Lower Extremity Amputation in Fracture-Related Infection.

OBJECTIVES: To analyze demographics, comorbidities, fracture characteristics, presenting characteristics, microbiology, and treatment course of patients with fracture-related infections (FRIs) to determine risk factors leading to amputation. DESIGN: Retrospective cohort. SETTING: Single Level I Trauma Center (2013-2020). PATIENT SELECTION CRITERIA: Adults with lower extremity (femur and tibia) FRIs were identified through a review of an institutional database. Inclusion criteria were operatively managed fracture of the femur or tibia with an FRI and adequate documentation present in the electronic medical record. This included patients whose primary injury was managed at this institution and who were referred to this institution after the onset of FRI as long as all characteristics and risk factors assessed in the analysis were documented. Exclusion criteria were infected chronic osteomyelitis from a non-fracture-related pathology and a follow-up of less than 6 months. OUTCOME MEASURES AND COMPARISONS: Risk factors (demographics, comorbidities, and surgical, injury, and perioperative characteristics) leading to amputation in patients with FRIs were evaluated. RESULTS: A total of 196 patients were included in this study. The average age of the study group was 44±16 years. Most patients were men (63%) and White (71%). The overall amputation rate was 9.2%. There were significantly higher rates of chronic kidney disease (CKD; P = 0.039), open fractures (P = 0.034), transfusion required during open reduction internal fixation (P = 0.033), Gram-negative infections (P = 0.048), and FRI-related operations (P = 0.001) in the amputation cohort. On multivariate, patients with CKD were 28.8 times more likely to undergo amputation (aOR = 28.8 [2.27 to 366, P = 0.010). A subanalysis of 79 patients with either a methicillin-sensitive Staphylococcus aureus or methicillin-resistant S. aureus (MRSA) infection showed that patients with MRSA were significantly more likely to undergo amputation compared with patients with methicillin-sensitive Staphylococcus aureus (P = 0.031). MRSA was present in all cases of amputation in the Staphylococcal subanalysis. CONCLUSIONS: Findings from this study highlight CKD as a risk factor of amputation in the tibia and femur with fracture-related infection. In addition, MRSA was present in all cases of Staphylococcal amputation. Identifying patients and infection patterns that carry a higher risk of amputation can assist surgeons in minimizing the burden on these individuals. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Staged Management for Distal Femur Fractures: Impacts on Reoperation, Stiffness, and Overall Outcomes.

OBJECTIVES: To evaluate the outcomes of staged management with external fixation (ex-fix) prior to definitive fixation of distal femur fractures. METHODS: Design: Retrospective cohort. SETTING: Single Level I Trauma Center. PATIENT SELECTION CRITERIA: Adults treated operatively between 2004 and 2019 for distal femur fractures (OTA/AO 33A/33C) were identified using Current Procedural Terminology codes. Excluded cases were those with screw only fixation, acute distal femur replacement, 33B fracture pattern, no radiographs available, or did not have 6-months of follow-up. OUTCOME MEASURES AND COMPARISONS: Postoperative complication rates including surgical site infection [SSI], reoperation to promote bone healing, final knee arc of motion <90 degrees, heterotopic ossification formation, and reoperation for stiffness were compared between patients treated with ex-fix prior to definitive fixation and those not requiring ex-fix. RESULTS: A total of 407 patients were included with a mean follow-up of 27 months (median [IQR] of 12 [7,33] months), (range 6-192 months). Most patients were male (52%) with an average age of 48 [Range: 18-92] years. Ex-fix was utilized in 150 (37%) cases and 257 (63%) cases underwent primary definitive fixation. There was no difference in SSI rates (p=0.12), final knee arc of motion <90 degrees (p=0.51), and reoperation for stiffness (p=0.41) between the ex-fix and no ex-fix groups. The 150 patients requiring ex-fix spent an average of 4.2 days (SD 3.3) in the ex-fix before definitive fixation. These patients were further analyzed by comparing the duration of time spent in ex-fix, <4 days (n=82) and ≥4 days (n=68). Despite longer time spent in ex-fix prior to definitive fixation, there was again no significant difference in any of the complication and reoperation rates when comparing the two groups, including final knee arc of motion <90 degrees (p=0.63), reoperation for stiffness (p=1.00), and SSI (p=0.79). CONCLUSION: Ex-fix of distal femur fractures as a means of temporary stabilization prior to definitive ORIF does not increase the risk of complications such as SSI, final knee arc of motion <90 degrees, or reoperations for bone healing or stiffness when compared to single stage ORIF of distal femur fractures. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Variability in white matter structure relates to hallucination proneness.

