Short-term complication rates of open reduction and plate fixation and intramedullary nailing in the treatment of humeral shaft fractures: a propensity score matched analysis.

INTRODUCTION: This is a retrospective cohort study designed to compare short-term postoperative complication rates between closed humeral shaft fractures treated by open reduction and internal fixation (ORIF) versus intramedullary nailing (IMN), as well as secondary independent risk factors for adverse outcomes. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried using CPT codes to identify patients that underwent an open reduction and plate fixation or intramedullary nailing procedure for a closed humeral shaft fracture from 2010 to 2021. Cohorts were matched using propensity scores to account for demographic differences and rates of complications were compared between the two groups. RESULTS: From the database, a total of 4,222 patients were identified who met inclusion criteria, with 3,326 and 896 undergoing ORIF and IMN respectively. After propensity score matching, 866 of the nearest-neighbor matches were included in each cohort for a total of 1,732 patients in the final analysis. The rate of any adverse event (AAE) was significantly higher in the ORIF cohort (16.3%) than the IMN cohort (12.1%, p = 0.01). The ORIF group had higher rates of postoperative transfusion (p = 0.002), return to OR (p = 0.005), and surgical site infection (SSI, p = 0.03). After multivariate analysis, ASA class 4, increasing age, increasing operative time, and history of bleeding disorder were found to increase the risk of AAE in both ORIF and IMN patients. CONCLUSIONS: While prior studies have claimed higher complication rates in IMN patients, this study found a significantly higher short-term risk of AAE in ORIF patients when compared in matched cohorts. However, individual 30-day complication rates do not differ significantly between procedures, and both have been shown to be safe and effective tools in the management of humeral shaft fractures.

Haemophilia Carriers Experience Study (CARES): A mixed method exploration into the experience of women who are carriers of Haemophilia.

INTRODUCTION: Haemophilia research has traditionally focused on patients diagnosed with haemophilia and although research priorities are rapidly changing, there is still a lot more we need to understand about the experiences and psychosocial issues facing women who are diagnosed as carriers of haemophilia (Haemophilia, https://doi.org/10.1111/hae.14043). One study noted that the understanding of carriers' experience of bleeding by healthcare professionals is limited and that many women have had negative experiences of healthcare (Haemophilia, 17, 2011, 237). The carrier population does not typically receive much support for themselves as individuals as they are often not registered at Haemophilia Centres in their own right. AIM: This study aimed to look at the emotional wellbeing of carriers in more detail. METHOD: This was initially investigated through the use of focus groups and individual interviews with 16 participants (Stage 1) and then widening the study using an online questionnaire battery developed from the themes identified from these interviews (Stage 2). The questionnaire battery was completed by 226 participants. RESULTS: Descriptive statistics are reported on the endorsement of themes identified in Stage 1 and around participants' experiences of their carriership and healthcare. Results demonstrated that the participants have had a number of difficulties with accessing helpful information and support during key times in their lives, for example, at diagnosis and when deciding whether to start a family. They also showed that although participants endorsing a higher number of bleeding symptoms scored statistically significantly higher in measures of depression, anxiety and negative affect, this difference was not clinically significant. CONCLUSION: These results lend support to the growing evidence base that women who are carriers of haemophilia have a distinct set of (currently unmet) needs that need assessing and treating.

An analysis of the social, cultural, and ecological factors that affect the implementation of biosecurity measures on smallholder commercial swine farms in Italy in the context of an emerging African Swine Fever outbreak.

