Citations

Abstract Objective To formulate clinical practice guidelines for the endocrine treatment of hypothalamic–pituitary and growth disorders in survivors of childhood cancer. Participants An Endocrine Society–appointed guideline writing committee of six medical experts and a methodologist. Conclusions Due to remarkable improvements in childhood cancer treatment and supportive care during the past several decades, 5-year survival rates for childhood cancer currently are >80%. However, by virtue of their disease and its treatments, childhood cancer survivors are at increased risk for a wide range of serious health conditions, including disorders of the endocrine system. Recent data indicate that 40% to 50% of survivors will develop an endocrine disorder during their lifetime. Risk factors for endocrine complications include both host (e.g., age, sex) and treatment factors (e.g., radiation). Radiation exposure to key endocrine organs (e.g., hypothalamus, pituitary, thyroid, and gonads) places cancer survivors at the highest risk of developing an endocrine abnormality over time; these endocrinopathies can develop decades following cancer treatment, underscoring the importance of lifelong surveillance. The following guideline addresses the diagnosis and treatment of hypothalamic–pituitary and growth disorders commonly encountered in childhood cancer survivors.

SummaryBackgroundThere are limited data to inform positioning of agents for treating moderate‐severe Crohn's disease (CD).AimWe assessed comparative efficacy and safety of first‐line (biologic‐naïve) and second‐line (prior exposure to anti‐tumour necrosis factor [TNF]‐α) agents) biologic therapy for moderate‐severe CD, through a systematic review and network meta‐analysis, and appraised quality of evidence (QoE) using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.MethodsWe identified randomised controlled trials (RCTs) in adults with moderate‐severe CD treated with approved anti‐TNF agents, anti‐integrin agents and anti‐IL12/23 agents, first‐line or second‐line, and compared with placebo or another active agent. Efficacy outcomes were induction and maintenance of clinical remission; safety outcomes were serious adverse events and infections. Network meta‐analyses were performed, and ranking was assessed using surface under the cumulative ranking (SUCRA) probabilities.ResultsNo head‐to‐head trials were identified. In biologic‐naïve patients, infliximab (SUCRA,0.93) and adalimumab (SUCRA,0.75) were ranked highest for induction of clinical remission (moderate QoE). In patients with prior anti‐TNF exposure, adalimumab (SUCRA, 0.91; low QoE, in patients with prior response or intolerance to anti‐TNF agents) and ustekinumab (SUCRA, 0.71) were ranked highest for induction of clinical remission. In patients with response to induction therapy, adalimumab (SUCRA, 0.97) and infliximab (SUCRA, 0.68) were ranked highest for maintenance of remission. Ustekinumab had lowest risk of serious adverse events (SUCRA, 0.72) and infection (SUCRA, 0.71; along with infliximab, SUCRA, 0.83) in maintenance trials.ConclusionIndirect comparisons suggest that infliximab or adalimumab may be preferred first‐line agents, and ustekinumab a preferred second‐line agent, for induction of remission in patients with moderate‐severe CD. Head‐to‐head trials are warranted.

Objective Peribiliary cysts are usually benign, although severe complications and mortality may occur, and they may be confounded with other diseases. No classification delineating their different characteristics exists. Design We performed a systematic review of the frequency and clinical manifestations of peribiliary cysts. Two reviewers identified studies after searching multiple databases on 2 August 2017. Results These cysts were prevalent in cirrhosis (9%). A total of 135 patients were reported in 72 papers with sufficient clinical data (10 countries, 65% from Japan, median age 63 years (range: 4–88), and 80% were males). Symptoms were present in 70%. Misdiagnosis occurred in 40%, and 33% underwent therapeutic misadventures. Cysts were solitary in 10%. Obstructive features and cholangitis were observed in 36% and 12.5%, respectively. Cysts progression was observed in 37.5% over a median of 18 months. Mortality was 24%, mostly due to cirrhosis. A classification framework is proposed, wherein type I includes hepatic, type II extrahepatic and type III mixed hepatic and extrahepatic cysts, each having distinct features. Specifically, type II was more frequent in females, solitary, without cirrhosis, presenting with obstructive jaundice, more difficult to diagnose and required more surgical interventions (all p<0.05). Conclusion Although rarely studied in the literature, peribiliary cysts were frequent in studies designed to evaluate their prevalence, and were mostly asymptomatic. Inaccurate diagnosis, therapeutic misadventures, cysts progression and cysts-related complications are frequent. In a novel classification framework based on location, extrahepatic peribiliary cysts have distinct characteristics and require a special approach for diagnosis and management.

Background The relationship between delayed gastric emptying and upper GI symptoms (UGI Sx) is controversial. Objective To assess association between gastric emptying and UGI Sx, independent of treatment. Design We performed a systematic review and meta-analysis of the literature from 2007 to 2017, review of references and additional papers identified by content expert. We included studies evaluating the association between gastric emptying and nausea, vomiting, early satiety/postprandial fullness, abdominal pain and bloating. Covariate analyses included optimal gastric emptying test method, gastric emptying type (breath test or scintigraphy) and patient category. Meta-regression compared the differences based on type of gastric emptying tests. Results Systematic review included 92 gastric emptying studies (26 breath test, 62 scintigraphy, 1 ultrasound and 3 wireless motility capsule); 25 of these studies provided quantitative data for meta-analysis (15 scintigraphy studies enrolling 4056 participants and 10 breath test studies enrolling 2231 participants). Meta-regression demonstrated a significant difference between optimal and suboptimal gastric emptying test methods when comparing delayed gastric emptying with nausea and vomiting. On evaluating studies using optimal gastric emptying test methodology, there were significant associations between gastric emptying and nausea (OR 1.6, 95% CI 1.4 to 1.8), vomiting (OR 2.0, 95% CI 1.6 to 2.7), abdominal pain (OR 1.5, 95% CI 1.0 to 2.2 ) and early satiety/fullness (OR 1.8, 95% CI 1.2 to 2.6) for patients with UGI Sx; gastric emptying and early satiety/fullness in patients with diabetes; gastric emptying and nausea in patients with gastroparesis. Conclusions The systematic review and meta-analysis supports an association between optimally measured delayed gastric emptying and UGI Sx.

