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.

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.

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.

Associations between postpartum pain type, pain intensity and opioid use in patients with and without opioid use disorder: a cross-sectional study.

BACKGROUND: Pain is a multidimensional construct. The purpose of this cross-sectional, single-centre study was to evaluate the relationship between postpartum pain type with pain intensity and opioid use in people with and without opioid use disorder (OUD). METHODS: Postpartum pain type was coded from McGill Pain Questionnaire and Patient-Reported Outcome Measurement Information System (PROMIS) inventories in people with or without OUD after childbirth in a 4-month period. The co-primary outcomes were pain intensity (0-10 scale) and total inpatient oxycodone (mg). Multivariable linear mixed-effects models assessed between- and within-person relationships for pain type (primary predictor) and outcomes. RESULTS: There were 44 522 unique pain scores and types from 2610 people. Pain types were associated with pain intensity (P<0.001). Between-person comparisons showed affective pain was associated with a small but higher total oxycodone dose (difference 1.04 mg compared with no affective pain, P<0.001). Among people with OUD, within-person comparisons showed that the presence of affective pain resulted in pain scores 1 point higher than when affective pain was not present (P=0.002); between-person comparisons showed that people with affective pain had pain scores 6 points higher (P=0.048). Within-person and between-person comparisons among OUD showed that nociceptive/neuropathic pain was associated with a higher total oxycodone dose (1.6 and 11.4 mg, respectively). CONCLUSIONS: Postpartum pain type was associated with pain intensity and opioid use. Further research is required to address the multiple dimensions of postpartum pain in people with and without OUD to improve treatment of postpartum pain.

What Is New in Obstetric Anesthesia: The 2021 Gerard W. Ostheimer Lecture.

The Gerard W. Ostheimer lecture is given annually to members of the Society for Obstetric Anesthesia and Perinatology. This lecture summarizes new and emerging literature that informs the clinical practice of obstetric anesthesiologists. In this review, some of the most influential articles discussed in the 2021 virtual lecture are highlighted. Themes include maternal mortality; disparities and social determinants of health; cognitive function, mental health, and recovery; quality and safety; operations, value, and economics; clinical controversies and dogmas; epidemics and pandemics; fetal-neonatal and child health; general clinical care; basic and translational science; and the future of peripartum anesthetic care. Practice-changing evidence is presented and evaluated. A priority list for clinical updates, systems, and quality improvement initiatives is presented.

Development of obstetric anesthesia core competencies for USA residency programs through a Delphi process.

PURPOSE: The standard for anesthesia residency training in the USA mainly relies on the Accreditation Council for Graduate Medical Education (ACGME) Outcome Project, a framework that lacks specific directives for subspecialties including obstetric anesthesia. We aimed to identify core competencies in obstetric anesthesiology that can be adapted to different residency training programs to help improve the quality of training and accountability of the institutions within the USA. METHODS: We identified a preliminary list of competencies from review of existing competency-based obstetric anesthesia training curricula and practice guidelines. We used a modified Delphi methodology to achieve expert consensus among members of the Society for Obstetric Anesthesia and Perinatology education committee. The panellists were asked to evaluate the importance of each competency using a five-point Likert scale, with consensus after two rounds defined at 80% agreement. The responders were also asked at which level of training each competency should be attained. RESULTS: The Delphi rounds had 75% response rate and derived 94 competencies that were categorized under the six ACGME domains: patient care (38), medical knowledge (45), system-based practice (two), practice-based learning and improvement (five), interpersonal communication skills (two), and professionalism (two). CONCLUSION: We generated a residency training competency list for obstetric anesthesiology through expert consensus. This list can be used by residency training programs to develop a structured competency-based curriculum with tangible milestones, thereby reducing heterogeneity in the standard of training.

