Outcomes of First-Generation EGFR-TKIs Against Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Post Hoc Analysis of the BE-POSITIVE Study

Background

Beyond progression after tyrosine kinase inhibitor in EGFR-positive non-small-cell lung cancer patients (BE-POSITIVE) was the first Italian multicenter observational study that reported the outcomes of first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in a “real-life” Caucasian EGFR-mutated non-small-cell lung cancer (NSCLC) population. The sharing of multi-institutional experiences represents a crucial strategy to enrich knowledge about uncommon EGFR mutations. Therefore, we performed a post hoc analysis of the BE-POSITIVE study.

Status epilepticus and the presence of SARS‐COV‐2 in the cerebrospinal fluid: A case report

A growing number of studies indicate a broad range of neurological manifestations, including seizures, occur in patients with COVID‐19 infection. We report a 29‐year‐old female patient with status epilepticus and positive SARS‐CoV‐2 in the cerebrospinal fluid. Our findings support previous reports suggesting seizure as a possible symptom of COVID‐19 infection.     

Inflammatory and Hemostatic Markers in COVID-19 Patients with Arterial Thrombosis Are Significantly Lower at Hospital Admission than in COVID-19 Patients without Thrombosis

Patients with Coronavirus disease 2019 (COVID-19) are at increased risk of venous thromboembolism (VTE); however, data on arterial thromboembolism (ATE) is still limited. We report a case series of thromboembolic events (TE) in 290 COVID-19 patients admitted between October and December 2020 to a Portuguese hospital. Admission levels of various laboratory parameters were evaluated and compared between COVID-19 patients with (TE) and without thrombotic events (non-TE). The overall incidence of isolated ATE was 5.52%, isolated VTE was 2.41% and multiple mixed events was 0.7%. A total of 68% events were detected upon admission to the hospital with 76% corresponding to ATE. Admissions to the Intensive Care Unit were higher in patients with TE, when comparing with the non-TE group (44% vs. 27.2%; p = 0.003). Patients with ATE presented significantly lower levels of CRP (p = 0.007), ferritin (p = 0.045), LDH (p = 0.037), fibrinogen (p = 0.010) and higher monocyte counts (p = 0.033) comparatively to the non-TE patients. These results point to an early occurrence of TE and an increased incidence of ATE over VTE. The less prominent inflammation markers in patients with TE and the early presence of TE in patients with otherwise no reason for hospitalization, may suggest a direct role of SARS-CoV-2 in the thrombotic process.     

The Impact of the COVID-19 Lockdown on Sugar-Sweetened Beverage Consumption in Children in Saudi Arabia: A Mixed-Methods Study

(1) Background: In 2020, there seems to have been a global shift in lifestyle and eating habits with the emergence of the coronavirus disease 2019 (COVID-19) and the ensuing lockdowns implemented by national governments. This study assessed the impact of the COVID-19 lockdown on SSBs consumption among healthy 6–11 years old children in Saudi Arabia; (2) Methods: This is a mixed-methods study, incorporating a quantitative component, which was a validated Arabic online questionnaire completed by parents, and a qualitative component, involving structured interviews with 10 selected parents using a criterion sampling method; (3) Results: There was a small decrease in consumption reported during lockdown across all SSBs types (soft drinks, n = 58 (13.9%); juices: n = 115 (27.6%); flavored milk: n = 93 (22.3%)). The results showed that with every increase in the dental pain scale there was a positive odd (AOR:0.64; p = 0.001) of decreased consumption of SSBs. Several themes related to increase and decrease SSBs consumption emerged; (4) Conclusions: There was a small decrease in SSBs consumption during lockdown reported by parents. Several themes emerged that can be used to strategize against problematic eating behavior, enabling such provisions as family dietary interventions, which target both parents and children.     

Sleep,Brain, and Cognition Special Feature: Understanding the roles of central and autonomic activity during sleep in the improvement of working memory and episodic memory

The last decade has seen significant progress in identifying sleep mechanisms that support cognition. Most of these studies focus on the link between electrophysiological events of the central nervous system during sleep and improvements in different cognitive domains, while the dynamic shifts of the autonomic nervous system across sleep have been largely overlooked. Recent studies, however, have identified significant contributions of autonomic inputs during sleep to cognition. Yet, there remain considerable gaps in understanding how central and autonomic systems work together during sleep to facilitate cognitive improvement. In this article we examine the evidence for the independent and interactive roles of central and autonomic activities during sleep and wake in cognitive processing. We specifically focus on the prefrontal–subcortical structures supporting working memory and mechanisms underlying the formation of hippocampal-dependent episodic memory. Our Slow Oscillation Switch Model identifies separate and competing underlying mechanisms supporting the two memory domains at the synaptic, systems, and behavioral levels. We propose that sleep is a competitive arena in which both memory domains vie for limited resources, experimentally demonstrated when boosting one system leads to a functional trade-off in electrophysiological and behavioral outcomes. As these findings inevitably lead to further questions, we suggest areas of future research to better understand how the brain and body interact to support a wide range of cognitive domains during a single sleep episode.     

