Liraglutide-Induced Pancreatitis: A Case Report and Literature Review.

Liraglutide is an anti-diabetic medication used for the treatment of type 2 diabetes mellitus, obesity, and chronic weight management. It is a glucagon-like peptide-1 (GLP-1) agonist that helps reduce postprandial hyperglycemia for up to 24 h after administration. It stimulates endogenous insulin secretion according to glucose levels, and also delays gastric emptying and suppresses prandial glucagon secretion. Some of the common complications associated with liraglutide include hypoglycemia, headache, diarrhea, nausea, and vomiting. Uncommon adverse effects include pancreatitis, kidney failure, pancreatic cancer, and injection site reactions. In this article, we discussed a case of a 73-year-old male with a history of uncontrolled type 2 diabetes mellitus on long-term insulin and liraglutide who presented with abdominal pain, subjective fevers, dry heaves, tachycardia, and mildly reduced oxygen saturation. The patient was diagnosed with pancreatitis on the basis of laboratory and imaging findings. Liraglutide was discontinued, and the patient received supportive care with significant clinical improvement. The use of GLP-1 inhibitors has been increasing not only for diabetes mellitus management, but also for its promising effect on weight management. The literature review endorses our case report findings, and also discusses other complications of liraglutide. Therefore, we recommend to be cognizant of these side-effects upon starting liraglutide.

Comprehensive Review of Red Meat Consumption and the Risk of Cancer.

Red and processed meat consumption rates are increasing in the United States. In this review, we present the current evidence that links red meat consumption and cancer development. A literature search was conducted in the PubMed and Google Scholar databases to review red meat consumption and its association with breast cancer and gastrointestinal cancer. Due to the presence of heme iron, which triggers oxidative reactions that eventually result in tumor formation, red meat consumption is strongly associated with the development of breast cancer. Ingestion of red meat increases Helicobacter pylori infections, resulting in enhanced expression of the CagA gene and the secretion of pro-inflammatory cytokines. This is the leading cause of gastric cancer. There is a strong correlation between heterocyclic amines and polycyclic aromatic hydrocarbons in red meat and the development of pancreatic cancer. However, additional research is necessary to confirm this finding. Adult colorectal cancer is caused by the formation of heterocyclic amines and DNA adducts due to the intake of red and processed meats cooked at higher temperatures. The consumption of poultry is associated with a reduced risk of breast and gastrointestinal cancers, but the results are inconsistent. The evidence is strong for the association between red meat and breast cancer and most gastric cancers. The presence of aromatic hydrocarbons, heterocyclic amines, and heme iron in red meat has been found to be behind tumorigenesis. Poultry has been shown to have a low association with cancer, but additional research is needed.

ViSHWaS: Violence Study of Healthcare Workers and Systems-a global survey.

OBJECTIVE: To provide insights into the nature, risk factors, impact and existing measures for reporting and preventing violence in the healthcare system. The under-reporting of violence against healthcare workers (HCWs) globally highlights the need for increased public awareness and education. METHODS: The Violence Study of Healthcare Workers and Systems study used a survey questionnaire created using Research Electronic Data Capture (REDCap) forms and distributed from 6 June to 9 August 2022. Logistic regression analysis evaluated violence predictors, including gender, age, years of experience, institution type, respondent profession and night shift frequency. A χ2 test was performed to determine the association between gender and different violence forms. RESULTS: A total of 5405 responses from 79 countries were analysed. India, the USA and Venezuela were the top three contributors. Female respondents comprised 53%. The majority (45%) fell within the 26-35 age group. Medical students (21%), consultants (20%), residents/fellows (15%) and nurses (10%) constituted highest responders. Nearly 55% HCWs reported firsthand violence experience, and 16% reported violence against their colleagues. Perpetrators were identified as patients or family members in over 50% of cases, while supervisor-incited violence accounted for 16%. Around 80% stated that violence incidence either remained constant or increased during the COVID-19 pandemic. Among HCWs who experienced violence, 55% felt less motivated or more dissatisfied with their jobs afterward, and 25% expressed willingness to quit. Univariate analysis revealed that HCWs aged 26-65 years, nurses, physicians, ancillary staff, those working in public settings, with >1 year of experience, and frequent night shift workers were at significantly higher risk of experiencing violence. These results remained significant in multivariate analysis, except for the 55-65 age group, which lost statistical significance. CONCLUSION: This global cross-sectional study highlights that a majority of HCWs have experienced violence, and the incidence either increased or remained the same during the COVID-19 pandemic. This has resulted in decreased job satisfaction.

Curcumin as a Potential Therapeutic Agent in Certain Cancer Types.

