Within-Person Blood Pressure Variability During Hospitalization and Clinical Outcomes Following First-Ever Acute Ischemic Stroke.

BACKGROUND: Uncertainty remains over the relationship between blood pressure (BP) variability (BPV), measured in hospital settings, and clinical outcomes following acute ischemic stroke (AIS). We examined the association between within-person systolic blood pressure (SBP) variability (SBPV) during hospitalization and readmission-free survival, all-cause readmission, or all-cause mortality 1 year after AIS. METHODS: In a cohort of 862 consecutive patients (age [mean ± SD] 75 ± 15 years, 55% women) with AIS (2005-2018, follow-up through 2019), we measured SBPV as quartiles of standard deviations (SD) and coefficient of variation (CV) from a median of 16 SBP readings obtained throughout hospitalization. RESULTS: In the cumulative cohort, the measured SD and CV of SBP in mmHg were 16 ± 6 and 10 ± 5, respectively. The hazard ratios (HR) for readmission-free survival between the highest vs. lowest quartiles were 1.44 (95% confidence interval [CI] 1.04-1.81) for SD and 1.29 (95% CI 0.94-1.78) for CV after adjustment for demographics and comorbidities. Similarly, incident readmission or mortality remained consistent between the highest vs. lowest quartiles of SD and CV (readmission: HR 1.29 [95% CI 0.90-1.78] for SD, HR 1.29 [95% CI 0.94-1.78] for CV; mortality: HR 1.15 [95% CI 0.71-1.87] for SD, HR 0.86 [95% CI 0.55-1.36] for CV). CONCULSIONS: In patients with first AIS, SBPV measured as quartiles of SD or CV based on multiple readings throughout hospitalization has no independent prognostic implications for the readmission-free survival, readmission, or mortality. This underscores the importance of overall patient care rather than a specific focus on BP parameters during hospitalization for AIS.

Recurrence and mortality rates with different treatment approaches of Merkel cell carcinoma: a systematic review and meta-analysis.

BACKGROUND: Comprehensive treatment recommendations for Merkel cell carcinoma are complex. We aimed to systematically review the published data on recurrence and mortality rates associated with various treatment approaches for Merkel cell carcinoma. METHODS: Search of MEDLINE, Embase, Web of Science, and Scopus from inception to August 2015. Studies were included that reported comparative survival and recurrence data for two or more treatment modalities. Two reviewers independently reviewed and abstracted recurrence and mortality rates. Event rates for individual treatment arms in each study were pooled and meta-analyzed across studies using a random-effects model. RESULTS: Fifty-two retrospective studies met inclusion criteria, revealing a total of 1,804 patients with primary Merkel cell carcinoma with data available for analyses. The recurrence rate was higher for surgery alone (55.0%) versus a combination of surgery and radiotherapy (39.0%) (odds ratio, 2.089; 95% CI, 1.374-3.177; P < 0.001). Combination therapy including surgery, radiotherapy, and chemotherapy had a higher mortality rate (44.6%) than did combined surgery and radiotherapy (23.2%) (odds ratio, 2.688; 95% CI, 1.196-6.037; P = 0.02). CONCLUSIONS: The treatment of Merkel cell carcinoma with surgery plus adjuvant radiotherapy may produce lower recurrence rates.

Chronic mesenteric ischemia: clinical practice guidelines from the Society for Vascular Surgery