RéSUMé: OBJECTIF: La norme pour la formation en résidence en anesthésie aux États-Unis repose principalement sur le Projet de résultats (Outcome Project) de l'Accreditation Council for Graduate Medical Education (ACGME), un cadre qui ne dispose pas de directives spécifiques pour les surspécialités, notamment pour l'anesthésie obstétricale. Notre objectif était d'identifier les compétences de base en anesthésiologie obstétricale qui pourraient être adaptées aux différents programmes de formation en résidence afin d'améliorer la qualité de la formation et la responsabilisation des établissements aux États-Unis. MéTHODE: Nous avons dressé une liste préliminaire de compétences en passant en revue les programmes de formation axés sur les compétences et les lignes directrices de pratique existants en anesthésie obstétricale. Nous avons utilisé une méthodologie Delphi modifiée pour parvenir à un consensus d'expert·es parmi les membres du comité d'éducation de la Society for Obstetric Anesthesia and Perinatology. Les panélistes ont été invité·es à évaluer l'importance de chaque compétence à l'aide d'une échelle de Likert à cinq points, le consensus étant défini à 80 % d'accord après deux tours. On a également demandé aux répondant·es à quel niveau de formation chaque compétence devrait être atteinte. RéSULTATS: Les étapes du processus Delphi ont eu un taux de réponse de 75 % et ont permis de déterminer 94 compétences qui ont été classées dans les six domaines ACGME : soins aux patient·es (38), connaissances médicales (45), pratique systémique (deux), apprentissage et amélioration basés sur la pratique (cinq), compétences en communication interpersonnelle (deux) et professionnalisme (deux). CONCLUSION: Nous avons généré une liste de compétences pour la formation de résidence en anesthésiologie obstétricale grâce à un consensus d'expert·es. Cette liste peut être utilisée par les programmes de formation en résidence pour élaborer un programme structuré axé sur les compétences avec des jalons tangibles, réduisant ainsi l'hétérogénéité dans la norme de formation.

Obstetric operating room staffing and operating efficiency using queueing theory.

INTRODUCTION: Strategies to achieve efficiency in non-operating room locations have been described, but emergencies and competing priorities in a birth unit can make setting optimal staffing and operation benchmarks challenging. This study used Queuing Theory Analysis (QTA) to identify optimal birth center operating room (OR) and staffing resources using real-world data. METHODS: Data from a Level 4 Maternity Center (9,626 births/year, cesarean delivery (CD) rate 32%) were abstracted for all labor and delivery operating room activity from July 2019-June 2020. QTA has two variables: Mean Arrival Rate, λ and Mean Service Rate µ. QTA formulas computed probabilities: P0 = 1-(λ/ µ) and Pn = P0 (λ/µ)n where n = number of patients. P0…n is the probability there are zero patients in the queue at a given time. Multiphase multichannel analysis was used to gain insights on optimal staff and space utilization assuming a priori safety parameters (i.e., 30 min decision to incision in unscheduled CD; ≤ 5 min for emergent CD; no greater than 8 h for nil per os time). To achieve these safety targets, a < 0.5% probability that a patient would need to wait was assumed. RESULTS: There were 4,017 total activities in the operating room and 3,092 CD in the study period. Arrival rate λ was 0.45 (patients per hour) at peak hours 07:00-19:00 while λ was 0.34 over all 24 h. The service rate per OR team (µ) was 0.87 (patients per hour) regardless of peak or overall hours. The number of server teams (s) dedicated to OR activity was varied between two and five. Over 24 h, the probability of no patients in the system was P0 = 0.61, while the probability of 1 patient in the system was P1 = 0.23, and the probability of 2 or more patients in the system was P≥2 = 0.05 (P3 = 0.006). However, between peak hours 07:00-19:00, λ was 0.45, µ was 0.87, s was 3, P0 was 0.48; P1 was 0.25; and P≥2 was 0.07 (P3 = 0.01, P4 = 0.002, P5 = 0.0003). CONCLUSION: QTA is a useful tool to inform birth center OR efficiency while upholding assumed safety standards and factoring peaks and troughs of daily activity. Our findings suggest QTA is feasible to guide staffing for maternity centers of all volumes through varying model parameters. QTA can inform individual hospital-level decisions in setting staffing and space requirements to achieve safe and efficient maternity perioperative care.

