Evolution of HIV Health Care Workforce Needs in the U.S. Mountain West During the COVID-19 Pandemic: A Mixed Method Study.

ABSTRACT: The COVID-19 pandemic drastically affected health care delivery for vulnerable populations. Many facilities shifted services to telemedicine, and people with HIV or at risk of acquiring HIV experienced interruptions in care. Simultaneously, traditional training approaches to help providers adapt were disrupted. Using a mixed method approach to examine changes over time, we integrated data on trainee needs collected by the Mountain West AIDS Education and Training Center (AETC): a 10-state needs assessment survey in 2020; feedback from a 2020 community of practice; aggregate training data from 2000 to 2022; and a second survey in 2022. HIV care providers' training needs evolved from wanting support on telemedicine and COVID-19 patient care issues, to a later focus on mental health and substance use, social determinants of health, and care coordination. This integrative analysis demonstrates the vital role that AETCs can play in addressing evolving and emergent public health challenges for the HIV workforce.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

The Gene Expression Landscape of Disease Genes.

Fine-mapping and gene-prioritisation techniques applied to the latest Genome-Wide Association Study (GWAS) results have prioritised hundreds of genes as causally associated with disease. Here we leverage these recently compiled lists of high-confidence causal genes to interrogate where in the body disease genes operate. Specifically, we combine GWAS summary statistics, gene prioritisation results and gene expression RNA-seq data from 46 tissues and 204 cell types in relation to 16 major diseases (including 8 cancers). In tissues and cell types with well-established relevance to the disease, the prioritised genes typically have higher absolute and relative (i.e. tissue/cell specific) expression compared to non-prioritised 'control' genes. Examples include brain tissues in psychiatric disorders (P-value < 1×10-7), microglia cells in Alzheimer's Disease (P-value = 9.8×10-3) and colon mucosa in colorectal cancer (P-value < 1×10-3). We also observe significantly higher expression for disease genes in multiple tissues and cell types with no established links to the corresponding disease. While some of these results may be explained by cell types that span multiple tissues, such as macrophages in brain, blood, lung and spleen in relation to Alzheimer's disease (P-values < 1×10-3), the cause for others is unclear and motivates further investigation that may provide novel insights into disease etiology. For example, mammary tissue in Type 2 Diabetes (P-value < 1×10-7); reproductive tissues such as breast, uterus, vagina, and prostate in Coronary Artery Disease (P-value < 1×10-4); and motor neurons in psychiatric disorders (P-value < 3×10-4). In the GTEx dataset, tissue type is the major predictor of gene expression but the contribution of each predictor (tissue, sample, subject, batch) varies widely among disease-associated genes. Finally, we highlight genes with the highest levels of gene expression in relevant tissues to guide functional follow-up studies. Our results could offer novel insights into the tissues and cells involved in disease initiation, inform drug target and delivery strategies, highlighting potential off-target effects, and exemplify the relative performance of different statistical tests for linking disease genes with tissue and cell type gene expression.

Impact of sex on clinical outcome in early Multiple Sclerosis.

BACKGROUND: Previous evidence suggests sex differences in the clinical course of relapsing remitting multiple sclerosis (RRMS), but comprehensive early-stage prospective studies are lacking. We aim to quantify the impact of sex on clinical outcomes in early-stage RRMS. METHODS: Utilizing prospective cohort data, we assessed the impact of biological sex on time-to-relapse, disability progression (Expanded Disability Status Scale [EDSS]), extremity function (Nine-Hole Peg Test, Timed-25-food walk test), cognition (Paced Auditory Serial Addition Test, Symbol Digit Modalities Test), quality-of-life (Hamburg Quality of Life Questionnaire in Multiple Sclerosis, Short-Form-36), fatigue (Fatigue Severity Scale, Fatigue Scale for Motor and Cognitive functions), and depression (Beck Depression Inventory-II) in clinically isolated syndrome (CIS) or RRMS patients. Inclusion was within 12 months of symptom onset. Linear, negative binomial, mixed, and Cox models estimated male vs. female effects at the four-year follow-up including baseline-to-follow-up course. RESULTS: We included 149 patients (65.1 % female). Eighty-five completed four-year follow-up. No sex differences in time-to-relapse emerged (HR = 0.91;95 %CI = 0.53-1.58). Males had no increased risk of EDSS worsening (OR = 0.75;95 %CI = 0.21-2.35) compared to females. Similarly, minor/no sex differences emerged in other outcomes. CONCLUSIONS: Four years after first manifestation, neither disease activity (disability progression and relapse rate) nor patient-reported outcomes showed sex-related disparities in this early-MS-cohort. GOV IDENTIFIER: NCT01371071.

