Real World Outcome of High-Risk Multiple Myeloma: An Indian Tertiary Care Centre Experience.

INTRODUCTION: High risk myeloma is heterogeneous with significant variation in risk stratifications. Real world outcomes differ from controlled clinical trials and affected by socioeconomical determinants. MATERIAL AND METHODS: This retrospective study was performed in a North Indian teriarty care cancer hospital. Out of 384,76(19.7%) high risk myeloma patients (median age 58 years) were analyzed. RESULT AND CONCLUSION: Most common HRCA was 1 q gain 36(47.4%) followed by del17p 32(42.1%). 61/76(80.2%) received bortezomib based triplets and 15(19.74%) daratumumab based quadruplets induction, 31(40.79%) received ASCT. Median duration of follow up was 19.5 months. The 2 year OS and PFS was 73.8%, 52.6% respectively. Estimated 3 year OS was 74.7% in ASCT cohort versus 52.9% (P = .0067) without. Estimated 3-year PFS in the ASCT cohort was 72.1% versus 30.3% (P = .0026) without. Estimated 3-year OS for single hit and multi hit ultra HRMM was 67.7% and 61.9% (P = .642) whereas PFS was 58.2% and 35.2% (P = .486) respectively. In multivariate analysis ASCT correlated with better OS (HR 0.3, P = .041) and PFS (HR 0.35, P = .012). Absence of baseline renal impairment correlated with better OS (HR 4.12, P = .004) only. Early aggressive therapy with prompt ASCT translates to a better survival in high risk myeloma. Emphasis on real world clinical outcome is the need of the hour for addressing practical issues and improving global myeloma outcome.

A tertiary care centre experience with Elranatamab: A report of three cases.

Introduction: The introduction of proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies has changed the treatment paradigm of multiple myeloma. With the advent of these new therapeutic options, life expectancy has substantially increased for myeloma patients which has led to an increased number of patients with triple-class refractory disease. Thus, there remains an unmet need for effective novel therapies with good tolerability and safety profile. Elranatamab, is the most widely used bispecific antibody currently in the Indian setting. However, it has only been used on a clinical trial basis till now, and real-world data especially in the Indian setting is missing. Here, we present our experience with three cases of multi-line treated relapsed/refractory multiple myeloma on elranatamab monotherapy. Case report: We here discuss three of our patients with triple class refractory multiple myeloma who recieved elranatamab monotherapy. While one of our patient had been switched to fortnightly treatment, two patients were still continuing weekly treatment. The common adverse effects observed were grade 1-2 cytokine release syndrome, cytopenias, CMV reactivation and hypo-gammaglobulinemia. While two of our patients are doing well, one patient had grade 3 neurological toxicity, likely drug related and succumbed. Discussion: B-cell maturation antigen is highly expressed on mature B cells and is critical for the survival and proliferation of plasma cells. It has emerged as a novel target for anti-myeloma therapies in the form of bispecific cell engager, antibody-drug conjugates, and chimeric antigen receptor (CAR) T-cell therapies.The phase II MM3 trial showed a promising efficacy with an ORR of 61% with a CR rate of >35%. With a median follow-up of 14.7 months, the median PFS was not reached and the 15-month PFS rate was 50.9%. While it is too early to comment on long term survival with the monotherapy, we here discuss response of Indian patients in the real world setting. Conclusion: Elranatamab monotherapy could prove to be an efficacious option for the treatment of relapsed /refractory multiple myeloma patients with triple-class refractory disease, with limited therapeutic options. However, patients need to be screened for infectious complications with appropriate prophylaxis and immunoglobulin replacement, if required. Also, a high suspicion is required for the neurological complications of the drug and a longitudinal neuro-cognitive screening is required for the patients.

Insights into In Situ Benthic Caging Tests for Ecotoxicity Assessments Targeting Discharging Groundwater Contaminant Plumes.

