Temporal Control of Mammalian Cortical Neurogenesis by m6A Methylation.

N6-methyladenosine (m6A), installed by the Mettl3/Mettl14 methyltransferase complex, is the most prevalent internal mRNA modification. Whether m6A regulates mammalian brain development is unknown. Here, we show that m6A depletion by Mettl14 knockout in embryonic mouse brains prolongs the cell cycle of radial glia cells and extends cortical neurogenesis into postnatal stages. m6A depletion by Mettl3 knockdown also leads to a prolonged cell cycle and maintenance of radial glia cells. m6A sequencing of embryonic mouse cortex reveals enrichment of mRNAs related to transcription factors, neurogenesis, the cell cycle, and neuronal differentiation, and m6A tagging promotes their decay. Further analysis uncovers previously unappreciated transcriptional prepatterning in cortical neural stem cells. m6A signaling also regulates human cortical neurogenesis in forebrain organoids. Comparison of m6A-mRNA landscapes between mouse and human cortical neurogenesis reveals enrichment of human-specific m6A tagging of transcripts related to brain-disorder risk genes. Our study identifies an epitranscriptomic mechanism in heightened transcriptional coordination during mammalian cortical neurogenesis.

N6-methyldeoxyadenosine marks active transcription start sites in Chlamydomonas.

N(6)-methyldeoxyadenosine (6mA or m(6)A) is a DNA modification preserved in prokaryotes to eukaryotes. It is widespread in bacteria and functions in DNA mismatch repair, chromosome segregation, and virulence regulation. In contrast, the distribution and function of 6mA in eukaryotes have been unclear. Here, we present a comprehensive analysis of the 6mA landscape in the genome of Chlamydomonas using new sequencing approaches. We identified the 6mA modification in 84% of genes in Chlamydomonas. We found that 6mA mainly locates at ApT dinucleotides around transcription start sites (TSS) with a bimodal distribution and appears to mark active genes. A periodic pattern of 6mA deposition was also observed at base resolution, which is associated with nucleosome distribution near the TSS, suggesting a possible role in nucleosome positioning. The new genome-wide mapping of 6mA and its unique distribution in the Chlamydomonas genome suggest potential regulatory roles of 6mA in gene expression in eukaryotic organisms.

Neural signatures of sleep in zebrafish.

Slow-wave sleep and rapid eye movement (or paradoxical) sleep have been found in mammals, birds and lizards, but it is unclear whether these neuronal signatures are found in non-amniotic vertebrates. Here we develop non-invasive fluorescence-based polysomnography for zebrafish, and show-using unbiased, brain-wide activity recording coupled with assessment of eye movement, muscle dynamics and heart rate-that there are at least two major sleep signatures in zebrafish. These signatures, which we term slow bursting sleep and propagating wave sleep, share commonalities with those of slow-wave sleep and paradoxical or rapid eye movement sleep, respectively. Further, we find that melanin-concentrating hormone signalling (which is involved in mammalian sleep) also regulates propagating wave sleep signatures and the overall amount of sleep in zebrafish, probably via activation of ependymal cells. These observations suggest that common neural signatures of sleep may have emerged in the vertebrate brain over 450 million years ago.

Accessing Highly Substituted Indoles via B(C6F5)3-Catalyzed Secondary Alkyl Group Transfer.

Herein, we report a synthetic method to access a range of highly substituted indoles via the B(C6F5)3-catalyzed transfer of 2° alkyl groups from amines. The transition-metal-free catalytic approach has been demonstrated across a broad range of indoles and amine 2° alkyl donors, including various substituents on both reacting components, to access useful C(3)-alkylated indole products. The alkyl transfer process can be performed using Schlenk line techniques in combination with commercially available B(C6F5)3·nH2O and solvents, which obviates the requirement for specialized equipment (e.g., glovebox).

Characterization of Demographical Histologic Diversity in Small Renal Masses With the Clear Cell Likelihood Score.

