A Case study of polypharmacy-induced serotonin syndrome in a cancer patient.

ABSTRACT: Polypharmacy in cancer care can be complex and detrimental, particularly among younger patients, who can be easily overlooked. This report showcases a 54-year-old woman with cancer, treated for dapsone-induced methemoglobinemia with methylene blue (MB), subsequently developing serotonin syndrome (SS) due to concurrent serotonin-active medications. This case highlights the critical impact of polypharmacy, emphasizing the necessity for acute care providers to diligently assess medication interactions, especially in emergencies. It underscores the importance of considering alternative treatments and the vigilant monitoring of symptoms indicative of adverse drug interactions to ensure patient safety and optimize outcomes in complex therapeutic scenarios.

Essential Review of Oncological Emergencies.

Innovations in oncology have expanded treatment eligibility, leading to a rise in cancer patients requiring critical care. This necessitates that all critical care clinicians possess a fundamental knowledge of prevalent oncological conditions and identify emergent scenarios requiring immediate action. This article will explore key oncological complications and their management approaches.

Use of mixed gas pneumoperitoneum during minimally invasive surgery: a systematic review of human and mouse modelled laparoscopic interventions.

The formation of pneumoperitoneum involves the process of inflating the peritoneal cavity during laparoscopic and typically uses CO2 as the insufflation gas. This review aims to identify ideal gas mixtures for establishing the pneumoperitoneum with animal and human studies undertaken up to the writing of this review. A systematic search of PubMed, OVID, and clinicaltrials.gov was performed to identify studies on the utilisation of mixed gases in laparoscopic surgery, including non-randomised/randomised trials, animal and human studies, and studies with inflating pressures between 12 and 16 mmHg. ROBINS-I and RoB2 tool was used to assess the risk of bias. A narrative synthesis of results was performed due to the heterogeneity of the studies. 5 studies from the database search and 5 studies from citation search comprising 128 animal subjects and 61 human patients were found. These studies collated results based on adhesion formation (6 studies), pain scores (2 studies) and other outcomes, with results favouring the use of carbon dioxide + 10% nitrous oxide + 4% oxygen. This has shown a significant reduction in adhesion formation, pain scores and inflammation. The use of this gas mixture provides promising results for future practice. Several of the studies available require larger sample sizes to develop a more definitive answer on the effects of different gas mixtures. Furthermore, the number of confounding factors in randomised trials should be reduced so that each component of the current suggested gas mixture can be tested for safety and efficacy.

A Case Series of Patients With Complex Airway Disease and Large Thyroid Tumors Anterior to the Trachea Precluding Tracheostomy.

BACKGROUND: This case series explores the management of respiratory failure in patients with large anterior tracheal thyroid tumors where tracheostomy is not an option. To our knowledge, this study is the first to address the challenges associated with caring for such patients. CASE SUMMARY: We present the clinical courses of four intubated adults with advanced thyroid cancer and complex airway issues that preclude surgical tracheostomy. Interventions included custom airway stents, long-term intubation, and oncological therapies. Ethical quandaries around patient autonomy and capacity emerged, exacerbated by the absence of viable exit strategies for prolonged intubation, notably the performance of a tracheostomy, causing emotional distress in patients, families, and staff. CONCLUSIONS: This study showcases the multifaceted challenges in medical, ethical, and emotional domains associated with managing intubated patients with complex disease precluding tracheotomies. We advocate for a nuanced, multidisciplinary, and personalized approach to confront unique issues in airway management, ethical considerations, and disposition.

Elevated brain natriuretic peptide in a patient with metastatic cancer without heart failure: A case study.

ABSTRACT: Brain natriuretic peptide (BNP) is a well-established biomarker for heart failure (HF). However, its diagnostic utility can be limited in patients with comorbidities that independently elevate serum BNP levels, including chronic renal failure and sepsis. We describe a rare occurrence of significantly elevated serum BNP levels in a patient with metastatic urothelial cancer without HF or obvious signs of sepsis. The report highlights the need for considering alternative causes for increased serum BNP levels, especially in the presence of malignancy.

Management of Pericardial Effusion in Patients With Solid Tumor: An Algorithmic, Multidisciplinary Approach Results in Reduced Mortality After Paradoxical Hemodynamic Instability.

