Management of Meniscus Pathology with Concomitant Anterior Cruciate Ligament Injury.

PURPOSE OF REVIEW: The purpose of this review is to summarize current clinical knowledge on the prevalence and types of meniscus pathology seen with concomitant anterior cruciate ligament (ACL) injury, as well as surgical techniques, clinical outcomes, and rehabilitation following operative management of these pathologies. RECENT FINDINGS: Meniscus pathology with concomitant ACL injury is relatively common, with reports of meniscus pathology identified in 21-64% of operative ACL injuries. These concomitant injuries have been associated with increased age and body mass index. Lateral meniscus pathology is more common in acute ACL injury, while medial meniscus pathology is more typical in chronic ACL deficiency. Meniscus tear patterns associated with concomitant ACL injury include meniscus root tears, lateral meniscus oblique radial tears of the posterior horn (14%), and ramp lesions of the medial meniscus (8-24%). These meniscal pathologies with concomitant ACL injury are associated with increased rotational laxity and meniscal extrusion. There is a paucity of comparative studies to determine the optimal meniscus repair technique, as well as rehabilitation protocol, depending on specific tear pattern, location, and ACL reconstruction technique. There has been a substantial increase in recent publications demonstrating the importance of meniscus repair at the time of ACL repair or reconstruction to restore knee biomechanics and reduce the risk of progressive osteoarthritic degeneration. Through these studies, there has been a growing understanding of the meniscus tear patterns commonly identified or nearly missed during ACL reconstruction. Surgical management of meniscal pathology with concomitant ACL injury implements the same principles as utilized in the setting of isolated meniscus repair alone: anatomic reduction, biologic preparation and augmentation, and circumferential compression. Advances in repair techniques have demonstrated promising clinical outcomes, and the ability to restore and preserve the meniscus in pathologies previously deemed irreparable. Further research to determine the optimal surgical technique for specific tear patterns, as well as rehabilitation protocols for meniscus pathology with concomitant ACL injury, is warranted.

Role of dietary fibres in cardiometabolic diseases.

PURPOSE OF REVIEW: This review highlights recent developments in understanding the role of dietary fibre and specific fibre types on risk and management of cardiometabolic disease with a focus on the causal pathways leading to cardiometabolic diseases, namely weight management, glycaemic control, and lipid levels, as well as the latest findings for cardiovascular disease outcomes such as coronary heart disease, stroke, and mortality. Evidence for mechanisms through gut microbiota are also briefly reviewed. RECENT FINDINGS: Dietary fibre intake is associated with improved weight management, the extent of which may depend on the subtype of dietary fibre. Overall dietary fibre intake reduces blood glucose and HbA1c, however soluble fibres may be particularly effective in reducing HbA1c, fasting blood glucose and blood lipids. Individual meta-analyses and umbrella reviews of observational studies on dietary fibre, as well as major fibre types, observed inverse associations with incident coronary heart disease, stroke, and mortality due to cardiovascular disease. As different types of fibres exerted different health benefits, fibre diversity (i.e. combinations of fibres) should be further investigated. SUMMARY: Dietary fibres improve both short-term and long-term cardiometabolic disease risk factors and outcomes, and thus should be on every menu.

Hypoglobus, Exophthalmos, and Interpupillary Distance: Measuring Globe Dystopia in Thyroid Eye Disease.

