The ALR-RSI score can be used to evaluate psychological readiness to return to sport after acute Achilles tendon tear.

PURPOSE: The return to sport is one of the main goals following Achilles tendon tear repair. Several psychological factors influence the return to sport after a sports injury. The traditional tools to assess the return to sport do not take into account psychological factors. The ankle ligament reconstruction-return to sport injury (ALR-RSI), validated for ankle instability, is a score to evaluate psychological readiness to return to sport. The goal of this study was to validate the ALR-RSI score for the assessment of the readiness to return to sport after Achilles tendon repair. METHODS: The ALR-RSI score, adapted from the anterior cruciate ligament-return to sport injury (ACL-RSI) score used following knee ligament reconstruction, was validated according to the international COSMIN methodology. Patients operated for Achilles tendon repair responded to the questionnaire during the rehabilitation period. The EFAS, FAAM and VISA-A scores were used as reference questionnaires. RESULTS: A total of 50 patients were included. The ALR-RSI score was strongly (r > 0.5) correlated to the EFAS score: r = 0.68 [0.50-0.80] the FAMM sport score: r = 0.7 [0.52-0.84] the FAAM AVQ score (r = 0.6 [0.35-0.78]), and the VISA-A score (r = 0.54 [0.26-0.76]). The discriminant validity was good with the ALR-RSI, which was significantly lower in the patients that did not return to sport: 60.7 (40-81.4) compared to those that did: 83.2 (64.3-100) p = 0.001. Reproducibility was excellent with an intra-class correlation coefficient ρ of 0.99 [097-1.00]. The internal consistency was excellent (alpha coefficient = 0.95). CONCLUSION: The ALR-RSI score provides a valid, reproducible assessment of the psychological readiness to return to sport in patients who undergo surgical Achilles tendon suture repair. LEVEL OF EVIDENCE: III.

Multidimensional Analysis of the Mother-to-child Transmission Risk Factors in Chronic Hepatitis B Virus Infection in Pregnant Women in Vietnam.

Background: Hepatitis B virus (HBV) infection remains a major public health problem. The interaction between HBV and the host inflammatory response is an important factor contributing to liver damage and disease development. We investigate of the correlation between peripheral blood cell levels, HBV DNA, and the risk of transmission to the baby in pregnant women infected with hepatitis B. Methods: A multidimensional analysis was performed on data collected from 60 Vietnamese pregnant women and their babies (cord blood). Results: Taking the risk ratio test results of cord blood HBsAg as a positive probability, the boundary of maternal PBMC concentration is 8.03x106 cells/ml (with negative correlation) and for CBMCs is 6.64x106 cells/ml (with positive correlation). That means that HBsAg positivity in the blood may be related to the increasing of CBMCs and the diminution of maternal PBMCs. When the maternal viral load is higher than 5x107 copies/ml, the risk of being HBsAg-positive in cord blood is 123% (RR=2.23 [1.48,3.36]); when the viral load is lower than this baseline, the risk is decreased by 55% (RR=0.45 [0.30,0.67]) (p<0.001). Conclusions: With several steps of the analysis, this study found maternal peripheral blood cell levels and cord blood positively cor-related in pregnant women with a load lower than 5x107 copies of HBV DNA/ml. The study's results suggest that the role of PBMCs and HBV DNA in vertical infection is essential.

Hip Joint Infections Caused by Multidrug-Resistant Enterobacterales Among Patients With Spinal Cord Injury: Experience of a Reference Center in the Greater Paris Area.