Association between labor and delivery pain and postpartum pain with symptoms and clinical diagnosis of postpartum depression in patients with overweight and obesity.

PURPOSE: Childbirth pain has been associated with the risk for postpartum depression. However, existing studies have been limited by the use of depression screening tools as outcomes, and none to date have used a structured clinical interview for DSM-V (SCID), which is considered the gold standard for psychiatric diagnoses. This study aimed to quantify the relationships between labor and postpartum pain and postpartum depression diagnosis detected by SCID, as well as depression symptoms detected by the Center for Epidemiological Studies Depression Scale (CESD) screening tool, among a high-risk cohort. METHODS: The study was a secondary analysis of a prospective observational study of a cohort of women enriched for high risk for depression, i.e., pregnant women originally enrolled in a prospective study investigating factors leading to excessive gestational weight gain. Subjects were assessed prospectively for depression using both SCID and CESD at the third trimester and at 6 months postpartum. Overweight and obesity were defined as pre-gravid body mass index (BMI) ≥ 25 kg/m2. Both vaginal and cesarean deliveries were included in the cohort. Pain scores (0-10 numeric rating scale) during childbirth and after delivery were correlated with CESD and SCID. Propensity score matching was performed with propensity groups defined as those with low-moderate postpartum pain and those with high postpartum pain. The relationships between pain measures and 6-month postpartum depression diagnosis by SCID, and between pain measures and 6-month postpartum depression symptoms by CESD, were assessed by unweighted logistic regression and by logistic regression weighted by propensity score derived by average treatment effect (ATE) adjusted for baseline covariates. RESULTS: There were 237 subjects in the cohort for analysis. Labor and postpartum pain were not associated with depression diagnosis by SCID at 6 months postpartum. However, postpartum pain, but not labor pain, was associated with depressive symptoms on the CESD at 6 months postpartum. Women with higher maximum postpartum pain scores had significantly higher odds of developing clinically significant postpartum depressive symptoms at 6 months, compared to those with lower pain scores in the unweighted model (OR: 1.3, 95% CI 1.0, 1.5; P = 0.005) and ATE-weighted models (OR: 1.2, 95% CI 1.0, 1.5; P = 0.03). Consistent with prior work, SCID and CESD were strongly associated, and 92.9% (13/14) of participants with postpartum depression diagnosis by 6-month SCID also showed high CESD symptomology, P < 0.0001). CONCLUSIONS: Although labor and postpartum pain were not associated with clinical diagnosis of depression (SCID) at 6 months postpartum, postpartum pain was linked to 6-month postpartum depression symptoms. Depressive symptoms are more likely to be exhibited in women with higher postpartum pain, potentially reflecting poorer birth recovery. The contribution of postpartum pain and depressive symptoms to overall patterns of poor recovery after childbirth should be assessed further.

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.

Lewy Body-like Inclusions in Human Midbrain Organoids Carrying Glucocerebrosidase and α-Synuclein Mutations.

