultrasound imaging in adolescent idiopathic scoliosis

Radiation exposure remains a big concern in adolescent idiopathic scoliosis (AIS). Ultrasound imaging of the spine could significantly reduce or possibly even eliminate this radiation hazard. The spinous processes (SP) and transverse processes (TP), were used to measure the coronal deformity. Both landmarks provided reliable information on the severity of the curve as related to the traditional Cobb angle. However, it remained unclear which coronal ultrasound angle is the most appropriate method to measure the curve severity.

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Risk factors and pharmacologic prophylaxis for venous thromboembolism in elective spine surgery

Venous thromboembolism (VTE) is a known complication after spine surgery, but prophylaxis guidelines are ambiguous for patients undergoing elective spine surgery.

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Can the Relationship between Pelvic Incidence, Pelvic Tilt and Sacral Slope be Affected by Changing Pelvic Position?

BACKGROUND CONTEXT: It is typically accepted that pelvic incidence (PI) is fixed for an individual, but recent evidence suggests it may change with age and sagittal pelvic rotation. Our previous research data, taken from measures with a healthy population, supports the latter. If PI, which is composed of pelvic tilt (PT) and sacral sulcus (SS), is not fixed, then PT and/or SS must also be changing. The relationship between these parameters that occurs with pelvic movement has not been studied.

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Declining Trends in Primary and Revision Laminectomy Surgeries in the United States from 2006 to 2014

BACKGROUND CONTEXT: Given the increasing focus on health care utilization and value-based care, it is essential to determine the number and trends in primary and revision laminectomies per year throughout the United States. Patient demographics and economic data associated with primary and revision laminectomy cases is critical to understanding and improving optimal health care utilization.

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Clinical impact of endoscopic ultrasonography on the management of neuroendocrine tumors: lights and shadows

The incidence of gastroenteropancreatic neuroendocrine neoplasms has increased in the recent decades.An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature (retrospective and prospective studies, systematic reviews, case series) published mostly between year 1997 and June 2017, using both medical subject heading (MeSH) terms and free-language keywords about the accuracy and diagnostic and therapeutic role of endoscopic ultrasound in the context of gastro-entero-pancreatic neuroendocrine neoplasms.

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Histological Features of Ileitis Differentiating Pediatric Crohn Disease From Ulcerative Colitis with Backwash Ileitis

Pediatric ileocolonic Crohn disease (CD) may be difficult to distinguish from ulcerative colitis (UC) with backwash ileitis (BWI). The primary aim of the study was to determine the probability of CD in children with a confluent colitis and ileitis when newly diagnosed with inflammatory bowel disease (IBD).

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Clinical impact of endoscopic ultrasonography on the management of neuroendocrine tumors: lights and shadows

The incidence of gastroenteropancreatic neuroendocrine neoplasms has increased in the recent decades.An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature (retrospective and prospective studies, systematic reviews, case series) published mostly between year 1997 and June 2017, using both medical subject heading (MeSH) terms and free-language keywords about the accuracy and diagnostic and therapeutic role of endoscopic ultrasound in the context of gastro-entero-pancreatic neuroendocrine neoplasms.

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Histological Features of Ileitis Differentiating Pediatric Crohn Disease From Ulcerative Colitis with Backwash Ileitis

Pediatric ileocolonic Crohn disease (CD) may be difficult to distinguish from ulcerative colitis (UC) with backwash ileitis (BWI). The primary aim of the study was to determine the probability of CD in children with a confluent colitis and ileitis when newly diagnosed with inflammatory bowel disease (IBD).

