Fixed-Duration Pirtobrutinib plus Venetoclax with or without Rituximab in Relapsed/Refractory CLL: Phase 1b BRUIN Trial.

Pirtobrutinib is a highly selective, non-covalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). Patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) were treated with fixed-duration pirtobrutinib plus venetoclax (PV) or pirtobrutinib plus venetoclax and rituximab (PVR) in this phase 1b trial (NCT03740529). Prior covalent BTKi therapy was allowed, but not prior venetoclax. Patients were assigned to receive PV (n=15) or PVR (n=10) for 25 cycles. Median age was 66 years (range, 39-78). Median prior lines of therapy was 2 (range, 1-4), and 17 (68%) patients had received prior covalent BTKi. At the data-cutoff date (May 5, 2023), median time on study was 27.0 months for PV and 23.3 months for PVR. Overall response rates were 93.3% (95% CI:68.1-99.8%) for PV and 100% (95% CI:69.2-100.0%) for PVR, with 10 complete responses (PV:7; PVR:3). After 12 cycles of treatment, 85.7% (95% CI:57.2-98.2%) of PV and 90.0% (95% CI:55.5-99.7%) of PVR patients achieved undetectable minimal residual disease assessed in peripheral blood by clonoSEQ® assay at a sensitivity of <1x10-4. Progression-free survival at 18 months was 92.9% (95% CI: 59.1-99.0) for PV patients and 80.0% (95% CI: 40.9-94.6) for PVR patients. No DLTs were observed in either treatment combination during the 5-week assessment period. The most common grade ≥3 adverse events for all patients included neutropenia (52%) and anemia (16%). Adverse events led to dose reduction in 3 patients and discontinuation in 2. In conclusion, fixed-duration PV or PVR was well tolerated and had promising efficacy in patients with R/R CLL, including patients previously treated with a covalent BTKi.

Consensus recommendations on the management of toxicity associated with CD3×CD20 bispecific antibody therapy.

ABSTRACT: Bispecific antibodies (BsAb) that target CD3 and CD20 represent a new milestone in the treatment of patients with B-cell non-Hodgkin lymphoma. These drugs have demonstrated remarkable single-agent activity in patients with heavily pretreated disease, and 3 drugs have so far received regulatory approvals in various countries. However, BsAbs can potentially lead to severe toxicity associated with T-cell activation, particularly cytokine release syndrome (CRS). The anticipated widespread use of these off-the-shelf products poses challenges for implementation and highlights the need for guidance in anticipating, mitigating, and managing adverse events. In clinical trials, guidance for the evaluation and treatment of CRS and neurotoxicity associated with BsAb therapy has been modeled after algorithms originally created for chimeric antigen receptor (CAR) T-cell therapies and other immune effector therapies, yet notable differences in timing, quality, and severity exist between the toxicities of BsAbs and CAR T-cell therapies. We therefore convened an international panel of academic and community practice physicians, advanced practitioners, registered nurses, and pharmacists with experience using CD3×CD20 BsAbs in clinical trial and off-trial settings to provide comprehensive, consensus-based recommendations specific to the assessment and management of CD3×CD20 BsAb-related toxicities.

Interaction between cold ischemia time and Kidney Donor Profile Index on postrenal transplant outcomes.