Hallucinations are a prominent transdiagnostic psychiatric symptom but are also prevalent in individuals who do not require clinical care. Moreover, persistent psychosis-like experience in otherwise healthy individuals may be related to an increased risk to transition to a psychotic disorder. This suggests a common etiology across clinical and non-clinical individuals along a multidimensional psychosis continuum that may be detectable in structural variations of the brain. The current diffusion tensor imaging study assessed 50 healthy individuals (35 females) to identify possible differences in white matter associated with hallucination proneness (HP). This approach circumvents potential confounds related to medication, hospitalization, and disease progression common in clinical individuals. We determined how HP relates to white matter structure in selected association, commissural, and projection fiber pathways putatively linked to psychosis. Increased HP was associated with enhanced fractional anisotropy (FA) in the right uncinate fasciculus, the right anterior and posterior arcuate fasciculus, and the corpus callosum. These findings support the notion of a psychosis continuum, providing first evidence of structural white matter variability associated with HP in healthy individuals. Furthermore, alterations in the targeted pathways likely indicate an association between HP-related structural variations and the putative salience and attention mechanisms that these pathways subserve.

Eco-evolutionary Guided Pathomic Analysis to Predict DCIS Upstaging.

Cancers evolve in a dynamic ecosystem. Thus, characterizing cancer's ecological dynamics is crucial to understanding cancer evolution and can lead to discovering novel biomarkers to predict disease progression. Ductal carcinoma in situ (DCIS) is an early-stage breast cancer characterized by abnormal epithelial cell growth confined within the milk ducts. Although there has been extensive research on genetic and epigenetic causes of breast carcinogenesis, none of these studies have successfully identified a biomarker for the progression and/or upstaging of DCIS. In this study, we show that ecological habitat analysis of hypoxia and acidosis biomarkers can significantly improve prediction of DCIS upstaging. First, we developed a novel eco-evolutionary designed approach to define habitats in the tumor intra-ductal microenvironment based on oxygen diffusion distance in our DCIS cohort of 84 patients. Then, we identify cancer cells with metabolic phenotypes attributed to their habitat conditions, such as the expression of CA9 indicating hypoxia responding phenotype, and LAMP2b indicating a hypoxia-induced acid adaptation. Traditionally these markers have shown limited predictive capabilities for DCIS upstaging, if any. However, when analyzed from an ecological perspective, their power to differentiate between indolent and upstaged DCIS increased significantly. Second, using eco-evolutionary guided computational and digital pathology techniques, we discovered distinct spatial patterns of these biomarkers and used the distribution of such patterns to predict patient upstaging. The patterns were characterized by both cellular features and spatial features. With a 5-fold validation on the biopsy cohort, we trained a random forest classifier to achieve the area under curve(AUC) of 0.74. Our results affirm the importance of using eco-evolutionary-designed approaches in biomarkers discovery studies in the era of digital pathology by demonstrating the role of eco-evolution dynamics in predicting cancer progression.

Use of locking fibular plates versus non-locking dual plate fixation: A biomechanical study.

Introduction: Distal fibula osteoporotic comminuted fractures are challenging to treat and are often treated with periarticular locking plates. This study examined the biomechanical difference between locked plating and dual non-locked one-third tubular plating. Methods: Using an osteoporotic Sawbones fibula model, simulated fracture were fixated with one-third tubular dual plating and locked periarticular plating. The samples were then torqued to failure and peak torque, stiffness, and displacement were recorded. Results: The peak torque of the dual plating group was found to be statistically higher than the periarticular locked plating group (0.841 Nm and 0.740 Nm respectively; p = 0.024). However overall stiffness calculated at each 10° increment of displacement was noted to have no significant difference between the two constructs. Conclusion: Dual non-locked plating of distal fibula osteoporotic comminuted fractures is biomechanically equivalent to locked periarticular plating.

Global 30-Day Morbidity and Mortality of Primary Bariatric Surgery Combined with Another Procedure: The BLEND Study.

