The association of body mass index and odds of type 2 diabetes mellitus varies by race/ethnicity.

OBJECTIVE: This study aimed to examine the association between body mass index (BMI; weight [kilogram]/height2 [meter]) and type 2 diabetes mellitus (T2DM) among the largest three largest racial/ethnic groups in the United States. METHODS: We compiled 10 waves of the continuous National Health and Nutrition Examination Survey from 1999-2000 through 2017-2018. Participants (N = 45,514) were those who had data on BMI, HbA1c, and demographics. We estimated associations between BMI and prediabetes/T2DM odds for Black, Latine, and White participants. RESULTS: BMI was associated with 10% higher odds of prediabetes/T2DM vs. having normal HbA1c levels (odds ratio = 1.10, 95% confidence interval = 1.10-1.11) for Latine and White individuals. However, the association between BMI and prediabetes/T2DM was significantly weaker among Black individuals. When focusing on T2DM prevalence, the association with BMI for Black participants was even weaker (odds ratio = 0.97, 95% confidence interval = 0.95-0.98). CONCLUSIONS: The unstable associations between BMI and T2DM across race indicate that BMI has received unwarranted focus as a prime predictor of T2DM. Relying on BMI introduces bias in T2DM risk estimations especially in Black individuals. Focusing on BMI places the onus on individuals to change and increases weight stigma, which can worsen health outcomes. Instead, policymakers should focus on social determinants of T2DM and its concomitant racial/ethnic disparities.

Efficacy of different surgical treatments for management of anal fistula: a network meta-analysis.

PURPOSE: Currently, the anal fistula treatment which optimises healing and preserves bowel continence remains unclear. The aim of our study was to compare the relative efficacy of different surgical treatments for AF through a network meta-analysis. METHODS: Systematic searches of MEDLINE, EMBASE and CENTRAL databases up to October 2022 identified randomised controlled trials (RCTs) comparing surgical treatments for anal fistulae. Fistulae were classified as simple (inter-sphincteric or low trans-sphincteric fistulae crossing less than 30% of the external anal sphincter (EAS)) and complex (high trans-sphincteric fistulae involving more than 30% of the EAS). Treatments evaluated in only one trial were excluded from the primary analyses to minimise bias. The primary outcomes were rates of success in achieving AF healing and bowel incontinence. RESULTS: Fifty-two RCTs were included. Of the 14 treatments considered, there were no significant differences regarding short-term (6 months or less postoperatively) and long-term (more than 6 months postoperatively) success rates between any of the treatments in patients with both simple and complex anal fistula. Ligation of the inter-sphincteric fistula tract (LIFT) ranked best for minimising bowel incontinence in simple (99.1% of comparisons; 3 trials, n = 70 patients) and complex anal fistula (86.2% of comparisons; 3 trials, n = 102 patients). CONCLUSIONS: There is insufficient evidence in existing RCTs to recommend one treatment over another regarding their short and long-term efficacy in successfully facilitating healing of both simple and complex anal fistulae. However, LIFT appears to be associated with the least impairment of bowel continence, irrespective of AF classification.

Rare metabolic disease mimicking COL4A1/COL4A2 fetal brain phenotype.

Pathogenic variants of collagen type IV alpha 1 and 2 (COL4A1/COL4A2) genes cause various phenotypic anomalies, including intracerebral hemorrhage and a wide spectrum of developmental anomalies. Only 20% of fetuses referred for COL4A1/COL4A2 molecular screening (fetuses with a suspected intracerebral hemorrhage) carry a pathogenic variant in these genes, raising questions regarding the causative anomaly in the remaining 80% of these fetuses. We examined, following termination of pregnancy or in-utero fetal death, a series of 113 unrelated fetuses referred for COL4A1/COL4A2 molecular screening, in which targeted sequencing was negative. Using exome sequencing data and a gene-based collapsing test, we searched for enrichment of rare qualifying variants in our fetal cohort in comparison to the Genome Aggregation Database (gnomAD) control cohort (n = 71 702). Qualifying variants in pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) were overrepresented in our cohort, reaching genome-wide significance (P = 2.11 × 10-7 ). Heterozygous PDHA1 loss-of-function variants were identified in three female fetuses. Among these three cases, we observed microcephaly, ventriculomegaly, germinolytic pseudocysts, agenesis/dysgenesis of the corpus callosum and white-matter anomalies that initially suggested cerebral hypoxic-ischemic and hemorrhagic lesions. However, a careful a-posteriori reanalysis of imaging and postmortem data showed that the observed lesions were also consistent with those observed in fetuses carrying PDHA1 pathogenic variants, strongly suggesting that these two phenotypes may overlap. Exome sequencing should therefore be performed in fetuses referred for COL4A1/COL4A2 molecular screening which are screen-negative, with particular attention paid to the PDHA1 gene. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Predicting Placenta Accreta Spectrum: Validation of the Placenta Accreta Index.