AbstractBackground & AimsAcute liver failure caused by hepatitis E virus genotype 3 and 4 has been rarely described. Because of the presence of a short golden therapeutic window in patients with viral acute liver failure from other causes, it is possible that early recognition and treatment might reduce the morbidity and mortality. We performed a systematic review and pooled analysis of acute liver failure caused by hepatitis E virus genotype 3 and 4.MethodsTwo reviewers appraised studies after searching multiple databases on June 12th, 2017. Appropriate tests were used to compare hepatitis E virus genotype 3 vs 4, suspected vs confirmed genotypes, hepatitis E virus‐RNA positive vs negative, and to discern important mortality risk factors.ResultsWe identified 65 patients, with median age 58 years (range: 3‐79), and a male to female ratio of 1.2:1. The median bilirubin, ALT, AST and alkaline phosphatase (expressed by multiplication of the upper limit of normal) levels were 14.8, 45.3, 34.8 and 1.63 respectively. Antihepatitis E virus IgG, antihepatitis E virus IgM and hepatitis E virus‐RNA were positive in 84%, 91% and 86% of patients respectively. The median interval from symptoms onset to acute liver failure was 23 days, and 16 patients underwent liver transplantation. Final outcome was reported in 58 patients and mortality was 46%. Age was a predictor of poor prognosis in multivariate analysis. No important differences were found between patients infected with genotype 3 vs 4, patients with confirmed vs suspected genotypes, or patients with positive vs negative RNA.ConclusionAcute liver failure caused by hepatitis E virus genotype 3 and 4 is rare, similar between genotypes, occurs commonly in middle‐aged/elderly patients and has a very high mortality. Age is predictive of poor prognosis in multivariate analysis.

Publication bias occurs when studies with statistically significant results have increased likelihood of being published. Publication bias is commonly associated with inflated treatment effect which lowers the certainty of decision makers about the evidence. In this guide we propose that systematic reviewers and decision makers consider the direction and magnitude of publication bias, as opposed to just the binary determination of the presence of this bias, before lowering their certainty in the evidence. Direction of bias may not always exaggerate the treatment effect. The presence of bias with a trivial magnitude may not affect the decision at hand. Various statistical approaches are available to determine the direction and magnitude of publication bias.

The data on speckle-tracking echocardiography (STE) in patients with sepsis are limited. This systematic review from 1975 to 2016 included studies in adults and children evaluating cardiovascular dysfunction in sepsis, severe sepsis, and septic shock utilizing STE for systolic global longitudinal strain (GLS). The primary outcome was short- or long-term mortality. Given the significant methodological and statistical differences between published studies, combining the data using meta-analysis methods was not appropriate. A total of 120 studies were identified, with 5 studies (561 patients) included in the final analysis. All studies were prospective observational studies using the 2001 criteria for defining sepsis. Three studies demonstrated worse systolic GLS to be associated with higher mortality, whereas 2 did not show a statistically significant association. Various cutoffs between −10% and −17% were used to define abnormal GLS across studies. This systematic review revealed that STE may predict mortality in patients with sepsis; however, the strength of evidence is low due to heterogeneity in study populations, GLS technologies, cutoffs, and timing of STE. Further dedicated studies are needed to understand the optimal application of STE in patients with sepsis.

Study Design. Systematic review and meta-analysis of observational studies. Objective. The aim of the study is to evaluate different treatment modalities in the management of sacrococcygeal chordoma. Summary of Background Data. Chordomas are primary malignant bone tumors associated with considerable morbidity and mortality. Methods. We searched MEDLINE, EMBASE, Cochrane Central-Register of Controlled Trials, and Scopus from inception to July 2015. Eligible studies included patients with sacrococcygeal chordoma treated exclusively with surgery, radiotherapy, or both. Two reviewers independently assessed the eligibility of potential studies, risk of bias, and extracted data. Outcomes of interest were all-cause mortality, progression-free survival, and metastases. We analyzed further surgical outcomes by resection margin. All outcomes were assessed at 60 months and more than 60 months following intervention. Results. We included 33 noncomparative studies reporting on 501 patients (mean age 57 years). Overall mortality rate was (16%) after surgical resection with adjuvant radiotherapy and (28%) after surgical resection, and (43%) after radiotherapy (P = 0.28). All-cause mortality following wide surgical resection was (32%) compared to (40%) after marginal resection (P = 0.51). Overall progression-free survival rate was (58%) after surgical resection with adjuvant radiotherapy and (55%) after surgery (P = 0.92). However, at more than 60 months follow-up, progression-free survival rates were significantly higher (P = 0.024) following surgical resection with adjuvant radiotherapy (74%) in comparison to surgery (55%) and radiotherapy (36%). Overall progression-free survival rates were nonsignificantly higher after wide surgical resection (66%) than marginal resection (33%) (P = 0.16). However, at 60 months follow-up, progression-free survival rates were significantly higher following wide surgical resection (73%) than marginal resection (33%) (P = 0.047). Conclusion. Sacrococcygeal chordoma is a difficult to treat disease entity. Until comparative studies become available, wide surgical resection and multidisciplinary management are the recommended approaches to improve patient outcomes. Level of Evidence: 3