Impact of hospital internships on success in university summative objective structured clinical examinations: Large-scale experience in a French medical school.

BACKGROUND: Objective structured clinical examinations (OSCEs) are extensively used in many medical schools worldwide with the stated objective to assess students' clinical skills acquired during internships. The objective of the present study was to assess the factors associated with success in university summative OSCEs, especially the impact of previous hospital internships in corresponding disciplines and supervision during internships. METHODS: This was a cross-sectional study assessing the results in the summative OSCEs of 4th year medical students during the 2021-2022 academic year in a French medical school. The summative OSCEs included five stations for each student. Each student answered a survey at the end of summative OSCEs about previous internships, the supervision they had and perceived difficulty levels for each station. The scores in each station were assessed according to previous hospital internships in the corresponding discipline. Analysis of predictive factors of success in OSCEs, defined by a score ≥ 10/20 at each station, were performed using univariate and multivariate logistic regression. RESULTS: Out of the 220 students participating in the summative OSCEs, 182 (83%) answered the survey. One hundred and forty-four (79%) of these students had carried out hospital internships in at least one of the disciplines evaluated during the OSCEs. Students having completed an internship in the corresponding discipline had significantly higher OSCEs scores for interrogation, communication, therapeutic education and procedure stations compared to those who had not. Previous internship in corresponding disciplines was independently associated with success in OSCEs in interrogation (OR 9.45 [1.34-66.8] p = 0.02), clinical examination (OR 6.93 [1.88-25.57] p = 0.004, and therapeutic education (OR 3.09 [1.22-7.82] p = 0.02) stations. CONCLUSION: Previous hospital internships in the discipline evaluated by the OSCEs are associated with success in summative OSCEs. This reinforces the importance of student involvement during their hospital internships.

Assessing Functional Capacity in Directly and Remotely Monitored Home-Based Settings in Individuals With Chronic Respiratory Diseases: Protocol for a Multinational Validation Study.

BACKGROUND: Pulmonary rehabilitation is widely recommended to improve functional status and as secondary and tertiary prevention in individuals with chronic pulmonary diseases. Unfortunately, access to timely and appropriate rehabilitation remains limited. To help close this inaccessibility gap, telerehabilitation has been proposed. However, exercise testing is necessary for effective and safe exercise prescription. Current gold-standard tests, such as maximal cardiopulmonary exercise testing (CPET) and the 6-minute walk test (6MWT), are poorly adapted to home-based or telerehabilitation settings. This was an obstacle to the continuity of services during the COVID-19 pandemic. It is essential to validate tests adapted to these new realities, such as the 6-minute stepper test (6MST). This test, strongly inspired by 6MWT, consists of taking as many steps as possible on a "stepper" for 6 minutes. OBJECTIVE: This study aims to evaluate the metrological qualities of 6MST by (1) establishing concurrent validity and agreement between the 6MST and CPET, as well as with the 6MWT; (2) determining test-retest reliability in a home-based setting with direct and remote (videoconferencing) monitoring; and (3) documenting adverse events and participant perspectives when performing the 6MST in home-based settings. METHODS: Three centers (Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec in Québec, Groupement des Hôpitaux de l'Institut Catholique de Lille in France, and FormAction Santé in France) will be involved in this multinational project, which is divided into 2 studies. For study 1 (objective 1), 30 participants (Québec, n=15; France, n=15) will be recruited. Two laboratory visits will be performed to assess anthropometric data, pulmonary function, and the 3 exercise tolerance tests (CPET, 6MWT, and 6MST). Concurrent validity (paired sample t tests and Pearson correlations) and agreement (Bland-Altman plots with 95% agreement limits) will be evaluated. For study 2 (objectives 2 and 3), 52 participants (Québec, n=26; France, n=26) will be recruited. Following a familiarization trial (trial 1), the 6MST will be conducted on 2 separate occasions (trials 2 and 3), once under direct supervision and once under remote supervision, in a randomized order. Paired sample t test, Bland-Altman plots, and intraclass correlations will be used to compare trials 2 and 3. A semistructured interview will be conducted after the third trial to collect participants' perspectives. RESULTS: Ethical approval was received for this project (October 12, 2023, in Québec and September 25, 2023, in France) and the first participant was recruited in February 2024. CONCLUSIONS: This study innovates by validating a new clinical test necessary for the development and implementation of new models of rehabilitation adapted to home and telerehabilitation contexts. This study also aligns with the United Nations Sustainable Development Goals by contributing to augmenting health care service delivery (goal 3) and reducing health care access inequalities (goal 11). TRIAL REGISTRATION: ClinicalTrials.gov NCT06447831; https://clinicaltrials.gov/study/NCT06447831. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57404.

