Prokop, Larry J.

e16522 Background: Cisplatin-based neoadjuvant chemotherapy is the standard of care for muscle invasive bladder cancer (MIBC) in cisplatin-eligible patients. This systematic review and meta-analysis provide an updated efficacy and safety comparison between the two most commonly used cisplatin-based regimens; dose-dense (dd) or conventional MVAC versus GC. Methods: We searched different databases for studies comparing MVAC versus GC in the neoadjuvant setting. Outcomes of interest included overall survival, downstaging to pT≤1, pathologic complete response (pCR), recurrence, and toxicity. Meta-analysis was conducted using the random-effects model. Results: We identified 24 studies from inception to March 2020; among them 17 were peer reviewed and 7 were only reported as abstracts in national or international meetings, including a phase 3, randomized-controlled clinical trial. Among peer-reviewed published studies, efficacy outcomes such as OS, downstaging and pCR were comparable between conventional MVAC and GC for MIBC. If including non-peer-reviewed studies, dd-MVAC was associated with favorable efficacy compared to GC in terms of downstaging (OR 1.45; 95% CI 1.15–1.82), and OS at longest follow-up (OR 0.63; 95% CI 0.44–0.81). However, GC was associated with a better safety profile in terms of febrile neutropenia (OR 0.32; 95% CI 0.13–0.80), anemia (OR 0.32; 95% CI 0.18–0.54), nausea and vomiting (OR 0.27; 95% CI 0.12–0.65) compared to dd-MVAC. Compared to MVAC, patients receiving GC had an increased risk of developing grade 3–4 thrombocytopenia (OR 4.70; 95% CI 1.59–13.89) and a lower risk of nausea and vomiting (OR 0.05; 95% CI 0.01-0.31). Certainty in the estimates was very low for most outcomes. Conclusions: Among peer-reviewed published studies, efficacy and safety outcomes were comparable between conventional MVAC and GC for MIBC. However, If including non-peer-reviewed studies, this analysis showed higher efficacy with dd-MVAC. A phase III randomized trial comparing the two regimens is needed to guide clinical practice

Objective Shared decision making (SDM) tools can help implement guideline recommendations for patients with atrial fibrillation (AF) considering stroke prevention strategies. We sought to characterize all available SDM tools for this purpose and examine their quality and clinical impact. Methods We searched through multiple bibliographic databases, social media, and an SDM tool repository from inception to May 2020 and contacted authors of identified SDM tools. Eligible tools had to offer information about warfarin and ≥1 direct oral anticoagulant. We extracted tool characteristics, assessed their adherence to the International Patient Decision Aids Standards, and obtained information about their efficacy in promoting SDM. Results We found 14 SDM tools. Most tools provided up-to-date information about the options, but very few included practical considerations (e.g., out-of-pocket cost). Five of these SDM tools, all used by patients prior to the encounter, were tested in trials at high risk of bias and were found to produce small improvements in patient knowledge and reductions in decisional conflict. Conclusion Several SDM tools for stroke prevention in AF are available, but whether they promote high-quality SDM is yet to be known. The implementation of guidelines for SDM in this context requires user-centered development and evaluation of SDM tools that can effectively promote high-quality SDM and improve stroke prevention in patients with AF.

AbstractObjectiveTo describe the presentation and outcomes of patients with adrenal ganglioneuromas (AGNs).DesignSingle‐centre retrospective cohort study (1 January 1995 to 31 December 2019) and systematic review of literature (1 January 1980 to 19 November 2019).PatientsDiagnosed with histologically confirmed AGN.MeasurementsBaseline clinical, imaging and biochemical characteristics, recurrence rates and mortality. Subgroup analysis was performed on tumours with histologic elements of ganglioneuroma and pheochromocytoma (ie composite tumours).ResultsThe cohort study included 45 patients with AGN, 20 (44%) of which had composite tumours. Compared to pure AGN, patients with composite tumour were older (median age, 62.5 vs. 35 years, p < .001), had smaller tumours (median size, 3.9 vs. 5.7 cm, p = .016) and were discovered incidentally less frequently (65% vs. 84%, p = .009). No recurrences or ganglioneuroma‐specific mortality occurred during follow‐up (range, 0–266 months). The systematic review included 14 additional studies and 421 patients. The mean age of diagnosis was 39 years, and 47% were women. AGNs were discovered incidentally in 72% of patients, were predominantly unilateral (99%) and had a mean diameter of 5.8 cm and an unenhanced computed tomography (CT) attenuation of −118 to 49 Hounsfield units (HU). On imaging, 69% of AGNs were homogenous, 41% demonstrated calcifications, and 40% were lobulated.ConclusionsAGNs are rare benign tumours that present with variable imaging features including large size, unenhanced CT attenuation >20 HU, calcifications and lobulated shape. Imaging characteristics can assist in establishing a diagnosis and avoiding an unnecessary adrenalectomy. The association of pheochromocytomas with AGNs is frequent. Diagnosis should include biochemical testing.