While in situ toxicity testing with caged organisms has been used to assess surface water and sediment contamination, no successful application to benthic organisms exposed to highly contaminated groundwater plumes discharging to surface waters has been reported. The objective of this study was to demonstrate and evaluate this application using four sets of tests performed at three previously reported contaminated groundwater sites, which include one river site affected by volatile organic contaminant plumes, and two sites, one pond and one small urban stream, impacted by landfill plumes. The study examined multiple cage designs and orientations and two test organisms: an amphipod (Hyalella azteca) and midge larvae (Chironomus riparius; only one study). Cages were deployed for between 5 and 28 days and assessed for organism survival and growth. At all sites and for some deployment conditions, cages exposed to high contaminant concentrations in the plume footprint had greater mortality compared to those exposed to lower or background concentrations. Organism growth was less clear as a metric of toxicity. Vertically oriented cages typically showed high mortality to plume contaminants, but some were also affected by other non-target groundwater conditions (e.g., low dissolved oxygen, other contaminant sources), while horizontally oriented cages were rarely responsive to either groundwater influence. A hybrid cage design showed much promise in its single study. Useful observations on the test organisms and on potentially problematic site conditions were also made. The informed use of in situ toxicity cages could be an additional beneficial tool for groundwater contaminated site assessments.

Vaccination protocols in Québec dairy herds.

Information is needed on vaccination protocols used by veterinarians and dairy producers to prevent and control infections in dairy herds. This observational study described farm's vaccination standard operating procedures (SOP) developed by veterinarians in collaboration with dairy producers in Québec. Data pertaining to vaccination protocols and dairy producer practices were collected as part of the biosecurity component of the National Mandatory Quality Assurance Certification Program (proAction). Generalized statistical mixed-effects models were used to assess associations between dairy herd characteristics and the vaccination SOP, encompassing various vaccination types. These included any vaccination, core vaccines only (bovine respiratory syncytial virus, infectious bovine rhinotracheitis herpesvirus, parainfluenza virus type 3, bovine viral diarrhea virus type 1 and type 2), and vaccination against diarrhea, mastitis, or clostridial diseases. These models accounted for random variations related to clustering by veterinarians and veterinary clinics. Furthermore, the variance of the outcome was partitioned into producer, veterinarian, and veterinary clinic levels to explore the proportion of the total variance attributable to each group. A total of 3,759 standardized vaccination procedures completed between 2018 and 2021 were analyzed. At least one vaccination target was included in the vaccination SOP in 90% of the dairy herds. The most frequently included vaccine in the SOP was core vaccines, comprising 88%, followed by mastitis (22%), neonatal diarrhea (18%), and clostridial disease vaccines (15%). The vaccination SOP, particularly core, mastitis, and diarrhea vaccinations, mainly varied due to the veterinarian's characteristics, followed by the clinic's characteristics. In contrast, the decision to included clostridial vaccination primarily varied with the veterinary clinic (76%). Organic producers generally included fewer vaccinations in their SOP, including core vaccines, than conventional producers. In addition, producers who were providing access to pasture had fewer vaccination SOP for vaccination against mastitis and neonatal diarrhea but more vaccination SOP for clostridial vaccination.

Validity of luminometry and bacteriological tests for diagnosing intramammary infection at dry-off in dairy cows.