Delayed Facial Nerve Dysfunction Following CyberKnife® Radiosurgery for Vestibular Schwannoma.

OBJECTIVE: The incidence and risk factors for facial nerve dysfunction (FND) following CyberKnife® therapy for vestibular schwannoma (VS) remain poorly understood. This study investigates whether differential radiation doses to vulnerable segments of the facial nerve may be associated with FND outcomes. METHODS: Patients were identified who underwent CyberKnife® radiosurgery for VS at a single institution. Basic demographics, tumor characteristics, and facial nerve function were collected. Total radiation doses to tumor, internal auditory canal (IAC), and labyrinthine segment of facial nerve (LSFN) were evaluated. RESULTS: Six out of 64 patients experienced FND following CyberKnife® treatment for VS (9.38%, 6/64). Patients with FND were compared to those without FND (control). Of the 64 patients, complete radiation records were obtained for 30 patients (6 FND vs. 24 control). There were no significant differences in demographic or tumor characteristics between control and FND cohorts. More severe FND (HB ≥ 4) had significantly larger tumors (3.74 vs. 1.27 cm3, p = 0.037) with directionally decreased time to FND (3.50 vs. 33.5 months, p = 0.106) than patients with HB < 4, respectively. There were directionally, nonsignificant differences between maximum radiation doses to the LSFN (2492.4 vs. 2557.0 cGy, p = 0.121) and IAC (2877.3 vs. 2895.5 cGy, p = 0.824) between the control and FND cohorts, respectively. CONCLUSIONS: FND may represent an underrecognized sequelae of CyberKnife® radiosurgery for VS that can occur many months following treatment. Further studies are needed to elucidate the effect of differential radiation exposure to the facial nerve with FND following treatment. LEVEL OF EVIDENCE: III (Retrospective Cohort Study) Laryngoscope, 2024.

Optimization of pyrazolopyridine 4-carboxamides with potent antimalarial activity for which resistance is associated with the P. falciparum transporter ABCI3.

Emerging resistance to current antimalarials is reducing their effectiveness and therefore there is a need to develop new antimalarial therapies. Toward this goal, high throughput screens against the P. falciparum asexual parasite identified the pyrazolopyridine 4-carboxamide scaffold. Structure-activity relationship analysis of this chemotype defined that the N1-tert-butyl group and aliphatic foliage in the 3- and 6-positions were necessary for activity, while the inclusion of a 7'-aza-benzomorpholine on the 4-carboxamide motif resulted in potent anti-parasitic activity and increased aqueous solubility. A previous report that resistance to the pyrazolopyridine class is associated with the ABCI3 transporter was confirmed, with pyrazolopyridine 4-carboxamides showing an increase in potency against parasites when the ABCI3 transporter was knocked down. The low metabolic stability intrinsic to the pyrazolopyridine scaffold and the slow rate by which the compounds kill asexual parasites resulted in poor performance in a P. berghei asexual blood stage mouse model. Lowering the risk of resistance and mitigating the metabolic stability and cytochrome P450 inhibition will be challenges in the future development of the pyrazolopyrimidine antimalarial class.

The autophagy adaptor TRIAD3A promotes tau fibrillation by nested phase separation.