OBJECTIVES: The placenta accreta spectrum (PAS) incidence has risen substantially over the past century, paralleling a rise in cesarean delivery (CD) rates. Prenatal diagnosis of PAS improves maternal outcomes. The Placenta Accreta Index (PAI) is a standardized approach to prenatal diagnosis of PAS incorporating clinical risk and ultrasound (US) findings suggestive of placental invasion. We sought to validate the PAI for prediction of PAS in pregnancies with prior CD. METHODS: This work was a retrospective cohort study of pregnancies with 1 or more prior CDs that received a US diagnosis of placenta previa or low-lying placenta in the third trimester. Images of third-trimester US with a complete placental evaluation were read by 2 blinded physicians, and the PAI was applied. Surgical outcomes and pathologic findings were reviewed. Placenta accreta spectrum was diagnosed if clinical evidence of invasion was seen at time of delivery or if any placental invasion was identified histologically. International Federation of Gynecology and Obstetrics criteria were used. RESULTS: A total of 194 women met inclusion criteria. Cesarean hysterectomy was performed in 92 (47%), CD in 97 (50%), and vaginal delivery in 5 (3%). Of those who underwent hysterectomy, PAS was histologically confirmed in 79 (85%) pregnancies. Of the remaining 13 who underwent hysterectomy, all met International Federation of Gynecology and Obstetrics grade 1 clinical criteria for PAS. With a threshold of greater than 4, the PAI has a sensitivity of 87%, specificity of 77%, positive predictive value of 72%, and negative predictive value of 90% for PAS diagnosis. CONCLUSIONS: Contemporaneous application of the PAI, a standardized approach to US diagnosis, is useful in the prenatal prediction of PAS.

The impact of transanal tube design for preventing anastomotic leak in anterior resection: a systematic review and meta-analysis.

BACKGROUND: Placement of a transanal tube (TAT) into the rectum is a strategy used to attempt to prevent anastomotic leak (AL) in anterior resection surgery. There is a wide variation in materials and tube design in devices used as TATs and previous meta-analyses have not considered TAT design in their analyses. This study reviews the impact that design of TAT has on AL rates. METHODS: A systematic review of the literature was performed with the aim of identifying studies evaluating the use of TATs for preventing AL and then defining the design of TATs. Studies were then compared in groups based on TAT design in a meta-analysis to evaluate whether design is an important variable in outcomes. RESULTS: Thirty-three studies were included. There was a wide variety of tubes used as TATs. On meta-analysis, catheter-type TATs were associated with a substantially lower rate of AL (OR: 0.46; 95% CI 0.30, 0.68). By contrast, stent-type TATs were not associated with any reduction in the incidence of AL (OR: 1.06, 95% CI 0.50, 2.22). Catheter-type TATs were also associated with substantial reductions in the rate of reoperation (OR: 0.32; 95% CI 0.20, 0.50), whereas stent-type TATs showed no benefit in the rate of reoperation (OR: 0.79; 95% CI 0.37, 1.65). CONCLUSIONS: Off-the-shelf catheter-type transanal tubes appeared effective in preventing AL, whereas custom-designed stent-type TATs were not demonstrated to be effective; although high quality evidence is limited. TAT design should be an important consideration in further research of the use of TATs in anterior resection surgery.

Network meta-analysis of local and regional analgesia following colorectal resection.

BACKGROUND: Postoperative pain management after colorectal surgery remains challenging. Systemic opiates delivered on demand or via a patient-controlled pump have traditionally been the mainstay of treatment. Opiate analgesia is associated with slower gastrointestinal recovery and unpleasant side-effects; many regional and local analgesic techniques have been developed as alternatives. METHODS: MEDLINE, Embase and CENTRAL databases were searched systematically for RCTs comparing analgesic techniques after major colorectal resection. A network meta-analysis was performed using a Bayesian random-effects framework with a non-informative prior. Primary outcomes included pain at rest and cumulative opiate consumption 24 h after surgery. Secondary outcomes included pain at rest and cumulative opiate consumption at 48 h, pain on movement and cough at 24 and 48 h, time to first stool, time to tolerance of oral diet, duration of hospital stay, nausea and vomiting, and postoperative complications. RESULTS: Seventy-four RCTs, including 5101 patients and 11 different techniques, were included. Some inconsistency and heterogeneity was found. SUCRA scores showed that spinal analgesia was the best intervention for postoperative pain and opiate reduction at 24 h. Transversus abdominus plane blocks were effective in reducing pain and opiate consumption 24 h after surgery. Subgroup analysis showed similar results for open versus minimally invasive surgical approaches, and enhanced recovery after surgery programmes. CONCLUSION: Spinal analgesia and transversus abdominus plane blocks best balanced pain control and opiate minimization in the immediate postoperative phase following colorectal resection. Multimodal analgesia reduces pain, minimizes systemic opiate use and optimizes postoperative recovery.

