Early safety of endoscopic sleeve gastroplasty in super obesity (body mass index > 50).

BACKGROUND: The prevalence of super obesity (body mass index [BMI] > 50) continues to rise. However, the adoption of bariatric surgery in this population remains very low. There are limited studies evaluating the utility of endoscopic sleeve gastroplasty (ESG) in super obesity. OBJECTIVES: The purpose of this study is to evaluate the short-term safety profile of ESG in patients with super obesity using data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database. SETTING: United States. METHODS: We retrospectively analyzed patients who underwent ESG and sleeve gastrectomy (SG) from 2016 to 2021. Patients with BMI >50 who underwent ESG were compared to ESG patients with BMI <50 and also SG patients with BMI >50. Primary outcomes included the incidence of severe adverse events (AEs), hospital readmission, reintervention, and reoperation within 30 days of the primary procedure. Secondary outcomes included procedure time, hospital length of stay, and total body weight loss at 30 days. RESULTS: There were no significant differences in AE, reoperations, hospital readmissions, or reinterventions for patients with super obesity undergoing ESG, compared to patients with BMI below 50. Mean total body weight loss was greater in patients with super obesity. There were no significant differences in AEs for patients with super obesity who underwent ESG versus SG, although ESG patients had more hospital readmissions, reinterventions, and reoperations. CONCLUSIONS: ESG may be performed safely, with comparable safety to SG, in patients with BMI as high as 70. However, further studies are needed to validate the feasibility and long-term efficacy prior to clinical implementation.

Carboxylesterase 1 mediates a distinctive metabolic profile of dendritic cells to attain an inflammatory phenotype.

The metabolic profile of dendritic cells (DCs) shapes their phenotype and functions. Carboxylestrase 1 (CES1) enzyme is highly expressed in mononuclear myeloid cells however its exact role in DCs is elusive. We used a CES1 inhibitor (WWL113) and genetic overexpression to explore the role of CES1 in DCs differentiation in inflammatory models. CES1 expression was analyzed during CD14+ monocytes differentiation to DCs (MoDCs) using quantitative PCR. CES1 Inhibitor (WWL113) was applied during MoDCs differentiation. Surface markers, secreted cytokines, lactic acid production, phagocytic and T cell polarization capacity were analyzed. Transcriptomic and metabolic profile were assessed with RNA-sequencing and mass spectrometry. Cellular respiration was assessed with seahorse respirometry. Transgenic mice were used to assess CES1 overexpression in DCs in inflammatory models. CES1 expression peaks early during MoDCs differentiation. Pharmacological inhibition of CES1 led to higher expression of CD209, CD86 and MHCII. WWL113 treated MoDCs secreted higher quantities of IL6, IL8, TNF and IL10 and demonstrated stronger phagocytic ability and higher capacity to polarize Th17 differentiation in autologous DCs-T cells co-culture model. Transcriptomic profiling revealed enrichment of multiple inflammatory and metabolic pathways. Functional metabolic analysis shows impaired maximal mitochondrial respiration capacity, increased lactate production and decreased intracellular amino acids and TCA intermediates. Transgenic human CES1 overexpression in murine DCs generated less inflammatory phenotype and increased resistance to T cell mediated colitis. In conclusion, CES1 inhibition directs DCs differentiation towards more inflammatory phenotype, that shows stronger phagocytic capacity and supports Th17 skewing. This is associated with disrupted mitochondrial respiration and amino acids depletion.

Comparative accuracy of four guidelines to predict high-grade dysplasia or malignancy in surgically resected pancreatic intraductal papillary mucinous neoplasms: Small nuances between guidelines lead to vastly different results.