We analyzed whether there is an interaction between the Kidney Donor Profile Index (KDPI) and cold ischemia time (CIT) in recipients of deceased donor kidney transplant (KTs). Adults who underwent KTs in the United States between 2014 and 2020 were included and divided into 3 KDPI groups (≤20%, 21%-85%, >85%) and 4 CIT strata (<12, 12-17.9, 18-23.9, ≥24 hours). Multivariate analyses were used to test the interaction between KDPI and CIT for the following outcomes: primary graft nonfunction (PGNF), delayed graft function (DGF), estimated glomerular filtration rate (eGFR) at 6 and 12 months, patient survival, graft survival, and death-censored graft survival (DCGS). A total of 69,490 recipients were analyzed: 18,241 (26.3%) received a graft with KDPI ≤20%, 46,953 (67.6%) with KDPI 21%-85%, and 4,296 (6.2%) with KDPI >85%. Increasing KDPI and CIT were associated with worse post-KT outcomes. Contrary to our hypothesis, howerver, the interaction between KDPI and CIT was statistically significant only for PGNF and DGF and eGFR at 6 months. Paradoxically, the negative coefficient of the interaction suggested that increasing duration of CIT was more detrimental for low and intermediate-KDPI organs relative to high-KDPI grafts. Conversely, for mortality, graft survival, and DCGS, we found that the interaction between CIT and KDPI was not statistically significant. We conclude that, high KDPI and prolonged CIT are independent risk factors for inferior outcomes after KT. Their interaction, however, is statistically significant only for the short-term outcomes and more pronounced on low and intermediate-KDPI grafts than high-KDPI kidneys.

Population pharmacokinetics and humanized dosage regimens matching the peak, area, trough, and range of amikacin plasma concentrations in immune-competent murine bloodstream and lung infection models.

Amikacin is an FDA-approved aminoglycoside antibiotic that is commonly used. However, validated dosage regimens that achieve clinically relevant exposure profiles in mice are lacking. We aimed to design and validate humanized dosage regimens for amikacin in immune-competent murine bloodstream and lung infection models of Acinetobacter baumannii. Plasma and lung epithelial lining fluid (ELF) concentrations after single subcutaneous doses of 1.37, 13.7, and 137 mg/kg of body weight were simultaneously modeled via population pharmacokinetics. Then, humanized amikacin dosage regimens in mice were designed and prospectively validated to match the peak, area, trough, and range of plasma concentration profiles in critically ill patients (clinical dose: 25-30 mg/kg of body weight). The pharmacokinetics of amikacin were linear, with a clearance of 9.93 mL/h in both infection models after a single dose. However, the volume of distribution differed between models, resulting in an elimination half-life of 48 min for the bloodstream and 36 min for the lung model. The drug exposure in ELF was 72.7% compared to that in plasma. After multiple q6h dosing, clearance decreased by ~80% from the first (7.35 mL/h) to the last two dosing intervals (~1.50 mL/h) in the bloodstream model. Likewise, clearance decreased by 41% from 7.44 to 4.39 mL/h in the lung model. The humanized dosage regimens were 117 mg/kg of body weight/day in mice [administered in four fractions 6 h apart (q6h): 61.9%, 18.6%, 11.3%, and 8.21% of total dose] for the bloodstream and 96.7 mg/kg of body weight/day (given q6h as 65.1%, 16.9%, 10.5%, and 7.41%) for the lung model. These validated humanized dosage regimens and population pharmacokinetic models support translational studies with clinically relevant amikacin exposure profiles.

Beyond Brick and Mortar: The Rise of Street Medicine.

In 2023, approximately 650,000 people experienced homelessness (PEH) nightly in the United States, the highest number recorded in the country's history. This alarming statistic has made homelessness a key issue in the 2024 elections, especially with the White House's goal to reduce homelessness by 25% by 2025. Despite efforts and investments, homelessness remains a persistent public health challenge. The recent inclusion of street medicine services in Center for Medicare and Medicaid Services (CMS) billing codes represents a significant step forward. Street medicine, defined by CMS as healthcare provided in non-permanent locations to unsheltered individuals, now qualifies for Medicare reimbursement. This policy change, alongside state-level initiatives, aims to improve healthcare access for the unhoused, particularly older adults. However, challenges remain in establishing adequate fee schedules and integrating care management. Despite these obstacles, the integration of healthcare and housing services is crucial for addressing homelessness effectively, promoting stability, and improving health outcomes for PEH. This manuscript explores the history, practical guidance, and potential impacts of these developments on homelessness and public health.

Knowledge, skills, and confidence gaps impacting treatment decision making in relapsed/refractory chronic lymphocytic leukemia and mantle cell lymphoma: a quantitative survey study in France, Germany, and the United States.