PURPOSE: Thyroid eye disease (TED) is characterized by a variety of disfiguring periocular changes. Vertical globe changes affecting the relative position of the eyelids are not well understood in patients with TED. This study seeks to determine the effect of orbital decompression on vertical globe displacement in patients with TED, without TED, and with intraconal tumor (ICT). METHODS: For this cross-sectional study, a clinical database was used to identify patients with TED. Comparison groups were drawn from separate anonymized databases. Vertical position and interpupillary distance (IPD) were measured from photographs and exophthalmos was measured via Hertel's exophthalmometer. Primary outcomes were vertical globe position at baseline and postoperatively in patients with TED and ICT. Secondary outcomes included the relationship between vertical globe position, exophthalmos, and IPD. RESULTS: Among 269 participants meeting the inclusion criteria, mean vertical globe position was significantly lower in patients with TED following lateral decompression surgery compared to controls, after accounting for race, age, and sex. While patients with ICT had a significant difference in preoperative and postoperative IPD, patients with TED did not. Medial or inferior decompression did not significantly change globe position and lateral decompression did not cause lateral canthal dystopia in patients with TED. No association between postoperative changes in exophthalmometry, IPD, and globe position was found in patients with TED. CONCLUSIONS: Patients with TED experience hypoglobus that does not improve following decompression surgery. There was no correlation between change in vertical globe position and exophthalmos or IPD among patients with TED. Surgeons should discuss the possibility of hypoglobus as a persistent finding for patients with TED undergoing decompression surgery.

Implementing automated Medicaid eligibility renewals was not associated with higher levels of program participation.

Increasing participation in Medicaid among eligible individuals is critical for improving access to care among low-income populations. The administrative burdens of enrolling and renewing eligibility are a major barrier to participation. To reduce these burdens, the Affordable Care Act required states to adopt automated renewal processes that use available databases to verify ongoing eligibility. By 2019, nearly all states adopted automated renewals, but little is known about how this policy affected Medicaid participation rates. Using the 2015-2019 American Community Survey, we found that participation rates among nondisabled, nonelderly adults and children varied widely by state, with an average of 70.8% and 90.7%, respectively. Among Medicaid-eligible adults, participation was lower among younger adults, males, unmarried individuals, childless households, and those living in non-expansion states compared with their counterparts. State adoption of automated renewals varied over time, but participation rates were not associated with adoption. This finding could reflect limitations to current automated renewal processes or barriers to participation outside of the eligibility renewal process, which will be important to address as additional states expand Medicaid and pandemic-era protections on enrollment expire.

Poglut2/3 double knockout in mice results in neonatal lethality with reduced levels of fibrillin in lung tissues.

Fibrillin microfibrils play a critical role in the formation of elastic fibers, tissue/organ development, and cardiopulmonary function. These microfibrils not only provide structural support and flexibility to tissues, but they also regulate growth factor signaling through a plethora of microfibril-binding proteins in the extracellular space. Mutations in fibrillins are associated with human diseases affecting cardiovascular, pulmonary, skeletal, and ocular systems. Fibrillins consist of up to 47 epidermal growth factor (EGF)-like repeats, of which more than half are modified by protein O-glucosyltransferase 2 (POGLUT2) and/or POGLUT3. Loss of these modifications reduces secretion of N-terminal fibrillin constructs overexpressed in vitro. Here, we investigated the role of POGLUT2 and POGLUT3 in vivo using a Poglut2/3 double knockout (DKO) mouse model. Blocking O-glucosylation caused neonatal death with skeletal, pulmonary, and eye defects reminiscent of fibrillin/elastin mutations. Proteomic analyses of DKO dermal fibroblast medium and extracellular matrix provided evidence that fibrillins were more sensitive to loss of O-glucose compared to other POGLUT2/3 substrates. This conclusion was supported by immunofluorescent analyses of late gestation DKO lungs where FBN levels were reduced and microfibrils appeared fragmented in the pulmonary arteries and veins, bronchioles, and developing saccules. Defects in fibrillin microfibrils likely contributed to impaired elastic fiber formation and histological changes observed in DKO lung blood vessels, bronchioles, and saccules. Collectively, these results highlight the importance of POGLUT2/3-mediated O-glucosylation in vivo and open the possibility that O-glucose modifications on fibrillin influence microfibril assembly and or protein interactions in the ECM environment.

Racial and Ethnic Disparities in Medicaid Disenrollment After the End of the COVID-19 Public Health Emergency.

This survey study reports the proportions of and reasons for Medicaid coverage loss among racially and ethnically minoritized individuals.

Binding requirements for latent transforming growth factor Beta2 activation.