Backgrounds/Aims: The guidelines regarding the management of intraductal papillary mucinous neoplasms (IPMNs) all have slightly different surgical indications for high-risk lesions. We aim to retrospectively compare the accuracy of four guidelines in recommending surgery for high-risk IPMNs, and assess the accuracy of elevated CA-19-9 levels and imaging characteristics of IPMNs considered high-risk in predicting malignancy or high-grade dysplasia (HGD). Methods: The final histopathological diagnosis of surgically resected high-risk IPMNs during 2013-2020 were compared to preoperative surgical indications, as enumerated in four guidelines: the 2015 American Gastroenterological Association (AGA), 2017 International Consensus, 2018 European Study Group, and 2018 American College of Gastroenterology (ACG). Surgery was considered "justified" if histopathology of the surgical specimen showed HGD/malignancy, or there was postoperative symptomatic improvement. Results: Surgery was postoperatively justified in 26/65 (40.0%) cases. All IPMNs with HGD/malignancy were detected by the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines. The combined ("high-risk stigmata" and "worrisome features") 2017 International guideline missed 1/19 (5.3%) IPMNs with HGD/malignancy. The 2015 AGA guideline missed the most cases (11/19, 57.9%) of IPMNs with HGD/malignancy. We found the features most-associated with HGD/malignancy were pancreatic ductal dilation, and elevated CA-19-9 levels. Conclusions: Following the 2015 AGA guideline results in the highest rate of missed HGD/malignancy, but the lowest rate of operating on IPMNs without these features; meanwhile, the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines result in more operations for IPMNs without HGD/malignancy, but the lowest rates of missed HGD/malignancy in IPMNs.

A Clinical Perspective on Plasma Cell Leukemia: A Single-Center Experience.

Circulating plasma cells (CPCs) are detected in most multiple myeloma (MM) patients, both at diagnosis and on relapse. A small subset, plasma cell leukemia (PCL), represents a different biology and has a poor prognosis. In this retrospective analysis, we evaluated patients with primary (pPCL, n = 35) or secondary (sPCL, n = 49), with ≥5% CPCs and a smaller subset with lower CPCs of 1-4% (n = 20). The median age was 61 years; 45% were men and 54% were Black. High-risk cytogenetics were found in 87% and extramedullary disease in 47%. For the entire cohort, 75% received a proteasome inhibitor, 70% chemotherapy, 54% an immunomodulatory drug, 24% a daratumumab-based regimen and 26% an autologous stem cell transplant (ASCT). The treatments marginally improved the overall survival (OS) for pPCL vs. sPCL (13 vs. 3.5 months p = 0.002). However, the 5-year survival for the whole cohort was dismal at 11%. High-risk cytogenetics, low platelets, extramedullary disease and high LDH were independently associated with poor outcomes. Further research is urgently needed to expand the treatment options and improve the outcomes in PCL.

Pre-intervention wait time and survival in people with rheumatic heart disease in Uganda.

BACKGROUND: There is an unmet surgical burden among people living with rheumatic heart disease (RHD) in Uganda. Nevertheless, risk factors associated with time to first intervention and preoperative mortality is poorly understood. METHODS: Individuals with RHD who met indications for valve surgery were identified using the Uganda National RHD Registry (Jan. 2010- Aug. 2022). Kaplan-Meier estimates and multivariable Cox proportional hazard models were utilized. RESULTS: 64% of the cohort with clinical RHD (1452 of 2269) met criteria for index operation. Of those, 13.5% obtained surgical intervention while 30.6% died before surgery. The estimated likelihood of first surgery was 50% at 9.3 years of follow up (95% CI 8.1-upper limit not reached). Intervention was more likely in men vs. women (hazard ratio [HR] 1.78; 95% CI 1.21-2.64), those with post-secondary education vs. primary school or less (HR 3.60; 95% CI 1.88-6.89), and those with history of atrial fibrillation (HR 2.78; 95% CI 1.63-4.76). Surgery was less likely for adults (vs. those <18 years; HR 0.49; 95% CI 0.32-0.77) and those with NYHA class III/IV (vs. I/II; HR 0.51; 95% CI 0.32-0.83). The median preoperative survival time among those awaiting surgery was 4.6 years (95% CI, 3.9-5.7). History of infective endocarditis, RV dysfunction, pericardial effusion, atrial fibrillation, and having surgical indications for multiple valves were associated with increased mortality. CONCLUSIONS: Our analysis revealed a prolonged time to first surgical intervention and high pre-intervention mortality for RHD in Uganda, with factors such as age, sex, and education level remaining barriers to obtaining surgery.

