Characteristics, treatment patterns, and outcomes in patients with high-risk locally advanced cervical cancer.

OBJECTIVE: To characterize the real-world treatment patterns and outcomes of patients with high-risk locally advanced cervical cancer (HR-LACC). METHODS: This retrospective study identified and randomly selected adults diagnosed between 2010 and 2018 from the ConcertAI Oncology Dataset. For patients initially treated with concurrent chemoradiotherapy (CCRT), we estimated real-world progression-free survival (rwPFS) among those with persistent disease, real-world time on CCRT, and recurrence-free survival (rwRFS) using Kaplan-Meier methods. RESULTS: The cohort included 300 patients. Median age at diagnosis was 51 years. 53.7 % were White and 30.0 % were Black; 52.0 % were premenopausal; 89.3 % had squamous cell histology; 75.3 % had stage III disease, and 92.7 % had no evidence of performance status impairment. Initial treatment included CCRT (N = 229), surgery (N = 28), antineoplastics only (N = 11), and radiation only (N = 5). Twenty-seven patients were untreated. Baseline characteristics for the CCRT-first patients were similar to the overall cohort; their median real-world time on treatment was 1.6 months; 78.2 % received cisplatin for a median of 1.2 months; 28.4 % received antineoplastics after CCRT, and 11.8 % initiated a second antineoplastic therapy. Of the CCRT-first patients, 27/143 with a complete response had subsequent recurrent disease (median rwRFS not reached). 179 patients had persistent disease, among whom median (95 % confidence interval [CI]) rwPFS was 29.7 (16.9-59.3) months. CONCLUSION: In this study of United States-based clinical practices, most HR-LACC patients received CCRT as initial treatment. Many patients developed persistent disease after CCRT indicating a need for improved first treatment and maintenance options.

Does previous fragility fracture impact upon mortality in a hip fracture cohort? a retrospective study.

BACKGROUND: Fragility fractures are described as fractures resulting from low-energy trauma and are considered diagnostic of reduced bone mineral density or osteoporosis. They often present as hip fractures with hip fractures remaining a common but devastating injury among older patients. Many factors influence a patient's risk of hip fracture and their subsequent risk of death. AIM: In this study, we examined if previous fragility fracture impacts upon mortality after hip fracture. METHODS: This was a retrospective single-center cohort study of patients included in the Irish Hip Fracture registry over a 5-year time period. Epidemiological data including gender, age, type of fracture, type of surgery, bone protection medication, American Society of Anesthetics (ASA) grade, and post-fracture outcomes including death at 30 days and death at 1 year were recorded. The presence or absence of a previous fragility fracture was examined to explore if a previous fragility fracture was an independent predictor of mortality. RESULTS: There were 964 patients included, and 290 of whom had sustained a previous fragility fracture; 289 patients were males and 675 females, 33 patients had died in the 30 days following their surgery, and 180 patients had died within 1 year. We found statistically significant results for gender and age but not for previous fragility fracture influencing mortality (p value 0.230). CONCLUSION: We found that previous fragility fracture does not impact upon mortality in a hip fracture cohort. However, gender and age did impact upon mortality in this study.

Prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water and sleep quality in adulthood: a retrospective cohort study.

BACKGROUND: Communities in Cape Cod, Massachusetts were exposed to tetrachloroethylene (PCE) through contaminated drinking water from 1969 to 1983. PCE exposure during adulthood has well-established neurotoxic effects; however, long-term impacts stemming from early life exposure, especially adverse effects on sleep quality, are not well understood. METHODS: The present analysis was based on data from the Cape Cod Health Study, a retrospective cohort study of the long-term neurotoxic impacts of early-life exposure to PCE-contaminated drinking water. Exposure to PCE-contaminated water was estimated using a validated leaching and transport model. Measures of sleep quality were obtained from self-administered questionnaires. Generalized estimating equations were used to generate risk ratios and 95% confidence intervals to estimate the association between early-life PCE exposure and sleep quality among 604 participants. RESULTS: Compared to unexposed participants, any PCE exposure during early life was associated with 1.57 times the risk of reporting breathing pauses during sleep (95% CI 0.92-2.68). Low-level exposure to PCE was associated with 1.50 times the risk of reporting sleep apnea or other sleep disorders (95% CI 0.78-2.89), while high levels of exposure had comparable risk compared to no exposure (RR = 0.94, 95% CI 0.50-1.79). Weak or no associations were observed for other sleep quality outcomes. In stratified analyses participants with mental illness and/or substance use disorder had increased risk ratios for short sleep duration associated with PCE exposure. CONCLUSION: These findings suggest that early-life exposure to PCE may be associated with a moderate increase in the risk of reporting breathing pauses during sleep in adulthood and that a history of mental illness and/or substance use disorder may exacerbate the risk of short sleep duration.

Adverse events and clinical outcomes in patients treated with PD-(L)1 blockade for advanced non-small-cell lung cancer.

