Impact of the development of an endoscopic eradication program for Barrett's esophagus with high grade dysplasia or early adenocarcinoma on the frequency of surgery

Background and aims  The impact of the advent of an institutional endoscopic eradication therapy (EET) program on surgical practice for Barrett's esophagus (BE)-associated high grade dysplasia (HGD) or suspected T1a esophageal adenocarcinoma (EAC) is unknown. The aims of this study are to evaluate the different endoscopic modalities used during development of our EET program and factors associated with the use of EET or surgery for these patients after its development. Methods  Patients who underwent primary endoscopic or surgical treatment for BE-HGD or early EAC at our hospital between January 1992 and December 2014 were retrospectively identified. They were categorized by their initial modality of treatment during the first year, and the impact over time for choice of therapy was assessed by multivariable logistic regression. Results  We identified 386 patients and 80 patients who underwent EET and surgery, respectively. EET included single modality therapy in 254 (66 %) patients and multimodal therapy in 132 (34 %) patients. Multivariable logistic regression showed that, for each subsequent study year, EET was more likely to be performed in patients who were older ( P  = 0.0009), with shorter BE lengths ( P  < 0.0001), and with a pretreatment diagnosis of HGD ( P  = 0.0054) compared to surgical patients. The diagnosis of EAC did not increase the utilization of EET compared to surgery as time progressed ( P  = 0.8165). Conclusion  The introduction of an EET program at our hospital increased the odds of utilizing EET versus surgery over time for initial treatment of patients who were older, had shorter BE lengths or the diagnosis of BE-HGD, but not in patients with EAC

Association of epidural analgesia in women in labor with neonatal and childhood outcomes in a population cohort

Importance: Although use of epidural analgesia during labor is safe, detailed information about its association with neonatal and child outcomes is limited. Objective: To investigate the association of labor epidural analgesia with neonatal outcomes and childhood development during the first 1000 days of life. Design, Setting, and Participants: This population-based cohort study used Scottish National Health Service hospital administrative data of all 435 281 singleton live births in Scotland between January 1, 2007, and December 31, 2016, with follow-up over the first 1000 days of life. All 435 281 mother-infant pairs delivering between 24 weeks 0 days and 43 weeks 6 days’ gestation who were in active labor with cephalic presentation and who delivered vaginally or via unplanned cesarean delivery were included. Stillbirths and infants with known congenital anomalies were excluded. Data were analyzed between August 1, 2020, and July 23, 2021. Exposures: Epidural analgesia in labor. Main Outcomes and Measures: Neonatal outcomes included resuscitation, Apgar score less than 7 at 5 minutes, and neonatal unit admission. Childhood development measures (gross and fine motor function, communication, and social functioning) were obtained from standardized national childhood surveillance assessments performed at 2 years. Results: This study included a total of 435 281 live births with cephalic presentation in labor (median gestational age at delivery, 40 weeks [IQR, 39-41 weeks]; 221 153 male infants [50.8%]), of which 94 323 (21.7%) had labor epidural. Epidural analgesia was associated with a reduction in spontaneous vaginal deliveries (confounder-adjusted [Cadj] relative risk [RR], 0.46; 95% CI, 0.42-0.50), an increased risk of neonatal resuscitation (Cadj RR, 1.07; 95% CI, 1.03-1.11), and an increased risk of neonatal unit admission (Cadj RR, 1.14; 95% CI, 1.11-1.17). With additional analysis for mediation by mode of delivery (CMadj), these associations were reversed (CMadj RR, 0.83; 95% CI, 0.79-0.86 for neonatal resuscitation and CMadj RR, 0.94; 95% CI, 0.91-0.97 for neonatal unit admission). Epidural analgesia was associated with a reduced risk of an Apgar score less than 7 at 5 minutes in both confounder and confounder/mediation analyses. Epidural analgesia was associated with a reduced risk of having developmental concern in any domain at 2 years in confounder and confounder/mediation analyses (CMadj RR, 0.96; 95% CI, 0.93-0.98), with specifically fewer concerns regarding communication (CMadj RR, 0.96; 95% CI, 0.93-0.99) and fine motor skills (CMadj RR, 0.89; 95% CI, 0.82-0.97). Conclusions and Relevance: The results of this cohort study suggest that labor epidural analgesia is not independently associated with adverse neonatal or childhood development outcomes. Associations with neonatal resuscitation and admission were likely mediated by mode of delivery

