Translational research updates in female health anesthesiology: a narrative review.

Background and Objective: Females represent 49.6% of the global population and constitute a significant proportion of surgical patients and hospital admissions. Little is known about the bi-directional effects of sex and anesthetics or the impact of anesthetic interventions on long-term female health outcomes. Sex differences in pain pathways can influence pain experience and treatment effectiveness. The impact of anesthetic management on the recurrence of breast cancer is poorly understood, as are the long-term consequences of cardiovascular disease and safe and effective treatments in pregnancy. This review aims to outline recent advances in translational science in female health anesthesiology research and highlight critical research opportunities in pain, cancer outcomes, and cardiovascular disorders. Methods: We searched PubMed and summarized relevant articles published in English between December 2021 and June 2022. Key Content and Findings: Studies reveal sex differences in pain pathways and highlight the importance of sex as a biological variable in experimental designs and translational medicine. Sex differences have also been observed in side effects attributed to opioid analgesics. We summarize some of the neural circuits that might underlie these differences. In the perioperative setting, specific anesthetics are implicated in metastatic seeding potential and acute and chronic pain outcomes, suggesting the importance of anesthetic selection in comprehensive care during oncologic surgery. In the peridelivery setting, preeclampsia, a cardiovascular disorder of pregnancy, affects maternal outcomes; however, biomarkers can risk-stratify females at risk for preeclampsia and hold promise for identifying the risk of adverse neurological and other health outcomes. Conclusions: Research that builds diagnostic and predictive tools in pain and cardiovascular disease will help anesthesiologists minimize sex-related risks and side effects associated with anesthetics and peri-hospital treatments. Sex-specific anesthesia care will improve outcomes, as will the provision of practical information to patients and clinicians about the effectiveness of therapies and behavioral interventions. However, more research studies and specific analytic plans are needed to continue addressing sex-based outcomes in anesthesiology.

Parkin regulates neuronal lipid homeostasis through SREBP2-lipoprotein lipase pathway-implications for Parkinson's disease.

Abnormal lipid homeostasis has been observed in the brain of Parkinson's disease (PD) patients and experimental models, although the mechanism underlying this phenomenon is unclear. Notably, previous studies have reported that the PD-linked protein Parkin functionally interacts with important lipid regulators, including Sterol Regulatory Element-Binding Proteins (SREBPs) and cluster of differentiation 36 (CD36). Here, we demonstrate a functional relationship between Parkin and lipoprotein lipase (LPL), a triglyceride lipase that is widely expressed in the brain. Using a human neuroblastoma cell line and a Parkin knockout mouse model, we demonstrate that Parkin expression level positively correlates with neuronal LPL protein level and activity. Importantly, our study identified SREBP2, a major regulator of sterol and fatty acid synthesis, as a potential mediator between Parkin and LPL. Supporting this, SREBP2 genetic ablation abolished Parkin effect on LPL expression. We further demonstrate that Parkin-LPL pathway regulates the formation of intracellular lipid droplets, and that this pathway is upregulated upon exposure to PD-linked oxidative stress induced by rotenone. Finally, we show that inhibition of either LPL or SREBP2 exacerbates rotenone-induced cell death. Taken together, our findings reveal a novel pathway linking Parkin, SREBP2 and LPL in neuronal lipid homeostasis that may be relevant to the pathogenesis of PD.

An Observational Data Meta-analysis on the Differences in Prevalence and Risk Factors Between MAFLD vs NAFLD.

BACKGROUND & AIMS: The shift to redefine nonalcoholic fatty liver disease (NAFLD) as metabolic associated fatty liver disease (MAFLD) can profoundly affect patient care, health care professionals, and progress within the field. To date, there remains no consensus on the characterization of NAFLD vs MAFLD. Thus, this study sought to compare the differences between the natural history of NAFLD and MAFLD. METHODS: Medline and Embase databases were searched to include articles on prevalence, risk factors, or outcomes of patients with MAFLD or NAFLD. Meta-analysis of proportions was conducted using the generalized linear mix model. Risk factors and outcomes were evaluated in conventional pairwise meta-analysis. RESULTS: Twenty-two articles involving 379,801 patients were included. Pooled prevalence of MAFLD was 39.22% (95% confidence interval [CI], 30.96%-48.15%) with the highest prevalence in Europe and Asia, followed by North America. The current MAFLD Definition only accounted for 81.59% (95% CI, 66.51%-90.82%) of NAFLD diagnoses. Patients had increased odds of being diagnosed with MAFLD compared with NAFLD (odds ratio, 1.37; 95% CI, 1.16-1.63; P < .001). Imaging modality resulted in a significantly higher odds of being diagnosed with MAFLD compared with NAFLD, but not biopsy. MAFLD was significantly associated with males, higher body mass index, hypertension, diabetes, lipids, transaminitis, and greater fibrosis scores compared with NAFLD. CONCLUSIONS: There were stark differences in the prevalence and risk factors between MAFLD and NAFLD. However, in the use of the MAFLD Definition, a greater emphasis on the management of concomitant metabolic diseases and a collaborative effort is required to explore the complex pathophysiologic mechanisms underlying the disease.

