Citations

Background: Complementary and alternative medicine (CAM) interventions are growing in popularity as possible treatments for long COVID symptoms. However, comprehensive analysis of current evidence in this setting is still lacking. Objective: This study aims to review existing published studies on the use of CAM interventions for patients experiencing long COVID through a systematic review. Design: Systematic review of randomized controlled trials (RCTs). Methods: A comprehensive electronic literature search was performed in multiple databases and clinical trial registries from September 2019 to January 2023. RCTs evaluating efficacy and safety of CAM for long COVID were included. Methodological quality of each included trial was appraised with the Cochrane ‘risk of bias’ tool. A qualitative analysis was conducted due to heterogeneity of included studies. Results: A total of 14 RCTs with 1195 participants were included in this review. Study findings demonstrated that CAM interventions could benefit patients with long COVID, especially those suffering from neuropsychiatric disorders, olfactory dysfunction, cognitive impairment, fatigue, breathlessness, and mild-to-moderate lung fibrosis. The main interventions reported were self-administered transcutaneous auricular vagus nerve stimulation, neuro-meditation, dietary supplements, olfactory training, aromatherapy, inspiratory muscle training, concurrent training, and an online breathing and well-being program. Conclusion: CAM interventions may be effective, safe, and acceptable to patients with symptoms of long COVID. However, the findings from this systematic review should be interpreted with caution due to various methodological limitations. More rigorous trials focused on CAM for long COVID are warranted in the future.

AbstractBackgroundAs heart transplant guidelines evolve, the clinical indication for 73% of durable left ventricular assist device (LVAD) implants is now destination therapy. Although completely magnetically levitated LVAD devices have demonstrated improved durability relative to previous models, LVAD replacement procedures are still required for a variety of indications. Thus, the population of patients with a replaced LVAD is growing. There is a paucity of data regarding the outcomes and risk factors for those patients receiving first‐time LVAD replacements.MethodsThe study cohort consisted of all consecutive patients between 2006 and 2020 that received a first‐time LVAD replacement at a single institution. Preoperative clinical and laboratory variables were collected retrospectively. The primary endpoint was death or need for an additional LVAD replacement. Data were subjected to Kaplan–Meier, univariate, and multivariate Cox hazard ratio analyses.ResultsIn total, 152 patients were included in the study, of which 101 experienced the primary endpoint. On multivariate analysis, patients receiving HeartMate 3 (HM3) LVADs as the replacement device showed superior outcomes (HR 0.15, 95% CI 0.065–0.35, p < 0.0001). Independent risk factors for death or need for additional replacement included preoperative extracorporeal membrane oxygenation (ECMO) (HR 4.44, 95% CI 1.87–14.45, and p = 0.00042), increased number of sternotomies (HR 5.20, 95% CI 1.87–14.45, and p = 0.0016), and preoperative mechanical ventilation (HR 1.98, 95% CI 1.01–3.86, and p = 0.045).ConclusionsReplacement with HM3 showed superior outcomes compared to all other pump types when controlling for both initial pump type and other independent predictors of death or LVAD replacement. Preoperative ECMO, mechanical ventilation, and multiple sternotomies also increased the odds for death or the need for subsequent replacement.