OBJECTIVE: We utilized human midbrain-like organoids (hMLOs) generated from human pluripotent stem cells carrying glucocerebrosidase gene (GBA1) and α-synuclein (α-syn; SNCA) perturbations to investigate genotype-to-phenotype relationships in Parkinson disease, with the particular aim of recapitulating α-syn- and Lewy body-related pathologies and the process of neurodegeneration in the hMLO model. METHODS: We generated and characterized hMLOs from GBA1-/- and SNCA overexpressing isogenic embryonic stem cells and also generated Lewy body-like inclusions in GBA1/SNCA dual perturbation hMLOs and conduritol-b-epoxide-treated SNCA triplication hMLOs. RESULTS: We identified for the first time that the loss of glucocerebrosidase, coupled with wild-type α-syn overexpression, results in a substantial accumulation of detergent-resistant, ß-sheet-rich α-syn aggregates and Lewy body-like inclusions in hMLOs. These Lewy body-like inclusions exhibit a spherically symmetric morphology with an eosinophilic core, containing α-syn with ubiquitin, and can also be formed in Parkinson disease patient-derived hMLOs. We also demonstrate that impaired glucocerebrosidase function promotes the formation of Lewy body-like inclusions in hMLOs derived from patients carrying the SNCA triplication. INTERPRETATION: Taken together, the data indicate that our hMLOs harboring 2 major risk factors (glucocerebrosidase deficiency and wild-type α-syn overproduction) of Parkinson disease provide a tractable model to further elucidate the underlying mechanisms for progressive Lewy body formation. ANN NEUROL 2021;90:490-505.

Obstetric Anesthesia Procedure-Based Workload and Facility Utilization of Society of Obstetric Anesthesia and Perinatology Centers of Excellence Designated Institutions.

BACKGROUND: Optimal workload and staffing for obstetric anesthesia services have yet to be determined. We surveyed Society of Obstetric Anesthesia and Perinatology (SOAP) Centers of Excellence (COE) for Obstetric Anesthesia Care institutions to evaluate procedure-based obstetric anesthesia workload and facility use. METHODS: After institutional review board (IRB) exemption, an online survey instrument (REDCap) was sent by email (1 initial and 2 reminders) to all SOAP COEs. Survey data included the number of deliveries, cesarean delivery rate, neuraxial labor analgesia rate, the number of labor and operating rooms, and the number of in-house and backup obstetric anesthesia providers. Obstetric anesthesia activity was estimated using a time-based workload ratio per provider (Stanford Work Index, 1.0 = clinically working every minute of every hour on duty) during weekday, weeknight, and weekend shifts. We compared workload between academic and nonacademic centers and correlated operating and labor rooms with cesarean and vaginal delivery volume. RESULTS: Fifty-one of 53 surveys were returned (96% response rate). Data from 33 academic and 14 nonacademic US institutions were analyzed. For academic centers, median Stanford Work Index for all staff (included trainees and Certified Registered Nurse Anesthetists) was 0.20 (weekday) and 0.19 (weeknight and weekends); nonacademic centers were 0.33 (weekday, P < .001 versus academic), 0.23 (weeknight, P = .009 versus academic), and 0.23 (weekends, P = .03 versus academic practices). Attending-only Stanford Work Indices were similar between academic and nonacademic centers. Total number of rooms on the obstetric suite (operating, labor, or triage room) was strongly correlated with delivery volume ( R2 = 0.55). CONCLUSIONS: The results outline staffing procedure-based workload ratios and facility utilization at SOAP COEs in the United States. These data can be used by other institutions that provide obstetric anesthesia services to guide their obstetric anesthesia staffing. The importance of considering the workload associated with different shifts and between academic and nonacademic centers is also highlighted. The results show that approximately one-third of an obstetric anesthesiologist's workload is spent on performing procedures. We did not, however, measure the other tasks anesthesiologists practice as peripartum physicians (eg, managing critically ill parturients, doing pre- and postprocedural evaluations, or performing emergent and unexpected procedures), and future studies are required to determine the time required to perform these tasks. Studies to determine the optimal staffing models to handle workload fluctuations and improve outcomes are also required.

A Systematic Scoping Review of Peridelivery Pain Management for Pregnant People With Opioid Use Disorder: From the Society for Obstetric Anesthesia and Perinatology and Society for Maternal Fetal Medicine.