The objective of this cross-sectional study was to estimate the validity of laboratory culture, Petrifilm and Tri-Plate on-farm culture systems, as well as luminometry to correctly identify IMI at dry-off in dairy cows, considering all tests to be imperfect. From September 2020 until December 2021, we collected composite milk samples from cows before dry-off and divided them into 4 aliquots for luminometry, Petrifilm (aerobic count), Tri-Plate, and laboratory culture tests. We assessed multiple thresholds of relative light units (RLU) for luminometry, and we used thresholds of ≥100 cfu/mL for the laboratory culture, ≥50 cfu/mL for Petrifilm, and ≥1 cfu for Tri-Plate tests. We fitted Bayesian latent class analysis models to estimate the sensitivity (Se) and specificity (Sp) for each test to identify IMI, with 95% credibility interval (BCI). Using different prevalence measures (0.30, 0.50, and 0.70), we calculated the predictive values (PV) and misclassification cost terms (MCT) at different false negative-to-false-positive ratios (FN:FP). A total of 333 cows were enrolled in the study from one commercial Holstein herd. The validity of the luminometry was poor for all thresholds, with an Se of 0.51 (95% BCI = 0.43-0.59) and Sp of 0.38 (95% BCI = 0.26-0.50) when using a threshold of ≥150 RLU. The laboratory culture had an Se of 0.93 (95% BCI = 0.85-0.98) and Sp of 0.69 (95% BCI = 0.49-0.89); the Petrifilm had an Se of 0.91 (95% BCI = 0.80-0.98) and Sp of 0.71 (95% BCI = 0.51-0.90); and the Tri-Plate had an Se of 0.65 (95% BCI = 0.53-0.82) and Sp of 0.85 (95% BCI = 0.66-0.97). Bacteriological tests had good PV, with comparable positive PV for all 3 tests, but lower negative PV for the Tri-Plate compared with the laboratory culture and the Petrifilm. For a prevalence of IMI of 0.30, all 3 tests had similar MCT, but for prevalence of 0.50 and 0.70, the Tri-Plate had higher MCT in scenarios where leaving a cow with IMI untreated is considered to have greater detrimental effects than treating a healthy cow (i.e., FN:FP of 3:1). Our results showed that the bacteriological tests have adequate validity to diagnose IMI at dry-off, but luminometry does not. We concluded that although luminometry is not useful to identify IMI at dry-off, the Petrifilm and Tri-Plate tests performed similarly to laboratory culture, depending on the prevalence and importance of the FP and FN results.

Repeated Exposure of Vancomycin to Vancomycin-Susceptible Staphylococcus aureus (VSSA) Parent Emerged VISA and VRSA Strains with Enhanced Virulence Potentials.

The emergence of resistance against the last-resort antibiotic vancomycin in staphylococcal infections is a serious concern for human health. Although various drug-resistant pathogens of diverse genetic backgrounds show higher virulence potential, the underlying mechanism behind this is not yet clear due to variability in their genetic dispositions. In this study, we investigated the correlation between resistance and virulence in adaptively evolved isogenic strains. The vancomycin-susceptible Staphylococcus aureus USA300 was exposed to various concentrations of vancomycin repeatedly as a mimic of the clinical regimen to obtain mutation(s)-accrued-clonally-selected (MACS) strains. The phenotypic analyses followed by expression of the representative genes responsible for virulence and resistance of MACS strains were investigated. MACS strains obtained under 2 and 8 µg/ml vancomycin, named Van2 and Van8, respectively; showed enhanced vancomycin minimal inhibitory concentrations (MIC) to 4 and 16 µg/ml, respectively. The cell adhesion and invasion of MACS strains increased in proportion to their MICs. The correlation between resistance and virulence potential was partially explained by the differential expression of genes known to be involved in both virulence and resistance in MACS strains compared to parent S. aureus USA300. Repeated treatment of vancomycin against vancomycin-susceptible S. aureus (VSSA) leads to the emergence of vancomycin-resistant strains with variable levels of enhanced virulence potentials.

Real world outcome of B ALL with t (1; 19) (q23; p13)/TCF3::PBX1 in adolescents and adults treated with intensive regimes.