Although the mechanism for activation of latent TGFß1 and TGFß3 is understood to involve the binding of the TGFß propeptide (LAP) to both an integrin and an insoluble substrate, the activation of latent TGFß2 has been unclear because the TGFß2 LAP does not have the classical integrin binding sequence found in the other two TGFß isoform LAPs. To assess the potential requirement for covalent linkage with a matrix or cell surface protein for the activation of latent TGFß2, we generated mice in which the TGFß2 Cys residue predicted to be involved in binding was mutated to Ser (Tgfb2C24S). We reasoned that, if covalent interaction with a second molecule is required for latent TGFß2 activation, mutant mice should display a Tgfb2 null (Tgfb2-/-)-like phenotype. Tgfb2C24S mice closely phenocopy Tgfb2-/- mice with death in utero between E18 and P1 and with congenital heart and kidney defects similar to those described for Tgfb2-/- mice. The mutant latent TGFß2 is secreted at levels similar to WT, yet TGFß signaling monitored as nuclear pSmad2 is suppressed. We conclude that, like latent TGFß1, latent TGFß2 activation requires binding to an immobilized matrix or plasma membrane molecule.

Preclinical development of EXT608, an investigational parathyroid hormone derivative with extended half-life for the treatment of hypoparathyroidism.

Hypoparathyroidism, a deficiency of parathyroid hormone (PTH), results in hypocalcemia, hyperphosphatemia, and hypercalciuria. The disease is poorly controlled by calcium and vitamin D supplements or native PTH(1-84) replacement therapy. A version of PTH is being developed using D-VITylation technology, whereby vitamin D is conjugated to a therapeutic peptide, which confers a long plasma half-life by virtue of binding to the abundant vitamin D binding protein (DBP). D-VITylation of PTH caused no reduction in activity at the PTHR1 receptor, and resulted in a plasma elimination half-life of 7-15 h in rats and 24-32 h in cynomolgus monkeys. Analysis of steady-state pharmacokinetics as a function of dose showed flat profiles with smaller peak:trough ratios at low doses, indicative of slower subcutaneous absorption. In thyroparathyroidectomized (TPTx) rats, PTH(1-34)-vitamin D conjugates restored serum calcium and phosphate levels into the normal range over the 24 h dosing period, and increased bone turnover markers and reduced bone mineral density. Urinary calcium was initially elevated, but normalized by the end of treatment on day 27. In healthy monkeys, a single dose of PTH(1-34)-vitamin D conjugates elevated serum calcium levels above the normal range for a period of 24-48 h while simultaneously reducing urinary calcium. Therefore, the lead compound, EXT608, is a promising candidate as a therapeutic that can truly mimic the endogenous activity of PTH and warrants further study in patients with hypoparathyroidism.

Inferior Ophthalmic Vein-Dominant Dural Cavernous Fistula Embolization via Combined Orbitotomy and Direct Puncture of Inferior Ophthalmic Vein: A Case Report and Literature Review.

Dural carotid-cavernous fistulas (DCF) typically drain into the superior ophthalmic vein. Predominant involvement of the inferior ophthalmic vein (IOV) is rare, with only 4 documented cases in the literature. Here, the authors describe a case of a 51-year-old man who presented with acute left-sided proptosis, dysmotility, and vision loss and was found to have an IOV-dominant type D dural carotid-cavernous fistulas. The fistula could not be embolized by transfemoral endovascular access or orbitotomy alone and was ultimately managed with combined orbitotomy and direct IOV puncture. All previous reports of IOV-dominant dural carotid-cavernous fistulas in the literature were similarly inaccessible via the transfemoral approach. This case highlights the challenges of IOV cutdown and proposes an alternative management strategy. When IOV cutdown is precluded by the fragile, collapsed, or deep nature of the vessel, conversion to percutaneous IOV puncture may offer a safe and effective approach and mitigate the risks of direct puncture alone.

The Association between Type of Insurance Plan, Out-of-Pocket Cost, and Adherence to Antihypertensive Medications in Medicare Supplement Insurance Enrollees.