OBJECTIVE: This study aimed to develop a diagnostic model to estimate the distribution of small renal mass (SRM; ≤4 cm) histologic subtypes for patients with different demographic backgrounds and clear cell likelihood score (ccLS) designations. MATERIALS AND METHODS: A bi-institution retrospective cohort study was conducted where 347 patients (366 SRMs) underwent magnetic resonance imaging and received a ccLS before pathologic confirmation between June 2016 and November 2021. Age, sex, race, ethnicity, socioeconomic status, body mass index (BMI), and the ccLS were tabulated. The socioeconomic status for each patient was determined using the Area Deprivation Index associated with their residential address. The magnetic resonance imaging-derived ccLS assists in the characterization of SRMs by providing a likelihood of clear cell renal cell carcinoma (ccRCC). Pathological subtypes were grouped into four categories (ccRCC, papillary renal cell carcinoma, other renal cell carcinomas, or benign). Generalized estimating equations were used to estimate probabilities of the pathological subtypes across different patient subgroups. RESULTS: Race and ethnicity, BMI, and ccLS were significant predictors of histology (all P < 0.001). Obese (BMI, ≥30 kg/m 2 ) Hispanic patients with ccLS of ≥4 had the highest estimated rate of ccRCC (97.1%), and normal-weight (BMI, <25 kg/m 2 ) non-Hispanic Black patients with ccLS ≤2 had the lowest (0.2%). The highest estimated rates of papillary renal cell carcinoma were found in overweight (BMI, 25-30 kg/m 2 ) non-Hispanic Black patients with ccLS ≤2 (92.3%), and the lowest, in obese Hispanic patients with ccLS ≥4 (<0.1%). CONCLUSIONS: Patient race, ethnicity, BMI, and ccLS offer synergistic information to estimate the probabilities of SRM histologic subtypes.

Measurement of joint angles for the objective assessment of limb conformation in dairy calves.

Poor limb conformation in cattle is believed to be closely associated with claw and limb disorders. Limb conformation is part of genetic evaluation and is assessed visually. In this descriptive study, the assessment of conformation in calves was evaluated objectively using joint angle measurements. A total of 100, 30- to 90-d-old, heifer calves of the Brown Swiss (n = 50) and Holstein (n = 50) breeds were photographed from both sides and the front and rear. Carpal, tarsal, autopodium and fetlock joint angles of the fore- or hind limbs were measured on the images using anatomic reference points and the ImageJ/Fiji® program. Each angle was measured 3 times, and the mean was used for analysis. Values from both sides were pooled. Deviations from defined standard angles were classified as slight or moderate. The positions of the front and hind feet were measured and scored. On average, the calves had moderate "knock-kneed" carpal conformation, and the autopodium of the front limb had a slight lateral deviation. In the rear view, the calves had slight, but close to moderate, "cow-hocked" tarsal conformation, and the autopodium of the hind limbs was parallel, but close to slightly deviated. Holstein calves were moderately, and Brown Swiss calves were slightly "cow-hocked". A moderate lateral deviation occurred in the metacarpal-digit angle in the front view and a slight lateral deviation occurred in the metatarsal-digit angle in the rear view. The front feet position score was >17° in 69% of the calves, and the hind feet position score was <17° in 90% of the calves. In the side views, the calves were slightly "over at the carpus" and slightly "straight-hocked" and had average fetlock conformation. In the mean values, most measured joint angles did not correspond to the straight or parallel classifications in our calves; moderate "knock-kneed" and slight "cow-hocked", and "toed-out" classifications were most common. The limb angles measured were based on anatomical features and therefore are unlikely to change substantially with increasing age. These aspects should be considered when assessing linear traits and investigating the relationship between limb conformation and claw diseases.

Postoperative Elbow Instability: Options for Revision Stabilization.

Persistent and recurrent postoperative elbow instability includes a spectrum of pathologies ranging from joint incongruity and subluxation to dislocation. Restoration of osseous anatomy, particularly the coronoid, is a priority in restoring elbow alignment and maintaining ulnohumeral joint stability. After managing bony deficiencies, soft-tissue and ligamentous structures are typically addressed. When required, both static and dynamic adjunctive stabilization procedures have been described, which aid in maintaining a concentric reduction. In these complex procedures, both complication avoidance and early recognition of postoperative complications assist in obtaining a good result. In this review, we discuss current treatment options for revision stabilization for patients with persistent and recurrent elbow subluxation or dislocation after primary stabilization.

Sensitivity, Specificity, and Reliability of the CTS-6 for Carpal Tunnel Syndrome Administered by Medical Assistants.

