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The biomechanical efficacy of nail–plate constructs (NPCs) used in the treatment of traumatic distal femur fractures (DFFs) remains understudied compared to traditional approaches. This systematic review examines the biomechanical efficacy of NPCs compared to alternative approaches for the surgical fixation of DFFs to guide surgical decision-making and improve patient outcomes. This systematic review searched the PubMed, CINAHL, MEDLINE, Web of Science, and SPORT Discus databases from inception until 24 January 2024. Inclusion criteria were biomechanical studies that involved nail–plate combination constructs for DFFs. Six observational studies were included. Of the included studies, five studies utilized synthetic bone models in testing, and one study used both synthetic and cadaveric bone models. All studies found NPCs to have significantly higher axial and torsional stiffness and resistance to loading than distal lateral femoral locking plate (DLFLP) constructs. The 11 mm NPCs were significantly stiffer than the 9 mm NPCs under torsional and axial loading. Only one of two studies found NPCs to have greater axial stiffness than dual-plate (DP) constructs. NPCs and DP constructs had greater torsional and axial stiffness than the plate-only or DP with medial distal tibial plate constructs. NPCs had less displacement and torque than the plate- or nail-only constructs under axial and torsional loads. NPCs demonstrate superior axial and torsional stiffness and resistance to mechanical loads compared to DLFLP. The varying performance between 11 mm and 9 mm NPCs suggests that construct diameter plays a role in mechanical stability. NPCs and DP constructs performed better than plate-only constructs. Future research should explore the impact of varying nail diameters and plate configurations on stability, as well as the clinical efficacy of NPCs across different patient populations, particularly those with varying bone densities, to better understand their performance in real-world scenarios.

Abstract Background Orthopedic procedures often require removing bone or pathological tissue, with traditional methods involving instruments like curettes and rongeurs. However, these methods can be time-consuming and lead to increased blood loss. To mitigate these side effects, vacuum-assisted tools have been developed to aid in tissue removal. These devices enable surgeons to suction tissue without discarding it, potentially improving outcomes in conditions such as osteomyelitis or tumor removal while enabling collection of the material for downstream applications. Despite limited research, vacuum-assisted devices show promise beyond bone marrow harvesting. This study assesses infection and clearance rates, estimated blood loss, and total procedure time associated with the use of vacuum-assisted tissue removal, with a goal to understand if these devices can be used for tissue removal across a variety of pathologic conditions. Methods A retrospective cohort study was conducted on patients undergoing orthopedic procedures with the Avitus® Bone Harvester repurposed from its original design from December 1, 2021, to July 1, 2023. Procedures were categorized into oncology, and debridement for infection cases. Infection cases were further categorized into those secondary to trauma and those involving primary infections (osteomyelitis and periprosthetic joint infection). Clinical variables, including demographics, intraoperative details, complications, and follow-up, were reviewed. Statistical analysis included descriptive statistics computed with R Studio. Results The study included 44 patients, with debridement for infection cases being the most common (primary infection: 45.5%; infection secondary to trauma: 18.1%), followed by oncology cases (36.4%). In all oncology cases, a definitive diagnosis was established using the device, and no post-operative infections were reported. The infection clearance rate was 85.0% for primary infection cases and 50.0% for cases of infection following trauma. Across the entire cohort, the average blood loss was 314.52 mL (sd: 486.74), and the average total procedure time was 160.93 min (sd: 91.07). The overall reoperation rate was 47.7%, with an unplanned reoperation rate of 11.4%. Conclusion The vacuum-assisted bone harvester was effectively utilized in a wide range of debridement and curettage procedures across diverse orthopedic surgeries. In oncology cases, the device enabled effective tissue removal with comparable recurrence rates, demonstrating its potential to minimize contamination while preserving tissue for accurate diagnoses. Additionally, a high rate of osteomyelitis eradication was observed in debridement for primary infection cases (85%). Despite the relatively high reoperation rate of 47.7%, it is crucial to interpret this figure within the context of the varied reasons for reoperation. Many of these reoperations were planned as part of a staged approach to treatment or were unrelated to the device's performance. It is crucial to acknowledge that isolating the device's contribution to these results can be difficult. The utilization of the device should be guided by considerations of cost-effectiveness and patient-specific risk factors.

