Preoperative Fascia Iliaca Blocks Associated with Decreased Opioid Consumption in Femoral Shaft and Distal Femur Fractures.

OBJECTIVES: To examine the impact of fascia iliaca (FI) blocks performed in the emergency department on femoral shaft and distal femur fracture patients on opioid consumption, length of stay, and readmission rate. DESIGN: Prospective cohort study. SETTING: Community-based level 1 trauma center. PATIENT SELECTION CRITERIA: Patients with isolated low energy femoral shaft or distal femur fractures (OTA/AO 32 and 33) presenting from January 1, 2020 to May 31, 2022 were included. OUTCOME MEASURES AND COMPARISONS: Opioid consumption, length of stay, discharge disposition, and 30-day readmission rate were compared between patients undergoing fascia iliaca compartment block and not receiving the block. RESULTS: 136 patients were included. Twenty-four received fascia iliaca block. Both cohorts were primarily female gender 66.7% and 66.9%, respectively for the FI block and no FI block cohort. The majority of the FI block cohort (62.5%) had femoral shaft fractures, while the no FI block cohort had mostly distal femur fractures (56.2%). Mean body mass index, fracture type, and surgical procedure were similar between patients undergoing FI block and not receiving FI block The FI block group had significantly lower opioid consumption pre-operatively (36.1 vs 55.3 morphine milliequivalents (MMEs), p=0.030), post-operatively (71.7 vs 130.6 MMEs, p=0.041), over total hospital stay (107.9 vs 185.9 MMEs), and mean opioid consumption per day of hospital stay (25.9 vs 48.4 MMEs, p=0.003). There was no significant difference in length of stay (4.9 vs 5.0 days, p=0.900), discharge disposition destination (p=0.200), or 30 day readmissions (12.5% vs 4.5%, p=0.148) between groups. CONCLUSIONS: Undergoing fascia iliaca block in the emergency department was associated with decreased opioid consumption in patients with femoral shaft or distal femur fractures. There was no associated difference in length of stay, discharge disposition, or 30-day readmissions. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Portable Nanopore sequencing solution for next-generation HIV drug resistance testing.

BACKGROUND: Tackling HIV drug resistance is one of major challenges for ending AIDS epidemic, but the elevated expense of cutting-edge genomics hampers the advancement of HIV genotype testing for clinical care. METHODS: We developed a HIV genotype testing pipeline that centers on a cost-efficient portable Nanopore sequencer. Accuracy verification was conducted through comparison with parallel data obtained via fixed-site Pacbio sequencing. Our complete pol-gene sequencing strategy coupled with portable high-throughput sequencing was applied to identify drug resistance mutations across 58 samples sourced from the ART-treated Los Angeles General Medical Center Rand Schrader Clinic (LARSC) cohort (7 samples from 7 individuals) and the ART-naïve Center for HIV/AIDS Vaccine Immunology (CHAVI) cohort (51 samples from 38 individuals). RESULTS: A total of 472 HIV consensus sequences, each tagged with a unique molecular identifier, were produced from over 1.4 million bases acquired through portable Nanopore sequencing, which matched those obtained independently via Pacbio sequencing. With this desirable accuracy, we first documented the linkage of multidrug cross-resistance mutations across Integrase Strand Transfer inhibitors (INSTIs) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) from an individual failing a second-generation INSTI regimen. By producing more than 500 full-length HIV pol gene sequences in a single portable sequencing run, we detected Protease Inhibitor (PI), Nucleoside Reverse Transcriptase Inhibitor (NRTI), NNRTI and INSTI resistance mutations. All drug resistance mutations identified through portable sequencing were cross-validated using fixed-site Pacbio sequencing. CONCLUSIONS: Our accurate and affordable HIV drug resistance testing solution is adaptable for both individual patient care and large-scale surveillance initiatives.

Health-Related Quality of Life Outcomes in Meningioma Patients Based upon Tumor Location and Treatment Modality: A Systematic Review and Meta-Analysis.