BACKGROUND As the use of injectable skin fillers increase in popularity, an increase in the reported adverse events is expected. OBJECTIVE This systematic review supports the development of American Society for Dermatologic Surgery practice guideline on the management of adverse events of skin fillers. METHODS AND MATERIALS Several databases for studies on risk factors or treatments of injection-related visual compromise (IRVC), skin necrosis, inflammatory events, and nodules were searched. Meta-analysis was conducted when feasible. RESULTS The review included 182 studies. However, IRVC was very rare (1–2/1,000,000 patients) but had poor prognosis with improvement in 19% of cases. Skin necrosis was more common (approximately 5/1,000) with better prognosis (up to 77% of cases showing improvement). Treatments of IRVC and skin necrosis primarily depend on hyaluronidase injections. Risk of skin necrosis, inflammatory events, and nodules may be lower with certain fillers, brands, injection techniques, and volume. Treatment of inflammatory events and nodules with antibiotics, corticosteroids, 5-FU, and hyaluronidase was associated with high response rate (75%–80%). Most of the studies were small and noncomparative, making the evidence certainty very low. CONCLUSION Practitioners must have adequate knowledge of anatomy, elicit history of skin filler use, and establish preemptive protocols that prepare the clinical practice to manage complications.

CONTEXT: Unplanned PICU readmissions within 48 hours of discharge (to home or a different hospital setting) are considered a quality metric of critical care. OBJECTIVE: We sought to determine identifiable risk factors associated with early unplanned PICU readmissions. DATA SOURCES: A comprehensive search of Medline, Embase, the Cochrane Database of Systematic Reviews, and Scopus was conducted from each database’s inception to July 16, 2018. STUDY SELECTION: Observational studies of early unplanned PICU readmissions (&lt;48 hours) in children (&lt;18 years of age) published in any language were included. DATA EXTRACTION: Two reviewers selected and appraised studies independently and abstracted data. A meta-analysis was performed by using the random-effects model. RESULTS: We included 11 observational studies in which 128 974 children (mean age: 5 years) were evaluated. The presence of complex chronic diseases (odds ratio 2.42; 95% confidence interval 1.06 to 5.55; I2 79.90%) and moderate to severe disability (odds ratio 2.85; 95% confidence interval 2.40 to 3.40; I2 11.20%) had the highest odds of early unplanned PICU readmission. Other significant risk factors included an unplanned index admission, initial admission to a general medical ward, spring season, respiratory diagnoses, and longer initial PICU stay. Readmission was less likely after trauma- and surgery-related index admissions, after direct admission from home, or during the summer season. Modifiable risk factors, such as evening or weekend discharge, revealed no statistically significant association. Included studies were retrospective, which limited our ability to account for all potential confounders and establish causality. CONCLUSIONS: Many risk factors for early unplanned PICU readmission are not modifiable, which brings into question the usefulness of this quality measure.

Abstract Background Abdominal pain is a debilitating symptom affecting ∼80% of pancreatic cancer (PC) patients. Pancreatic duct (PD) decompression has been reported to alleviate this pain, although this practice has not been widely adopted. We aimed to evaluate the role, efficacy, and safety of endoscopic PD decompression for palliation of PC post-prandial obstructive-type pain. Methods A systematic review until 7 October 2020 was performed. Two independent reviewers selected studies, extracted data, and assessed the methodological quality. Results We identified 12 publications with a total of 192 patients with PC presenting with abdominal pain, in whom PD decompression was attempted, and was successful in 167 patients (mean age 62.5 years, 58.7% males). The use of plastic stents was reported in 159 patients (95.2%). All included studies reported partial or complete improvement in pain levels after PD stenting, with an improvement rate of 93% (95% confidence interval, 79%–100%). The mean duration of pain improvement was 94 ± 16 days. Endoscopic retrograde cholangiopancreatography (ERCP)-related adverse events (AEs) were post-sphincterotomy bleeding (1.8%), post-ERCP pancreatitis (0.6%), and hemosuccus pancreaticus (0.6%). AEs were not reported in two patients who underwent endoscopic ultrasound-guided PD decompression. In the 167 patients with technical success, the stent-migration and stent-occlusion rates were 3.6% and 3.0%, respectively. No AE-related mortality was reported. The methodological quality assessment showed the majority of the studies having low or unclear quality. Conclusion In this exploratory analysis, endoscopic PD drainage may be an effective and safe option in selected patients for the management of obstructive-type PC pain. However, a randomized–controlled trial is needed to delineate the role of this invasive practice.