Objectives: Monitoring tools that could provide quick predictions of tuberculosis (TB) treatment outcomes are urgently needed. Here, we assessed whether the evolution of selected biomarkers of innate immunity may help monitoring TB treatment response within 2 weeks of treatment initiation. Methods: ANRS12394-LILAC-TB was a proof-of-concept prospective study: adults with a rifampicin-susceptible TB who are HIV-negative and HIV-infected documented by a positive Xpert MTB/RIF test were enrolled in Cambodia and Côte d'Ivoire. Plasma concentrations of interleukin-1 receptor antagonist (IL-1Ra), interferon-γ–induced protein-10 and clusters of differentiation (CD) (scavenging CD163) were measured by commercial enzyme-linked immunosorbent assay kits. A Wilcoxon test for paired data was used for longitudinal comparisons. Results: A total of 55 patients were enrolled (women: 31%, median age: 37 years; median CD4 count in the 10 of 13 participants with HIV: 53 cells/mm3). Overall, 83% were considered in TB treatment success. Compared with baseline, the IL-1Ra plasma levels significantly decreased as soon as week (W) 1, independent of HIV status (−71% in HIV-positive vs −33% in HIV-negative; P

Background: Artificial intelligence (AI) in medicine has primarily focused on diagnosing and treating diseases and assisting in the development of academic scholarly work. This study aimed to evaluate a new use of AI in orthopaedics: content generation for professional medical education. Quality, accuracy, and time were compared between content created by ChatGPT and orthopaedic surgery clinical fellows. Methods: ChatGPT and 3 orthopaedic adult reconstruction fellows were tasked with creating educational summaries of 5 total joint arthroplasty-related topics. Responses were evaluated across 5 domains by 4 blinded reviewers from different institutions who are all current or former total joint arthroplasty fellowship directors or national arthroplasty board review course directors. Results: ChatGPT created better orthopaedic content than fellows when mean aggregate scores for all 5 topics and domains were compared (P ≤ .001). The only domain in which fellows outperformed ChatGPT was the integration of key points and references (P = .006). ChatGPT outperformed the fellows in response time, averaging 16.6 seconds vs the fellows' 94 minutes per prompt (P = .002). Conclusions: With its efficient and accurate content generation, the current findings underscore ChatGPT's potential as an adjunctive tool to enhance orthopaedic arthroplasty graduate medical education. Future studies are warranted to explore AI's role further and optimize its utility in augmenting the educational development of arthroplasty trainees.

Background: Orthopedic Relief Services International (ORSI), in partnership with the Foundation for Orthopedic Trauma and the department of Orthopedic Surgery of La Paix University Hospital in Haiti, has developed a year-round Orthopedic Grand Round series. This series is moderated by Haitian faculty, features presentations by American orthopedic surgeons, and is broadcast to major state hospitals in Haiti for residents and attendings. Objective: To introduce clinical concepts and increase knowledge in an area that is medically underserved, especially in the field of orthopedics, through lectures that tailor to the educational needs of Haiti. Methods: Topics for lecture series are requested by Haitian attending orthopedic surgeons and residents in collaboration with American orthopedic surgeons to meet the educational needs of the residents in Haiti. These lectures reflect the case mix typically seen at state hospitals in Haiti and consider the infrastructural capacity of participating centers. Grand rounds are held an average of twice per month for an hour each, encompassing an educational lesson followed by an open forum for questions and case discussion. Feedback is taken from Haitian residents to ensure the sessions are beneficial to their learning. Findings and Conclusions: To date 95 sessions hosted by 32 lecturers have been completed over Zoom between the US and Haiti. The fourth year of the lecture series is currently ongoing with an expansion of topics. In an underserved medical area such as Haiti, programs that educate local surgeons are crucial to continuing the growth and development of the medical community. Programs like this have the potential to contribute to the educational infrastructure of countries in need, regardless of the specialty. The model of this program can be used to produce similar curricula in various specialties and areas around the world.

Background: The indications for Below-Knee Amputation (BKA) are expansive and etiologic subgroups are not well defined. This analysis uses primary ICD-10 diagnosis codes to stratify patients undergoing BKA, and examines differences in subgroup characteristics and 30-day outcomes. Methods: We performed a retrospective analysis of patients in the NSQIP database who underwent BKA between 2015 and 2020. Approximately 80% of the 12,157 NSQIP BKA entries with primary ICD-10 diagnosis codes were stratified to diabetic (n = 3,363), vascular (n = 3,632), or infectious (n = 2,743) etiological subgroups. Results: Patients with vascular etiologies were older, more likely to be female, underweight, ASA classification of four, and active tobacco users than patients in the other groups. Across all groups, there were incidences of 37.5% for 30-day inpatient complications, 7.0% for Clavien-Dindo Grade IV 30-day complications, 10.2% for 30-day readmission, and 4.2% for 30-day mortality. On bivariate analysis, infectious patients had the highest incidences of inpatient complications (38.6%, p = 0.030) and Clavien-Dindo Grade IV complications (7.8%, p = 0.055). Patients in the vascular group had the highest rates of readmission (12.7%, p

