Corticosteroid administration for cancer-related indications is an unfavorable prognostic factor in solid cancer patients receiving immune checkpoint inhibitor treatment.

OBJECTIVE: Immunotherapies targeting immune checkpoints have achieved encouraging survival benefits in patients with various solid cancers. Corticosteroids are frequently administrated for cancer/non-cancer related indications and immune-related adverse events (irAEs). This study aimed to clarify the prognostic significance of corticosteroid administration in solid cancer patients receiving immune checkpoint inhibitor (ICI) treatment. METHOD: First, a meta-analysis was performed using the literatures searched from PubMed, Cochrane Library, Web of Science, Embase, and Clinicaltrials.gov before January 2021. The Hazard ratios (HRs) coupled with 95% confidence intervals (CIs) were used to evaluate the correlation of corticosteroid administration with overall survival (OS) and progression-free survival (PFS). Then, a retrospective analysis enrolling 118 ICI-treated cancer patients was performed for validation, among which 26 patients received corticosteroids for cancer-related indications. RESULT: In the meta-analysis, corticosteroid administration for cancer-related indications was significantly correlated with worse PFS (HR = 1.735(1.381-2.180)) and OS (HR = 1.936(1.587-2.361)) of the ICI-treated patients. However, corticosteroid administration for non-cancer-related indications and irAEs was unrelated with PFS (non-cancer-related indications: HR = 0.830(0.645-1.067); irAEs: HR = 1.302(0.628-2.696)) and OS (non-cancer-related indications: HR = 0.786(0.512-1.206); irAEs: HR = 1.107(0.832-1.474)) of the ICI-treated patients. The following retrospective analysis identified corticosteroid administration for cancer-related indications was an independent unfavorable predictor for PFS (P = 0.006) and OS (P = 0.044) of the ICI-treated patients. The subgroup analysis based on non-small cell lung cancer (NSCLC) demonstrated the similar results (P = 0.002 for PFS and P = 0.047 for OS). CONCLUSION: Our study demonstrated corticosteroid administration for cancer-related indications is an unfavorable prognostic factor in solid cancer patients receiving ICI treatment. Therefore, careful selection of corticosteroid-treated patients for ICI therapy is quite necessary in individualized clinical management.

TRough versus AUC Monitoring of cyclosporine: A randomized comparison of adverse drug reactions in adult allogeneic stem cell recipients (TRAM study).

OBJECTIVE: To investigate the incidence and severity of adverse drug reactions of cyclosporine using AUC-targeted therapeutic drug monitoring (TDM) compared to trough level (Ctrough )-targeted TDM in adult allogeneic stem cell recipients. METHODS: Blind, monocenter, intervention study. Subjects were 1:1 randomized into either an AUC group or a Ctrough group. Adverse drug reactions were accessed two and four weeks after start of treatment. RESULTS: Forty patients were included, resulting in 15 evaluable subjects (AUC group) and 13 evaluable subjects (Ctrough group). Grade two/three toxicity was observed in 46% (Ctrough group) versus 60% of subjects (AUC group) (P = .463). There was no significant difference between two and four weeks after start of cyclosporine for nausea (P = .142 resp. P = .122), renal dysfunction (P = .464 resp. P = 1.000), and hypomagnesemia (P = 1.000 resp. P = .411). Subjects in the AUC group reached the therapeutic goal earlier (72,7% versus 43,0% at third sampling point, P = .332) and were within the target range more consistently. CONCLUSION: This study showed no reduction in incidence and severity of cyclosporine-induced toxicity with AUC- versus trough level-targeted TDM. Although modeled dosing based on AUC led to faster optimal target attainment, this did not result in less toxicity in the early days after transplantation.

A clinical classification system for grading platinum hypersensitivity reactions.

OBJECTIVES: Current grading systems for platinum hypersensitivities (pHSR) rely on subjective features rather than objective clinical signs leading to inconsistencies in grading. To standardize classification of pHSR, a clinical grading system was developed at our institution. We report the clinical outcomes our classification system and evaluate its correlation with the classification systems currently published and used in practice. METHODS: This was a retrospective review of patients with pHSR from 2011 to 2017. Demographics, chemotherapeutic histories (CT), and details of their initial HSR were collected. Mild reactions were defined as local skin manifestations only. Moderate-low reactions included widespread skin, respiratory or GI findings. Moderate-standard reactions were defined as transient cardiovascular compromise (CVC), hypoxia or neurologic changes whereas sustained changes (>10 min) were used to define severe reaction. Fischer Exact Tests (p < .05) and binary logistic regression analyses were performed. Spearman correlation were used to assess relationships between our grading system and the NCCN and CTCAEv4.0 criteria. RESULTS: 87 patients were identified with most having ovarian cancer (n = 55, 63.2%), receiving carboplatin (n = 62, 71.3%), and on second-line CT (n = 34, 42.5%). Chest pain was associated with transient CVC (OR 10.0, 95% CI 1.148-87.133) while nausea/vomiting (OR 8.420, 95% CI 1.263-55.275) was associated with transient hypoxia albeit less closely than transient hypotension (OR 17.010, 95% CI 2.026-142.825). Only presyncope/syncope remained associated with sustained CVC (OR 38.0, 95% CI 2.815-512.912) on logistic regression. The classification system was most strongly correlated with the NCCN grading system (ρ 0.761, p < .001). CONCLUSIONS: This classification system offers an objective means of grading pHSR severity and correlates with currently-used grading systems.