BACKGROUND: No robust data are available on the safety of primary bariatric and metabolic surgery (BMS) alone compared to primary BMS combined with other procedures. OBJECTIVES: The objective of this study is to collect a 30-day mortality and morbidity of primary BMS combined with cholecystectomy, ventral hernia repair, or hiatal hernia repair. SETTING: This is as an international, multicenter, prospective, and observational audit of patients undergoing primary BMS combined with one or more additional procedures. METHODS: The audit took place from January 1 to June 30, 2022. A descriptive analysis was conducted. A propensity score matching analysis compared the BLEND study patients with those from the GENEVA cohort to obtain objective evaluation between combined procedures and primary BMS alone. RESULTS: A total of 75 centers submitted data on 1036 patients. Sleeve gastrectomy was the most commonly primary BMS (N = 653, 63%), and hiatal hernia repair was the most commonly concomitant procedure (N = 447, 43.1%). RYGB accounted for the highest percentage (20.6%) of a 30-day morbidity, followed by SG (10.5%). More than one combined procedures had the highest morbidities among all combinations (17.1%). Out of overall 134 complications, 129 (96.2%) were Clavien-Dindo I-III, and 4 were CD V. Patients who underwent a primary bariatric surgery combined with another procedure had a pronounced increase in a 30-day complication rate compared with patients who underwent only BMS (12.7% vs. 7.1%). CONCLUSION: Combining BMS with another procedure increases the risk of complications, but most are minor and require no further treatment. Combined procedures with primary BMS is a viable option to consider in selected patients following multi-disciplinary discussion.

Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release.

Nociceptin/orphanin-FQ (N/OFQ) is a recently appreciated critical opioid peptide with key regulatory functions in several central behavioral processes including motivation, stress, feeding, and sleep. The functional relevance of N/OFQ action in the mammalian brain remains unclear due to a lack of high-resolution approaches to detect this neuropeptide with appropriate spatial and temporal resolution. Here we develop and characterize NOPLight, a genetically encoded sensor that sensitively reports changes in endogenous N/OFQ release. We characterized the affinity, pharmacological profile, spectral properties, kinetics, ligand selectivity, and potential interaction with intracellular signal transducers of NOPLight in vitro. Its functionality was established in acute brain slices by exogeneous N/OFQ application and chemogenetic induction of endogenous N/OFQ release from PNOC neurons. In vivo studies with fibre photometry enabled direct recording of NOPLight binding to exogenous N/OFQ receptor ligands, as well as detection of endogenous N/OFQ release within the paranigral ventral tegmental area (pnVTA) during natural behaviors and chemogenetic activation of PNOC neurons. In summary, we show here that NOPLight can be used to detect N/OFQ opioid peptide signal dynamics in tissue and freely behaving animals.

Impact of the Timing of Percutaneous Catheter Drainage following Endoscopic Drainage on Outcomes in Acute Necrotizing Pancreatitis.

Background The role of dual-modality drainage of walled-off necrosis (WON) in patients with acute pancreatitis (AP) is established. However, there are no data on the association of clinical outcomes with the timing of percutaneous catheter drainage (PCD). We investigated the impact of the timing of PCD following endoscopic drainage of WON on clinical outcomes in AP. Materials and Methods This retrospective study comprised consecutive patients with necrotizing AP who underwent endoscopic cystogastrostomy (CG) of WON followed by PCD between September 2018 and March 2023. Based on endoscopic CG to PCD interval, patients were divided into groups (≤ and >3 days, ≤ and >1 week, ≤ and >10 days, and ≤ and >2 weeks). Baseline characteristics and indications of CG and PCD were recorded. Clinical outcomes were compared between the groups, including length of hospitalization, length of intensive care unit stay, need for surgical necrosectomy, and death during hospitalization. Results Thirty patients (mean age ± standard deviation, 35.5 ± 12.7 years) were evaluated. The mean CG to PCD interval was 11.2 ± 7.5 days. There were no significant differences in baseline characteristics and indications of CG and PCD between the groups. The mean pain to CG interval was not significantly different between the groups. Endoscopic necrosectomy was performed in a significantly greater proportion of patients undergoing CG after 10 days ( p = 0.003) and after 2 weeks ( p = 0.032). There were no significant differences in the complications and clinical outcomes between the groups. Conclusion The timing of PCD following endoscopic CG does not affect clinical outcomes.

Capture rates of Eptesicus fuscus increase following white-nose syndrome across the eastern US.