Systematic analysis of NDUFAF6 in complex I assembly and mitochondrial disease.

Isolated complex I (CI) deficiencies are a major cause of primary mitochondrial disease. A substantial proportion of CI deficiencies are believed to arise from defects in CI assembly factors (CIAFs) that are not part of the CI holoenzyme. The biochemistry of these CIAFs is poorly defined, making their role in CI assembly unclear, and confounding interpretation of potential disease-causing genetic variants. To address these challenges, we devised a deep mutational scanning approach to systematically assess the function of thousands of NDUFAF6 genetic variants. Guided by these data, biochemical analyses and cross-linking mass spectrometry, we discovered that the CIAF NDUFAF6 facilitates incorporation of NDUFS8 into CI and reveal that NDUFS8 overexpression rectifies NDUFAF6 deficiency. Our data further provide experimental support of pathogenicity for seven novel NDUFAF6 variants associated with human pathology and introduce functional evidence for over 5,000 additional variants. Overall, our work defines the molecular function of NDUFAF6 and provides a clinical resource for aiding diagnosis of NDUFAF6-related diseases.

Efficacy of Cooled-Radiofrequency Ablation of the Genicular Nerve as Treatment for Chronic Knee Pain: A Retrospective Study.

INTRODUCTION: Chronic pain is one of the leading causes of reduced quality of life in the USA, with knee pain commonly reported. Multiple therapeutic modalities are traditionally utilized for pain management; however, some patients may have pain refractory to these techniques. Cooled radiofrequency ablation (c-RFA) of the geniculate nerve is a growing and promising therapy offering a potentially long-term solution to chronic knee pain. METHODS: This study assessed the efficacy, average duration of relief, and potential adverse events using a retrospective chart review of 406 procedures. A two-tailed paired t test was used to assess the statistical significance between pre-RFA vs. post-RFA visual analog scale (VAS) pain scores self-reported by patients. An analysis of variance (ANOVA) test was used to evaluate for statistical differences in pre-RFA pain scores and post-RFA pain scores among the categories of age, sex, body mass index (BMI), and diagnosis group. RESULTS: The mean percent in pain improvement calculated was 65.5% with an average duration of relief of 7.20 months. The average pre-RFA pain score on the VAS was 6.26 out of 10 and 2.59 out of 10 post-RFA. The ANOVA post-RFA pain scores demonstrated statistically significant differences among the categories of age and sex. A total of 54 adverse events were reported, including worsening pain, numbness, paresthesia, and knee swelling. CONCLUSION: The study demonstrated that c-RFA can potentially be utilized as an alternative safe therapy for chronic knee pain, providing pain relief with a relatively prolonged duration. Inherent challenges of retrospective studies remain a part of the limitations of this study.

Methylene blue dose-dependently induces cutaneous inflammation and heat hyperalgesia in a novel rat model.

Methylene blue (MB) has been shown to reduce mortality and morbidity in vasoplegic patients after cardiac surgery. Though MB is considered to be safe, extravasation of MB leading to cutaneous toxicity has been reported. In this study, we sought to characterize MB-induced cutaneous toxicity and investigate the underlying mechanisms. To induce MB-induced cutaneous toxicity, we injected 64 adult male Sprague-Dawley rates with 200 µL saline (vehicle) or 1%, 0.1%, or 0.01% MB in the plantar hind paws. Paw swelling, skin histologic changes, and heat and mechanical hyperalgesia were measured. Injection of 1%, but not 0.1% or 0.01% MB, produced significant paw swelling compared to saline. Injection of 1% MB produced heat hyperalgesia but not mechanical hyperalgesia. Pain behaviors were unchanged following injections of 0.1% or 0.01% MB. Global transcriptomic analysis by RNAseq identified 117 differentially expressed genes (111 upregulated, 6 downregulated). Ingenuity Pathway Analysis showed an increased quantity of leukocytes, increased lipids, and decreased apoptosis of myeloid cells and phagocytes with activation of IL-1ß and Fos as the two major regulatory hubs. qPCR showed a 16-fold increase in IL-6 mRNA. Thus, using a novel rat model of MB-induced cutaneous toxicity, we show that infiltration of 1% MB into cutaneous tissue causes a dose-dependent pro-inflammatory response, highlighting potential roles of IL-6, IL-1ß, and Fos. Thus, anesthesiologists should administer dilute MB intravenously through peripheral venous catheters. Higher concentrations of MB (1%) should be administered through a central venous catheter to minimize the risk of cutaneous toxicity.