BACKGROUND: With recent advancements in the treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), healthcare specialists may face challenges making treatment and management decisions based on latest evidence for the optimal care of patients with these conditions. This study aimed to identify specific knowledge, skills, and confidence gaps impacting the treatment of CLL and MCL, to inform future educational activities. METHODS: Hematologists and hemato-oncologists (HCPs, n = 224) from France (academic settings), Germany, and the United States (academic and community settings) responded to a 15-minute quantitative needs assessment survey that measured perceived knowledge, skills, and confidence levels regarding different aspects of treatment and management of CLL and MCL patients, as well as clinical case questions. Descriptive statistics (cross tabulations) and Chi-square tests were conducted. RESULTS: Four areas of educational need were identified: (1) sub-optimal knowledge of treatment guidelines; (2) sub-optimal knowledge of molecular testing to inform CLL/MCL treatment decisions; (3) sub-optimal skills when making treatment decisions according to patient profile (co-morbidities, molecular testing results); and (4) challenges balancing the risk of toxicities with benefits of treatment. Over one-third of the respondents reported skill gaps when selecting suitable treatment options and prescribing therapies and reported a lack in confidence to initiate and manage treatment. Larger gaps in knowledge of guidelines and skills in patient assessment were identified in MCL, compared to CLL. CONCLUSIONS: This study suggests the need for continuing medical education specifically to improve knowledge of treatment guidelines, and to assist clinicians in developing skills and confidence when faced with clinical decision-making scenarios of patients with specific comorbidities and/or molecular test results, for example, through case-based learning activities.

Safety of Extended Pirtobrutinib Exposure in Relapsed and/or Refractory B-Cell Malignancies.

INTRODUCTION: Pirtobrutinib, a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor, has demonstrated promising efficacy in B-cell malignancies and is associated with low rates of discontinuation and dose reduction. Pirtobrutinib is administered until disease progression or toxicity, necessitating an understanding of the safety profile in patients with extended treatment. METHODS: Here we report the safety of pirtobrutinib in patients with relapsed/refractory B-cell malignancies with extended (≥12 months) drug exposure from the BRUIN trial. Assessments included median time-to-first-occurrence of adverse events (AEs), dose reductions, and discontinuations due to treatment-emergent AEs (TEAEs) and select AEs of interest (AESIs). RESULTS: Of 773 patients enrolled, 326 (42%) received treatment for ≥12 months. In the extended exposure cohort, the median time-on-treatment was 19 months. The most common all-cause TEAEs were fatigue (32%) and diarrhea (31%). TEAEs leading to dose reduction occurred in 23 (7%) and discontinuations in 11 (3%) extended exposure patients. One patient had a fatal treatment-related AE (COVID-19 pneumonia). Infections (73.0%) were the most common AESI with a median time-to-first-occurrence of 7.4 months. Majority of TEAEs and AESIs occurred during the first year of therapy. CONCLUSIONS: Pirtobrutinib therapy continues to demonstrate an excellent safety profile amenable to long-term administration without evidence of new or worsening toxicity signals.

Association between maternal employment status and presence of children with major congenital anomalies in Denmark.