Aims: To describe, in patients with advanced/metastatic non-small-cell lung cancer, the relationship between baseline immunosuppressive drug (ISD)/corticosteroid (CS) use, as well as the incidence of mild/moderate adverse events (AEs), and the clinical effectiveness of PD (L)-1 blockade. Patients & methods: This was a retrospective cohort study of patients with no evidence (n = 131) or positive evidence (n = 269) of ISD/CS use. Results: Duration of treatment, time to next treatment, progression-free survival and overall survival were significantly reduced for patients with evidence of prior ISD/CS use. Occurrence of mild/moderate AEs did not affect any clinical outcomes. Conclusion: Prior ISD/CS use was associated with a poorer prognosis in advanced/metastatic non-small-cell lung cancer patients treated with PD-(L)1 inhibitors, but the occurrence of AEs had no effect.

What is the article about? Patients with advanced/metastatic non-small-cell lung cancer (aNSCLC) are often treated with a class of drugs known as checkpoint inhibitors. There have been previous reports that treatment with corticosteroids and other drugs that suppress the immune system in the period leading up to treatment with checkpoint inhibitors may result in poorer outcomes, but most of these reports focus on serious adverse events leading to hospitalizations or emergency room visits that result from treatment. This study aimed to determine whether treatment with corticosteroids in these patients had any impact on the occurrence of mild or moderate adverse events and long-term treatment outcomes. What were the results? By looking back at deidentified medical insurance claims from patients with aNSCLC, we found that patients who were treated with corticosteroids or other immunosuppressive drugs (vs those who did not receive these drugs) in the months leading up to treatment with checkpoint inhibitors had poorer treatment outcomes (e.g., shorter overall survival). What do the results of the study mean? This study investigated the real-world outcomes in aNSCLC patients treated with checkpoint inhibitors and found that the use of corticosteroids or other immunosuppressive drugs may have an adverse effect. However, we are unable to rule out the possibility that there was an underlying difference between these two sets of patients that caused the difference in treatment outcomes. Further studies with larger sample sizes are needed.

A Case of Multi-focal Osteonecrosis in the Context of Liver Transplant Following Ingestion of Amanita phalloides Mushroom Toxin.

We present the case of a 44-year-old female who presented with atraumatic avascular necrosis (AVN) of the patella and hips bilaterally, following ingestion of the deadly fungus Amanita phalloides or 'death cap' and subsequent liver transplant. Upon presentation, in the hours following ingestion, our patient required a liver transplant and ICU admission. She was treated by a multidisciplinary team, with input from various specialities. Our patient required steroids in the months following this event. Six months after the liver transplant and subsequent ICU admission, our patient developed hip pain, thus limiting her mobility, ability to engage in physiotherapy and rehabilitation. X-rays were performed that excluded any acute pathology. She was still receiving high-dose steroids at this time. When the pain did not resolve with analgesia, MRI of pelvis and knee was performed and the patient was found to have polyarticular AVN. Acute bilateral total hip replacement was performed and within weeks, the patient returned to physiotherapy and to full rehabilitation. Conservative management of the patella was favoured. Over two years later, the patient can now mobilise independently. The role of acute total hip replacement is evident in this case, and how in performing this surgery, the overall conditioning and health of our patient improved drastically. Currently, cases reporting A. phalloides ingestion are few and we wish to use this case to highlight the differential diagnosis in a patient presenting with joint pain in this context of fungus ingestion, organ transplant or prolonged steroid use.

Mosquito aging modulates the heart rate and the proportional directionality of heart contractions.

Mosquito aging impacts a myriad of physiological processes, including digestion, flight, mating, reproductive success, and immunity. In the present study, we conducted intravital video imaging in 1, 3, 5, 10, 15 and 20-day-old Anopheles gambiae female adults to assess whether aging impacts mosquito heart physiology. We found that the heart contraction rate increases over the first 15days of adulthood and then decreases. These changes occur for both contraction directions, although aging results in a relative change in the anterograde versus retrograde contraction rates. That is, whereas for the first 5days of life the anterograde and retrograde contraction rates are similar, from day 10 to day 20 the retrograde contraction rate is higher than the anterograde contraction rate. Aging also biases the proportional directionality of heart contractions, from approximately two thirds of the time being spent contracting in the anterograde direction and two thirds of the contractions propagating anterograde during the first 5days of life to an approximately even split between anterograde and retrograde when the mosquitoes have reached 10 to 20days of age. Transcriptional analyses of crustacean cardioactive peptide (CCAP), FMRFamide, calcium-calmodulin dependent kinase II (CaMKII), pygopus, manganese-iron superoxide dismutase (MnSOD1) and vinculin by quantitative RT-PCR revealed age-associated changes in gene expression, with MnSOD1 and vinculin expression showing a declining trend with age. RNAi-based knockdown of MnSOD1 or vinculin resulted in heart physiology that trended toward the aging phenotype for every parameter that was measured, suggesting that these two genes are involved in cardiac aging.