French version of the short form of the Neurogenic Bladder Symptom Score: Cross-cultural adaptation and validation

IntroductionThis study aimed to empirically validate a French version of the Neurogenic Bladder Symptoms Score-Short From (NBSS-SF), a psychometric multidimensional tool to assess lower urinary tract symptoms (LUTS) for patients with a neurological condition.MethodsOne hundred and five participants with multiple sclerosis or spinal cord injury prospectively completed the questionnaire at baseline and 7–14 days later. The α coefficient of Cronbach (internal consistency) and the intraclass correlation coefficient (ICC) (test-retest reliability) were calculated.ResultsThe internal consistency for the overall questionnaire was high (Cronbach’s α coefficients from 0.79), while coefficients for each subscale were variable (urinary incontinence 0.91; storage and voiding 0.69; consequences 0.25). For test-retest reliability, 88/105 (84%) patients filled and sent back their questionnaire 10 days (±3.6 days) after baseline version. ICC was 0.90 for the total score and was 0.73 for the urinary incontinence subdomain, 0.79 for storage and voiding, and 0.75 for consequences.ConclusionsThe psychometric qualities of the French version of the NBSS-SF are well-supported, thus providing a valid tool to measure bladder symptoms across three different domains in patients with neurogenic bladder.     

KSR induces RAS‐independent MAPK pathway activation and modulates the efficacy of KRAS inhibitors

The kinase suppressor of rat sarcoma (RAS) proteins (KSR1 and KSR2) have long been considered as scaffolding proteins required for optimal mitogen‐activated protein kinase (MAPK) pathway signalling. However, recent evidence suggests that they play a more complex role within this pathway. Here, we demonstrate that ectopic expression of KSR1 or KSR2 is sufficient to activate the MAPK pathway and to induce cell proliferation in the absence of RAS proteins. In contrast, the ectopic expression of KSR proteins is not sufficient to induce cell proliferation in the absence of either rapidly accelerated fibrosarcoma (RAF) or MAPK‐ERK kinase proteins, indicating that they act upstream of RAF. Indeed, KSR1 requires dimerization with at least one member of the RAF family to stimulate proliferation, an event that results in the translocation of the heterodimerized RAF protein to the cell membrane. Mutations in the conserved aspartic acid–phenylalanine–glycine motif of KSR1 that affect ATP binding impair the induction of cell proliferation. We also show that increased expression levels of KSR1 decrease the responsiveness to the KRAS^G12C inhibitor sotorasib in human cancer cell lines, thus suggesting that increased levels of expression of KSR may make tumour cells less dependent on KRAS oncogenic signalling.     

Risk factors associated with heat-related illness among sugarcane farmers in Thailand

Heatstroke is defined as severe symptoms of heat-related illness, which could lead to death. Sugarcane farmers are at high risk of heatstroke under extremely hot outdoor working conditions. We explored the prevalence of heat-related illness symptoms and risk factors related to heat-related illness among sugarcane farmers working in the summer. We conducted a cross-sectional study using questionnaire interviews among 200 sugarcane farmers in Kamphaeng Phet Province, Thailand. The questionnaire addressed demographics, heat-related symptoms experienced during summer at work, and occupational factors. Bioelectrical impedance analysis was used to assess body mass index and body fat percentage. Watson formula equations were used to estimate total body water. The prevalence of heat-related illness symptoms was 48%; symptoms included heavy sweating, weakness/fatigue, dizziness, muscle cramps, headache, and vertigo. Factors associated with heat-related illness included women and clothing. Sugarcane farmers wearing two-layer shirts had a higher risk of heat-related illness. Farmers with fluid intake 3.1–5.0 liters per day had a 79% lower risk of heat-related illness. Our findings demonstrated that sugarcane farmers are at risk of heat-related illness. We confirmed that working conditions, including wearing proper clothing and water-drinking habits, can reduce this risk.