Novel modified endoscopic mucosal resection of large GI lesions (> 20 mm) using an external additional working channel (AWC) may improve R0 resection rate: initial clinical experience

Background En-bloc resection of large, flat dysplastic mucosal lesions of the luminal GI tract can be challenging. In order to improve the efficacy of resection for lesions ≥2 cm and to optimize R0 resection rates of lesions suspected of harboring high-grade dysplasia or early adenocarcinoma, a novel grasp and snare EMR technique utilizing a novel over the scope additional accessory channel, termed EMR Plus (EMR+), was developed. The aim of this pilot study is to describe the early safety and efficacy data from the first in human clinical cases. Methods A novel external over-the-scope additional working channel (AWC) (Ovesco, Tuebingen, Germany) was utilized for the EMR+ procedure, allowing a second endoscopic device to be used through the AWC while using otherwise standard endoscopic equipment. The EMR+ technique allows tissue retraction and a degree of triangulation during endoscopic resection. We performed EMR+ procedure in 6 patients between 02/2018–12/2018 for lesions in the upper and lower GI tract. Results The EMR+ technique utilizing the AWC was performed successfully in 6 resection procedures of the upper and/or lower GI tract in 6 patients in 2 endoscopy centers. All resections were performed successfully with the EMR+ technique, all achieving an R0 resection. No severe adverse events occurred in any of the procedures. Conclusions The EMR+ technique, utilizing an additional working channel, had an acceptable safety and efficacy profile in this preliminary study demonstrating it’s first use in humans. This technique may allow an additional option to providers to remove complex, large mucosal-based lesions in the GI tract using standard endoscopic equipment and a novel AWC device

Neonatal and early childhood outcomes following maternal anesthesia for cesarean section: a population-based cohort study

Background: The fetus is vulnerable to maternal drug exposure. We determined associations of exposure to spinal, epidural, or general anesthesia on neonatal and childhood development outcomes during the first 1000 days of life. Methods: Population-based study of all singleton, cesarean livebirths of 24+0 to 43+6 weeks gestation between January 2007 and December 2016 in Scotland, stratified by urgency with follow-up to age 2 years. Models were adjusted for: maternal age, weight, ethnicity, socioeconomic status, smoking, drug-use, induction, parity, previous cesarean or abortion, pre-eclampsia, gestation, birth weight, and sex. Results: 140 866 mothers underwent cesarean section (41.2% (57,971/140,866) elective, 58.8% (82,895/140,866) emergency) with general anesthesia used in 3.2% (1877/57,971) elective and 9.8% (8158/82,895) of emergency cases. In elective cases, general anesthesia versus spinal was associated with: neonatal resuscitation (crude event rate 16.2% vs 1.9% (adjusted RR 8.20, 95% CI 7.20 to 9.33), Apgar &lt;7 at 5 min (4.6% vs 0.4% (adjRR 11.44, 95% CI 8.88 to 14.75)), and neonatal admission (8.6% vs 4.9% (adjRR 1.65, 95% CI 1.40 to 1.94)). Associations were similar in emergencies; resuscitation (32.2% vs 12.3% (adjRR 2.40, 95% CI 2.30 to 2.50)), Apgar &lt;7 (12.6% vs 2.8% (adjRR 3.87, 95% CI 3.56 to 4.20), and admission (31.6% vs 19.9% (adjRR 1.20, 95% CI 1.15 to 1.25). There was a weak association between general anesthesia in emergency cases and having ≥1 concern noted in developmental assessment at 2 years (21.0% vs 16.5% (adjRR 1.08, 95% CI 1.01 to 1.16)). Conclusions: General anesthesia for cesarean section, irrespective of urgency, is associated with neonatal resuscitation, low Apgar, and neonatal unit admission. Associations were strongest in non-urgent cases and at term. Further evaluation of long-term outcomes is warranted

