Diagnosis and management of longitudinal erythronychia: A clinical review by an expert panel.

Longitudinal erythronychia (LE) is defined as a longitudinal red band of the nail(s) and is classified as localized (involvement of 1 nail) or polydactylous (involvement of more than 1 nail). The differential diagnosis is distinct for these classifications. The etiologies of localized longitudinal erythronychia are most frequently benign subungual neoplasms and less often malignancies. Polydactylous longitudinal erythronychia is typically secondary to regional or systemic diseases, including lichen planus and Darier disease. LE is a common but underrecognized clinical finding. Increased dermatologist awareness of the clinical characteristics and differential diagnosis for LE is necessary given the possibility for malignancy and associated systemic disease. In this clinical review, the clinical features, differential diagnosis, evaluation, and management of LE are described.

Prognostic value of neutrophil-to-lymphocyte ratio in patients with metastatic castration-resistant prostate cancer receiving prostate-specific membrane antigen targeted radionuclide therapy.

BACKGROUND: Neutrophil count:lymphocyte count ratio (NLR) may be a prognostic factor for men with advanced prostate cancer. We hypothesized that it is associated with prostate-specific antigen (PSA) response and survival in men treated with prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT). METHODS: Data of 180 men with metastatic castration-resistant prostate cancer (mCRPC) who were treated in sequential prospective radionuclide clinical trials from 2002 to 2021 (utilizing 177Lu-J591, 90Y-J591, 177Lu-PSMA-617, or 225Ac-J591) were retrospectively analyzed. We used a logistic regression to determine the association between NLR and ≥50% PSA decline (PSA50) and a Cox proportional hazards model to investigate the association between NLR and overall survival (OS). RESULTS: A total of 94 subjects (52.2%) received 177Lu-J591, 51 (28.3%) 177Lu-PSMA-617, 28 (15.6%) 225Ac-J591, and 7 (3.9%) 90Y-J591. The median NLR of 3.75 was used as cut-off (low vs. high NLR; n = 90, respectively). On univariate analysis, NLR was not associated with PSA50 (HR 1.08; 95% confidence interval [CI] 0.99-1.17, p = 0.067). However, it was associated with worse OS (hazard ratio [HR] 1.06, 95% CI 1.02-1.09, p = 0.002), also after controlling for circulating tumor cell count and cancer and leukemia group B risk group (HR 1.05; 95% CI 1.003-1.11, p = 0.036). Men with high NLR were at a higher hazard of death from all causes (HR 1.43, 95% CI 1.05-1.94, p = 0.024). CONCLUSIONS: NLR provides prognostic information in the setting of patients with mCRPC receiving treatment with PSMA-TRT.

Antibody-drug conjugates for urothelial carcinoma.

The standard of care for advanced urothelial carcinoma includes platinum chemotherapy and immunotherapy. Antibody-drug conjugates (ADCs), originally developed for hematologic malignancies, involve potent cytotoxic agents linked to antibodies that recognize tumor-specific antigens; this rational drug design allows for more on-target efficacy, while mitigating systemic toxicity. Herein, we review the emerging landscape of ADCs in urothelial carcinoma. The anti-Nectin-4 ADC enfortumab vedotin has demonstrated efficacy in prospective studies in patients with advanced urothelial carcinoma in several settings either alone or in combination with pembrolizumab. The anti-Trop-2 ADC sacituzumab govitecan has also shown efficacy in single-armed studies. Both conjugates have full or accelerated approval from the Food and Drug Administration. Common adverse events include rash and neuropathy for enfortumab vedotin and myelosuppression and diarrhea for sacituzumab govitecan. Several anti-human epidermal growth factor receptor 2 ADCs are in clinical trials, and in localized bladder cancer, the anti-epithelial cell adhesion molecule ADC oportuzumab monatox is being studied in patients refractory to intravesical bacillus calmette-guerin therapy. Antibody-drug conjugates for urothelial carcinoma are approved and emerging as therapies for patients with advanced urothelial carcinoma, filling a prior void for treatment of progressive disease. Ongoing studies are also evaluating these agents in the neoadjuvant and adjuvant settings.