Background: Hip arthroscopy continues to advance and become increasingly commonly performed. With the evolution of techniques and instrumentation, labral repair rather than debridement has emerged as the treatment of choice for labral pathology. There remains a lack of data on long-term outcomes after labral repair. Purpose: To (1) evaluate long-term patient-reported outcomes of primary hip arthroscopy with labral repair for femoroacetabular impingement, (2) report achievement rates of Patient Acceptable Symptom State (PASS) and minimal clinically important difference (MCID), and (3) investigate rates of reoperation and progression to total hip arthroplasty (THA). Study Design: Case series; Level of evidence, 4. Methods: Prospectively collected data were reviewed for patients who underwent primary hip arthroscopy with labral repair between 2010 and 2013. Patients’ medical records were reviewed for demographic characteristics, intraoperative findings, reoperation, and progression to THA. Patients were assessed pre- and postoperatively using the following scales: visual analog scale (VAS) for pain; Tegner activity scale; modified Harris Hip Score (mHHS); 12-item International Hip Outcome Tool (iHOT-12); Hip Outcome Score–Activities of Daily Living (HOS-ADL); HOS–Sport-Specific Subscale (HOS-SSS); and Non-Arthritic Hip Score. Patients were also surveyed for satisfaction, subjective improvement, and level of function. Results: A total of 32 patients (n = 24 women; n = 8 men) with a mean age of 27.7 years (range, 13.6-51 years) were evaluated for a mean of 9.4 years (range, 9-12.1 years). Patients achieved significant mean improvements in VAS pain at rest of 2 points, VAS pain with use of 1.9, mHHS of 19.9 points, iHOT-12 of 33.5 points, HOS-ADL of 17.4 points, and HOS-SSS of 29.5 points ( P≤ .015 for all). Eleven patients (34.4%) underwent reoperation and 4 (12.5%) progressed to THA during the study period. At the final follow-up, the MCID achievement rate was ≥68%, the PASS achievement rates ranged from 39% to 65%, and the mean patient satisfaction was 8.1 on a 1 to 10 scale, with 10 denoting most satisfied. Conclusion: Patients demonstrated significant postoperative improvements in pain, mHHS, iHOT-12, HOS-ADL, and HOS-SSS scores at 9 years postoperatively. The all-cause reoperation rate was 34.4%, and 12.5% of patients progressed to THA.

Background: Due to lacking evidence on surveillance for gastric cancer (GC), this study aimed to determine the optimal postsurgical surveillance strategy for pathological stage (pStage) II/III GC patients and compare its cost-effectiveness with traditional surveillance strategies. Methods: Prospectively collected data from stage II/III GC patients (n=1661) who underwent upfront surgery at a large-volume tertiary cancer center in China (FJMUUH cohort) between January 2010 and October 2015. For external validation, two independent cohorts were included, which were composed of 380 stage II/III GC patients at an tertiary cancer center in U.S.A (Mayo cohort) between July 1991 and July 2012 and 270 stage II/III GC patients at another tertiary cancer center in China (QUAH cohort) between May 2010 and October 2014. Random forest models were used to predict dynamic recurrence hazards and to construct individual surveillance strategies for stage II/III GC. Cost-effectiveness was assessed by the Markov model. Results: The median follow-up period of the FJMUUH, the Mayo, and QUAH cohorts were 55, 158, and 70 months, respectively. In the FJMUUH cohort, the 5-year recurrence risk was higher in pStage III compared with pStage II GC patients (P<0.001). Our novel individual surveillance strategy achieved optimal cost-effectiveness for pStage II GC patients (ICER =$490/QALY). The most intensive NCCN surveillance guideline was more cost-effective (ICER =$983/QALY) for pStage III GC patients. The external validations confirmed our results. Conclusion: For patients with pStage II GC, individualized risk-based surveillance outperformed the JGCTG and NCCN surveillance guidelines. However, the NCCN surveillance guideline may be more suitable for patients with pStage III GC. Even though our results are limited by the retrospective study design, the authors believe that our findings should be considered when recommending postoperative surveillance for stage II/III GC with upfront surgery in the absence of a randomized clinical trial.

Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency (VLCADD) is a fatty acid oxidation disorder characterized by the decreased ability of the enzyme very-long-chain acyl-CoA dehydrogenase to break down fatty acids with 14 to 20-long carbon chains. The resulting clinical manifestations are variable in severity and include hypoketotic hypoglycemia, rhabdomyolysis, and cardiomyopathy. Treatment can consist of limiting the dietary intake of long-chain fatty acids, the prevention of fasting, and the supplementation of medium-chain fats. This study, conducted in the context of a 5-year long-term follow-up on VLCADD, evaluates how the diagnosis of this fatty acid disorder impacts the family, specifically as it relates to the medical diet and barriers to care. Caregivers (n = 10) of individuals with VLCADD responded to a survey about how VLCADD potentially impacts their family. The review included the clinical outcomes of the patients (n = 11), covering instances of rhabdomyolysis, cardiomyopathy, and hospitalizations related to VLCADD. Families affected by VLCADD experience barriers to care, including difficulties with finances, ability to work, and access to nutrition.