Chronic mesenteric ischemia (CMI) results from the inability to achieve adequate postprandial intestinal blood flow, usually from atherosclerotic occlusive disease at the origins of the mesenteric vessels. Patients typically present with postprandial pain, food fear, and weight loss, although they can present with acute mesenteric ischemia and bowel infarction. The diagnosis requires a combination of the appropriate clinical symptoms and significant mesenteric artery occlusive disease, although it is often delayed given the spectrum of gastrointestinal disorders associated with abdominal pain and weight loss. The treatment goals include relieving the presenting symptoms, preventing progression to acute mesenteric ischemia, and improving overall quality of life. These practice guidelines were developed to provide the best possible evidence for the diagnosis and treatment of patients with CMI from atherosclerosis. The Society for Vascular Surgery established a committee composed of vascular surgeons and individuals experienced with evidence-based reviews. The committee focused on six specific areas, including the diagnostic evaluation, indications for treatment, choice of treatment, perioperative evaluation, endovascular/open revascularization, and surveillance/remediation. A formal systematic review was performed by the evidence team to identify the optimal technique for revascularization. Specific practice recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation system based on review of literature, the strength of the data, and consensus. Patients with symptoms consistent with CMI should undergo an expedited workup, including a computed tomography arteriogram, to exclude other potential causes. The diagnosis is supported by significant arterial occlusive disease in the mesenteric vessels, particularly the superior mesenteric artery. Treatment requires revascularization with the primary target being the superior mesenteric artery. Endovascular revascularization with a balloon-expandable covered intraluminal stent is the recommended initial treatment with open repair reserved for select younger patients and those who are not endovascular candidates. Long-term follow-up and surveillance are recommended after revascularization and for asymptomatic patients with severe mesenteric occlusive disease. Patient with recurrent symptoms after revascularization owing to recurrent stenoses should be treated with an endovascular-first approach, similar to the de novo lesion. These practice guidelines were developed based on the best available evidence. They should help to optimize the care of patients with CMI. Multiple areas for future research were identified.

Normal liver stiffness and influencing factors in healthy children: An individual participant data meta-analysis.

BACKGROUND & AIMS: Although transient elastography (TE) is used to determine liver stiffness as a surrogate to hepatic fibrosis, the normal range in children is not well defined. We performed a systematic review and individual participant data (IPD) meta-analysis to determine the range of liver stiffness in healthy children and evaluate the influence of important biological parameters. METHODS: We pooled data from 10 studies that examined healthy children using TE. We divided 1702 children into two groups: ≥3 years (older group) and < 3 years of age (younger group). Univariate and multivariate linear regression models predicting liver stiffness were conducted. RESULTS: After excluding children with obesity, diabetes, or abnormal liver tests, 652 children were analysed. Among older children, mean liver stiffness was 4.45 kPa (95% confidence interval 4.34-4.56), and increased liver stiffness was associated with age, sedation status, and S probe use. In the younger group, the mean liver stiffness was 4.79 kPa (95% confidence interval 4.46-5.12), and increased liver stiffness was associated with sedation status and Caucasian race. In a subgroup analysis, hepatic steatosis on ultrasound was significantly associated with increased liver stiffness. We define a reference range for normal liver stiffness in healthy children as 2.45-5.56 kPa. CONCLUSIONS: We have established TE-derived liver stiffness ranges for healthy children and propose an upper limit of liver stiffness in healthy children to be 5.56 kPa. We have identified increasing age, use of sedation, probe size, and presence of steatosis on ultrasound as factors that can significantly increase liver stiffness.

Long-Term Rupture Risk in Patients with Unruptured Intracranial Aneurysms Treated with Endovascular Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: Surveillance imaging of previously unruptured, coiled aneurysms remains routine even though reports of rupture of these aneurysms are extremely rare. PURPOSE: We performed meta-analysis to examine long-term rupture risk over ≥1-year follow-up duration in patients with unruptured intracranial aneurysm who underwent endovascular therapy. DATA SOURCES: Multiple databases were searched for relevant publications between 1995 and 2018. STUDY SELECTION: Studies reporting outcome of long-term rupture risk over ≥1-year follow-up in treated patients with unruptured intracranial aneurysms were included. DATA ANALYSIS: Random effects meta-analysis was used, and results were expressed as long-term rupture rate per 100 patient-year with respective 95% CIs. For ruptured aneurysms during follow-up, data were collected on size and completeness of initial Treatment. DATA SYNTHESIS: Twenty-four studies were identified. Among 4842 patients with a mean follow-up duration of 3.2 years, a total of 12 patients (0.25%) experienced rupture of previous unruptured intracranial aneurysms after endovascular treatment. Nine of these 12 patients harbored aneurysms that were large, incompletely treated, or both. A total of 2 anterior circulation, small, completely coiled aneurysms subsequently ruptured. The long-term rupture rate per 100 patient-year for unruptured intracranial aneurysms treated with endovascular therapy was 0.48 (95% CI, 0.45-0.51). Retreatment was carried out in 236 (4.9%) of these 4842 patients. LIMITATIONS: A limitation of the study is that a lack of systematic nature of follow-up and mean follow-up duration of 3.2 years are not sufficient to make general recommendations about aneurysm followup paradigms. CONCLUSIONS: Given a 5% retreatment rate, postcoil embolization spontaneous rupture of previously unruptured, small- and medium-sized, well-treated aneurysms is exceedingly rare.