Diagnostic Strategy Using Color Doppler Ultrasound of Temporal Arteries in Patients With High Clinical Suspicion of Giant Cell Arteritis : A Prospective Cohort Study.

BACKGROUND: Giant cell arteritis (GCA) is the most prevalent systemic vasculitis in people older than 50 years. Any delay in diagnosis impairs patients' quality of life and can lead to permanent damage, particularly vision loss. OBJECTIVE: To evaluate a diagnostic strategy for GCA using color Doppler ultrasound of the temporal artery as a first-line diagnostic test, temporal artery biopsy (TAB) as a secondary test, and physician expertise as the reference method. DESIGN: Prospective multicenter study with a 2-year follow-up. (ClinicalTrials.gov: NCT02703922). SETTING: Patients were referred by their general practitioner or ophthalmologist to a physician with extensive experience in GCA diagnosis and management in one of the participating centers: 4 general and 2 university hospitals. PATIENTS: 165 patients with high clinical suspicion of GCA, aged 79 years (IQR, 73 to 85 years). INTERVENTION: The diagnostic procedure was ultrasound, performed less than 7 days after initiation of corticosteroid therapy. Only ultrasound-negative patients underwent TAB. MEASUREMENTS: Bilateral temporal halo signs seen on ultrasound were considered positive. Ultrasound and TAB results were compared with physician-diagnosed GCA based on clinical findings and other imaging. RESULTS: Diagnosis of GCA was confirmed in 44%, 17%, and 21% of patients by ultrasound, TAB, and clinical expertise and/or other imaging tests, respectively. Their diagnosis remained unchanged at 1 month, and 2 years for those with available follow-up data. An alternative diagnosis was made in 18% of patients. The proportion of ultrasound-positive patients among patients with a clinical GCA diagnosis was 54% (95% CI, 45% to 62%). LIMITATION: Small sample size, no blinding of ultrasound and TAB results, lack of an objective gold-standard comparator, and single diagnostic strategy. CONCLUSION: By using ultrasound of the temporal arteries as a first-line diagnostic tool in patients with high clinical suspicion of GCA, further diagnostic tests for patients with positive ultrasound were avoided. PRIMARY FUNDING SOURCE: Tender "Recherche CH-CHU Poitou-Charentes 2014."

Belimumab corticosteroid-sparing treatment in systemic lupus erythematosus: a real-life observational study (BESST study).

Data about the impact of Belimumab on corticosteroid sparing in real life are scarce. To assess the corticosteroid-sparing effect among patients with systemic lupus erythematosus (SLE) treated with Belimumab in real-life settings. Multicentric observational retrospective study including patients with SLE and having received Belimumab for at least 6 months between 2011 and 2020, in eight French hospitals. "Low dose" referred to patients receiving up to 7.5 mg of prednisone a day and "Very low dose" to those receiving strictly ≤ 5 mg prednisone a day The primary endpoint was the reduction of daily prednisone dose after six months of Belimumab. The secondary endpoint was a change in the proportion of patients with low or very low dose of prednisone as well as those without prednisone during the Belimumab course. Censoring occurred for patients who stopped Belimumab. Bivariate analyses were performed using the Wilcoxon signed-rank test. The threshold for statistical significance was set at p < 0.05. Thirty patients were included. All were female with a median age of 38 years. A significant reduction in prednisone dose was observed at month 6 (10 [7-20] vs 6.75 [2-9] mg, p < 0.0001), continued until month 12 (10 [7-20] mg vs 5 [0-7.12] mg, p < 0.001) and was sustained until month 24. The proportion of patients with very low dose of prednisone and those without prednisone progressively increased during the Belimumab course. Introducing Belimumab in patients with SLE, in real-life conditions, is associated with early and sustained corticosteroid-sparing effect.