Mortality Outcomes by Fibrosis Stage in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Fibrosis is a key determinant of clinical outcomes in nonalcoholic fatty liver disease (NAFLD), but time-dependent risk of mortality has not been reported in previous meta-analyses. We performed an updated time-to-event meta-analysis to provide robust estimates for all-cause and liver-related mortality in biopsy-confirmed NAFLD with comparisons between fibrosis stages. METHODS: Medline and Embase databases were searched to include cohort studies reporting survival outcomes by fibrosis stage in biopsy-proven NAFLD. Survival estimates were pooled using reconstructed individual participant data. Conventional meta-analysis was conducted to pool adjusted hazard ratios (HRs) using DerSimonian and Laird random effects model. RESULTS: A total of 14 articles involving 17,301 patients with NAFLD were included. All-cause mortality at 1, 5, and 10 years for stage 0 to 2 fibrosis was 0.1%, 3.3%, and 7.7% vs 0.3%, 20.6%, and 41.5% for stage 4 fibrosis. Compared with stage 0 fibrosis, all-cause mortality increased with fibrosis stage: stage 2; HR, 1.46 (95% confidence interval [CI], 1.08-1.98), stage 3; HR, 1.96 (95% CI, 1.41-2.72), and stage 4; HR, 3.66 (95% CI, 2.65-5.05). Risk for liver-related mortality increased exponentially as fibrosis stage increased: stage 2; HR, 4.07 (95% CI, 1.44-11.5), stage 3; HR, 7.59 (95% CI, 2.80-20.5), and stage 4; HR, 15.1 (95% CI, 5.27-43.4). Stage 3 to 4 fibrosis had a higher all-cause (HR, 3.32) and liver-related mortality (HR, 10.40) compared with stage 0 to 2 fibrosis, whereas stage 4 fibrosis had higher all-cause (HR, 2.67; 95% CI, 1.47-4.83) and liver-related mortality (HR, 2.57; 95% CI, 1.22-5.42) vs stage 3 fibrosis. CONCLUSIONS: Risk of all-cause and liver-related mortality increases substantially with fibrosis stage. These data have important implications for prognostication and trial design.

A Class Effect Network Meta-analysis of Lipid Modulation in Non-alcoholic Steatohepatitis for Dyslipidemia.

Background and Aims: Pharmaceutical therapy for NASH is associated with lipid modulation, but the consensus on drug treatment is limited and lacks comparative analysis of effectiveness. A network meta-analysis was conducted to compare NASH drug classes in lipid modulation. Methods: Online databases were searched for randomized controlled trails (RCTs) evaluating NASH treatments in biopsy-proven NASH patients. Treatments were classified into four groups: (1) inflammation, (2) energy, (3) bile acids, and (4) fibrosis based on the mechanism of action. A Bayesian network analysis was conducted with outcome measured by mean difference (MD) with credible intervals (Crl) and surface under the cumulative ranking curve (SUCRA). Results: Forty-four RCTs were included in the analysis. Bile acid modulating treatments (MD: 0.05, Crl: 0.03-0.07) were the best treatment for improvement in high-density lipid (HDL) cholesterol, followed by treatments modulating energy (MD: 0.03, Crl: 0.02-0.04) and fibrosis (MD: 0.01, Crl: -0.12 to 0.14) compared with placebo. The top three treatments for reduction in triglycerides were treatments modulating energy (MD: -0.46, Crl: -0.49 to -0.43), bile acids (MD: -0.22, Crl: -0.35 to -0.09), and inflammation (MD: -0.08, Crl: -0.13 to -0.03) compared with placebo. SUCRA found treatment modulating fibrosis (MD: -1.27, Crl: -1.76 to -0.79) was the best treatment for reduction in low-density lipid (LDL) cholesterol followed by treatment modulating inflammation (MD: -1.03, Crl: -1.09 to -0.97) and energy (MD: -0.37, Crl: -0.39 to -0.34) compared with placebo, but LDL cholesterol was worsened by treatments modulating bile acids. Conclusions: Network analysis comparing the class effects of dyslipidemia modulation in NASH found that treatment targets can include optimization of atherogenic dyslipidemia. Future studies are required to evaluate the cardiovascular outcomes.