The prevalence of pregnant people with opioid use disorder (OUD), including those receiving medications for opioid use disorder (MOUD), is increasing. Challenges associated with pain management in people with OUD include tolerance, opioid-induced hyperalgesia, and risk for return to use. Yet, there are few evidence-based recommendations for pain management in the setting of pregnancy and the postpartum period, and many peripartum pain management studies exclude people with OUD. This scoping review summarized the available literature on peridelivery pain management in people with OUD, methodologies used, and identified specific areas of knowledge gaps. PubMed and Embase were comprehensively searched for publications in all languages on peripartum pain management among people with OUD, both treated with MOUD and untreated. Potential articles were screened by title, abstract, and full text. Data abstracted were descriptively analyzed to map available evidence and identify areas of limited or no evidence. A total of 994 publications were imported for screening on title, abstracts, and full text, yielding 84 publications identified for full review: 32 (38.1%) review articles, 14 (16.7%) retrospective studies, and 8 (9.5%) case reports. There were 5 randomized controlled trials. Most studies (64%) were published in perinatology (32; 38.1%) journals or anesthesiology (22; 26.2%) journals. Specific areas lacking trial or systematic review evidence include: (1) methods to optimize psychological and psychosocial comorbidities relevant to acute pain management around delivery; (2) alternative nonopioid and nonpharmacologic analgesia methods; (3) whether or not to use opioids for severe breakthrough pain and how best to prescribe and monitor its use after discharge; (4) monitoring for respiratory depression and sedation with coadministration of other analgesics; (5) optimal neuraxial analgesia dosing and adjuncts; and (6) benefits of abdominal wall blocks after cesarean delivery. No publications discussed naloxone coprescribing in the labor and delivery setting. We observed an increasing number of publications on peripartum pain management in pregnant people with OUD. However, existing published works are low on the pyramid of evidence (reviews, opinions, and retrospective studies), with a paucity of original research articles (<6%). Opinions are conflicting on the utility and disutility of various analgesic interventions. Studies generating high-quality evidence on this topic are needed to inform care for pregnant people with OUD. Specific research areas are identified, including utility and disutility of short-term opioid use for postpartum pain management, role of continuous wound infiltration and truncal nerve blocks, nonpharmacologic analgesia options, and the best methods to support psychosocial aspects of pain management.

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.

Evaluation of Therapies for Peripheral and Neuraxial Opioid-induced Pruritus based on Molecular and Cellular Discoveries.

Opioids are a mainstay of treatment for pain worldwide. Pruritus, a common side effect of opioids, is a patient dissatisfier that limits their use in many clinical settings. Both parenteral and neuraxial administration of opioids frequently evoke pruritus. The ability of opioids to suppress pain while causing itch continues to perplex clinicians and researchers alike. Several mechanisms have been proposed to explain how opioids can give rise to pruritus, but specific knowledge gaps perpetuate debate. This review summarizes the clinical burden of opioid-induced pruritus and emphasizes recent discoveries of peripheral and central mechanisms for opioid-induced pruritus, particularly with respect to scientific and conceptual advances in spinal cord circuitry and mast cell biology. The mechanisms and effectiveness of existing medications used for clinical management of pruritus will be evaluated, and we will highlight the emerging preclinical utility of selective κ-opioid receptor agonists, such as nalfurafine, for the management of opioid-induced pruritus.

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.

Resource utilization across the continuum of HIV care: An emergency department-based cohort study.

BACKGROUND: The objective of this study was to determine the healthcare resource utilization for people living with HIV (PLWH) presenting to the emergency department (ED) across the HIV Care Continuum. METHODS: This prospective study enrolled PLWH presenting to an urban ED between June 2016 and March 2017. Subjects were categorized as being linked to care, retained in care, on antiretroviral therapy (ART), and virally suppressed (<200 copies/ml). Data on ED visit rates, duration of stay, and hospital admission rates were compared to local metrics. RESULTS: Overall, 94.3% of 159 enrollees had been linked to care, 75.5% retained in care, 81.1% on ART, and 62.8% virally suppressed. Compared to the general population of the city and of the ED, participants had a higher ED visit rate (3.0 v. 1.2 visits per person-per year) in the past two years, a higher median duration of ED stay (12.6 v. 7.6 h), and a higher hospital admission rate (36.5% v. 24.9%) during their index ED visit. Viral suppression was negatively associated with admission (OR = 0.35, 95% CI: 0.17, 0.72). Forty-eight (30.2%) participants who had at least eight ED visits in the past two years were more likely to have a diagnosed mental health disorder (79.2% v. 62.2%, p=0.036). CONCLUSIONS: Our results showed that PLWH use more ED resources than the general population and a better engagement in HIV care is linked to lesser ED resource utilization for PLWH, indicating the importance of improved HIV care engagement in healthcare utilization management.