Emerging infectious diseases threaten wildlife globally. While the effects of infectious diseases on hosts with severe infections and high mortality rates often receive considerable attention, effects on hosts that persist despite infection are less frequently studied. To understand how persisting host populations change in the face of disease, we quantified changes to the capture rates of Eptesicus fuscus (big brown bats), a persisting species susceptible to infection by the invasive fungal pathogen Pseudogymnoascus destructans (Pd; causative agent for white-nose syndrome), across the eastern US using a 30-year dataset. Capture rates of male and female E. fuscus increased from preinvasion to pathogen establishment years, with greater increases to the capture rates of females than males. Among females, capture rates of pregnant and post-lactating females increased by pathogen establishment. We outline potential mechanisms for these broad demographic changes in E. fuscus capture rates (i.e., increases to foraging from energy deficits created by Pd infection, increases to relative abundance, or changes to reproductive cycles), and suggest future research for identifying mechanisms for increasing capture rates across the eastern US. These data highlight the importance of understanding how populations of persisting host species change following pathogen invasion across a broad spatial scale. Understanding changes to population composition following pathogen invasion can identify broad ecological patterns across space and time, and open new avenues for research to identify drivers of those patterns.

Colchicine and/or Naltrexone for Hospitalized COVID-19 Patients Not Requiring High Levels of Ventilatory Support (COLTREXONE): A Prospective, Randomized, Open-Label Trial.

We assessed the efficacy and safety of colchicine and low-dose naltrexone (LDN), alone and in combination, in preventing progression to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this prospective, randomized, open-label trial, colchicine and LDN were compared to standard of care (SOC) in patients hospitalized with SARS-CoV-2 not requiring high levels of ventilatory support. Patients were randomly assigned to colchicine alone, LDN alone, colchicine/LDN in combination, or SOC. The primary outcome was time to disease recovery. Secondary outcomes included total time hospitalized, study enrollment, level of care, oxygen support, and adverse events.  One-hundred and thirty-seven patients were randomized (Nc = 34, Nc+ldn = 33, Nldn = 35, Nsoc = 35). Eighty-four patients (61%) achieved disease recovery by day 5. There was no significant difference in the proportion of patients who experienced the primary efficacy outcome among those who received colchicine, LDN, or between the four study arms.Patients receiving colchicine had a shorter length of enrollment but not a significant reduction in the length of stay. Diarrhea was the most common adverse reaction. In adults hospitalized with SARS-CoV-2 not requiring high-level ventilatory support, colchicine and LDN, alone and in combination, were not associated with significant reductions in progression to severe disease.

Variational solution to the lattice Boltzmann method for Couette flow.

Literature studies of the lattice Boltzmann method (LBM) demonstrate hydrodynamics beyond the continuum limit. This includes exact analytical solutions to the LBM, for the bulk velocity and shear stress of Couette flow under diffuse reflection at the walls through the solution of equivalent moment equations. We prove that the bulk velocity and shear stress of Couette flow with Maxwell-type boundary conditions at the walls, as specified by two-dimensional isothermal lattice Boltzmann models, are inherently linear in Mach number. Our finding enables a systematic variational approach to be formulated that exhibits superior computational efficiency than the previously reported moment method. Specifically, the number of partial differential equations (PDEs) in the variational method grows linearly with quadrature order while the number of moment method PDEs grows quadratically. The variational method directly yields a system of linear PDEs that provide exact analytical solutions to the LBM bulk velocity field and shear stress for Couette flow with Maxwell-type boundary conditions. It is anticipated that this variational approach will find utility in calculating analytical solutions for novel lattice Boltzmann quadrature schemes and other flows.

Developmental and adult striatal patterning of nociceptin ligand marks striosomal population with direct dopamine projections.

Circuit influences on the midbrain dopamine system are crucial to adaptive behavior and cognition. Recent developments in the study of neuropeptide systems have enabled high-resolution investigations of the intersection of neuromodulatory signals with basal ganglia circuitry, identifying the nociceptin/orphanin FQ (N/OFQ) endogenous opioid peptide system as a prospective regulator of striatal dopamine signaling. Using a prepronociceptin-Cre reporter mouse line, we characterized highly selective striosomal patterning of Pnoc mRNA expression in mouse dorsal striatum, reflecting early developmental expression of Pnoc . In the ventral striatum, Pnoc expression was was clustered across the nucleus accumbens core and medial shell, including in adult striatum. We found that Pnoc tdTomato reporter cells largely comprise a population of dopamine receptor D1 ( Drd1 ) expressing medium spiny projection neurons localized in dorsal striosomes, known to be unique among striatal projections neurons for their direct innervation of midbrain dopamine neurons. These findings provide new understanding of the intersection of the N/OFQ system among basal ganglia circuits with particular implications for developmental regulation or wiring of striatal-nigral circuits.