NSS-Bridge Device for Post-Cesarean Delivery Analgesia: A Randomized Controlled Trial.

Introduction: Percutaneous auricular nerve stimulation has been used for the treatment of symptoms associated with opioid withdrawal, including abdominal pain, nausea, and general discomfort. However, its potential utility for pain management and opioid minimization after surgery has not been investigated. The purpose of this study was to test the feasibility and acceptability of a trial protocol designed to assess the effectiveness of the NSS2-Bridge device as a non-pharmacologic alternative to opioids after cesarean delivery. Methods: In a randomized control design, healthy women receiving cesarean delivery were randomized to receive the active device, placebo device, or no device. Devices were placed on the ear following cesarean delivery and left in place for 5 days. Feasibility and acceptability of the device was assessed by patient reports of device tolerability (rated on a 100mm visual analog scale where 0 is not tolerable at all and 100 is the most tolerable) as well as qualitative reporting. Additional outcomes assessed included proportion of patients not using opioids in hospital, as well as pain at rest, pain with movement, and total opioid consumption in the hospital and for the first 5 days after surgery. Results: There were 60 patients included in the final analysis. Device tolerability was rated highly, with an average daily score of >75 mm on the visual analog scale. The trial retention rate was 89.7% with most exclusions (42.9%) occurring due to unanticipated development of care complexity (e.g., hemorrhage and additional surgical procedures), with only 1 exclusion (14.3%) due to device discomfort. The active device group achieved the highest proportion of opioid-free hospitalizations (40%) compared to placebo (20%) and no device groups (30%). Pain at rest and with movement was similar between treatment groups. Conclusions: This trial protocol designed to test the efficacy of NSS2-Bridge device for post-cesarean pain management is feasible and acceptable. Larger proportions of patients not using opioids in the active device group justifies additional investigation on device effectiveness in pregnant and postpartum people at highest risk for pain.

Risk of Hepatocellular Carcinoma With Tenofovir vs Entecavir Treatment for Chronic Hepatitis B Virus: A Reconstructed Individual Patient Data Meta-analysis.

Importance: Conventional meta-analyses with aggregated study-level data have yielded conflicting results for the comparative effectiveness of tenofovir disoproxil fumarate vs entecavir in reducing hepatocellular carcinoma (HCC) risk among patients with chronic hepatitis B virus. Within-study heterogeneity, between-study heterogeneity, and the inability of conventional meta-analyses to capture time-to-event data were associated with these results. Objective: To perform a reconstructed individual patient data meta-analysis of high-quality propensity score-matched studies to provide robust estimates for comparative HCC risk between groups receiving tenofovir or entecavir. Data Sources: Medline and Embase databases were searched from inception to October 6, 2021. Study Selection: The initial search yielded 3435 articles. Fourteen studies that used propensity score matching to balance baseline characteristics were included in the final analysis. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was followed. Individual patient data were reconstructed from Kaplan-Meier curves. Risk of HCC was evaluated using random-effects hazard ratios (HRs) via a shared-frailty model and a Cox proportional hazards model stratified by study group. Restricted mean survival time (RMST) analysis was conducted to account for varying estimated treatment effect across time. Main Outcomes and Measures: The comparative risk of HCC with tenofovir vs entecavir treatment. Results: From analysis of 14 studes with 24 269 patients (10 534 receiving tenofovir and 13 735 receiving entecavir; mean age, 49.86 [95% CI, 48.35-51.36] years; 65.05% [95% CI, 58.60%-71.00%] men), tenofovir was associated with decreased HCC incidence compared with entecavir (stratified Cox HR, 0.85 [95% CI, 0.76-0.94] at 5 years; P = .002). However, there was no significant difference in subanalysis of clinical cohort studies (stratified Cox HR, 0.92 [95% CI, 0.80-1.06] at 5 years; P = .24). Among administrative database studies, proportionality was violated, and HRs could not be obtained via Cox proporational hazards-based models. The mean time to HCC development in RMST analysis was 2.8 (95% CI, 1.8-3.7) weeks longer (P < .001) for tenofovir vs entecavir at 5 years. The RMST analyses for other subgroups revealed either insignificant or minimal differences (<3 weeks) in the mean time to HCC at 5 years. Conclusions and Relevance: In this meta-analysis, there was no clinically meaningful difference in the risk of HCC between patients who received entecavir and patients who received tenofovir. There was no difference between tenofovir and entecavir among clinical cohort studies, whereas the mean time to HCC development was less than 3 weeks longer for patients who received tenofovir vs those who received entecavir at year 5 among administrative database studies. The choice between tenofovir or entecavir should be decided based on patient convenience and tolerability.