Patients with meningiomas may have reduced health-related quality of life (HRQoL) due to postoperative neurological deficits, cognitive dysfunction, and psychosocial burden. Although advances in surgery and radiotherapy have improved progression-free survival rates, there is limited evidence regarding treatment outcomes on HRQoL. This review examines HRQoL outcomes based on tumor location and treatment modality. A systematic search in PubMed yielded 28 studies with 3167 patients. The mean age was 54.27 years and most patients were female (70.8%). Approximately 78% of meningiomas were located in the skull base (10.8% anterior, 23.3% middle, and 39.7% posterior fossae). Treatment modalities included craniotomy (73.6%), radiotherapy (11.4%), and endoscopic endonasal approach (EEA) (4.0%). The Karnofsky Performance Scale (KPS) was the most commonly utilized HRQoL instrument (27%). Preoperative KPS scores > 80 were associated with increased occurrence of postoperative neurological deficits. A significant difference was found between pre- and post-operative KPS scores for anterior/middle skull base meningiomas (SBMs) in comparison to posterior (SBMs) when treated with craniotomy. Post-craniotomy SF-36 scores were lower for posterior SBMs in comparison to those in the anterior and middle fossae. Risk factors for poor neurological outcomes include a high preoperative KPS score and patients with posterior SBMs may experience a greater burden in HRQoL.

Precision detection of recent HIV infections using high-throughput genomic incidence assay.

HIV incidence is a key measure for tracking disease spread and identifying populations and geographic regions where new infections are most concentrated. The HIV sequence population provides a robust signal for the stage of infection. Large-scale and high-precision HIV sequencing is crucial for effective genomic incidence surveillance. We produced 1,034 full-length envelope gene sequences from a seroconversion cohort by conducting HIV microdrop sequencing and measuring the genomic incidence assay's genome similarity index (GSI) dynamics. The measured dynamics of 9 of 12 individuals aligned with the GSI distribution estimated independently using 417 publicly available incident samples. We enhanced the capacity to identify individuals with recent infections, achieving predicted detection accuracies of 92% (89%-94%) for cases within 6 months and 81% (74%-87%) for cases within 9 months. These accuracy levels agreed with the observed detection accuracy intervals of an independent validation data set. Additionally, we produced 131 full-length envelope gene sequences from eight individuals with chronic HIV infection. This analysis confirmed a false recency rate (FRR) of 0%, which was consistent with 162 publicly available chronic samples. The mean duration of recent infection (MDRI) was 238 (209-267) days, indicating an 83% improvement in performance compared to current recent infection testing algorithms. The shifted Poisson mixture model was then used to estimate the time since infection, and the model estimates showed an 88% consistency with the days post infection derived from HIV RNA test dates and/or seroconversion dates. HIV microdrop sequencing provides unique prospects for large-scale incidence surveillance using high-throughput sequencing. IMPORTANCE Accurate identification of recently infected individuals is vital for prioritizing specific populations for interventions, reducing onward transmission risks, and optimizing public health services. However, current HIV-specific antibody-based methods have not been satisfactory in accurately identifying incident cases, hindering the use of HIV recency testing for prevention efforts and partner protection. Genomic incidence assays offer a promising alternative for identifying recent infections. In our study, we used microdroplet technologies to produce a large number of complete HIV envelope gene sequences, enabling the accurate detection of early infection signs. We assessed the dynamics of the incidence assay's metrics and compared them with statistical models. Our approach demonstrated high accuracy in identifying individuals with recent infections, achieving predicted detection rates exceeding 90% within 6 months and over 80% within 9 months of infection. This high-resolution method holds significant potential for enhancing the effectiveness of HIV incidence screening for case-based surveillance in public health initiatives.

What are patients asking and reading online? An analysis of online patient searches for rotator cuff repair.

