Bile Acids in Pancreatic Carcinogenesis.

Pancreatic cancer (PC) is a dangerous digestive tract tumor that is becoming increasingly common and fatal. The most common form of PC is pancreatic ductal adenocarcinoma (PDAC). Bile acids (BAs) are closely linked to the growth and progression of PC. They can change the intestinal flora, increasing intestinal permeability and allowing gut microbes to enter the bloodstream, leading to chronic inflammation. High dietary lipids can increase BA secretion into the duodenum and fecal BA levels. BAs can cause genetic mutations, mitochondrial dysfunction, abnormal activation of intracellular trypsin, cytoskeletal damage, activation of NF-κB, acute pancreatitis, cell injury, and cell necrosis. They can act on different types of pancreatic cells and receptors, altering Ca2+ and iron levels, and related signals. Elevated levels of Ca2+ and iron are associated with cell necrosis and ferroptosis. Bile reflux into the pancreatic ducts can speed up the kinetics of epithelial cells, promoting the development of pancreatic intraductal papillary carcinoma. BAs can cause the enormous secretion of Glucagon-like peptide-1 (GLP-1), leading to the proliferation of pancreatic ß-cells. Using Glucagon-like peptide-1 receptor agonist (GLP-1RA) increases the risk of pancreatitis and PC. Therefore, our objective was to explore various studies and thoroughly examine the role of BAs in PC.

The Effect of L-Carnitine on Critical Illnesses Such as Traumatic Brain Injury (TBI), Acute Kidney Injury (AKI), and Hyperammonemia (HA).

L-carnitine (LC) through diet is highly beneficial for critical patients. Studies have found that acetyl-L-carnitine (ALC) can reduce cerebral edema and neurological complications in TBI patients. It significantly improves their neurobehavioral and neurocognitive functions. ALC has also been shown to have a neuroprotective effect in cases of global and focal cerebral ischemia. Moreover, it is an effective agent in reducing nephrotoxicity by suppressing downstream mitochondrial fragmentation. LC can reduce the severity of renal ischemia-reperfusion injury, renal cast formation, tubular necrosis, iron accumulation in the tubular epithelium, CK activity, urea levels, Cr levels, and MDA levels and restore the function of enzymes such as SOD, catalase, and GPx. LC can also be administered to patients with hyperammonemia (HA), as it can suppress ammonia levels. It is important to note, however, that LC levels are dysregulated in various conditions such as aging, cirrhosis, cardiomyopathy, malnutrition, sepsis, endocrine disorders, diabetes, trauma, starvation, obesity, and medication interactions. There is limited research on the effects of LC supplementation in critical illnesses such as TBI, AKI, and HA. This scarcity of studies highlights the need for further research in this area.

Bebtelovimab-Induced Bradycardia Leading to Cardiac Arrest.

Bebtelovimab is a monoclonal antibody used to prevent progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Complications of SARS-CoV-2 infection can include cardiac effects including sinus bradycardia. CASE SUMMARY: We describe the case of an 86-year-old male infected with SARS-CoV-2 who experienced bradycardia with cardiac arrest immediately following infusion of Bebtelovimab with return of spontaneous circulation obtained following 1 minute of chest compressions and administration of atropine. His bradycardia resolved, and he was extubated on hospital day 1, found to be neurologically intact, and discharged on hospital day 9. CONCLUSIONS: Due to the time course of the patient's symptomatology, we attribute the bradycardic arrest to the Bebtelovimab infusion. This case illustrates the need for further research into the etiology of bradycardia due to SARS-CoV-2 infection and to examine potential links to monoclonal antibody infusion. It also serves as important caution to maintain close cardiac monitoring while administering monoclonal antibodies for SARS-CoV-2.

A case of SARS-CoV-2-associated arthritis with detection of viral RNA in synovial fluid.

Severe acute respiratory distress syndrome-coronavirus-2 (SARS-CoV-2) provokes symptoms ranging from mild viral illness to a systemic inflammatory syndrome with multi-organ failure and has been associated with cases of arthritis. We report a clinical case of SARS-CoV-2 associated arthritis in which analysis of synovial fluid detected SARS-CoV-2 ribonucleic acid.

Polyomaviruses-associated respiratory infections in HIV-infected and HIV-uninfected children.