Normal B cells express ZAP70 in chronic lymphocytic leukemia: A link between autoimmunity and lymphoproliferation?

ZAP70 has a prognostic value in chronic lymphocytic leukemia (CLL), through altered B-cell receptor signaling, which is important in CLL pathogenesis. A good correlation between ZAP70 expression in CLL cells and the occurrence of autoimmune phenomena has been reported. Yet, the great majority of CLL-associated autoimmune cytopenia is due to polyclonal immunoglobulin (Ig) G synthesized by nonmalignant B cells, and this phenomenon is poorly understood. Here, we show, using flow cytometry, that a substantial percentage of CD5- nonmalignant B cells from CLL patients expresses ZAP70 compared with CD5- B cells from healthy subjects. This ZAP70 expression in normal B cells from CLL patients was also evidenced by the detection of ZAP70 mRNA at single-cell level with polyclonal Ig heavy- and light-chain gene transcripts. ZAP70+ normal B cells belong to various B-cell subsets and their presence in the naïve B-cell subset suggests that ZAP70 expression may occur during early B-cell development in CLL patients and potentially before malignant transformation. The presence of ZAP70+ normal B cells is associated with autoimmune cytopenia in CLL patients in our cohort of patients, and recombinant antibodies produced from these ZAP70+ nonmalignant B cells were frequently autoreactive including anti-platelet reactivity. These results provide a better understanding of the implication of ZAP70 in CLL leukemogenesis and the mechanisms of autoimmune complications of CLL.

Home-Based Resistance Training Programme in Fontan Patients: It Is Feasible, Safe, and Efficient.

Background: Fontan physiology is characterized by a single functional systemic ventricle that reduces cardiac output adaptation and exercise capacity. Peripheral muscle pump is crucial for venous return, and resistance training of the peripheral muscles may be particularly beneficial for cardiac function in these patients. This study explores the feasibility of a training programme including safety and effectiveness, maximal exercise capacity, cardiorespiratory endurance, and quality of life in a Fontan population. Methods: Twelve Fontan patients (18-32 years old) with New York Heart Association functional classes I and II were recruited. The intervention was 12 weeks of home-based exercise programme of 3 sessions per week supervised online by a physiotherapist. Pre- and postintervention evaluations assessed lean body mass, segmental forces with a hand-held dynamometer, maximal oxygen consumption (VO2max), cardiovascular endurance, leg endurance with a 1-minute-sit-to-stand test, and quality of life with a 36-item Short-Form Survey. Results: A total of 11 of 12 participants completed 35 of 36 workouts, exceeding our 80% threshold for completion. No adverse events were reported. Leg muscle strength increased significantly (knee extensors improved by 22.8 ± 22.8 N m [17.7%], P = 0.019). Despite no change in VO2max, endurance time showed a significant improvement of 5.3 minutes (72%). Perceived physical condition evaluated with a self-perception scale improved significantly. There was no significant difference in the lean body mass and in quality of life. Conclusion: In this small group of post-Fontan patients with mild functional impairments, we describe a structured, accessible, and feasible home-based resistance training programme that seems safe and show improvements in strength and perceived physical condition.