OBJECTIVE: This study compared outcomes in patients with solid tumor treated for pericardial effusion with surgical drainage versus interventional radiology (IR) percutaneous drainage and compared incidence of paradoxical hemodynamic instability (PHI) between cohorts. BACKGROUND: Patients with advanced-stage solid malignancies may develop large pericardial effusions requiring intervention. PHI is a fatal and underreported complication that occurs following pericardial effusion drainage. METHODS: Clinical characteristics and outcomes were compared between patients with solid tumors who underwent s urgical drainage or IR percutaneous drainage for pericardial effusion from 2010 to 2020. RESULTS: Among 447 patients, 243 were treated with surgical drainage, of which 27 (11%) developed PHI, compared with 7 of 204 patients (3%) who were treated with IR percutaneous drainage ( P =0.002); overall incidence of PHI decreased during the study period. Rates of reintervention (30-day: 1% vs 4%; 90-day: 4% vs 6%, P =0.7) and mortality (30-day: 21% vs 17%, P =0.3; 90-day: 39% vs 37%, P =0.7) were not different between patients treated with surgical drainage and IR percutaneous drainage. For both interventions, OS was shorter among patients with PHI than among patients without PHI (surgical drainage, median [95% confidence interval] OS, 0.89 mo [0.33-2.1] vs 6.5 mo [5.0-8.9], P <0.001; IR percutaneous drainage, 3.7 mo [0.23-6.8] vs 5.0 mo [4.0-8.1], P =0.044). CONCLUSIONS: With a coordinated multidisciplinary approach focusing on prompt clinical and echocardiographic evaluation, triage with bias toward IR percutaneous drainage than surgical drainage and postintervention intensive care resulted in lower incidence of PHI and improved outcomes.

Point-of-care Ultrasound (POCUS) Program for Critical Care Nurse Practitioners and Physician Assistants in an Oncological Intensive Care Unit and Rapid Response Team.

ABSTRACT: Implementation of a comprehensive point-of-care ultrasound (POCUS) program for nurse practitioners (NPs) and physician assistants (PAs) in an intensive care unit (ICU) setting improves their diagnostic and therapeutic skills and enhances patient care. Overcoming staffing, IT infrastructure, and administrative challenges has allowed our critical care medicine service to develop a successful program that empowers NPs and PAs and boosts their professional growth. Our POCUS program underscores the necessity of institutional support, dedicated mentorship, collaboration with qualified faculty, and creation and maintenance of a curriculum that adheres to accepted national guidelines. Insights gained from our experiences can serve as a valuable resource for institutions aiming to develop their own POCUS programs.

Targeted Therapy and Immunotherapy in Nonmelanoma Skin Cancer.

Advanced nonmelanoma skin cancers (NMSC) are tumors not amenable to surgery and/or radiation. Early systemic treatment attempts with cytotoxic chemotherapy demonstrated low response rates, short durations of response, and high toxicity. Over the last decade, modern therapies for advanced NMSC include targeted therapies and immunotherapies. Hedgehog pathway inhibitors and programmed death-1 inhibitors are available first-line therapies for the treatment of advanced basal cell carcinomas and squamous cell carcinomas, respectively.

High risk of relapsed disease in patients with NK/T-cell chronic active Epstein-Barr virus disease outside of Asia.

Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is characterized by high levels of EBV predominantly in T and/or natural killer cells with lymphoproliferation, organ failure due to infiltration of tissues with virus-infected cells, hemophagocytic lymphohistiocytosis, and/or lymphoma. The disease is more common in Asia than in the United States and Europe. Although allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only curative therapy for CAEBV, its efficacy and the best treatment modality to reduce disease severity prior to HSCT is unknown. Here, we retrospectively assessed an international cohort of 57 patients outside of Asia. Treatment of the disease varied widely, although most patients ultimately proceeded to HSCT. Though patients undergoing HSCT had better survival than those who did not (55% vs 25%, P < .01), there was still a high rate of death in both groups. Mortality was largely not affected by age, ethnicity, cell-type involvement, or disease complications, but development of lymphoma showed a trend with increased mortality (56% vs 35%, P = .1). The overwhelming majority (75%) of patients who died after HSCT succumbed to relapsed disease. CAEBV remains challenging to treat when advanced disease is present. Outcomes would likely improve with better disease control strategies, earlier referral for HSCT, and close follow-up after HSCT including aggressive management of rising EBV DNA levels in the blood.