IMPORTANCE: The burden of caring for children with complex medical problems such as major congenital anomalies falls principally on mothers, who in turn suffer a variety of potentially severe economic consequences. As well, health consequences of caregiving often further impact the social and economic prospects of mothers of children with major congenital anomalies (MCMCAs). Evaluating the long-term economic consequences of extensive in-home caregiving among MCMCAs can inform strategies to mitigate these effects. OBJECTIVE: To assess whether MCMCAs face reduced employment and increased need for disability benefits over a 20-year period. DESIGN: A population-based matched cohort study. SETTING: Denmark. PARTICIPANTS: All women who gave birth to a singleton child with a major congenital anomaly in Denmark between January 1, 1997 and December 31, 2017 (n = 23,637) and a comparison cohort of mothers matched by maternal age, parity, and infant's year of birth (n = 234,586). EXPOSURES: Liveborn infant with a major congenital anomaly. MAIN OUTCOMES AND MEASURES: The primary outcome was mothers' employment status, stratified by their child's age. Employment status was categorized as employed, outside the workforce (on temporary leave, holding a flexible job, or pursuing education), or unemployed; the number of weeks in each category was measured over time. The secondary outcome was time to receipt of a disability pension, which in Denmark implies permanent exit from the labor market. We used a negative binomial regression model to estimate the number of weeks in each employment category, stratified by the child's age (i.e., 0-1 year, > 1-6 years, 7-13 years, 14-18 years). A Cox proportional hazards regression model was used to compute hazard ratios as a measure of the relative risk of receiving a disability pension. Rate ratios and hazard ratios were adjusted for maternal demographics, pregnancy history, health, and infant's year of birth. RESULTS: During 1-6 years after delivery, MCMCAs were outside the workforce for a median of 50 weeks (IQR, 6-107 weeks), while members of the comparison cohort were outside the workforce for a median of 48 weeks (IQR, 4-98 weeks), corresponding to an adjusted rate ratio [ARR] of 1.05 (95% confidence interval [CI], 1.04-1.07). During the first year after delivery, MCMCAs were more likely to be employed than mothers in the comparison cohort (ARR, 1.08; 95% CI, 1.06-1.10). At all timepoints thereafter, MCMCAs had a lower rate of workforce participation. The rate of being outside the workforce was 5% higher than mothers in the comparison cohort during 1-6 years after delivery (ARR, 1.05; 95% CI, 1.04-1.07), 9% higher during 7-13 years after delivery (ARR, 1.09; 95% CI, 1.06-1.12), and 12% higher during 14-18 years after delivery (ARR, 1.12; 95% CI, 1.07-1.18). Overall, MCMCAs had a 20% increased risk of receiving a disability pension during follow-up than mothers in the matched comparison cohort [incidence rates 3.10 per 1000 person-years (95% CI, 2.89-3.32) vs. 2.34 per 1000 person-years (95% CI, 2.29-2.40), adjusted hazard ratio, 1.20; 95% CI, 1.11-1.29]. CONCLUSION AND RELEVANCE: MCMCAs were less likely to participate in the Danish workforce, less likely to be employed, and more likely to receive disability pensions than mothers of unaffected children. The rate of leaving the workforce intensified as their affected children grew older. The high demands of caregiving among MCMCAs may have long-term employment consequences even in nations with comprehensive and heavily tax-supported childcare systems, such as Denmark.

Intraoperative hypoglycemia among adults with intraoperative glucose measurements: a cross-sectional multicentre retrospective cohort study.

PURPOSE: Intraoperative hypoglycemia is presumed to be rare, but generalizable multicentre incidence and risk factor data for adult patients are lacking. We used a multicentre registry to characterize adults with intraoperative hypoglycemia and hypothesized that intraoperative insulin administration would be associated with hypoglycemia. METHODS: We conducted a cross-sectional retrospective multicentre cohort study. We searched the Multicenter Perioperative Outcomes Group registry to identify adult patients with intraoperative hypoglycemia (glucose < 3.3 mmol·L-1 [< 60 mg·dL-1]) from 1 January 2015 to 31 December 2019. We evaluated characteristics of patients with intraoperative glucose measurements and with intraoperative hypoglycemia. RESULTS: Of 516,045 patients with intraoperative glucose measurements, 3,900 (0.76%) had intraoperative hypoglycemia. Diabetes mellitus and chronic kidney disease were more common in the cohort with intraoperative hypoglycemia. The odds of intraoperative hypoglycemia were higher for the youngest age category (18-30 yr) compared with the odds for every age category above 40 yr (odds ratio [OR], 1.57-3.18; P < 0.001), and were higher for underweight or normal weight patients compared with patients with obesity (OR, 1.48-2.53; P < 0.001). Parenteral nutrition was associated with lower odds of hypoglycemia (OR, 0.23; 95% confidence interval [CI], 0.11 to 0.47; P < 0.001). Intraoperative insulin use was not associated with hypoglycemia (OR, 0.996; 95% CI, 0.91 to 1.09; P = 0.93). CONCLUSION: In this large cross-sectional retrospective multicentre cohort study, intraoperative hypoglycemia was a rare event. Intraoperative insulin use was not associated with hypoglycemia.