BACKGROUND: Medicare supplement insurance, or Medigap, covers 21% of Medicare beneficiaries. Despite offsetting some out-of-pocket (OOP) expenses, remaining OOP costs may pose a barrier to medication adherence. This study aims to evaluate how OOP costs and insurance plan types influence medication adherence among beneficiaries covered by Medicare Supplement plans. METHODS: We conducted a retrospective analysis of the MerativeTM MarketScan® Medicare Supplement Database (2017-2019) in Medigap enrollees (≥ 65 years) with hypertension. Proportion of days covered (PDC) was a continuous measure of medication adherence and was also dichotomized (PDC ≥ 0.8) to quantify adequate adherence. Beta-binomial and logistic regression models were used to estimate associations between these outcomes and insurance plan type and log-transformed OOP costs, adjusting for patient characteristics. RESULTS: Among 27,407 patients with hypertension, the average PDC was 0.68 ± 0.31; 47.5% achieved adequate adherence. A mean $1 higher in 30-day OOP costs was associated with a 0.06 (95% Confidence intervals [CI]: -0.09 - -0.03) lower probability of adequate adherence, or a 5% (95% C.I.: 4% - 7%) decrease in PDC. Compared to comprehensive plan enrollees, the odds of adequate adherence were lower among those with point-of-service plans (O.R.: 0.69, 95%C.I.: 0.62 - 0.77), but higher among those with preferred provider organization (PPO) plans (O.R.: 1.08, 95%C.I.: 1.01 - 1.15). Moreover, the association between OOP costs and PDC was significantly greater for PPO enrollees. CONCLUSIONS: While Medicare supplement insurance alleviates some OOP costs, different insurance plans and remaining OOP costs influence medication adherence. Reducing patient cost-sharing may improve medication adherence.

Work-Related Musculoskeletal Injury Rates, Risk Factors, and Ergonomics in Different Endoscopic Specialties: A Review.

Endoscopy-related musculoskeletal injuries (ERIs) are frequent among gastrointestinal, pulmonary, nasal, and urologic endoscopists, impacting the healthcare system. The present review aims to compare the ERI rates, risk factors, and ergonomic recommendations in the different endoscopic fields. A review was conducted using PubMed and Cochrane Library for articles based on surveys and published until 10 January 2024. Demographic, work, and ERI data from 46 publications were included, covering 10,539 responders. The ERI incidence ranged between 14% and 97%, highlighting the need of intervention independent of the specialties. The neck, back, and shoulder were the most frequent ERI locations, while gender, age, years of experience, and procedure volume the most common risk factors. Ergonomic recommendations suggest concentrating on endoscope design changes, especially in gastrointestinal endoscopy, to increase the comfort, adaptability of the equipment in the operating room, and workflow/institutional policy changes. The inclusion of an ergonomic timeout guarantees the correct equipment positioning, the neutralisation of the endoscopist's posture, and an indirect break between procedures. Ergonomic training to increase awareness and best practice should be promoted, also using new technologies. Future research should concentrate on intervention and comparative studies to evaluate to which extent prevention measures and newly designed equipment could reduce ERI incidence.

Correspondence on "Organo-Mediator Enabled Electrochemical Deuteration of Styrenes".

The recently reported electrochemical, organo-mediator enabled deuteration of styrenes, a reaction referred to as "electrochemical deuterium atom transfer", differs mechanistically from reported direct electrochemical hydrogenations/deuterations only by a mediated, homogeneous SET to the substrates. By comparing direct vs. mediated processes in general and for styrene reduction, we display that Qiu's work does not change the concept of this chemistry. Experiments with mediators and the direct reduction of examples from the reported scope show that even electron-rich substrates can be reduced when our direct protocol, published six months before Qiu's work, is applied.

Teamwork and Nurse Care Coordination in Home Healthcare.