PURPOSE: The CTS-6 can be used clinically to diagnose carpal tunnel syndrome (CTS) and has demonstrated high levels of interrater reliability when administered by nonexpert clinicians. Our purpose was to assess sensitivity (Sn), specificity (Sp), and interrater reliability of the CTS-6 when administered by medical assistants (MAs). METHODS: A series of patients presenting to an academic, upper-extremity surgery clinic were screened using CTS-6 between May and June of 2023. The CTS-6 was first administered by one of seven MAs and then by one of four fellowship-trained upper-extremity surgeons. In addition to recording baseline demographics, the results of each of the six history and examination components of the CTS-6 were recorded, as was the cumulative CTS-6 score (0-26). Surgeons were blinded to the scores obtained by the MAs. Interrater reliability (Cohen's kappa) was determined between the groups with respect to the diagnosis of CTS and the individual CTS-6 items. Sensitivity/specificity was calculated for the MA-administered CTS-6, using the score obtained by the surgeon as the reference standard. A CTS-6 score >12 was considered diagnostic of CTS. RESULTS: Two hundred eighteen patients were included, and 26% had a diagnosis of CTS. The MA group demonstrated a Sn/Sp of 84%/91% for the diagnosis of CTS. Interrater reliability was substantial (Cohen's kappa: 0.72, 95% confidence interval: 0.62-0.83) for MAs compared with hand surgeons for the diagnosis of CTS. For individual CTS-6 components, agreement was lowest for the assessment of two-point discrimination (fair) and highest for the assessment of subjective numbness (near perfect). CONCLUSIONS: The CTS-6 demonstrates substantial reliability and high Sn/Sp when administrated by MAs in an upper-extremity clinic. These data may be used to inform the development of CTS screening programs and future investigations in the primary care setting. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.

Surgeon Factors and Trends Associated With the Use of Subacromial Decompression at the Time of Rotator Cuff Repair.

PURPOSE: Subacromial decompression (SAD) has historically been described as an essential part of the surgical treatment of rotator cuff disorders. However, investigations throughout the 21st century have increasingly questioned the need for routine SAD during rotator cuff repair (RCR). Our purpose was to assess for changes in the incidence of SAD performed during RCR over a 12-year period. In addition, we aimed to characterize surgeon and practice factors associated with SAD use. METHODS: Records from two large tertiary referral systems in the United States from 2010 to 2021 were reviewed. All cases of RCR with and without SAD were identified. The outcome of interest was the proportion of SAD performed during RCR across years and by surgeon. Surgeon-specific characteristics included institution, fellowship training, surgical volume, academic practice, and years in practice. Yearly trends were assessed using binomial logistic regression modeling, with a random effect accounting for surgeon-specific variability. RESULTS: During the study period, 37,165 RCR surgeries were performed by 104 surgeons. Of these cases, 71% underwent SAD during RCR. SAD use decreased by 11%. The multivariable model found that surgeons in academic practice, those with lower surgical volume, and those with increasing years in practice were significantly associated with increased odds of performing SAD. Surgeons with fellowship training were significantly more likely to use SAD over time, with the greatest odds of SAD noted for sports medicine surgeons (odds ratio = 3.04). CONCLUSIONS: Although SAD use during RCR appears to be decreasing, multiple surgeon and practice factors (years in practice, fellowship training, volume, and academic practice) are associated with a change in SAD use. CLINICAL RELEVANCE: These data suggest that early-career surgeons entering practice are likely driving the trend of declining SAD. Despite evidence suggesting limited clinical benefits, SAD remains commonly performed; future studies should endeavor to determine factors associated with practice changes among surgeons.

A Comparison of Amyloid Deposition in Endoscopic and Open Carpal Tunnel Release.

