Genetic counseling and genetic testing for pathogenic germline mutations among high-risk patients previously diagnosed with breast cancer: a traceback approach.

Genetic counseling and testing are more accessible than ever due to reduced costs, expanding indications and public awareness. Nonetheless, many patients missed the opportunity of genetic counseling and testing due to barriers that existed at that time of their cancer diagnoses. Given the identified implications of pathogenic mutations on patients' treatment and familial outcomes, an opportunity exists to utilize a 'traceback' approach to retrospectively examine their genetic makeup and provide consequent insights to their disease and treatment. In this study, we identified living patients diagnosed with breast cancer (BC) between July 2007 and January 2022 who would have been eligible for testing, but not tested. Overall, 422 patients met the eligibility criteria, 282 were reached and invited to participate, and germline testing was performed for 238, accounting for 84.4% of those invited. The median age (range) was 39.5 (24-64) years at BC diagnosis and 49 (31-75) years at the date of testing. Genetic testing revealed that 25 (10.5%) patients had pathogenic/likely pathogenic (P/LP) variants; mostly in BRCA2 and BRCA1. We concluded that long overdue genetic referral through a traceback approach is feasible and effective to diagnose P/LP variants in patients with history of BC who had missed the opportunity of genetic testing, with potential clinical implications for patients and their relatives.

Mapping the supportive care needs and quality of life of adult survivors of childhood cancer at a comprehensive cancer center in the Middle East.

Assessing unmet needs is crucial to achieving quality care and patient satisfaction. Between September and December 2021, we assessed unmet supportive care needs in a consecutive sample of adult survivors of childhood cancer at KHCC (King Hussien Cancer Center). Two hundred and ninety-seven adult survivors of childhood cancer completed the study questionnaire. The average needs score across all domains was 24.80 (SD = 19.65), with the financial domain scoring the highest 30.39 (SD = 31.95) and sexuality scoring the lowest 7.67 (SD = 19.67). Using a multivariate linear regression model, female gender was independently associated with significantly high scores in all need domains (p < 0.001), except for sexuality. Monthly income, comorbidities, socioeconomic challenges, time since diagnosis, and age at diagnosis have emerged as predictors of needs in many domains. Mean quality of life (QoL) was significantly and inversely associated with the mean score in multiple domains: psychological (p < 0.001), sexuality (p = 0.038), financial (p < 0.001), and overall needs (p = 0.004). Following a content analysis of qualitative data, educational difficulties, and work-related challenges were identified as other unmet needs. Cancer experiences during childhood significantly influence supportive care needs in adulthood. There is a need for more tailored studies assessing different populations of cancer survivors and avoiding the one-size-fits-all survivorship care.

Prevalence and Predictors of Multi-Drug Resistant Organisms Among Ambulatory Cancer Patients with Urinary Tract Infections.

Purpose: Urinary tract infections (UTIs) are among the most common community-acquired infections in patients with cancer. Though the prevalence of multi-drug resistant organisms (MDROs) has increased, there are limited studies on MDROs among ambulatory cancer patients with UTIs. Therefore, we aimed to evaluate the prevalence and predictors of MDROs in this patient population. Patients and Methods: A retrospective study of adult cancer patients treated for bacterial UTIs in the ambulatory setting at King Hussein Cancer Center. The medical laboratory's system was used to identify positive urine cultures taken in the ambulatory setting, between Aug 2020 and March 2021. UTIs were defined as a positive urine culture along with the initiation of antibiotics empirically or as definitive therapy. Patient characteristics, as well as the type and sensitivity of the bacterial organisms, were recorded. MDROs were defined as intrinsic or acquired non-susceptibility to at least one agent in three or more antimicrobial categories. Logistic regression was used to identify predictors that were independently associated with MDROs. Results: A total of 376 patients had UTIs that met the inclusion criteria; mean age 60.5±15.1 (SD) years and 330 (87.8%) had solid tumors. Gram-negative bacteria was recorded in the majority of UTIs (n = 368, 97.9%), the most common being Escherichia-coli (n = 220, 59.8%) and Klebsiella-pneumonia (n = 68, 18.5%). MDROs were recorded in 226 (60.1%) of urine cultures, with the majority being extended-spectrum-beta-lactamase producing organisms (n = 142, 62.8%). The only significant predictor was having had a UTI with MDRO within the past 6 months (OR 5.6, 95% CI 2.1-15.2). Conclusion: More than half of the positive urine cultures of cancer patients treated for UTIs in the ambulatory setting were MDROs. A subsequent UTI due to MDROs is more likely to occur in patients who had a UTI with an MDRO within the past 6 months.

Clinical Manifestations of Monkeypox.

Monkeypox is a global health issue caused by the monkeypox virus. It can spread from person to person through respiratory secretions, direct exposure to dermatological lesions of infected patients, or exposure to contaminated objects. It is more common in homosexual men, and most patients are asymptomatic. The gold standard for diagnosis is a real-time polymerase chain reaction. In the absence of testing facilities, clinicians rely upon detailed history to exclude other causes of fever with rashes. Initially, there is a prodrome phase of a few days, which is followed by the appearance of rashes. The dermatological manifestations are in the form of an exanthematous rash, which transforms through a macular, papular, and vesicular phase and disappears after crusting in approximately 3 weeks. There can be associated lymphadenopathy in these patients. Respiratory manifestations include nasal congestion and shortness of breath that may result in secondary bacterial infections. Additionally, patients can have neurological involvement in the form of encephalitis. Furthermore, ocular involvement can occur in the form of conjunctivitis, keratitis, and corneal ulceration. Other symptoms can include diarrhea, vomiting, myalgia, and backache. Since most patients do not require hospitalization, the approach to treatment is mainly vigilant monitoring, antiviral therapy, and management of associated complications.

Involvement of ß-catenin in Androgen-induced Mesenchymal Transition of Breast MDA-MB-453 Cancer Cells.

Purpose The cellular and molecular dynamics of DHT-induced EMT in MDA-MB-453 cells were investigated.Methods:PCR arrays were used to examine the expression of EMT-regulatory genes. Immunoblotting was used to detect protein levels and confirm protein-protein interaction following immunoprecipitation. Immunofluorescence was used to observe rearrangement of the actin cytoskeleton and cell morphology. Cell migration was assessed by transwell assayResults: Change of cell morphology was concomitant with increased cell migration after treating cells with DHT. Exposure of cells to DHT for one hour was sufficient to induce changes in cell morphology and actin cytoskeleton after 72 hours indicating altered gene expression. A long-term lasting nuclear translocation of AR was observed after a short exposure of cells to DHT. Investigating the expression of 84 EMT-related genes revealed down-expression of ß-catenin, N-cadherin, and TCF-4 and increased expression of Slug, all of which were confirmed at the protein level. Yet, not only early interaction of AR and ß-catenin was observed following AR activation, inhibition of ß-catenin blocked DHT-induced mesenchymal transition and migration. Wnt signaling was found to be partially important in DHT-induced morphological alteration. The mesenchymal transition of cells could be induced by treating cells with an inhibitor of glycogen synthase kinase-3ß, an enzyme that inhibits ß-catenin; this morphological transition could be reversed by antagonizing AR suggesting that AR functions downstream of ß-catenin.Conclusions: These results suggest that MDA-MB-453 cells undergo partial EMT induced by DHT, ß-catenin is critical for this phenotypic change, and AR probably reciprocally mediates the mesenchymal transition of these cells upon activation of GSK-3 ß.