Efficacy of live and inactivated recombinant Newcastle disease virus vaccines expressing clade 2.3.4.4b H5 hemagglutinin against H5N1 highly pathogenic avian influenza in SPF chickens, Broilers, and domestic ducks.

A Newcastle disease virus (NDV)-vectored vaccine expressing clade 2.3.4.4b H5 Hemagglutinin was developed and assessed for efficacy against H5N1 highly pathogenic avian influenza (HPAI) in specific pathogen-free (SPF) chickens, broilers, and domestic ducks. In SPF chickens, the live recombinant NDV-vectored vaccine, rK148/22-H5, achieved complete survival against HPAI and NDV challenges and significantly reduced viral shedding. Notably, the live rK148/22-H5 vaccine conferred good clinical protection in broilers despite the presence of maternally derived antibodies. Good clinical protection was observed in domestic ducks, with decreased viral shedding. It demonstrated complete survival and reduced cloacal viral shedding when used as an inactivated vaccine from SPF chickens. The rK148/22-H5 vaccine is potentially a viable and supportive option for biosecurity measure, effectively protecting in chickens against the deadly clade 2.3.4.4b H5 HPAI and NDV infections. Furthermore, it aligns with the strategy of Differentiating Infected from Vaccinated Animals (DIVA).

Vitamin D, Alzheimer's disease and related dementia.

Vitamin D has been proposed as a potential strategy to mitigate age-related cognitive decline and dementia, including Alzheimer's dementia, the predominant type of dementia. Rodent studies have provided insight into the potential mechanisms underlying the role of vitamin D in Alzheimer's disease and dementia. However, inconsistencies with respect to age, sex, and genetic background of the rodent models used poses some limitations regarding scientific rigor and translation. Several human observational studies have evaluated the association of vitamin D status with cognitive decline and dementia, and the results are conflicting. Randomized clinical trials of vitamin D supplementation have included cognitive outcomes. However, most of the available trials have not been designed specifically to test the effect of vitamin D on age-related cognitive decline and dementia, so it remains questionable how much additional vitamin D will improve cognitive performance. Here we evaluate the strengths and limitations of the available evidence regarding the role of vitamin D in AD, cognitive decline, dementia.

The Dermatology Life Quality Index (DLQI) as the Primary Outcome in Randomised Clinical Trials: A systematic review.

BACKGROUND: Primary endpoint measures in clinical trials are typically measures of disease severity, with patient reported outcome measures (PROMs) relegated as secondary endpoints. However validation of some PROMs may be more rigorous than that of disease severity measures, arguing for a primary role for PROMs. OBJECTIVES: This study reports on 24 peer reviewed journal articles that used the Dermatology Life Quality Index (DLQI) as primary outcome, derived from a systematic review of randomised controlled trials (RCTs) utlising DLQI covering all diseases and interventions. MATERIALS AND METHOD: The study protocol was prospectively published on the PROSPERO database, and the study followed PRISMA guidelines. Searches were made with Medline, Cochrane library, EMBASE, Web of Science, SCOPUS, CINAHL(EBSCO) and PsycINFO databases and records combined into an Endnote database. Records were filtered for duplicates and selected by study inclusion/exclusion criteria. Full text articles were sourced and data was extracted by two reviewers into a bespoke REDCap database, with a third reviewer adjudicating differences. The Jadad scoring method was used to determine risk of bias. RESULTS: Of the 3,220 publications retrieved from online searching, 457 articles met eligibility criteria and included 198,587 patients. DLQI scores were primary outcomes in 24 (5.3%) of these studies comprising 15 different diseases and 3,436 patients. Most study interventions (17/24 studies, 68%) were systemic drugs with biologics (liraglutide, alefacept, secukinumab, ustekinumab, adalimumab) accounting for five out of 25 pharmacological interventions (20%). Topical treaments comprised 32% (8 studies) whereas non-pharmacological interventions (8) were 24% of the total interventions (33). Three studies used non-traditional medicines. Eight studies were multicentred (33.3%), with trials conducted in at least 14 different countries, and four (16.7%) were conducted in multiple countries. The Jadad risk of bias scale showed that bias was uncertain or low, as 87.5% of studies had Jadad scores of ≥3. CONCLUSIONS: This study provides evidence for use of the DLQI as primary outcome in clinical trials to inform researchers' and clinicians' decisions for its further use.