PD-1 inhibitors for cutaneous squamous cell carcinoma: A meta-analysis.

PD-1 inhibitors are immunotherapeutic agents used in the treatment of advanced cutaneous squamous cell carcinoma (cSCC). This study aimed to determine the pooled objective response and disease control rates of patients with advanced cSCC treated with PD-1 inhibitors. Pubmed, Cochrane Library and EMBASE databases were searched up to 1 January 2021 to include eligible articles. Objective response rate (ORR) and disease control rate (DCR) were pooled and analysed. Subgroup analysis of the odds ratio (OR) for ORR for patients by PD-L1 tumour proportion score (TPS) was performed. Seven articles including a total of 453 patients were identified and included. Pooled estimate of ORR was 44% (95% CI: 39-49%, I2 = 23.7%) and of DCR was 66% (95% CI: 57-74%, I2 = 68.2%). Pooled odds ratio of ORR for patients by PD-L1 TPS was 2.81 (95% CI: 1.22-6.51, I2 = 0.0%). These results were derived from single-arm studies, some of which were retrospective. No head-to-head trials comparing PD-1 inhibitors have been reported. We present aggregate estimates of ORR and DCR for patients with advanced cSCC treated with PD-1 inhibitors, as well as subgroup analysis for ORR for patients by PD-L1 TPS.

Switching Hedgehog inhibitors and other strategies to address resistance when treating advanced basal cell carcinoma.

Although basal cell carcinoma (BCC) is often managed successfully with surgery, patients with locally advanced BCC (laBCC) or metastatic BCC (mBCC) who are not candidates for surgery or radiotherapy have limited treatment options. Most BCCs result from aberrant Hedgehog pathway activation in keratinocyte tumor cells, caused by sporadic or inherited mutations. Mutations in the patched homologue 1 gene that remove its inhibitory regulation of Smoothened homologue (SMO) or mutations in SMO that make it constitutively active, lead to Hedgehog pathway dysregulation and downstream activation of GLI1/2 transcription factors, promoting cell differentiation and proliferation. Hedgehog inhibitors (HHIs) block overactive signaling of this pathway by inhibiting SMO and are currently the only approved treatments for advanced BCC. Two small-molecule SMO inhibitors, vismodegib and sonidegib, have shown efficacy and safety in clinical trials of advanced BCC patients. Although these agents are effective and tolerable for many patients, HHI resistance occurs in some patients. Mechanisms of resistance include mutations in SMO, noncanonical cell identity switching leading to tumor cell resistance, and non-canonical pathway crosstalk causing Hedgehog pathway activation. Approaches to managing HHI resistance include switching HHIs, HHI and radiotherapy combination therapy, photodynamic therapy, and targeting Hedgehog pathway downstream effectors. Increasing understanding of the control of downstream effectors has identified new therapy targets and potential agents for evaluation in BCC. Identification of biomarkers of resistance or response is needed to optimize HHI use in patients with advanced BCC. This review examines HHI resistance, its underlying mechanisms, and methods of management for patients with advanced BCC.

Spatiotemporal dynamics of inner ear sensory and non-sensory cells revealed by single-cell transcriptomics.

The utricle is a vestibular sensory organ that requires mechanosensitive hair cells to detect linear acceleration. In neonatal mice, new hair cells are derived from non-sensory supporting cells, yet cell type diversity and mechanisms of cell addition remain poorly characterized. Here, we perform computational analyses on single-cell transcriptomes to categorize cell types and resolve 14 individual sensory and non-sensory subtypes. Along the periphery of the sensory epithelium, we uncover distinct groups of transitional epithelial cells, marked by Islr, Cnmd, and Enpep expression. By reconstructing de novo trajectories and gene dynamics, we show that as the utricle expands, Islr+ transitional epithelial cells exhibit a dynamic and proliferative phase to generate new supporting cells, followed by coordinated differentiation into hair cells. Taken together, our study reveals a sequential and coordinated process by which non-sensory epithelial cells contribute to growth of the postnatal mouse sensory epithelium.