ANTECEDENTES: El tratamiento del dolor postoperatorio después de cirugía colorrectal sigue siendo difícil. Los opiáceos sistémicos administrados a demanda o mediante una bomba controlada por el paciente ha sido tradicionalmente el principal tratamiento. Sin embargo, la analgesia con opiáceos se asocia con una recuperación gastrointestinal más lenta y con efectos secundarios desagradables, lo que dado lugar al desarrollo de numerosas técnicas analgésicas regionales y locales como modalidades alternativas. MÉTODOS: Se realizaron búsquedas sistemáticas en las bases de datos Medline, Embase y CENTRAL para identificar ensayos controlados aleatorizados (randomized controlled trials, RCTs) que compararan técnicas analgésicas después de una resección colorrectal mayor. Se realizó un metaanálisis en red utilizando un marco bayesiano de efectos aleatorios con una distribución a priori no informativa. Los criterios de valoración primarios incluyeron dolor en reposo y el consumo de opiáceos a las 24 horas después de la operación. Los criterios de valoración secundarios incluyeron dolor en reposo y el consumo de opiáceos a las 48 horas, dolor con el movimiento y al toser (a las 24 y 48 horas), tiempo hasta la primera deposición, tiempo hasta tolerar la dieta oral, duración de la estancia hospitalaria, náuseas y vómitos, y complicaciones postoperatorias. RESULTADOS: Se incluyeron 74 RCTs, con un total de 5.101 pacientes y 11 técnicas diferentes. Se encontró cierta inconsistencia y heterogeneidad. Las puntuaciones de dolor en reposo más bajas y la menor ingesta de opiáceos postoperatorios a las 24 horas correspondieron a la analgesia espinal. Los bloqueos del plano transverso del abdomen fueron efectivos para reducir el dolor y el consumo de opiáceos a las 24 horas después de la cirugía. El análisis de subgrupos mostró resultados similares para los abordajes quirúrgicos abiertos versus mínimamente invasivos y para los programas de recuperación intensificada después de la cirugía (Enhanced Recovery After Surgery, ERAS). CONCLUSIÓN: La analgesia espinal y el bloqueo del plano transverso del abdomen consiguieron un mejor control del dolor y una disminución de los opiáceos en el postoperatorio inmediato tras la cirugía colorrectal. La analgesia multimodal reduce el dolor, minimiza el uso de opiáceos sistémicos y optimiza la recuperación postoperatoria.

Establishing core outcome sets for gastrointestinal recovery in studies of postoperative ileus and small bowel obstruction: protocol for a nested methodological study.

INTRODUCTION: Gastrointestinal recovery describes the restoration of normal bowel function in patients with bowel disease. This may be prolonged in two common clinical settings: postoperative ileus and small bowel obstruction. Improving gastrointestinal recovery is a research priority but researchers are limited by variation in outcome reporting across clinical studies. This protocol describes the development of core outcome sets for gastrointestinal recovery in the contexts of postoperative ileus and small bowel obstruction. METHOD: An international Steering Group consisting of patient and clinician representatives has been established. As overlap between clinical contexts is anticipated, both outcome sets will be co-developed and may be combined to form a common output with disease-specific domains. The development process will comprise three phases, including definition of outcomes relevant to postoperative ileus and small bowel obstruction from systematic literature reviews and nominal-group stakeholder discussions; online-facilitated Delphi surveys via international networks; and a consensus meeting to ratify the final output. A nested study will explore if the development of overlapping outcome sets can be rationalized. DISSEMINATION AND IMPLEMENTATION: The final output will be registered with the Core Outcome Measures in Effectiveness Trials initiative. A multi-faceted, quality improvement campaign for the reporting of gastrointestinal recovery in clinical studies will be launched, targeting international professional and patient groups, charitable organizations and editorial committees. Success will be explored via an updated systematic review of outcomes 5 years after registration of the core outcome set.