African Swine Fever (ASF) is a contagious viral disease that infects wild and domesticated swine. In early 2022, the virus was found in wild boar in the Apennine mountains of mainland Italy.2 Since then, it has spread from wild boar to domesticated swine. To control the spread of ASF, an effective surveillance system and the implementation of strict biosecurity measures on farms are required yet are unevenly implemented across husbandry systems. Smallholder farms in particular are known to have low levels of biosecurity. In the Apennine mountains of Italy, small commercial farms have been found to have low levels of biosecurity despite being located in areas with high densities of wild boar, and, hence, being high-risk sites for potential ASF incursion and subsequent diffusion. To address the question as to why the level of biosecurity is low, interviews and participant observation were conducted with smallholder commercial farmers. The interviews identified the social, cultural, and ecological factors that affect the implementation of biosecurity measures in small commercial swine farms in the Apennines. Farmers expressed knowledge of priority biosecurity measures and an overall willingness to follow rules and regulations; however, the application of the measures in practice was uneven across farms. Economic, political, and ecological factors as well as farmer beliefs about biosecurity emerged as important factors affecting the implementation of biosecurity measures. These include economic constraints, challenges posed by the mountain environment, a shifting regulatory environment, and ideas about animal welfare. Other important factors include cultural factors such as the use of traditional agricultural methods and norms about customer access to animals, time constraints and the perceived hassle of implementing the measures, farmer age, farmer relationships with government officials and veterinarians, and the role of pigs in reducing farm waste. The study confirmed that wild boar are present in high numbers and in close proximity to smallholder commercial farms in the Apennines.

Open Biceps Tenodesis and Tenotomy Have Low 30-Day Postoperative Complication Rates.

Purpose: To compare 30-day postoperative rates of adverse events, particularly infection rates, between open biceps tenodesis and biceps tenotomy. Methods: The American College of Surgeons National Surgical Quality Improvement Program was filtered using Current Procedural Terminology codes to identify patients undergoing open biceps tenodesis and tenotomy from 2010 to 2021. Patients were divided into cohorts based on procedure type. Propensity score matching was used to account for confounding variables. Statistical analyses were conducted to compare 30-day postoperative outcomes between cohorts, as well as to evaluate secondary risk factors for complications. Results: Overall, 12,367 patients were included in the study with 11,417 undergoing open biceps tenodesis and 950 undergoing biceps tenotomy. After matching, 1,900 patients were included in the final analysis. The rate of outpatient procedures in the tenodesis cohort was significantly higher than in the tenotomy cohort. Rates of any adverse event (AAE), sepsis, pneumonia, reoperation, and extended length of stay (LOS) were significantly higher in the tenotomy cohort compared with the tenodesis cohort. There was no difference in infection rates or wound dehiscence between the 2 groups. After multivariable analysis, increasing age, longer operative time, and history of bleeding disorders were associated with significantly higher odds of developing AAE. Conclusions: In this study, we found that tenotomy and open tenodesis are both safe options for treatment of biceps pathology. The overall rate of developing AAE and the rate of postoperative sepsis were higher in the tenotomy cohort. In addition, rates of postoperative infection and wound dehiscence did not vary between the 2 groups. Small differences were additionally observed in rates of pneumonia, return to the operating room, and extended LOS, and these rates were higher in the tenotomy cohort. Level of Evidence: Level III, retrospective comparative study.

Combining Wearable Technology and Telehealth Counseling for Rehabilitation After Lumbar Spine Surgery: Feasibility and Acceptability of a Physical Activity Intervention.

OBJECTIVE: The purpose of this study was to examine the feasibility and acceptability of a wearable device and telehealth counseling physical activity intervention early after lumbar spine surgery. METHODS: Sixteen patients were randomized to an 8-session physical activity intervention or to usual postoperative care after surgery. The intervention included a wearable device (ie, Fitbit) and telehealth counseling by a licensed physical therapist. The feasibility of study procedures was assessed through recruitment, randomization, retention, and participation rates. Acceptability was assessed through a satisfaction survey and median within-participant change in objective physical activity (steps per day and time spent in moderate-to-vigorous physical activity [MVPA]) and patient-reported outcomes. RESULTS: Of 64 participants who were eligible, recruitment and randomization rates were 41 and 62%, respectively. Retention for objective physical activity and patient-reported outcomes was 94 and 100%, respectively, at 6-month follow-up. Seven (88%) participants in the intervention group completed all telehealth sessions, and 6 (75%) met step goals over the 8 sessions. All participants in the intervention group found the wearable device and telehealth counseling to be helpful and reported it much or somewhat more important than other postoperative services. Median within-participant change for steps per day improved from baseline (preoperative) to 6 months after surgery for both the intervention (1070) and usual care (679) groups, while MVPA only improved for the intervention group (2.2. minutes per day). Improvements in back and leg pain and disability were noted for both groups. No adverse events were reported in the study. CONCLUSION: Combining wearable technology and telehealth counseling is a feasible approach to promote the physical activity during the early postoperative period after spine surgery. Future randomized controlled trials are needed to investigate the efficacy of leveraging wearables and telehealth during postoperative rehabilitation. IMPACT: This study has implications for the clinical dissemination of physical activity strategies in the rehabilitation setting.