BACKGROUND: Patients undergoing rotator cuff surgery often search the internet for information regarding the procedure. One popular source, Google, compiles frequently asked questions and links to websites that may provide answers. This study provides an analysis of the most frequently searched questions associated with rotator cuff surgery. We hypothesize that there will be distinct search patterns associated with online queries about rotator cuff surgery that could provide unique insights into patient concerns. METHODS: A set of search terms were entered into Google Web Search using a clean-install Google Chrome browser. Frequently associated questions and their webpages were extracted to a database via a data mining extension. Questions were categorized by topics relevant for rotator cuff arthroscopy. Websites were categorized by source and scored for quality using the JAMA Benchmark Criteria. Pearson's χ2 tests were used to analyze nominal data. Student t tests were performed to compare JAMA Benchmark Scores. RESULTS: Of the 595 questions generated from the initial search, 372 unique questions associated with 293 websites were extracted and categorized. The most popular question topics were activities/restrictions (20.7%), pain (18.8%), and indications/management (13.2%). The 2 most common websites searched were academic (35.2%) and medical practice (27.4%). Commercial websites were significantly more likely to be associated with questions about cost (57.1% of all cost questions, P = .01), anatomy/function (62.5%, P = .001), and evaluation of surgery (47.6%, P < .001). Academic websites were more likely to be associated with questions about technical details of surgery (58.1%, P < .001). Medical practice and social media websites were more likely associated with activities/restrictions (48.1%, P < .001, and 15.6%, P < .001, respectively). Government websites were more likely associated with timeline of recovery (12.8%, P = .01). On a scale of 0-4, commercial and academic websites had the highest JAMA scores (3.06 and 2.39, respectively). CONCLUSION: Patients seeking information regarding rotator cuff repair primarily use the Google search engine to ask questions regarding postoperative activity and restrictions, followed by pain, indications, and management. Academic websites, which were associated with technical details of surgery, and medical practice websites, which were associated with activities/restrictions, were the 2 most commonly searched resources. These results emphasize the need for orthopedic surgeons to provide detailed and informative instructions to patients undergoing rotator cuff repair, especially in the postoperative setting.

All lockdowns are not equal: Reducing epidemic impact through evolutionary computation.

The impact of different lockdown strategies upon the total number of infections in an epidemic are evaluated for two models of infection: one in which the disease confers permanent immunity, and one in which it does not. The strategies are based upon the proportion of the population infected at a time in order to trigger lockdown, combined with the proportion of interactions removed during lockdown. The population, its interactions, and the relative strengths of those interactions are stored in a weighted contact network, from which edges are removed during lockdown. These edges are selected using an evolutionary algorithm (EA) designed to minimize total infections. Using the EA to select edges significantly reduces total infections in comparison to random selection. In fact, the EA results for the least strict conditions were similar or better to the random results for the most strict conditions, showing that a judicious choice of restrictions during lockdown has the greatest effect on reducing infections. Further, when using the most strict rules a smaller proportion of interactions can be removed to obtain similar or better results in comparison to removing a higher proportion of interactions for less strict rules.

Full-spectrum HIV drug resistance mutation detection by high-resolution complete pol gene sequencing.

BACKGROUND: Drug resistance mutation testing is a key element for HIV clinical management, informing effective treatment regimens. However, resistance screening in current clinical practice is limited in reporting linked cross-class resistance mutations and minority variants, both of which may increase the risk of virological failure. METHODS: To address these limitations, we obtained 358 full-length pol gene sequences from 52 specimens of 20 HIV infected individuals by combining microdroplet amplification, unique molecular identifier (UMI) labeling, and long-read high-throughput sequencing. RESULTS: We conducted a rigorous assessment of the accuracy of our pipeline for precision drug resistance mutation detection, verifying that a sequencing depth of 35 high-throughput reads achieved complete, error-free pol gene sequencing. We detected 26 distinct drug resistance mutations to Protease Inhibitors (PIs), Nucleoside Reverse Transcriptase Inhibitors (NRTIs), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), and Integrase Strand Transfer Inhibitors (INSTIs). We detected linked cross-class drug resistance mutations (PI+NRTI, PI+NNRTI, and NRTI+NNRTI) that confer cross-resistance to multiple drugs in different classes. Fourteen different types of minority mutations were also detected with frequencies ranging from 3.2% to 19%, and the presence of these mutations was verified by Sanger reference sequencing. We detected a putative transmitted drug resistance mutation (TDRM) in one individual that persisted for over seven months from the first sample collected at the acute stage of infection prior to seroconversion. CONCLUSIONS: Our comprehensive drug resistance mutation profiling can advance clinical practice by reporting mutation linkage and minority variants to better guide antiretroviral therapy options.

Thyrotoxicosis-Induced Cardiomyopathy With Systolic Dysfunction.