Minimization and complete loss of general transcription factor proteins in the intracellular parasite Encephalitozoon cuniculi.

Genome compaction is a common evolutionary feature of parasites. The unicellular, obligate intracellular parasite Encephalitozoon cuniculi has one of smallest known eukaryotic genomes, and is nearly four times smaller than its distant fungi relative, the budding yeast Saccharomyces cerevisiae. Comparison of the proteins encoded by compacted genomes to those encoded by larger genomes can reveal the most highly conserved features of the encoded proteins. In this study, we identified the proteins comprising the RNA polymerases and their corresponding general transcription factors by using several bioinformatic approaches to compare the transcription machinery of E. cuniculi and S. cerevisiae. Surprisingly, our analyses revealed an overall reduction in the size of the proteins comprising transcription machinery of E. cuniculi, which includes the loss of entire regions or functional domains from proteins, as well as the loss of entire proteins and complexes. Unexpectedly, we found that the E. cuniculi ortholog of Rpc37 (a RNA Polymerase III subunit) more closely resembles the H. sapiens ortholog of Rpc37 than the S. cerevisiae ortholog of Rpc37, in both size and structure. Overall, our findings provide new insight into the minimal core eukaryotic transcription machinery and help define the most critical features of Pol components and general transcription factors.

Aggressive interactions among white-tailed deer (Artiodactyla: Cervidae) at 4-poster devices for host-targeted tick control.

White-tailed deer, Odocoileus virginianus Zimmermann (Artiodactyla: Cervidae), are the primary wildlife host for adult stages of blacklegged ticks (Acari: Ixodidae: Ixodes scapularis Say) and an important host for lone star ticks (Acari: Ixodidae: Amblyomma americanum Linnaeus), both of which are vectors of numerous tick-borne pathogens. The 4-poster passive deer treatment device is a topical, host-targeted method to control free-living tick populations and has been proven to successfully reduce tick abundance in several states. Aggressive behavior of white-tailed deer at concentrated feeding stations is hypothesized to interfere with the effective use of 4-poster devices and deer contact with acaricide applicators. We analyzed images collected by camera traps at 4-poster feeding stations deployed at 3 sites in Maryland and found a negative relationship between some aggressive interactions and contact with applicators. Our results emphasize the need for further investigation into whether deer social dynamics can impact 4-poster efficacy for tick control. This study serves as a reminder that intraspecific interactions are important to consider when using host-targeted acaricide approaches.

Repellent activity of essential oils to the Lone Star tick, Amblyomma americanum.

