Single-dose replicating poxvirus vector-based RBD vaccine drives robust humoral and T cell immune response against SARS-CoV-2 infection

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Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer

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China special issue on gastrointestinal tumors-Radiological features of pathological complete response in mismatch repair deficient colorectal cancer after neoadjuvant PD-1 blockade: A post hoc analysis of the PICC phase II trial

Neoadjuvant programmed cell death protein 1 (PD-1) blockade exhibits promising efficacy in patients with mismatch repair deficient (dMMR) colorectal cancer (CRC). However, discrepancies between radiological and histological findings have been reported in the PICC phase II trial (NCT 03926338). Therefore, we strived to discern radiological features associated with pathological complete response (pCR) based on computed tomography (CT) images. Data were obtained from the PICC trial that included 36 tumors from 34 locally advanced dMMR CRC patients, who received neoadjuvant PD-1 blockade for 3 months. Among the 36 tumors, 28 (77.8%) tumors achieved pCR. There were no statistically significant differences in tumor longitudinal diameter, the percentage change in tumor longitudinal diameter from baseline, primary tumor sidedness, clinical stage, extramural venous invasion status, intratumoral calcification, peritumoral fat infiltration, intestinal fistula and tumor necrosis between the pCR and non-pCR tumors. Otherwise, tumors with pCR had smaller posttreatment tumor maximum thickness (median: 10 mm vs 13 mm, P = .004) and higher percentage decrease in tumor maximum thickness from baseline (52.9% vs 21.6%, P = .005) compared to non-pCR tumors. Additionally, a higher proportion of the absence of vascular sign (P = .003, odds ratio [OR] = 25.870 [95% CI, 1.357-493.110]), nodular sign (P < .001, OR = 189.000 [95% CI, 10.464-3413.803]) and extramural enhancement sign (P = .003, OR = 21.667 [2.848-164.830]) was observed in tumors with pCR. In conclusion, these CT-defined radiological features may have the potential to serve as valuable tools for clinicians in identifying patients who have achieved pCR after neoadjuvant PD-1 blockade, particularly in individuals who are willing to adopt a watch-and-wait strategy.     

Pan-cancer proteomic map of 949 human cell lines

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Sofosbuvir-velpatasvir en pacientes mexicanos con hepatitis C: una revisión retrospectiva

IntroductionThe sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking.MethodsA retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment.ResultsOverall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported.ConclusionTreatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.     

Return to sport and beyond following intramuscular tendon hamstring injury: A case report of an English Premier League football player

BackgroundHamstring strain injuries are the most common type of injury in elite football and are associated with a high risk of reinjury, particularly those involving the intramuscular tendon (IMT). Limited information is available regarding the rehabilitation and return to sport (RTS) processes following such injuries. This case study describes the clinical presentation of an elite football player following IMT hamstring injury, their on- and off-pitch rehabilitation alongside performance monitoring throughout RTS and beyond.Case scenarioAn elite football player suffered a grade 2c hamstring injury during an English Premier League (EPL) match. The player underwent early post-injury management, alongside progressive off-pitch physical preparation. The ‘control-chaos continuum’ was used as a framework for on-pitch rehabilitation to prepare the player for a return to full team training and competition. Objective and subjective markers of the player's response to progressive on- and off-pitch loading were monitored throughout RTS and beyond.OutcomesThe player returned to on-pitch rehabilitation after 11 days, to full team training having achieved weekly pre-injury chronic running load outputs after 35 days and played in the EPL 40 days post-injury. The player did not suffer reinjury for the rest of the EPL season.ConclusionAn understanding the unique structural and mechanical properties of the IMT, alongside expected RTS timeframes are important to inform rehabilitation and decision-making processes post-injury. Performance and frequent load-response monitoring throughout RTS and beyond, in conjunction with practitioner experience and effective communication are critical in facilitating effective RTS and reduce risk of reinjury following IMT injury.     

Robust antibody response after a third BNT162b2 vaccine compared to the second among immunocompromised and healthy individuals,a prospective longitudinal cohort study

PurposeAs protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion.MethodsA prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6 months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster.ResultsAmong 110 participants, 56 (51%) were women. Mean age was 61.7 ± 1.9 years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95 %CI 5.25–11.67) folds and 2.40 (95 %CI 1.90–3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95 %CI 32.5–79.1) fold in the immunocompromised group and 25.7 (95 %CI 19.1–34.7) fold in and immunocompetent group, was observed.ConclusionA third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.     

Rucaparib in the landscape of PARP inhibition in ovarian cancer

Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.

Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.

Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited.     

Orientation and mobility outcome measures

Despite orientation and mobility (O&M) being a significant factor determining quality of life of people with low vision or blindness, there are no gold standard measures or agreement on how to measure O&M performance. In the first part of this systematic review, an inventory of O&M outcome measures used by recent studies to assess the performance of orientation and/or mobility of adults with vision impairment (low vision and blindness) is presented. A wide variety of O&M outcome measures have been implemented in different fields of study, such as epidemiologic research and interventional studies evaluating training, assistive technology, vision rehabilitation and vision restoration. The most frequent aspect of outcome measures is efficiency such as time, distance, speed and percentage of preferred walking speed, followed by obstacle contacts and avoidance, and dis/orientation and veering. Other less commonly used aspects are target identification, safety and social interaction and self-reported outcome measures. Some studies employ sophisticated equipment to capture and analyse O&M performance in a laboratory setting, while others carry out their assessment in real-world indoor or outdoor environments. In the second part of this review, the appropriateness of implementing the identified outcome measures to assess O&M performance in clinical and functional O&M practice is evaluated. Nearly a half of these outcome measures meet all four criteria of face validity (either clinical or functional), responsiveness, reliability and feasibility and have the potential to be implemented in clinical or functional O&M practice. The findings of this review confirm the complicated and dynamic nature of O&M. Multiple measures are required in any evaluation of O&M performance to facilitate holistic assessment of O&M abilities and limitations of each individual.     

面肌痉挛微血管减压术中异常肌反应变化特点与术后疗效关系探究

目的探究面肌痉挛患者微血管减压术(MVD)中异常肌反应(AMR)的变化特点与术后疗效的关系。方法回顾性分析73例MVD术中采用AMR全程定量化监测患者的AMR变化特点,减压操作前AMR阈值较基础阈值升高≥1倍为A1组、1倍为A2组,手术结束时AMR完全消失为B1组、未消失为B2组,B2组中AMR阈值较基础阈值升高≥1倍为B2a组、1倍为B2b组,对各组的术后疗效进行对比分析。结果 A1组21例中,19例立即治愈,1例延迟治愈,1例未愈; A2组52例中,35例立即治愈,9例延迟治愈,8例未愈。A1组较A2组疗效好(P=0. 046)。B1组50例中,42例立即治愈,5例延迟治愈,3例未愈; B2组23例中,12例立即治愈,5例延迟治愈,6例未愈。B1组较B2组疗效好(P=0. 003)。B2 a组的治愈比例较B2 b组高(分别为14/16、3/7),差异有统计学意义(P=0. 045)。结论 AMR在术中的变化特点对术者有重要参考意义,AMR在减压前升高、在手术结束时完全消失、未消失但升高较基础阈值≥1倍者术后疗效相对较好。