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.

Obstetric pain correlates with postpartum depression symptoms: a pilot prospective observational study.

BACKGROUND: Data linking labor pain and postpartum depression are emerging. Robust, prospective evaluations of this relationship while factoring other important variables are lacking. We assessed perinatal pain and other factors predicting postpartum depression (PPD) symptoms. METHODS: Third trimester women, stratified by a priori plan to receive or avoid labor epidural analgesia, were longitudinally followed from the prenatal period through labor and delivery, until 6 weeks and 3 months postpartum. Electronic pain data was collected hourly during labor in real time, capturing pain unpleasantness, intensity, pain management satisfaction, and expectations. Prenatal and postpartum data included anxiety, depression, the Brief Pain Inventory (BPI), pain catastrophizing, resiliency, and perceived social support and stress. The primary outcome was Edinburgh Postnatal Depression Score (EPDS) as a marker of PPD symptoms. The primary pain variable of interest was labor pain emotional valence (unpleasantness burden, area under the curve for entire labor duration). Single and multivariable linear regressions examined perinatal pain variables in relation to EPDS. RESULTS: Of 72 subjects included, 55 planned/received labor epidural analgesia and 17 planned avoidance/avoided it. In the planned epidural group, the emotional valence of labor pain independently predicted six-week EPDS (labor pain unpleasantness burden, R2 = 0.42, P = 0.002). In addition to labor pain, prenatal and postpartum pain variables from the BPI independently predicted six-week EPDS. Three-month depression scores were linked to labor and acute pain (6 weeks postpartum), but not to chronic (3 months postpartum) pain variables. Intrapartum pain management satisfaction and expectations were largely met or exceeded and did not differ between analgesia groups. CONCLUSION: For susceptible women, pain at all perinatal time points-prenatal, labor, and postpartum-appear to be independently linked to depression scores at 6 weeks postpartum. The relationships are true, even though satisfaction and expectations regarding labor pain management were met or exceeded. These data support the concept that labor and acute postpartum pain influences both acute and long-term PPD symptoms, although additional data are needed to assess how analgesia preference interacts with these relationships.

The Histamine 3 Receptor Is Expressed in the Heart and Its Activation Opposes Adverse Cardiac Remodeling in the Angiotensin II Mouse Model.

Histamine is a basic amine stored in mast cells, with its release capable of activating one of four histamine receptors. The histamine 3 receptor (H3R) is known to be cardioprotective during acute ischemia by acting to limit norepinephrine release. However, a recent study reported that myofibroblasts isolated from the infarct zone of rat hearts responded to H3R activation by up-regulating collagen production. Thus, it is necessary to clarify the potential role of the H3R in relation to fibrosis in the heart. We identified that the mouse left ventricle (LV) expresses the H3R. Isolation of mouse cardiac fibroblasts determined that while angiotensin II (Ang II) increased levels of the H3R, these cells did not produce excess collagen in response to H3R activation. Using the Ang II mouse model of adverse cardiac remodeling, we found that while H3R blockade had little effect on cardiac fibrosis, activation of the H3R reduced cardiac fibrosis and macrophage infiltration. These findings suggest that when activated, the H3R is anti-inflammatory and anti-fibrotic in the mouse heart and may be a promising target for protecting against cardiac fibrosis.