The effect of immunosuppressive therapies on the endothelial host response in critically ill COVID-19 patients.

While several effective therapies for critically ill patients with COVID-19 have been identified in large, well-conducted trials, the mechanisms underlying these therapies have not been investigated in depth. Our aim is to investigate the association between various immunosuppressive therapies (corticosteroids, tocilizumab and anakinra) and the change in endothelial host response over time in critically ill COVID-19 patients. We conducted a pre-specified multicenter post-hoc analysis in a Dutch cohort of COVID-19 patients admitted to the ICU between March 2020 and September 2021 due to hypoxemic respiratory failure. A panel of 18 immune response biomarkers in the complement, coagulation and endothelial function domains were measured using ELISA or Luminex. Biomarkers were measured on day 0-1, day 2-4 and day 6-8 after start of COVID-19 treatment. Patients were categorized into four treatment groups: no immunomodulatory treatment, corticosteroids, anakinra plus corticosteroids, or tocilizumab plus corticosteroids. The association between treatment group and the change in concentrations of biomarkers was estimated with linear mixed-effects models, using no immunomodulatory treatment as reference group. 109 patients with a median age of 62 years [IQR 54-70] of whom 72% (n = 78) was male, were included in this analysis. Both anakinra plus corticosteroids (n = 22) and tocilizumab plus corticosteroids (n = 38) were associated with an increase in angiopoietin-1 compared to no immune modulator (n = 23) (beta of 0.033 [0.002-0.064] and 0.041 [0.013-0.070] per day, respectively). These treatments, as well as corticosteroids alone (n = 26), were further associated with a decrease in the ratio of angiopoietin-2/angiopoietin-1 (beta of 0.071 [0.034-0.107], 0.060 [0.030-0.091] and 0.043 [0.001-0.085] per day, respectively). Anakinra plus corticosteroids and tocilizumab plus corticosteroids were associated with a decrease in concentrations of complement complex 5b-9 compared to no immunomodulatory treatment (0.038 [0.006-0.071] and 0.023 [0.000-0.047], respectively). Currently established treatments for critically ill COVID-19 patients are associated with a change in biomarkers of the angiopoietin and complement pathways, possibly indicating a role for stability of the endothelium. These results increase the understanding of the mechanisms of interventions and are possibly useful for stratification of patients with other inflammatory conditions which may potentially benefit from these treatments.

Effects of choice white grease or poultry fat on growth performance, carcass leanness, and meat quality characteristics of growing-finishing pigs.

Eighty-four crossbred gilts were used to evaluate the effects of dietary choice white grease (CWG) or poultry fat (PF) on growth performance, carcass characteristics, and quality characteristics of longissimus muscle (LM), belly, and bacon of growing-finishing pigs. Pigs (initially 60 kg) were fed a control diet with no added fat or diets containing 2, 4, or 6% CWG or PF. Diets were fed from 60 to 110 kg and contained 2.26 g lysine/Mcal ME. Data were analyzed as a 2 x 3 factorial plus a control with main effects of fat source (CWG and PF) and fat level (2, 4, and 6%). Pigs fed the control diet, 2% fat, and 4% fat had greater (P < 0.05) ADFI than pigs fed 6% fat. Pigs fed 6% fat had greater (P < 0.05) gain/feed (G/F) than pigs fed the control diet or other fat levels. Subcutaneous fat over the longissimus muscle from pigs fed CWG had more (P < 0.05) moisture than that from pigs fed PF. Feeding dietary fat (regardless of source or level) reduced (P < 0.05) the amount of saturated fats present in the LM. Similarly, 4 or 6% fat decreased (P < 0.05) the amount of saturated fats and increased unsaturated fats present in the bacon. No differences (P > 0.05) were observed for ADG, dressing percentage, leaf fat weight, LM pH, backfat depth, LM area, percentage lean, LM visual evaluation, LM waterholding capacity, Warner-Bratzler shear and sensory evaluation of the LM and bacon, fat color and firmness measurements, or bacon processing characteristics. Adding dietary fat improved G/F and altered the fatty acid profiles of the LM and bacon, but differences in growth rate, carcass characteristics, and quality and sensory characteristics of the LM and bacon were minimal. Dietary additions of up to 6% CWG or PF can be made with little effect on quality of pork LM, belly, or bacon.