BACKGROUND: The Lone Star tick, Amblyomma americanum is important to human health because of a variety of pathogenic organisms transmitted to humans during feeding events, which underscores the need to identify novel approaches to prevent tick bites. Thus, the goal of this study was to test natural and synthetic molecules for repellent activity against ticks in spatial, contact and human fingertip bioassays. METHODS: The efficacy of essential oils and naturally derived compounds as repellents to Am. americanum nymphs was compared in three different bioassays: contact, spatial and fingertip repellent bioassays. RESULTS: Concentration response curves after contact exposure to 1R-trans-chrysanthemic acid (TCA) indicated a 5.6 µg/cm2 concentration required to repel 50% of ticks (RC50), which was five- and sevenfold more active than DEET and nootkatone, respectively. For contact repellency, the rank order of repellency at 50 µg/cm2 for natural oils was clove > geranium > oregano > cedarwood > thyme > amyris > patchouli > citronella > juniper berry > peppermint > cassia. For spatial bioassays, TCA was approximately twofold more active than DEET and nootkatone at 50 µg/cm2 but was not significantly different at 10 µg/cm2. In spatial assays, thyme and cassia were the most active compounds tested with 100% and 80% ticks repelled within 15 min of exposure respectively and was approximately twofold more effective than DEET at the same concentration. To translate these non-host assays to efficacy when used on the human host, we quantified repellency using a finger-climbing assay. TCA, nootkatone and DEET were equally effective in the fingertip assay, and patchouli oil was the only natural oil that significantly repelled ticks. CONCLUSIONS: The differences in repellent potency based on the assay type suggests that the ability to discover active tick repellents suitable for development may be more complicated than with other arthropod species; furthermore, the field delivery mechanism must be considered early in development to ensure translation to field efficacy. TCA, which is naturally derived, is a promising candidate for a tick repellent that has comparable repellency to commercialized tick repellents.

Outcomes and care quality metrics for people living with rheumatic heart disease and atrial fibrillation in Uganda.

Background: Atrial fibrillation (AF) is a common complication of rheumatic heart disease (RHD) and is challenging to treat in lower-resourced settings in which RHD remains endemic. Objective: We characterized demographics, treatment outcomes, and factors leading to care retention for participants with RHD and AF in Uganda. Methods: We conducted a retrospective analysis of the Uganda national RHD registry between June 2009 and May 2018. Participants with AF or atrial flutter were included. Demographics, survival, and care metrics were compared with participants without AF. Multivariable logistic regression was used to identify factors associated with retention in care among participants with AF. Results: A total of 1530 participants with RHD were analyzed and 293 (19%) had AF. The median age was 24 (interquartile range 14-38) years. Mortality was similar in both groups (adjusted hazard ratio 1.183, P = .77) over a median follow-up of 203 (interquartile range 98-275) days. A total of 79% of AF participants were prescribed anticoagulation, and 43% were aware of their target international normalized ratio. Retention in care was higher in participants with AF (18% vs 12%, P < .01). Factors associated with decreased retention in care include New York Heart Association functional class III/IV (adjusted odds ratio [OR] 0.48, 95% confidence interval [CI] 0.30-0.76) and distance to nearest health center (adjusted OR 0.94, 95% CI 0.90-0.99). Anticoagulation prescription was associated with enhanced care retention (adjusted OR 1.86, 95% CI 1.24-2.79). Conclusion: Participants with RHD and AF in Uganda do not experience higher mortality than those without AF. Anticoagulation prescription rates are high. Although retention in care is poor among RHD participants, those with concurrent AF are more likely to be retained.

Educational Limitations of ChatGPT in Neurosurgery Board Preparation.

Objective This study evaluated the potential of Chat Generative Pre-trained Transformer (ChatGPT) as an educational tool for neurosurgery residents preparing for the American Board of Neurological Surgery (ABNS) primary examination. Methods Non-imaging questions from the Congress of Neurological Surgeons (CNS) Self-Assessment in Neurological Surgery (SANS) online question bank were input into ChatGPT. Accuracy was evaluated and compared to human performance across subcategories. To quantify ChatGPT's educational potential, the concordance and insight of explanations were assessed by multiple neurosurgical faculty. Associations among these metrics as well as question length were evaluated. Results ChatGPT had an accuracy of 50.4% (1,068/2,120), with the highest and lowest accuracies in the pharmacology (81.2%, 13/16) and vascular (32.9%, 91/277) subcategories, respectively. ChatGPT performed worse than humans overall, as well as in the functional, other, peripheral, radiology, spine, trauma, tumor, and vascular subcategories. There were no subjects in which ChatGPT performed better than humans and its accuracy was below that required to pass the exam. The mean concordance was 93.4% (198/212) and the mean insight score was 2.7. Accuracy was negatively associated with question length (R2=0.29, p=0.03) but positively associated with both concordance (p<0.001, q<0.001) and insight (p<0.001, q<0.001). Conclusions The current study provides the largest and most comprehensive assessment of the accuracy and explanatory quality of ChatGPT in answering ABNS primary exam questions. The findings demonstrate shortcomings regarding ChatGPT's ability to pass, let alone teach, the neurosurgical boards.