RéSUMé: OBJECTIF: L'hypoglycémie peropératoire est présumée rare, mais il n'existe pas de données généralisables sur l'incidence multicentrique et les facteurs de risque chez la patientèle adulte. Nous avons utilisé un registre multicentrique pour caractériser les personnes adultes atteintes d'hypoglycémie peropératoire et émis l'hypothèse que l'administration peropératoire d'insuline serait associée à l'hypoglycémie. MéTHODE: Nous avons réalisé une étude de cohorte multicentrique rétrospective transversale. Nous avons effectué des recherches dans le registre du Multicenter Perioperative Outcomes Group afin d'identifier les patient·es adultes atteint·es d'hypoglycémie peropératoire (glucose < 3,3 mmol· L−1 [< 60 mg·dL−1]) du 1er janvier 2015 au 31 décembre 2019. Nous avons évalué les caractéristiques des patient·es présentant des mesures de glucose et une hypoglycémie peropératoires. RéSULTATS: Sur 516 045 patient·es ayant des mesures de glucose peropératoires, 3900 (0,76 %) ont présenté une hypoglycémie peropératoire. Le diabète sucré et l'insuffisance rénale chronique étaient plus fréquents dans la cohorte présentant une hypoglycémie peropératoire. Les risques d'hypoglycémie peropératoire étaient plus élevés pour la catégorie d'âge la plus jeune (18-30 ans) par rapport aux catégories d'âge au-dessus de 40 ans (rapport des cotes [RC], 1,57-3,18; P < 0,001), et étaient plus élevés chez les patient·es de poids insuffisant ou de poids normal par rapport aux patient·es obèses (RC, 1,48-2,53; P < 0,001). La nutrition parentérale était associée à une probabilité plus faible d'hypoglycémie (RC, 0,23; intervalle de confiance [IC] à 95 %, 0,11 à 0,47; P < 0,001). L'utilisation peropératoire d'insuline n'était pas associée à l'hypoglycémie (RC, 0,996; IC 95 %, 0,91 à 1,09; P = 0,93). CONCLUSION: Dans cette vaste étude de cohorte multicentrique rétrospective transversale, l'hypoglycémie peropératoire était un événement rare. L'utilisation peropératoire d'insuline n'était pas associée à l'hypoglycémie.

The role of noncovalent BTK inhibitors in the era of covalent BTK inhibitors.

Despite significantly improving outcomes in patients with B-cell malignancies, covalent Bruton tyrosine kinase (BTK) inhibitors are limited by toxicities and the development of resistance. Some toxicities can be life-threatening, such as cardiotoxicity. These toxicities result from off-target effects of covalent BTK inhibitors and frequently lead to dose reductions and discontinuations of the drug. Noncovalent BTK inhibitors bind BTK in a unique fashion and, to date, have demonstrated an excellent safety profile as well as efficacy against a variety of B-cell malignancies. In addition, noncovalent BTK inhibitors have, for the first time, demonstrated efficacy in patients who progressed on other BTK inhibitors. Long-term data and comparative studies are needed to further investigate their efficacy and role in the landscape covalent BTK Inhibitors.

Randomized Placebo-Controlled Trial of 60-Day Percutaneous Peripheral Nerve Stimulation Treatment Indicates Relief of Persistent Postoperative Pain, and Improved Function After Knee Replacement.

