Soluble Glycoprotein VI Predicts Abdominal Aortic Aneurysm Growth Rate and is a Novel Therapeutic Target.

A common feature in patients with abdominal aortic aneurysms (AAA) is the formation of a nonocclusive intraluminal thrombus (ILT) in regions of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation impacts the pathogenesis of AAA. Using RNA-sequencing, we identify that the platelet-associated transcripts are significantly enriched in the ILT compared to the adjacent aneurysm wall and healthy control aortas. We found that the platelet specific receptor glycoprotein VI (GPVI) is among the top enriched genes in AAA ILT and is increased on the platelet surface of AAA patients. Examination of a specific indicator of platelet activity, soluble GPVI (sGPVI), in two independent AAA patient cohorts is highly predictive of a AAA diagnosis and associates more strongly with aneurysm growth rate when compared to D-dimer in humans. Finally, intervention with the anti-GPVI antibody (JAQ1) in mice with established aneurysms blunted the progression of AAA in two independent mouse models. In conclusion, we show that levels of sGPVI in humans can predict a diagnosis of AAA and AAA growth rate, which may be critical in the identification of high-risk patients. We also identify GPVI as a novel platelet-specific AAA therapeutic target, with minimal risk of adverse bleeding complications, where none currently exist.

A proposed stratification system to address the heterogeneity of Subdural Hematoma Outcome reporting in the literature.

A major challenge within the academic literature on SDHs has been inconsistent outcomes reported across studies. Historically, patients have been categorized by the blood-product age identified on imaging (i.e., acute, subacute, or chronic). However, this schematic has likely played a central role in producing the heterogeneity encountered in the literature. In this investigation, a total of 494 patients that underwent SDH evacuation at a tertiary medical center between November 2013-December 2021 were retrospectively identified. Mechanism of injury was reviewed by the authors and categorized as either positive or negative for a high-velocity impact (HVI) injury. Any head strike injury leading to the formation of a SDH while traveling at a velocity beyond that of normal locomotion or daily activities was categorized as an HVI. Patients were subsequently stratified by those with an acute SDHs after a high-velocity impact (aSDHHVI), those with an acute SDH without a high-velocity impact injury (aSDHWO), and those with any combination of subacute or chronic blood products (mixed-SDH [mSDH]). Nine percent (n = 44) of patients experienced an aSDHHVI, 23% (n = 113) aSDHWO, and 68% (n = 337) mSDH. Between these groups, highly distinct patient populations were identified using several metrics for comparison. Most notably, aSDHHVI had a significantly worse neurological status at discharge (50% vs. 23% aSDHWO vs. 8% mSDH; p < 0.001) and mortality (25% vs. 8% aSDHWO vs. 4% mSDH; p < 0.001). Controlling for gender, midline shift (mm), and anticoagulation use in the acute SDH population, multivariable logistic regression revealed a 6.85x odds ratio (p < 0.001) for poor outcomes in those with a positive history for a high-velocity impact injury. As such, the distribution of patients that suffer an HVI related acute SDH versus those that do not can significantly affect the outcomes reported. Adoption of this stratification system will help address the heterogeneity of SDH reporting in the literature while still closely aligning with conventional reporting.

Federalism for Bioethics?

In the wake of the Dobbs decision withdrawing federal constitutional protection for reproductive rights, the United States is in the throes of federalist conflicts. Some states are enacting draconian prohibitions of abortion or gender-affirming care, whereas other states are attempting to shield providers and their patients seeking care. This article explores standard arguments supporting federalism, including that it allows for cultural differences to remain along with a structure that provides for the advantages of common security and commerce, that it provides a laboratory for confined experiments, that it is government closer to the people and thus more informed about local needs and preferences, and that it creates layers of government that can constrain one another and thus doubly protect rights. We contend that these arguments do not justify significant differences among states with respect to the recognition of important aspects of well-being; significant injustices among subnational units cannot be justified by federalism. However, as nonideal theorists, we also observe that federalism presents the possibility of some states protecting rights that others do not. Assuming that movement among subnational units is protected, those who are fortunate enough to be able to travel will be able to access rights they cannot access at home. Nonetheless, movement may not be readily available to minors, people without documentation, people with disabilities, people who lack economic resources, or people who have responsibilities that preclude travel. Only rights protection at the federal level will suffice in such cases.