Metabolic Associated Fatty Liver Disease Increases the Risk of Systemic Complications and Mortality. A Meta-Analysis and Systematic Review of 12 620 736 Individuals.

OBJECTIVE: The recent introduction of the term metabolic associated fatty liver disease (MAFLD) sought to reclassify nonalcoholic fatty liver disease (NAFLD). MAFLD is thought to improve the encapsulation of metabolic dysregulation. However, recent evidence has found significant differences between MAFLD and NAFLD, and prevailing knowledge has largely arisen from studies on NAFLD. Hence, we conducted a meta-analysis and systematic review of the outcomes associated with MAFLD. METHODS: MEDLINE and Embase databases were searched for articles relating to outcomes in MAFLD. Analysis was conducted in random effects with hazard ratios (HRs) to account for longitudinal risk assessment of mortality and systemic complications. RESULTS: A total of 554 articles were identified, of which 17 articles were included. MAFLD resulted in an increase in the overall mortality (HR, 1.24; confidence interval [CI], 1.13-1.34), cancer-related mortality (HR, 1.27; CI, 1.01-1.54), and cardiovascular disease mortality (HR, 1.28, 1.03-1.53; P = .04) compared with non-MAFLD. MAFLD also increases the risk of cardiovascular events (HR, 1.49; CI, 1.34-1.64; P < .01), stroke (HR, 1.55; CI, 1.37-1.73; P < .01), and chronic kidney disease (HR, 1.53; CI, 1.38-1.68). The presence of MAFLD was also associated with an increased risk of heart failure, obstructive sleep apnea, and malignancy. CONCLUSION: MAFLD can significantly elevate the risk of systemic diseases and mortality. The care of MAFLD thus requires interdisciplinary collaboration, and future clinical trials conducted on MAFLD should aim to reduce the incidence of end-organ damage aside from improving liver histology.

Meta-analysis: analysis of mechanistic pathways in the treatment of non-alcoholic steatohepatitis. Evidence from a Bayesian network meta-analysis.

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) is the most common cause of liver disease. However, there is lack of comparison of efficacy between different NASH drug classes. We conducted a network meta-analysis evaluating drug classes through comparing histological outcomes and targets of drugs. APPROACH AND RESULTS: Medline, EMBASE and CENTRAL were searched for randomised controlled trials evaluating NASH drugs in biopsy-proven NASH patients. Primary outcomes included NASH resolution without worsening of fibrosis, at least 2-point reduction in Non-alcoholic fatty liver disease Activity Score (NAS) without worsening of fibrosis and at least 1-point reduction in fibrosis. Treatments were classified into inflammation, energy, bile acid and fibrosis modulators. The analysis was conducted with Bayesian network model and surface under the cumulative ranking curve (SUCRA) analysis. Among 49 included trials, treatments modulating energy (Risk ratio (RR): 1.92, Credible intervals (Crl): 1.59-2.34) were most likely to achieve NASH resolution followed by treatments modulating fibrosis (RR 1.66, Crl: 0.65-4.50), bile acids (RR: 1.37, Crl: 0.99-1.92) and inflammation (RR: 1.00, Crl: 0.75-1.33). Energy and bile acids modulation were effective in at least 2-point NAS reduction without worsening of fibrosis (RR: 1.52, Crl 1.30-1.77; RR: 1.69, Crl 1.41-2.03) and at least 1-point reduction in fibrosis (RR: 1.26, Crl:1.05-1.49; RR: 1.54, Crl: 1.20-1.97). CONCLUSIONS: This network analysis demonstrates the relative superiority of drugs modulating energy pathways and bile acids in NASH treatment. This guides the development and selection of drugs for combination therapies.