Resilience Improves Patient-Reported Outcomes After Orthopaedic Trauma.

OBJECTIVES: To analyze the relationship between patient resilience and patient-reported outcomes after orthopaedic trauma. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Single Level 1 Trauma Center. PATIENT SELECTION CRITERIA: Patients were selected based on completion of the Patient-Reported Outcomes Measurement Information System (PROMIS) and Brief Resilience Scale (BRS) surveys 6 months after undergoing operative fracture fixation following orthopaedic trauma. Patients were excluded if they did not complete all PROMIS and BRS surveys. OUTCOME MEASURES AND COMPARISONS: Resilience, measured by the BRS, was analyzed for its effect on patient-reported outcomes, measured by PROMIS Global Physical Health, Physical Function, Pain Interference, Global Mental Health, Depression, and Anxiety. Variables collected were demographics (age, gender, race, body mass index), injury severity score, and postoperative complications (nonunion, infection). All variables were analyzed with univariate for effect on all PROMIS scores. Variables with significance were included in multivariate analysis. Patients were then separated into high resilience (BRS >4.3) and low resilience (BRS <3.0) groups for additional analysis. RESULTS: A total of 99 patients were included in the analysis. Most patients were male (53%) with an average age of 47 years. Postoperative BRS scores significantly correlated with PROMIS Global Physical Health, Pain Interference, Physical Function, Global Mental Health, Depression, and Anxiety ( P ≤ 0.001 for all scores) at 6 months after injury on both univariate and multivariate analyses. The high resilience group had significantly higher PROMIS Global Physical Health, Physical Function, and Global Mental Health scores and significantly lower PROMIS Pain Interference, Depression, and Anxiety scores ( P ≤ 0.001 for all scores). CONCLUSIONS: Resilience in orthopaedic trauma has a positive association with patient outcomes at 6 months postoperatively. Patients with higher resilience report higher scores in all PROMIS categories regardless of injury severity. Future studies directed at increasing resilience may improve outcomes in patients who experience orthopaedic trauma. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Histology-guided mathematical model of tumor oxygenation: sensitivity analysis of physical and computational parameters.

A hybrid off-lattice agent-based model has been developed to reconstruct the tumor tissue oxygenation landscape based on histology images and simulated interactions between vasculature and cells with microenvironment metabolites. Here, we performed a robustness sensitivity analysis of that model's physical and computational parameters. We found that changes in the domain boundary conditions, the initial conditions, and the Michaelis constant are negligible and, thus, do not affect the model outputs. The model is also not sensitive to small perturbations of the vascular influx or the maximum consumption rate of oxygen. However, the model is sensitive to large perturbations of these parameters and changes in the tissue boundary condition, emphasizing an imperative aim to measure these parameters experimentally.

Pathogenic Roles for RNASET2 in Clear Cell Renal Cell Carcinoma.

A specific splicing isoform of RNASET2 is associated with worse oncologic outcomes in clear cell renal cell carcinoma (ccRCC). However, the interplay between wild-type RNASET2 and its splice variant and how this might contribute to the pathogenesis of ccRCC remains poorly understood. We sought to better understand the relationship of RNASET2 in the pathogenesis of ccRCC and the interplay with a pathogenic splicing isoform (RNASET2-SV) and the tumor immune microenvironment. Using data from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium, we correlated clinical variables to RNASET2 expression and the presence of a specific RNASET2-SV. Immunohistochemical staining with matched RNA sequencing of ccRCC patients was then utilized to understand the spatial relationships of RNASET2 with immune cells. Finally, in vitro studies were performed to demonstrate the oncogenic role of RNASET2 and highlight its potential mechanisms. RNASET2 gene expression is associated with higher grade tumors and worse overall survival in The Cancer Genome Atlas cohort. The presence of the RNASET2-SV was associated with increased expression of the wild-type RNASET2 protein and epigenetic modifications of the gene. Immunohistochemical staining revealed increased intracellular accumulation of RNASET2 in patients with increased RNA expression of RNASET2-SV. In vitro experiments reveal that this accumulation results in increased cell proliferation, potentially from altered metabolic pathways. RNASET2 exhibits a tumor-promoting role in the pathogenesis of ccRCC that is increased in the presence of a specific RNASET2-SV and associated with changes in the cellular localization of the protein.