Comparative Evaluation of the Strength of Denture Base Resin repaired with Glass Fiber-reinforced Acrylic Resin: An in vitro Study.

AIM: The present study aimed at evaluating and comparing the transverse strength of heat polymerizing acrylic resin samples repaired using glass fiber-reinforced autopolymerizing acrylic resin with varying gap widths at the fracture site. MATERIALS AND METHODS: Heat polymerizing acrylic resin samples of dimensions 65 * 10 * 2.5 mm each were fabricated. Ten of these were used as control. In the rest of samples, two grooves were fabricated and surface treated with ethyl acetate. The repair gap width was standardized at 4, 3, 2, and 1 mm. Totally, 80 samples were equally divided into these four groups. Glass fiber-reinforced autopolymerizing acrylic resin was used to repair these samples. The repaired samples and the control groups were subjected to three-point bending test, and the findings were analyzed statistically. RESULTS: It was observed that with increase in gap width, their transverse strength decreased. Most of the fractures occurred at the joint interface of parent and repair material. The fracture within the repaired material occurred highest in the group that had 4 mm gap, followed by groups that had 3 and 2 mm gaps. In the group with 1 mm gap, there was no occurrence of fracture within the repaired material. CONCLUSION: To achieve optimum repair strength of a repaired denture, the gap width should not be greater than 1 mm. CLINICAL SIGNIFICANCE: The study will aid in determining the ideal gap width for denture repair to prevent fracture and also the clinical application of glass fiber-reinforced autopolymerizing acrylic resin.

Effects of Oritavancin on Coagulation Tests in the Clinical Laboratory.

Previous studies have shown that some lipoglycopeptide and lipopeptide antimicrobial agents may cause falsely elevated values for some phospholipid-dependent coagulation tests. The effect of oritavancin, a lipoglycopeptide antibiotic, on coagulation test results was explored using pooled human plasma samples spiked with drug and in a clinical study after an infusion of a single 1,200-mg intravenous dose of oritavancin in normal healthy volunteers. Pooled plasma with oritavancin added ex vivo showed concentration-dependent prolongation of prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), and dilute Russell viper venom time (DRVVT) test results. In contrast, oritavancin had no effect on the activated protein C resistance assay, chromogenic anti-factor Xa assay (anti-FXa), thrombin time, and an immunoassay for the laboratory diagnosis of heparin-induced thrombocytopenia. In participants that received a single dose of oritavancin, elevations in PT/INR result, aPTT, DRVVT, activated clotting time, and silica clotting time occurred, with the maximum times to resolution of test interference determined to be 12, 120, 72, 24, and 18 h, respectively. The anti-FXa assay was unaffected, whereas transient elevations in D dimer levels were observed in 30% of participants, with a maximum time to resolution of 72 h. Although oritavancin has no impact on the coagulation system in vivo, a single dose of oritavancin can produce falsely elevated values of some coagulation tests used to monitor hemostasis. The interference of oritavancin on affected tests is transient, and the test results revert to normal ranges within specified times after dosing.

CD32a antibodies induce thrombocytopenia and type II hypersensitivity reactions in FCGR2A mice.

