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.

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.

Difficulty with Oral Health Complications in Adolescents with Developmental Disability and Obesity.

INTRODUCTION: Developmental disabilities (DDs), obesity, and dental caries are highly prevalent health conditions among adolescents. Evidence indicates that a significant proportion of adolescents with DDs are obese, and those with obesity and dental caries share common risk factors. OBJECTIVE: In this first-ever US-based cross-sectional national study, we assessed the likelihood of adolescents with DDs and obesity experiencing chronic difficulty with decayed teeth, toothaches, bleeding gums, and eating and swallowing due to a health condition among adolescents with DDs and obesity compared to adolescents with no DDs or obesity. METHODS: For this secondary data analysis study, we used data of 68,942 adolescents aged 10 to 17 y from the 2016 through 2019 National Survey of Children's Health. Weighted descriptive and bivariate analyses were conducted. Four multiple logistic regression models predicting chronic difficulty in the past 12 mo with decayed teeth, toothaches, bleeding gums, and eating and swallowing due to a health condition were conducted, controlling for other variables. RESULTS: The adjusted odds ratio (aOR) of experiencing chronic difficulty in the past 12 mo for adolescents with no DDs or obesity was significantly lower for decayed teeth (aOR, 0.64; 95% confidence interval [CI], 0.51-0.80; P < 0.0001), toothaches (aOR, 0.43; 95% CI, 0.30-0.60; P < 0.0001), bleeding gums (aOR, 0.48; 95% CI, 0.33-0.70; P < 0.0001), and eating or swallowing due to a health condition (aOR, 0.34; 95% CI, 0.20-0.57; P < 0.0001) compared to adolescents with both DDs and obesity. CONCLUSIONS: Results from this study indicate that DD adolescents with obesity have more/greater impending oral health needs than adolescents with no DDs or obesity. KNOWLEDGE TRANSFER STATEMENT: Results of this study highlight the high oral health needs and the chronic difficulty adolescents with developmental disabilities and obesity experience compared to adolescents without developmental disabilities and obesity. Targeted oral health policies and interventions that will promote oral health among this high-risk group are recommended.

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.

Nifedipine for Acute Tocolysis of Preterm Labor: A Placebo-Controlled Randomized Trial.

OBJECTIVE: To evaluate the effectiveness of acute nifedipine tocolysis in preventing preterm birth in women in preterm labor. METHOD: This was a randomized, double-blind, placebo-controlled trial of nifedipine in women with a singleton pregnancy between 28 0/7 and 33 6/7 weeks of gestation who were admitted with uterine activity, intact membranes, and cervical dilatation from 2 to 4 cm. Women were randomized to receive nifedipine 20 mg or placebo orally, followed by a repeat dose after 90 minutes if contractions persisted. The study drug was continued every 4 hours to complete a 48-hour regimen. The primary outcome was birth before 37 weeks of gestation. A total of 150 women were necessary to detect a one-third reduction in this outcome. After treating 88 patients, a preplanned interim analysis of blinded outcomes by the Data Safety Monitoring Committee recommended discontinuation of the trial due to futility. RESULTS: A total of 90 women were enrolled between May 2014 and November 2017. After two women withdrew, 88 were analyzed: 46 in the nifedipine group and 42 in the placebo group. There was no significant difference in the primary outcome of delivery before 37 weeks of gestation in the nifedipine group compared with the placebo group (52% vs 48%, relative risk [RR] 1.1, 95% CI 0.7-1.7), nor in the secondary outcome of delivery at least 48 hours from randomization (78% vs 71%, respectively, RR 1.1, 95% CI 0.9-1.4). There were also no significant differences between groups in neonatal outcomes. CONCLUSION: Acute tocolysis of preterm labor with nifedipine did not affect preterm birth rates, delivery within 48 hours, or neonatal outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02132533.