Background: We aimed to describe the management and treatment of hip joint infections caused by multidrug-resistant Enterobacterales among patients with spinal cord injury (SCI). Methods: We included all hip joint infections associated with grade IV decubitus ulcers caused by extended-spectrum beta-lactamase producing Enterobacterales (ESBL-PE) and carbapenemase-producing Enterobacterales treated in a reference center for bone and joint infections over 9 years in a retrospective study. Results: Seventeen SCI patients with ischial pressure ulcers breaching the hip capsule (mean age 52 ± 15 years) were analyzed. In 16 patients, paraplegia was secondary to trauma and 1 was secondary to multiple sclerosis. Infections were mostly polymicrobial (n = 15; 88.2%), notably caused by Klebsiella pneumoniae (n = 10) and Staphylococcus aureus (n = 10). The carbapenemases identified were exclusively OXA-48-type (n = 3) including 2 isolates coexpressed with ESBL-PE within the same bacterial host. Multidrug-resistant Enterobacterales were commonly resistant to fluoroquinolones (n = 12; 70.6%). Most therapies were based on carbapenems (n = 10) and combination therapies (n = 13). Median duration of treatment was 45 (6-60) days. Of 17 cases of hip joint infections, 94.1% (n = 16) benefited from a femoral head and neck resection. Infection control was initially achieved in 58.8% (n = 10) of cases and up to 88.2% after revision surgeries, after a median follow-up of 3 (1-36) months. Conclusions: Hip infections among SCI patients caused by multidrug-resistant Enterobacterales are often polymicrobial and fluoroquinolones-resistant infections caused by Klebsiella pneumoniae and S aureus, highlighting the need for expert centers with pluridisciplinary meetings associating experienced surgeons, clinical microbiologists, and infectious disease specialists.

Breakdown of Spin-to-Helicity Locking at the Nanoscale in Topological Photonic Crystal Edge States.

We measure the local near-field spin in topological edge state waveguides that emulate the quantum spin Hall effect. We reveal a highly structured spin density distribution that is not linked to a unique pseudospin value. From experimental near-field real-space maps and numerical calculations, we confirm that this local structure is essential in understanding the properties of optical edge states and light-matter interactions. The global spin is reduced by a factor of 30 in the near field and, for certain frequencies, flipped compared to the pseudospin measured in the far field. We experimentally reveal the influence of higher-order Bloch harmonics in spin inhomogeneity, leading to a breakdown in the coupling between local helicity and global spin.

First-in-human phase 1 study of the anti-TIGIT antibody vibostolimab as monotherapy or with pembrolizumab for advanced solid tumors, including non-small-cell lung cancer☆.

BACKGROUND: In this first-in-human phase 1 study (NCT02964013; MK-7684-001), we investigated the safety and efficacy of the anti-TIGIT (T cell immunoglobulin and ITIM domain) antibody vibostolimab as monotherapy or in combination with pembrolizumab. PATIENTS AND METHODS: Part A enrolled patients with advanced solid tumors, and part B enrolled patients with non-small-cell lung cancer (NSCLC). Patients received vibostolimab 2.1-700 mg alone or with pembrolizumab 200 mg in part A and vibostolimab 200 mg alone or with pembrolizumab 200 mg in part B. Primary endpoints were safety and tolerability. Secondary endpoints included pharmacokinetics and objective response rate (ORR) per RECIST v1.1. RESULTS: Part A enrolled 76 patients (monotherapy, 34; combination therapy, 42). No dose-limiting toxicities were reported. Across doses, 56% of patients receiving monotherapy and 62% receiving combination therapy had treatment-related adverse events (TRAEs); grade 3-4 TRAEs occurred in 9% and 17% of patients, respectively. The most common TRAEs were fatigue (15%) and pruritus (15%) with monotherapy and pruritus (17%) and rash (14%) with combination therapy. Confirmed ORR was 0% with monotherapy and 7% with combination therapy. In part B, 39 patients had anti-PD-1 (programmed cell death protein 1)/PD-L1 (programmed death-ligand 1)-naive NSCLC (all received combination therapy), and 67 had anti-PD-1/PD-L1-refractory NSCLC (monotherapy, 34; combination therapy, 33). In patients with anti-PD-1/PD-L1-naive NSCLC: 85% had TRAEs-the most common were pruritus (38%) and hypoalbuminemia (31%); confirmed ORR was 26%, with responses occurring in both PD-L1-positive and PD-L1-negative tumors. In patients with anti-PD-1/PD-L1-refractory NSCLC: 56% receiving monotherapy and 70% receiving combination therapy had TRAEs-the most common were rash and fatigue (21% each) with monotherapy and pruritus (36%) and fatigue (24%) with combination therapy; confirmed ORR was 3% with monotherapy and 3% with combination therapy. CONCLUSIONS: Vibostolimab plus pembrolizumab was well tolerated and demonstrated antitumor activity in patients with advanced solid tumors, including patients with advanced NSCLC.