The CD32a immunoglobulin G (IgG) receptor (Fcγ receptor IIa) is a potential therapeutic target for diseases in which IgG immune complexes (ICs) mediate inflammation, such as heparin-induced thrombocytopenia, rheumatoid arthritis, and systemic lupus erythematosus. Monoclonal antibodies (mAbs) are a promising strategy for treating such diseases. However, IV.3, perhaps the best characterized CD32a-blocking mAb, was recently shown to induce anaphylaxis in immunocompromised "3KO" mice. This anaphylactic reaction required a human CD32a transgene because mice lack an equivalent of this gene. The finding that IV.3 induces anaphylaxis in CD32a-transgenic mice was surprising because IV.3 had long been thought to lack the intrinsic capacity to trigger cellular activation via CD32a. Such an anaphylactic reaction would also limit potential therapeutic applications of IV.3. In the present study, we examine the molecular mechanisms by which IV.3 induces anaphylaxis. We now report that IV.3 induces anaphylaxis in immunocompetent CD32a-transgenic "FCGR2A" mice, along with the novel finding that IV.3 and 2 other well-characterized CD32a-blocking mAbs, AT-10 and MDE-8, also induce severe thrombocytopenia in FCGR2A mice. Using recombinant variants of these same mAbs, we show that IgG "Fc" effector function is necessary for the induction of anaphylaxis and thrombocytopenia in FCGR2A mice. Variants of these mAbs lacking the capacity to activate mouse IgG receptors not only failed to induce anaphylaxis or thrombocytopenia, but also very potently protected FCGR2A mice from near lethal doses of IgG ICs. Our findings show that effector-deficient IV.3, AT-10, and MDE-8 are promising candidates for developing therapeutic mAbs to treat CD32a-mediated diseases.

Chordoma arising from benign multifocal notochordal tumors.

This case reports a 25-year-old woman initially diagnosed with adjacent benign notochordal cell tumors (BNCTs) of L3 and L4 based on needle biopsy of L3 and stable imaging over a 3-year period who was ultimately found to have a chordoma arising from a BNCT at L3. It illustrates the potential relationship between benign and malignant notochordal tumors and the difficulty in distinguishing them by clinical, radiological, and even histopathological means.

Aflibercept exhibits VEGF binding stoichiometry distinct from bevacizumab and does not support formation of immune-like complexes.

Anti-vascular endothelial growth factor (VEGF) therapies have improved clinical outcomes for patients with cancers and retinal vascular diseases. Three anti-VEGF agents, pegaptanib, ranibizumab, and aflibercept, are approved for ophthalmic indications, while bevacizumab is approved to treat colorectal, lung, and renal cancers, but is also used off-label to treat ocular vascular diseases. The efficacy of bevacizumab relative to ranibizumab in treating neovascular age-related macular degeneration has been assessed in several trials. However, questions persist regarding its safety, as bevacizumab can form large complexes with dimeric VEGF165, resulting in multimerization of the Fc domain and platelet activation. Here, we compare binding stoichiometry, Fcγ receptor affinity, platelet activation, and binding to epithelial and endothelial cells in vitro for bevacizumab and aflibercept, in the absence or presence of VEGF. In contrast to bevacizumab, aflibercept forms a homogenous 1:1 complex with each VEGF dimer. Unlike multimeric bevacizumab:VEGF complexes, the monomeric aflibercept:VEGF complex does not exhibit increased affinity for low-affinity Fcγ receptors, does not activate platelets, nor does it bind to the surface of epithelial or endothelial cells to a greater degree than unbound aflibercept or control Fc. The latter finding reflects the fact that aflibercept binds VEGF in a unique manner, distinct from antibodies not only blocking the amino acids necessary for VEGFR1/R2 binding but also occluding the heparin-binding site on VEGF165.

Increased Levels of Macrophage Inflammatory Proteins Result in Resistance to R5-Tropic HIV-1 in a Subset of Elite Controllers.