American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults.

BACKGROUND: Central nervous system (CNS) complications are among the most common, devastating sequelae of sickle cell disease (SCD) occurring throughout the lifespan. OBJECTIVE: These evidence-based guidelines of the American Society of Hematology are intended to support the SCD community in decisions about prevention, diagnosis, and treatment of the most common neurological morbidities in SCD. METHODS: The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic evidence reviews. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations. RESULTS: The panel placed a higher value on maintaining cognitive function than on being alive with significantly less than baseline cognitive function. The panel developed 19 recommendations with evidence-based strategies to prevent, diagnose, and treat CNS complications of SCD in low-middle- and high-income settings. CONCLUSIONS: Three of 19 recommendations immediately impact clinical care. These recommendations include: use of transcranial Doppler ultrasound screening and hydroxyurea for primary stroke prevention in children with hemoglobin SS (HbSS) and hemoglobin Sß0 (HbSß0) thalassemia living in low-middle-income settings; surveillance for developmental delay, cognitive impairments, and neurodevelopmental disorders in children; and use of magnetic resonance imaging of the brain without sedation to detect silent cerebral infarcts at least once in early-school-age children and once in adults with HbSS or HbSß0 thalassemia. Individuals with SCD, their family members, and clinicians should become aware of and implement these recommendations to reduce the burden of CNS complications in children and adults with SCD.

Immune checkpoint inhibitor-induced Type 1 diabetes: a systematic review and meta-analysis.

AIM: To conduct a systematic review and meta-analysis to understand the timing and factors associated with anti-programmed cell death protein-1 (PD-1)/anti-programmed cell death protein-1 ligand (PD-L1) inhibitor-induced Type 1 diabetes. METHODS: We searched MEDLINE, EMBASE, SCOPUS and Cochrane databases (August 2000-2018) for studies of any design on immune checkpoint inhibitors. A total of 71 cases were reviewed from 56 publications. Comparisons were made using Fisher's exact and Student's t-tests. RESULTS: The mean ± sd age at Type 1 diabetes presentation was 61.7±12.2 years, 55% of cases were in men, and melanoma (53.5%) was the most frequent cancer. The median time to Type 1 diabetes onset was 49 (5-448) days with ketoacidosis in 76% of cases. The average ± sd HbA1c concentration was 62 ± 0.3 mmol/mol (7.84±1.0%) at presentation. All cases had insulin deficiency and required permanent exogenous insulin treatment. Half of the cases had Type 1 diabetes-associated antibodies at presentation, and those with antibodies had a more rapid onset (P=0.005) and higher incidence of diabetic ketoacidosis (P=0.02) compared to people without antibodies. CONCLUSIONS: Many people developed Type 1 diabetes within 3 months of initial PD-1/PD-L1 inhibitor exposure. People presenting with Type 1 diabetes-associated antibodies had a more rapid onset and higher incidence of ketoacidosis than those without antibodies. Healthcare providers caring for people receiving these state-of-the-art therapies need to be aware of this potential severe adverse event.

Routine laboratory measures of heparin anticoagulation for children on extracorporeal membrane oxygenation: Systematic review and meta-analysis.