Significant heterogeneity has been reported in outcome of Acute lymphoblastic leukemia with t(1;19)(q23;p13)/TCF3::PBX1 in adolescents and adults leading to a lack of consensus on precise risk stratification. We evaluated clinical outcome of 17 adult ALL cases (≥15 years) with this genotype treated on intensive regimes.13/17 received COG0232 and 4/17 cases received UK-ALL protocol. All achieved CR (100%) with above treatment. End of induction MRD was evaluated in 14/17 cases of which 11 (78.5%) achieved MRD negativity. Total nine patients relapsed (7 marrows, 2 CNS). Overall survival at 2 years was 53.3%. The 2 year estimated PFS was 42.9%. The 2 years CIR was 54.2%. Adults with this genotype perform poorly despite early favorable response. Incorporation of novel immunotherapies and prompt HSCT should be strongly considered with this genotype. Targeted NGS panels for additional genetic aberrations can further help in risk stratifying and guiding therapy for this genotype.

Evaluation of microbial occurrence in reusable robotic instruments for minimally invasive surgery: A pilot study.

In recent decades, minimally invasive surgery has become the favoured surgical technique, with increasing utilisation of robotic surgery to enhance patient outcomes. However, the design complexity of surgical robotic instruments can pose challenges in maintaining adequate cleaning, disinfection and sterilisation-particularly of the device's interior. In our hospital, robotic instruments are reused for a maximum of ten successive patients, following the manufacturer's guidelines. To the best of our knowledge, neither the manufacturer nor ISO standards have specified any methods to determine the sterility of robotic instruments after cleaning, disinfection and sterilisation procedures. In a small pilot study, we used a locally developed protocol to evaluate the sterility of 20 da Vinci SI robotic instruments, with the aim of determining whether the recommended cleaning, disinfection and sterilisation process is adequate to achieve safe usage in subsequent patients. None of the 20 instruments showed viable micro-organisms, therefore the robotic instruments were considered sterile, and suitable for re-use. We recommend our protocol to other hospitals, to be used as an essential control element in the assessment of their unique reprocessing technique for robotic instruments.

Herd-level associations between the proportion of elevated prepartum nonesterified fatty acid concentrations and postpartum diseases, reproduction, or culling on dairy farms.

The objectives of this herd-level prospective observational cohort study were to describe the proportion of cows with elevated prepartum nonesterified fatty acid concentrations (PropElevNEFA) in dairy herds and to assess the herd-level associations between PropElevNEFA and postpartum diseases, reproductive performance, and culling. From November 2018 to December 2020, a convenience sample of 49 herds was enrolled in this study. Blood sampling (16 to 29 cows per herd) was performed during the week before and during the 2 wk following calving to quantify the concentration of nonesterified fatty acids (NEFA) and ß-hydroxybutyrate acids (BHBA), respectively. Elevated NEFA was defined as ≥280 µmol/L and hyperketonemia as BHBA ≥1.4 mmol/L. Retained placenta, metritis, purulent vaginal discharge, endometritis, and mastitis were diagnosed on-farm following standardized definitions, and success at first artificial insemination (AI) and culling events were recorded. The associations between PropElevNEFA and each individual disease, success at first AI, and culling were evaluated using Bayesian aggregated binomial regression models with weakly informative priors, from the which odds ratio (OR) and the 95% credible intervals (BCI) were obtained. A total of 981 cows were included in the statistical analyses representing 16 to 29 (median = 19) cows per herd. Cows were enrolled in the prepartum period of their first to tenth (median = third) lactation, and 41% of them had an elevated prepartum NEFA concentration. At the herd level, PropElevNEFA varied between 11% and 78% (median = 39%). The odds of metritis (OR = 1.37, 95% BCI = 1.13-1.67) increased for every 10-point increase in PropElevNEFA, whereas the odds of success at first AI decreased (OR = 0.69, 95% BCI = 0.59-0.80). The PropElevNEFA was not associated with the other tested diseases or culling. Our results suggest that the herd-level proportion of cows having elevated prepartum NEFA concentrations is associated with metritis and poor success at first AI in dairy herds.

Biosecurity adoption in Québec dairy farms: Results from a risk assessment questionnaire analyzed using conventional and unsupervised artificial intelligence methods.