Clinical characteristics, surveillance, treatment allocation, and outcomes of non-alcoholic fatty liver disease-related hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: The clinical presentation and outcomes of non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma are unclear when compared with hepatocellular carcinoma due to other causes. We aimed to establish the prevalence, clinical features, surveillance rates, treatment allocation, and outcomes of NAFLD-related hepatocellular carcinoma. METHODS: In this systematic review and meta-analysis, we searched MEDLINE and Embase from inception until Jan 17, 2022, for articles in English that compared clinical features, and outcomes of NAFLD-related hepatocellular carcinoma versus hepatocellular carcinoma due to other causes. We included cross-sectional and longitudinal observational studies and excluded paediatric studies. Study-level data were extracted from the published reports. The primary outcomes were (1) the proportion of hepatocellular carcinoma secondary to NAFLD, (2) comparison of patient and tumour characteristics of NAFLD-related hepatocellular carcinoma versus other causes, and (3) comparison of surveillance, treatment allocation, and overall and disease-free survival outcomes of NAFLD-related versus non-NAFLD-related hepatocellular carcinoma. We analysed proportional data using a generalised linear mixed model. Pairwise meta-analysis was done to obtain odds ratio (OR) or mean difference, comparing NAFLD-related with non-NAFLD-related hepatocellular carcinoma. We evaluated survival outcomes using pooled analysis of hazard ratios. FINDINGS: Of 3631 records identified, 61 studies (done between January, 1980, and May, 2021; 94 636 patients) met inclusion criteria. Overall, the proportion of hepatocellular carcinoma cases secondary to NAFLD was 15·1% (95% CI 11·9-18·9). Patients with NAFLD-related hepatocellular carcinoma were older (p<0·0001), had higher BMI (p<0·0001), and were more likely to present with metabolic comorbidities (diabetes [p<0·0001], hypertension [p<0·0001], and hyperlipidaemia [p<0·0001]) or cardiovascular disease at presentation (p=0·0055) than patients with hepatocellular carcinoma due to other causes. They were also more likely to be non-cirrhotic (38·5%, 27·9-50·2 vs 14·6%, 8·7-23·4 for hepatocellular carcinoma due to other causes; p<0·0001). Patients with NAFLD-related hepatocellular carcinoma had larger tumour diameters (p=0·0087), were more likely to have uninodular lesions (p=0·0003), and had similar odds of Barcelona Clinic Liver Cancer stages, TNM stages, alpha fetoprotein concentration, and Eastern Cooperative Oncology Group (ECOG) performance status to patients with non-NAFLD-related hepatocellular carcinoma. A lower proportion of patients with NAFLD-related hepatocellular carcinoma underwent surveillance (32·8%, 12·0-63·7) than did patients with hepatocellular carcinoma due to other causes (55·7%, 24·0-83·3; p<0·0001). There were no significant differences in treatment allocation (curative therapy, palliative therapy, and best supportive care) between patients with NAFLD-related hepatocellular carcinoma and those with hepatocellular carcinoma due to other causes. Overall survival did not differ between the two groups (hazard ratio 1·05, 95% CI 0·92-1·20, p=0·43), but disease-free survival was longer for patients with NAFLD-related hepatocellular carcinoma (0·79, 0·63-0·99; p=0·044). There was substantial heterogeneity in most analyses (I2>75%), and all articles had low-to-moderate risk of bias. INTERPRETATION: NAFLD-related hepatocellular carcinoma is associated with a higher proportion of patients without cirrhosis and lower surveillance rates than hepatocellular carcinoma due to other causes. Surveillance strategies should be developed for patients with NAFLD without cirrhosis who are at high risk of developing hepatocellular carcinoma. FUNDING: None.

A Diagnostic Test Meta-Analysis Evaluating Imaging-Based and Blood Biomarker-Based Assessment Tools for Fibrosis After Liver Transplantation.