Multiple neurodegenerative diseases are characterized by aberrant proteinaceous accumulations of tau. Here, we report a RING-in-between-RING-type E3 ligase, TRIAD3A, that functions as an autophagy adaptor for tau. TRIAD3A(RNF216) is an essential gene with mutations causing age-progressive neurodegeneration. Our studies reveal that TRIAD3A E3 ligase catalyses mixed K11/K63 polyubiquitin chains and self-assembles into liquid-liquid phase separated (LLPS) droplets. Tau is ubiquitinated and accumulates within TRIAD3A LLPS droplets and, via LC3 interacting regions, targets tau for autophagic degradation. Unexpectedly, tau sequestered within TRIAD3A droplets rapidly converts to fibrillar aggregates without the transitional liquid phase of tau. In vivo studies show that TRIAD3A decreases the accumulation of phosphorylated tau in a tauopathy mouse model, and a disease-associated mutation of TRIAD3A increases accumulation of phosphorylated tau, exacerbates gliosis and increases pathological tau spreading. In human Alzheimer disease brain, TRIAD3A co-localizes with tau amyloid in multiple histological forms, suggesting a role in tau proteostasis. TRIAD3A is an autophagic adaptor that utilizes E3 ligase and LLPS as a mechanism to capture cargo and appears especially relevant to neurodegenerative diseases.

Radiation Principles, Protection and Reporting for Interventional Pulmonology.

The use and availability of diverse advanced X-ray based imaging and guidance systems in the field of interventional pulmonology is rapidly growing. This popularity links inextricably to an increase in ionizing radiation use. Knowing ionizing radiation is hazardous, knowledge and competent use of X-ray imaging and guidance systems are important. The globally implemented As Low As Reasonably Achievable (ALARA) principle demands careful attention to minimizing radiation exposure while achieving the precise goals of the intervention and imaging therein. To allow careful and targeted weighing of risk against reward while using X-ray based equipment, proper background knowledge of physics as well as imaging system aspects are needed. This white paper summarizes the principles of ionizing radiation which are crucial to enhance awareness and interpretation of dosimetric quantities. Consecutively, a consensus on standards for reporting radiation exposure in interventional pulmonology procedures is indicated to facilitate comparisons between different systems, approaches and results. Last but not least, it provides a list of practical measures, considerations and tips to optimize procedural imaging as well as reduce radiation dose to patients and staff.

Evaluating the categorisation of interventions in individual working practice aimed at preventing work-related musculoskeletal disorders: An international experts consultation.

In a previous scoping review, eight categories of interventions in individual work practice were defined. The aim of the present study is to evaluate the relevance and completeness of these eight categories and to increase the clarity of the nomenclature and definitions of each category. An international expert consultation has been carried out for this purpose. Thirty-eight experts from 13 countries participated. Data collection was conducted using a survey design comprising structured questions. Consensus was reached if 75% of the experts answered 'Strongly agree' or 'Agree' on a 5-point Likert scale. For the topic 'Relevance', there was consensus for six of the eight categories (range 78%-86%), the exceptions were the categories: 'Exercising' (72%) and 'Professional manners' (64%). With regard to the topic 'Nomenclature', consensus was reached for six categories and for the topic 'Definition' this was five categories. The present definitions have been improved based on the expert recommendations. With respect to the topic 'Completeness': although a limited number of suggestions were given, this did not lead to one or more categories being added to the existing eight categories. The final 'Nomenclature' for the categories is: 'Variation', 'Professional behaviour', 'Motoric skills', 'Vocational working techniques', 'Physical workplace', 'Physical training', 'Assistive devices and tools' and 'Task content and task organisation'. This expert consultation has provided a solid basis for endorsing the categorisation of interventions in IWP and is an important step in building a framework to develop and evaluate interventions in IWP.

Biflavonoid Methylchamaejasmin and Khaya grandifoliola Extract Inhibit NLRP3 Inflammasome in THP-1 Cell Model of Neuroinflammation.

Neuroinflammation is a common hallmark of Alzheimer's disease (AD), with NLRP3 inflammasome proven to be activated in microglia of AD patients' brains. In this study, a newly isolated biflavonoid (7,7'-di-O-methylchamaejasmin/M8) and a crude extract of the plant Khaya grandifoliola (KG) were investigated for their inhibitory effect on inflammasome activation. In preliminary experiments, M8 and KG showed no cytotoxicity on human macrophage-like differentiated THP-1 cells and exhibited anti-inflammatory inhibition of nitric oxide produced following lipopolysaccharide stimulation. Furthermore, M8 and KG blocked IL-1ß and IL-18 production by reducing NLRP3 inflammasome components including NFκB, NLRP3, Caspase-1, pro-IL-1ß, and pro-IL-18 at the mRNA and protein levels. Regarding the formation of ASC (apoptosis-associated speck-like protein containing a CARD) specks during inflammasome activation, the size and fluorescent intensity of the existing specks were unchanged across all treatment conditions. However, M8 and KG treatments were shown to prevent further speck formation. In addition, experiments on amyloid ß phagocytosis showed that M8 and KG pretreatments can restore the phagocytic activity of THP-1 cells, which was impaired following inflammasome activation. Altogether, our findings describe for the first time a promising role of biflavonoids and KG extract in preventing inflammasome activation and protecting against neuroinflammation, a key factor in AD development.