Native bone and joint infections caused by extended-spectrum ß-lactamase-producing Enterobacterales: experience of a reference centre in the Greater Paris area.

Antibiotic treatment of native osteomyelitis caused by extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) is a challenge. Limited epidemiological and outcome data are available. This retrospective cohort study included osteomyelitis patients with ESBL-PE infections treated in a reference centre for bone and joint infections (BJIs) between 2011-2019. Twenty-nine patients with native BJI (mean age, 44.4 ± 15.7 years) were analysed. Fifteen cases were paraplegic patients with ischial pressure sores breaching the hip capsule. Other cases included eight other hip infections, four tibial infections and two foot infections. Infections were mostly polymicrobial (n = 23; 79.3%), including Staphylococcus aureus (n = 13; 8 methicillin-resistant). Klebsiella pneumoniae (n = 13) was the most frequent ESBL-producing species identified, followed by Escherichia coli (n = 10), including 3 E. coli/K. pneumoniae co-infections, and Enterobacter spp. (n = 9). ESBL-PE were rarely susceptible to fluoroquinolones (n = 4; 13.8%). Most therapies were based on carbapenems (n = 22) and combination therapies (n = 19). The median duration of treatment was 41 (5-60) days. Primary control of the infection was achieved in 62.1% (18/29) of cases and up to 86.2% after second look surgeries, after a median follow-up of 6 (1-36) months. Infection with ESBL-producing K. pneumoniae was associated with failure (P = 0.001), whereas age, infection location, prior colonisation and antimicrobial therapy were not found to be predictors of outcome. ESBL-PE native BJIs are often polymicrobial and fluoroquinolone-resistant infections caused by K. pneumoniae, highlighting the need for expert centres with pluridisciplinary meetings with experienced surgeons.

[Mutations in the A34R gene increase the immunogenicity of vaccinia virus]. / Мутации в гене A34R, приводящие к увеличению иммуногенности вируса осповакцины.

Vaccination is the most simple and reliable approach of protection to virus infections. The most effective agents are live vaccines, usually low-virulence organisms for humans and closely related to pathogenic viruses or attenuated as a result of mutations/deletions in the genome of pathogenic virus. Smallpox vaccination with live vaccinia virus (VACV) closely related to smallpox virus played a key role in the success of the global smallpox eradication program carried out under the World Health Organization auspices. As a result of the WHO decision as of 1980 to stop smallpox vaccination, humankind has lost immunity not only to smallpox, but also to other zoonotic, orthopoxviruscaused human infections. This new situation allows orthopoxviruses to circulate in the human population and, as a consequence, to alter several established concepts of the ecology and range of sensitive hosts for various orthopoxvirus species. Classic VACV-based live vaccine for vaccination against orthopoxvirus infections is out of the question, because it can cause severe side effects. Therefore, the development of new safe vaccines against orthopoxviral infections of humans and animals is an important problem. VACV attenuation by modern approaches carried out by targeted inactivation of certain virus genes and usually leads to a decrease in the effectiveness of VACV in vivo propagation. As a result, it can cause a diminishing of the immune response after administration of attenuated virus to patients at standard doses. The gene for thymidine kinase is frequently used for insertion/inactivation of foreign genes and it causes virus attenuation. In this research, the effect of the introduction of two point mutations into the A34R gene of attenuated strain LIVP-GFP (ТК-), which increase the yield of extracellular enveloped virions (EEV), on the pathogenicity and immunogenicity of VACV LIVP-GFP-A34R administered intranasally to laboratory mice were studied. It was shown that increase in EEV production by recombinant strain VACV LIVP-GFP-A34R does not change the attenuated phenotype characteristic of the parental strain LIVP-GFP, but causes a significantly larger production of VACV-specific antibodies.