Left-Handed Palming of the Needle Driver: A Technical Report for Surgical Trainees.

Left-handed surgical trainees are uniquely challenged when learning how to suture using standard needle drivers designed for right-handed individuals and often feel disadvantaged in comparison to their right-handed peers. "Palming," a suturing technique that improves suturing mechanics and efficiency, cannot be achieved in the standard manner using the left hand. This paper proposes a previously undescribed technique for palming using the left hand that provides many of the same benefits as standard palming methods using the right hand, potentially reducing a common source of inequity in surgical training.

Impact of Depression and Anxiety on Patient Reported Outcomes Measures after Lumbar Fusion.

BACKGROUND: Depression and anxiety are common in patients undergoing spinal surgery and might negatively impact outcomes. This study investigates the possible effect of these diagnoses on patient reported outcomes following lumbar fusion. METHODS: Retrospective review of a registry containing prospectively collected data of lumbar fusion procedures at a single institution was performed from May 23, 2012 to June 15, 2022. Patients with a minimum of two year follow-up were included. Demographic information, diagnoses, medications, patient-reported outcomes measures (PROMs), and complications data at preoperative, three months, six months, 1 year, and two years postoperative were collected. Statistical analysis was performed using Student's t-tests, χ2, binomial correlation, odds ratios, logistic regression, and mean clinically important difference. RESULTS: A total of 156 patients were included (60 males, 96 females) with mean age 62.6 ± 11.1 years at surgery. Thirty-nine (25%) had depression and/or anxiety (DA). Baseline Oswestry Disability Index (ODI) and EuroQol Group 5D questionnaire (EQ5D) scores were significantly worse in the DA cohort compared to controls (ODI 51.1 ± 18.3 vs. 42.9 ± 15.8; P = 0.010, EQ5D 0.46 ± 0.21 vs. 0.57 ± 0.21; P = 0.005). Both cohorts experienced similar relative improvement at two years (delta ODI -18.2 ± 27.9 vs. -17.8 ± 22.1; P = 0.924, EQ5D 6.8 ± 33.8 vs. 8.1 ± 32.9; P = 0.830). Absolute outcome scores were worse in the DA cohort at all intervals. DA were not independently predictive of changes in PROMs (delta ODI mean difference 4.49, r2 = 0.36, P = 0.924). CONCLUSIONS: The present study showed similar improvement in PROMs following lumbar fusion for patients with anxiety and depression compared to healthy controls. These data suggest these patients are no less likely to benefit from appropriately planned lumbar fusion.

Coenzyme Q4 is a functional substitute for coenzyme Q10 and can be targeted to the mitochondria.

Coenzyme Q10 (CoQ10) is an important cofactor and antioxidant for numerous cellular processes, and its deficiency has been linked to human disorders including mitochondrial disease, heart failure, Parkinson's disease, and hypertension. Unfortunately, treatment with exogenous CoQ10 is often ineffective, likely due to its extreme hydrophobicity and high molecular weight. Here, we show that less hydrophobic CoQ species with shorter isoprenoid tails can serve as viable substitutes for CoQ10 in human cells. We demonstrate that CoQ4 can perform multiple functions of CoQ10 in CoQ-deficient cells at markedly lower treatment concentrations, motivating further investigation of CoQ4 as a supplement for CoQ10 deficiencies. In addition, we describe the synthesis and evaluation of an initial set of compounds designed to target CoQ4 selectively to mitochondria using triphenylphosphonium. Our results indicate that select versions of these compounds can successfully be delivered to mitochondria in a cell model and be cleaved to produce CoQ4, laying the groundwork for further development.