Home healthcare agencies provide interdisciplinary care to millions of individuals annually. Care is typically led by registered nurses who often determine additional disciplines need to be included in the plan of care. We found that, although persons living with dementia represent about 30% of the home healthcare population, data from our home healthcare system showed that over a 1-year period with 36,443 home care episodes, only 29.6% had one or more social worker visits. Recognizing Alzheimer's disease-related dementia as a terminal condition and shifting toward a palliative care approach can be a challenge in home healthcare where care is focused on restorative care or rehabilitative goals with a primary focus on improvement in condition. The goal of this article is to present insights into nurse-led care coordination and teamwork and provide implications for practice.

Managing Modern Antiretroviral Therapy in the Intensive Care Unit: Overcoming Challenges for Critically Ill People With Human Immunodeficiency Virus.

People with human immunodeficiency virus (HIV) have a 50% excess risk for intensive care unit (ICU) admission, often for non-HIV-related conditions. Despite this, clear guidance for managing antiretroviral therapy (ART) in this setting is lacking. Selecting appropriate ART in the ICU is complex due to drug interactions, absorption issues, and dosing adjustments. Continuing ART in the ICU can be challenging due to organ dysfunction, drug interactions, and formulary limitations. However, with careful consideration, continuation is often feasible through dose adjustments or alternative administration methods. Temporary discontinuation of ART may be beneficial depending on the clinical scenario. Clinicians should actively seek resources and support to mitigate adverse events and drug interactions in critically ill people with HIV. Navigating challenges in the ICU can optimize ART and improve care and outcomes for critically ill people with HIV. This review aims to identify strategies for addressing the challenges associated with the use of modern ART in the ICU.

Mononuclear phagocyte morphologic response to chemoattractants is dependent on geranylgeranyl pyrophosphate.

Statins are used to treat hypercholesterolemia and function by inhibiting the production of the rate-limiting metabolite mevalonate. As such, statin treatment not only inhibits de novo synthesis of cholesterol but also isoprenoids that are involved in prenylation, the post-translational lipid modification of proteins. The immunomodulatory effects of statins are broad and often conflicting. Previous work demonstrated that statins increased survival and inhibited myeloid cell trafficking in a murine model of sepsis, but the exact mechanisms underlying this phenomenon were unclear. Herein we investigated the role of prenylation in chemoattractant responses. We found that simvastatin treatment abolished chemoattractant responses induced by stimulation by C5a and FMLP. The inhibitory effect of simvastatin treatment was unaffected by the addition of either farnesyl pyrophosphate (FPP) or squalene, but was reversed by restoring geranylgeranyl pyrophosphate (GGPP). Treatment with prenyltransferase inhibitors showed that the chemoattractant response to both chemoattractants was dependent on geranylgeranylation. Proteomic analysis of C15AlkOPP-prenylated proteins identified several geranylgeranylated proteins involved in chemoattractant responses, including RHOA, RAC1, CDC42, and GNG2. Chemoattractant responses in THP-1 human macrophages were also geranylgeranylation dependent. These studies provide data that help clarify paradoxical findings on the immunomodulatory effects of statins. Furthermore, they establish the role of geranylgeranylation in mediating the morphologic response to chemoattractant C5a.

Sex-based differences in treatment approaches and outcomes among patients with mpox: Limitations of real-world data.

BACKGROUND: Limited data on females with mpox restricts understanding of potential sex-based disparities in treatment and outcomes. This study aims to investigate these differences using administrative claims and clinical data repositories. METHODS: We retrospectively analyzed adults diagnosed with mpox using TriNetX, stratifying cohorts by sex. The primary outcome included urgent care, emergency room, and hospitalization visits, with secondary outcomes including clinical findings, vaccination, and treatment. RESULTS: Among 2011 cases, 90% were male. Males were older, more likely to identify as Hispanic or Latino, and had higher HIV prevalence and sexually transmitted infection rates. Hospitalization rates were low for both groups, with similar healthcare utilization. However, males received fewer opioid analgesics, glucocorticoids, and antiemetics versus females. Vaccination and tecovirimat use were minimal in both groups. CONCLUSION: Addressing sex disparities in mpox treatment and outcomes is crucial, but existing data sources like administrative claims and clinical data repositories pose limitations.

