Bacterial and fungal co-infection is a major barrier in COVID-19 patients: A specific management and therapeutic strategy is required

Microbial co-infections are another primary concern in patients with coronavirus disease 2019 (COVID-19), yet it is an untouched area among researchers. Preliminary data and systematic reviews only show the type of pathogens responsible for that, but its pathophysiology is still unknown. Studies show that these microbial co-infections are hospital-acquired/nosocomial infections, and patients admitted to intensive care units with invasive mechanical ventilation are highly susceptible to it. Patients with COVID-19 had elevated inflammatory cytokines and a weakened cell-mediated immune response, with lower CD4⁺ T and CD8⁺ T cell counts, indicating vulnerability to various co-infections. Despite this, there are only a few studies that recommend the management of co-infections.     

Machine learning to predict myocardial injury and death after non-cardiac surgery

Myocardial injury due to ischaemia within 30 days of non-cardiac surgery is prognostically relevant. We aimed to determine the discrimination, calibration, accuracy, sensitivity and specificity of single-layer and multiple-layer neural networks for myocardial injury and death within 30 postoperative days. We analysed data from 24,589 participants in the Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation study. Validation was performed on a randomly selected subset of the study population. Discrimination for myocardial injury by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.70 (0.69–0.72) vs. 0.71 (0.70–0.73) with variables available before surgical referral, p < 0.001; 0.73 (0.72–0.75) vs. 0.75 (0.74–0.76) with additional variables available on admission, but before surgery, p < 0.001; and 0.76 (0.75–0.77) vs. 0.77 (0.76–0.78) with the addition of subsequent variables, p < 0.001. Discrimination for death by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.71 (0.66–0.76) vs. 0.74 (0.71–0.77) with variables available before surgical referral, p = 0.04; 0.78 (0.73–0.82) vs. 0.83 (0.79–0.86) with additional variables available on admission but before surgery, p = 0.01; and 0.87 (0.83–0.89) vs. 0.87 (0.85–0.90) with the addition of subsequent variables, p = 0.52. The accuracy of the multiple-layer model for myocardial injury and death with all variables was 70% and 89%, respectively.     

Major complications of airway management: a prospective multicentre observational study

We conducted an observational study of serious airway complications, using similar methods to the fourth UK National Audit Project (NAP4) over a period of 1 year across four hospitals in one region in the UK. We also conducted an activity survey over a week, using NAP4 methods to yield an estimate for relevant denominators to help interpret the primary data. There were 17 serious airway complications, defined as: failed airway management leading to cancellation of surgery (eight); airway management in recovery (five); unplanned intensive care admission (three); and unplanned emergency front of neck access (one). There were no reports of death or brain damage. This was an estimate of 0.028% (1 in 3600) complications using the denominator of 61,000 general anaesthetics per year in the region. Complications in patients with ‘predicted easy’ airways were rare (approximately 1 in 14,200), but 45 times more common in those with ‘predicted difficult’ airways (approximately 1 in 315). Airway management in both groups was similar (induction of anaesthesia followed by supraglottic airway or tracheal tube). Use of awake/sedation intubation, videolaryngoscopy and high-flow nasal oxygenation were uncommon even in the predicted difficult airway patients (in 2.7%, 32.4% and 9.5% of patients, respectively). We conclude that the incidence of serious airway complications is at least as high as it was during NAP4. Despite airway prediction being used, this is not informing subsequent management.     

Biogenic silver,gold and copper nanoparticles - A sustainable green chemistry approach for cancer therapy

The advent of nanotechnology has revolutionized the way clinicians are treating cancers. Treatment for cancer includes surgery, radiotherapy, hormonal therapy, chemotherapy, and now nano therapy, which could be a possible alternative. This new treatment regime can be beneficial since it shows minimum side effects as compared to other treatment methods. Metallic nanoparticles synthesized through green chemistry by using biological entities minimizes the side effects and enhances the properties of the metal against cancer cells. These green nanoparticles are widely used in research and have shown promising cytotoxic activity against various cancer cell lines. Mechanistically, these nanoparticles can enter the cancer cell and cause cell death by the activation of various molecular pathways such as apoptosis, necrosis and autophagy. This review focuses on the metal nanoparticles (silver, gold and copper) synthesized by the green chemistry approach that have been utilized to study the cancer cell death and we are also discussing the underlying molecular pathways.     