OBJECTIVES: Total knee arthroplasty (TKA) is an effective surgery for end-stage knee osteoarthritis, but chronic postoperative pain and reduced function affect up to 20% of patients who undergo such surgery. There are limited treatment options, but percutaneous peripheral nerve stimulation (PNS) is a promising nonopioid treatment option for chronic, persistent postoperative pain. The objective of the present study was to evaluate the effect of a 60-day percutaneous PNS treatment in a multicenter, randomized, double-blind, placebo-controlled trial for treating persistent postoperative pain after TKA. MATERIALS AND METHODS: Patients with postoperative pain after knee replacement were screened for this postmarket, institutional review board-approved, prospectively registered (NCT04341948) trial. Subjects were randomized to receive either active PNS or placebo (sham) stimulation. Subjects and a designated evaluator were blinded to group assignments. Subjects in both groups underwent ultrasound-guided placement of percutaneous fine-wire coiled leads targeting the femoral and sciatic nerves on the leg with postoperative pain. Leads were indwelling for eight weeks, and the primary efficacy outcome compared the proportion of subjects in each group reporting ≥50% reduction in average pain relative to baseline during weeks five to eight. Functional outcomes (6-minute walk test; 6MWT and Western Ontario and McMaster Universities Osteoarthritis Index) and quality of life (Patient Global Impression of Change) also were evaluated at end of treatment (EOT). RESULTS: A greater proportion of subjects in the PNS groups (60%; 12/20) than in the placebo (sham) group (24%; 5/21) responded with ≥50% pain relief relative to baseline (p = 0.028) during the primary endpoint (weeks 5-8). Subjects in the PNS group also walked a significantly greater distance at EOT than did those in the placebo (sham) group (6MWT; +47% vs -9% change from baseline; p = 0.048, n = 18 vs n = 20 completed the test, respectively). Prospective follow-up to 12 months is ongoing. CONCLUSIONS: This study provides evidence that percutaneous PNS decreases persistent pain, which leads to improved functional outcomes after TKA at EOT.

Decentralizing Health Care: History and Opportunities of Web3.

This paper explores the relationship between the development of the internet and health care, highlighting their parallel growth and mutual influence. It delves into the transition from the early, static days of Web 1.0, akin to siloed physician expertise in health care, to the more interactive and patient-centric era of Web 2.0, which was accompanied by advancements in medical technologies and patient engagement. This paper then focuses on the emerging era of Web3-the decentralized web-which promises a transformative shift in health care, particularly in how patient data are managed, accessed, and used. This shift toward Web3 involves using blockchain technology for decentralized data storage to enhance patient data access, control, privacy, and value. This paper also examines current applications and pilot projects demonstrating Web3's practical use in health care and discusses key questions and considerations for its successful implementation.

Hydroxyapatite ceramic-coated femoral components in younger patients followed up for 27 to 32 years.

Aims: This study reports the results of 38 total hip arthroplasties (THAs) in 33 patients aged less than 50 years, using the JRI Furlong hydroxyapatite ceramic (HAC)-coated femoral component. Methods: We describe the survival, radiological, and functional outcomes of 33 patients (38 THAs) at a mean follow-up of 27 years (25 to 32) between 1988 and 2018. Results: Of the surviving 30 patients (34 THAs), there were four periprosthetic fractures: one underwent femoral revision after 21 years, two had surgical fixation as the stem was deemed stable, and one was treated nonoperatively due to the patient's comorbidities. The periprosthetic fracture patients showed radiological evidence of change in bone stock around the femoral stem, which may have contributed to the fractures; this was reflected in change of the canal flare index at the proximal femur. Two patients (two hips) were lost to follow-up. Using aseptic loosening as the endpoint, 16 patients (18 hips; 48%) needed acetabular revision. None of the femoral components were revised for aseptic loosening, demonstrating 100% survival. The estimate of the cumulative proportion surviving for revisions due to any cause was 0.97 (standard error 0.03). Conclusion: In young patients with high demands, the Furlong HAC-coated femoral component gives excellent long-term results.

Continuous Remote Patient Monitoring for Post-Discharge Heart Failure Management: Workflow Modeling Using Discrete Event Simulation.