UNLABELLED: Elite controllers (ECs) are a rare group of HIV seropositive individuals who are able to control viral replication without antiretroviral therapy. The mechanisms responsible for this phenotype, however, have not been fully elucidated. In this study, we examined CD4(+) T cell resistance to HIV in a cohort of elite controllers and explored transcriptional signatures associated with cellular resistance. We demonstrate that a subgroup of elite controllers possess CD4(+) T cells that are specifically resistant to R5-tropic HIV while remaining fully susceptible to X4-tropic and vesicular stomatitis virus G (VSV-G)-pseudotyped viruses. Transcriptome analysis revealed 17 genes that were differentially regulated in resistant elite controllers relative to healthy controls. Notably, the genes encoding macrophage inflammatory protein 1α (MIP-1α), CCL3 and CCL3L1, were found to be upregulated. The MIP-1α, MIP-1ß, and RANTES chemokines are natural ligands of CCR5 and are known to interfere with HIV replication. For three elite controllers, we observed increased production of MIP-1α and/or MIP-1ß at the protein level. The supernatant from resistant EC cells contained MIP-1α and MIP-1ß and was sufficient to confer R5-tropic resistance to susceptible CD4(+) T cells. Additionally, this effect was reversed by using inhibitory anti-MIP antibodies. These results suggest that the T cells of these particular elite controllers may be naturally resistant to HIV infection by blocking R5-tropic viral entry. IMPORTANCE: HIV is a pandemic health problem, and the majority of seropositive individuals will eventually progress to AIDS unless antiretroviral therapy (ART) is administered. However, rare patients, termed elite controllers, have a natural ability to control HIV infection in the absence of ART, but the mechanisms by which they achieve this phenotype have not been fully explored. This paper identifies one mechanism that may contribute to this natural resistance: some elite controllers have CD4(+) T cells that produce high levels of MIP chemokines, which block R5-tropic HIV entry. This mechanism could potentially be exploited to achieve a therapeutic effect in other HIV-seropositive individuals.

Recruitment of monocytes/macrophages by tissue factor-mediated coagulation is essential for metastatic cell survival and premetastatic niche establishment in mice.

Tissue factor (TF) expression by tumor cells correlates with metastasis clinically and supports metastasis in experimental settings. However, the precise pathways coupling TF to malignancy remain incompletely defined. Here, we show that clot formation by TF indirectly enhances tumor cell survival after arrest in the lung, during experimental lung metastasis, by recruiting macrophages characterized by CD11b, CD68, F4/80, and CX(3)CR1 (but not CD11c) expression. Genetic or pharmacologic inhibition of coagulation, by either induction of TF pathway inhibitor ex-pression or by treatment with hirudin, respectively, abrogated macrophage recruitment and tumor cell survival. Furthermore, impairment of macrophage function, in either Mac1-deficient mice or in CD11b-diphtheria toxin receptor mice in which CD11b-positive cells were ablated, decreased tumor cell survival without altering clot formation, demonstrating that the recruitment of functional macrophages was essential for tumor cell survival. This effect was independent of NK cells. Moreover, a similar population of macrophages was also recruited to the lung during the formation of a premetastatic niche. Anticoagulation inhibited their accumulation and prevented the enhanced metastasis associated with the formation of the niche. Our study, for the first time, links TF induced coagulation to macrophage recruitment in the metastatic process.

Optimism and challenge for science-based conservation of migratory species in and out of U.S. National Parks.

Public agencies sometimes seek outside guidance when capacity to achieve their mission is limited. Through a cooperative agreement and collaborations with the U.S. National Park Service (NPS), we developed recommendations for a conservation program for migratory species. Although NPS manages ∼ 36 million hectares of land and water in 401 units, there is no centralized program to conserve wild animals reliant on NPS units that also migrate hundreds to thousands of kilometers beyond parks. Migrations are imperiled by habitat destruction, unsustainable harvest, climate change, and other impediments. A successful program to counter these challenges requires public support, national and international outreach, and flourishing migrant populations. We recommended two initial steps. First, in the short term, launch or build on a suite of projects for high-profile migratory species that can serve as proof to demonstrate the centrality of NPS units to conservation at different scales. Second, over the longer term, build new capacity to conserve migratory species. Capacity building will entail increasing the limited knowledge among park staff about how and where species or populations migrate, conditions that enable migration, and identifying species' needs and resolving them both within and beyond parks. Building capacity will also require ensuring that park superintendents and staff at all levels support conservation beyond statutory borders. Until additional diverse stakeholders and a broader American public realize what can be lost and do more to protect it and engage more with land management agencies to implement actions that facilitate conservation, long distance migrations are increasingly likely to become phenomena of the past.