Cancer is a devastating disease condition and is the second most common etiology of death globally. After decades of research in the field of hematological malignancies and cellular therapeutics, we are still looking for therapeutic agents with the most efficacies and least toxicities. Curcumin is one of the cancer therapeutic agents that is derived from the Curcuma longa (turmeric) plant, and still in vitro and in vivo research is going on to find its beneficial effects on various cancers. Due to its potency to affect multiple targets of different cellular pathways, it is considered a promising agent to tackle various cancers alone or in combination with the existing chemotherapies. This review covers basic properties, mechanism of action, potential targets (molecules and cell-signaling pathways) of curcumin, as well as its effect on various solid and hematological malignancies.

Association of dementia and patient outcomes among COVID-19 patients: A multi-center retrospective case-control study.

Background: We conducted a retrospective cohort study on COVID-19 patients with and without dementia by extracting data from the HCA Healthcare Enterprise Data Warehouse between January-September 2020. Aims: To describe the role of patients' baseline characteristics specifically dementia in determining overall health outcomes in COVID-19 patients. Methods: We grouped in-patients who had ICD-10 codes for dementia (DM) with age and gender-matched (1:2) patients without dementia (ND). Our primary outcome variables were in-hospital mortality, length of stay, Intensive Care Unit (ICU) admission, ICU-free days, mechanical ventilation (MV) use, MV-free days and 90-day re-admission. Results: Matching provided similar age and sex in DM and ND groups. BMI (median, 25.8 vs. 27.6) and proportion of patients who had smoked (23.3 vs. 31.3%) were lower in DM than in ND patients. The median (IQR) Elixhauser Comorbidity Index was higher in dementia patients 7 (5-10) vs. 5 (3-7, p < 0.01). Higher mortality was observed in DM group (30.8%) vs. ND group (26.4%, p < 0.01) as an unadjusted univariate analysis. The 90-day readmission was not different (32.1 vs. 31.8%, p = 0.8). In logistic regression analysis, the odds of dying were not different between patients in DM and ND groups (OR = 1.0; 95% CI 0.86-1.17), but the odds of ICU admissions were significantly lower for dementia patients (OR = 0.58, 95% CI 0.51-0.66). Conclusions: Our data showed that COVID-19 patients with dementia did not fare substantially worse, but in fact, fared better when certain metrics were considered.

Functional cooperativity of p97 and histone deacetylase 6 in mediating DNA repair in mantle cell lymphoma cells.

p97 is an ATPase that works in concert with histone deacetylase 6 (HDAC6), to facilitate the degradation of misfolded proteins by autophagosomes. p97 has also been implicated in DNA repair and maintaining genomic stability. In this study, we determined the effect of combined inhibition of p97 and HDAC6 activities in mantle cell lymphoma (MCL) cells. We report that treatment with p97 inhibitors induces dose-dependent apoptosis in MCL cells. The p97 inhibitor CB-5083 induces ER stress markers GRP78 and CHOP and results in the accumulation of polyubiquitylated proteins. Co-treatment with CB-5083 and the HDAC6 inhibitor ACY-1215 result in marked downregulation of CDK4, Cyclin D1, and BRCA1 levels without inhibiting autophagic flux. Consequently, treatment with CB-5083 accentuates DNA damage in response to treatment with ACY-1215 resulting in enhanced accumulation of H2AX-γ and synergistic apoptosis. Furthermore, ATM loss severely impairs phosphorylation of 53BP1 following co-treatment with CB-5083 and ACY-1215 in response to gamma irradiation. Finally, co-treatment CB-5083 and ACY-1215 results in reduced tumor volumes and improves survival in Z138C and Jeko-1 xenografts in NSG mice. These observations suggest that combined inhibition of p97 and HDAC6 abrogates resolution of proteotoxic stress and impairs DNA repair mechanisms in MCL cells.

Targeting p97 to Disrupt Protein Homeostasis in Cancer.

Cancer cells are addicted to numerous non-oncogenic traits that enable them to thrive. Proteotoxic stress is one such non-oncogenic trait that is experienced by all tumor cells owing to increased genomic abnormalities and the resulting synthesis and accumulation of non-stoichiometric amounts of cellular proteins. This imbalance in the amounts of proteins ultimately culminates in proteotoxic stress. p97, or valosin-containing protein (VCP), is an ATPase whose function is essential to restore protein homeostasis in the cells. Working in concert with the ubiquitin proteasome system, p97 promotes the retrotranslocation from cellular organelles and/or degradation of misfolded proteins. Consequently, p97 inhibition has emerged as a novel therapeutic target in cancer cells, especially those that have a highly secretory phenotype. This review summarizes our current understanding of the function of p97 in maintaining protein homeostasis and its inhibition with small molecule inhibitors as an emerging strategy to target cancer cells.