Early detection of liver graft fibrosis is crucial for risk stratification to identify patients for liver biopsy and timely treatment. However, diagnostic accuracy of noninvasive tests (NITs) remains unclear. Thus, this study sought to evaluate diagnostic accuracy of NITs in assessing liver allograft fibrosis and compare the differences in specificities and sensitivities among NITs. Medline and Embase databases were searched to include articles on diagnostic tests in liver transplantation (LT) patients with fibrosis. A meta-analysis on diagnostic test accuracy was conducted in a random-effects model. Sensitivities and specificities among the diagnostic tests were compared, and threshold values were calculated where applicable. A total of 25 articles were included. Vibration-controlled transient elastography (VCTE) met the minimum diagnostic accuracy requirements, yielding sensitivity, specificity, and diagnostic odds ratios of 0.9 (CI, 0.8-1.0), 0.9 (CI, 0.8-1.0), and 379.6 (CI, 45.8-1728.7), respectively. In the threshold assessment, the optimal cutoff was 9.30 kPa with a sensitivity, specificity, and area under the curve of 0.7 (CI, 0.5-0.9), 0.9 (CI, 0.8-0.9), and 0.9 (CI, 0.8-0.9), respectively. For significant fibrosis, acoustic radiation force impulse (ARFI) was superior to FibroTest (LabCorp [Burlington, NC]) and magnetic resonance elastography (MRE) in sensitivity. VCTE was superior to FibroTest in specificity. For advanced fibrosis, ARFI was superior to the Fibrosis-4 Index (FIB-4) in sensitivity. VCTE was superior to the AST to Platelet Ratio Index (APRI), MRE, and FIB-4 in specificity. In cirrhosis, VCTE was superior to APRI in specificity (P = 0.004) with comparable sensitivity. This study demonstrates the potential of VCTE and ARFI as diagnostic tools for fibrosis in LT recipients compared with blood-based NITs, which were shown to be less optimal.

Endoscopic submucosal dissection versus endoscopic mucosal resection for rectal carcinoid tumor. A meta-analysis and meta-regression with single-arm analysis.

OBJECTIVE: As there has been so far no consensus on the best endoscopic resection technique, a meta-analysis was conducted to compare the efficacy and safety of endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for treating rectal carcinoid tumors. METHODS: MEDLINE and EMBASE databases were searched for articles on the treatment of rectal carcinoid tumors using ESD vs EMR published up to October 2020 for outcomes including en bloc and complete resection, margin involvement, procedure time, requirement for additional surgery, bleeding, perforation and recurrence. Risk ratio and weighted mean differences were used for a DerSimonian and Laird random effects pairwise meta-analysis. Single-arm meta-analyses of proportions and random effects meta-regression analysis were also conducted. RESULTS: Twenty-two studies involving 1360 rectal carcinoid tumors were included, in which 655 and 705 rectal carcinoid tumors were resected with ESD and EMR, respectively. The resection efficacy of ESD was comparable to that of EMR for tumors <10 mm. However, there were a significantly higher complete resection rate, and lower rates of vertical margin involvement and requirement for additional surgery using ESD than using EMR for tumors ≤20 mm. ESD had a longer procedure time and an increased likelihood of bleeding than EMR. CONCLUSIONS: ESD is more effective in providing a curative treatment for rectal carcinoid tumors ≤20 mm in size as ESD can achieve a higher complete resection rate with lower vertical margin involvement than EMR. While they are suitable for treating rectal carcinoid tumors <10 mm as both techniques provide similar efficacy.

Are Surgical Patients Satisfied With Remote Consultations? A Comparison of Remote Versus Conventional Outpatient Clinic Follow-Up for Surgical Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Access to remote appointments (RA) by telephone or video is increasing as technology advances and becomes more available to patients. This meta-analysis of randomized controlled trials (RCTs) aims to discover whether surgical patients are satisfied with RAs when compared with conventional outpatient clinics (OPC). A literature search of RCTs of surgical patient satisfaction of RAs versus OPC appointments was performed. The PubMed, EMBASE, OVID, Cochrane Library, and Google Scholar databases were searched to include articles from January 2000 to 2020. A random-effects meta-analysis model was used to compare outcomes. All 7 RCTs showed that patients were as satisfied with RAs as OPC appointments (RR = 1.00, [0.98-1.02]; P = .73). Furthermore, both patient cohorts would prefer RAs for future follow-up (RR = 2.29, [1.96-2.97]; P < .00001). One RCT found the cost to institutions was less in the RA group ($19.05 vs $52.76) and another found the patients would save $9.96 on transportation costs. The majority of RCTs suggested cost to patients and or institutions would be less for RA. In conclusion, surgical patients are satisfied with RAs and in fact would prefer them.