Efecto del Programa de Prevención de Lesiones en Seleccionados Masculinos de Hockey sobre Césped / Effect of the Injury Prevention Program on Selected Men's Field Hockey Teams

Introducción: La implementación de programas de prevención de lesiones en deportistas es fundamental para evitar las consecuencias físicas, de rendimiento y salud que puede provocar una lesión. No obstante, en hockey sobre césped la evidencia es escasa y poco transferible a jugadores masculinos de élite, existiendo así la necesidad de desarrollar estudios en esta población específica. Objetivos: Determinar el efecto de un programa de prevención de lesiones en seleccionados masculinos de hockey sobre césped en relación a la cantidad de lesiones en extremidades inferiores y zona lumbar presentadas por los jugadores en los Juegos Panamericanos. Métodos: Se analizó a 30 jugadores realizando una comparación mediante un análisis estadístico de las lesiones registradas en seleccionados nacionales de hockey sobre césped durante los Juegos Panamericanos del año 2015 (grupo control, sin programa de prevención de lesiones) y durante los Juegos Panamericanos del año 2019 (grupo intervenido con programa de prevención de lesiones). Resultados: No se encontró diferencia estadísticamente significativa en cuanto a cantidad de lesiones presentadas por los jugadores comparando los años 2015 y 2019 (p=0,068). Se encontró diferencia estadísticamente significativa en cuanto a cantidad de jugadores lesionados comparando los años 2015 y 2019 (p= 0.04). Conclusión: Se evidencia una reducción significativa en la cantidad de jugadores lesionados, en el grupo de jugadores que realizó el programa de prevención de lesiones previo a los Juegos Panamericanos de Lima 2019.

Introduction: The implementation of injury prevention programs in athletes is essential to avoid the physical, performance and health consequences that an injury can cause. However, the evidence in field hockey is scarce and not very transferable to elite male athletes, thus there is a need to carry out studies in this specific population. Objectives: To determine the effect of an injury prevention program in national selected male field hockey players in relation to the amount of injuries in the lower extremities (LES) and lumbar area presented by the players in the Pan American Games. Methods: 30 players were analyzed by making a comparison through a statistical analysis of the injuries registered in selected national field hockey players during the Pan American Games of 2015 (control group, without injury prevention program) and during the Pan American Games of 2019 (group intervened with injury prevention program). Results: No statistically significant difference was found in terms of the amount of injuries presented by the players comparing the years 2015 and 2019 (p = 0.068). A statistically significant difference was found in terms of the number of injured players comparing the years 2015 and 2019 (p = 0.04). Conclusion: A significant reduction in the number of injured players is evidenced in the group of players that carried out the injury prevention program prior to the Lima 2019 Pan American Games.

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.

The impact of baseline proteinuria in pregnant women with pregestational diabetes mellitus.

BACKGROUND: The incidence of diabetes in pregnancy has increased dramatically with the rising rates of obesity. Because there are a number of recognized adverse maternal and fetal outcomes associated with diabetes, there have been several attempts to classify this disorder for perinatal risk stratification. One of the first classification systems for pregnancy was developed by White nearly 70 years ago. More recently, efforts to stratify diabetic disease severity according to vasculopathy have been adopted. Regardless of classification system, vasculopathy-associated effects have been associated with worsening pregnancy outcomes. Defining vasculopathy within an organ system, however, has not been consistent. For example, definitions of diabetic kidney disease differ from the previously used threshold of ≥500 mg/d by White for pregnancy to varying thresholds of albuminuria by the American Diabetes Association. OBJECTIVE: To evaluate a proteinuria threshold that was a relevant determinant of perinatal risk in a cohort of women with type 2 diabetes. MATERIALS AND METHODS: This was a retrospective cohort study of women with pregestational diabetes delivered of nonanomalous, singleton, liveborn infants. All women were assessed for baseline maternal disease burden with a 24-hour proteinuria quantification performed before 20 weeks' gestation. Women with <500 mg/d on 24-hour urine collections were included. Perinatal outcomes were analyzed according to the following protein excretion values: 50-100, 101-200, 201-300, and 301-499 mg/d. Based on trends noted in these results and using the prior definition of the American Diabetes Association of 300 mg/d of albumin for diabetic kidney disease, women were then analyzed according to 24-hour urine collections of ≤300 or >300 mg/d. RESULTS: Between 2009 and 2016, a total of 594 women with pregestational diabetes were found to meet study criteria. When analyzed according to protein excretion values 50-100, 101-200, 201-300, and 301-499 mg/d, there were no differences in maternal demographics. The rate of preeclampsia with severe features (P for trend = .02), preterm birth at <37 weeks (P for trend <.001), and birthweight <10th percentile (P for trend = .02) were significantly associated with increasing proteinuria excretion, with the highest rates in the >300 mg/d group. Perinatal outcomes were then examined in the context of 24-hour urine protein excretion values of ≤300 or >300 mg/d, with no differences in maternal demographics. Protein excretion values >300 mg/d were significantly associated with preterm birth <37 weeks (P = .003), preeclampsia with severe features (P = .002), and birthweight <10th percentile (P = .048). CONCLUSION: White's classification in 1949 was developed to stratify perinatal risks based on maternal disease burden, and it was found that urinary protein excretion of >500 mg/d was associated with adverse pregnancy outcomes. In a contemporary cohort of pregnant women, proteinuria >300 mg/d was associated with preterm birth, preeclampsia with severe features, and birthweight <10th percentile.