Population implications of cessation of IVF during the COVID-19 pandemic

Research question: Discontinuation of IVF cycles has been part of the radical transformation of healthcare provision to enable reallocation of staff and resources to deal with the COVID-19 pandemic. This study sought to estimate the impact of cessation of treatment on individual prognosis and US population live birth rates. Design: Data from 271,438 ovarian stimulation UK IVF cycles was used to model the effect of age as a continuous, yet non-linear, function on cumulative live birth rate. This model was recalibrated to cumulative live birth rates reported for the 135,673 stimulation cycles undertaken in the USA in 2016, with live birth follow-up to October 2018. The effect of a 1-month, 3-month and 6-month shutdown in IVF treatment was calculated as the effect of the equivalent increase in a woman's age, stratified by age group. Results: The average reduction in cumulative live birth rate would be 0.3% (95% confidence interval [CI] 0.3–0.3), 0.8% (95% CI 0.8–0.8) and 1.6% (95% CI 1.6–1.6) for 1-month, 3-month and 6-month shutdowns. This corresponds to a reduction of 369 (95% CI 360–378), 1098 (95% CI 1071–1123) and 2166 (95% CI 2116–2216) live births in the cohort, respectively. Th e greatest contribution to this reduction was from older mothers. Conclusions: The study demonstrated that the discontinuation of fertility treatment for even 1 month in the USA could result in 369 fewer women having a live birth, due to the increase in patients’ age during the shutdown. As a result of reductions in cumulative live birth rate, more cycles may be required to overcome infertility at individual and population levels

The continuum of complications in survivors of necrotizing pancreatitis

Background: Necrotizing pancreatitis survivors develop complications beyond infected necrosis that often require invasive intervention. Remarkably few data have cataloged these late complications after acute necrotizing pancreatitis resolution. We sought to identify the types and incidence of complications after necrotizing pancreatitis. Design: An observational study was performed evaluating 647 patients with necrotizing pancreatitis captured in a single-institution database between 2005 and 2017 at a tertiary care hospital. Retrospective review and analysis of newly diagnosed conditions attributable to necrotizing pancreatitis was performed. Exclusion criteria included the following: death before disease resolution (n = 57, 9%) and patients lost to follow-up (n = 12, 2%). Results: A total of 578 patients were followed for a median of 46 months (range, 8 months to 15 y) after necrotizing pancreatitis. In 489 (85%) patients 1 or more complications developed and included symptomatic disconnected pancreatic duct syndrome (285 of 578, 49%), splanchnic vein thrombosis (257 of 572, 45%), new endocrine insufficiency (195 of 549, 35%), new exocrine insufficiency (108 of 571, 19%), symptomatic chronic pancreatitis (93 of 571, 16%), incisional hernia (89 of 420, 21%), biliary stricture (90 of 576, 16%), chronic pain (44 of 575, 8%), gastrointestinal fistula (44 of 578, 8%), pancreatic duct stricture (30 of 578, 5%), and duodenal stricture (28 of 578, 5%). During the follow-up period, a total of 340 (59%) patients required an invasive intervention after necrotizing pancreatitis resolution. Invasive pancreatobiliary intervention was required in 230 (40%) patients. Conclusion: Late complications are common in necrotizing pancreatitis survivors. A broad variety of problems manifest themselves after resolution of the acute disease process and often require invasive intervention. Necrotizing pancreatitis patients should be followed lifelong by experienced clinicians

Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques

Acute myeloid leukaemia (AML) is a life threatening cancer for which there is an urgent clinical need for novel therapeutic approaches. A redeployed drug combination of bezafibrate and medroxyprogesterone acetate (BaP) has shown anti-leukaemic activity in vitro and in vivo. Elucidation of the BaP mechanism of action is required in order to understand how to maximise the clinical benefit. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, Synchrotron radiation FTIR (S-FTIR) and Raman microspectroscopy are powerful complementary techniques which were employed to probe the biochemical composition of two AML cell lines in the presence and absence of BaP. Analysis was performed on single living cells along with dehydrated and fixed cells to provide a large and detailed data set. A consideration of the main spectral differences in conjunction with multivariate statistical analysis reveals a significant change to the cellular lipid composition with drug treatment; furthermore, this response is not caused by cell apoptosis. No change to the DNA of either cell line was observed suggesting this combination therapy primarily targets lipid biosynthesis or effects bioactive lipids that activate specific signalling pathways

Expiratory flow rate, breath hold and anatomic dead space influence electronic nose ability to detect lung cancer