Targeting refractory/recurrent neuroblastoma and osteosarcoma with anti-CD3×anti-GD2 bispecific antibody armed T cells.

BACKGROUND: The survival benefit observed in children with neuroblastoma (NB) and minimal residual disease who received treatment with anti-GD2 monoclonal antibodies prompted our investigation into the safety and potential clinical benefits of anti-CD3×anti-GD2 bispecific antibody (GD2Bi) armed T cells (GD2BATs). Preclinical studies demonstrated the high cytotoxicity of GD2BATs against GD2+cell lines, leading to the initiation of a phase I/II study in recurrent/refractory patients. METHODS: The 3+3 dose escalation phase I study (NCT02173093) encompassed nine evaluable patients with NB (n=5), osteosarcoma (n=3), and desmoplastic small round cell tumors (n=1). Patients received twice-weekly infusions of GD2BATs at 40, 80, or 160×106 GD2BATs/kg/infusion complemented by daily interleukin-2 (300,000 IU/m2) and twice-weekly granulocyte macrophage colony-stimulating factor (250 µg/m2). The phase II segment focused on patients with NB at the dose 3 level of 160×106 GD2BATs/kg/infusion. RESULTS: Of the 12 patients enrolled, 9 completed therapy in phase I with no dose-limiting toxicities. Mild and manageable cytokine release syndrome occurred in all patients, presenting as grade 2-3 fevers/chills, headaches, and occasional hypotension up to 72 hours after GD2BAT infusions. GD2-antibody-associated pain was minimal. Median overall survival (OS) for phase I and the limited phase II was 18.0 and 31.2 months, respectively, with a combined OS of 21.1 months. A phase I NB patient had a complete bone marrow response with overall stable disease. In phase II, 10 of 12 patients were evaluable: 1 achieved partial response, and 3 showed clinical benefit with prolonged stable disease. Over 50% of evaluable patients exhibited augmented immune responses to GD2+targets post-GD2BATs, as indicated by interferon-gamma (IFN-γ) EliSpots, Th1 cytokines, and/or chemokines. CONCLUSIONS: This study demonstrated the safety of GD2BATs up to 160×106 cells/kg/infusion. Coupled with evidence of post-treatment endogenous immune responses, our findings support further investigation of GD2BATs in larger phase II clinical trials.

Race-Related Differences in Sipuleucel-T Response among Men with Metastatic Castrate-Resistant Prostate Cancer.