Genome-Wide Association Study of Treatment-Resistant Depression: Shared Biology With Metabolic Traits.

OBJECTIVE: Treatment-resistant depression (TRD) occurs in roughly one-third of all individuals with major depressive disorder (MDD). Although research has suggested a significant common variant genetic component of liability to TRD, with heritability estimated at 8% when compared with non-treatment-resistant MDD, no replicated genetic loci have been identified, and the genetic architecture of TRD remains unclear. A key barrier to this work has been the paucity of adequately powered cohorts for investigation, largely because of the challenge in prospectively investigating this phenotype. The objective of this study was to perform a well-powered genetic study of TRD. METHODS: Using receipt of electroconvulsive therapy (ECT) as a surrogate for TRD, the authors applied standard machine learning methods to electronic health record data to derive predicted probabilities of receiving ECT. These probabilities were then applied as a quantitative trait in a genome-wide association study of 154,433 genotyped patients across four large biobanks. RESULTS: Heritability estimates ranged from 2% to 4.2%, and significant genetic overlap was observed with cognition, attention deficit hyperactivity disorder, schizophrenia, alcohol and smoking traits, and body mass index. Two genome-wide significant loci were identified, both previously implicated in metabolic traits, suggesting shared biology and potential pharmacological implications. CONCLUSIONS: This work provides support for the utility of estimation of disease probability for genomic investigation and provides insights into the genetic architecture and biology of TRD.

Counting the Cost of Daptomycin Versus Vancomycin in Hospitalized Patients: A Cost Minimization Analysis.

Daptomycin use for gram-positive infections has increased. This cost minimization analysis aimed to determine cost and/or time savings of daptomycin over vancomycin. The estimated hospital cost savings was US$166.41 per patient, and pharmacist time saved of almost 20 minutes per patient. Daptomycin has the potential to save both time and money.

The association of gender-affirming hormone therapy duration and body mass index on bone mineral density in gender diverse adults.

Introduction: Feminizing and masculinizing gender-affirming hormone therapy (fGAHT, mGAHT) results in bone mineral density (BMD) maintenance or improvement over time in transgender and gender diverse (TGD) adults. Mostly European TGD studies have explored GAHT's impact on BMD, but the association of BMI and BMD in TGD adults deserves further study. Objective: To determine whether GAHT duration or BMI are associated with BMD and Z-scores among TGD young adults. Methods: Cross-sectional study of nonsmoking TGD adults aged 18-40 years without prior gonadectomy or gonadotropin-releasing hormone agonist (GnRHa) therapy taking GAHT for > 1 year. BMD and Z-scores were collected from dual-energy x-ray absorptiometry. Associations between femoral neck, total hip, and lumbar spine BMDs and Z-scores and the predictors, GAHT duration and BMI, were estimated using linear regression. Results: Among 15 fGAHT and 15 mGAHT, mean BMIs were 27.6 +/- standard deviation (SD) 6.4 kg/m2 and 25.3 +/- 5.9 kg/m2, respectively. Both groups had mean BMDs and Z-scores within expected male and female reference ranges at all three sites. Higher BMI among mGAHT was associated with higher femoral neck and total hip BMDs (femoral neck: ß = 0.019 +/- standard error [SE] 0.007 g/cm2, total hip: ß = 0.017 +/- 0.006 g/cm2; both p < 0.05) and Z-scores using male and female references. GAHT duration was not associated with BMDs or Z-scores for either group. Conclusions: Z-scores in young, nonsmoking TGD adults taking GAHT for > 1 year, without prior gonadectomy or GnRHa, and with mean BMIs in the overweight range, were reassuringly within the expected ranges for age based on male and female references. Higher BMI, but not longer GAHT duration, was associated with higher femoral neck and total hip BMDs and Z-scores among mGAHT. Larger, prospective studies are needed to understand how body composition changes, normal or low BMIs, and gonadectomy affect bone density in TGD adults.