Delayed diagnosis and subsequently increased severity of acute appendicitis (compatible with clinical-pathologic grounds) during the COVID-19 pandemic: an observational case-control study.

BACKGROUND: During a global crisis like the current COVID-19 pandemic, delayed admission to hospital in cases of emergent medical illness may lead to serious adverse consequences. We aimed to determine whether such delayed admission affected the severity of an inflammatory process regarding acute appendicitis, and its convalescence. METHODS: In a retrospective observational cohort case-control study, we analyzed the medical data of 60 patients who were emergently and consecutively admitted to our hospital due to acute appendicitis as established by clinical presentation and imaging modalities, during the period of the COVID-19 pandemic (our study group). We matched a statistically control group consisting of 97 patients who were admitted during a previous 12-month period for the same etiology. All underwent laparoscopic appendectomy. The main study parameters included intraoperative findings (validated by histopathology), duration of abdominal pain prior to admission, hospital stay and postoperative convalescence (reflecting the consequences of delay in diagnosis and surgery). RESULTS: The mean duration of abdominal pain until surgery was significantly longer in the study group. The rate of advanced appendicitis (suppurative and gangrenous appendicitis as well as peri-appendicular abscess) was greater in the study than in the control group (38.3 vs. 21.6%, 23.3 vs. 16.5%, and 5 vs. 1% respectively), as well as mean hospital stay. CONCLUSIONS: A global crisis like the current viral pandemic may significantly affect emergent admissions to hospital (as in case of acute appendicitis), leading to delayed surgical interventions and its consequences.

Anti-SARS-CoV-2 antibodies elicited by COVID-19 mRNA vaccine exhibit a unique glycosylation pattern.

Messenger RNA-based vaccines against COVID-19 induce a robust anti-SARS-CoV-2 antibody response with potent viral neutralization activity. Antibody effector functions are determined by their constant region subclasses and by their glycosylation patterns, but their role in vaccine efficacy is unclear. Moreover, whether vaccination induces antibodies similar to those in patients with COVID-19 remains unknown. We analyze BNT162b2 vaccine-induced IgG subclass distribution and Fc glycosylation patterns and their potential to drive effector function via Fcγ receptors and complement pathways. We identify unique and dynamic pro-inflammatory Fc compositions that are distinct from those in patients with COVID-19 and convalescents. Vaccine-induced anti-Spike IgG is characterized by distinct Fab- and Fc-mediated functions between different age groups and in comparison to antibodies generated during natural viral infection. These data highlight the heterogeneity of Fc responses to SARS-CoV-2 infection and vaccination and suggest that they support long-lasting protection differently.

Impaired COMMD10-Mediated Regulation of Ly6Chi Monocyte-Driven Inflammation Disrupts Gut Barrier Function.

Ly6Chi monocyte tissue infiltrates play important roles in mediating local inflammation, bacterial elimination and resolution during sepsis and inflammatory bowel disease (IBD). Yet, the immunoregulatory pathways dictating their activity remain poorly understood. COMMD family proteins are emerging as key regulators of signaling and protein trafficking events during inflammation, but the specific role of COMMD10 in governing Ly6Chi monocyte-driven inflammation is unknown. Here we report that COMMD10 curbs canonical and non-canonical inflammasome activity in Ly6Chi monocytes in a model of LPS-induced systemic inflammation. Accordingly, its deficiency in myeloid cells, but not in tissue resident macrophages, resulted in increased Ly6Chi monocyte liver and colonic infiltrates, elevated systemic cytokine storm, increased activation of caspase-1 and-11 in the liver and colon, and augmented IL-1ß production systemically and specifically in LPS-challenged circulating Ly6Chi monocytes. These inflammatory manifestations were accompanied by impaired intestinal barrier function with ensuing bacterial dissemination to the mesenteric lymph nodes and liver leading to increased mortality. The increased inflammasome activity and intestinal barrier leakage were ameliorated by the inducible ablation of COMMD10-deficient Ly6Chi monocytes. In consistence with these results, COMMD10-deficiency in Ly6Chi monocytes, but not in intestinal-resident lamina propria macrophages, led to increased IL-1ß production and aggravated colonic inflammation in a model of DSS-induced colitis. Finally, COMMD10 expression was reduced in Ly6Chi monocytes and their corresponding human CD14hi monocytes sorted from mice subjected to DSS-induced colitis or from IBD patients, respectively. Collectively, these results highlight COMMD10 as a negative regulator of Ly6Chi monocyte inflammasome activity during systemic inflammation and IBD.

Diagnosis of posttraumatic stress disorder after surgery for primary rhegmatogenous retinal detachment.

PURPOSES: To investigate the prevalence of posttraumatic stress disorder (PTSD) in patients who underwent surgery for primary rhegmatogenous retinal detachment and to explore variables associated with the disorder. METHODS: Subjects eligible for the study were patients aged 18 years or older, who underwent surgery for primary rhegmatogenous retinal detachment at the Goldschleger Eye Institute, from January 1, 2004, to December 31, 2009, and were followed for at least 1 month. Study patients were screened for the existence of PTSD symptoms via a telephone survey, and positively identified patients were asked to undergo a structured psychiatric interview. Posttraumatic stress disorder was assessed by the Clinician Administered PTSD Scale, and the 25-item National Eye Institute visual function questionnaire (NEI-VFQ-25) was used as a measure of vision-related quality of life. Objective clinical measures were obtained from the patient's medical records. Clinical variables were compared between PTSD-diagnosed patients, patients who were screened for PTSD but were found to be PTSD negative in the interview (false-positive group), and patients who were found negative for PTSD in the screening survey. RESULTS: Of the 547 eligible patients, 366 were enrolled in the study. Nine patients (2.5%) met the criteria for PTSD diagnosis. Posttraumatic stress disorder patients reported significantly more traumatic events in their past (P = 0.015), and for these patients, NEI-VFQ-25 composite score was significantly lower (P < 0.001). Clinical measures were not found as independent risk factors for PTSD prediction. CONCLUSION: Posttraumatic stress disorder may develop in the aftermath of primary rhegmatogenous retinal detachment. Previous traumatic events and NEI-VFQ-25 scores were found as independent risk factors for PTSD prediction.