This study documents the current state of biosecurity on dairy farms in Québec following the implementation of a mandatory biosecurity risk evaluation that was part of the proAction accreditation program developed by Dairy Farmers of Canada. Using a cross-sectional design, 3,825 risk assessment questionnaires completed between 2018 and 2021 were extracted from Vigil-Vet database, which is a software used by veterinarians for conducting the proAction risk assessment. Descriptive statistics were used to summarize the practices adopted by dairy producers. Additionally, multiple correspondence analysis was used to explore the association between the diseases of most concern and the adoption of biosecurity practices. Moreover, we used a hierarchical cluster analysis on principal components to identify distinct patterns of biosecurity practices among dairy producers. This analysis enabled the identification of typologies or clusters of farms based on the specific biosecurity practices they currently employ. The results of the descriptive statistics indicated that mastitis was the disease of most concern for most dairy farmers (40%). Moreover, given that only 10% of the 2,237 dairy farmers who acquired animals adhered to quarantine practices, there seems to be a need for improved implementation of biosecurity measures aimed at restricting the introduction of diseases when introducing new animals. Conversely, cleaning stalls and health equipment were adequately addressed by 95% and 86% of dairy producers, respectively. The multiple correspondence analysis indicated no significant association between the disease of most concern and the farm's biosecurity profile, except for respondents who identified digital dermatitis as their disease of most concern. Through the hierarchical cluster analysis, 3 clusters were identified among 3,581 farms: (1) Cluster 1 included farms with good management of sick animals; (2) Cluster 2 included farms with good management of young animals; and (3) Cluster 3 included farms with poor management of sick animals and young animals. Our study makes an important contribution by providing valuable insights into the biosecurity practices currently adopted on Québec dairy farms. It establishes a baseline for assessing progress in biosecurity practices adoption and serves as a reference point for future evaluations. In addition, these findings play a key role in monitoring the effectiveness of interventions aimed at improving biosecurity on dairy farms. By making use of this knowledge, stakeholders can make informed decisions that prioritize animal health, increase productivity, and ensure sustainability of the dairy industry.

Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula: A Randomized Clinical Trial.

Importance: Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. Objective: To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Intervention: Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. Main Outcomes and Measures: The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Results: Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Conclusions and Relevance: Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. Trial Registration: ClinicalTrials.gov Identifier: NCT01534481.

Model of P-Glycoprotein Ligand Binding and Validation with Efflux Substrate Matched Pairs.

The blood-brain barrier (BBB) poses a significant obstacle in developing therapeutics for neurodegenerative diseases and central nervous system (CNS) disorders. P-glycoprotein (P-gp), a multidrug resistance protein, is a critical gatekeeper in the BBB and plays a role in cancer chemoresistance. This paper uses cryo-EM P-gp structures as starting points with an induced fit docking (IFD) model to evaluate 19 pairs of compounds with known P-gp efflux data. The study reveals significant differences in binding energy and sheds light on structural modifications' impact on efflux properties. In the cases examined, fluorine incorporation influences the efflux by altering the molecular conformation rather than proximal heteroatom basicity. Although there are limitations in addressing covalent interactions or when binding extends into the more flexible vestibule region of the protein, the results provide valuable insights and potential strategies to overcome P-gp efflux, contributing to the advancement of drug development for both CNS disorders and cancer therapies.

Increasing Prevalence of Cerebral Palsy Among Two-Year-Old Children Born at <27 Weeks of Gestation: A Cohort Study.