Thyrotoxicosis-induced dilated cardiomyopathy is a rare but potentially life-threatening complication of thyrotoxicosis, with an incidence of <1%. This condition is characterized by a dilatation of the ventricular chamber and a decrease in cardiac contractility. Untreated, it can lead to irreversible changes in cardiac structure and function, including dilated ventricular chamber, a decrease in ejection fraction (EF), and an increased risk of atrial fibrillation. We present a case of a 39-year-old patient with a diagnosis of thyrotoxicosis-induced acute heart failure. A two-dimensional (2D) echocardiogram disclosed an ejection fraction of 36%, with diffuse mild dilation of the atria and ventricles with trace mitral and tricuspid regurgitation. The anti-thyroid-stimulating hormone (TSH) receptor was positive, and Grave's disease was diagnosed. The patient eventually returned to baseline functional status and could return to basic activities of daily living without limitations. The patient was encouraged to follow up with outpatient cardiology. Early diagnosis of cardiac involvement in patients with thyrotoxicosis is critical. Promptly delivered intensive treatment with the rapid achievement of euthyroid state can potentially reverse cardiac dysfunction and improve patient outcomes.

Stage-of-change Assessment Predicts Short-term Treatment Engagement for Opioid Use Disorder Patients Initiated on Buprenorphine.

INTRODUCTION: The emergency department (ED) is an effective setting for initiating medication for opioid use disorder (MOUD); however, predicting who will remain in treatment remains a central challenge. We hypothesize that baseline stage-of-change (SOC) assessment is associated with short-term treatment retention outcomes. METHODS: This is a longitudinal cohort study of all patients enrolled in an ED MOUD program over 12 months. Eligible and willing patients were treated with buprenorphine at baseline and had addiction medicine specialist follow-up arranged. Treatment retention at 30 and 90 days was determined by review of the Prescription Drug Monitoring Program. We used uni- and multivariate logistic regression to evaluate associations between patient variables and treatment retention at 30 and 90 days. RESULTS: From June 2018-May 2019, 279 patients were enrolled in the ED MOUD program. Of those patients 151 (54.1%) and 120 (43.0%) remained engaged in MOUD treatment at 30 and 90 days, respectively. The odds of treatment adherence at 30 days were significantly higher for those with advanced SOC (preparation/action/maintenance) compared to those presenting with limited SOC (pre-contemplation/contemplation) (60.0% vs 40.8%; odds ratio 2.18; 95% confidence interval 1.15 to 4.1; P <0.05). At 30 days, multivariate logistic regression determined that advanced SOC, age >40, having medical insurance, and being employed were significant predictors of continued treatment adherence. At 90 days, advanced SOC, non-White race, age > 40, and having insurance were all significantly associated with higher likelihood of treatment engagement. CONCLUSION: Greater stage-of-change was significantly associated with MOUD treatment retention at 30 and 90 days post index ED visit.

Randomized Trial of Individualized Texting for Adherence Building (iTAB) Plus Motivational Interviewing for PrEP Adherence in Transgender Individuals: The iM-PrEPT Study.

BACKGROUND: Transgender and nonbinary individuals at risk for HIV may benefit from adherence support for pre-exposure prophylaxis. METHODS: Between June 2017 and September 2020, 255 transgender and nonbinary individuals received daily oral tenofovir disoproxil fumarate/emtricitabine for 48 weeks randomized 1:1 to receive individualized Texting for Adherence Building (iTAB) or iTAB plus motivational interviewing (iTAB + MI) through phone for nonadherence. The primary end point was dried blood spot tenofovir diphosphate concentrations at weeks 12 and 48 (or last on-drug study visit) ≥1246 fmol/punch consistent with ≥7 doses/week (ie, near-perfect adherence). Secondary outcomes included dried blood spot tenofovir diphosphate concentrations ≥719 fmol/punch consistent with ≥4 doses/week (ie, adequate adherence) and self-reported adherence by daily text messages. RESULTS: Adherence for the outcome ≥1246 fmol/punch and ≥719 fmol/punch, respectively, was 49.1% and 57.9% for transgender men, 37.7% and 47.2% for nonbinary individuals, and 31.0% and 44.1% for transgender women. No difference was seen in iTAB + MI compared with iTAB alone by drug levels except where it approached significance in transgender women for the outcome of ≥719 fmol/punch in the iTAB + MI group compared with iTAB only (52% versus 35.7%, P = 0.065). There was a significant difference in self-reported daily dose adherence in the iTAB + MI group compared with iTAB alone (57.9% of days versus 46.4%, P = 0.009). In transgender women, the mean percentage of daily doses taken was 58.5% with iTAB + MI and 37.3% with iTAB alone ( P < 0.001). CONCLUSIONS: In addition to automated approaches to adherence promotion, phone-based MI triggered by repeatedly missing doses may improve pre-exposure prophylaxis adherence among transgender women.