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 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.

Identification of a Sacral, Visceral Sensory Transcriptome in Embryonic and Adult Mice.

Visceral sensory neurons encode distinct sensations from healthy organs and initiate pain states that are resistant to common analgesics. Transcriptome analysis is transforming our understanding of sensory neuron subtypes but has generally focused on somatic sensory neurons or the total population of neurons in which visceral neurons form the minority. Our aim was to define transcripts specifically expressed by sacral visceral sensory neurons, as a step towards understanding the unique biology of these neurons and potentially leading to identification of new analgesic targets for pelvic visceral pain. Our strategy was to identify genes differentially expressed between sacral dorsal root ganglia (DRG) that include somatic neurons and sacral visceral neurons, and adjacent lumbar DRG that comprise exclusively of somatic sensory neurons. This was performed in adult and E18.5 male and female mice. By developing a method to restrict analyses to nociceptive Trpv1 neurons, a larger group of genes were detected as differentially expressed between spinal levels. We identified many novel genes that had not previously been associated with pelvic visceral sensation or nociception. Limited sex differences were detected across the transcriptome of sensory ganglia, but more were revealed in sacral levels and especially in Trpv1 nociceptive neurons. These data will facilitate development of new tools to modify mature and developing sensory neurons and nociceptive pathways.

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.

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.

Dental Fluorosis Trends in US Oral Health Surveys: 1986 to 2012.

INTRODUCTION: Dental fluorosis has been assessed only 3 times in nationally representative oral health surveys in the United States. The first survey was conducted by the National Institute of Dental Research from 1986 to 1987. Subsequently, the National Health and Nutrition Examination Survey (NHANES) conducted fluorosis assessments from 1999 to 2004 and more recently from 2011 to 2012. A large increase in prevalence and severity of fluorosis occurred between the 1986-1987 and 1999-2004 surveys. OBJECTIVES: To determine whether the trend of increasing fluorosis continued in the 2011-2012 survey. METHODS: We analyzed publicly available data from the 2011-2012 NHANES, calculating fluorosis prevalence and severity using 3 measures: person-level Dean's Index score, total prevalence of those with Dean's Index of very mild degree and greater, and Dean's Community Fluorosis Index. We examined these fluorosis measures by several sociodemographic factors and compared results with the 2 previous surveys. Analyses accounted for the complex design of the surveys to provide nationally representative estimates. RESULTS: Large increases in severity and prevalence were found in the 2011-2012 NHANES as compared with the previous surveys, for all sociodemographic categories. For ages 12 to 15 y-an age range displaying fluorosis most clearly-total prevalence increased from 22% to 41% to 65% in the 1986-1987, 1999-2004, and 2011-2012 surveys, respectively. The rate of combined moderate and severe degrees increased the most, from 1.2% to 3.7% to 30.4%. The Community Fluorosis Index increased from 0.44 to 0.67 to 1.47. No clear differences were found in fluorosis rates among categories for most of the sociodemographic variables in the 2011-2012 survey. CONCLUSION: Large increases in fluorosis prevalence and severity occurred. We considered several possible spurious explanations for these increases but largely ruled them out based on counterevidence. We suggest several possible real explanations for the increases. KNOWLEDGE TRANSFER STATEMENT: The results of this study greatly increase the evidence base indicating that objectionable dental fluorosis has increased in the United States. Dental fluorosis is an undesirable side effect of too much fluoride ingestion during the early years of life. Policy makers and professionals can use the presented evidence to weigh the risks and benefits of water fluoridation and early exposure to fluoridated toothpaste.

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.