Sipuleucel-T is an autologous cellular immunotherapy that targets prostatic acid phosphatase (PAP) and is available for treatment of men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). In this single-arm, two-cohort, multicenter clinical study, potential racial differences in immune responses to sipuleucel-T in men with mCRPC were explored. Patients' blood samples were obtained to assess serum cytokines, humoral responses, and cellular immunity markers before and after treatment. Baseline cumulative product parameters (total nucleated and CD54+ cell counts and CD54 upregulation) were evaluated. IgM titers against the immunogen PA2024, the target antigen PAP, prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA) were quantified by ELISA. Cytotoxic T-lymphocyte activity was determined by ELISpots, and cytokine and chemokine concentrations were determined by Luminex.Twenty-nine African American (AA) men and 28 non-African American (non-AA) men with mCRPC received sipuleucel-T. Baseline total nucleated cell count, CD54+ cell count, CD54 expression, and cumulative product parameters were higher in non-AA men. Although PSA baseline levels were higher in AA men, there were no racial differences in IgM antibody and IFNγ ELISpots responses against PA2024, PAP, PSA, and PSMA before and after treatment. Expression of co-stimulatory receptor ICOS on CD4+ and CD8+ T cells, and the levels of Th1 cytokine granulocyte-macrophage colony-stimulating factor and chemokines CCL4 and CCL5, were significantly higher in AA men before and/or after treatment. Despite no difference in the overall survival, PSA changes from baseline were significantly different between the two races. The data suggest that immune correlates in blood differ in AA and non-AA men with mCRPC pre- and post-sipuleucel-T. SIGNIFICANCE: Our novel findings of higher expression of co-stimulatory receptor ICOS on CD4+ and CD8+ T cells in African American patients with metastatic castrate-resistant prostate cancer (mCRPC) prior and post-sipuleucel-T suggest activation of CD4+ and CD8+ T cells. The data indicate that racial differences observed in these and other immune correlates before and after sipuleucel-T warrant additional investigation to further our understanding of the immune system in African American men and other men with mCRPC.

Phase II Trial of Pembrolizumab and Anti-CD3 x Anti-HER2 Bispecific Antibody-Armed Activated T Cells in Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: A phase II study was conducted to evaluate the safety and efficacy of the combination of HER2 bispecific antibody (HER2Bi)-armed activated T cells (HER2 BAT) and programmed death 1 inhibitor, pembrolizumab. PATIENTS AND METHODS: Patients with metastatic castration-resistant prostate cancer (mCRPC) with 0 to 1 performance status and normal liver, kidney, and marrow function, pre- or post-docetaxel chemotherapy were eligible. Primary endpoint was 6-month progression-free survival (PFS). Peripheral blood mononuclear cells were obtained by a single apheresis, shipped to University of Virginia, activated with OKT3 and expanded for 14 days in IL2, harvested, and armed with HER2Bi and cryopreserved. HER2 BATs were infused twice weekly for 4 weeks and pembrolizumab was administered every 21 days for a maximum duration of 6 months starting 1 to 3 weeks prior to HER2 BATs infusion. RESULTS: Fourteen patients were enrolled with a median age of 69 (range 57-82 years) and median PSA of 143.4 (range 8.2-4210 ng/dL). Two patients had peritoneal metastases, 1 had lymph node (LN) only metastases and 11 had bone metastases of which 7 had bone and LN metastases. All were pretreated with androgen receptor axis targeted agents and 7 (50%) had prior docetaxel chemotherapy. The toxicities were grade1-2 infusion reactions with fever, chills, headaches, nausea and/or myalgias. Primary endpoint of 6 month PFS was achieved in 5 of 14 patients (38.5%; 95% confidence interval, 19.5%-76.5%). Median PFS was 5 months and median survival was 31.6 months. CONCLUSIONS: The safety and promising efficacy makes this combination worthy of future investigation in mCRPC.

Dried blood spot microbiological assay indicates high prevalence of folate deficiency in rural adult men and women in the Haitian Central Plateau.

BACKGROUND: Although folate deficiency is linked to adverse health effects, limited data exist characterizing the problem in rural settings. This study determined the prevalence of folate deficiency and anemia in rural adults in the Haitian Central Plateau using combined laboratory methods. METHODS: Dried blood spots (DBSs) and hemoglobin measurements were collected from adult men and women selected by cluster random sampling in Haiti's Central Plateau. DBSs were analyzed for folate using a microbiological assay. Hemoglobin levels were determined using both a HemoCue photometer and the sodium lauryl sulfate microplate method. Red cell folate (RCF) levels were determined by normalizing DBS folate to hemoglobin. RESULTS: Of the 197 subjects assessed for hemoglobin, 11.4% of males and 21.0% of females were anemic (male: hemoglobin<12 g/dL; female: hemoglobin<11 g/dL). Of the 173 subjects assessed for RCF, 27.9% of men and 14.9% of women were folate deficient (RCF<340 nmol/L). Among reproductive-age women, 83.6% had RCF levels associated with a risk of neural tube defects of >14 per 10 000 live births (RCF≤699 nmol/L). CONCLUSIONS: Adults in the Haitian Central Plateau suffer from high rates of anemia and folate deficiency, putting the population at elevated risk for disease. DBSs and microbiological assay make folate evaluation feasible, even in low-resource regions.