Nutritional Assessment and Interventions in Elective Hip and Knee Arthroplasty: a Detailed Review and Guide to Management.

PURPOSE OF REVIEW: 8.5 to 50% of total joint arthroplasty (TJA) patients are reported to have preoperative malnutrition. The narrative review identifies the relationship between preoperative malnutrition for TJA patients and postoperative outcomes as well as the use of perioperative nutritional intervention to improve postoperative complications. RECENT FINDINGS: Biochemical/laboratory, anthropometric, and clinical measures have been widely used to identify preoperative nutritional deficiency. Specifically, serum albumin is the most prevalent used marker in TJA because it has been proven to be correlated with protein-energy malnutrition due to the surgical stress response. However, there remains a sustained incidence of preoperative malnutrition in total knee arthroplasty (TKA) and total hip arthroplasty (THA) patients due to a lack of agreement among the available nutritional screening tools and utilization of isolated laboratory, anthropometric, and clinical variables. Previous investigations have also suggested preoperative malnutrition to be a prognostic indicator of complications in general, cardiac, vascular, and orthopaedic surgery specialties. Serum albumin, prealbumin, transferrin, and total lymphocyte count (TLC) can be used to identify at-risk patients. It is important to employ these markers in the preoperative setting because malnourished TKA and THA patients have shown to have worse postoperative outcomes including prolonged length, increased reoperation rates, increased infection rates, and increased mortality rates. Although benefits from high-protein and high-anti-inflammatory diets have been exhibited, additional research is needed to confirm the use of perioperative nutritional intervention as an appropriate treatment for preoperative TJA patients.

Low incidence and prevalence of hepatitis C in two cohorts of HIV pre-exposure prophylaxis adherence interventions in men who have sex with men in Southern California.

HIV pre-exposure prophylaxis (PrEP) has been associated with incident hepatitis C virus (HCV) infection in men who have sex with men (MSM) due to decreased condom use. We examined rates of HCV among MSM and transgender women at high-risk of HIV on PrEP in Southern California using data from two trials (NCT01761643 and NCT01781806). Five of 599 participants (0.84%, 95% CI, 0.27-1.93) had HCV antibodies detected at entry. Factors associated with HCV seropositivity included being older (p = .002) and lower education level (p < .001). HCV-positive participants had no reported cases of sexually transmitted infection (rectal, urethral or pharyngeal gonorrhoea and/or chlamydia) at entry while HCV-negative participants had a prevalence of 18% (95% CI, 15%-21%). There were no significant differences in substance use and sexual risk behaviour between HCV-positive and HCV-negative participants 1-3 months prior to entry. Among early PrEP adopters, incident HCV did not occur despite ongoing condomless intercourse. Screening intervals for HCV in MSM on PrEP should be led by a risk behaviour assessment.

Sexually transmitted infections among participants in an HIV PrEP adherence trial.

BACKGROUND: HIV PrEP effectiveness is highly dependent on adherence. High STI incidence has been reported among PrEP users. We assessed the relationship between STI incidence (CT, NG, and syphilis) and PrEP adherence. METHODS: We performed a subanalysis of a controlled, open-label, two-arm, randomized clinical demonstration project of a text-message based adherence intervention. Participants had 48 weeks of follow-up and had STI testing every 12 or 24 weeks. PrEP adherence was measured at week 48 using intracellular tenofovir-diphosphate drug concentrations. We calculated incidence rate ratios for STIs among those adherent as compared with those not adherent to PrEP. RESULTS: Of the 381 assessed for CT, NG and syphilis at one or more follow-up visits, there were 16 cases of syphilis or 5.0 per 100 person years (95% CI: 2.6, 7.5); 63 cases of NG or 26.3 per 100 person years (95% CI: 19.8, 32.8); and 81 cases of CT or 36.3 per 100 person years (95% CI: 28.4, 44.2). We found no association between adequate PrEP adherence and STI incidence (aIRR: 0.97 95% CI: 0.67, 1.40). CONCLUSIONS: We found that the incidence of STIs was not significantly different between those adherent to PrEP and those non-adherent. Further research is needed to assess how PrEP use may impact STIs over time.