Conservative Management of Acute Sports-Related Concussions: A Narrative Review.

This review explores the application of the conservative management model for pain to sports-related concussions (SRCs), framing concussions as a distinct form of pain syndrome with a pathophysiological foundation in central sensitization. Drawing parallels with proven pain management models, we underscore the significance of a proactive approach to concussion management. Recognizing concussions as a pain syndrome allows for the tailoring of interventions in alignment with conservative principles. This review first covers the epidemiology and controversies surrounding prolonged concussion recovery and persistent post-concussion symptoms (PPCS). Next, the pathophysiology of concussions is presented within the central sensitization framework, emphasizing the need for early intervention to mitigate the neuroplastic changes that lead to heightened pain sensitivity. Five components of the central sensitization process specific to concussion injuries are highlighted as targets for conservative interventions in the acute period: peripheral sensitization, cerebral metabolic dysfunction, neuroinflammation, glymphatic system dysfunction, and pain catastrophizing. These proactive interventions are emphasized as pivotal in accelerating concussion recovery and reducing the risk of prolonged symptoms and PPCS, in line with the philosophy of conservative management.

Are Medical School Curricula Adapting With Their Students? A Survey on How Medical Students Study and How it Relates to USMLE Step 1 Scores.

OBJECTIVES: Over the years, medical schools have evolved their curricula in response to the medical field, faculty, and students. The current study aims to examine how medical students study, what resources they most commonly use, and how it relates to United States Medical Licensing Examination (USMLE) Step 1 scores. METHODS: A cross-sectional survey study of United States medical students was distributed via social media, GroupMe school chats, and school listservs from September 8, 2020, to December 12, 2020. The survey gathered data including, demographic and school information, resources students, time spent using each resource, and USMLE Step 1 scores. RESULTS: The survey was completed by 560 students from 102 different United States medical schools. Study guides as online resources (83.2%) were mostly used, lecture (82.5%), Anki (spaced repetition flashcards, 68.3%), and school-organized sessions (workshops, labs, and small groups) (60.7%). Of the students surveyed, 90% attended schools with a recorded lecture option. Only 54% of these students watched their lectures live. When watched online, the average watching speed was 1.75 ± 0.4× with a mode of 2× speed. In examining different medical school styles, schools with a 1.5-year preclinical curriculum had higher USMLE Step 1 scores (244.5 ± 15.6 vs 236.9 ± 16.2, P-score = .024) compared to schools that did not (1- or 2-year preclinical curriculum). CONCLUSION: Medical students seem to be using third-party resources in addition to their medical school curriculums. Because students are already broadly using these, medical schools could allow their curriculums to reference, require, or complement third-party online resources. Additionally, because of their increased cost, medical schools could consider ways to alleviate the cost on medical students as a means of equitable support. Lastly, Step 1 scores significantly correlated with schools with a 1.5-year preclinical curriculum, although the exact reasoning for this remains uncertain.

The Relationship of Low-Serum Vitamin D and Early Dental Implant Failure.

The study is aimed to assess the effects of serum vitamin D levels and their relationship to early dental implant failures. A total of 174 implants in 109 patients were placed and serum vitamin D levels were noted on the day of implant placement. Implants were followed up until restoration, approximately 3-6 months later, and any implant failure was reported based on 50% or more bone loss or implant mobility. Eight individuals had an implant fail early and their vitamin D levels had a mean of 42.54 ng/mL compared with the successful patients' levels of 31.92 ng/mL. Although not statistically significant, there was no correlation between patients' low serum vitamin D levels and early implant failure.

Focal motor weakness and recovery following chronic subdural hematoma evacuation.