OBJECTIVE: To evaluate changes in prevalence and severity of cerebral palsy (CP) among surviving children born at <27 weeks of gestation over time and to determine associations between CP and other developmental domains, functional impairment, medical morbidities, and resource use among 2-year-old children who were born extremely preterm. STUDY DESIGN: Retrospective cohort study using prospective registry data, conducted at 25 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Participants were children born at <27 weeks of gestation and followed at 18 through 26 months of corrected age from 2008 through 2019. Outcomes of interest were changes in prevalence of any CP and severity of CP over time and associations between CP and other neurodevelopmental outcomes, functional impairment, and medical comorbidities. Adjusted logistic, linear, multinomial logistic, and robust Poisson regression evaluated the relationships between child characteristics, CP severity, and outcomes. RESULTS: Among 6927 surviving children with complete follow-up data, 3717 (53.7%) had normal neurologic examinations, 1303 (18.8%) had CP, and the remainder had abnormal neurologic examinations not classified as CP. Adjusted rates of any CP increased each year of the study period (aOR 1.11 per year, 95% CI 1.08-1.14). Cognitive development was significantly associated with severity of CP. Children with CP were more likely to have multiple medical comorbidities, neurosensory problems, and poor growth at follow-up. CONCLUSIONS: The rate of CP among surviving children who were born extremely preterm increased from 2008 through 2019. At 18 to 26 months of corrected age, neurodevelopmental and medical comorbidities are strongly associated with all severity levels of CP.

Feeding predictability as a cognitive enrichment protects brain function and physiological status in rainbow trout: a multidisciplinary approach to assess fish welfare.

Cognitive enrichment is a promising but understudied type of environmental enrichment that aims to stimulate the cognitive abilities of animals by providing them with more opportunities to interact with (namely, to predict events than can occur) and to control their environment. In a previous study, we highlighted that farmed rainbow trout can predict daily feedings after two weeks of conditioning, the highest conditioned response being elicited by the combination of both temporal and signalled predictability. In the present study, we tested the feeding predictability that elicited the highest conditioned response in rainbow trout (both temporal and signalled by bubbles, BUBBLE + TIME treatment) as a cognitive enrichment strategy to improve their welfare. We thus analysed the long-term effects of this feeding predictability condition as compared with an unpredictable feeding condition (RANDOM treatment) on the welfare of rainbow trout, including the markers in the modulation of brain function, through a multidisciplinary approach. To reveal the brain regulatory pathways and networks involved in the long-term effects of feeding predictability, we measured gene markers of cerebral activity and plasticity, neurotransmitter pathways and physiological status of fish (oxidative stress, inflammatory status, cell type and stress status). After almost three months under these predictability conditions of feeding, we found clear evidence of improved welfare in fish from BUBBLE + TIME treatment. Feeding predictability allowed for a food anticipatory activity and resulted in fewer aggressive behaviours, burst of accelerations, and jumps before mealtime. BUBBLE + TIME fish were also less active between meals, which is in line with the observed decreased expression of transcripts related to the dopaminergic system. BUBBLE + TIME fish tented to present fewer eroded dorsal fin and infections to the pathogen Flavobacterium psychrophilum. Decreased expression of most of the studied mRNA involved in oxidative stress and immune responses confirm these tendencies else suggesting a strong role of feeding predictability on fish health status and that RANDOM fish may have undergone chronic stress. Fish emotional reactivity while isolated in a novel-tank as measured by fear behaviour and plasma cortisol levels were similar between the two treatments, as well as fish weight and size. To conclude, signalled combined with temporal predictability of feeding appears to be a promising approach of cognitive enrichment to protect brain function via the physiological status of farmed rainbow trout in the long term.

Methylprednisolone taper is an effective addition to multimodal pain regimens after total shoulder arthroplasty: results of a randomized controlled trial: 2022 Neer Award winner.