An open-source analytical platform for analysis of C. elegans swimming-induced paralysis.

BACKGROUND: The nematode Caenhorhabditis elegans offers great power for the identification and characterization of genes that regulate behavior. In support of this effort, analytical methods are required that provide dimensional analyses of subcomponents of behavior. Previously, we demonstrated that loss of the presynaptic dopamine (DA) transporter, dat-1, evokes DA-dependent Swimming-Induced Paralysis (Swip) (Mcdonald et al., 2007), a behavior compatible with forward genetic screens (Hardaway et al., 2012). NEW METHOD: Here, we detail the development and implementation of SwimR, a set of tools that provide for an automated, kinetic analysis of C. elegans Swip. SwimR relies on open source programs that can be freely implemented and modified. RESULTS: We show that SwimR can display time-dependent alterations of swimming behavior induced by drug-treatment, illustrating this capacity with the dat-1 blocker and tricyclic antidepressant imipramine (IMI). We demonstrate the capacity of SwimR to extract multiple kinetic parameters that are impractical to obtain in manual assays. COMPARISON WITH EXISTING METHODS: Standard measurements of C. elegans swimming utilizes manual assessments of the number of animals exhibiting swimming versus paralysis. Our approach deconstructs the time course and rates of movement in an automated fashion, offering a significant increase in the information that can be obtained from swimming behavior. CONCLUSIONS: The SwimR platform is a powerful tool for the deconstruction of worm thrashing behavior in the context of both genetic and pharmacological manipulations that can be used to segregate pathways that underlie nematode swimming mechanics.

Forward genetic analysis to identify determinants of dopamine signaling in Caenorhabditis elegans using swimming-induced paralysis.

Disrupted dopamine (DA) signaling is believed to contribute to the core features of multiple neuropsychiatric and neurodegenerative disorders. Essential features of DA neurotransmission are conserved in the nematode Caenorhabditis elegans, providing us with an opportunity to implement forward genetic approaches that may reveal novel, in vivo regulators of DA signaling. Previously, we identified a robust phenotype, termed Swimming-induced paralysis (Swip), that emerges in animals deficient in the plasma membrane DA transporter. Here, we report the use and quantitative analysis of Swip in the identification of mutant genes that control DA signaling. Two lines captured in our screen (vt21 and vt22) bear novel dat-1 alleles that disrupt expression and surface trafficking of transporter proteins in vitro and in vivo. Two additional lines, vt25 and vt29, lack transporter mutations but exhibit genetic, biochemical, and behavioral phenotypes consistent with distinct perturbations of DA signaling. Our studies validate the utility of the Swip screen, demonstrate the functional relevance of DA transporter structural elements, and reveal novel genomic loci that encode regulators of DA signaling.

Neural developmental changes in processing inverted faces.

We explored developmental changes in neural substrates for face processing, using fMRI. Children and adults performed a perceptual-matching task with upright and inverted face and animal stimuli. Behaviorally, inversion disrupted face processing more than animal processing for adults and older children. In line with this behavioral pattern, the left middle occipital gyrus showed a strongerface than animal inversion effect in adults. Moreover, a superior aspect of this region showed a greater face inversion effect in older than in younger children, indicating a developmental change in the processing of inverted faces. The visual regions recruited for inverted face processing in adults also overlapped more with brain regions involved in the viewing of upright objects than with regions involved in the viewing of upright faces in an independent localizer task. Hence, when faces are inverted, adults recruit regions normally engaged for recognizing objects, possibly pointing to a role for the featural processing of inverted faces.