OBJECTIVE: The incidence of chronic subdural hematomas (cSDHs) is expected to climb precipitously in the coming decades because of the aging populous. Neurological weakness is one of the most common presenting neurological symptoms of cSDH. Yet, the recovery rates of motor strength recovery are seldom documented, as neurological outcomes have predominantly focused on broader functional assessment scores or mortality. In this study, the authors performed one of the first detailed analyses on functional motor weakness and recovery in patients who underwent cSDH evacuation. METHODS: Patients who underwent evacuation of a cSDH at a tertiary academic medical center between November 2013 and December 2021 were retrospectively identified using ICD-9 and ICD-10 billing codes. The presence of focal motor weakness was subcategorized by location as upper extremity (UE) or lower extremity (LE). Postoperative improvement, worsening, or resolution of weakness was recorded at the time of discharge. Statistical analysis included univariate and backward stepwise multivariable logistic regression modeling. RESULTS: A total of 311 patients were included in the analysis. Patients were significantly more likely to experience UE weakness than LE weakness (29% vs 18%, p < 0.001). Forty-one percent (43/104) had both UE and LE weakness present. Risk factors for the development of focal motor weakness at the time of presentation were older age (OR 1.02, p = 0.03), increased cSDH size (OR 1.04, p = 0.02), and the presence of a unilateral cSDH (OR 2.32, p = 0.008). The majority of patients (68%, 71/104) experienced motor strength improvement following cSDH evacuation, with 58% (60/104) having complete resolution of weakness. Multivariable logistic regression analysis revealed that longer symptom duration was associated with lower rates of improvement (OR 0.96, p = 0.024). Older age was also associated with reduced resolution of weakness (OR 0.96, p = 0.02). CONCLUSIONS: This study represents one of the first in-depth analyses investigating the rates of motor strength weakness and recovery following cSDH evacuation. Nearly two-thirds of all patients had complete resolution of their weakness by the time of discharge, and more than three-quarters had partial improvement. Risk factors for impaired neurological recovery were longer symptom duration prior to treatment and older age.

Extreme-aged patients (≥ 85 years) experience similar outcomes as younger geriatric patients following chronic subdural hematoma evacuation: a matched cohort study.

Subdural hematoma (SDH) evacuation represents one of the most frequently performed neurosurgical procedures. Several reports cite a rise in both the age and number of patient's requiring treatment, due in part to an aging population and expanded anticoagulation use. However, limited data and conflicting conclusions exist on extreme-aged geriatric patients (≥ 85 years of age) after undergoing surgery. Patients undergoing SDH evacuation at a tertiary academic medical center between November 2013-December 2021 were retrospectively identified. The study group consisted of patients ≥ 85 years (Group 1) diagnosed with a chronic SDH surgically evacuated. A control group was created matching patients by 70-84 years of age, gender, and anticoagulation use (Group 2). Multiple metrics were evaluated between the two including length-of hospital-stay, tracheostomy/PEG placement, reoperation rate, complications, discharge location, neurological outcome at the time of discharge, and survival. A total of 130 patients were included; 65 in Group 1 and 65 in Group 2. Patient demographics, medical comorbidities, SDH characteristics, international normalized ratio, partial thromboplastin time, and use of blood thinning agents were similar between the two groups. Kaplan Meier survival analysis at one-year was 80% for Group 1 and 76% for Group 2. No significant difference was identified using the log-rank test for equality of survivor functions (p = 0.26). All measured outcomes including GCS at time of discharge, length of stay, rate of reoperations, and neurological outcome were statistically similar between the two groups. Backwards stepwise conditional logistic regression revealed no significant association between poor outcomes at the time of discharge and age. Alternatively, anticoagulation use was found to be associated with poor outcomes (OR 3.55, 95% CI 1.08-11.60; p = 0.036). Several outcome metrics and statistical analyses were used to compare patients ≥ 85 years of age to younger geriatric patients (70-84 years) in a matched cohort study. Adjusting for age group, gender, and anticoagulation use, no significant difference was found between the two groups including neurological outcome at discharge, reoperation rate, and survival.