Contexte: La physiologie qui découle de l'intervention de Fontan se caractérise par un cœur univentriculaire fonctionnel pour la circulation générale, ce qui réduit l'adaptation du débit cardiaque et la tolérance à l'effort. Le pompage par les muscles périphériques est essentiel au retour veineux, et un entraînement musculaire pourrait donc être bénéfique pour la fonction cardiaque des patients qui ont subi cette intervention. Dans notre étude, nous évaluons la possibilité de mettre en place un programme d'entraînement et examinons l'innocuité et l'efficacité d'un tel programme, la tolérance à l'effort maximal, l'endurance cardiorespiratoire et la qualité de vie chez des patients présentant une circulation de Fontan. Méthodologie: Nous avons recruté 12 patients (âgés de 18 à 32 ans) présentant une circulation de Fontan avec les classes fonctionnelles I et II selon la New York Heart Association. L'intervention prenait la forme d'un programme d'exercice à domicile de trois séances par semaine pendant douze semaines, sous la supervision en ligne d'un physiothérapeute. Les évaluations réalisées avant et après l'intervention incluaient la masse maigre, la force de différents segments corporels évaluée par un dynamomètre portatif, la consommation maximale d'oxygène (VO2max), l'endurance cardiovasculaire, l'endurance des jambes évaluées par un test du lever de la chaise d'une minute et un court questionnaire de 36 questions sur la qualité de vie. Résultats: Au total, 11 des 12 participants ont réalisé 35 entraînements sur 36, ce qui dépassait le seuil de réussite du programme établi à 80 %. Aucun effet indésirable n'a été signalé. La force des muscles des jambes a significativement augmenté (l'amélioration de la force des extenseurs des genoux s'élevait à 22,8 ± 22,8 N m [17,7 %] [p = 0,019]). Malgré une valeur de VO2max restée stable, le temps d'endurance s'est amélioré significativement, soit de 5,3 minutes (72 %). La perception de la condition physique, mesurée sur une échelle d'autoévaluation par les patients, s'est améliorée significativement. Aucune différence significative n'a été relevée dans la masse maigre et la qualité de vie des patients. Conclusion: Dans un petit groupe de patients ayant subi une intervention de Fontan et présentant une atteinte fonctionnelle légère, nous décrivons un programme structuré de musculation à domicile accessible et réalisable qui semble sécuritaire et qui a amélioré la force et de la perception de la condition physique des patients.

Room-temperature continuous-wave topological Dirac-vortex microcavity lasers on silicon.

Robust laser sources are a fundamental building block for contemporary information technologies. Originating from condensed-matter physics, the concept of topology has recently entered the realm of optics, offering fundamentally new design principles for lasers with enhanced robustness. In analogy to the well-known Majorana fermions in topological superconductors, Dirac-vortex states have recently been investigated in passive photonic systems and are now considered as a promising candidate for robust lasers. Here, we experimentally realize the topological Dirac-vortex microcavity lasers in InAs/InGaAs quantum-dot materials monolithically grown on a silicon substrate. We observe room-temperature continuous-wave linearly polarized vertical laser emission at a telecom wavelength. We confirm that the wavelength of the Dirac-vortex laser is topologically robust against variations in the cavity size, and its free spectral range defies the universal inverse scaling law with the cavity size. These lasers will play an important role in CMOS-compatible photonic and optoelectronic systems on a chip.

Polyclonal hypergammaglobulinaemia: towards definition of a threshold.

BACKGROUND: Polyclonal hypergammaglobulinaemia (PH) represents a classic diagnosis problem in internal medicine. However, there is no consensus threshold for PH. The aim of this study was to define a threshold for PH. METHODS: We conducted a retrospective multicentric study using laboratory biological databases between 1 January 2016 and 31 December 2016 in two university hospitals and one non-university hospital. All patients 18 years old or over and with at least one serum protein electrophoresis (SPE) available in 2016 were included. Exclusion criteria were monoclonal, biclonal, or oligoclonal spikes or, in case of hypogammaglobulinaemia, proven free light chain gammopathy. The main endpoint was to define the threshold values for PH in this population. Another objective was to define the 95th percentile of the distribution. RESULTS: 20 766 SPEs were included in this cohort. The PH threshold on 95th percentile was 18.9 g/L. The threshold varied according to geographical areas. CONCLUSIONS: This is the first study to scientifically define a PH threshold. The main limitation is that our threshold is only biological. The study was not designed to associate this threshold with a clinically active disease. In conclusion, while the 19 g/L cut-off seems the most relevant threshold, but it will need to be validated by prospective studies.