Beam power scale-up in micro-electromechanical systems based multi-beam ion accelerators.

We report on the development of multi-beam radio frequency (RF) linear ion accelerators that are formed from stacks of low cost wafers and describe the status of beam power scale-up using an array of 112 beams. The total argon ion current extracted from the 112-beamlet extraction column was 0.5 mA. The measured energy gain in each RF gap reached as high as 7.25 keV. We present a path toward using this technology to achieve ion currents >1 mA and ion energies >100 keV for applications in material processing.

Ski- and snowboard related open peroneal nerve injury: A 20-year retrospective case series study.

INTRODUCTION: Traumatic peroneal nerve injury (PNI) caused by ski or snowboard edges is a severe but scarcely reported accident. METHODS: In a 20-year retrospective study, all skiers and snowboarders with this injury treated surgically at the Department of Plastic, Reconstructive and Aesthetic Surgery at the Medical University of Innsbruck, Austria, were included, covering a period from 1999/2000 to 2018/2019. RESULTS: In total, 34 patients were included in this study (30 males (88.2%) and 4 (11.8%) females). Of these 34 injured skiers or snowboarders, 33 (97.1%) were recreational athletes and Non-Austrian citizens, and 21 (61.8%) patients sustained accidental injuries without collision. All of the injuries under investigation, i.e., open lacerations, most often with complete transection, were the patients' main injuries. Surgery was performed with direct coaptation in 24 patients (70.6%), and with a suralis nerve graft in the other 10 patients (29.4%). CONCLUSION: Traumatic laceration of the peroneal nerve at the knee level by sharp ski or snowboard edges is a rare but severe injury. Causes for this injury may be multifactorial. Recommendations to reduce the risk of such an injury may follow general instructions and warnings to skiers and snowboarders regarding equipment, familiarity with the region, as well as appropriate skills and training.

Intracranial and extracranial efficacy of lorlatinib in patients with ALK-positive non-small-cell lung cancer previously treated with second-generation ALK TKIs.

BACKGROUND: Lorlatinib, a potent, brain-penetrant, third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), has substantial activity against ALK-positive non-small-cell lung cancer (NSCLC). This study assessed the overall, intracranial, and extracranial efficacy of lorlatinib in ALK-positive NSCLC that progressed on second-generation ALK TKIs. PATIENTS AND METHODS: In the ongoing phase II study (NCT01970865), patients with ALK-positive advanced NSCLC treated with ≥1 prior second-generation ALK TKI ± chemotherapy were enrolled in expansion cohorts (EXP) based on treatment history. Overall, intracranial and extracranial antitumor activity were assessed independently per modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. RESULTS: Of the 139 patients with ≥1 prior second-generation ALK TKI (EXP3B-5), 28 received one prior second-generation ALK TKI (EXP3B), 65 two prior ALK TKIs (EXP4), and 46 three prior ALK TKIs (EXP5). In EXP3B-5, the objective response rate (ORR) [95% confidence intervals] was 39.6% (31.4-48.2), intracranial ORR (IC-ORR) was 56.1% (42.4-69.3), extracranial ORR (EC-ORR) was 36.7% (28.7-45.3), median duration of response (DOR) was 9.6 months [5.6-16.7; IC-DOR, 12.4 (6.0-37.1); EC-DOR, 9.7 (6.1-33.3)], median progression-free survival was 6.6 (5.4-7.4) months, and median overall survival was 20.7 months (16.1-30.3). In EXP3B, the ORR was 42.9% (24.5-62.8), the IC-ORR was 66.7% (29.9-92.5), and the EC-ORR was 32.1% (15.9-52.4). In EXP4 and EXP5, the ORR was 38.7% (29.6-48.5), the IC-ORR was 54.2% (39.2-68.6), and the EC-ORR was 37.8% (28.8-47.5). CONCLUSIONS: Lorlatinib had clinically meaningful intracranial and extracranial antitumor activity in the post-second-generation ALK TKI setting, with elevated intracranial versus extracranial ORR, particularly in patients with fewer lines of therapy.