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Cryoconites from Alpine glaciers: Radionuclide accumulation and age estimation with Pu and Cs isotopes and 210Pb

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Publication date: Available online 19 October 2017
Source:Journal of Environmental Radioactivity
Author(s): T. Wilflinger, H. Lettner, A. Hubmer, P. Bossew, B. Sattler, H. Slupetzky
Cryoconites ("cold dust", derived from the Greek) are aeolian sediments accumulated on glacier surfaces. In cryoconites from the surface of the Stubacher Sonnblickkees, a temperate Austrian glacier, extremely high activity concentrations of artificial and natural radionuclides were found. Artificial radionuclides stem from two clearly distinguishable sources, global fallout from the nuclear weapons testing era deposited over a period of years until roughly 1966 and the fallout from Chernobyl in 1986, which was essentially deposited as a single input during one week. Anthropogenic radionuclides identified were 137Cs, 134Cs, 238Pu, 239+240Pu, 90Sr, 241Am, 60Co, 125Sb, 154Eu, and 207Bi. The naturally occurring radionuclides detected were the long-lived radon decay product 210Pb, the primordial radionuclide 4 K and the cosmogenic 7Be.Isotopic ratios of 134Cs/137Cs and 239+240Pu/238Pu were used to separate the nuclide inventory into the contributions of the two aforementioned sources, which show varying degrees of mixing and provide information on the mixing age of the cryoconites. Since isotopic ratios of Pu often have high uncertainties due to low absolute concentrations, age estimation based on this method can be quite inaccurate. Additional information about the age of cryoconites was obtained through analysis of 210Pb, which is constantly deposited over time.



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What EMS leaders, educators can learn from continuing education data

LAS VEGAS — More than 8.7 million continuing education completion records revealed that nationally certified EMS providers complete more CE than state only certified providers, hundreds of thousands of courses are completed after a provider's certification has expired and virtual instructor led training represents only one percent of EMT and paramedic refresher course. The data behind these ...

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Relationships, excellence and caring: The components of an EMS provider

By Kerri Hatt, EMS1 Senior Editor The Clark County Fire Department, law enforcement and EMS providers did not expect a MCI impacting 22,000 people, with more than 400 shot from above as thousands fled the scene. And yet, they had prepared – through training, and through building relationships between agencies. The Las Vegas shooting that occurred ...

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Successful chemotherapy with modified FOLFIRINOX for pancreatic acinar cell carcinoma

Abstract

Abdominal ultrasonography revealed a pancreatic mass in a 67-year-old man with diabetes mellitus. Endoscopic ultrasound-guided fine needle aspiration led to the histological diagnosis of acinar cell carcinoma. The clinical stage was determined to be IVb based on findings of multiple metastatic lesions in the liver and lymph nodes, as well as splenic vein infiltration. Because the patient was not a surgical candidate, he underwent chemotherapy with modified FOLFIRINOX. In the absence of any severe adverse events, 12 courses of chemotherapy were delivered, resulting in marked shrinkage of both the primary and metastatic lesions. The outcome was judged to be a partial response, which was maintained even 9 months from the introduction of the chemotherapy. The results of this case suggest that modified FOLFIRINOX is safe and effective in the treatment of pancreatic acinar cell carcinoma.



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Tumor-suppressive miRNA-135a inhibits breast cancer cell proliferation by targeting ELK1 and ELK3 oncogenes

Abstract

Breast cancer is the most common malignant disease amongst women. miRNAs are small, non-coding RNAs that regulate gene expression, thus have the potential to play an important role during cancer development. Emerging evidence shows that miR-135a is down-regulated in breast cancer cells, but the functional roles of miR-135a in breast cancer cells remains unexplored. For this purpose, we investigated the expression of miR-135a in breast cancer cells and explored its functional role during breast cancer progression. In vitro study showed that miR-135a may be a novel tumor suppressor. Further studies showed that transcription factors ELK1 and ELK3 are direct target genes of miR-135a that modulates the suppressive function of miR-135a in breast cancer cells. Induced expression of miR-135a significantly downregulated the expression of ELK1 and ELK3 both at mRNA and protein levels. Furthermore, the effect of miR-135a in MCF-7 and T47D cells was investigated by the overexpression of miR-135a mimics. In vitro, induced expression of miR-135a in breast cancer cells inhibited cell Proliferation and clongenicity. Moreover, a luciferase activity assay revealed that miR-135a could directly target the 3′-untranslated region (3′ UTRS) of ELK1 and ELK3 oncogenes. In addition, rescue experiment demonstrated that the promoted cell growth by transcription factors ELK1 and ELK3 was attenuated by the over-expression of miR-135a. Our study demonstrates that miR-135a regulates cell proliferation in breast cancer by targeting ELK1 and ELK3 oncogenes, and suggests that miR-135a potentially can act as a tumor suppressor.