Characteristics of Femoral Shaft Fractures That Predict Ipsilateral Femoral Neck Fractures.

INTRODUCTION: This study aims to characterize radiographic features and fracture characteristics in femoral shaft fractures with associated femoral neck fractures, with the goal of establishing predictive indicators for the presence of ipsilateral femoral neck fractures (IFNFs). METHODS: A retrospective cohort was collected from the electronic medical record of three level I trauma centers over a 5-year period (2017 to 2022) by current procedural terminology (CPT) codes. Current CPT codes for combined femoral shaft and IFNFs were identified to generate our study group. CPT codes for isolated femur fractures were identified to generate a control group. RESULTS: One hundred forty patients comprised our IFNF cohort, and 280 comprised the control cohort. On univariate, there were significant differences in mechanism of injury (P < 0.001), Orthopedic Trauma Association (OTA)/Arbeitsgemeinshaft fur Osteosynthesefragen (AO) classification (P = 0.002), and fracture location (P < 0.001) between cohorts. On multivariate, motor vehicle crashes were more commonly associated with IFNFs compared with other mechanism of injuries. OTA/AO 32A fractures were more commonly associated with IFNFs when compared with OTA/AO 32B fractures (adjusted odds ratio = 0.36, P < 0.001). Fractures through the isthmus were significantly more commonly associated with IFNFs than fractures more proximal (adjusted odds ratio = 2.52, P = 0.011). DISCUSSION: Detecting IFNFs in femoral shaft fractures is challenging. Motor vehicle crashes and motorcycle collisions, OTA/AO type 32A fractures, and isthmus fractures are predictive of IFNFs.

Androgen drives melanoma invasiveness and metastatic spread by inducing tumorigenic fucosylation.

Melanoma incidence and mortality rates are historically higher for men than women. Although emerging studies have highlighted tumorigenic roles for the male sex hormone androgen and its receptor (AR) in melanoma, cellular and molecular mechanisms underlying these sex-associated discrepancies are poorly defined. Here, we delineate a previously undisclosed mechanism by which androgen-activated AR transcriptionally upregulates fucosyltransferase 4 (FUT4) expression, which drives melanoma invasiveness by interfering with adherens junctions (AJs). Global phosphoproteomic and fucoproteomic profiling, coupled with in vitro and in vivo functional validation, further reveal that AR-induced FUT4 fucosylates L1 cell adhesion molecule (L1CAM), which is required for FUT4-increased metastatic capacity. Tumor microarray and gene expression analyses demonstrate that AR-FUT4-L1CAM-AJs signaling correlates with pathological staging in melanoma patients. By delineating key androgen-triggered signaling that enhances metastatic aggressiveness, our findings help explain sex-associated clinical outcome disparities and highlight AR/FUT4 and its effectors as potential prognostic biomarkers and therapeutic targets in melanoma.

Effective conservation of subterranean-roosting bats.

Bats frequently inhabit caves and other subterranean habitats and play a critical role in subterranean food webs. With escalating threats to subterranean ecosystems, identifying the most effective measures to protect subterranean-roosting bats is critical. We conducted a meta-analysis to evaluate the effectiveness of conservation and management interventions for subterranean-roosting bats. We used network analyses to determine to what extent interventions for bats overlap those used for other subterranean taxa. We conducted our analyses with data extracted from 345 papers recommending a total of 910 conservation interventions. Gating of roost entrances was applied to preserve bat populations in 21 studies, but its effectiveness was unclear. Habitat restoration and disturbance reduction positively affected bat populations and bat behavior, respectively, in ≤4 studies. Decontamination was assessed in 2 studies and positively affected bat populations, particularly in studies focused on reducing fungal spores associated with white-nose syndrome in North America. Monitoring of bat populations as an effective conservation strategy was unclear and infrequently tested. Only 4% of bat studies simultaneously considered other subterranean organisms. However, effective interventions for bat conservation had similarities with all other organisms. If other subterranean organisms are considered when applying interventions to conserve bats, they might also benefit.