Monolithically integrated photonic crystal surface emitters on silicon with a vortex beam by using bound states in the continuum.

Optical resonant cavities with high quality factor (Q-factor) are widely used in science and technology for their capabilities of strong confinement of light and enhanced light-matter interaction. The 2D photonic crystal structure with bound states in the continuum (BICs) is a novel concept for resonators with ultra-compact device size, which can be used to generate surface emitting vortex beams based on symmetry-protected BICs at the Γ point. Here, to the best of our knowledge, we demonstrate the first photonic crystal surface emitter with a vortex beam by using BICs monolithically grown on CMOS-compatible silicon substrate. The fabricated quantum-dot BICs-based surface emitter operates at 1.3 µm under room temperature (RT) with a low continuous wave (CW) optically pumped condition. We also reveal the BIC's amplified spontaneous emission with the property of a polarization vortex beam, which is promising to provide a novel degree of freedom in classical and quantum realms.

Prognostic factors in giant cell arteritis associated aortitis with PET/CT and CT angiography at diagnosis.

BACKGROUND: Prognosis data on giant-cell arteritis (GCA)-associated aortitis are scarce and heterogeneous. The aim of this study was to compare the relapses of patients with GCA-associated aortitis according to the presence of aortitis on CT-angiography (CTA) and/or on FDG-PET/CT. METHODS: This multicenter study included GCA patients with aortitis at diagnosis; each case underwent both CTA and FDG-PET/CT at diagnosis. A centralized review of image was performed and identified patients with both CTA and FDG-PET/CT positive for aortitis (Ao-CTA+/PET+); patients with positive FDG-PET/CT but negative CTA for aortitis (Ao-CTA-/PET+), and patients solely positive on CTA. RESULTS: Eighty-two patients were included with 62 (77%) of female sex. Mean age was 67±8 years; 64 patients (78%) were in the Ao-CTA+/PET+ group; 17 (22%) in the Ao-CTA-/PET+ group and 1 had aortitis only on CTA. Overall, 51 (62%) patients had at least one relapse during follow-up: 45/64 (70%) in the Ao-CTA+/PET+ group and 5/17 (29%) in the Ao-CTA-/PET+ group (log rank, p = 0.019). In multivariate analysis, aortitis on CTA (Hazard Ratio 2.90, p = 0.03) was associated with an increased risk of relapse. CONCLUSION: Positivity of both CTA and FDG-PET/CT for GCA-related aortitis was associated with an increased risk of relapse. Aortic wall thickening on CTA was a risk factor of relapse compared with isolated aortic wall FDG uptake.

Use of platelet inhibitors for digital ulcers related to systemic sclerosis: EUSTAR study on derivation and validation of the DU-VASC model.

OBJECTIVE: To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. METHODS: We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. RESULTS: Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. CONCLUSION: The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

Severe Infections in Patients Treated with Tocilizumab for Systemic Diseases Other Than Rheumatoid Arthritis: A Retrospective Multicenter Observational Study.

OBJECTIVE: This study aimed to describe severe infections in patients treated with tocilizumab for systemic diseases other than rheumatoid arthritis. METHODS: Data from patients receiving at least 2 doses of tocilizumab for systemic diseases other than rheumatoid arthritis between January 1, 2012, and July 1, 2020, in the region Poitou-Charentes (France) were retrospectively collected from medical records. Psoriatic arthritis and systemic juvenile idiopathic arthritis were also excluded as usually treated with similar modalities to rheumatoid arthritis. RESULTS: Of 37 patients, mainly suffering from giant cell arteritis, 25 patients (68%) had at least 1 infectious event and 15 severe infections occurred in 6 patients (3.2/100 patient-years), mainly bacterial. Lower respiratory tract and skin were the main sites. Severe bacterial infections were associated with a marked biological inflammatory syndrome, even under a cycle of administration of tocilizumab. Two severe zonas and 1 severe diverticulitis occurred. No tuberculosis or viral hepatitis reactivation was observed. CONCLUSION: The incidence rate of severe infections was 3.2/100 patient-years and seems lower than that reported in rheumatoid arthritis. C-reactive protein dosage could be helpful for the diagnosis of bacterial infectious adverse events in patients on tocilizumab. Further larger studies are needed to confirm these results to assess potential risk factors for severe infections.

