Patient-reported disruptions to cancer care during the COVID-19 pandemic: A national cross-sectional study

Background: The aim of this study is to evaluate the extent and associations with patient-reported disruptions to cancer treatment and cancer-related care during the COVID-19 pandemic utilizing nationally representative data. Methods: This analysis uses data from the 2020 National Health Interview Survey (NHIS), an annual, cross-sectional survey of US adults. Adults (age >18) who reported requiring current cancer treatment or other cancer-related medical care in the second half of 2020 were included. Estimated proportions of patients with self-reported changes, delays, or cancelations to cancer treatment or other cancer care due to the COVID-19 pandemic were calculated using sampling weights and associations with sociodemographic and other health-related variables were analyzed. Results: In total, 574 (sample-weighted estimate of 2,867,326) adults reported requiring cancer treatment and/or other cancer care since the start of the COVID-19 pandemic. An estimated 32.1% reported any change, delay, or cancelation. On sample-weighted univariable analysis, patients who were younger, female, had one or fewer comorbidities, and uninsured were significantly more likely to report disruptions. On sample-weighted, multivariable analysis, patients who were younger and female remained significant predictors. Nearly 90% of patients included in the study reported virtual appointment use. Patients reporting disruptions were also significantly more likely to report feelings of anxiety. Conclusions: An estimated 1/3 of patients experienced disruptions to cancer care due to the COVID-19 pandemic. Patients experiencing disruptions in care were more likely to be female or younger which may reflect risk stratification strategies in the early stages of the pandemic, and also had higher rates of anxiety. The longitudinal impact of these disruptions on outcomes merits further study

Global Kidney Exchange Should Expand Wisely.

We read with great interest and appreciation the careful consideration and analysis by Ambagtsheer et al. of the most critical ethical objections to Global Kidney Exchange (GKE). Ambagtsheer et al. conclude that implementation of GKE is a means to increase access to transplantation ethically and effectively

Controversy and consensus on the management of elevated sperm DNA fragmentation in male infertility: A global survey, current guidelines, and expert recommendations

Purpose Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. Materials and Methods An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method. Results A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4–6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. Conclusions This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians

Deciphering the Roles of Thiazolidinediones and PPARγ in Bladder Cancer

The use of thiazolidinedione (TZD) therapy in type II diabetic patients has proven useful in the lowering of blood glucose levels. However, recent investigations have shown that there may be potential health concerns associated, including the risk of developing bladder cancer as well as complications in the cardiovasculature. TZDs are ligands for the nuclear receptor PPARγ, and activation causes lipid uptake and insulin sensitization, both of which are critical processes for diabetic patients whose bodies are unable to utilize insulin effectively. Several studies have shown that PPARγ/TZDs decrease IGF-1 levels and, thus, reduce cancer growth in carcinomas such as the pancreas, colon, liver, and prostate. However, other studies have shed light on the potential of the receptor as a biomarker for uroepithelial carcinomas, particularly due to its stimulatory effect on migration of bladder cancer cells. Furthermore, PPARγ may provide the tumor-promoting microenvironment by de novo synthesis of nutrients that are needed for bladder cancer development. In this review, we closely examine the TZD class of drugs and their effects on PPARγ in patient studies along with additional molecular factors that are positive modulators, such as protein phosphatase 5 (PP5), which may have considerable implications for bladder cancer therapy

Sterility, an Overlooked Health Condition

Clinically, infertility is defined as the inability to conceive after a certain period. In contrast, sterility is defined as the inability to produce a biological child; however, this is not a practical definition that can be applied in a clinical setting to a patient’s diagnosis. Unlike infertility, sterility is rarely discussed in biomedical and clinical literature and is often used synonymously with infertility. Infertility affects about 10% of couples globally, but the prevalence of sterility remains unknown. We divide sterility into three subtypes natural, clinical, and hardship. To estimate sterility prevalence, we analyzed primary literature and meta-analysis papers on the rates of live births and pregnancies throughout several treatments of infertile couples (e.g., untreated patients, in vitro fertilization-treated, and patients administered other treatments). This analysis indicates that all treatments fail in delivering a biological child to most couples, suggesting that most infertile couples may fail to conceive. More comprehensive primary studies are needed to provide a precise estimate of sterility. Furthermore, research is needed to study the causes of sterility, as well as develop methods for diagnosis and treatment that are financially affordable and emotionally tolerable. Altogether, sterility is an under-discussed condition that is more common than expected, as many infertile couples are unable to conceive and are, in effect, sterile

p53-stabilizing Agent CP-31398 Prevents Growth and Invasion of Urothelial Cancer of the Bladder in Transgenic UPII-SV40T Mice

The high prevalence of bladder cancer and its recurrence make it an important target for chemoprevention. About half of invasive urothelial tumors have mutations in p53. We determined the chemopreventive efficacy of a p53-stabilizing agent, CP-31398, in a transgenic UPII-SV40T mouse model of bladder transitional cell carcinoma (TCC) that strongly resembles human TCC. After genotyping, six-week-old UPII-SV40T mice (n = 30/group) were fed control (AIN-76A) or experimental diets containing 150 or 300 ppm of CP-31398 for 34 weeks. Progression of bladder cancer growth was monitored by magnetic resonance imaging. At 40 weeks of age, all mice were killed; urinary bladders were collected to determine weights, tumor incidence, and histopathology. There was a significant increase in bladder weights of transgenic versus wild-type mice (male: 140.2 mg vs 27.3 mg, P < .0001; female: 34.2 mg vs 14.8 mg, P < .0001). A significant decrease in the bladder tumor weights (by 68.6–80.2%, P < .0001 in males and by 36.9–55.3%, P < .0001 in females) was observed in CP-31398-treated mice. Invasive papillary TCC incidence was 100% in transgenic mice fed control diet. Both male and female mice exposed to CP-31398 showed inhibition of invasive TCC. CP-31398 (300 ppm) completely blocked invasion in female mice. Molecular analysis of the bladder tumors showed an increase in apoptosis markers (p53, p21, Bax, and Annexin V) with a decrease in vascular endothelial growth factor in transgenic mice fed CP-31398. These results suggest that p53-modulating agents can serve as potential chemopreventive agents for bladder TCC

Fluorescence-Based Ratiometric Analysis of Sperm Centrioles (FRAC) Finds Patient Age and Sperm Morphology Are Associated With Centriole Quality

A large proportion of infertility and miscarriage causes are unknown. One potential cause is a defective sperm centriole, a subcellular structure essential for sperm motility and embryonic development. Yet, the extent to which centriolar maladies contribute to male infertility is unknown due to the lack of a convenient way to assess centriole quality. We developed a robust, location-based, ratiometric assay to overcome this roadblock, the Fluorescence-based Ratiometric Assessment of Centrioles (FRAC). We performed a case series study with semen samples from 33 patients, separated using differential gradient centrifugation into higher-grade (pellet) and lower-grade (interface) sperm fractions. Using a reference population of higher-grade sperm from infertile men with morphologically standard sperm, we found that 79% of higher-grade sperm of infertile men with substandard sperm morphology have suboptimal centrioles ( P = 0.0005). Moreover, tubulin labeling of the sperm distal centriole correlates negatively with age ( P = 0.004, R = −0.66). These findings suggest that FRAC is a sensitive method and that patient age and sperm morphology are associated with centriole quality