Although risk calculators are used to prognosticate postoperative outcomes following revision total hip and knee arthroplasty (total joint arthroplasty [TJA]), machine learning (ML) based predictive tools have emerged as a promising alternative for improved risk stratification. This study aimed to compare the predictive ability of ML models for 30-day mortality following revision TJA to that of traditional risk-assessment indices such as the CARDE-B score (congestive heart failure, albumin (< 3.5 mg/dL), renal failure on dialysis, dependence for daily living, elderly (> 65 years of age), and body mass index (BMI) of < 25 kg/m2), 5-item modified frailty index (5MFI), and 6MFI. Adult patients undergoing revision TJA between 2013 and 2020 were selected from the American College of Surgeons National Surgical Quality Improvement Program database and randomly split 80:20 to compose the training and validation cohorts. There were 3 ML models - extreme gradient boosting, random forest, and elastic-net penalized logistic regression (NEPLR) - that were developed and evaluated using discrimination, calibration metrics, and accuracy. The discrimination of CARDE-B, 5MFI, and 6MFI scores was assessed individually and compared to that of ML models. All models were equally accurate (Brier score = 0.005) and demonstrated outstanding discrimination with similar areas under the receiver operating characteristic curve (AUCs, extreme gradient boosting = 0.94, random forest = NEPLR = 0.93). The NEPLR was the best-calibrated model overall (slope = 0.54, intercept = −0.004). The CARDE-B had the highest discrimination among the scores (AUC = 0.89), followed by 6MFI (AUC = 0.80), and 5MFI (AUC = 0.68). Albumin < 3.5 mg/dL and BMI (< 30.15) were the most important predictors of 30-day mortality following revision TJA. The ML models outperform traditional risk-assessment indices in predicting postoperative 30-day mortality after revision TJA. Our findings highlight the utility of ML for risk stratification in a clinical setting. The identification of hypoalbuminemia and BMI as prognostic markers may allow patient-specific perioperative optimization strategies to improve outcomes following revision TJA. [ABSTRACT FROM AUTHOR]

The purpose of this study is to systematically review the evidence in the literature to ascertain the functional outcomes, range of motion (ROM), and complication and reoperation rates after revision reverse shoulder arthroplasty (RSA) for a failed primary total shoulder arthroplasty (TSA) or hemiarthroplasty (HA). Two independent reviewers performed the literature search based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the EMBASE, MEDLINE, and The Cochrane Library databases. Studies were included if they reported clinical outcomes for revision RSA for a failed primary TSA or HA. Our review found 23 studies including 1041 shoulders (627 TSA and 414 HA) meeting our inclusion criteria. The majority of patients were female (66.1%), with an average age of 69.0 years (range: 39-93 years) and a mean follow-up of 46.3 months. American Shoulder and Elbow Surgeons and visual analog scale pain scores improved from 32.6 to 61.9 and 6.7 to 2.7, respectively. ROM results include forward flexion, abduction, and external rotation, which improved from 59.4° to 107.7°, 50.7° to 104.4°, and 19.8° to 26.3°, respectively. Only 1 of the 10 studies reporting internal rotation found a statistically significant difference, with the mean internal rotation improving from S1-S3 preoperatively to L4-L5 postoperatively for patients undergoing HA. The overall complication rate and reoperation rate were 23.4% and 12.5%, respectively. The most common complications were glenoid component loosening (6.0%), fracture (periprosthetic, intraoperative, or other scapula fractures) (n = 4.7%), and infection (n = 3.3%). Revision RSA for a failed primary TSA and HA has been shown to result in excellent functional outcomes and improved ROM, suggesting that patients who have failed TSA or HA may benefit from a revision RSA. [ABSTRACT FROM AUTHOR]

IRIS is a common complication in HIV-infected patients treated for tuberculosis (TB) and cART. Our aim was to evaluate NK cell reconstitution in HIV-infected patients with TB-IRIS compared to those without IRIS. 147 HIV-infected patients with TB from the CAMELIA trial were enrolled. HIV+TB+ patients were followed for 32 weeks. The NK cell repertoire was assessed in whole blood at different time points. As CAMELIA has two arms (early and late cART initiation), we analysed them separately. At enrolment, individuals had low CD4 cell counts (27 cells/mm3) and high plasma viral loads (5.76 and 5.50 log/mL for IRIS and non-IRIS individuals, respectively). Thirty-seven people developed IRIS (in the early and late arms). In the early and late arms, we observed similar proportions of total NK and NK cell subsets in TB-IRIS and non-IRIS individuals during follow-up, except for the CD56dimCD16pos (both arms) and CD56dimCD16neg (late arm only) subsets, which were higher in TB-IRIS and non-IRIS individuals, respectively, after cART. Regarding the repertoire and markers of NK cells, significant differences (lower expression of NKp30, NKG2A (CD159a), NKG2D (CD314) were observed in TB-IRIS compared to non-IRIS individuals after the start of cART. In the late arm, some changes (increased expression of CD69, NKG2C, CD158i) were observed in TB-IRIS compared to non-IRIS individuals, but only before cART initiation (during TB treatment). KIR expression by NK cells (CD158a and CD158i) was similar in both groups. CD69 expression by NK cells decreased in all groups. Expression of the NCR repertoire (NKp30, NKp44, NKp46) has similar kinetics in TB-IRIS subjects compared to non-IRIS subjects regardless of the arm analysed. NK cell reconstitution appeared to be better in TB-IRIS subjects. Although NK cell reconstitution is impaired in HIV infection after cART, as previously reported, it does not appear to be affected by the development of IRIS in HIV and TB-infected individuals.