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Characterization and comparative expression analysis of CUL1 genes in rice

Abstract

Cullin-RING E3 ubiquitin ligase (CRL) complex is known as the largest family of E3 ligases. The most widely characterized CRL, SCF complex (CRL1), utilizes CUL1 as a scaffold protein to assemble the complex components. To better understand CRL1-mediated cellular processes in rice, three CUL1 genes (OsCUL1s) were isolated in Oryza sativa. Although all OsCUL1 proteins exhibited high levels of amino acid similarities with each other, OsCUL1-3 had a somewhat distinct structure from OsCUL1-1 and OsCUL1-2. Basal expression levels of OsCUL1-3 were much lower than those of OsCUL1-1 and OsCUL1-2 in all selected samples, showing that OsCUL1-1 and OsCUL1-2 play predominant roles relative to OsCUL1-3 in rice. OsCUL1-1 and OsCUL1-2 genes were commonly upregulated in dry seeds and by ABA and salt/drought stresses, implying their involvement in ABA-mediated processes. These genes also showed similar expression patterns in response to various hormones and abiotic stresses, alluding to their functional redundancy. Expression of the OsCUL1-3 gene was also induced in dry seeds and by ABA-related salt and drought stresses, implying their participation in ABA responses. However, its expression pattern in response to hormones and abiotic stresses was somehow different from those of the OsCUL1-1 and OsCUL1-2 genes. Taken together, these findings suggest that the biological role and function of OsCUL1-3 may be distinct from those of OsCUL1-1 and OsCUL1-2. The results of expression analysis of OsCUL1 genes in this study will serve as a useful platform to better understand overlapping and distinct roles of OsCUL1 proteins and CRL1-mediated cellular processes in rice plants.



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Conserved expression of ultra-conserved noncoding RNA in mammalian nervous system

Publication date: Available online 18 October 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Junjie Zhou, Ruiyu Wang, Jing Zhang, Liyuan Zhu, Wei Liu, Shuaiyao Lu, Pan Chen, Hanlu Li, Bin Yin, Jiangang Yuan, Boqin Qiang, Pengcheng Shu, Xiaozhong Peng
T-UCRs, a class of long non-coding RNAs that are transcribed from ultra-conserved regions (UCRs), might play an important role in development and diseases. However, the amount of T-UCRs that are conservatively expressed in the developing nervous systems of mice, monkeys and humans is still unknown. In this study, we screened the RNA sequence signals of 481 identified UCRs in an E14.5 mouse brain from the ENCODE database and found 76 UCRs that may be transcribed into T-UCRs. To verify the expression of these potential T-UCRs, we used an RT-PCR experiment and identified that 60 T-UCRs can be expressed in the E14.5 mouse brain. Furthermore, we detected the expression conservation of 76 potential T-UCRs in two comparisons: postnatal day 0 brains of a mouse and a rhesus monkey and neural stem cell of mouse and human by RT-PCR experimentation. It was found that up to 65% of these T-UCRs were expressed in mouse, rhesus monkey and human nervous systems. Next, by testing the spatiotemporal expression pattern of these T-UCRs expressed in mouse, rhesus monkey and human nervous systems, we found that approximately 30% of the T-UCRs showed a relatively high and dynamical expression during mouse brain development. Finally, through biological process and molecular function gene ontology analysis of the host genes of intronic or exonic-antisense T-UCRs, it was discovered that most of the genes were involved in RNA splicing or RNA binding. These results suggest that T-UCRs are likely to participate in nervous system development through RNA processing.