The Cascade-HF protocol is a Continuous Remote Patient Monitoring (CRPM) study at a major health system in the United States to reduce Heart Failure (HF)-related hospitalizations and readmissions using wearable biosensors to collect physiological data over a 30-day period to determine decompensation risk among HF patients. The alerts produced, coupled with electronic patient-reported outcomes, are utilized daily by the home health team, and escalated to the heart failure team as needed, for proactive actions. Limited research has examined anticipating the implementation and workflow challenges of such complex CRPM studies such as resource planning and staffing decisions that leverage the recorded data to drive clinical preparedness and operational efficiency. This preliminary analysis applies discrete event simulation modeling to the Cascade-HF protocol using pilot data from a soft launch to assess workload of the clinical team, evaluate escalation patterns and provide decision support recommendations to enable scale-up for all post-discharge patients.

Microneurosurgery for Ruptured Aneurysm of Distal Intracranial Vertebral Artery: A Case Report.

The International Subarachnoid Aneurysm Trial led to a shift from clipping to endovascular coiling as the primary therapy for cerebral aneurysm particularly in the management of posterior circulation aneurysm. However, endovascular therapy is often unavailable in low-resource settings, emphasizing the importance of maintaining surgical skill sets in resource-poor countries. This article presents a detailed case report on the successful microneurosurgical management of a 65-year-old female with a history of headache and weakness with past history of hypertension and a right posterior cerebral artery territory infarct who was diagnosed with a ruptured aneurysm situated within the intracranial vertebral artery. Patient was operated with the far lateral approach and clipping of the aneurysm. This case report elucidates the intricate surgical techniques employed, and the challenges neurosurgeons encountered in treating posterior circulation intracranial aneurysms, particularly those with ruptured complications. The aneurysms' intricate anatomy and increased rupture risk necessitate a meticulous microneurosurgical approach. The severity of subarachnoid hemorrhage from ruptured aneurysms increases morbidity and mortality rates.

Comparison of Patch Testing Results of White and Black Patients.

Patch testing is the standard diagnostic test used for patients presenting with symptoms of allergic contact dermatitis. The grading of patch test results classically varies from 1 to 3. The assessment of these results begins with a visual inspection of the presence of erythema, vesiculation, and induration. This leads to a subjectivity in visual evaluation of a patch test. Positive patch testing results can present differently in patients with darker skin tones. A greater variety of images of allergic contact dermatitis in patients with darker skin phototypes can better guide the diagnosis of this condition in skin of color. People with darker phototypes are historically underrepresented in dermatologic images and texts; thus, identifying erythema in darker phototypes may be more difficult for dermatologists, whether or not they were trained in areas of decreased phototype diversity. In this article, we present positive patch testing findings on several different phototypes, with the intention of contributing to images of phototypes underrepresented in dermatology literature.

Immunoglobulin High Throughput Sequencing (Ig-HTS) Minimal Residual Disease (MRD) Analysis is an Effective Surveillance Tool in Patients With Mantle Cell Lymphoma.

INTRODUCTION: Mantle cell lymphoma (MCL) accounts for 4% to 6% of B-cell non-Hodgkin lymphoma with historically poor outcomes. With the advent of intensive first-line, targeted, and cellular therapies, outcomes have improved, and initial remission can be 8 to 10 years or longer. As patients experience longer remissions, this raises the question of the optimal surveillance modality. Peripheral blood minimal residual disease (MRD) analysis offers a potential alternative to surveillance imaging that is sensitive, less costly, and eliminates the risk of radiation exposure. MATERIALS AND METHODS: The clonoSEQ assay (Adaptive Biotechnologies) is an FDA-cleared commercially available Ig-HTS MRD assay with a sensitivity of 1 cell in 1,000,000. We performed a retrospective analysis of 34 patients from 2015 to 2021, who underwent MRD testing after achieving remission with first-line therapy. RESULTS: With a median follow-up of 6.5 years, 10-year progression free survival (PFS) was 60% and 10-year overall survival was 92% of the entire cohort. Among 12 patients who sustained a radiographic relapse, peripheral blood became MRD+ either at or prior to the time of relapse in 11 patients (92%). The first MRD+ test had a lead time of 0 to 24 months (median 34 days) prior to radiographic relapse. Only 1 patient had a MRD- result while being found to have progressive disease on imaging. Among 22 patients who sustained continuous clinical remission, 21 have remained MRD-. Several patients were able to enjoy 2 to 4-year intervals without surveillance imaging. CONCLUSIONS: Our data suggest that the clonoSEQ MRD assay is an effective surveillance tool for MCL patients following first-line therapy and is predictive of relapse prior to imaging.