18F-Labeled Fluorodeoxyglucose-Positron Emission Tomography (18F-FDG PET) is a molecular imaging tool commonly used in practice for the assessment of many cancers. Thanks to its properties, its use has been progressively extended to numerous inflammatory conditions, including chronic inflammatory rheumatism (CIR) such as rheumatoid arthritis (RA), spondylarthritis (SpAs) and polymyalgia rheumatica (PMR). 18F-FDG PET is currently not recommended for the diagnostic of CIRs. However, this whole-body imaging tool has emerged in clinical practice, providing a general overview of systemic involvement occurring in CIRs. Numerous studies have highlighted the capacity of 18F-FDG PET to detect articular and extra articular involvements in RA and PMR. However, the lack of specificity of 18F-FDG limits its use for diagnosis purpose. Finally, the key question is the definition of the best way to integrate this whole-body imaging tool in the patient’s management workflow.

We identify concerns pertinent to establishing trust necessary to support adoptees’ confidence in and uptake of genetic testing that might allow them to benefit from early screening and medical intervention. Using principles of community-based participatory research, our study sought to build a foundation of trust to document such perspectives. Three focus groups were held with 12 adult adoptees. Transcripts were analyzed using thematic content analysis. Comments highlighted aspects related to genomics and health history in the context of adoption, specifically: (1) trust in the intention of the research study; (2) trust that the adoption community will benefit from the results of research; and (3) trust in the protection from misuse and abuse of genomic data. Results reinforce the call for proper security of data and oversight of the ways it is used and point to the value of including researchers who are a part of the community under study.

Reverse shoulder arthroplasty (RSA) is a widely performed surgical procedure to address various shoulder pathologies. Several studies have suggested that radiographic soft-tissue thickness may play a role in predicting complications after orthopedic surgery, but there have been limited studies determining the use of radiographic soft-tissue thickness in RSA. The purpose of this study was to evaluate whether radiographic soft-tissue thickness could predict clinical outcomes after RSA and compare the predictive capabilities against body mass index (BMI). We hypothesized that increased radiographic shoulder soft-tissue thickness would be a strong predictor of operative time, length of stay (LOS), and infection in elective RSA. A retrospective review of patients undergoing RSA at an academic institution was conducted. Preoperative radiographic images were evaluated including measurements of the radius from the humeral head center to the skin (HS), deltoid radius–to–humeral head radius ratio (DHR), deltoid size, and subcutaneous tissue size. Different correlation coefficients were used to analyze various types of relationships, and the strength of these associations was classified based on predefined boundaries. Subsequently, multivariable linear and logistic regressions were performed to determine whether HS, DHR, deltoid size, and subcutaneous tissue size could predict LOS, operative time, or infection while controlling for patient factors. HS was the most influential factor in predicting both operative time and LOS after RSA, with strong associations indicated by standardized β coefficients of 0.234 for operative time and 0.432 for LOS. Subcutaneous tissue size, deltoid size, and DHR also showed stronger predictive values than BMI for both outcomes. In terms of prosthetic joint infection, HS, deltoid size, and DHR were significant predictors, with HS demonstrating the highest predictive power (Nagelkerke R 2 = 0.44), whereas BMI did not show a statistically significant association with infection. Low event counts resulted in wide confidence intervals for odds ratios in the infection analysis. Greater shoulder soft-tissue thickness as measured with concentric circles on radiographs is a strong predictor of operative time, LOS, and postoperative infection in elective primary RSA patients. [ABSTRACT FROM AUTHOR]