Prospective First-Trimester Ultrasound Imaging of Low Implantation and Placenta Accreta Spectrum.

OBJECTIVES: To prospectively evaluate low implantation of the gestational sac and other first-trimester ultrasound (US) parameters for prediction of placenta accreta spectrum (PAS). METHODS: Women with a diagnosis of low implantation on clinically indicated first-trimester US underwent a transvaginal US examination at 10 to 13 weeks' gestation to assess the trophoblast location, anechoic areas, bridging vessels, and smallest myometrial thickness (SMT). The placental location was evaluated in the second trimester, and serial US examinations were performed in cases of low placentation. Placenta accreta spectrum was based on clinical findings and confirmed by histologic results. RESULTS: Of 68 women, 40 (59%) had prior cesarean delivery (CD). Hysterectomy was performed in 8, all with prior CD. Of these, 7 (88%) had US suspicion of PAS. In 16 with prior CD and basalis overlying the internal os, 9 (56%) had second-trimester placenta previa, and 7 of 9 (78%) underwent hysterectomy with pathologic confirmation of PAS. Of 28 without prior CD, there were no cases of persistent low placentation in the third trimester regardless of the trophoblast location. Ultrasound parameters associated with PAS were a smaller distance from the inferior trophoblastic border to the external os, disruption of the bladder-serosal interface, bridging vessels, anechoic areas, and the SMT. In women with prior CD, use of the SMT in the sagittal plane yielded an area under the receiver operating characteristic curve of 0.96 (95% confidence interval, 0.91-1.00). CONCLUSIONS: First-trimester low implantation increases the risk of persistent placenta previa and PAS in women with prior CD. All parameters were associated with PAS, the most predictive being the SMT.

Network meta-analysis comparing techniques and outcomes of stump closure after distal pancreatectomy.

BACKGROUND: The incidence of postoperative pancreatic fistula (POPF) after distal pancreatectomy remains high, and different pancreatic stump closure techniques have been used to reduce the incidence. A network meta-analysis was undertaken to compare the most frequently performed pancreatic stump closure techniques after distal pancreatectomy and determine the technique associated with the lowest POPF rate. METHODS: A systematic search of the Scopus, PubMed, MEDLINE and Embase databases was conducted to identify eligible RCTs. The primary outcome was the occurrence of clinically relevant POPF. Secondary outcomes were duration of operation, blood loss, intrabdominal collections, postoperative complications and 30-day mortality. RESULTS: Sixteen RCTs including 1984 patients and eight different pancreatic stump closure techniques were included in the network meta-analysis. Patch coverage of the pancreatic stump (round ligament or seromuscular patch) after stapler or suture closure ranked best, with the lowest rates of clinically relevant POPF, lowest volume of intraoperative blood loss, fewer intra-abdominal abscesses, and lower rates of overall complications and 30-day mortality. Round ligament patch closure outperformed seromuscular patch closure in preventing clinically relevant POPF with a significantly larger cohort for comparative analysis. Pancreaticoenteric anastomotic closure consistently ranked poorly for most reported postoperative outcomes. CONCLUSION: Patch coverage after stapler or suture closure has the lowest POPF rate and best outcomes among stump closure techniques after distal pancreatectomy.

ANTECEDENTES: La incidencia de fístula pancreática (postoperative pancreatic fistula, POPF) tras una pancreatectomía distal sigue siendo alta y se han utilizado diferentes técnicas para el cierre del muñón pancreático con la intención de reducir su incidencia. Se realizó un metaanálisis en red para comparar las técnicas de cierre del muñón pancreático realizadas con más frecuencia después de la pancreatectomía distal y determinar qué técnica se asocia a una menor tasa de POPF. MÉTODOS: Se realizó una búsqueda sistemática en las bases de datos Scopus, PubMed, Medline y EMBASE de los RCTs que podían ser incluidos en estudio. La variable principal fue la aparición de POPF clínicamente relevante. Las variables secundarias fueron el tiempo operatorio, la pérdida de sangre, las colecciones intraabdominales, las complicaciones postoperatorias y la mortalidad a los 30 días. RESULTADOS: En el metaanálisis se incluyeron 16 RCTs con 1.984 pacientes y 8 técnicas diferentes de cierre del muñón pancreático. Los mejores resultados (menor tasa de POPF clínicamente relevante, menor pérdida sanguínea intraoperatoria, menor número de abscesos intraabdominales, menor tasa de complicaciones generales y menor mortalidad a los 30 días) se obtuvieron con el refuerzo del muñón pancreático con parches (de ligamento redondo o seromuscular), seguidos del grapado quirúrgico o la sutura simple. El cierre con parche del ligamento redondo fue superior al parche seromuscular en la prevención de POPF clínicamente relevante en una cohorte suficiente para el análisis estadístico comparativo. Los peores resultados en la mayoría de las variables postoperatorias se obtuvieron con el cierre simple. CONCLUSIÓN: En la pancreatectomía distal, la menor tasa de POPF y los mejores resultados perioperatorios se obtuvieron con el refuerzo con parches, seguidos del grapado quirúrgico o la sutura simple.

