Gormanklavsen0036

Postoperative nodal downstaging (ypN0-1) was observed in 37 patients (67%). Fifty-one (93%) resected patients had an R0 resection. There was no significant effect of pretreatment PD-L1 expression on MPR or nodal downstaging. The 1-year EFS rate was 73% (two-sided 90% CI, 63 to 82). Median EFS and overall survival were not reached after 28.6 months of median follow-up. Fifty-nine (88%) patients had an adverse event grade ≥ 3 including two fatal adverse events that were judged not to be treatment-related.

The addition of perioperative durvalumab to neoadjuvant chemotherapy in patients with stage IIIA(N2) non-small-cell lung cancer is safe and exceeds historical data of chemotherapy alone with a high MPR and an encouraging 1-year EFS rate of 73%.

The addition of perioperative durvalumab to neoadjuvant chemotherapy in patients with stage IIIA(N2) non-small-cell lung cancer is safe and exceeds historical data of chemotherapy alone with a high MPR and an encouraging 1-year EFS rate of 73%.

We identified the incidence of acquired cryptorchidism among patients with proximal and mid shaft hypospadias, predictors of acquired cryptorchidism, and the prevalence of testis-epididymis nonfusion with ascended testes. We hypothesized that proximal hypospadias would be associated with higher incidence of acquired cryptorchidism than mid shaft hypospadias, and that ascended testes would exhibit increased prevalence of testis-epididymis nonfusion similar to anatomical findings in an undescended testis.

A retrospective cohort study of patients who underwent primary proximal and mid shaft hypospadias repair from 2010 to 2016 was conducted. Clinical and operative notes were reviewed. Patients with congenitally undescended testes or differences of sex development were excluded.

A total of 175 patients were identified. Those with proximal hypospadias (14/104, 13%) were more likely than those with mid shaft hypospadias (1/71, 1%) to develop acquired cryptorchidism (p=0.04). Among proximal hypospadias patientsting these testes morphologically resemble undescended testes. Close followup of testis position is needed in these patients, and the threshold to perform orchiopexy may need to be lower in select patients.

Deciding when patients are ready to return to sport (RTS) after an anterior cruciate ligament (ACL) reconstruction (ACLR) is challenging. The understanding of which factors affect readiness and how they may be related is limited. Therefore, despite widespread use of RTS testing, there is a lack of knowledge about which tests are informative on the ability to resume sports.

To examine whether there is an association between knee laxity and psychological readiness to RTS after ACLR and to evaluate the predictive value of these measures on sports resumption.

Cohort study; Level of evidence, 2.

Patients aged ≥16 years engaged in physical activity/sports before injury were recruited at routine clinical assessment 9-12 months after ACLR. Exclusion criteria were concomitant ligament surgery at ACLR and/or previous ACL injury in the contralateral knee. At baseline, a project-specific activity questionnaire and the ACL-Return to Sport After Injury (ACL-RSI) scale were completed. Knee laxity was assessed by usessociations were found between measurements of psychological readiness and anterior tibial displacement, indicating that patients with less knee laxity after ACLR feel more ready to RTS. ACL-RSI and KT-1000 arthrometer measurements were independent predictors of 2-year RTS and should be considered in RTS assessments after ACLR.

Small but significant associations were found between measurements of psychological readiness and anterior tibial displacement, indicating that patients with less knee laxity after ACLR feel more ready to RTS. ACL-RSI and KT-1000 arthrometer measurements were independent predictors of 2-year RTS and should be considered in RTS assessments after ACLR.Bacteria can utilize Copper (Cu) as a trace element to support cellular processes; however, excess Cu can intoxicate bacteria. Here, we characterize the cop operon in group B streptococcus (GBS), and establish its role in evasion of Cu intoxication and the response to Cu stress on virulence. Growth of GBS mutants deficient in either the copA Cu exporter, or the copY repressor, were severely compromised in Cu-stress conditions. GBS survival of Cu stress reflected a mechanism of CopY de-repression of the CopA efflux system. However, neither mutant was attenuated for intracellular survival in macrophages. Analysis of global transcriptional responses to Cu by RNA-sequencing revealed a stress signature encompassing homeostasis of multiple metals. Genes induced by Cu stress included putative metal transporters for manganese import, whereas a system for iron export was repressed. In addition, copA promoted the ability of GBS to colonize the blood, liver and spleen of mice following disseminated infection. Together, these findings show that GBS copA mediates resistance to Cu intoxication, via regulation by the Cu-sensing transcriptional repressor, copY. BTK inhibitor chemical structure Cu stress responses in GBS reflect a transcriptional signature that heightens virulence and represents an important part of the bacteria's ability to survive in different environments. Importance Understanding how bacteria manage cellular levels of metal ions, such as copper, helps to explain how microbial cells can survive in different stressful environments. We show how the opportunistic pathogen group B Streptococcus (GBS) achieves homeostasis of intracellular copper through the activities of the genes that comprise the cop operon, and describe how this helps GBS survive in stressful environments, including in the mammalian host during systemic disseminated infection.Protein lysine acetylation is a conserved post-translational modification that modulates several cellular processes. Protein acetylation and its physiological implications are well understood in eukaryotes; however, its role is emerging in bacteria. Lysine acetylation in bacteria is fine-tuned by the concerted action of lysine acetyltransferases (KATs), protein deacetylases (KDACs), metabolic intermediates- acetyl-coenzyme A (Ac-CoA) and acetyl phosphate (AcP). AcP mediated nonenzymatic acetylation is predominant in bacteria due to its high acetyl transfer potential whereas, enzymatic acetylation by bacterial KATs (bKAT) are considered less abundant. SePat, the first bKAT discovered in Salmonella enterica, regulates the activity of the central metabolic enzyme- acetyl-CoA synthetase, through its acetylation. Recent studies have highlighted the role of bKATs in stress responses like pH tolerance, nutrient stress, persister cell formation, antibiotic resistance and pathogenesis. Bacterial genomes encode many putative bKATs of unknown biological function and significance.