BACKGROUND: Perioperative corticosteroids have shown potential as nonopioid analgesic adjuncts for various orthopedic pathologies, but there is a lack of research on their use in the postoperative setting after total shoulder arthroplasty (TSA). The purpose of this study was to assess the effect of a methylprednisolone taper on a multimodal pain regimen after TSA. METHODS: This study was a randomized controlled trial (clinicaltrials.gov NCT03661645) of opioid-naive patients undergoing TSA. Patients were randomly assigned to receive intraoperative dexamethasone only (control group) or intraoperative dexamethasone followed by a 6-day oral methylprednisolone (Medrol) taper course (treatment group). All patients received the same standardized perioperative pain management protocol. Standardized pain journal entries were used to record visual analog pain scores (VAS-pain), VAS-nausea scores, and quantity of opioid tablet consumption during the first 7 postoperative days (POD). Patients were followed for at least one year postoperatively for clinical evaluation, collection of patient-reported outcomes, and observation of complications. RESULTS: A total of 67 patients were enrolled in the study; 32 in the control group and 35 in the treatment group. The groups had similar demographics and comorbidities. The treatment group demonstrated a reduction in mean VAS pain scores over the first 7 POD. Between POD 1 and POD 7, patients in the control group consumed an average of 17.6 oxycodone tablets while those in the treatment group consumed an average of 5.5 tablets. This equated to oral morphine equivalents of 132.1 and 41.1 for the control and treatment groups, respectively. There were fewer opioid-related side effects during the first postoperative week in the treatment group. The treatment group reported improved VAS pain scores at 2-week, 6-week, and 12-week postoperatively. There were no differences in Europe Quality of Life, shoulder subjective value (SSV), at any time point between groups, although American Shoulder and Elbow Surgeons questionnaire scores showed a slight improvement at 6-weeks in the treatment group. At mean follow-up, (control group: 23.4 months; treatment group:19.4 months), there was 1 infection in the control group and 1 postoperative cubital tunnel syndrome in the treatment group. No other complications were reported. CONCLUSIONS: A methylprednisolone taper course shows promise in reducing acute pain and opioid consumption as part of a multimodal regimen following TSA. As a result of this study, we have included this 6-day methylprednisolone taper course in our multimodal regimen for all primary shoulder arthroplasties. We hope this trial serves as a foundation for future studies on the use of low-dose oral corticosteroids and other nonnarcotic modalities to control pain after shoulder surgeries.

Improving outcomes in emergency general surgery: Construct of a collaborative quality initiative.

BACKGROUND: Emergency general surgery conditions are common, costly, and highly morbid. The proportion of excess morbidity due to variation in health systems and processes of care is poorly understood. We constructed a collaborative quality initiative for emergency general surgery to investigate the emergency general surgery care provided and guide process improvements. METHODS: We collected data at 10 hospitals from July 2019 to December 2022. Five cohorts were defined: acute appendicitis, acute gallbladder disease, small bowel obstruction, emergency laparotomy, and overall aggregate. Processes and inpatient outcomes investigated included operative versus nonoperative management, mortality, morbidity (mortality and/or complication), readmissions, and length of stay. Multivariable risk adjustment accounted for variations in demographic, comorbid, anatomic, and disease traits. RESULTS: Of the 19,956 emergency general surgery patients, 56.8% were female and 82.8% were White, and the mean (SD) age was 53.3 (20.8) years. After accounting for patient and disease factors, the adjusted aggregate mortality rate was 3.5% (95% confidence interval [CI], 3.2-3.7), morbidity rate was 27.6% (95% CI, 27.0-28.3), and the readmission rate was 15.1% (95% CI, 14.6-15.6). Operative management varied between hospitals from 70.9% to 96.9% for acute appendicitis and 19.8% to 79.4% for small bowel obstruction. Significant differences in outcomes between hospitals were observed with high- and low-outlier performers identified after risk adjustment in the overall cohort for mortality, morbidity, and readmissions. The use of a Gastrografin challenge in patients with a small bowel obstruction ranged from 10.7% to 61.4% of patients. In patients who underwent initial nonoperative management of acute cholecystitis, 51.5% had a cholecystostomy tube placed. The cholecystostomy tube placement rate ranged from 23.5% to 62.1% across hospitals. CONCLUSION: A multihospital emergency general surgery collaborative reveals high morbidity with substantial variability in processes and outcomes among hospitals. A targeted collaborative quality improvement effort can identify outliers in emergency general surgery care and may provide a mechanism to optimize outcomes. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Longitudinal changes in resting state fMRI brain self-similarity of asymptomatic high school American football athletes.