Perinatal depression.

PURPOSE OF REVIEW: Perinatal depression is a common and debilitating complication of pregnancy and childbirth. Recent studies have elucidated relationships between acute birth events on depression risk, and novel treatments for postpartum depression have been discovered and approved. This article reviews current understandings about birth events on depression, new screening standards, and novel treatments for postpartum depression. RECENT FINDINGS: Pain, analgesia, and depression are complex traits that are inter-related during and after pregnancy. Certain individuals may benefit more than others from addressing pain and suffering around childbirth. Exposures to general anesthesia or postdural puncture headache are associated with postpartum depression symptoms, although a causal relationship is unlikely. Brexanolone, ketamine and its related compounds, and nonpharmacologic options offer new or alternative therapies for depression, although safety information for some of these treatments in pregnancy and lactation are needed. Maternal health bundles call for close attention to perinatal mental health screening with validated instruments, and for timely treatment referrals in the 'fourth trimester'. SUMMARY: Clinical monitoring and timely treatment of depression in the perinatal and postpartum periods is critical for maternal postpartum health and recovery. Perinatal specialists and researchers should continue to focus on tailored treatments specific to this special population.

Neutrophil-to-Lymphocyte Ratio Predicts Development of Immune-Related Adverse Events and Outcomes from Immune Checkpoint Blockade: A Case-Control Study.

The utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) utility in predicting immune-related adverse events (irAEs) and survival have not been well studied in the context of treatment with immune checkpoint inhibitors (ICIs). We performed a case-control study of cancer patients who received at least one dose of ICI in a tertiary hospital. We examined NLR and PLR in irAE cases and controls. Logistic and Cox regression models were used to identify independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). The study included 91 patients with irAEs and 56 controls. Multiple logistic regression showed that NLR < 3 at baseline was associated with higher occurrence of irAEs. Multivariate Cox regression showed that development of irAEs and reduction in NLR from baseline to week 6 were associated with longer PFS. Higher NLR values at baseline and/or week 6 were independently associated with shorter OS. A reduction in NLR from baseline to week 6 was associated with longer OS. In this study of cancer patients treated with ICIs, NLR has a bidirectional relationship with adverse outcomes. Lower NLR was associated with increased occurrence of irAEs while higher NLR values were associated with worse clinical outcomes.

Prevalence and risk factors for falls in patients with spondyloarthritis: A systematic review.

OBJECTIVE: Patients with spondyloarthritis (SpA) may have a greater risk of falling due to poor postural balance and decreased mobility. To our best knowledge, there are no published reviews that study falls in patients with SpA. Therefore, we aim to systematically review the literature and identify the prevalence and risk factors of falls in patients with SpA. METHODS: We conducted a systematic review using 5 electronic databases: PubMed, EMBASE, Scopus, Web of Science and Google Scholar using controlled vocabulary terms (eg MeSH terms) in the search strategy for the concepts: falls, fall risk, SpA and its subtypes. RESULTS: We identified 7279 articles, of which 3 studies with a total of 441 patients were included. Prevalence of falls ranged from 13% to 25%. We identified 16 main factors across 5 categories. Under socio-demographic factors, functional limitation, decreased quality of life, advanced age and job loss were associated with an increased risk of falls. Poor balance and mobility and fear of falling were associated with increased risk of falls. Active disease and symptoms of SpA were medical factors that were associated with increased risk of falls. Medication factors including polypharmacy, myorelaxants and antidepressants were not associated with increased fall risk. CONCLUSION: We identified potentially modifiable risk factors associated with increased risk of falls in patients with SpA, including functional limitation, poor balance and mobility, fear of falling and active disease. Clinicians should recognize these factors and address them in the holistic management of patients with SpA, thereby reducing falls and their complications.

Society for Obstetric Anesthesia and Perinatology: Consensus Statement and Recommendations for Enhanced Recovery After Cesarean.