OBJECTIVE: Specific protocols for anticoagulation for children on ECMO vary across institutions, with most using a continuous infusion of unfractionated heparin. The goal of this study is to aid clinician's decision on the best measure of heparin anticoagulation test; which would be the one that correlates well with heparin activity and helps in predicting hemorrhagic and thrombotic complications. DATA SOURCES: A comprehensive search of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus was conducted from each database's inception to 07/13/2018. STUDY SELECTION: Studies evaluating children (<18 years) treated with ECMO and evaluating ACT, aPTT, TEG and Anti-Xa in any language were included. DATA EXTRACTION: Two reviewers selected and appraised studies independently, and abstracted data. RESULTS: We included 19 studies (759 patients, mean age 19.8 months). Meta-analysis showed strong correlation between heparin dosing and anti-Xa. Additionally, there was not a strong correlation between laboratory tests and complications (hemorrhagic and thrombosis), or mortality. CONCLUSION: Based on current evidence, Anti-Xa is the only laboratory test that shows strong correlation with heparin infusion dose and seems like the most suitable test for monitoring of anticoagulation with heparin in children on ECMO.

Treatment of Dupuytren's contracture: a systematic review.

Aims: Dupuytren's contracture is a benign, myoproliferative condition affecting the palmar fascia that results in progressive contractures of the fingers. Despite increased knowledge of the cellular and connective tissue changes involved, neither a cure nor an optimum form of treatment exists. The aim of this systematic review was to summarize the best available evidence on the management of this condition. Materials and Methods: A comprehensive database search for randomized controlled trials (RCTs) was performed until August 2017. We studied RCTs comparing open fasciectomy with percutaneous needle aponeurotomy (PNA), collagenase clostridium histolyticum (CCH) with placebo, and CCH with PNA, in addition to adjuvant treatments aiming to improve the outcome of open fasciectomy. A total of 20 studies, involving 1584 patients, were included. Results: PNA tended to provide higher patient satisfaction with fewer adverse events, but had a higher rate of recurrence compared with limited fasciectomy. Although efficacious, treatment with CCH had notable recurrence rates and a high rate of transient adverse events. Recent comparative studies have shown no difference in clinical outcome between patients treated with PNA and those treated with CCH. Conclusion: Currently there remains limited evidence to guide the management of patients with Dupuytren's contracture. Cite this article: Bone Joint J 2018;100-B:1138-45.

Systematic review and network meta-analysis: first- and second-line biologic therapies for moderate-severe Crohn's disease.

BACKGROUND: There are limited data to inform positioning of agents for treating moderate-severe Crohn's disease (CD). AIM: We 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. METHODS: We 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. RESULTS: No 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. CONCLUSION: Indirect 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.

Does natriuretic peptide monitoring improve outcomes in heart failure patients? A systematic review and meta-analysis.

BACKGROUND: Current guidelines do not support the use of serial natriuretic peptide (NP) monitoring for heart failure with preserved (HFpEF) or reduced ejection fraction (HFrEF) treatment, despite some studies showing benefit. We conducted an updated meta-analysis to address whether medical therapy in HFpEF or HFrEF should be titrated according to NP levels. METHODS: MEDLINE, Scopus and Cochrane CENTRAL databases were searched for randomized controlled trials (RCTs) comparing NP versus guideline directed titration in HF patients through December 2017. The key outcomes of interest were mortality, HF hospitalizations and all-cause hospitalizations. Risk ratios and 95% confidence intervals were pooled using random effects model. Sub-group analyses were performed for type of NP used, average age and acute or chronic HF. RESULTS: Eighteen trials including 5116 patients were included. Meta-analysis showed no significant difference between the NP-guided arm versus guideline directed titration in all-cause mortality (RR = 0.91 [0.81, 1.03]; p = 0.13), HF hospitalizations (RR = 0.81 [0.65, 1.01]; p = 0.06), and all cause hospitalizations (RR = 0.93 [0.86, 1.01]; p = 0.09). The results were consistent upon subgroup analysis by biomarker type (NT-proBNP or BNP) and type of heart failure (acute or chronic and HFrEF or HFpEF). Sub-group analysis suggested that NP-guided treatment was associated with decreased all-cause hospitalizations in patients younger than 72 years of age. CONCLUSION: The available evidence suggests that NP-guided therapy provides no additional benefit over guideline directed therapy in terms of all-cause mortality and HF-related hospitalizations in acute or chronic HF patients, regardless of their ejection fraction.