PURPOSE: Previous investigations assessing the incidence of amyloidosis detected with biopsy during carpal tunnel release (CTR) have focused on open CTR (OCTR). Prior authors have suggested that biopsy may be more technically challenging during endoscopic carpal tunnel release (ECTR). Our purpose was to compare differences in the incidence of amyloid deposition detected during ECTR versus OCTR. METHODS: We reviewed all primary ECTR and OCTR during which a biopsy for amyloid was obtained between February 2022 and June 2023. All procedures were performed by five upper-extremity surgeons from a single institution. Congo red staining was used to determine the presence of amyloid deposition in either the transverse carpal ligament (TCL) or tenosynovium. All positive cases underwent subtype analysis and protein identification through liquid chromatography-tandem mass spectrometry. Baseline demographics were recorded for each case, and the incidence of positive biopsy was compared between ECTR and OCTR cases. RESULTS: A total of 282 cases were included for analysis (143 ECTR and 139 OCTR). The mean age was 67 years, and 45% of cases were women. Baseline demographics were similar except for a significantly higher incidence of diabetes in OCTR cases (13% vs 33%). Overall, 13% of CTR cases had a positive biopsy. There was a statistically significant difference in the incidence of amyloid deposition detected during biopsy in ECTR cases (3.5%) compared with OCTR cases (23%). CONCLUSIONS: Biopsy performed during ECTR may result in a lower incidence of amyloid detection. Future basic science investigation may be necessary to determine histologic differences between tenosynovium proximal and distal to the leading edge of the TCL. When surgeons plan a biopsy during surgical release of the carpal tunnel, an open approach may be advantageous. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

A Comparison of Tenosynovial and Transverse Carpal Ligament Biopsy for Amyloid Detection in Open Carpal Tunnel Release.

PURPOSE: Our purpose was to compare differences in the incidence of amyloid deposition in tenosynovium (TS) versus transverse carpal ligament (TCL) biopsies obtained during open carpal tunnel release. We hypothesized that the incidence of amyloid would be similar between TCL and TS when obtaining both specimens from the same patient. METHODS: All primary, elective open carpal tunnel release cases that underwent biopsy for amyloid between January 2022 and September 2023 were reviewed. Tenosynovial and TCL specimens were independently evaluated by a pathologist to assess for amyloid. Demographic data were collected, and incidence of amyloid deposition was compared between the two samples. Agreement statistics, sensitivity, and specificity were calculated for TCL, using TS as the reference standard. RESULTS: A total of 196 cases met either Tier 1 (n=180) or Tier 2 (n=16) biopsy criteria. Forty-eight cases were excluded for missed biopsies or laboratory processing errors, leaving 148 cases available for analysis. Amyloid deposition was present in 31 out of 148 (21%) TS specimens and 33 out of 148 (22%) TCL specimens. Overall, the results of the TS biopsy agreed with TCL biopsy in 138 out of 148 cases (93%). In the 10 cases for which the results of the TCL and TS biopsy differed, six cases had (+) TCL and (-) TS, and four cases had amyloid deposition in TS without evidence of deposition in the TCL. Sensitivity and specificity values for the TCL specimen were 87% and 95%, respectively. Positive and negative predictive values were 82% and 97%, respectively. CONCLUSIONS: For cases of open carpal tunnel release undergoing biopsy, amyloid deposition was noted in 21% of TS specimens and 22% of TCL specimens. Results of TS and TCL biopsies obtained from the same patient agreed in 93% of cases. Single-source biopsy for amyloid represents a reasonable diagnostic approach. Future cost analyses should be performed to determine whether the addition of two biopsy sources to improve diagnostic accuracy is justified. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

A Comparison of Early Complication Rates of Endoscopic Carpal Tunnel Release With and Without Resident Involvement.

PURPOSE: The purpose of this study was to compare the complication rates of endoscopic carpal tunnel release (ECTR) relative to orthopedic resident trainee involvement in the procedure. METHODS: All patients undergoing isolated, elective ECTR by two attending surgeons within a 59-month period were analyzed. Cases were categorized as the following according to the degree of resident involvement: ECTR performed by attending with either no resident or a resident as an assistant (group 1), resident performing a portion of the procedure (group 2), and resident performing the entire procedure (group 3). Early postoperative complications and/or intraoperative conversion to an open procedure were the outcomes of interest. We used a noninferiority design, hypothesizing that resident involvement would not be associated with inferior outcomes compared with cases without resident involvement. Multiple logistic regression models, adjusted for patient demographic and surgical characteristics, were fit to assess the relationship between resident involvement groups and complication/conversion outcomes. RESULTS: A total of 1,167 ECTR cases (895 patients) were performed and returned for postoperative follow-up for at least 2 weeks after surgery. Operative time was significantly shorter for group 1 cases versus group 2 and 3 cases. The early postoperative complication and conversion rates were 1.7% and 1.0%, respectively. Superficial infection (1.2%), deep infection (0.3%), and transient neuropraxia (0.3%) occurred infrequently and did not differ relative to resident involvement. No differences in the odds of complication and/or conversion relative to resident involvement were observed. CONCLUSIONS: The results of ECTR performed entirely or in part by attending-supervised resident trainees were not inferior to ECTR performed by an attending surgeon regarding the odds of experiencing complications or conversion to an open procedure. With appropriate supervision, ECTR can be performed safely by orthopedic and plastic surgery residents. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Eye of the Carpenter: How Well do Orthopaedic Surgeons Estimate Angular Measurements in Derotational Osteotomies?