Abstract Background Empirical antimicrobial therapy (EAT) is a challenge for community-acquired, hospital-acquired and ventilator-associated pneumonia, particularly in the context of the increasing occurrence of third-generation cephalosporin-resistant Enterobacterales (3GCR-E), including extended-spectrum beta-lactamase Enterobacterales (ESBL-E) and high-level expressed AmpC cephalosporinase-producing Enterobacterales (HLAC-E). To prevent the overuse of broad-spectrum antimicrobial therapies, such as carbapenems, we assessed the performance of screening for intestinal carriage of HLAC-E in addition to ESBL-E to predict 3GCR-E (ESBL-E and/or HLAC-E) presence or absence in respiratory samples in ICU, and to evaluate its potential impact on carbapenem prescription. Materials and methods This monocentric retrospective observational study was performed in a surgical ICU during a 4-year period (January 2013–December 2016). Patients were included if they had a positive culture on a respiratory sample and a previous intestinal carriage screening performed by rectal swabbing within 21 days. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and likelihood ratios were calculated for the screening for intestinal carriage of ESBL-E, HLAC-E and 3GCR-E (ESBL-E and/or HLAC-E) as predictor of their absence/presence in respiratory samples. Impact of HLAC-E and ESBL-E reporting on EAT was also studied. Results 765 respiratory samples, retrieved from 468 patients, were analyzed. ESBL-E prevalence was 23.8% in rectal swab and 4.4% in respiratory samples. HLAC-E prevalence was 9.0% in rectal swabs and 3.7% in respiratory samples. Overall, the 3GCR-E prevalence was 31.8% in rectal swabs and 7.7% in respiratory samples. NPVs were 98.8%, 98.0% and 96.6% for ESBL-E, HLAC-E and 3GCR-E, respectively. Over the study period, empirical antimicrobial therapy was initiated for 315 episodes of respiratory infections: 228/315 (72.4%) were associated with negative intestinal carriage screening for both HLAC-E and ESBL-E, of whom 28/228 (12.3%) were treated with carbapenems. Of 23/315 (7.3%) cases with screening for positive intestinal carriage with HLAC-E alone, 10/23 (43.5%) were treated with carbapenems. Conclusion Systematic screening and reporting of HLAC-E in addition to ESBL-E in intestinal carriage screening could help to predict the absence of 3GCR-E in respiratory samples of severe surgical ICU patients. This could improve the appropriateness of EAT in ICU patients with HAP and may prevent the overuse of carbapenems.

The duration of humoral and cellular immune memory following SARS-CoV-2 infection in populations in least developed countries remains understudied but is key to overcome the current SARS-CoV-2 pandemic. Sixty-four Cambodian individuals with laboratory-confirmed infection with asymptomatic or mild/moderate clinical presentation were evaluated for Spike (S)-binding and neutralizing antibodies and antibody effector functions during acute phase of infection and at 6-9 months follow-up. Antigen-specific B cells, CD4+ and CD8+ T cells were characterized, and T cells were interrogated for functionality at late convalescence. Anti-S antibody titers decreased over time, but effector functions mediated by S-specific antibodies remained stable. S- and nucleocapsid (N)-specific B cells could be detected in late convalescence in the activated memory B cell compartment and are mostly IgG+. CD4+ and CD8+ T cell immune memory was maintained to S and membrane (M) protein. Asymptomatic infection resulted in decreased antibody-dependent cellular cytotoxicity (ADCC) and frequency of SARS-CoV-2-specific CD4+ T cells at late convalescence. Whereas anti-S antibodies correlated with S-specific B cells, there was no correlation between T cell response and humoral immune memory. Hence, all aspects of a protective immune response are maintained up to nine months after SARS-CoV-2 infection and in the absence of re-infection.

After marketing authorisation, the development of a medicinal product often continues with studies investigating new therapeutic indications. Positive results can potentially lead to changes to the terms of the marketing authorisation, such as an extension of therapeutic indication(s). These studies can be initiated and sponsored by the marketing authorisation holder (MAH) or by others. When results from an investigator-initiated trial suggest that an authorised medicinal product is safe and effective for a new therapeutic indication, physicians may want to treat their patients with this medicinal product. In such a situation, it is desirable to extend the therapeutic indication(s) via the regulatory approval process, as this can facilitate patient access within the European Union. There may however be challenges when the MAH did not conduct the study and might not have access to the data. In this perspective, we focus on the possibilities to extend the therapeutic indication(s) of an already authorised medicinal product based on results from investigator-initiated trials. We address: (1) the advantages of an extension of indication; (2) the regulatory requirements for a variation application; (3) investigator-initiated trials as a basis for regulatory approval; (4) the role of the MAH in extending the indication. With this article, we want to emphasize the importance of a collaborative approach and dialogue between stakeholders with the aim to facilitate access to effective medicinal products.

Thermal mass of buildings and domestic hot water tanks represent interesting sources of thermal energy storage readily available in the existing building stock. To exploit them to their full potential, advanced control strategies and a coupling to the power grid with heat pump systems represent the most promising combination. In this paper, model predictive control (MPC) strategies are developed and tested in a semi-virtual environment laboratory setup: a real heat pump is operated from within a controlled climate chamber and coupled with loads of a virtual building, i.e., a detailed dynamic building simulation tool. Different MPC strategies are tested in this laboratory setup, with the goals to minimize either the delivered thermal energy to the building, the operational costs of the heat pump, or the CO2 emissions related to the heat pump use. The results highlight the ability of the MPC controller to perform load-shifting by charging the thermal energy storages at favorable times, and the satisfactory performance of the control strategies is analyzed in terms of different indicators, such as costs, comfort, carbon footprint, and energy flexibility. The practical challenges encountered during the implementation with a real heat pump are also discussed and provide additional valuable insights.