Neighborhood Deprivation is Associated With Hospital Length of Stay, Discharge Disposition, and Readmission Rates for Patients Who Survive Hospitalization With Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) is a leading cause of disability in the United States. Limited research exists on the influence of area-level socioeconomic status and outcomes after TBI. This study investigated the correlation between the Area Deprivation Index (ADI) and (1) 90-day hospital readmission rates, (2) facility discharge, and (3) prolonged (≥5 days) hospital length of stay (LOS). METHODS: Single-center retrospective review of adult (18 years or older) patients who were admitted for TBI during 2018 was performed. Patients were excluded if they were admitted for management of a chronic or subacute hematoma. We extracted relevant clinical and demographic data including sex, comorbidities, age, body mass index, smoking status, TBI mechanism, and national ADI. We categorized national ADI rankings into quartiles for analysis. Univariate, multivariate, and area under the receiver operating characteristic curve (AUROC) analyses were performed to assess the relationship between ADI and 90-day readmission, hospital LOS, and discharge disposition. RESULTS: A total of 523 patients were included in final analysis. Patients from neighborhoods in the fourth ADI quartile were more likely to be Black (P = .007), have a body mass index ≥30 kg/m2 (P = .03), have a Charlson Comorbidity Index ≥5 (P = .004), and have sustained a penetrating TBI (P = .01). After controlling for confounders in multivariate analyses, being from a neighborhood in the fourth ADI quartile was independently predictive of 90-day hospital readmission (odds ratio [OR]: 1.35 [1.12-1.91], P = .011) (model AUROC: 0.82), discharge to a facility (OR: 1.46 [1.09-1.78], P = .03) (model AUROC: 0.79), and prolonged hospital LOS (OR: 1.95 [1.29-2.43], P = .015) (model AUROC: 0.85). CONCLUSION: After adjusting for confounders, including comorbidities, TBI mechanism/severity, and age, higher ADI was independently predictive of longer hospital LOS, increased risk of 90-day readmission, and nonhome discharge. These results may help establish targeted interventions to identify at-risk patients after TBI.

Tolerability, safety, and immunogenicity of the novel oral polio vaccine type 2 in children aged 6 weeks to 59 months in an outbreak response campaign in The Gambia: an observational cohort study.

BACKGROUND: Novel oral polio vaccine type 2 (nOPV2) has been used to interrupt circulating vaccine-derived poliovirus type 2 outbreaks following its WHO emergency use listing. This study reports data on the safety and immunogenicity of nOPV2 over two rounds of a campaign in The Gambia. METHODS: This observational cohort study collected baseline symptoms (vomiting, diarrhoea, irritability, reduced feeding, and reduced activity) and axillary temperature from children aged 6 weeks to 59 months in The Gambia before a series of two rounds of a nOPV2 campaign that took place on Nov 20-26, 2021, and March 19-22, 2022. Serum and stool samples were collected from a subset of the participants. The same symptoms were re-assessed during the week following each dose of nOPV2. Stool samples were collected on days 7 and 28, and serum was collected on day 28 following each dose. Adverse events, including adverse events of special interest, were documented for 28 days after each campaign round. Serum neutralising antibodies were measured by microneutralisation assay, and stool poliovirus excretion was measured by real-time RT-PCR. FINDINGS: Of the 5635 children eligible for the study, 5504 (97·7%) received at least one dose of nOPV2. There was no increase in axillary temperature or in any of the baseline symptoms following either rounds of the campaigns. There were no adverse events of special interest and no other safety signals of concern. Poliovirus type 2 seroconversion rates were 70% (95% CI 62 to 78; 87 of 124 children) following one dose of nOPV2 and 91% (85 to 95; 113 of 124 children) following two doses. Poliovirus excretion on day 7 was lower after the second round (162 of 459 samples; 35·3%, 95% CI 31·1 to 39·8) than after the first round (292 of 658 samples; 44·4%, 40·6 to 48·2) of the campaign (difference -9·1%; 95% CI -14·8 to -3·3), showing the induction of mucosal immunity. INTERPRETATION: In a campaign in west Africa, nOPV2 was well tolerated and safe. High rates of seroconversion and evidence of mucosal immunity support the licensure and WHO prequalification of this vaccine. FUNDING: Bill & Melinda Gates Foundation.