SETDB1 acts as a topological accessory to Cohesin via an H3K9me3-independent, genomic shunt for regulating cell fates.

SETDB1 is a key regulator of lineage-specific genes and endogenous retroviral elements (ERVs) through its deposition of repressive H3K9me3 mark. Apart from its H3K9me3 regulatory role, SETDB1 has seldom been studied in terms of its other potential regulatory roles. To investigate this, a genomic survey of SETDB1 binding in mouse embryonic stem cells across multiple libraries was conducted, leading to the unexpected discovery of regions bereft of common repressive histone marks (H3K9me3, H3K27me3). These regions were enriched with the CTCF motif that is often associated with the topological regulator Cohesin. Further profiling of these non-H3K9me3 regions led to the discovery of a cluster of non-repeat loci that were co-bound by SETDB1 and Cohesin. These regions, which we named DiSCs (domains involving SETDB1 and Cohesin) were seen to be proximal to the gene promoters involved in embryonic stem cell pluripotency and lineage development. Importantly, it was found that SETDB1-Cohesin co-regulate target gene expression and genome topology at these DiSCs. Depletion of SETDB1 led to localized dysregulation of Cohesin binding thereby locally disrupting topological structures. Dysregulated gene expression trends revealed the importance of this cluster in ES cell maintenance as well as at gene 'islands' that drive differentiation to other lineages. The 'unearthing' of the DiSCs thus unravels a unique topological and transcriptional axis of control regulated chiefly by SETDB1.

An 11-Year Study of Home Hospice Service Trends in Singapore from 2000 to 2010.

BACKGROUND: Hospice care is most appropriate when a patient no longer benefits from curative treatment and has limited life expectancy. These patients may suffer from any type of life-limiting illness, including end-stage cancer, end-stage heart disease, end-stage renal failure, AIDS, and Alzheimer's disease, among other illnesses. Patients are managed on their pain and symptoms and home hospice care manages these patients in the comfort of their own home, enabling patients to spend their last days with dignity and have a good quality of life. OBJECTIVE: To describe the home hospice patients at HCA Hospice Care (HHC) Singapore from 2000 to 2010. Description of home care patients in terms of their sociodemographic profile and diagnosis at admission. We reviewed the Electronic Medical Records of patients admitted into HHC from 2000 to 2010. RESULTS: Patients had multiple admissions into HHC home hospice as identified in the Electronic Medical Records (EMR) between January 1, 2000, and December 31, 2010, but we only selected patient's first admission into HHC home hospice for this analysis. Of the 25,065 patients in the entire samples, 47.3% were males, 65.2% were married, and 84.3% were Chinese. 50.9% of the patients died at home, 75.5% were referred from public hospitals, 53.9% of primary caregivers were children, and the mean age of the patients was 68.0 years. Among all cancer patients admitted into HHC home hospice, lung cancer (23.6%) was the most common principal diagnosis for admission, followed by colorectal (10.5%) and liver cancers (7.7%). Among noncancer patients, renal failure (7.0%) was the most common diagnosis. Among male patients admitted into HHC home hospice, lung cancer (29.6%) was the most common diagnosis, followed by liver cancer (10.8%), colorectal cancer (10.0%), and end-stage renal failure (5.5%). For female patients, lung cancer (16.9%) was the most common diagnosis, followed by breast cancer (15.9%), colorectal cancer (11.0%), and end-stage renal failure (8.7%). Ten-year trends of the sociodemographic profile and diagnosis at admission were further analyzed to determine home hospice services utilization and the needs of the home care patients. CONCLUSION: With an increasing emphasis to encourage aging and dying in the community and more attention given to building up the home hospice industry's capacity and capability, it is important to understand the profile of the patients who have been utilizing home hospice services. This also helps to plan and develop similar services in other parts of the world.