Necrotizing fasciitis associated with malignancy.

Necrotizing fasciitis (NF) is a rare soft-tissue condition with a high mortality rate even with treatment. Diagnosis is challenging due to an absence of specific symptoms at the early stages of clinical presentation. NF is typically associated with traumatic injuries, superficial skin breakdown, and surgical procedures. Diabetes mellitus and immunosuppression also increase the risk of developing NF. NF predominantly occurs in the lower extremities, the peritoneum, and the perineum. Treatments include antimicrobials, supportive care, and surgical source control. It is important for clinicians to recognize the association of spontaneous atraumatic NF caused by Clostridium septicum with malignancy, so they can maintain a high index of suspicion and provide timely interventions to optimize patient outcomes.

Review of systemic agents in the treatment of advanced cutaneous squamous cell carcinoma.

Advanced cutaneous squamous cell carcinoma (cSCC) accounts for only 5% of all cases of cSCC but up to 60% of disease related deaths. Historically, this disease has lacked effective treatment options due to a combination of poor response rate, poor response durability and significant treatment-associated morbidity. Autumn of 2018 marked the first time ever that an agent received US FDA approval for advanced cSCC and the future is looking much brighter for this previously neglected patient population. The purpose of this article is to review the various systemic treatment options for advanced cSCC moving from the past to the present, highlighting their relative merits and shortcomings, and to briefly speculate on future developments in the field of advanced cSCC.

Spurious Laboratory Values in Patients With Leukocytosis.

Physiological derangements such as hypoxemia and hyperkalemia are medical emergencies that warrant prompt interventions to prevent further patient clinical deterioration. However, in patients with myeloproliferative diseases or malignancies that result in extreme leukocytosis, hypoxemia and hyperkalemia demonstrated in laboratory results could be deceiving due to in vitro reactions and may not reflect actual patient condition. Clinicians have to be familiar with these phenomena so as to not cause harm by treating these spurious laboratory values.

Emerging Nonsurgical Therapies for Locally Advanced and Metastatic Nonmelanoma Skin Cancer.

BACKGROUND: Locally advanced and metastatic nonmelanoma skin cancer (NMSC) not amenable to surgical resection requires a different approach to therapy. OBJECTIVE: To review the efficacy and adverse effects of emerging treatment options for locally advanced and metastatic NMSC. MATERIALS AND METHODS: A comprehensive search on PubMed was conducted to identify relevant literature investigating the role of program cell death 1 (PD-1) inhibitor, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor, epidermal growth factor receptor (EGFR) inhibitor, and Hedgehog pathway inhibitors in the treatment of NMSC. RESULTS: PD-1 inhibitor and CTLA-4 inhibitor have shown promising efficacy with tolerable side-effect profiles in the treatment of NMSC, although the number of cases reported is limited. Currently, 3 larger-scale clinical trials are investigating PD-1 inhibitor therapy for NMSC. Similarly, EGFR inhibitor demonstrated marginal success in unresectable cutaneous squamous cell carcinomas. Hedgehog pathway inhibitors were approved by the US FDA for treatment of locally advanced and metastatic basal cell carcinomas and have shown favorable efficacy. Common adverse effects included muscle spasm, alopecia, and dysgeusia. CONCLUSION: Systemic therapies including PD-1 inhibitors and CTLA-4 inhibitors have demonstrated early promising results for difficult-to-treat NMSC. Future studies are necessary to optimize treatment outcome.

A case report of bosutinib-induced interstitial granulomatous drug reaction in a patient with chronic myelogenous leukemia: a case report.

Bosutinib is a BCR-ABL tyrosine kinase inhibitor approved for the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia. We report a case of bosutinib-induced interstitial granulomatous drug reaction in a 50-year-old Caucasian female with chronic myelogenous leukemia. Histologic analysis of a punch biopsy showed diffuse interstitial granulomatous infiltrates consisting of histiocytes amid thickened collagen accompanied by eosinophils. Her lesions improved with clobetasol 0.05% cream. No cases describing BCR-ABL tyrosine kinase inhibitor-associated interstitial granulomatous drug reaction were found in a search of the literature. It is important for physicians to be aware of the risk of interstitial granulomatous drug reaction associated with bosutinib treatment.