Joint Statement (DZK, DGRh, DDG) on the Tuberculosis Risk with Treatment Using Novel Non-TNF-Alpha Biologicals.

BACKGROUND: While the risk of tuberculosis (TB) reactivation is adequately documented in relation to TNF-alpha inhibitors (TNFi), the question of what the tuberculosis risk is for newer, non-TNF biologics (non-TNFi) has not been thoroughly addressed. METHODS: We conducted a systematic review of randomized phase 2 and phase 3 studies, and long-term extensions of same, published through March 2019. Of interest was information pertaining to screening and treating of latent tuberculosis (LTBI) in association with the use of 12 particular non-TNFi. Only rituximab was excluded. We searched MEDLINE and the ClinicalTrial.gov database for any and all candidate studies meeting these criteria. RESULTS: 677 citations were retrieved; 127 studies comprising a total of 34,293 patients who received non-TNFi were eligible for evaluation. Only 80 out of the 127 studies, or 63 %, captured active TB (or at least opportunistic diseases) as potential outcomes and 25 TB cases were reported. More than two thirds of publications (86/127, 68 %) mentioned LTBI screening prior to inclusion of study participants in the respective trial, whereas in only 4 studies LTBI screening was explicitly considered redundant. In 21 studies, patients with LTBI were generally excluded from the trials and in 42 out of the 127 trials, or 33 %, latently infected patients were reported to receive preventive therapy (PT) at least 3 weeks prior to non-TNFi treatment. CONCLUSIONS: The lack of information in many non-TNFi studies on the number of patients with LTBI who were either excluded prior to participating or had been offered PT hampers assessment of the actual TB risk when applying the novel biologics. Therefore, in case of insufficient information about drugs or drug classes, the existing recommendations of the German Central Committee against Tuberculosis should be applied in the same way as is done prior to administering TNFi. Well designed, long-term "real world" register studies on TB progression risk in relation to individual substances for IGRA-positive cases without prior or concomitant PT may help to reduce selection bias and to achieve valid conclusions in the future.

[125 Years German Central Committee for the Fight against Tuberculosis (DZK)]. / 125 Jahre Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose e. V. (DZK).

The German Central Committee for the Fight against Tuberculosis (DZK) celebrates this year its 125th birthday. On this occasion, the DZK as one of the oldest TB organizations worldwide is looking back on the development during its history and records the results in a comprehensive book, summarized in this article. In the book, the various political changes with their impact on the DZK are mirrored, starting with the German Empire, the Weimar Republic, the so-called "Third Reich", the two German states separated after the Second World War and the current FRG. Tuberculosis (TB) was the dominant widespread disease in the 19th century, today it is the leading infectious disease worldwide. As a consequence of migration, this affects also Germany. After meanwhile - in particular in 2015/16 - risen numbers of new cases (especially of those not born in Germany, which in 2019 accounted for 72 % of all cases), the impact of drug-resistant tuberculosis (in 2019, 11.4 % of all new cases had some resistance (384 cases), including 87 cases of MDR-TB, and of these 8 cases of XDR-TB and 27 cases of pre-XDR-TB), as well as the high proportion (81,5 %) - in 2019 - of open and thus very infectious pulmonary TB among new TB cases in Germany, impressively show that TB continues to be a health problem that should not be underestimated and that is increasingly concentrated in risk groups (socially disadvantaged persons, people from high-prevalence countries, homeless people, drug addicts, alcoholics, HIV-infected persons). The DZK therefore continues to play an important role in TB control as a link between the national and international organizations responsible for combating TB.