BACKGROUND: Femoral derotational osteotomies are used by orthopaedic surgeons to decrease version in a variety of pathologies. Intraoperatively, the goal of the surgery is to decrease the rotation of the femur to within physiological range. Surgeons generally visually estimate the angle of correction based on bone markers at the rotating cylindrical portion of the femur. This study sought first to assess the accuracy and inter-rater reliability of surgeons with respect to angle creation, and then to implement a training intervention. METHODS: A rotational femur model was constructed and tested among surgeons and nonsurgeons. Surgeons were then randomized into an experimental and control cohort with training on the model as the intervention. Subjects were asked to create target angles of 15, 30, 45, and 60 degrees using only Kirschner wires and then only bone marks for reference. Independent and paired t -tests were performed to determine variability between cohorts. RESULTS: The mean angle creation error and range of the surgeon cohort were significantly lower than those of the nonsurgeon cohort. Within the nonsurgeon cohort, the mean angle creation error and range of the wire modality were significantly lower than that of the mark modality. The mean angle creation error and range of the trained cohort were significantly lower than the untrained cohort. CONCLUSIONS: The considerable inter-subject range within the surgeon cohort highlights a need for the reinforcement of basic geometric principles within orthopaedic instruction. This model allows for immediate, accurate feedback on angle creation, and training appears to be both time and cost-effective. The physiological range allows for a level of variability between surgical outcomes without consequence. However, the more than 20 degree range determined by this study does not fall within those bounds and should be addressed. CLINICAL RELEVANCE: Moving forward, rotational estimation as a surgical skill should increase in prominence within orthopaedic instruction to maximize future joint health, and additional emphasis should be placed on fundamental spatial orientation during training.

Cu segregation in Au-Cu nanoparticles exposed to hydrogen atmospheric pressure: how is fcc symmetry maintained?

In a recent work [A. Nassereddine et al., Small 2021, 17, 2104571] we reported the atomic-scale structure and dynamics of sub-4 nm sized Au nanoparticles (NPs) supported on titania in H2 at atmospheric pressure obtained by using aberration-corrected environmental transmission electron microscopy (ETEM), density functional theory (DFT) optimizations and ab initio molecular dynamic (AIMD) simulations. Our results showed unstable Au NPs losing their face-centred cubic (fcc) symmetry (from fcc to non-fcc symmetries) and revealed the drastic effect of hydrogen adsorption. In this work, we use the same approach to study the dynamics of equiatomic Au-Cu NPs in the same range of size and the results show an enhanced structural stability upon alloying by Cu. In spite of the morphology evolution from facetted to rounded shapes, the observed Au-Cu NPs are found to keep their fcc symmetry under atmospheric hydrogen pressure. AIMD simulation evidences a Cu segregation process from the sub-surface toward the upper surface layer, and a reversed segregation of Au atoms from the surface towards the sub-surface sites. The analysis of the chemical ordering in the core shows a tendency to a local chemical ordering where Au-Cu hetero-atomic bindings are favoured. The segregating Cu seems to play a major role in reducing the fluxionality of Au-Cu NPs in H2 and thus, maintaining their fcc symmetry.

Parkinson's disease genome-wide association study-linked PARK16 variant is associated with a lower risk of cognitive impairment: A 4-year observational study.