Team Approach: Nutritional Assessment and Interventions in Elective Hip and Knee Arthroplasty.

¼: Nutritional assessment is a critical element of routine preoperative assessment and should be approached by an interdisciplinary team that involves the primary care physician, dietitian, and orthopaedist. ¼: Patients should be stratified on the basis of their nutritional risk, which influences downstream optimization and deficiency reversal. ¼: The scientific literature indicates that nutritional supplementation affords protection against adverse outcomes and helps functional recovery, even among patients who are not at nutritional risk. ¼: Published investigations recommend a sufficient preoperative interval (at least 4 weeks) to ensure an adequate nutritional intervention in malnourished patients as opposed to regarding them as nonsurgical candidates.

Method of Calculating Renal Function Estimates Could Inappropriately Exclude Transgender Patients Receiving Gender-Affirming Hormone Therapy from Pre-Exposure Prophylaxis Eligibility.

Purpose: Despite the importance of reliable renal function estimation among the growing transgender population, research describing the variability of existing equations is scarce. Study objectives were to (1) quantify the range of renal function estimates that would be observed if different gender coefficients are used in the estimating equations, (2) compare estimates of renal function (creatinine clearance [CLCR] or estimated glomerular filtration rate [GFR]) between users and nonusers of gender-affirming therapies, and (3) quantify the proportion of subjects who would be deemed ineligible for tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for pre-exposure prophylaxis (PrEP) based on the gender coefficient used. Methods: A retrospective analysis was performed among transgender PrEP users enrolled in a multicenter observational study between June 2017 and October 2021. The primary outcome was estimated kidney function, defined using calculated CLCR or GFR before initiating TDF/FTC for PrEP based on the three most commonly used estimating equations. Results: A total of 258 participants were evaluated. Median differences in renal function ranged from 13 to 25 mL/min based on which gender coefficient and equation was used. Regardless of the method used to compute renal function, there were significant differences between users and nonusers of gender-affirming therapy. There were 17 (6.6%) participants where at least one of the methods would potentially render them ineligible to receive TDF/FTC for PrEP. Conclusions: Renal function estimates vary considerably with different estimating equations in the transgender population and are modified by use of gender-affirming therapy. These variations could result in exclusion from drug therapies such as TDF/FTC for PrEP.

Mechanical design of a new device to assist eating in people with movement disorders.

Many people living with neurological disorders, such as cerebral palsy, stroke, muscular dystrophy or dystonia, experience upper limb impairments (muscle spasticity, loss of selective motor control, muscle weakness or tremors) and are unable to eat independently. This article presents the development of a new device to assist with eating, aimed at stabilizing the movement of people who have movement disorders. The design was guided by insights gathered through focus groups, with occupational therapists and engineers, about the challenges faced by individuals who have movement disorders and difficulty in eating autonomously. The proposed assistive device prototype is designed to be fixed on a table and to support a spoon. The mechanism is designed so that the spoon maintains a position parallel to the ground for the user. Dampers and inertia allow stabilizing the user's motion. A preliminary trial with five individuals living with cerebral palsy is presented to assess the prototype's performance and to guide future iterations of the prototype. Task completion time generally decreased and movement fluidity generally improved when using the assistive device prototype. The prototype showed good potential in stabilizing the spoon for the user and improving movement fluidity.

Adipokines, Weight Gain and Metabolic and Inflammatory Markers After Antiretroviral Therapy Initiation: AIDS Clinical Trials Group (ACTG) A5260s.