Adoptive transfer of personalized neoantigen-reactive TCR-transduced T cells in metastatic colorectal cancer: phase 2 trial interim results.

Adoptive cell transfer (ACT) with neoantigen-reactive T lymphocytes can mediate cancer regression. Here we isolated unique, personalized, neoantigen-reactive T cell receptors (TCRs) from tumor-infiltrating lymphocytes of patients with metastatic gastrointestinal cancers and incorporated the TCR α and ß chains into gamma retroviral vectors. We transduced autologous peripheral blood lymphocytes and adoptively transferred these cells into patients after lymphodepleting chemotherapy. In a phase 2 single-arm study, we treated seven patients with metastatic, mismatch repair-proficient colorectal cancers who had progressive disease following multiple previous therapies. The primary end point of the study was the objective response rate as measured using RECIST 1.1, and the secondary end points were safety and tolerability. There was no prespecified interim analysis defined in this study. Three patients had objective clinical responses by RECIST criteria including regressions of metastases to the liver, lungs and lymph nodes lasting 4 to 7 months. All patients received T cell populations containing ≥50% TCR-transduced cells, and all T cell populations were polyfunctional in that they secreted IFNγ, GM-CSF, IL-2 and granzyme B specifically in response to mutant peptides compared with wild-type counterparts. TCR-transduced cells were detected in the peripheral blood of five patients, including the three responders, at levels ≥10% of CD3+ cells 1 month post-ACT. In one patient who responded to therapy, ~20% of CD3+ peripheral blood lymphocytes expressed transduced TCRs more than 2 years after treatment. This study provides early results suggesting that ACT with T cells genetically modified to express personalized neoantigen-reactive TCRs can be tolerated and can mediate tumor regression in patients with metastatic colorectal cancers. ClinicalTrials.gov registration: NCT03412877 .

Quantitative Digital Subtraction Angiography Measurement of Arterial Velocity at Low Radiation Dose Rates.

PURPOSE: Quantitative digital subtraction angiography (qDSA) has been proposed to quantify blood velocity for monitoring treatment progress during blood flow altering interventions. The method requires high frame rate imaging [~ 30 frame per second (fps)] to capture temporal dynamics. This work investigates performance of qDSA in low radiation dose acquisitions to facilitate clinical translation. MATERIALS AND METHODS: Velocity quantification accuracy was evaluated at five radiation dose rates in vitro and in vivo. Angiographic technique ranged from 30 fps digital subtraction angiography ( 29.3 ± 1.7 mGy / s at the interventional reference point) down to a 30 fps protocol at 23% higher radiation dose per frame than fluoroscopy ( 1.1 ± 0.2 mGy / s ). The in vitro setup consisted of a 3D-printed model of a swine hepatic arterial tree connected to a pulsatile displacement pump. Five different flow rates (3.5-8.8 mL/s) were investigated in vitro. Angiography-based fluid velocity measurements were compared across dose rates using ANOVA and Bland-Altman analysis. The experiment was then repeated in a swine study (n = 4). RESULTS: Radiation dose rate reductions for the lowest dose protocol were 99% and 96% for the phantom and swine study, respectively. No significant difference was found between angiography-based velocity measurements at different dose rates in vitro or in vivo. Bland-Altman analysis found little bias for all lower-dose protocols (range: [- 0.1, 0.1] cm/s), with the widest limits of agreement ([- 3.3, 3.5] cm/s) occurring at the lowest dose protocol. CONCLUSIONS: This study demonstrates the feasibility of quantitative blood velocity measurements from angiographic images acquired at reduced radiation dose rates.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

Excess Folic Acid and Vitamin B12 Deficiency: Clinical Implications?