BACKGROUND: Two recently discovered polyomaviruses (PyV), WU and KI, have been identified in respiratory-tract specimens from children with acute respiratory infections, although there are limited data in HIV-infected children. OBJECTIVES: To determine the prevalence and clinical manifestations of WUPyV and KIPyV-associated lower respiratory tract infections (LRTIs) hospitalization in HIV-infected and -uninfected children; and probe the role of pneumococcal co-infection. STUDY DESIGN: Nasopharyngeal aspirates were collected from a cohort of 39,836 children randomized to receive 9-valent pneumococcal conjugate vaccine (PCV9) or placebo when hospitalized for LRTIs, and were screened by PCR for WUPyV, KIPyV and other respiratory viruses. RESULTS: In placebo-recipients the prevalence of WUPyV was 6.3% (18/285) in HIV-infected and 13.9% (66/476) in HIV-uninfected children (p=0.002). In WUPyV-positive LRTIs HIV-infected children had lower oxygen saturation at admission and a higher case fatality rate (11.1% vs. 0%; p=0.04). KIPyV was identified in 10.2% (29/285) of HIV-infected and in 7.4% (35/476) of HIV-uninfected placebo-recipients with LRTIs (p=0.13). HIV-infected compared to HIV-uninfected children with KIPyV-positive LRTIs had lower oxygen saturation, higher respiratory rate and longer duration of hospitalization. Co-infections with other respiratory-viruses were detected in 65.5% of WUPyV-positive LRTIs and in 75.0% of KIPyV-positive LRTIs. Among HIV-uninfected children, there was a lower incidence of hospitalization for clinical pneumonia episodes in which KIPyV (80%; 95% CI: 41, 93) and WUPyV (49%; 95% CI: 9, 71) were identified among PCV9-recipients compared to placebo-recipients. CONCLUSIONS: Polyomaviruses were commonly identified in HIV-infected and -uninfected children hospitalized for LRTIs, frequently in association with other viruses and may contribute to the pathogenesis of pneumococcal pneumonia.

Clinical epidemiology of bocavirus, rhinovirus, two polyomaviruses and four coronaviruses in HIV-infected and HIV-uninfected South African children.

BACKGROUND: Advances in molecular diagnostics have implicated newly-discovered respiratory viruses in the pathogenesis of pneumonia. We aimed to determine the prevalence and clinical characteristics of human bocavirus (hBoV), human rhinovirus (hRV), polyomavirus-WU (WUPyV) and -KI (KIPyV) and human coronaviruses (CoV)-OC43, -NL63, -HKU1 and -229E among children hospitalized with lower respiratory tract infections (LRTI). METHODS: Multiplex real-time reverse-transcriptase polymerase chain reaction was undertaken on archived nasopharyngeal aspirates from HIV-infected and -uninfected children (<2 years age) hospitalized for LRTI, who had been previously investigated for respiratory syncytial virus, human metapneumovirus, parainfluenza I-III, adenovirus and influenza A/B. RESULTS: At least one of these viruses were identified in 274 (53.0%) of 517 and in 509 (54.0%) of 943 LRTI-episodes in HIV-infected and -uninfected children, respectively. Human rhinovirus was the most prevalent in HIV-infected (31.7%) and -uninfected children (32.0%), followed by CoV-OC43 (12.2%) and hBoV (9.5%) in HIV-infected; and by hBoV (13.3%) and WUPyV (11.9%) in HIV-uninfected children. Polyomavirus-KI (8.9% vs. 4.8%; p = 0.002) and CoV-OC43 (12.2% vs. 3.6%; p<0.001) were more prevalent in HIV-infected than -uninfected children. Combined with previously-tested viruses, respiratory viruses were identified in 60.9% of HIV-infected and 78.3% of HIV-uninfected children. The newly tested viruses were detected at high frequency in association with other respiratory viruses, including previously-investigated viruses (22.8% in HIV-infected and 28.5% in HIV-uninfected children). CONCLUSIONS: We established that combined with previously-investigated viruses, at least one respiratory virus was identified in the majority of HIV-infected and HIV-uninfected children hospitalized for LRTI. The high frequency of viral co-infections illustrates the complexities in attributing causality to specific viruses in the aetiology of LRTI and may indicate a synergetic role of viral co-infections in the pathogenesis of childhood LRTI.