Knowledge strongly affects attitudes toward waste management; thus, embedding an environmental mentality at a young age is crucial. Game-based interventions, such as gamification and game-based learning, have huge potential to be effective learning tools. This paper examines the potential of gamification to improve waste management practices among schoolchildren through a narrative review of 25 papers on gamification for waste management and gamification for schoolchildren. The effectiveness of game-based learning and gamification in mitigating waste management issues with schoolchildren has not yet been well-described in the literature; however, the evolving market in related sectors is a strong indication of their potential. A robust understanding of social and behavioral theories is necessary for implementing gamification and game-based learning effectively. Additionally, the game elements, design, and mechanics that can achieve the most positive impacts should be explored further. It is hoped that this study will contribute to the body of knowledge in the environmental sector on gamification as an innovative process for improving household-level waste management behavior among schoolchildren.

On the 15 November 2018, the Committee for Medicinal Products for Human Use adopted an extension to an existing indication for the use of nivolumab (Opdivo) in combination with ipilimumab (Yervoy) for the first-line treatment of adult patients with intermediate/poor-risk advanced renal cell carcinoma (RCC). The approval was based on results from the Pivotal CA209214 study, a randomised, open-label, phase III study, comparing nivolumab +ipilimumab with sunitinib in subjects≥18 years of age with previously untreated advanced RCC (not amenable for surgery or radiotherapy) or metastatic RCC, with a clear-cell component. A total of 1096 patients were randomised in the trial, of which 847 patients had intermediate/poor-risk RCC and received either nivolumab (n=425) in combination with ipilimumab administered every 3 weeks for 4 doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks or sunitinib (n=422) administered orally for 4 weeks followed by 2 weeks off, every cycle. A statistically significant difference in overall survival (OS) was observed in the nivolumab + ipilimumab group compared with the sunitinib group in intermediate/poor-risk subjects (HR 0.63 (99.8% CI 0.44 to 0.89); stratified log-rank 2-sided p-value

Invasive cardiovascular infections by Mycobacterium chimaera associated with open-heart surgery have been reported worldwide since 2013. Here, we report a case of a 61 year old man, without any other particular medical background, who underwent cardiac surgery for replacing part of the ascending aorta by a bio-prosthetic graft. Eighteen months later, the patient was painful at the lower back with fever. A pyogenic vertebral osteomyelitis due to M. chimaera associated to graft infection was diagnosed after 6 months of sub-acute infection. The patient presented a disseminated disease with cerebral lesions, chorioretinitis, and chronic renal failure. Despite adequate antimicrobial treatment and graft explantation, the patient died after 6 years. We reviewed the literature on M. chimaera infections associated with open-heart surgery. The worldwide outbreak has been explained by airborne bioaerosol generated by the 3T heater–cooler unit (HCU) used during cardiac by-pass surgical procedures. These infections are difficult to diagnose because of a long latency period (up to several years), with no specific symptoms and a highly specialized microbiological diagnosis. The treatment is based on antibiotics and surgery. These infections are also difficult to treat, since the mortality rate is high around 50%. Prevention is necessary by modifying the use of HCUs in operating rooms.

The purpose of this study was to perform a meta-analysis of randomized controlled trials (RCTs) to compare outcomes following intramedullary nailing (IMN) vs. open reduction–internal fixation (ORIF) for humeral shaft fractures. A literature search of 3 databases was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RCTs comparing IMN and ORIF for humeral shaft fractures were included. Clinical outcomes were compared using RevMan. P <.05 was considered statistically significant. Ten RCTs with 512 patients were included. Overall, 8.4% of patients treated with IMN and 6.4% of patients treated with ORIF had nonunion (P =.57, I 2 = 0%), with a significantly faster time to union with IMN (10 weeks vs. 11.9 weeks, P <.05). There was no significant difference in the rate of reoperation (11.6% in IMN group vs. 7.6% in ORIF group, P =.26) or radial nerve palsy (2.8% in IMN group vs. 4.2% in ORIF group, P =.58). A lower rate of infection was noted with IMN (1.2% vs. 5.3%, P <.05). Additionally, there was a lower operative time with IMN (61 minutes vs. 88 minutes, P <.05). The Level I evidence in the literature does not show a significant difference in rates of union, reoperation, or radial nerve palsy between IMN and ORIF for humeral shaft fractures. Overall, treatment with IMN results in a lower infection rate, less operative time, and a modestly quicker time to union. The optimal treatment strategy for humeral shaft fractures may be best informed by fracture pattern and surgeon preference. [ABSTRACT FROM AUTHOR]