BACKGROUND: The adipokines leptin and adiponectin, produced primarily by adipose tissue, have diverse endocrine and immunologic effects, and circulating levels reflect adipocyte lipid content, local inflammation, and tissue composition. We assessed relationships between changes in regional fat depots, leptin and adiponectin levels, and metabolic and inflammatory markers over 96 weeks in the AIDS Clinical Trials Group (ACTG) A5260s metabolic substudy of the A5257 randomized trial of tenofovir disoproxil fumarate/emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir among treatment-naive persons with human immunodeficiency virus (PWH). METHODS: Fat depots were measured using dual-energy absorptiometry and abdominal computed tomographic imaging at treatment initiation and 96 weeks later. Serum leptin and adiponectin, homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hsCRP) were measured at the same timepoints. Multivariable regression models assessed relationships between fat depots, adipokines, HOMA-IR, and hsCRP at week 96. RESULTS: Two hundred thirty-four participants maintained viral suppression through 96 weeks (90% male, 29% black, median age 36 years). Serum leptin increased over 96 weeks (mean change 22%) while adiponectin did not (mean change 1%), which did not differ by study arm. Greater trunk, limb, and abdominal subcutaneous and visceral fat were associated with higher HOMA-IR and hsCRP at 96 weeks, but serum leptin level was a stronger determinant of these endpoints using a mediation model approach. A similar mediating effect was not observed for adiponectin. CONCLUSIONS: Higher circulating leptin is associated with greater HOMA-IR and hsCRP independent of fat depot size, suggesting that greater adipocyte lipid content may contribute to impaired glucose tolerance and systemic inflammation among PWH starting antiretroviral therapy.

COVID-19 and Subsequent Development of Pancytopenia With Concurrent Disseminated Intravascular Coagulation.

Complications resulting from coronavirus disease 2019 (COVID-19) sequelae have been well documented. These include blood conditions such as lymphopenia, thrombocytopenia, and hypercoagulability. Less common problems that may arise are disseminated intravascular coagulation (DIC), immune thrombocytopenic purpura (ITP), and pancytopenia. Furthermore, the majority of COVID-19 patients to develop pancytopenia have been immunosuppressed. We present a case of a previously immunocompetent patient who subsequently developed pancytopenia, DIC, as well as symptoms of ITP one month after being diagnosed with COVID-19.

A Randomized, Placebo-Controlled Trial Assessing the Effect of VISBIOME ES Probiotic in People With HIV on Antiretroviral Therapy.

BACKGROUND: A5350, a phase II, randomized, double-blind study, evaluated the safety and tolerability of the probiotic Visbiome Extra Strength (ES) over 24 weeks and measured effects on inflammation and intestinal barrier function. METHODS: The primary outcome was change in soluble CD14 (sCD14) levels; secondary outcomes included safety and tolerability, markers of inflammation and cellular activation, and microbiome. In a substudy, gut permeability was assessed by paired colonic biopsies measuring the area of lamina propria occupied by CD4+ cells, interleukin (IL)-17+ cells, and myeloperoxidase (MPO). Changes between arms were compared with the 2-sample t test with equal variance or the Wilcoxon rank-sum test. For safety, the highest graded adverse events (AEs) were compared between arms using the Fisher exact test. RESULTS: Overall, 93 participants enrolled: 86% male, median age 51 years, median CD4 count 712 cells/mm3. Visbiome ES was safe and well tolerated. There was no difference in mean change in sCD14 from baseline to week 25/26 between placebo (mean change, 92.3 µg/L; 95% CI, -48.5 to 233 µg/L) and Visbiome ES (mean change, 41.0 µg/L; 95% CI, -94.1 to 176.2 µg/L; P=.60). Similarly, no statistically significant differences between arms in inflammatory marker changes were identified. In substudy participants, no statistical differences between arms for change in cellular marker expression or gut permeability were observed (P>.05 for all). The microbiome demonstrated increased probiotic species and a significant decrease in Gammaproteobacteria (P=.044) in the Visbiome ES arm. CONCLUSIONS: Visbiome ES was safe and altered the microbiome but demonstrated no effect on systemic inflammatory markers, pathology, or gut permeability in antiretroviral therapy-treated people with HIV.

Veillonella Bacteremia in Alcoholic Hepatitis.

Veillonella species are commensal bacteria of the human oral, gut, and vaginal microbiota that are rarely identified as clinically relevant pathogens. Here, we describe a novel case of Veillonella atypica bacteremia in a patient with biopsy-proven alcoholic hepatitis. Veillonella species have been correlated with disease severity and hepatic encephalopathy in liver diseases such as autoimmune hepatitis and cirrhosis. Their abundance has also been recently observed to be increased in alcoholic hepatitis, where postinflammatory infections are known to impact mortality. This case report highlights the possible clinical manifestations that result from significant gut dysbiosis in patients with severe alcoholic hepatitis. Early identification and treatment of Veillonella bacteremia in susceptible populations could be crucial to survival given this organism's predilection for causing life-threatening infections, including meningitis, endocarditis, and osteomyelitis.