BACKGROUND AND PURPOSE: A genome-wide association study-linked variant (PARK16 rs6679073) modulates the risk of Parkinson's disease (PD). We postulate that there may be differences in clinical characteristics between PARK16 rs6679073 carriers and noncarriers. In a prospective study, we investigate the clinical characteristics between PARK16 rs6679073 A allele carriers and noncarriers over 4 years. METHODS: A total of 204 PD patients, comprising 158 PARK16 rs6679073 A allele carriers and 46 noncarriers, were recruited. All patients underwent motor and nonmotor symptom and cognitive assessments yearly over 4 years. RESULTS: PARK16 rs6679073 carriers were less likely to have mild cognitive impairment (MCI) compared to noncarriers at both baseline (48.1% vs. 67.4%, p = 0.027) and 4-year follow-up (29.3% vs. 58.6%, p = 0.007). CONCLUSIONS: PD PARK16 rs6679073 carriers had significantly lower frequency of MCI in a 4-year follow-up study, suggesting that the variant may have a neuroprotective effect on cognitive functions.

Identifying clinical features and blood biomarkers associated with mild cognitive impairment in Parkinson disease using machine learning.

BACKGROUND AND PURPOSE: A broad list of variables associated with mild cognitive impairment (MCI) in Parkinson disease (PD) have been investigated separately. However, there is as yet no study including all of them to assess variable importance. Shapley variable importance cloud (ShapleyVIC) can robustly assess variable importance while accounting for correlation between variables. Objectives of this study were (i) to prioritize the important variables associated with PD-MCI and (ii) to explore new blood biomarkers related to PD-MCI. METHODS: ShapleyVIC-assisted variable selection was used to identify a subset of variables from 41 variables potentially associated with PD-MCI in a cross-sectional study. Backward selection was used to further identify the variables associated with PD-MCI. Relative risk was used to quantify the association of final associated variables and PD-MCI in the final multivariable log-binomial regression model. RESULTS: Among 41 variables analysed, 22 variables were identified as significantly important variables associated with PD-MCI and eight variables were subsequently selected in the final model, indicating fewer years of education, shorter history of hypertension, higher Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor score, higher levels of triglyceride (TG) and apolipoprotein A1 (ApoA1), and SNCA rs6826785 noncarrier status were associated with increased risk of PD-MCI (p < 0.05). CONCLUSIONS: Our study highlighted the strong association between TG, ApoA1, SNCA rs6826785, and PD-MCI by machine learning approach. Screening and management of high TG and ApoA1 levels might help prevent cognitive impairment in early PD patients. SNCA rs6826785 could be a novel therapeutic target for PD-MCI. ShapleyVIC-assisted variable selection is a novel and robust alternative to traditional approaches for future clinical study to prioritize the variables of interest.

A framework for assessing confidence in freedom from infection in animal disease control programmes.

In the Surveillance Tool for Outcome-based Comparison of FREEdom from infection (STOC free) project (https://www.stocfree.eu), a data collection tool was constructed to facilitate standardised collection of input data, and a model was developed to allow a standardised and harmonised comparison of the outputs of different control programmes (CPs) for cattle diseases. The STOC free model can be used to evaluate the probability of freedom from infection for herds in CPs and to determine whether these CPs comply with the European Union's pre-defined output-based standards. Bovine viral diarrhoea virus (BVDV) was chosen as the case disease for this project because of the diversity in CPs in the six participating countries. Detailed BVDV CP and risk factor information was collected using the data collection tool. For inclusion of the data in the STOC free model, key aspects and default values were quantified. A Bayesian hidden Markov model was deemed appropriate, and a model was developed for BVDV CPs. The model was tested and validated using real BVDV CP data from partner countries, and corresponding computer code was made publicly available. The STOC free model focuses on herd-level data, although that animal-level data can be included after aggregation to herd level. The STOC free model is applicable to diseases that are endemic, given that it needs the presence of some infection to estimate parameters and enable convergence. In countries where infection-free status has been achieved, a scenario tree model could be a better suited tool. Further work is recommended to generalise the STOC free model to other diseases.