Evaluating the Cost-Effectiveness of Hydrogel Rectal Spacer in Prostate Cancer Radiation Therapy

Purpose

A hydrogel rectal spacer (HRS) is a medical device that is approved by the U.S. Food and Drug Administration to increase the separation between the prostate and rectum. We conducted a cost-effectiveness analysis of HRS use for reduction in radiation therapy (RT) toxicities in patients with prostate cancer (PC) undergoing external beam RT (EBRT).

Exposure to ambient air pollution and the incidence of lung cancer and breast cancer in the Ontario Population Health and Environment Cohort

Lung and female breast cancers are highly prevalent worldwide. Although the association between exposure to ambient fine particulate matter (PM_2.5) and lung cancer has been recognized, there is less evidence for associations with other common air pollutants such as nitrogen dioxide (NO₂) and ozone (O₃). Even less is known about potential associations between these pollutants and breast cancer. We conducted a population-based cohort study to investigate the associations of chronic exposure to PM_2.5, NO₂, O₃ and redox-weighted average of NO₂ and O₃ (O_x) with incident lung and breast cancer, using the Ontario Population Health and Environment Cohort (ONPHEC), which includes all long-term residents aged 35–85 years who lived in Ontario, Canada, 2001–2015. Incident lung and breast cancers were ascertained using the Ontario Cancer Registry. Annual estimates of exposures were assigned to the residential postal codes of subjects for each year during follow-up. We used Cox proportional-hazards models adjusting for personal- and neighborhood-level covariates. Our cohorts for lung and breast cancer analyses included ~4.9 million individuals and ~2.5 million women, respectively. During follow-up, 100,146 incident cases of lung cancer and 91,146 incident cases of breast cancer were diagnosed. The fully adjusted analyses showed positive associations of lung cancer incidence with PM_2.5 (hazard ratio [HR] = 1.02 [95% CI: 1.01–1.05] per 5.3 μg/m³) and NO₂ (HR = 1.05 [95% CI: 1.03–1.07] per 14 ppb). No associations with lung cancer were observed for O₃ or O_x. Relationships between PM_2.5 and NO₂ with lung cancer exhibited a sublinear shape. We did not find compelling evidence linking air pollution to breast cancer.     

Phase I and pharmacokinetic study of veliparib,a PARP inhibitor,and pegylated liposomal doxorubicin (PLD) in recurrent gynecologic cancer and triple negative breast cancer with long-term follow-up

Poly(ADP-ribosyl) polymerases (PARPs) are nuclear enzymes with roles in DNA damage recognition and repair. PARP1 inhibition enhances the effects of DNA-damaging agents like doxorubicin. We sought to determine the recommended phase two dose (RP2D) of veliparib with pegylated liposomal doxorubicin (PLD) in breast and recurrent gynecologic cancer patients. Veliparib and PLD were administered in a standard phase 1, 3 + 3 dose-escalation design starting at 50 mg veliparib BID on days 1–14 with PLD 40 mg/mg2 on day 1 of a 28-day cycle. Dose escalation proceeded in two strata: A (prior PLD exposure) and B (no prior PLD exposure). Patients underwent limited pharmacokinetic (PK) sampling; an expansion PK cohort was added. 44 patients with recurrent ovarian or triple negative breast cancer were enrolled. Median age 56 years; 23 patients BRCA mutation carriers; median prior regimens four. Patients received a median of four cycles of veliparib/PLD. Grade 3/4 toxicities were observed in 10% of patients. Antitumor activity was observed in both sporadic and BRCA-deficient cancers. Two BRCA mutation carriers had complete responses. Two BRCA patients developed oral squamous cell cancers after completing this regimen. PLD exposure was observed to be higher when veliparib doses were > 200 mg BID. The RP2D is 200 mg veliparib BID on days 1–14 with 40 mg/m2 PLD on day 1 of a 28-day cycle. Anti-tumor activity was seen in both strata. However, given development of long-term squamous cell cancers and the PK interaction observed, efforts should focus on other targeted combinations to improve efficacy.