Abstract Background Excess adipose tissue is associated with an abnormal lipid profile that may improve with weight reduction. In this meta-analysis, we aimed to estimate the magnitude of change in lipid parameters associated with weight loss in adults who are overweight or obese. Methods We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus from 2013 to September, 2018. We included randomized controlled trials (RCTs) that evaluated interventions to treat adult obesity (lifestyle, pharmacologic and surgical) with follow-up of 6 months or more. Results We included 73 RCTs with moderate-to-low risk of bias, enrolling 32 496 patients (mean age, 48.1 years; weight, 101.6 kg; and body mass index [BMI], 36.3 kg/m2). Lifestyle interventions (diet, exercise, or both), pharmacotherapy, and bariatric surgery were associated with reduced triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) concentrations and increased high-density lipoprotein cholesterol (HDL-C) at 6 and 12 months. The following data are for changes in lipid parameters after 12 months of the intervention with 95% CI. Following lifestyle interventions, per 1 kg of weight lost, TGs were reduced by –4.0 mg/dL (95% CI, –5.24 to –2.77 mg/dL), LDL-C was reduced by –1.28 mg/dL (95% CI, –2.19 to –0.37 mg/dL), and HDL-C increased by 0.46 mg/dL (95% CI, 0.20 to 0.71 mg/dL). Following pharmacologic interventions, per 1 kg of weight lost, TGs were reduced by –1.25 mg/dL (95% CI, –2.94 to 0.43 mg/dL), LDL-C was reduced by –1.67 mg/dL (95% CI, –2.28 to –1.06 mg/dL), and HDL-C increased by 0.37 mg/dL (95% CI, 0.23 to 0.52 mg/dL). Following bariatric surgery, per 1 kg of weight lost, TGs were reduced by –2.47 mg/dL (95% CI, –3.14 to –1.80 mg/dL), LDL-C was reduced by –0.33 mg/dL (95% CI, –0.77 to 0.10 mg/dL), and HDL-C increased by 0.42 mg/dL (95% CI, 0.37 to 0.47 mg/dL). Low-carbohydrate diets resulted in reductions in TGs and increases in HDL-C, whereas low-fat diets resulted in reductions in TGs and LDL-C and increases in HDL-C. Results were consistent across malabsorptive and restrictive surgery. Conclusions Weight loss in adults is associated with statistically significant changes in serum lipids. The reported magnitude of improvement can help in setting expectations, inform shared decision making, and facilitate counseling.

Abstract Context Hyperthyroidism is associated with low levels of cholesterol and triglycerides, and hypothyroidism is associated with hypercholesterolemia and hypertriglyceridemia. Objective The aim of this systematic review was to investigate the impact of therapy for overt and subclinical hyper- and hypothyroidism on serum lipids. Data Sources We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus from 1970 through April 5, 2018. Study Selection Pairs of independent reviewers selected randomized and observational studies evaluating lipid parameters in patients undergoing treatment for hyper- or hypothyroidism. Data Extraction Pairs of independent reviewers extracted data and appraised studies. Data Synthesis Treatment of overt hyperthyroidism showed a significant increase in total cholesterol (TC) by 44.50 mg/dL (95% confidence interval [CI]: 37.99, 51.02), low-density lipoprotein cholesterol (LDL-C) by 31.13 mg/dL (95% CI: 24.33, 37.93), high-density lipoprotein cholesterol (HDL-C) by 5.52 mg/dL (95% CI: 1.48, 9.56), apolipoprotein A (Apo A) by 15.6 mg/dL (95% CI: 10.38, 20.81), apolipoprotein B (apo B) by 26.12 mg/dL (95% CI: 22.67, 29.57), and lipoprotein (Lp[a]) by 4.18 mg/dL (95% CI: 1.65, 6.71). There was no significant change in triglyceride (TG) levels. Treatment of subclinical hyperthyroidism did not change any lipid parameters significantly. Levothyroxine therapy in overt hypothyroidism showed a statistically significant decrease in TC by -58.4 mg/dL (95% CI: -64.70, -52.09), LDL-C by -41.11 mg/dL (95% CI: -46.53, -35.69), HDL-C by -4.14 mg/dL (95% CI: -5.67, -2.61), TGs by -7.25 mg/dL (95% CI: -36.63, 17.87), apo A by -12.59 mg/dL (95% CI: -17.98, -7.19), apo B by -33.96 mg/dL (95% CI: 41.14, -26.77), and Lp(a) by -5.6 mg/dL (95% CI: -9.06, -2.14). Levothyroxine therapy in subclinical hypothyroidism showed similar changes but with a smaller magnitude. The studies contained varied population characteristics, severity of thyroid dysfunction, and follow-up duration. Conclusions Treatment of overt but not subclinical hyperthyroidism is associated with worsening of the lipid profile. Levothyroxine therapy in both overt and subclinical hypothyroidism leads to improvement in the lipid profile, with a smaller magnitude of improvement in subclinical hypothyroidism.