Dans le cadre du projet européen STOC free (Surveillance Tool for Outcome-based Comparison of FREEdom from infection, outil de surveillance permettant de comparer les probabilités d'absence d'infection sur la base des résultats, https://www.stocfree.eu), un outil de recueil des données a été construit pour faciliter une collecte normalisée des données d'entrée ; un modèle a également été élaboré pour permettre une comparaison normalisée et harmonisée des données sur les résultats des différents programmes de contrôle des maladies des bovins. Le modèle STOC free peut être utilisé pour évaluer la probabilité d'absence d'infection au sein des troupeaux dans le cadre des programmes de contrôle et déterminer si ces programmes sont conformes aux normes définies par l'Union européenne en termes de résultats attendus. L'infection par le virus de la diarrhée virale bovine a été choisie comme maladie d'étude pour ce projet en raison de la diversité des programmes de contrôle dans les six pays participants. Les informations relatives aux programmes de contrôle et aux facteurs de risque d'infection ont été recueillies à l'aide de l'outil de collecte des données. Les aspects clés et valeurs par défaut ont été quantifiés en vue d'être inclus dans le modèle STOC free. Un modèle de Markov caché dont les paramètres sont estimés par inférence bayésienne a été considéré comme le plus adapté et développé pour une application aux données issues des programmes de contrôle de la diarrhée virale bovine. Ce modèle a été testé et validé en utilisant des données réelles des programmes de contrôle du virus de la diarrhée virale bovine des pays participants ; le code informatique correspondant a été rendu public. Le modèle STOC free utilise des données au niveau des troupeaux, même si des données au niveau des animaux individuels peuvent être incluses une fois agrégées au niveau du troupeau. Le modèle STOC free s'applique aux maladies endémiques, puisqu'un certain niveau de présence de l'infection est nécessaire pour estimer les paramètres et permettre la convergence. Dans les pays ayant obtenu le statut indemne d'infection, un modèle du type arbre de scénario pourrait être un outil plus adapté. Des travaux supplémentaires sont recommandés pour généraliser le modèle STOC free à d'autres maladies.

Como parte del proyecto europeo STOC free (Surveillance Tool for Outcome-based Comparison of FREEdom from infection, herramienta de vigilancia para comparaciones por resultados respecto a la ausencia de infecciones, https://www.stocfree.eu), se confeccionó una herramienta de obtención de datos para facilitar la recogida normalizada de datos entrantes y se elaboró un modelo que posibilitara una comparación normalizada y armonizada de los resultados (datos salientes) de distintos programas de control de enfermedades bovinas. El modelo STOC free puede servir para calcular la probabilidad de ausencia de infección en los rebaños como parte de los programas de control y para determinar si estos programas se ajustan a las normas predefinidas de resultados de la Unión Europea. Como ejemplo de estudio para el proyecto se eligió el virus de la diarrea viral bovina (virus DVB) por la diversidad que presentaban los correspondientes programas de control de los seis países participantes. Empleando la herramienta de obtención de datos, se reunió información pormenorizada de los programas de control del virus DVB y los factores de riesgo. Para incluir los datos en el modelo STOC free, se cifraron unos aspectos clave y valores predeterminados Juzgando conveniente el empleo de un modelo oculto de Markov cuyos parámetros se estiman por inferencia bayesiana, se elaboró un modelo de esta índole aplicable a los programas de control del virus DVB. Para ensayar y validar el modelo se utilizaron datos reales de los programas de control del virus DVB de los países participantes, tras lo cual se hizo público el correspondiente código informático. El modelo STOC free trabaja con los datos por rebaño, aunque tras la agregación por rebaños pueden incluirse también datos por individuo. Para que este modelo sea aplicable a una enfermedad es preciso que esta sea endémica, pues el modelo requiere la presencia de cierto nivel de infección para calcular los parámetros y determinar convergencias. En aquellos países donde ya esté reconocida la ausencia de infección, sería más apropiado utilizar como herramienta un modelo de árbol de hipótesis. Los autores recomiendan ahondar en esta línea de trabajo para poder extender a otras enfermedades el uso del modelo STOC free.

Controversies in the Management of Bicolumnar Fractures of the Distal Humerus.