BACKGROUND: Electronic noses are composites of nanosensor arrays. Numerous studies showed their potential to detect lung cancer from breath samples by analysing exhaled volatile compound pattern ("breathprint"). Expiratory flow rate, breath hold and inclusion of anatomic dead space may influence the exhaled levels of some volatile compounds; however it has not been fully addressed how these factors affect electronic nose data. Therefore, the aim of the study was to investigate these effects. METHODS: 37 healthy subjects (44 +/- 14 years) and 27 patients with lung cancer (60 +/- 10 years) participated in the study. After deep inhalation through a volatile organic compound filter, subjects exhaled at two different flow rates (50 ml/sec and 75 ml/sec) into Teflon-coated bags. The effect of breath hold was analysed after 10 seconds of deep inhalation. We also studied the effect of anatomic dead space by excluding this fraction and comparing alveolar air to mixed (alveolar + anatomic dead space) air samples. Exhaled air samples were processed with Cyranose 320 electronic nose. RESULTS: Expiratory flow rate, breath hold and the inclusion of anatomic dead space significantly altered "breathprints" in healthy individuals (p 0.05). These factors also influenced the discrimination ability of the electronic nose to detect lung cancer significantly. CONCLUSIONS: We have shown that expiratory flow, breath hold and dead space influence exhaled volatile compound pattern assessed with electronic nose. These findings suggest critical methodological recommendations to standardise sample collections for electronic nose measurements

Transpapillary drainage has no added benefit on treatment outcomes in patients undergoing EUS-guided transmural drainage of pancreatic pseudocysts: a large multicenter study

Background and Aims The need for transpapillary drainage (TPD) in patients undergoing transmural drainage (TMD) of pancreatic fluid collections (PFCs) remains unclear. The aims of this study were to compare treatment outcomes between patients with pancreatic pseudocysts undergoing TMD versus combined (TMD and TPD) drainage (CD) and to identify predictors of symptomatic and radiologic resolution. Methods This is a retrospective review of 375 consecutive patients with PFCs who underwent EUS-guided TMD from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TMD and CD technical success, treatment outcomes (symptomatic and radiologic resolution) at follow-up, and predictors of treatment outcomes on logistic regression. Results A total of 375 patients underwent EUS-guided TMD of PFCs, of which 174 were pseudocysts. TMD alone was performed in 95 (55%) and CD in 79 (45%) pseudocysts. Technical success was as follows: TMD, 92 (97%) versus CD, 35 (44%) (P = .0001). There was no difference in adverse events between the TMD (15%) and CD (14%) cohorts (P = .23). Median long-term (LT) follow-up after transmural stent removal was 324 days (interquartile range, 72-493 days) for TMD and 201 days (interquartile range, 150-493 days) (P = .37). There was no difference in LT symptomatic resolution (TMD, 69% vs CD, 62%; P = .61) or LT radiologic resolution (TMD, 71% vs CD, 67%; P = .79). TPD attempt was negatively associated with LT radiologic resolution of pseudocyst (odds ratio, 0.11; 95% confidence interval, 0.02-0.8; P = .03). Conclusions TPD has no benefit on treatment outcomes in patients undergoing EUS-guided TMD of pancreatic pseudocysts and negatively affects LT resolution of PFCs

Mechanical properties measured by Atomic Force Microscopy define health biomarkers in ageing C. elegans

Genetic and environmental factors are key drivers regulating organismal lifespan but how these impact healthspan is less well understood. Techniques capturing biomechanical properties of tissues on a nano-scale level are providing new insights into disease mechanisms. Here, we apply Atomic Force Microscopy (AFM) to quantitatively measure the change in biomechanical properties associated with ageing Caenorhabditis elegans in addition to capturing high-resolution topographical images of cuticle senescence. We show that distinct dietary restriction regimes and genetic pathways that increase lifespan lead to radically different healthspan outcomes. Hence, our data support the view that prolonged lifespan does not always coincide with extended healthspan. Importantly, we identify the insulin signalling pathway in C. elegans and interventions altering bacterial physiology as increasing both lifespan and healthspan. Overall, AFM provides a highly sensitive technique to measure organismal biomechanical fitness and delivers an approach to screen for health-improving conditions, an essential step towards healthy ageing