BackgroundDespite expansion of interest among American medical students in global health (GH), academic medical centers face multiple obstacles to the development of structured GH curricula and career guidance. To meet these demands we sought to provide a systematic analysis of the accounts of GH experts.MethodsWe developed a collaborative, interview-based, qualitative analysis of GH experiences across six career-related themes that are relevant to medical students interested in GH: justification, medical education, economics, research prospects, law and ethics, and work-life balance. Seven GH faculty members were interviewed for 30-90 minutes using sample questions as guidelines. We applied a grounded theory approach to analyze the interview transcripts to discover an emerging theory pertinent to GH trainees.FindingsRegarding 'justification,' 4 respondents defined GH as work with the underserved irrespective of geographic location; 5 respondents found sustainability imperative; and all respondents believe GH creates better physicians. Respondents identified many physician competencies developed through GH 'medical education,' with 5 respondents agreeing that work with underserved populations has transformative potential. Concerning 'economics', 3 respondents acknowledged GH's popularity among trainees, resulting in increased training opportunities, and 2 respondents emphasized an associated deficiency in program quality. All respondents described career models across specialties. Four respondents noted funding challenges when discussing 'research prospects'. Within the theme of 'laws and ethics', 4 respondents perceived inadequate accountability, and 6 respondents identified ways to create accountability. Finally, 6 respondents recognized family demands can compromise one's GH career and thus 'work-life balance'.ConclusionDespite diverse perspectives on the meaning and sustainability of GH work, this analysis provides a nascent framework that may inform curricular development for GH trainees. Suggestions are offered for elaborating this framework to fully exploit the transformative potential of GH training in medical education.

Objectives: In this study, we document the clinical characteristics and investigated risk factors for uncomplicated and severe forms of EV-A71 disease in Cambodian children. Methods: From March to July 2014 inclusive, all patients with suspicion of EV-A71 infection presenting to Kantha Bopha Hospitals in Phnom Penh and Siem Reap and confirmed by the Virology Unit at the Institut Pasteur du Cambodge were prospectively enrolled in this study. Throat swabs, rectal swabs and serum samples were collected from all consecutive patients with suspected EV-A71 infection. In addition, CSF was also collected from patients with suspected EV-A71 associated encephalitis. A total of 122 patients (29 with uncomplicated disease and 93 with severe disease) with confirmed EV-A71 infection with all available demographic and clinical data for clinical classification and further analysis were included in the study. Results: In this prospective EV-A71 study in Cambodia, we confirmed the previously reported association of male gender and absence of mouth or skin lesions with severe disease. We also highlighted the strong association of neutrophils in blood, but also in CSF in patients with pulmonary oedema. More importantly, we identified new putative nutrition-related risk factors for severe disease. Conclusions: EV-A71 is an important cause of encephalitis in the Asia-Pacific region. Further studies to determine the risk factors associated with severe EV-A71 disease are needed.

Background: Human Immunodeficiency Virus 1 (HIV-1) and Mycobacterium Tuberculosis (Mtb) co-infected patients are commonly at risk of immune reconstitution inflammatory syndrome (IRIS) when initiating antiretroviral treatment (ART). Evidence indicates that innate immunity plays a role in TB-IRIS. Here, we evaluate the phenotype of Gamma-delta (γδ) T cells and invariant Natural Killer (iNK) T cells in tuberculosis-associated IRIS.Methods: Forty-eight HIV+/TB+ patients (21 IRIS) and three control groups: HIV–/TB– (HD, n = 11), HIV+/TB– (n = 26), and HIV–/TB+ (n = 22) were studied. Samples were taken at ART initiation (week 2 of anti-tuberculosis treatment) and at the diagnosis of IRIS for HIV+/TB+; before ART for HIV+/TB-, and at week 2 of anti-tuberculosis treatment for HIV–/TB+ patients. γδ T cells and Invariant natural killer T (iNKT) cells were analyzed by flow cytometry.Results: Before ART, IRIS, and non-IRIS patients showed a similar proportion of γδpos T and iNKT cells. HLA-DR on γδpos T cells and δ2posγδpos T cells was significantly higher in TB-IRIS vs. non-IRIS patients and controls (p < 0.0001). NKG2D expression on γδpos T cells and the δ2posγδpos T cell subset was lower in HIV+/TB+ patients than controls. CD158a expression on γδpos T cells was higher in TB-IRIS than non-IRIS (p = 0.02), HIV+/TB–, and HIV–/TB- patients.Conclusion: The higher activation of γδposT cells and the γδ2posγδpos T cell subset suggests that γδ T cells may play a role in the pathogenesis of TB-IRIS.

An amendment to this paper has been published and can be accessed via the original article.

