Pulmonary complications and mortality among COVID-19 patients undergoing a surgery: a multicentre cohort study.

Objectives: Our primary objective was to assess the association between symptoms at the time of surgery and postoperative pulmonary complications and mortality in patients with COVID-19. Our secondary objective was to compare postoperative outcomes between patients who had recovered from COVID-19 and asymptomatic patients and explore the effect of the time elapsed between infection and surgery in the former. Our hypotheses were that symptomatic patients had a higher risk of pulmonary complications, whereas patients who had recovered from the infection would exhibit outcomes similar to those of asymptomatic patients.

Discovery of the Potent and Selective ATR Inhibitor Camonsertib (RP-3500).

ATR is a key kinase in the DNA-damage response (DDR) that is synthetic lethal with several other DDR proteins, making it an attractive target for the treatment of genetically selected solid tumors. Herein we describe the discovery of a novel ATR inhibitor guided by a pharmacophore model to position a key hydrogen bond. Optimization was driven by potency and selectivity over the related kinase mTOR, resulting in the identification of camonsertib (RP-3500) with high potency and excellent ADME properties.

Characterisation of FLT3 alterations in childhood acute lymphoblastic leukaemia.

Background: Alterations of FLT3 are among the most common driver events in acute leukaemia with important clinical implications, since it allows patient classification into prognostic groups and the possibility of personalising therapy thanks to the availability of FLT3 inhibitors. Most of the knowledge on FLT3 implications comes from the study of acute myeloid leukaemia and so far, few studies have been performed in other leukaemias.

Methods: A comprehensive genomic (DNA-seq in 267 patients) and transcriptomic (RNA-seq in 160 patients) analysis of FLT3 in 342 childhood acute lymphoblastic leukaemia (ALL) patients was performed.

Efficacy of a propofol bolus against placebo to prevent cough at emergence from general anesthesia with desflurane: a randomized controlled trial.

Purpose: Emergence from anesthesia is a critical period and cough can result in adverse effects. Propofol inhibits airway reflexes and when infused it reduces cough more than inhalation anesthesia does. We evaluated the effect of a propofol bolus given at emergence on the incidence of coughing following a desflurane-based anesthesia.

The Quebec Cannabis Registry: Investigating the Safety and Effectiveness of Medical Cannabis.

To investigate the safety and effectiveness of medical cannabis (MC) in the real-world clinical practice setting. A 4-year prospective noncomparative registry of adult patients who initiated MC for a variety of indications. This paper reports on patients followed for up to 12 months, with interim visits at 3, 6, and 9 months after enrollment.

Discovery of an Orally Bioavailable and Selective PKMYT1 Inhibitor, RP-6306.

PKMYT1 is a regulator of CDK1 phosphorylation and is a compelling therapeutic target for the treatment of certain types of DNA damage response cancers due to its established synthetic lethal relationship with amplification. To date, no selective inhibitors have been reported for this kinase that would allow for investigation of the pharmacological role of PKMYT1. To address this need compound was identified as a weak PKMYT1 inhibitor.

Predictors of Pain Reduction Among Fibromyalgia Patients Using Medical Cannabis: A Long-Term Prospective Cohort Study.

Objective: Many patients with fibromyalgia (FM) report using cannabis as a strategy to improve pain. Given that pain often co-occurs with symptoms of anxiety and depression (i.e.

Genetic factors contributing to late adverse musculoskeletal effects in childhood acute lymphoblastic leukemia survivors.

Background: A substantial number of survivors of childhood acute lymphoblastic leukemia (ALL) suffer from treatment-related late adverse effects. While multiple studies have identified the effects of chemotherapeutics and radiation therapy on musculoskeletal outcomes, few have investigated their associations with genetic factors.

Methods: Here we analyzed musculoskeletal complications in relation to common and rare genetic variants derived through whole-exome sequencing of the PETALE cohort.

Postoperative outcomes in surgical COVID-19 patients: a multicenter cohort study.

Background: Data on postoperative outcomes of the COVID-19 patient population is limited. We described COVID-19 patients who underwent a surgery and the pandemic impact on surgical activities.

Methods: We conducted a multicenter cohort study between March 13 and June 192,020.