Hyperactive cyclic motor activity in the distal colon after colonic surgery as defined by high-resolution colonic manometry.

BACKGROUND: Recovery after colonic surgery is invariably delayed by disturbed gut motility. It is commonly assumed that colonic motility becomes quiescent after surgery, but this hypothesis has not been evaluated rigorously. This study quantified colonic motility through the early postoperative period using high-resolution colonic manometry. METHODS: Fibre-optic colonic manometry was performed continuously before, during and after surgery in the left colon and rectum of patients undergoing right hemicolectomy, and in healthy controls. Motor events were characterized by pattern, frequency, direction, velocity, amplitude and distance propagated. RESULTS: Eight patients undergoing hemicolectomy and nine healthy controls were included in the study. Colonic motility became markedly hyperactive in all operated patients, consistently dominated by cyclic motor patterns. Onset of cyclic motor patterns began to a minor extent before operation, occurring with increasing intensity nearer the time of surgery; the mean(s.d.) active duration was 12(7) per cent over 3 h before operation and 43(17) per cent within 1 h before surgery (P = 0.024); in fasted controls it was 2(4) per cent (P < 0·001). After surgery, cyclic motor patterns increased markedly in extent and intensity, becoming nearly continuous (active duration 94(13) per cent; P < 0·001), with peak frequency 2-4 cycles per min in the sigmoid colon. This postoperative cyclic pattern was substantially more prominent than in non-operative controls, including in the fed state (active duration 27(20) per cent; P < 0·001), and also showed higher antegrade velocity (P < 0·001). CONCLUSION: Distal gut motility becomes markedly hyperactive with colonic surgery, dominated by cyclic motor patterns. This hyperactivity likely represents a novel pathophysiological aspect of the surgical stress response. Hyperactive motility may contribute to gut dysfunction after surgery, potentially offering a new therapeutic target to enhance recovery.

TBL1XR1 mutations in Pierpont syndrome are not restricted to the recurrent p.Tyr446Cys mutation.

Pierpont syndrome is a rare and sporadic syndrome, including developmental delay, facial characteristics, and abnormal extremities. Recently, a recurrent de novo TBL1XR1 variant (c.1337A > G; p.Tyr446Cys) has been identified in eight patients by whole-exome sequencing. A dominant-negative effect of this mutation is strongly suspected, since patients with TBL1XR1 deletion and other variants predicting loss of function do not share the same phenotype. We report two patients with typical Pierpont-like syndrome features. Exome sequencing allowed identifying a de novo heterozygous missense TBL1XR1 variant in both patients, different from those already reported: p.Cys325Tyr and p.Tyr446His. The localization of these mutations and clinical features of Pierpont-like syndrome suggest that their functional consequences are comparable with the recurrent mutation previously described, and provided additional data to understand molecular mechanisms of TBL1XR1 anomalies.

Perinatal outcomes associated with abnormal cardiac remodeling in women with treated chronic hypertension.

