Although treatment with first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) plus antiangiogenic inhibitor has shown promising efficacies in patients with EGFR-mutated lung adenocarcinoma, recent single-arm studies have suggested that osimertinib plus antiangiogenic inhibitor might not work synergistically.

To explore the efficacy and safety of osimertinib plus bevacizumab compared with osimertinib alone in patients with lung adenocarcinoma with EGFR T790M mutation.

Patients with advanced lung adenocarcinoma that progressed with prior EGFR-TKI treatment (other than third-generation TKI) and acquired EGFR T790M mutation were enrolled. This study comprises a lead-in part with 6 patients and a subsequent phase 2 part. In phase 2, patients were randomized to osimertinib plus bevacizumab or osimertinib alone in a 11 ratio.

The combination arm received oral osimertinib (80 mg, every day) plus intravenous bevacizumab (15 mg/kg, every 3 weeks) until progression or unaccepta; P = .12). Median overall survival was not different in the combination arm vs osimertinib arm (not reached vs 22.1 months; P = .96). In the combination arm, common adverse events of grade 3 or higher were proteinuria (n = 9; 23%), hypertension (n = 8; 20%).

In this randomized clinical trial comparing osimertinib plus bevacizumab vs osimertinib alone, the combination arm failed to show prolongation of PFS in patients with advanced lung adenocarcinoma with EGFR T790M mutation.

UMIN Clinical Trials Registry Identifier UMIN000023761.

UMIN Clinical Trials Registry Identifier UMIN000023761.

It is unclear whether chronic use of immunosuppressive drugs worsens or improves the severity of coronavirus disease 2019 (COVID-19), with plausible mechanisms for both.

Retrospective cohort study in 2121 consecutive adults with acute inpatient hospital admission between 4 March and 29 August 2020 with confirmed or suspected COVID-19 in a large academic health system, with adjustment for confounding with propensity score-derived stabilized inverse probability of treatment weights. Chronic immunosuppression was defined as prescriptions for immunosuppressive drugs current at the time of admission. Outcomes included mechanical ventilation, in-hospital mortality, and length of stay.

There were 2121 patients admitted with laboratory-confirmed (1967, 93%) or suspected (154, 7%) COVID-19 during the study period, with a median age of 55 years (interquartile range, 40-67). Of these, 108 (5%) were classified as immunosuppressed before COVID-19, primarily with prednisone (>7.5 mg/day), tacrolimus, or mycophenolate mofetil. Among the entire cohort, 311 (15%) received mechanical ventilation; the median (interquartile range) length of stay was 5.2 (2.5-10.6) days, and 1927 (91%) survived to discharge. After adjustment, there were no significant differences in the risk of mechanical ventilation (hazard ratio [HR], .79; 95% confidence interval [CI], .46-1.35), in-hospital mortality (HR, .66; 95% CI, .28-1.55), or length of stay (HR, 1.16; 95% CI, .92-1.47) among individuals with immunosuppression and counterparts.

Chronic use of immunosuppressive drugs was neither associated with worse nor better clinical outcomes among adults hospitalized with COVID-19 in one US health system.

Chronic use of immunosuppressive drugs was neither associated with worse nor better clinical outcomes among adults hospitalized with COVID-19 in one US health system.Aptamers are single-stranded oligonucleotides that bind to a specific target with high affinity, and are widely applied in biomedical diagnostics and drug development. However, the use of aptamers has largely been limited to simple binders or inhibitors that interfere with the function of a target protein. Here, we show that an aptamer can also act as a positive allosteric modulator that enhances the activation of a receptor by stabilizing the binding of a ligand to that receptor. We developed an aptamer, named IR-A43, which binds to the insulin receptor, and confirmed that IR-A43 and insulin bind to the insulin receptor with mutual positive cooperativity. IR-A43 alone is inactive, but, in the presence of insulin, it potentiates autophosphorylation and downstream signaling of the insulin receptor. By using the species-specific activity of IR-A43 at the human insulin receptor, we demonstrate that residue Q272 in the cysteine-rich domain is directly involved in the insulin-enhancing activity of IR-A43. Therefore, we propose that the region containing residue Q272 is a hotspot that can be used to enhance insulin receptor activation. Moreover, our study implies that aptamers are promising reagents for the development of allosteric modulators that discriminate a specific conformation of a target receptor.

Concerns have been raised that military veterans are at greater risk of dementia due to increased rates of depression, post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) found in this population. The prevalence of dementia in English veterans and whether this is different to non-veterans, however, are currently unknown.

To study the risk of dementia in the English veteran population, we aimed to calculate the prevalence of dementia in a group of veterans and compare this with a similar group, with no history of military service.

Male veterans and non-veterans aged over 64 years old were identified from the 2007 Adult Psychiatric Morbidity Survey, a national survey of community-dwelling adults in England. This survey was conducted via face-to-face interviews and incorporated questions on previous military service. Methylene Blue Dementia was screened by using the modified Telephone Interview of Cognitive Status (TICS-M).

A total of 496 male veterans and 294 non-veterans were identified. TICS-M scores indicated possible dementia in 24% of veterans and 26% non-veterans; after adjusting for age, the odds of possible dementia was significantly lower in veterans than non-veterans (adjusted OR 0.56; 95% CI 0.38-0.84, P < 0.01).

English male veterans were less likely to have dementia than similar male non-veterans. This study did not find any evidence to support the view that dementia is more common in veterans than non-veterans.

English male veterans were less likely to have dementia than similar male non-veterans. This study did not find any evidence to support the view that dementia is more common in veterans than non-veterans.