Endovascular Management of Acute Stroke in the Elderly: A Systematic Review and Meta-Analysis.

BACKGROUND: Acute ischemic stroke occurs more frequently, presents with more severe symptoms, and has worse outcomes in elderly patients. The safety and efficacy of endovascular therapy for acute stroke in this age group has not been fully established. PURPOSE: We present the results of a systematic review and meta-analysis examining clinical, procedural, and radiologic outcomes of endovascular therapy for acute stroke in patients older than 80 years of age. DATA SOURCES: We searched PubMed, MEDLINE, and EMBASE from 1992 to week 35 of 2017 for studies evaluating endovascular therapy for acute stroke in the elderly. STUDY SELECTION: Two independent reviewers selected studies and abstracted data. The primary end point was good functional outcome at 3 months defined as modified Rankin Scale score of ≤2. DATA ANALYSIS: Data were analyzed using random-effects meta-analysis. DATA SYNTHESIS: Seventeen studies reporting on 860 patients were included. The rate of good functional outcome at 3 months was 27% (95% CI, 21%-32%). Mortality at 3 months was 34% (95% CI, 23%-44%). Successful recanalization was achieved in 78% of patients (95% CI, 72%-85%). Procedure-related complications occurred in 11% (95% CI, 4%-17%). The incidence of intracranial hemorrhage was 24% (95% CI, 15%-32%), and for symptomatic intracranial hemorrhage, it was 8% (95% CI, 5%-10%). The mean time to groin was 251 minutes (95% CI, 224-278 minutes). Procedure time was 99 minutes (95% CI, 67-131 minutes). LIMITATIONS: I2 values were above 50% for all outcomes, indicating substantial heterogeneity. CONCLUSIONS: Good functional recovery in octogenarians treated with endovascular therapy for acute stroke can be achieved in a high proportion of patients despite the higher incidence of comorbidity in this cohort. Outcomes are inferior to those reported for younger patients; however, endovascular therapy can allow at least 1 in 4 patients older than 80 years of age to regain independent function at 3 months. More research is required to improve patient selection in the elderly, but age should not be a discriminator when deciding to offer endovascular therapy for patients with acute stroke.

Systematic review with network meta-analysis: first- and second-line pharmacotherapy for moderate-severe ulcerative colitis.

BACKGROUND: There are limited data to inform positioning of agents for treating moderate-severe ulcerative colitis (UC). AIM: To assess comparative efficacy and safety of different therapies as first-line (biologic-naïve) and second-line (prior exposure to anti-tumour necrosis factor(TNF)-α) agents for moderate-severe UC, through a systematic review and network meta-analysis, and appraise quality of evidence (QoE) using grading of recommendations, assessment, development and evaluation (GRADE) approach. METHODS: We identified randomised controlled trials (RCTs) in adults with moderate-severe UC treated with anti-TNF agents, anti-integrin agents and janus kinase (JAK) inhibitors, as first-line or second-line agents, and compared with placebo or another active agent. Efficacy outcomes were induction/maintenance of remission and mucosal healing; and 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. RESULTS: In biologic-naïve patients (12 trials, no head-to-head comparisons), infliximab and vedolizumab were ranked highest for induction of clinical remission (infliximab: odds ratio [OR], 4.10 [95% confidence intervals [CI], 2.58-6.52]; SUCRA,0.85; vedolizumab:SUCRA,0.82) and mucosal healing (infliximab:SUCRA,0.91; vedolizumab:SUCRA,0.81) (moderate QoE). In patients with prior anti-TNF exposure (4 trials, no head-to-head comparisons), tofacitinib was ranked highest for induction of clinical remission (OR, 11.88 [2.32-60.89]; SUCRA, 0.96) and mucosal healing (moderate QoE). Differences in trial design limited comparability of trials of maintenance therapy for efficacy. Vedolizumab was ranked safest in terms of serious adverse events (SUCRA, 0.91), and infection (SUCRA, 0.75) in maintenance trials. CONCLUSIONS: Infliximab and vedolizumab are ranked highest as first-line agents, and tofacitinib is ranked highest as second-line agent, for induction of remission and mucosal healing in patients with moderate-severe UC, based on indirect comparisons. Head-to-head trials are warranted to inform clinical decision-making with greater confidence.

Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society clinical practice guideline

OBJECTIVE: To update the "Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline," published by the Endocrine Society in 2009. PARTICIPANTS: The participants include an Endocrine Society-appointed task force of nine experts, a methodologist, and a medical writer. EVIDENCE: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. CONSENSUS PROCESS: Group meetings, conference calls, and e-mail communications enabled consensus. Endocrine Society committees, members and cosponsoring organizations reviewed and commented on preliminary drafts of the guidelines. CONCLUSION: Gender affirmation is multidisciplinary treatment in which endocrinologists play an important role. Gender-dysphoric/gender-incongruent persons seek and/or are referred to endocrinologists to develop the physical characteristics of the affirmed gender. They require a safe and effective hormone regimen that will (1) suppress endogenous sex hormone secretion determined by the person's genetic/gonadal sex and (2) maintain sex hormone levels within the normal range for the person's affirmed gender. Hormone treatment is not recommended for prepubertal gender-dysphoric/gender-incongruent persons. Those clinicians who recommend gender-affirming endocrine treatments-appropriately trained diagnosing clinicians (required), a mental health provider for adolescents (required) and mental health professional for adults (recommended)-should be knowledgeable about the diagnostic criteria and criteria for gender-affirming treatment, have sufficient training and experience in assessing psychopathology, and be willing to participate in the ongoing care throughout the endocrine transition. We recommend treating gender-dysphoric/gender-incongruent adolescents who have entered puberty at Tanner Stage G2/B2 by suppression with gonadotropin-releasing hormone agonists. Clinicians may add gender-affirming hormones after a multidisciplinary team has confirmed the persistence of gender dysphoria/gender incongruence and sufficient mental capacity to give informed consent to this partially irreversible treatment. Most adolescents have this capacity by age 16 years old. We recognize that there may be compelling reasons to initiate sex hormone treatment prior to age 16 years, although there is minimal published experience treating prior to 13.5 to 14 years of age. For the care of peripubertal youths and older adolescents, we recommend that an expert multidisciplinary team comprised of medical professionals and mental health professionals manage this treatment. The treating physician must confirm the criteria for treatment used by the referring mental health practitioner and collaborate with them in decisions about gender-affirming surgery in older adolescents. For adult gender-dysphoric/gender-incongruent persons, the treating clinicians (collectively) should have expertise in transgender-specific diagnostic criteria, mental health, primary care, hormone treatment, and surgery, as needed by the patient. We suggest maintaining physiologic levels of gender-appropriate hormones and monitoring for known risks and complications. When high doses of sex steroids are required to suppress endogenous sex steroids and/or in advanced age, clinicians may consider surgically removing natal gonads along with reducing sex steroid treatment. Clinicians should monitor both transgender males (female to male) and transgender females (male to female) for reproductive organ cancer risk when surgical removal is incomplete. Additionally, clinicians should persistently monitor adverse effects of sex steroids. For gender-affirming surgeries in adults, the treating physician must collaborate with and confirm the criteria for treatment used by the referring physician. Clinicians should avoid harming individuals (via hormone treatment) who have conditions other than gender dysphoria/gender incongruence and who may not benefit from the physical changes associated with this treatment.

Endovascular Treatment of Vein of Galen Malformations: A Systematic Review and Meta-Analysis.

