Immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment, but their use is linked to immune-related adverse events (irAEs), including the rare ICI-associated myocarditis, myositis, and myasthenia gravis (MMM) overlap syndrome. This systematic review aims to highlight MMM’s clinical implications in emergency departments. PubMed and Embase were searched using a specific search strategy. Reports were eligible for inclusion if all three conditions were present and associated with the use of an ICI. Data were extracted by independent reviewers using the Rayyan web application for systematic reviews. Descriptive statistics and qualitative synthesis were used to summarize demographic, clinical, and treatment data for the reported cases. Among 50 cases, predominantly associated with melanoma, lung cancer, and renal cancer, the in-hospital mortality rate was 38.0%. The most commonly presenting symptoms were ptosis (58%), dyspnea (48%), diplopia (42%), or myalgia (36%). The median time from ICI initiation to MMM presentation was 21 days (interquartile range: 15–28 days). Corticosteroids were the primary treatment for the irAEs. MMM, a rare but potentially fatal complication of ICI therapy, requires prompt recognition in emergency settings. Corticosteroids should be initiated if suspected, without waiting for confirmation. Multidisciplinary collaboration is vital for diagnosis and treatment planning. Research on MMM’s link to specific cancers and ICIs is imperative for better risk assessment and interventions.

Weight loss and cachexia are common problems in colorectal cancer patients; thus, parenteral and enteral nutrition support play important roles in cancer care. However, the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied. In this study, we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival (P < 0.001) than those who did not. Cystine indeed robustly promotes colon cancer cell growth in vitro and in immunodeficient mice, predominately by inhibiting SESN2 transcription via the GCN2-ATF4 axis, resulting in mTORC1 activation. mTORC1 inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation. In addition, cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione. We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin. These findings indicate that cyst(e)ine, as part of supplemental nutrition, plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.

Sepsis remains a leading cause of death for humans and currently has no pathogenesis-specific therapy. Hampered progress is partly due to a lack of insight into deep mechanistic processes. In the past decade, deciphering the functions of small noncoding miRNAs in sepsis pathogenesis became a dynamic research topic. To screen for new miRNA targets for sepsis therapeutics, we used samples for miRNA array analysis of PBMCs from patients with sepsis and control individuals, blood samples from 2 cohorts of patients with sepsis, and multiple animal models: mouse cecum ligation puncture–induced (CLP-induced) sepsis, mouse viral miRNA challenge, and baboon Gram⁺ and Gram^– sepsis models. miR-93-5p met the criteria for a therapeutic target, as it was overexpressed in baboons that died early after induction of sepsis, was downregulated in patients who survived after sepsis, and correlated with negative clinical prognosticators for sepsis. Therapeutically, inhibition of miR-93-5p prolonged the overall survival of mice with CLP-induced sepsis, with a stronger effect in older mice. Mechanistically, anti–miR-93-5p therapy reduced inflammatory monocytes and increased circulating effector memory T cells, especially the CD4⁺ subset. AGO2 IP in miR-93–KO T cells identified important regulatory receptors, such as CD28, as direct miR-93-5p target genes. In conclusion, miR-93-5p is a potential therapeutic target in sepsis through the regulation of both innate and adaptive immunity, with possibly a greater benefit for elderly patients than for young patients.

Purpose In addition to tumor factors, poor nutritional status before and during anti-tumor treatment might compromise prognosis in several types of cancer. This study was done to determine the impact of weight loss during preoperative chemoradiotherapy (CRT) on the survival outcome of patients with locally advanced rectal cancer (LARC). Methods The retrospective study examined consecutive patients with LARC who underwent preoperative CRT followed by radical resection in a single institute, between 2003 and 2013. Correlation of proportional body mass index (BMI) change after preoperative CRT and patient’s demographics, tumor characteristics, treatment parameters, CRT-related toxicity, disease-free survival (DFS) and overall survival (OS) were investigated. Results A total of 364 patients were enrolled, and BMI loss was found in 243 patients (66.2 %) after preoperative CRT. Severe weight loss (SWL) was defined as BMI loss ≥7 %. Thirty-nine (10.7 %) cases were enrolled in SWL cohort and found to have higher incidence of diarrhea (P = 0.033), renal disorder (P = 0.033) and grade 3–4 radiation proctitis (P = 0.041). Although no significant difference was found in 3-year DFS, patients in SWL cohort showed significantly worse 3-year OS rate (71.8 vs 88.0 %, P = 0.030) than the others. In univariate analysis, BMI loss ≥7 %, completed dose of preoperative chemotherapy, pathologic T and N stages were correlated with OS (all P < 0.05). In multivariable analysis, BMI loss ≥7 % (HR 1.984; 95 % CI 1.061–3.709; P = 0.032) remained the independent prognostic factor for OS. Conclusions Our results demonstrate that SWL during preoperative CRT indeed compromises survival outcome in patients with LARC. Routine nutritional monitoring and nutritional support during preoperative CRT are suggested as the integral part of the multidisciplinary approach for these patients.