Immune Checkpoint Inhibitor-Related Cytopenias: About 68 Cases from the French Pharmacovigilance Database.

Immune checkpoint inhibitor (ICI)-related cytopenias have been poorly described. This study aimed to further characterize ICI-related cytopenias, using the French pharmacovigilance database. All grade ≥ 2 hematological adverse drug reactions involving at least one ICI coded as suspected or interacting drug according to the World Health Organization criteria and reported up to 31 March 2022, were extracted from the French pharmacovigilance database. Patients were included if they experienced ICI-related grade ≥ 2 cytopenia. We included 68 patients (75 ICI-related cytopenias). Sixty-three percent were male, and the median age was 63.0 years. Seven patients (10.3%) had a previous history of autoimmune disease. Immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) were the most frequently reported (50.7% and 25.3%, respectively). The median time to onset of ICI-related cytopenias was 2 months. Nearly half were grade ≥ 4, and three patients died from bleeding complications of refractory ITP and from thromboembolic disease with active AIHA. Out of 61 evaluable responses, complete or partial remission was observed after conventional treatment in 72.1% of ICI-related cytopenias. Among the 10 patients with ICI resumption after grade ≥ 2 ICI-related cytopenia, three relapsed. ICI-related cytopenias are rare but potentially life-threatening. Further studies are needed to identify risk factors of ICI-related cytopenias.

Role of progression of training volume on intramuscular adaptations in patients with chronic obstructive pulmonary disease.

Introduction: Quadriceps dysfunction is a common systemic manifestation of chronic obstructive pulmonary disease (COPD), for which treatment using resistance training is highly recommended. Even though training volume is suggested to be a key explanatory factor for intramuscular adaptation to resistance training in healthy older adults, knowledge is scarce on the role of progression of training volume for intramuscular adaptations in COPD. Methods: This study was a sub-analysis of a parallel-group randomized controlled trial. Thirteen patients with severe to very severe COPD (median 66 yrs, forced expiratory volume in 1 s 44% predicted) performed 8 weeks of low-load resistance training. In a post hoc analysis, they were divided into two groups according to their training volume progression. Those in whom training volume continued to increase after the first 4 weeks of training outlined the continued progression group (n = 9), while those with limited increase (<5%) or even reduction in training volume after the initial 4 weeks composed the discontinued progression group (n = 4). Fiber-type distribution and oxidative muscle protein levels, i.e., citrate synthase (CS), hydroxyacyl-coenzyme A dehydrogenase (HADH), mitochondrial transcription factor A (TfAM) as well as quadriceps endurance measures (total work from elastic band and isokinetic knee extension tests), were assessed before and after the intervention period. Results: The continued progression group sustained their training volume progression during weeks 5-8 compared to weeks 1-4 (median +25%), while the discontinued progression group did not (median -2%) (p = 0.007 between groups). Compared with baseline values, significant between-group differences in fiber type distribution and TfAM muscle protein levels (range ± 17-62%, p < 0.05) and in individual responses to change in Type I and Type IIa fiber type proportion, CS, HADH, and TfAM muscle protein levels outcomes (median 89 vs. 50%, p = 0.001) were seen in favor of the continued progression group. Moreover, only the continued progression group had a significant increase in HADH muscle protein levels (+24%, p = 0.004), elastic band (+56%, p = 0.004) and isokinetic (+7%, p = 0.004) quadriceps endurance, but the between-group differences did not reach statistical significance (range 14-29%, p = 0.330-1.000). Discussion: The novel findings of the current study were that patients with COPD who had a continued progression of training volume across the 8-weeks intervention had an increased proportion of Type I fibers, and TfAM muscle protein levels and decreased proportion of Type II fibers compared to those that did not continue to progress their training volume after the initial weeks. Additionally, HADH muscle protein levels and quadriceps endurance measurements only improved in the continued progression group, although no significant between-group differences were seen. These findings highlight the importance of continued progression of training volume during resistive training to counteract quadriceps dysfunction within the COPD population. Still, considering the small sample size and the post hoc nature of our analyses, these results should be interpreted cautiously, and further research is necessary.