Background: During a 3-year time frame, a partnership between medical trainees in Haiti and the United States was forged with the objective of implementing an emergency response skills curriculum at a medical school in Port-au-Prince. The effort sought to assess the validity of a near-peer, bidirectional, cross-cultural teaching format as both a global health experience for medical students and as an effective component of improving medical education and emergency response infrastructure in developing countries such as Haiti. Method: Medical students and emergency medicine (EM) residents from a North American medical school designed and taught a module on emergency response skills in PAP and certified medical students in basic cardiac life support (BLS) over 2 consecutive years. Five-point Likert scale self-efficacy (SE) surveys and multiple-choice fund of knowledge (FOK) assessments were distributed pre- and postmodule each year and analyzed with paired 't'tests and longitudinal follow-up of the first cohort. Narrative evaluations from participants were collected to gather feedback for improving the module. Findings: Challenges included bridging language barriers, maintaining continuity between cohorts, and adapting to unexpected schedule changes. Overall, 115 students were certified in BLS with significant postcurriculum improvements in SE scores (2.75 ± 0.93 in 2013 and 2.82 ± 1.06 in 2014; 'P' < 0.001) and FOK scores (22% ± 15% in 2013 and 41% ± 16% in 2014; 'P' < 0.001). Of 24 Haitian students surveyed at 1-year follow-up from the 2013 cohort, 7 (29.3%) reported using taught skills in real-life situations since completing the module. The US group was invited to repeat the project for a third year. Conclusions: Near-peer, cross-cultural academic exchange is an effective method of medical student–centered emergency training in Haiti. Limitations such as successfully implementing sustainability measures, addressing cultural differences, and coordinating between groups persist. This scalable, reproducible, and mutually beneficial collaboration between North American and Haitian medical trainees is a valid conduit for building Haiti's emergency response infrastructure and promoting global health.

The US Food and Drug Administration (FDA) oversees medical device regulation and oversight in the United States, and the majority of shoulder arthroplasty devices are cleared via the 510(k) pathway, in which a device demonstrates "substantial equivalence" to a previously cleared predicate. The purpose of this study was to determine an interconnected ancestral network of shoulder arthroplasty devices and determine equivalency ties to devices subsequently recalled by the FDA for design-related issues. The FDA 510(k) database was used to identify all legally marketed shoulder arthroplasty devices from May 28, 1976, to July 1, 2021. Direct predicate information obtained via clearance summary documents associated with each device was used to generate an ancestral genealogy network for all shoulder arthroplasty devices cleared between July 1, 2020, and July 1, 2021. FDA design recalls were analyzed, and the number of descendant devices was calculated for each recalled device. An evaluation of all 476 510(k) premarket notification pathway–cleared shoulder devices since 1976 identified 0-313 descendant devices for each. Eighty of these devices (16.8%) have since been recalled, of which 10 recalls were directly related to implant design issues. Furthermore, among 29 of the most recently cleared devices (July 1, 2020-July 1, 2021), 16 (55.2%) claim predicates devices that have subsequently been withdrawn from the market because of design-related failures. Shoulder arthroplasty devices are linked together via an interconnected FDA 510(k) equivalency approval network dating back to 1976 despite substantive changes in material specifications and device design, many of which have since been recalled. Many of the cleared modern devices claim predicates based on subsequently recalled prostheses. [ABSTRACT FROM AUTHOR]

Objective: There continues to be controversy over whether operative delay is necessary for patients on antiplatelet therapy, particularly for elderly patients with hip fractures. This study sought to assess current clinical practices of orthopedic surgeons regarding perioperative management of these patients. Methods: A 12-question, Web-based survey was distributed to orthopedic surgeons via e-mail. Questions regarding timing of surgery assumed patients were on antiplatelet therapy and assessed attitudes toward emergent and nonemergent orthopedic cases as well as operative delay for specific closed fracture types. Responses were compared using unpaired, 2-tailed Student t tests for continuous variables and Pearson chi-square tests with odds ratios (ORs) and 95% confidence intervals (CIs) for categorical variables. Statistical significance was defined as a P value

Introduction: Participants who sustain a fragility fracture are at increased risk for subsequent fractures. Despite the consequences of recurrent fractures, bone mineral density (BMD) testing and treatment rates for osteoporosis after a fracture remain low. The New York University (NYU) Langone Osteoporosis Model of Care was developed to identify women at increased risk for recurrent fractures and to reduce the rates of subsequent fracture through patient and physician education. Methods: Women aged 50 years and older who had a fracture and received their care at NYU affiliated hospitals were contacted via mail after discharge. Participants were provided educational materials explaining decreased bone strength and its possible relationship to their fracture and were asked to complete a questionnaire. One year postfracture, participants were sent follow-up questionnaires requesting their most recent fracture treatment and BMD information. Educational material was also provided to the treating orthopedic surgeons. Results: Overall, 524 patients were contacted and 210 (40%) enrolled. By the end of 24 months, 92 participants completed their 1-year questionnaire (44% of the enrollees). Forty-two (46%) participants had undergone new BMD testing and 37 (40%) were receiving antiresorptive medications, including 6 (6%) who had not been prescribed these medications before enrolling in the program. Conclusions: The Osteoporosis Model of Care is a simple and cost-effective educational program, which improved comprehensive fracture care in an actual clinical setting. Patient enrollment remains a challenge in implementing the program. Our program highlights difficulties in providing community-dwelling participants with appropriate postfracture care. With increasing concern among the public regarding the use of bone strengthening medications and continued low postfracture treatment rates, educating patients with high fracture risk is critical to reducing the rate of subsequent fracture. Our Model of Care Program demonstrates both the success and limitations of a postfracture educational approach using discharge diagnosis data to identify patients with fracture.