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Longitudinal perspectives on the psychosis spectrum in 22q11.2 deletion syndrome

The prevalence of psychotic disorders in individuals with 22q11.2 Deletion Syndrome (22q11DS) reaches 25–35% in young adulthood and may provide a neurogenetic model for clinical risk of psychotic disorders in the general population. This review focuses on prospective longitudinal studies in 22q11DS, which capture fluctuations in psychosis symptoms over time and may provide insights into potential demographic, clinical, cognitive, and neuroimaging predictors of psychosis-spectrum outcomes in the general population. Findings are compared and contrasted with those from idiopathic psychosis-spectrum populations. Onset of psychotic disorders in 22q11DS can occur over a wide range of ages, peaking in late adolescence. Symptoms may be gradually progressive or episodic in nature, highlighting the importance and challenge of risk and resilience prediction models. Converging results suggest that psychosis-spectrum outcomes in 22q11DS are predicted by lower baseline functioning, higher baseline psychosis-spectrum symptoms, presence of mood disturbance or anxiety, and lower baseline and subsequent decline in global measures of cognition. Predictors of transition to threshold psychotic disorders and ages of onset are similar in idiopathic clinical risk. They also share similarly global cognitive deficits, but not to the same extent as in 22q11DS. While neuroimaging studies in idiopathic clinical risk suggest loss of prefrontal gray matter, there is no consistent evidence yet emerging in the limited literature in 22q11DS. Interventional efforts in 22q11DS aimed at halting progression to psychosis or mitigating outcomes in early psychosis may be best implemented during the adolescent age range. Collaborative longitudinal efforts may help to address existing gaps in our understanding.



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Novel recessive PDZD7 biallelic mutations in two Chinese families with non-syndromic hearing loss

Autosomal recessive non-syndromic hearing loss (ARNSHL) is a highly heterogeneous genetic condition. PDZD7 has emerged as a new genetic etiology of ARNSHL. Biallelic mutations in the PDZD7 gene have been reported in two German families, four Iranian families, and a Pakistani family with ARNSHL. The effect of PDZD7 on ARNSHL in other population has yet to be elucidated. Two Chinese ARNSHL families, each of which had two affected siblings, were included in this study. The families underwent target region capture and high-throughput sequencing to analyze the exonic, splice-site, and intronic sequences of 128 genes. Furthermore, 1751 normal Chinese individuals served as controls, and 122 Chinese families segregating with apparent ARNSHL, who had been previously excluded for variants in the common deafness genes GJB2 and SLC26A4, were subjected to screening for candidate mutations. We identified a novel homozygous missense mutation (p.Arg66Leu) and novel compound heterozygous frameshift mutations (p.Arg56fsTer24 and p.His403fsTer36) in Chinese families with ARNSHL. This is the first report to identify PDZD7 as an ARNSHL-associated gene in the Chinese population. Our finding could expand the pathogenic spectrum and strengthens the clinical diagnostic role of the PDZD7 gene in ARNSHL patients.



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Biallelicframeshift mutation in RIN2 in a patient with intellectual disability and cataract, without RIN2 syndrome



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Beyond Down syndrome phenotype: Paternally derived isodicentric chromosome 21 with partial monosomy 21q22.3

Inverted isodicentric chromosome 21 is a rare form of chromosomal rearrangement that may result in trisomy 21; sometimes this rearrangement may also lead to segmental monosomy of the terminal long arm of chromosome 21. In this report, we describe the prenatal diagnosis and neonatal follow-up of a child with a paternally derived, de novo isodicentric chromosome 21 and a concurrent ∼1.2 Mb deletion of the 21q22.3 region [46,XX,idic(21)(q22.3)]. This child presented with unusual phenotype of Down syndrome and additional defects including esophageal atresia and tethered cord syndrome. The resulting phenotype in this infant might be a coalescence of the partial trisomy and monosomy 21, as well as homozygosity for idic (21). The utilization of chromosomal microarray in this case enabled accurate characterization of a rare chromosome abnormality, potentially contributes to future phenotype–genotype correlation and produced evidence for a molecular mechanism underlying this rearrangement.