Immune Checkpoint Inhibitors and Venous Thromboembolism: An Analysis of the WHO Pharmacovigilance Database.

Data on venous thromboembolic events (VTEs) in patients receiving immune checkpoint inhibitors (ICIs) are scarce and conflicting. This study investigated the risk of reporting VTEs associated with ICIs in comparison with all other anticancer drugs. The World Health Organization pharmacovigilance database (VigiBase), comprising >30 million individual case safety reports, was queried. All reports on patients with cancer, involving at least one anticancer drug as a suspect or interacting drug and registered from January 1, 2008, to May 31, 2021, were included. The association between ICIs and the risk of reporting VTEs was estimated using the reporting odds ratio (ROR) as a measure of disproportionality with all other anticancer drugs as comparators. RORs were estimated as crude and adjusted RORs for age, sex, and other medications (excluding anticancer drugs) associated with risk of VTEs. Among 1,196 patients experiencing VTEs after ICI treatment, the median age was 65 years and 57.6% were men. Anti-PD-1 agents (62.5%) were the most frequently reported. ICIs were not associated with higher reporting of VTEs when compared with other anticancer drugs (crude ROR 0.63, 95% confidence interval (CI) 0.60 to 0.67 and adjusted ROR 0.70, 95% CI 0.65-0.74). No signal of disproportionate reporting was found when considering each class of ICIs. In conclusion, ICIs were not associated with higher reporting of VTEs, in comparison with all other anticancer drugs in a large-scale pharmacovigilance database. Owing to the limitations inherent to pharmacovigilance studies, prospective studies, including an adequate comparison group, are needed to assess the risk of VTEs in ICI-treated patients.

Large-Scale Monolithic Fabrication of III-V Vertical Nanowires on a Standard Si(100) Microelectronic Substrate.

Vertical III-V nanowires are of great interest for a large number of applications, but their integration still suffers from manufacturing difficulties of these one-dimensional nanostructures on the standard Si(100) microelectronic platform at a large scale. Here, a top-down approach based on the structure of a thin III-V epitaxial layer on Si was proposed to obtain monolithic GaAs or GaSb nanowires as well as GaAs-Si nanowires with an axial heterostructure. Based on a few complementary metal-oxide-semiconductor-compatible fabrication steps, III-V nanowires with a high crystalline quality as well as a uniform diameter (30 nm), morphology, positioning, and orientation were fabricated. In addition, the patterning control of nanowires at the nanoscale was thoroughly characterized by structural and chemical analyses to finely tune the key process parameters. To properly control the morphology of the nanowires during reactive-ion etching (RIE), the balance between the plasma properties and the formation of a protective layer on the nanowire sidewall was studied in detail. Furthermore, high-resolution microscopy analyses were performed to gain a better understanding of the protective layer's composition and to observe the crystalline quality of the nanowires. This approach paves the way for the possible scale-up integration of III-V-based nanowire devices with conventional Si/complementary metal-oxide-semiconductor technology.

Safety of Immune Checkpoint Inhibitor Resumption after Interruption for Immune-Related Adverse Events, a Narrative Review.