Aspiration and sclerotherapy: a nonsurgical treatment option for hydroceles.

PURPOSE: We demonstrated that hydrocele aspiration and sclerotherapy with doxycycline is an effective and safe nonsurgical treatment option for hydrocele correction. MATERIALS AND METHODS: The medical records of patients who underwent hydrocele aspiration and sclerotherapy were analyzed in a retrospective cohort study for success rates as well as improvement in scrotal size and discomfort after a single hydrocele aspiration and sclerotherapy treatment. Patients who reported decreased scrotal size, improved physical symptoms and satisfaction with the procedure were considered as having success with hydrocele aspiration and sclerotherapy. RESULTS: A total of 29 patients (mean age 52.8 years) presenting with 32 nonseptated hydroceles underwent hydrocele aspiration and sclerotherapy with doxycycline between 2005 and 2012. Of the hydroceles 27 (84%) were successfully treated with a single aspiration and sclerotherapy procedure. Overall mean followup was 20.8 months. Three patients reported moderate pain which resolved in 2 to 3 days. Of those patients in whom hydrocele aspiration and sclerotherapy failed, 1 had hydrocele successfully resolved with a second aspiration and sclerotherapy treatment, 3 did not have success with a second procedure and underwent hydrocelectomy, and 1 wanted immediate surgical correction. CONCLUSIONS: Hydrocele aspiration and sclerotherapy was successful in correcting 84% of simple nonseptated hydroceles with a single treatment. This result is an increase from previously reported success rates involving a single hydrocele aspiration and sclerotherapy procedure with tetracycline (75%). The success rate of a single hydrocele aspiration and sclerotherapy procedure is similar to the reported success rates involving hydrocelectomy while avoiding the hospital expense and many other complications. We conclude that the hydrocele aspiration and sclerotherapy procedure is a reasonable, nonsurgical and underused treatment option for nonseptated simple hydroceles.

A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q.

This phase 3, randomized, double-blind study assessed the efficacy and safety of lenalidomide in 205 red blood cell (RBC) transfusion-dependent patients with International Prognostic Scoring System Low-/Intermediate-1-risk del5q31 myelodysplastic syndromes. Patients received lenalidomide 10 mg/day on days 1-21 (n = 69) or 5 mg/day on days 1-28 (n = 69) of 28-day cycles; or placebo (n = 67). Crossover to lenalidomide or higher dose was allowed after 16 weeks. More patients in the lenalidomide 10- and 5-mg groups achieved RBC-transfusion independence (TI) for ≥ 26 weeks (primary endpoint) versus placebo (56.1% and 42.6% vs 5.9%; both P < .001). Median duration of RBC-TI was not reached (median follow-up, 1.55 years), with 60% to 67% of responses ongoing in patients without progression to acute myeloid leukemia (AML). Cytogenetic response rates were 50.0% (10 mg) versus 25.0% (5 mg; P = .066). For the lenalidomide groups combined, 3-year overall survival and AML risk were 56.5% and 25.1%, respectively. RBC-TI for ≥ 8 weeks was associated with 47% and 42% reductions in the relative risks of death and AML progression or death, respectively (P = .021 and .048). The safety profile was consistent with previous reports. Lenalidomide is beneficial and has an acceptable safety profile in transfusion-dependent patients with Low-/Intermediate-1-risk del5q myelodysplastic syndrome. This trial was registered at www.clinicaltrials.gov as #NCT00179621.