BACKGROUND: Adverse maternal outcomes associated with chronic hypertension include accelerated hypertension and resultant target organ damage. One example is long-standing hypertension leading to maternal cardiac dysfunction. Our group has previously identified that features of such injury manifest as cardiac remodeling with left ventricular hypertrophy. Moreover, these features of cardiac remodeling identified in women with chronic hypertension during pregnancy were associated with adverse perinatal outcomes. Recent definitions of maternal cardiac remodeling using echocardiography have been expanded to include measurements of wall thickness. We hypothesized that these new features characterizing cardiac remodeling in women with chronic hypertension may also be associated with adverse perinatal outcomes. OBJECTIVE: There were 3 aims in this study of women with treated chronic hypertension during pregnancy: to (1) apply the updated definitions of maternal cardiac remodeling; (2) elucidate whether these features of cardiac remodeling were associated with adverse perinatal outcomes; and (3) determine which, if any, of the newly defined cardiac remodeling strata were most damaging when compared to women with normal cardiac geometry. STUDY DESIGN: This was a retrospective study of women with treated chronic hypertension during pregnancy delivered from January 2009 through January 2016. Cardiac remodeling was categorized by left ventricular mass index and relative wall thickness into 4 groups determined using the 2015 American Society of Echocardiography guidelines: normal geometry, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. Perinatal outcomes were analyzed according to each category of cardiac remodeling compared with outcomes in women with normal geometry. RESULTS: A total of 314 women with treated chronic hypertension underwent echocardiography at a mean gestational age of 17.9 weeks. There were no differences between maternal age (P = .896), habitus (P = .36), or duration of chronic hypertension (P = .212) among the 4 groups. Abnormal cardiac remodeling was found in 51% and was significantly associated with increased rates of superimposed preeclampsia (P = .015), preterm birth (P < .001), and neonatal intensive care admission (P = .003). These outcomes reached the greatest significance when comparisons were made between eccentric hypertrophy and normal geometry. CONCLUSION: Using current American Society of Echocardiography guidelines, 51% of women with treated chronic hypertension during pregnancy have some degree of abnormal cardiac remodeling. Any suggestion of maternal cardiac remodeling, regardless of subtype, was associated with increased risks for superimposed preeclampsia and preterm birth with its resultant perinatal sequelae. Eccentric ventricular hypertrophy, previously thought to mimic exercise physiology, appears to be the most associated with adverse perinatal outcomes. Despite evidence of cardiac remodeling, ejection fraction was preserved.

Association Between Circular Stapler Diameter and Stricture Rates Following Gastrointestinal Anastomosis: Systematic Review and Meta-analysis.

BACKGROUND: Stricture is a common complication of gastrointestinal (GI) anastomoses, associated with impaired quality of life, risk of malnutrition, and further interventions. This systematic review and meta-analysis aimed to determine the association between circular stapler diameter and anastomotic stricture rates throughout the GI tract. METHODS: A systematic literature search of EMBASE, MEDLINE and Cochrane Library was performed. The primary outcome was the rate of radiologically or endoscopically confirmed anastomotic stricture. Pooled odds ratios (OR) were calculated using random-effects models to determine the effect of circular stapler diameter on stricture rates in different regions of the GI tract. RESULTS: Twenty-one studies were identified: seven oesophageal, twelve gastric, and three lower GI. Smaller stapler sizes were strongly associated with higher anastomotic stricture rates throughout the GI tract. The oesophageal anastomosis studies showed; 21 versus 25 mm circular stapler: OR 4.39 ([95% CI 2.12, 9.07]; P < 0.0001); 25 versus 28/29 mm circular stapler: OR 1.71 ([95% CI 1.15, 2.53]; P < 0.008). Gastric studies showed; 21 versus 25 mm circular stapler: OR 3.12 ([95% CI 2.23, 4.36]; P < 0.00001); 25 versus 28/29 mm circular stapler: OR 7.67 ([95% CI 1.86, 31.57]; P < 0.005). Few lower GI studies were identified, though a similar trend was found: 25 versus 28/29 mm circular stapler: pooled OR 2.61 ([95% CI 0.82, 8.29]; P = 0.100). CONCLUSIONS: The use of larger circular stapler sizes is strongly associated with reduced risk of anastomotic stricture in the upper GI tract, though data from lower GI joins are limited.

Fungal-derived cues promote ocular autoimmunity through a Dectin-2/Card9-mediated mechanism.

Uveitis (intraocular inflammation) is a leading cause of loss of vision. Although its aetiology is largely speculative, it is thought to arise from complex genetic-environmental interactions that break immune tolerance to generate eye-specific autoreactive T cells. Experimental autoimmune uveitis (EAU), induced by immunization with the ocular antigen, interphotoreceptor retinoid binding protein (IRBP), in combination with mycobacteria-containing complete Freund's adjuvant (CFA), has many clinical and histopathological features of human posterior uveitis. Studies in EAU have focused on defining pathogenic CD4+ T cell effector responses, such as those of T helper type 17 (Th17) cells, but the innate receptor pathways precipitating development of autoreactive, eye-specific T cells remain poorly defined. In this study, we found that fungal-derived antigens possess autoimmune uveitis-promoting function akin to CFA in conventional EAU. The capacity of commensal fungi such as Candida albicans or Saccharomyces cerevisae to promote IRBP-triggered EAU was mediated by Card9. Because Card9 is an essential signalling molecule of a subgroup of C-type lectin receptors (CLRs) important in host defence, we evaluated further the proximal Card9-activating CLRs. Using single receptor-deficient mice we identified Dectin-2, but not Mincle or Dectin-1, as a predominant mediator of fungal-promoted uveitis. Conversely, Dectin-2 activation by α-mannan reproduced the uveitic phenotype of EAU sufficiently, in a process mediated by the Card9-coupled signalling axis and interleukin (IL)-17 production. Taken together, this report relates the potential of the Dectin-2/Card9-coupled pathway in ocular autoimmunity. Not only does it contribute to understanding of how innate immune receptors orchestrate T cell-mediated autoimmunity, it also reveals a previously unappreciated ability of fungal-derived signals to promote autoimmunity.