Adherence to stewardship recommendations for antibiotic discontinuation reduces antibiotic-associated adverse drug events.

Inappropriate antibiotic use may lead to increased adverse drug events (ADEs). This study assessed whether an antimicrobial stewardship recommendation to discontinue antibiotics in patients with low likelihood for bacterial infection reduced antibiotic duration and antibiotic-associated ADEs. At a 4-hospital system, hospitalized adult patients receiving empiric antibiotics for suspected infection were identified between May 2, 2016 and June 30, 2018. For those patients who were deemed unlikely to have a bacterial infection, a note was left by an infectious diseases physician recommending antibiotic discontinuation. Patient cases were considered "adherent" to recommendations if antibiotics were discontinued within 48 hours of the note and "non-adherent" to recommendations if antibiotics were continued beyond this. Duration of antibiotics and potential antibiotic-associated ADEs were collected retrospectively. Attribution of the adverse event to the antibiotic was decided upon by the investigators. The incidence of ADEs and duration of antibiotics between the adherent and non-adherent groups were compared. Of 253 patients deemed unlikely to have a bacterial infection, 114 (45%) treatment teams stopped antibiotics within 48 hours of the recommendation, and 139 (55%) continued antibiotics. The total number of ADEs was significantly higher in the non-adherent group compared to the adherent group (34 ADEs vs 9 ADEs, P = .001). The median number of total prescribed antibiotic days was higher in the non-adherent group than in the adherent group (5 days vs 1 day, P < .001). This study demonstrates that stewardship programs may prevent ADEs by recommending antibiotic discontinuation in patients with low suspicion for bacterial infection.

Outcomes of a hydroxyapatite ceramic-coated femoral stem in primary total hip arthroplasty: a report of excellent survivorship from a single United Kingdom centre.

BACKGROUND: Hydroxyapatite (HA) coated femoral stems were introduced to enhance the biological fixation at the implant-bone interface, aiming to increase the longevity and survival of the prostheses. We aimed to assess the long-term outcomes of an HA ceramic (HAC) coated stem in primary total hip arthroplasty (THA), assess the stem survival, and clinically evaluate the patients using patient-reported outcome measures (PROMs) and radiological evaluation of stem osseointegration. PATIENTS AND METHODS: This was a prospective evaluation of a retrospective cohort of 385 patients (442 hips) who underwent primary THA between June 2008 and December 2018. The mean age was 63.83 years (range, 30-82 years). During the follow-up duration, 23 patients died, and 36 patients (38 hips) were lost to follow-up. Prospective data collected for 326 patients (381 hips) was used to evaluate stem survival with the Kaplan-Meier method using aseptic loosening or any revision as the endpoint. Clinical evaluation was done using the EuroQol five-dimension (EQ-5D) scoring system and PROMs using the Oxford Hip Score (OHS) and Merle D'Aubigne Postel (MDP) score. Radiological assessments were performed using the Engh radiological criteria for stem osteointegration. RESULTS: The mean follow-up duration was 9.39 years (range, 4-14.5 years). The survival of the HAC-coated femoral stem was 100% (95% confidence interval [CI], 96.7-100%) at 14 years with aseptic loosening as the endpoint, and 98.9% (CI, 96.7-100%) at 14 years with stem revision for any reason as the endpoint. The mean OHS was 44.5 (range, 30-48), and the mean MDP score was 15.87 (range, 10-18). Radiological evaluations showed full osseointegration of all stems. CONCLUSION: This HAC-coated femoral stem has shown excellent survivorship, functional outcomes, and full osseointegration at the final follow-up.