Immune checkpoint inhibitors (ICIs) have become the standard of care for several types of cancer due to their superiority in terms of survival benefits in first- and second-line treatments compared to conventional therapies, and they present a better safety profile (lower absolute number of grade 1-5 adverse events), especially if used in monotherapy. However, the pattern of ICI-related adverse events is totally different, as they are characterized by the development of specific immune-related adverse events (irAEs) that are unique in terms of the organs involved, onset patterns, and severity. The decision to resume ICI treatment after its interruption due to irAEs is challenged by the need for tumor control versus the risk of occurrence of the same or different irAEs. Studies that specifically assess this point remain scarce, heterogenous and mostly based on small samples of patients or focused only on the recurrence rate of the same irAE after ICI resumption. Moreover, patients with grade ≥3 irAEs were excluded from many of these studies. Herein, we provide a narrative review on the field of safety of ICI resumption after interruption due to irAE(s).

Quadriceps physiological response during the 1-min sit-to-stand test in people with severe COPD and healthy controls.

We compared quadriceps oxygenation and surface electromyography (sEMG) responses during the 1-min sit-to-stand (1STS) in 14 people with severe COPD and 12 controls, in whom cardiorespiratory response, near-infrared spectroscopy signals (oxy [Hb-Mb], deoxy [Hb-Mb], total [Hb-Mb], and SmO2) and sEMG signals of the quadriceps were recorded. Time duration of each sit-to-stand cycle and the total work performed during the 1STS were measured. The quadriceps oxygenation parameters were normalized by reporting their values according to the total work during 1STS. The rate of sit-to-stand maneuvers decelerated in people with COPD leading to smaller total work compared with controls. The pattern of quadriceps oxygenation response during 1STS was similar between groups. However, in COPD, the recovery after 1STS was characterized by larger overshoots in oxy [Hb-Mb], total [Hb-Mb], and SmO2. When corrected for the cumulative total work, the increase in muscle O2 extraction (deoxy [Hb-Mb]) during the first 30 s of recovery was greater in people with COPD compared to controls. Quadriceps sEMG changes suggestive of a fatiguing contraction pattern was observed only in people with COPD. All together, these results highlighted physiological misadaptation of people with severe COPD to the 1STS.

Osteitis in Systemic Sclerosis: A Nationwide Case-Control Retrospective Study.

OBJECTIVE: Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by skin fibrosis, vasculopathy, and dysimmunity. Data regarding osteitis in SSc are scarce. METHODS: We performed a nationwide multicenter, retrospective, case-control study including patients with SSc, according to the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification, with a diagnosis of osteitis. The objectives of the study were to describe, to characterize, and to identify associated factors for osteitis in patients with SSc. RESULTS: Forty-eight patients were included. Twenty-six patients (54.1%) had osteitis beneath digital tip ulcers. Physical symptoms included pain (36 of 48, 75%), erythema (35 of 48, 73%), and local warmth (35 of 48, 73%). Thirty-one (65%) patients had median (interquartile range) C-reactive protein levels >2 mg/liter of 8 (2.7-44.3) mg/liter. On radiography, computed tomography, or magnetic resonance imaging, osteitis was characterized by swelling or abscess of soft tissues, with acro-osteolysis or lysis in 28 patients (58%). Microbiological sampling was performed in 45 (94%) patients. Most pathogens were Staphylococcus aureus (43.8%), anaerobes and Enterobacteriaceae (29.1%), and Pseudomonas aeruginosa (10.4%). Management comprised antibiotics in 37 (77.1%) patients and/or surgery in 26 (54.2%). Fluoroquinolones were used in 22 (45.8%) patients, and amoxicillin plus ß-lactamase inhibitor in 7 (14.6%). Six (12.6%) patients relapsed, 6 (12.6%) patients had osteitis recurrence, 15 (32%) sequelae, and 2 patients had septic shock and died. CONCLUSION: This study confirmed digital tip ulcers as an associated factor for osteitis and revealed a high rate of functional sequelae. Antimicrobial therapy with oral fluoroquinolone or intravenous amoxicillin and ß-lactamase inhibitor are used as first-line antibiotic therapy in SSc patients with osteitis.