BACKGROUND: Outcomes after endovascular embolization of vein of Galen malformations remain relatively poorly described. PURPOSE: We performed a systematic review of the literature to determine outcomes and predictors of good outcomes following endovascular treatment of vein of Galen malformations. DATA SOURCES: We used Ovid MEDLINE, Ovid Embase, and the Web of Science. STUDY SELECTION: Our study consisted of all case series with ≥4 patients receiving endovascular treatment of vein of Galen malformations published through January 2017. DATA ANALYSIS: We studied the following outcomes: complete/near-complete occlusion rates, technical complications, perioperative stroke, perioperative hemorrhage, technical mortality, all-cause mortality, poor neurologic outcomes, and good neurologic outcomes. Outcomes were stratified by age-group (neonate, infant, child). A random-effects meta-analysis was performed. DATA SYNTHESIS: A total of 27 series with 578 patients were included; 41.9% of patients were neonates, 45.0% of patients were infants, and 13.1% of patients were children. All-cause mortality was 14.0% (95% CI, 8.0%-22.0%). Overall good neurologic outcome rates were 62.0% (95% CI, 57.0%-67.0%). Overall poor neurologic outcome rates were 21.0% (95% CI, 17.0%-26.0%). Neonates were significantly less likely to have good neurologic outcomes than infants (48.0%; 95% CI, 35.0%-62.0% versus 77.0%; 95% CI, 70.0%-84.0%; P < .01). Treatment indications following the Bicêtre neonatal evaluation score resulted in significantly higher rates of good neurologic outcome (P = .04). Patients with congestive heart failure had significantly lower rates of good neurologic outcome (OR, 0.50; 95% CI, 0.28-0.88; P = .01). LIMITATIONS: Limitations were selection and publication biases. CONCLUSIONS: Patients receiving endovascular embolization of vein of Galen malformations experienced good long-term clinical outcomes in >60% of cases. Appropriate patient selection is key as treatment guided by the Bicêtre neonatal evaluation score was associated with improved neurologic outcomes.

Late boosting phenomenon in TST conversion among health care workers.

BACKGROUND: Available information is insufficient to guide determination of whether tuberculin skin test (TST) conversions of health care workers (HCWs) within 2 years of two-step testing are related to occupational exposures or to other causes, including late boosting. AIMS: To describe the epidemiologic factors of TST conversion in HCWs, comparing early TST conversion (≤2 years after two-step testing) with late conversion to possibly distinguish late boosting phenomenon from occupational TST conversion. METHODS: Retrospective analysis of a database of TSTs of HCWs from 1 January 1998, through 31 May 2014, in the United States Midwest. RESULTS: In total, 40142 HCWs had 197932 tests over the 16 years, with 123 conversions (conversion rate: 0.3%; 95% CI 0.3-0.4%). Among 61 HCWs with a negative two-step TST, 30 (49%) were found to have early TST conversion within 2 years; 31 (51%) had late conversion, with likely occupational exposure but no identifiable community risks. Persons with early conversion were more likely to be born outside the USA (89% versus 57%; P < 0.05), had a higher rate of prior bacille Calmette-Guérin (BCG) vaccination (89% versus 52%; P < 0.05) and had no identifiable risk factors for conversion (63% versus 58%; P < 0.05). CONCLUSIONS: Early conversions among HCWs after negative two-step TST are associated with various nonoccupational factors, including international birth and BCG vaccination history. Therefore, conversion is not a reliable indicator of recent tuberculosis contact in this population, and two-step TST is insufficient to discount a delayed boosting response for HCWs.

Systematic review with meta-analysis: the association between hepatitis E seroprevalence and haemodialysis.

BACKGROUND: Hepatitis E virus (HEV) infection appears to be more common than previously thought. HEV seroprevalence in patients on maintenance haemodialysis (HD) is unclear with a range from 0% to 44%. In addition, risk factors of transmission of HEV in patients on haemodialysis are unknown. AIM: To perform a systematic review and meta-analysis of HEV seroprevalence in HD patients compared with controls. METHODS: A systematic search of several databases identified all observational studies with comparative arms. Two reviewers extracted data and assessed the methodological quality. A random-effects model was used for pooled odds ratio (OR) and 95% confidence interval (CI) of positive anti-HEV IgG in both groups. Heterogeneity and publication bias were assessed with appropriate tests. RESULTS: We identified 31 studies from 17 countries between 1994 and 2016. Sixteen studies were judged to have adequate quality and 15 to have moderate limitations. HEV infection was more prevalent in patients on haemodialysis compared with controls (OR 2.47, 95% CI 1.79-3.40, I2 = 75.2%, P < .01). We conducted several subgroup analyses without difference in results. Egger regression test did not suggest publication bias (P = .83). Specific risk factors of HEV transmission in patients on haemodialysis were not clearly identified. CONCLUSIONS: Hepatitis E virus infection is more prevalent in patients on haemodialysis compared with non-haemodialysis control groups. Further studies are needed to determine risk factors of acquisition, impact on health, and risk for chronic HEV especially among those patients going to receive organ transplantation.