Abstract Cerebral malaria is the deadliest complication that can arise from Plasmodium infection. CD8 T-cell engagement of brain vasculature is a putative mechanism of neuropathology in cerebral malaria. To define contributions of brain endothelial cell major histocompatibility complex (MHC) class I antigen-presentation to CD8 T cells in establishing cerebral malaria pathology, we developed novel H-2Kb LoxP and H-2Db LoxP mice crossed with Cdh5-Cre mice to achieve targeted deletion of discrete class I molecules, specifically from brain endothelium. This strategy allowed us to avoid off-target effects on iron homeostasis and class I-like molecules, which are known to perturb Plasmodium infection. This is the first endothelial-specific ablation of individual class-I molecules enabling us to interrogate these molecular interactions. In these studies, we interrogated human and mouse transcriptomics data to compare antigen presentation capacity during cerebral malaria. Using the Plasmodium berghei ANKA model of experimental cerebral malaria (ECM), we observed that H-2Kb and H-2Db class I molecules regulate distinct patterns of disease onset, CD8 T-cell infiltration, targeted cell death and regional blood–brain barrier disruption. Strikingly, ablation of either molecule from brain endothelial cells resulted in reduced CD8 T-cell activation, attenuated T-cell interaction with brain vasculature, lessened targeted cell death, preserved blood–brain barrier integrity and prevention of ECM and the death of the animal. We were able to show that these events were brain-specific through the use of parabiosis and created the novel technique of dual small animal MRI to simultaneously scan conjoined parabionts during infection. These data demonstrate that interactions of CD8 T cells with discrete MHC class I molecules on brain endothelium differentially regulate development of ECM neuropathology. Therefore, targeting MHC class I interactions therapeutically may hold potential for treatment of cases of severe malaria.

Abstract Autism spectrum disorder (ASD) is a major neurodevelopmental disorder affecting 1 in 36 children in the United States. While neurons have been the focus to understand ASD, an altered neuro-immune response in the brain may be closely associated with ASD, and a neuro-immune interaction could play a role in the disease progression. As the resident immune cells of the brain, microglia regulate brain development and homeostasis via core functions including phagocytosis of synapses. While ASD has been traditionally considered a polygenic disorder, recent large-scale human genetic studies have identified SCN2A deficiency as a leading monogenic cause of ASD and intellectual disability. We generated a Scn2a-deficient mouse model, which displays major behavioral and neuronal phenotypes. However, the role of microglia in this disease model is unknown. Here, we reported that Scn2a-deficient mice have impaired learning and memory, accompanied by reduced synaptic transmission and lower spine density in neurons of the hippocampus. Microglia in Scn2a-deficient mice are partially activated, exerting excessive phagocytic pruning of post-synapses related to the complement C3 cascades during selective developmental stages. The ablation of microglia using PLX3397 partially restores synaptic transmission and spine density. To extend our findings from rodents to human cells, we established a microglial-incorporated human cerebral organoid model carrying an SCN2A protein-truncating mutation identified in children with ASD. We found that human microglia display increased elimination of post-synapse in cerebral organoids carrying the SCN2A mutation. Our study establishes a key role of microglia in multi-species autism-associated models of SCN2A deficiency from mouse to human cells.

ABSTRACT Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including Mycobacteroides abscessus (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, with secondary outcomes including clinical improvement and mortality at 6- and 12 mo, persistence or reemergence of infection, adverse effects, and reasons for OMC utilization. Seventy-five patients were included in this analysis. Most patients were female (48/75, 64.0%) or Caucasian (58/75, 77.3%), with a median (IQR) age of 59 yr (49–67). Most had NTM pulmonary disease (33/75, 44.0%), skin and soft tissue disease (19/75, 25.3%), or osteomyelitis (10/75, 13.3%), and Mycobacterium abscessus (60/75, 80%) was the most commonly isolated NTM pathogen. The median (IQR) treatment duration was 6 mo ( 4 – 14 ), and the most commonly co-administered antibiotic was azithromycin (33/70, 47.1%). Three-month clinical success was observed in 80.0% (60/75) of patients, and AEs attributable to OMC occurred in 32.0% (24/75) of patients, leading to drug discontinuation in 9.3% (7/75).