Clinical Insights into the Gastrointestinal Manifestations of COVID-19.

The month of December 2019 became a critical part of the time of humanity when the first case of coronavirus disease 2019 (COVID-19) was reported in the Wuhan, Hubei Province in China. As of April 13th, 2020, there have been approximately 1.9 million cases and 199,000 deaths across the world, which were associated with COVID-19. The COVID-19 is the seventh coronavirus to be identified to infect humans. In the past, Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome were the two coronaviruses that infected humans with a high fatality, particularly among the elderly. Fatalities due to COVID-19 are higher in patients older than 50 years of age or those with multimorbid conditions. The COVID-19 is mainly transmitted through respiratory droplets, with the most common symptoms being high fever, cough, myalgia, atypical symptoms included sputum production, headache, hemoptysis and diarrhea. However, the incubation period can range from 2 to 14 days without any symptoms. It is particularly true with gastrointestinal (GI) symptoms in which patients can still shed the virus even after pulmonary symptoms have resolved. Given the high percentage of COVID-19 patients that present with GI symptoms (e.g., nausea and diarrhea), screening patients for GI symptoms remain essential. Recently, cases of fecal-oral transmission of COVID-19 have been confirmed in the USA and China, indicating that the virus can replicate in both the respiratory and digestive tract. Moreover, the epidemiology, clinical characteristics, diagnostic procedures, treatments and prevention of the gastrointestinal manifestations of COVID-19 remain to be elucidated.

Neurological autoimmune disorders with prominent gastrointestinal manifestations: A review of presentation, evaluation, and treatment.

BACKGROUND: The identification of autoantibodies directed against neuronal antigens has led to the recognition of a wide spectrum of neurological autoimmune disorders (NAD). With timely recognition and treatment, many patients with NAD see rapid improvement. Symptoms associated with NAD can be diverse and are determined by the regions of the nervous system affected. In addition to neurological symptoms, a number of these disorders present with prominent gastrointestinal (GI) manifestations such as nausea, diarrhea, weight loss, and gastroparesis prompting an initial evaluation by gastroenterologists. PURPOSE: This review provides a general overview of autoantibodies within the nervous system, focusing on three scenarios in which nervous system autoimmunity may initially present with gut symptoms. A general approach to evaluation and treatment, including antibody testing, will be reviewed.

Intractable nausea and vomiting as an uncommon presentation in an anti-aquaporin 4-positive patient.

Autoantibodies targeting aquaporin 4 (AQP4) water channels are a sensitive and specific biomarker for neuromyelitis optica spectrum disorder (NMOSD). Presence of AQP4 antibodies distinguishes NMOSD from multiple sclerosis. We present our experience with an anti-AQP4 antibody-positive patient diagnosed with NMOSD who complained of intractable nausea and vomiting, not restricted to optic neuritis or acute myelitis during the first attack. Her symptoms partially resolved after appropriate therapy with intravenous methylprednisolone and oral prednisolone. Through this case, we hope to draw attention to an unusual neurological presentation of NMOSD which should be included in the differential diagnosis of intractable nausea and vomiting.

Sex-specific adaptation of endocrine and inflammatory responses to repeated nauseogenic body rotation.

It has been shown that stress changes stimulated pro-inflammatory cytokine production and the sensitivity of stimulated cytokine production to glucocorticoid suppression. While glucocorticoid secretion habituates in response repeated stimulation, it is not known whether stimulation and suppression of cytokine production are also subject to adaptation. Eight healthy young subjects were exposed to repeated nauseogenic body rotation on four consecutive days. On each day subjects were rotated around the vertical axis up to five times for a period of 1 min or until subjects chose to stop due to nausea. Blood and saliva samples were obtained before and after rotation for assessment of cortisol, ACTH, plasma vasopressin (ADH), in vitro TNF-alpha and IL-6 production and glucocorticoid sensitivity of TNF-alpha and IL-6 production. Rotation induced increases of ACTH, cortisol, and ADH in the first session. All endocrine responses habituated over time, except for the free cortisol response in men. Pro-inflammatory cytokine production showed a sex-specific response pattern with increases in men and decreases in women in the first session vs. increases in men and women in the last session. Response patterns of GC sensitivity also changed over time: in the first session, sensitivity increased only in men, but in the last session, GC sensitivity decreased in all subjects. In conclusion, in response to repeated nausea induction, habituation occurs only in the endocrine system and predominantly in women. In the immune system, response patterns change in the favor of inflammatory conditions, with increases in stimulated IL-6 and TNF-alpha and decreases in the effectiveness of glucocorticoid suppression of these cytokines. These presumably unfavorable changes in the inflammatory system are more pronounced men.