Secretory diarrhea and hypokalemia associated with colonic pseudo-obstruction: A case study and systematic analysis of the literature.

BACKGROUND: Colonic pseudo-obstruction (CPO) is characterized by colonic distention in the absence of mechanical obstruction or toxic megacolon. Concomitant secretory diarrhea (SD) with hypokalemia (SD-CPO) due to gastrointestinal (GI) loss requires further characterization. AIM: To perform a systematic review of SD-CPO, report a case study, and compare SD-CPO with classical CPO (C-CPO). METHODS: We performed a search of MEDLINE, EMBASE, Cochrane, and Scopus for reports based on a priori criteria for CPO, SD and GI loss of potassium. An additional case at Mayo Clinic was included. RESULTS: Nine publications met inclusion criteria, with a total of 14 cases. Six studies had high, three moderate, and our case high methodological quality. Median age was 74 years (66-97), with 2:1 male/female ratio. Kidney disease was present in 6/14 patients. Diarrhea was described as profuse, watery, or viscous in 10 patients. Median serum, stool, and urine potassium concentrations (mmol/L) were 2.4 (range: 1.9-3.1), 137 (100-180), and 17 (8-40), respectively. Maximal diameter of colon and cecum (median) were 10.2 cm and 10.5 cm, respectively. Conservative therapy alone was effective in five out of 14 patients. Median potassium supplementation was 124 mEq/d (40-300). Colonic decompression was effective in three out of six patients; one had a total colectomy; three out of 14 had died. The main differences between SD-CPO and C-CPO were lower responses to treatments: conservative measures (35.7% vs 73.6%, P=.01), neostigmine (17% vs 89.2%, P<.001), and colonic decompression (50% vs 82.4%, P=.02). CONCLUSION: SD-CPO is a rare phenotype associated with increased fecal potassium and is more difficult to treat than C-CPO.

Selective-versus-Standard Poststent Dilation for Carotid Artery Disease: A Systematic Review and Meta-Analysis.

BACKROUND: The safety and efficacy of standard poststent angioplasty in patients undergoing carotid artery stent placement have not been well-established. PURPOSE: We conducted a systematic review of the literature to evaluate the safety and efficacy of carotid artery stent placement and analyzed outcomes of standard-versus-selective poststent angioplasty. DATA SOURCES: A systematic search of MEDLINE, EMBASE, Scopus, and the Web of Science was performed for studies published between January 2000 and January 2015. STUDY SELECTION: We included studies with >30 patients describing standard or selective poststent angioplasty during carotid artery stent placement. DATA ANALYSIS: A random-effects meta-analysis was used to pool the following outcomes: periprocedural stroke/TIA, procedure-related neurologic/cardiovascular morbidity/mortality, bradycardia/hypotension, long-term stroke at last follow-up, long-term primary patency, and technical success. DATA SYNTHESIS: We included 87 studies with 19,684 patients with 20,378 carotid artery stenoses. There was no difference in clinical (P = .49) or angiographic outcomes (P = .93) in carotid artery stent placement treatment with selective or standard poststent balloon angioplasty. Both selective and standard poststent angioplasty groups had a very high technical success of >98% and a low procedure-related mortality of 0.9%. There were no significant differences between both groups in the incidence of restenosis (P = .93) or procedure-related complications (P = .37). LIMITATIONS: No comparison to a patient group without poststent dilation could be performed. CONCLUSIONS: Our meta-analysis demonstrated no significant difference in angiographic and clinical outcomes among series that performed standard poststent angioplasty and those that performed poststent angioplasty in only select patients.