BACKGROUND: In the 1940s to 1950s, high-dose folic acid supplements (>5 mg/d) were used clinically to reverse the megaloblastic anemia of vitamin B12 deficiency caused by pernicious anemia. However, this treatment strategy masked the underlying B12 deficiency and possibly exacerbated its neuropathological progression. The issue of masking and exacerbating B12 deficiency has recently been rekindled with the institution of folic acid fortification and the wide-spread use of folic acid supplements. OBJECTIVES: The objectives of this review are to describe clinical and epidemiological evidence that excess folic acid exacerbates B12 deficiency, to summarize a hypothesis to explain this phenomenon, and to provide guidance for clinicians. RESULTS: Cognitive function test scores are lower and blood homocysteine and methylmalonic acid concentrations are higher in people with low B12 and elevated folate than in those with low B12 and nonelevated folate. High-dose folic acid supplementation in patients with pernicious anemia or epilepsy cause significant reductions in serum B12. It is hypothesized that high-dose folic acid supplements cause depletion of serum holotranscobalamin and thus exacerbate B12 deficiency. CONCLUSION: The evidence for excess folic acid exacerbating B12 deficiency is primarily correlative or from uncontrolled clinical observations, and the hypothesis to explain the phenomenon has not yet been tested. Nonetheless, the evidence is sufficiently compelling to warrant increased vigilance for identifying B12 deficiency in at risk individuals, including older adults and others with low B12 intake or conditions that are associated with B12 malabsorption, who also ingest excessive folic acid or are prescribed folic acid in high doses.

Plain language titleExcess Folic Acid and Vitamin B12 Deficiency: Clinical Implications?Plain language summaryIt has been known for many decades that high doses of the B vitamin supplement, folic acid, can alleviate the anemia of vitamin B12 deficiency, at least temporarily. However, by alleviating the anemia, such folic acid supplements were said to "mask" the underlying vitamin B12 deficiency, thus allowing neurological damage to continue or possibly be exacerbated. Consequently, treating vitamin B12 deficiency with high dose folic acid was discontinued in the 1970s. The issue of whether folic acid supplements can exacerbate vitamin B12 deficiency reemerged in the 1990s with folic acid fortification of cereals and grains in the United States and Canada (and now in over 80 countries around the world) to prevent spina bifida and other birth defects. This narrative review summarizes the results of studies that have assessed the relationships between folic acid and folate and vitamin B12 status in patients and in populations. A recent hypothesis on how folic acid might exacerbate vitamin B12 deficiency is summarized, and recommendations to clinicians are made for increased vigilance in assessing vitamin B12 status in certain groups at risk of vitamin B12 deficiency, including older adults, people with gastrointestinal issues and other factors that cause vitamin B12 malabsorption, people with unexplained neurological problems, and people who follow vegan or vegetarian diets which are naturally low in vitamin B12.

Biceps tenotomy vs. tenodesis in patients undergoing transtendinous repair of partial thickness rotator cuff tears.

Background: Patients with partial thickness rotator cuff tears (PTRCTs) often present with concurrent pathology of the long head of the biceps tendon (LHBT). To address both conditions simultaneously, long head of the biceps (LHB) tenotomy or tenodesis can be performed at the time of arthroscopic rotator cuff repair (RCR). This study aims to compare postoperative shoulder active range of motion (AROM) and complications following transtendinous RCR with concurrent LHB tenodesis or tenotomy. Methods: A total of 90 patients with PTRCTs met inclusion criteria for this study. Patients who underwent tear-completion-and-repair, revision surgery, or open repair of the LHB tendon were excluded. Patients were stratified into tenotomy, arthroscopic suprapectoral tenodesis, or no biceps operation cohorts and were propensity matched 1:1:1 on age, sex, body mass index, and smoking status. Primary outcome measures included AROM in forward flexion, abduction, external rotation, and internal rotation at 6 weeks, 3 months, and 6 months postoperatively. The development of severe stiffness and rates of rotator cuff retear at final follow-up were recorded as secondary outcomes. Results: When comparing the tenotomy and tenodesis cohorts, tenotomy patients were found to have increased AROM at 3 months in forward flexion (153.2° vs. 130.1°, P = .004), abduction (138.6° vs. 114.2°, P = .019), and external rotation (60.4° vs. 43.8°, P = .014), with differences in forward flexion remaining significant at 6 months (162.4° vs. 149.4°, P = .009). There were no significant differences in interval rates of recovery in any plane between cohorts. Additionally, there were no significant differences in rates of symptomatic retears between groups (P = .458). Rates of severe postoperative stiffness approached but did not achieve statistical significance between tenotomy (4.2%) and tenodesis (29.2%) cohorts (P = .066). Smoking status was a significant predictor of severe stiffness (odds ratio, 13.69; P = .010). Conclusion: Despite significant differences in absolute AROM between cohorts, the decision to perform tenotomy or tenodesis was not found to differentially affect rates of AROM recovery for patients undergoing arthroscopic transtendinous RCR for PTRCT. Notably, however, transient stiffness complications were more commonly observed in smokers, and data trends suggested an increased risk of stiffness for patients undergoing LHB tenodesis. Overall, postoperative stiffness is likely multifactorial and attributable to both patient- and procedure-specific factors, and LHB tenotomy may be more appropriate for patients with risk factors for developing stiffness postoperatively.