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Mutations of KIF5C cause a neurodevelopmental disorder of infantile-onset epilepsy, absent language, and distinctive malformations of cortical development

The clinical diagnosis of malformations of cortical development (MCDs) is often challenging due to the complexity of the brain malformation by neuroimaging, the rarity of individual malformation syndromes, and the rapidly evolving genetic landscape of these disorders facilitated with the use of Next Generation Sequencing (NGS) methods. While the clinical and molecular diagnosis of severe cortical malformations, such as classic lissencephaly, is often straightforward, the diagnosis of more subtle and complex types of cortical malformations, such as pachygyria and polymicrogyria (PMG), can be more challenging due to limited knowledge regarding their genetic etiologies. Here, we report two individuals with the same de novo KIF5C mutation who present with subtle MCDs, early onset epilepsy and significant neurodevelopmental and behavioral issues including absent language. Our data, combined with the limited literature on KIF5C mutations, to date, support that KIF5C mutations are associated with a neurodevelopmental disorder characterized by infantile onset epilepsy, and subtle but recognizable types of brain malformations. We also show that the spectrum of KIF5C mutations is narrow, as five out of the six identified individuals have mutations affecting amino acid Glu237. Therefore, the identification of the clinical and neuroimaging features of this disorder may strongly facilitate rapid and efficient molecular diagnosis.



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EMS agency debuts pink ambulance for Breast Cancer Awareness month

Sunstar Paramedics said they have personally been impacted by breast cancer after losing an employee to the disease years ago

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Role of tube size and intranasal compression of the nasotracheal tube in respiratory pressure loss during nasotracheal intubation: a laboratory study.

Role of tube size and intranasal compression of the nasotracheal tube in respiratory pressure loss during nasotracheal intubation: a laboratory study.

BMC Anesthesiol. 2017 Oct 17;17(1):141

Authors: Futagawa K, Takasugi Y, Kobayashi T, Morishita S, Okuda T

Abstract
BACKGROUND: Small nasotracheal tubes (NTTs) and intranasal compression of the NTT in the nasal cavity may contribute to increasing airway resistance. Since the effects of size, shape, and partial compression of the NTT on airway resistance have not been investigated, values of airway resistance with partial compression of preformed NTTs of various sizes were determined.
METHODS: To determine the factors affecting the respiratory pressure loss during the nasotracheal intubation, physical and fluid dynamics simulations were used. The internal minor axes of NTTs in the nasal cavity of intubated patients were measured using dial calipers. In physical and fluid dynamics simulations, pressure losses through the tubular parts, compressed parts, and slip joints of NTTs with internal diameters (IDs) of 6.0, 6.5, 7.0, 7.5, and 8.0 mm were estimated under partial compression.
RESULTS: The median internal minor axes of the 7.0- and 7.5-mm ID NTTs in the nasal cavity were 5.2 (4.3-5.6) mm and 6.0 (4.2-7.0) mm, respectively. With a volumetric air flow rate of 30 L/min, pressure losses through uncompressed NTTs with IDs of 6.0-, 6.5-, 7.0-, 7.5- and 8.0-mm were 651.6 ± 5.7 (6.64 ± 0.06), 453.4 ± 3.9 (4.62 ± 0.04), 336.5 ± 2.2 (3.43 ± 0.02), 225.2 ± 0.2 (2.30 ± 0.00), and 179.0 ± 1.1 Pa (1.82 ± 0.01 cmH2O), respectively; the pressure losses through the slip joints were 220.3 (2.25), 131.1 (1.33), 86.8 (0.88), 57.1 (0.58), and 36.1 Pa (0.37 cmH2O), respectively; and the pressure losses through the curvature of the NTT were 71.6 (0.73), 69.0 (0.70), 64.8 (0.66), 32.5 (0.33), and 41.6 Pa (0.42 cmH2O), respectively. A maximum compression force of 34.1 N increased the pressure losses by 82.0 (0.84), 38.0 (0.39), 23.5 (0.24), 16.6 (0.17), and 9.3 Pa (0.09 cmH2O), respectively.
CONCLUSION: Pressure losses through NTTs are in inverse proportion to the tubes' IDs; greater pressure losses due to slip joints, acute bending, and partial compression of the NTT were obvious in small NTTs. Pressure losses through NTTs, especially in small NTTs, could increase the work of breathing to a greater extent than that through standard tubes; intranasal compression further increases the pressure loss.

PMID: 29041911 [PubMed - in process]



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