Molecular profiling of a primary cutaneous signet-ring cell/histiocytoid carcinoma of the eyelid.

Primary cutaneous signet-ring cell/histiocytoid carcinoma of the eyelid is a rare and aggressive neoplasm. Fewer than 50 cases have been reported in the literature, and the genetic driving mutations are unknown. Herein, we present a case of this rare disease along with the results of molecular profiling via targeted next-generation sequencing. The patient is an 85-year-old man who presented with left eyelid swelling initially thought to be a chalazion. After no response to incision and drainage and antibiotics, an incisional biopsy was performed. Histopathologic sections revealed a proliferation of cells with signet-ring and histiocytoid morphology arranged singly and in cords infiltrating the dermis, subcutaneous tissue, and muscle. The lesional cells strongly expressed cytoplasmic cytokeratin 7 and nuclear androgen receptor. Next-generation sequencing revealed a CDH1 mutation, which is known to confer signet-ring morphology in other carcinomas. Pathogenic mutations in NTRK3, CDKN1B, and PIK3CA were also detected. To our knowledge, this is the first documented genetic analysis of this rare disease with findings that offer insights into disease pathogenesis and potential therapeutic targets.

Systemic Therapy for Advanced Urothelial Carcinoma: Current Standards and Treatment Considerations.

Urothelial carcinoma is the sixth most common malignancy in the United States. Although most are diagnosed with non-muscle-invasive malignancy, many patients will develop recurrent disease within 5 years, with 10% to 20% developing advanced muscle-invasive or more distant incurable disease. For such patients, clinical outcomes have remained suboptimal, although recent therapeutic advances have brought new hope to the field. Here, we discuss the main systemic treatment options available for the treatment of patients with advanced disease. This review begins with traditional chemotherapy, which remains a first-line treatment option for many patients. The second section focuses on the evolving landscape of immunotherapy, specifically on approved checkpoint inhibitors and future challenges. Last, we address advances in targeted treatments, including angiogenesis and fibroblast growth factor receptor (FGFR) inhibitors as well as antibody-drug conjugates. As the number of available treatment options continues to expand, ongoing trials to investigate the best sequence and combination strategies to incorporate these drugs into clinical practice will help delineate the future.

Urothelial carcinoma: the evolving landscape of immunotherapy for patients with advanced disease.

Urothelial carcinoma is the sixth most common malignancy in the US. While most patients present with non-muscle-invasive disease, many will develop recurrent disease including some progressing to muscle invasive metastatic cancer. Treatment outcomes have remained poor and stagnant for those with more advanced illness, with typical 5-year survival rates in the range of ≤15%. While first-line, platinum-based chemotherapy remains the current standard for those eligible, the recent incorporation of checkpoint inhibitors into the management of advanced bladder cancer has resulted in an expansion of treatment options for a difficult-to-treat disease. This review will discuss the historic standard treatment options, followed by the more recent evolving role immune therapy has in the management of bladder cancer.

Validation of Test Performance and Clinical Time Zero for an Electronic Health Record Embedded Severe Sepsis Alert.

BACHGROUND: Increasing use of EHRs has generated interest in the potential of computerized clinical decision support to improve treatment of sepsis. Electronic sepsis alerts have had mixed results due to poor test characteristics, the inability to detect sepsis in a timely fashion and the use of outside software limiting widespread adoption. We describe the development, evaluation and validation of an accurate and timely severe sepsis alert with the potential to impact sepsis management. OBJECTIVE: To develop, evaluate, and validate an accurate and timely severe sepsis alert embedded in a commercial EHR. METHODS: The sepsis alert was developed by identifying the most common severe sepsis criteria among a cohort of patients with ICD 9 codes indicating a diagnosis of sepsis. This alert requires criteria in three categories: indicators of a systemic inflammatory response, evidence of suspected infection from physician orders, and markers of organ dysfunction. Chart review was used to evaluate test performance and the ability to detect clinical time zero, the point in time when a patient develops severe sepsis. RESULTS: Two physicians reviewed 100 positive cases and 75 negative cases. Based on this review, sensitivity was 74.5%, specificity was 86.0%, the positive predictive value was 50.3%, and the negative predictive value was 94.7%. The most common source of end-organ dysfunction was MAP less than 70 mm/Hg (59%). The alert was triggered at clinical time zero in 41% of cases and within three hours in 53.6% of cases. 96% of alerts triggered before a manual nurse screen. CONCLUSION: We are the first to report the time between a sepsis alert and physician chart-review clinical time zero. Incorporating physician orders in the alert criteria improves specificity while maintaining sensitivity, which is important to reduce alert fatigue. By leveraging standard EHR functionality, this alert could be implemented by other healthcare systems.

Integrating Palliative Care Into Oncology: A Way Forward.

BACKGROUND: Patients with cancer have complex physical, psychosocial, and spiritual needs that evolve throughout their disease trajectory. As patients are living longer with a diagnosis of cancer, the need is growing to address the morbidity due to the underlying illness as well as treatment-related adverse events. Palliative care includes treating physical symptoms as well as addressing psychosocial and spiritual needs. When these needs are addressed, the quality of care improves, costs decrease, and goals are aligned between the medical care provided and the patient and family. However, how best to integrate palliative care into oncology care is still an area of investigation. METHODS: The authors conducted a literature search, including randomized clinical trials and practice reviews, to evaluate the evidence for integrating palliative care into oncology care. Barriers to integration as well as sustainable paths forward are highlighted. The authors also utilize case studies as representative examples of integration. RESULTS: Current studies demonstrate that integrating palliative care into oncology care improves symptom control, rates of patient and family satisfaction, and quality of end-of-life care. However, for systemwide integration to be successful, commitment must be made to quality improvement, an infrastructure must be built to support palliative care screening, assessment, and intervention, and stakeholders must be engaged in the program. In addition, value must be demonstrated using metrics that affect quality, care utilization, and patient satisfaction. CONCLUSIONS: Even though most US cancer centers have a palliative care program, palliative care remains limited in scope. An integrated approach for palliative care with oncology care requires a systems-based approach, with agreement between all parties on shared common metrics for value.

Anesthesia subsidies: a strategic approach for financial executives.

Healthcare financial executives should employ a systematic approach to anesthesia contract negotiations that: Establishes costs and considers alternative options to reduce anesthesia expense. Defines expected value. Aligns compensation Defines performance parameters. Establishes tracking metrics.