Propensity weighting plus adjustment in proportional hazards model is not doubly robust.

Recently, it has become common for applied works to combine commonly used survival analysis modeling methods, such as the multivariable Cox model and propensity score weighting, with the intention of forming a doubly robust estimator of an exposure effect hazard ratio that is unbiased in large samples when either the Cox model or the propensity score model is correctly specified. This combination does not, in general, produce a doubly robust estimator, even after regression standardization, when there is truly a causal effect. We demonstrate via simulation this lack of double robustness for the semiparametric Cox model, the Weibull proportional hazards model, and a simple proportional hazards flexible parametric model, with both the latter models fit via maximum likelihood. We provide a novel proof that the combination of propensity score weighting and a proportional hazards survival model, fit either via full or partial likelihood, is consistent under the null of no causal effect of the exposure on the outcome under particular censoring mechanisms if either the propensity score or the outcome model is correctly specified and contains all confounders. Given our results suggesting that double robustness only exists under the null, we outline 2 simple alternative estimators that are doubly robust for the survival difference at a given time point (in the above sense), provided the censoring mechanism can be correctly modeled, and one doubly robust method of estimation for the full survival curve. We provide R code to use these estimators for estimation and inference in the supporting information.

Quantitative 2D Digital Subtraction Venography for Venous Interventions: Validation in Phantom and In Vivo Porcine Models.

PURPOSE: To determine the feasibility of using a 2D quantitative digital subtraction venography (qDSV) technique that employs a temporally modulated contrast injection to quantify blood velocity in phantom, normal, and stenotic porcine iliac vein models. MATERIALS AND METHODS: Blood velocity was calculated using qDSV following temporally-modulated, pulsed injections of iodinated contrast medium, and compared to Doppler ultrasound (US) measurements (phantom: in-line sensor, in vivo: diagnostic linear probe). Phantom evaluation was performed in a compliant polyethylene tube phantom with simulated venous flow. In vivo evaluation of qDSV was performed in normal (n=7) and stenotic (n=3) iliac vein models. Stenoses were created using endovenous radiofrequency ablation and blood velocities were determined at baseline, post-stenosis, post-venoplasty and post-stent placement. RESULTS: In the phantom model, qDSV-calculated blood velocities (12-50 cm/s) had very strong correlations with US-measured velocities (13-51 cm/s) across a range of baseline blood velocities and injection protocols (slope=[1.01-1.13], R2=[0.96-0.99]). qDSV velocities were similar to US regardless of injection method: custom injector, commercial injector, or hand injection. In the normal in vivo model, qDSV-calculated velocities (5-18 cm/s) had strong correlation (slope=1.22, R2=0.90) with US (3-20 cm/s). In the stenosis model, blood velocity at baseline, post-stenosis, post-venoplasty, and post-stent placement were similar on qDSV and US at all time points. CONCLUSION: Venous blood velocity was accurately quantified in a venousphantom and in vivo porcine models using qDSV. Intra-procedural changes in porcine iliac vein blood velocity were quantified with qDSV after creation of a stenosis and subsequently treating it with venoplasty and stent placement.