Bicolumnar fractures of the distal humerus pose numerous treatment challenges for upper-extremity surgeons. Although open reduction and internal fixation demonstrates advantages compared with nonsurgical treatment, restoration of osseous anatomy can be difficult, particularly for comminuted, intra-articular fractures. Despite well-recognized complications, total elbow arthroplasty remains an option for elderly patients with fractures not amenable to fixation. Although indications remain controversial, distal humerus hemiarthroplasty has emerged as a potential alternative to total elbow arthroplasty in carefully selected patients with nonreconstructable fractures. Numerous controversies remain with respect to the management decisions for these complex injuries, including the optimal surgical approach, management of the ulnar nerve, and ideal fixation constructs for open reduction internal fixation. Our purpose is to review the management of bicolumnar distal humerus fractures in adult patients and discuss current controversies related to treatment.

The Risk of Early Postoperative Complications Associated With Preoperative Immunosuppression in Patients Undergoing Total Elbow Arthroplasty.

PURPOSE: Patients considering total elbow arthroplasty (TEA) may be receiving immunosuppressive therapy; however, the relationship between immunosuppressive medications and postoperative complications is not well defined. Our purpose was to assess the relationship between preoperative immunosuppression and short-term complications following TEA. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was reviewed from 2005 to 2020 to identify patients undergoing TEA. Procedures indicated for malignancy or infection were excluded. Patients were grouped according to preoperative chronic immunosuppressive status. Demographic and operative characteristics were compared between groups. The 30-day incidence of complications and reoperations were compared between groups. Multiple logistic regression models, inverse-weighted by propensity scores, were used to calculate odds ratio (OR) of experiencing any complication or return to the operating room based on immunosuppression status and other demographic characteristics. RESULTS: A total of 769 patients undergoing TEA were included, of whom 142 (18.5%) received chronic immunosuppression. Distribution of age, sex, race, body mass index, diabetes, and American Society of Anesthesiologists classification differed significantly between groups. Most procedures were performed on an inpatient basis, and the median operative duration was 148 minutes. Most procedures were indicated for fracture in the nonimmunosuppressed group and rheumatoid arthritis in the immunosuppressed group. Overall complication rates were 7.0% for immunosuppressed patients and 10.2% for nonimmunosuppressed patients. The incidence of complications and reoperations did not significantly differ between groups. After controlling for confounding and adjusting for patient characteristics, immunosuppressed patients were 0.52 times less likely to experience a complication. Additionally, there was no association between immunosuppression status and odds of return to the operating room. CONCLUSION: Similar rates of complications were observed following TEA, regardless of preoperative immunosuppression status. Chronic immunosuppression does not appear to increase the rates of postoperative complications for patients undergoing TEA. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Impact of Bracing and Therapy Services on Perioperative Costs for Patients Undergoing Distal Biceps Tendon Repair.

PURPOSE: This study aimed to quantify and assess perioperative costs in an integrated healthcare system for patients undergoing distal biceps tendon (DBT) repair with and without the use of postoperative bracing and formal physical (PT) or occupational (OT) therapy services. In addition, we aimed to define clinical outcomes after DBT repair using a brace-free, therapy-free protocol. METHODS: We retrospectively reviewed all cases of DBT repairs within our integrated system from 2015 to 2021. We performed a retrospective review of a series of DBT repairs utilizing the brace-free, therapy-free protocol. For patients with our integrated insurance plan, a cost analysis was conducted. Claims were subdivided to assess total charges, costs to the insurer, and patient costs. Three groups were created for comparisons of total costs: (1) patients who had both postoperative bracing and PT/OT, (2) patients who had either postoperative bracing or PT/OT, and (3) patients who had neither postoperative bracing nor PT/OT. RESULTS: A total of 36 patients had our institutional insurance plan and were included in the cost analysis. For patients using both bracing and PT/OT, these services contributed 12% and 8% of the total perioperative costs, respectively. Implant costs accounted for 28% of the overall cost. Forty-four patients were included in the retrospective review with a mean follow-up of 17 months. The overall QuickDASH was 12; two cases resulted in unresolved neuropraxia, and there were no cases of re-rupture, infection, or reoperation. CONCLUSIONS: Within an integrated healthcare system, postoperative bracing and PT/OT services increase the cost of care for DBT repair and account for 20% of the total perioperative charges in cases where bracing and therapy are used. Considering the results of prior investigations indicating that formal PT/OT and bracing offer no clinical advantages over immediate range of motion (ROM) and self-directed rehabilitation, upper-extremity surgeons should forego routine brace and PT/OT utilization after DBT repair. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.