Conservación eficiente de murciélagos subterráneos Resumen Es común que los murciélagos habiten en cuevas y otros hábitats subterráneos y contribuyan a las redes alimenticias bajo tierra. Ya que estos ecosistemas cada vez se enfrentan a más amenazas, es importante identificar las medidas más efectivas para proteger a los murciélagos subterráneos. Realizamos un metaanálisis para evaluar la eficiencia de la conservación y las intervenciones de manejo para estos mamíferos. Usamos un análisis de redes para determinar el grado al que las intervenciones en pro de los murciélagos se traslapan con aquellas usadas para otros taxones subterráneos. Realizamos nuestros análisis con datos extraídos de 345 artículos que recomendaban 910 intervenciones de conservación. Se aplicó la colocación de compuertas en la entrada de los dormideros para conservar la población de murciélagos en 21 estudios, pero no quedó clara su efectividad. La restauración del hábitat y la reducción de las perturbaciones afectaron, respectivamente, a las poblaciones y al comportamiento de los murciélagos en ≤ 4 cuatro estudios. Se evaluó a la desinfección en dos estudios y ésta tuvo un efecto positivo sobre las poblaciones, particularmente en los estudios enfocados en la reducción de esporas micóticas asociadas con el síndrome de nariz blanca en América del Norte. La eficiencia del monitoreo de las poblaciones de murciélagos como una estrategia de conservación no fue clara y casi nunca se evaluó. Sólo el 4% de los estudios sobre murciélagos consideró simultáneamente a otros organismos subterráneos. Sin embargo, las intervenciones eficientes para la conservación de murciélagos tuvieron similitudes con las de todos los demás organismos. Otros organismos pueden beneficiarse si se les considera cuando se aplican las intervenciones para conservar a los murciélagos.

Coronoid Fragment Size in Monteggia Fractures Predicts Ultimate Function.

We sought to determine what effect the size of a displaced coronoid fracture fragment in Monteggia injuries has on clinical outcome. Sixty-seven patients presented to an academic medical center for operative fixation of a Monteggia fracture. Radiographs were assessed for length and height of the displaced coronoid fragment using measuring tools in our center's imaging archive system. Data were analyzed using binary logistic or linear regression, as appropriate, controlling for sex, age, and Charlson Comorbidity Index. Outcome measurements included radiographic healing, range of motion, postoperative complications, and reoperation. The cohort had a mean follow-up of 16.7 months. Mean coronoid fragment area was 362.4±155.9 mm2. Elbow range of motion decreased by 3.8° of elbow flexion (P<.001), 3.3° of elbow extension (P<.001), and 3.8° of forearm supination (P=.007) for every 1-cm2 increase in coronoid fragment area. Complications (P=.012) and reoperation (P=.036) were associated with increasing coronoid fragment area. Nonunion rate, nerve injury, and pronation range of motion were not correlated to increasing coronoid fracture fragment area (P=.777, P=.123, and P=.351, respectively). As displaced coronoid fragment size increases in Monteggia fracture patterns, elbow range of motion decreases linearly. Coronoid displacement was also associated with increased rates of postoperative complication and need for reoperation. [Orthopedics. 2024;47(1):15-21.].

Targeting intracellular oncoproteins with dimeric IgA promotes expulsion from the cytoplasm and immune-mediated control of epithelial cancers.

Dimeric IgA (dIgA) can move through cells via the IgA/IgM polymeric immunoglobulin receptor (PIGR), which is expressed mainly on mucosal epithelia. Here, we studied the ability of dIgA to target commonly mutated cytoplasmic oncodrivers. Mutation-specific dIgA, but not IgG, neutralized KRASG12D within ovarian carcinoma cells and expelled this oncodriver from tumor cells. dIgA binding changed endosomal trafficking of KRASG12D from accumulation in recycling endosomes to aggregation in the early/late endosomes through which dIgA transcytoses. dIgA targeting of KRASG12D abrogated tumor cell proliferation in cell culture assays. In vivo, KRASG12D-specific dIgA1 limited the growth of KRASG12D-mutated ovarian and lung carcinomas in a manner dependent on CD8+ T cells. dIgA specific for IDH1R132H reduced colon cancer growth, demonstrating effective targeting of a cytoplasmic oncodriver not associated with surface receptors. dIgA targeting of KRASG12D restricted tumor growth more effectively than small-molecule KRASG12D inhibitors, supporting the potential of this approach for the treatment of human cancers.