Mesenchymal Stromal Cells are Readily Recoverable from Lung Tissue, but not the Alveolar Space, in Healthy Humans.

Stromal support is critical for lung homeostasis and the maintenance of an effective epithelial barrier. Despite this, previous studies have found a positive association between the number of mesenchymal stromal cells (MSCs) isolated from the alveolar compartment and human lung diseases associated with epithelial dysfunction. We hypothesised that bronchoalveolar lavage derived MSCs (BAL-MSCs) are dysfunctional and distinct from resident lung tissue MSCs (LT-MSCs). In this study, we comprehensively interrogated the phenotype and transcriptome of human BAL-MSCs and LT-MSCs. We found that MSCs were rarely recoverable from the alveolar space in healthy humans, but could be readily isolated from lung transplant recipients by bronchoalveolar lavage. BAL-MSCs exhibited a CD90Hi , CD73Hi , CD45Neg , CD105Lo immunophenotype and were bipotent, lacking adipogenic potential. In contrast, MSCs were readily recoverable from healthy human lung tissue and were CD90Hi or Lo , CD73Hi , CD45Neg , CD105Int and had full tri-lineage potential. Transcriptional profiling of the two populations confirmed their status as bona fide MSCs and revealed a high degree of similarity between each other and the archetypal bone-marrow MSC. 105 genes were differentially expressed; 76 of which were increased in BAL-MSCs including genes involved in fibroblast activation, extracellular matrix deposition and tissue remodelling. Finally, we found the fibroblast markers collagen 1A1 and α-smooth muscle actin were increased in BAL-MSCs. Our data suggests that in healthy humans, lung MSCs reside within the tissue, but in disease can differentiate to acquire a profibrotic phenotype and migrate from their in-tissue niche into the alveolar space. Stem Cells 2016;34:2548-2558.

Frequency and consequences of ventricular hypertrophy in pregnant women with treated chronic hypertension.

BACKGROUND: Ventricular hypertrophy is a known sequela of long-standing chronic hypertension with associated morbidity and mortality. OBJECTIVE: We sought to assess the frequency and importance of left ventricular hypertrophy in gravidas treated for chronic hypertension during pregnancy. STUDY DESIGN: This was a retrospective study of pregnant women with chronic hypertension who were delivered at our hospital from January 2009 through February 2015. All women who were given antihypertensive therapy underwent maternal echocardiography and were managed in a dedicated, high-risk prenatal clinic. Left ventricular hypertrophy was defined using the criteria of the American Society of Echocardiography as left ventricular mass indexed to maternal body surface area with a value of >95 g/m2. Maternal and infant outcomes were then analyzed according to the presence or absence of left ventricular hypertrophy. RESULTS: Of 253 women who underwent echocardiography, 48 (19%) met criteria for left ventricular hypertrophy. Women in this latter cohort were significantly more likely to be African American (P = .031), but there were no other demographic differences. More than 85% of the entire cohort had a body mass index >30 kg/m2 and a third of all women had class III obesity with a body mass index of >40 kg/m2. Importantly, duration of chronic hypertension (P = .248) and gestational age at time of echocardiography (P = .316) did not differ significantly between the groups. Left ventricular function was preserved in both groups as measured by left ventricular ejection fraction (P = .303). Those with ventricular hypertrophy were at greater risk to be delivered preterm (P = .001), to develop superimposed preeclampsia (P = .028), and to have an infant requiring intensive care (P = .023) when compared with women without ventricular hypertrophy. These findings persisted after adjustment for age, race, and parity. The gestational age at delivery according to measured left ventricular size was also examined and with increasing ventricular mass there was a significant association with the severity of preterm birth (P < .001). CONCLUSION: Left ventricular hypertrophy was identified in 1 in 5 women given antepartum treatment for chronic hypertension. Further analysis showed that these women were at significantly greater risk for superimposed preeclampsia and its attendant perinatal sequelae of preterm birth.