Risk Factors for Seborrhoeic Dermatitis Flares: Case-control and Case-crossover Study.

Patients with flares of seborrhoeic dermatitis were compared with control outpatients seen during the same time-period in a case-control study, and with themselves while in remission in a case-crossover study. All patients consulted the same office-based dermatologist. During the study period, 189 cases and 189 controls were included in the case-control study, and 81 cases in the case-crossover study.

[PECS I block for postoperative analgesia in patients undergoing breast augmentation surgery: a randomized double-blind placebo-controlled study].

Background And Objectives: PECS I block was first described for surgery involving the pectoralis muscles. No randomized clinical trial has been conducted on surgeries that directly involve these muscles, such as subpectoral breast augmentation. We hypothesized that PECS I block would decrease pain in the postoperative period in this population.

HLA alleles associated with asparaginase hypersensitivity in childhood ALL: a report from the DFCI Consortium.

To evaluate the association between human leukocyte antigen (HLA) alleles and native asparaginase hypersensitivity (AH) in children with acute lymphoblastic leukemia (ALL) who received Dana-Farber Cancer Institute treatment protocols. , and alleles were retrieved from available whole exome sequencing data of a subset of childhood ALL patients from Quebec ALL cohort and analyzed for an association with AH. PCR assay was developed to analyze associated alleles in the entire discovery and replication cohorts.

Genes identified through genome-wide association studies of osteonecrosis in childhood acute lymphoblastic leukemia patients.

To evaluate top-ranking genes identified through genome-wide association studies for an association with corticosteroid-related osteonecrosis in children with acute lymphoblastic leukemia (ALL) who received Dana-Farber Cancer Institute treatment protocols. Lead SNPs from these studies, as well as other variants in the same genes, pooled from whole exome sequencing data, were analyzed for an association with osteonecrosis in childhood ALL patients from Quebec cohort. Top-ranking variants were verified in the replication patient group.

Influence of genetic factors on long-term treatment related neurocognitive complications, and on anxiety and depression in survivors of childhood acute lymphoblastic leukemia: The Petale study.

Background: A substantial number of survivors of childhood acute lymphoblastic leukemia suffer from treatment-related late adverse effects including neurocognitive impairment. While multiple studies have described neurocognitive outcomes in childhood acute lymphoblastic leukemia (ALL) survivors, relatively few have investigated their association with individual genetic constitution.

Methods: To further address this issue, genetic variants located in 99 genes relevant to the effects of anticancer drugs and in 360 genes implicated in nervous system function and predicted to affect protein function, were pooled from whole exome sequencing data of childhood ALL survivors (PETALE cohort) and analyzed for an association with neurocognitive complications, as well as with anxiety and depression.

Identification of genetic variants associated with skeletal muscle function deficit in childhood acute lymphoblastic leukemia survivors.

Although 80% of childhood acute lymphoblastic leukemia (ALL) cases are cured with current treatment protocols, exposure to chemotherapeutics or radiation therapy during a vulnerable period of child development has been associated with a high frequency of late adverse effects (LAE). Previous observations suggest important skeletal muscle size, density and function deficits in ALL survivors. Given that only a fraction of all patients will suffer from this particular complication, we investigated whether it could be predicted by genetic markers.

Identification of genetic association between cardiorespiratory fitness and the trainability genes in childhood acute lymphoblastic leukemia survivors.

Background: The progress of treatments of childhood acute lymphoblastic leukemia (ALL) has made it possible to reach a survival rate superior to 80%. However, the treatments lead to several long-term adverse effects, including cardiac toxicity. Although studies have reported associations between genetic variants and cardiorespiratory fitness, none has been performed on childhood ALL survivors.

Identification of a single-nucleotide polymorphism within gene associated with bone morbidity in childhood acute lymphoblastic leukemia survivors.

To identify genetic markers associated with late treatment-related skeletal morbidity in survivors of childhood acute lymphoblastic leukemia (ALL). To this end, we measured the association between reduction in bone mineral density or vertebral fractures prevalence and variants from 1039 genes derived through whole exome sequencing in 242 childhood ALL survivors. Top-ranking variants were confirmed through genotyping, and further explored with stratified analyses and multivariable models.