American football has become the focus of numerous studies highlighting a growing concern that cumulative exposure to repetitive, sports-related head acceleration events (HAEs) may have negative consequences for brain health, even in the absence of a diagnosed concussion. In this longitudinal study, brain functional connectivity was analyzed in a cohort of high school American football athletes over a single play season and compared against participants in non-collision high school sports. Football athletes underwent four resting-state functional magnetic resonance imaging sessions: once before (pre-season), twice during (in-season), and once 34-80 days after the contact activities play season ended (post-season). For each imaging session, functional connectomes (FCs) were computed for each athlete and compared across sessions using a metric reflecting the (self) similarity between two FCs. HAEs were monitored during all practices and games throughout the season using head-mounted sensors. Relative to the pre-season scan session, football athletes exhibited decreased FC self-similarity at the later in-season session, with apparent recovery of self-similarity by the time of the post-season session. In addition, both within and post-season self-similarity was correlated with cumulative exposure to head acceleration events. These results suggest that repetitive exposure to HAEs produces alterations in functional brain connectivity and highlight the necessity of collision-free recovery periods for football athletes.

Sorry to ask but how is apology effectiveness dependent on apology content and gender?

While it is well understood that the content included in an apology matters, what constitutes an effective apology may differ depending on the gender of the person delivering it. In this article, we test competing theoretical perspectives (i.e., role congruity theory and expectancy violation theory [EVT]) about the relative effectiveness of apologies that include language that conforms (or not) with the gender stereotypes ascribed to the apologizer. Results of four studies supported an EVT perspective and showed that apologies were perceived to be relatively more effective when they contradicted gender stereotypes (i.e., communal [agentic] apologies by men [women]). Specifically, Study 1 provided an initial test of the competing hypotheses using celebrity apologies on Twitter. Then, results of three experiments (Studies 2, 3a, and 3b) built upon these initial findings and tested the psychological mechanisms proposed by EVT to explain why counterstereotypical apologies are beneficial (i.e., attributions of interpersonal sensitivity [assertiveness] and enhanced perceptions of benevolence [competence] for men [women]). Our contributions to theory and practice are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Preoperative Depression Is Associated With Increased Complications Following Distal Radius Fracture Surgery.

BACKGROUND: Depression is a known risk factor for inferior outcomes after orthopedic procedures, but its specific relationship with distal radius fractures remains unknown. This study investigates the relationship between preoperative diagnosed depression and common postoperative complications occurring within the first year after open reduction internal fixation (ORIF) for distal radius fractures. METHODS: This retrospective study used Truven MarketScan database and the Current Procedural Terminology (CPT) codes to identify distal radius fracture patients who underwent ORIF in the United States between January 1, 2009, and December 31, 2019. International Classification of Diseases (ICD) codes were used to identify patients with and without a diagnosis of preoperative depression. Univariate, multivariate, t test, and χ2 analyses were performed to determine the association between preoperative depression and postoperative complications following a distal radius fracture surgery. RESULTS: Of the 75 098 eligible patients, 9.9% had at least one ICD code associated with preoperative depression. Preoperative depression was associated with increased odds for surgical site infection (odds ratio [OR] 1.25, confidence interval [CI] 1.14-1.37), emergency department visits for postoperative pain (OR 1.28, CI 1.15-1.36), hardware complication (OR 1.18, CI 1.07-1.30), removal of hardware within 1 year (OR 1.16, CI 1.09-1.27), wound complication (OR 1.17, CI 1.08-1.27), and 30-day readmission (OR 1.21, CI 1.07-1.31). CONCLUSIONS: Preoperative diagnosed depression is associated with increased complications following distal radius fracture surgery. These results can help guide preoperative and postoperative protocols in these higher risk patients. More research is needed to investigate if depression is a modifiable risk factor, as depression treatment could potentially improve postsurgical outcomes.