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. 相似文献
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. 相似文献
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. 相似文献
When the COVID-19 pandemic hit, blood transfusion services worldwide started collection of convalescent plasma as early as possible, as exemplified by the response in Norway. There were challenges related to donor selection, donor safety, testing for relevant antibodies and indications for and dosing of the convalescent plasma. As more knowledge became available, the product quality was more standardised. Multiple case reports, observational studies and some randomized studies were published during the pandemic, as well as laboratory studies reporting different approaches to antibody testing. The results were conflicting and the importance of convalescent plasma was disputed.Even though there has been strong international collaboration with involvement of many key organisations, we may better prepare for the next pandemic. An even stronger, more formalised collaboration between these organisations could provide more clear evidence of the importance of convalescent plasma, based on the principles of passive immunisation. 相似文献
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. 相似文献
Introduction: Collaborative interactions between several diverse biological processes govern the onset and progression of breast cancer. These processes include alterations in cellular metabolism, anti-tumor immune responses, DNA damage repair, proliferation, anti-apoptotic signals, autophagy, epithelial-mesenchymal transition, components of the non-coding genome or onco-mIRs, cancer stem cells and cellular invasiveness. The last two decades have revealed that each of these processes are also directly regulated by a component of the cell cycle apparatus, cyclin D1.
Area covered: The current review is provided to update recent developments in the clinical application of cyclin/CDK inhibitors to breast cancer with a focus on the anti-tumor immune response.
Expert opinion: The cyclin D1 gene encodes the regulatory subunit of a proline-directed serine-threonine kinase that phosphorylates several substrates. CDKs possess phosphorylation site selectivity, with the phosphate-acceptor residue preceding a proline. Several important proteins are substrates including all three retinoblastoma proteins, NRF1, GCN5, and FOXM1. Over 280 cyclin D3/CDK6 substrates have b\een identified. Given the diversity of substrates for cyclin/CDKs, and the altered thresholds for substrate phosphorylation that occurs during the cell cycle, it is exciting that small molecular inhibitors targeting cyclin D/CDK activity have encouraging results in specific tumors. 相似文献