Defining low anterior resection syndrome: a systematic review of the literature.

AIM: There is increasing awareness of the poor functional outcome suffered by many patients after sphincter-preserving rectal resection, termed 'low anterior resection syndrome' (LARS). There is no consensus definition of LARS and varying instruments have been employed to measure functional outcome, complicating research into prevalence, contributing factors and potential therapies. We therefore aimed to describe the instruments and outcome measures used in studies of bowel dysfunction after low anterior resection and identify major themes used in the assessment of LARS. METHOD: A systematic review of the literature was performed for studies published between 1986 and 2016. The instruments and outcome measures used to report bowel function after low anterior resection were extracted and their frequency of use calculated. RESULTS: The search revealed 128 eligible studies. These employed 18 instruments, over 30 symptoms, and follow-up time periods from 4 weeks to 14.6 years. The most frequent follow-up period was 12 months (48%). The most frequently reported outcomes were incontinence (97%), stool frequency (80%), urgency (67%), evacuatory dysfunction (47%), gas-stool discrimination (34%) and a measure of quality of life (80%). Faecal incontinence scoring systems were used frequently. The LARS score and the Bowel Function Instrument (BFI) were used in only nine studies. CONCLUSION: LARS is common, but there is substantial variation in the reporting of functional outcomes after low anterior resection. Most studies have focused on incontinence, omitting other symptoms that correlate with patients' quality of life. To improve and standardize research into LARS, a consensus definition should be developed, and these findings should inform this goal.

Cervical Length in Patients at Risk for Placenta Accreta.

OBJECTIVES: To evaluate cervical length measurements in women with placenta accreta compared to women with a nonadherent low-lying placenta or placenta previa and evaluate this relationship in terms of vaginal bleeding, preterm labor, and preterm birth. METHODS: We conducted a retrospective cohort study between 1997 and 2011 of gravidas with more than 1 prior cesarean delivery who had a transvaginal ultrasound examination between 24 and 34 weeks for a low-lying placenta or placenta previa. Cervical length was measured from archived images in accordance with national guidelines by a single investigator, who was blinded to outcomes and ultrasound reports. The diagnosis of placental accreta was based on histologic confirmation. For study purposes, preterm birth was defined as less than 36 weeks, and cervical lengths of 3 cm or less were considered short. Standard statistical analyses were used. RESULTS: A total of 125 patients met inclusion criteria. The cohort was divided into patients with (n = 43 [34%]) and without (n = 82 [66%]) placenta accreta and stratified by gestational age at the ultrasound examinations. Women with placenta accreta had shorter cervical length measurements during their 32- to 34-week ultrasound examinations (mean ± SD, 3.23 ± 0.98 versus 3.95 ± 1.0 cm; P < .01) and were more likely to have a short cervix of 3 cm or less (P = .001). However, these findings did not correlate with the degree of invasion (P = .3), or higher rates of vaginal bleeding and preterm labor (P = .19) resulting in preterm birth before 36 weeks (P = .64). CONCLUSIONS: Women with placenta accreta had shorter cervical lengths at 32 to 34 weeks than women with a nonadherent low-lying placenta or placenta previa, but this finding did not correlate with a higher risk of vaginal bleeding or preterm labor resulting in preterm birth before 36 weeks.

Access to treatment with controlled medicines rationale and recommendations for neutral, precise, and respectful language.

The European Pain Federation EFIC, the International Association for Hospice and Palliative Care, International Doctors for Healthier Drug Policies, the Swiss Romandy College for Addiction Medicine, the Swiss Society of Addiction Medicine, and the World Federation for the Treatment of Opioid Dependence called on medical journals to ensure that authors always use terminology that is neutral, precise, and respectful in relation to the use of psychoactive substances. It has been shown that language can propagate stigma, and that stigma can prevent people from seeking help and influence the effectiveness of social and public-health policies. The focus of using appropriate terminology should extend to all patients who need controlled medicines, avoiding negative wording. A narrow focus on a few terms and medical communication only should be avoided. The appropriateness of terms is not absolute and indeed varies between cultures and regions and over time. For this reason, it is important that communities establish their own consensus of what is 'neutral', 'precise', and 'respectful'. We identified twenty-three problematic terms (most of them we suggest avoiding) and their possible alternatives. The use of appropriate language improves scientific quality of articles and increases chances that patients will receive the best treatment and that government policies on psychoactive substance policies will be rational.