The purpose of this article is to provide a summary of the Enhanced Recovery After Cesarean delivery (ERAC) protocol written by a Society for Obstetric Anesthesia and Perinatology (SOAP) committee and approved by the SOAP Board of Directors in May 2019. The goal of the consensus statement is to provide both practical and where available, evidence-based recommendations regarding ERAC. These recommendations focus on optimizing maternal recovery, maternal-infant bonding, and perioperative outcomes after cesarean delivery. They also incorporate management strategies for this patient cohort, including recommendations from existing guidelines issued by professional organizations such as the American College of Obstetricians and Gynecologists and the American Society of Anesthesiologists. This consensus statement focuses on anesthesia-related and perioperative components of an enhanced recovery pathway for cesarean delivery and provides the level of evidence for each recommendation.

Validation of the clinical utility of 4 guidelines in the initial triage of mucinous cystic lesions of the pancreas based on cross-sectional imaging: Experience with 188 surgically-treated patients.

INTRODUCTION: Over the years, several guidelines have been introduced to guide management of mucinous pancreatic cystic neoplasms (mPCN). In this study, we aimed to evaluate and compare the clinically utility of the Sendai-06, Fukuoka-12, Fukuoka-17 and European-18 guidelines in predicting malignancy of mPCN. METHODS: One hundred and eighty-eight patients with mucinous cystic neoplasms (MCN) or intraductal papillary mucinous neoplasm (IPMN) who underwent surgery were retrospectively reviewed and classified under the 4 guidelines. Malignancy was defined as high grade dysplasia and invasive carcinoma. RESULTS: Raised CA19-9>37U/ml, enhancing mural nodule≥5 mm and main pancreatic duct≥10 mm were significantly associated with malignancy on multivariate analysis. Increasing number of high risk features, absolute indications (European-18), worrisome risk or relative indications (European-18) were significantly associated with an increased likelihood of malignancy. The positive predictive values (PPV) of high risk features for Sendai-06, Fukuoka-12, Fukuoka-17 and absolute indications (European-18) for malignancy were 53%, 76%, 78% and 78% respectively. The negative predictive values (NPV) of the Sendai-06, Fukuoka-12 and Fukuoka-17 were 100%, while that of the European-18 was 92%. Risk of malignancy for patients with ≥4 worrisome features (Fukuoka-17) and ≥3 relative indications (European-18) was 66.7% and 75.0% respectively. CONCLUSIONS: All 4 guidelines studied were useful in the initial triage of mPCN for the risk stratification of malignancy. The Fukuoka-17 had the highest PPV and NPV.

ETS Factor ETV5 Activates the Mutant Telomerase Reverse Transcriptase Promoter in Thyroid Cancer.

Background: Co-occurrence of TERT (telomerase reverse transcriptase) promoter (TERTp) mutations with BRAF/RAS mutations is associated with significantly more aggressive thyroid cancer. TERTp mutations are hypothesized to generate de novo binding sites for ETS transcription factors, which are themselves activated by BRAF/RAS-stimulated MEK-ERK activity. To date, a detailed study of this mechanism has been limited to only a few cancer types, and we hypothesized that ETS factors involved in TERTp activation could vary between different cancers. Methodology: Here we sought to identify ETS factor(s) required for TERTp activation in thyroid cancer, using a combination of in silico analyses of TCGA data, and experimentation using in vitro thyroid cell models analyzed by quantitative reverse transcription-PCR, immunoprecipitation (IP), chromatin IP, and gene reporter assays. Results: We found that ETV5 was abundantly expressed in papillary thyroid cancers from the TCGA data set, and in thyroid cancer cell line models. Furthermore, ETV5 was found to preferentially bind to the -124 bp(T) TERTp allele and stimulate TERT transcription in thyroid cancer cells devoid of GA binding protein transcription factor (GABP) activity. We also found that ETV5 functionally cooperates with the transcription factor FOXE1 to further enhance TERTp activity, a mechanism that may at least partially explain why FOXE1 represents a significant genetic determinant of thyroid cancer risk. Conclusions: ETS factors that activate mutant TERTp vary between cancer types, and here we show for the first time that ETV5 demonstrates mutant allele-specific affinity for TERTp in thyroid cancer, a property that has previously only been attributable to GABP.