Effect of regulations and guidelines on gastroenterology programs.

This paper reviews the standards of practice, regulations, and guidelines that govern gastrointestinal endoscopy and their effect on space and equipment, staff and physician quality of care, and educational programs. It also examines how all these considerations have affected the growth of an endoscopy center and describes the processes that have been instituted to ensure compliance with all relevant standards, regulations, and guidelines.

Role of colonoscopy in gallstone ileus:--a case report.

This paper reviews the role of colonoscopy in large-bowel obstruction by a gallstone. We report the case of an elderly female with a cholecystocolonic fistula who had a large-bowel obstruction caused by a gallstone that migrated to the level of narrowing in the large bowel. After multiple attempts at removal of the stone with a snare and basket retriever, the patient was taken to the operating room and the stone was removed. Colonscopy in these circumstances can be diagnostic and possibly therapeutic.

Pleurisy during the course of ulcerative colitis.

Extracolonic manifestations of inflammatory bowel disease have attracted considerable attention. We present two young men with ulcerative colitis who also developed pleurisy. While this association has not been reported previously, the temporal relationship and absence of another cause suggest that the pleuritis could be a systemic manifestation of inflammatory bowel disease.

Metastatic carcinoma of the breast: a cause of obstructive jaundice.

Two cases of jaundice are reported that were secondary to obstruction of the common bile duct by metastatic carcinoma of the breast and relieved by pallieative surgery. In one case, obstructive jaundice was the first evidence of spread beyond regional lymph nodes, in the other patient it was a late manifestation of the disease. In patients with prior history of carcinoma of the breast, jaundice may be secondary to obstruction of the common bile duct, and, because it is amenable to palliation, this possibility should be investigated before concluding that extensive hepatic involvement is the cause of jaundice.

Office screening for asymptomatic urinary tract infections. The evaluation of a practical, economic and reliable method screening the urines of asymptomatic girls in a busy pediatric office.

The urines of 3,270 asymptomatic girls were screened at annual physical examinations. The urines were collected in Dixie Cups without prior preparation of the perineum and cultured on 5% sheep cell agar. Less than 2 per cent of the specimens showed significant growth, thus requiring no follow-up visits by 98 per cent of the patients. Slightly less that 1/2 of one per cent were found to have asymptomatic urinary tract infections. The procedure was found to be practical, economically feasible and reliable, and was well accepted by both the parents and patients.

Complications of vagotomy.

Most operations performed for peptic ulcer disease in the United States include vagotomy as part of the surgical procedure. This paper reviews the complications associated specifically with or increased in frequency and severity by this procedure. Included in this review are technical complications, gastric retention, recurrent ulceration, postvagotomy diarrhea, postvagotomy dysphagia and achalasia, postvagotomy biliary disease and nutritional problems. The frequency of these complications, their pathophysiology and therapeutic modalities available are reviewed. The main emphasis is on postvagotomy syndrome that can be treated medically and on the various treatment forms that have been suggested.

Alcohol and dietary factors in cirrhosis. An epidemiological study of 304 alcoholic patients.

Alcohol intakes and dietary habits of 304 alcoholic, hospitalized patients were evaluated. There were 195 patients with hepatic cirrhosis, 40 precirrhotics, and 69 noncirrhotics. Alcohol contributed 50% to 58% of total calories. Two thirds of the patients drank excessively for more than 20 years. There were no statistically significant differences between the three groups in the duration or degree of alcohol excess. Dietary intakes were assessed for a period of at least two years before the presenting illness. Noncirrhotics had higher food caloric intakes and higher protein intakes than the cirrhotics (P less than .05). The findings suggest that dietary factors may be involved in the pathogenesis of the disease.

Cholestatic hepatitis after administration of furan derivatives.

A patient developed cholestatic hepatitis while being treated with nitrofurantoin. A second episode of jaundice followed the intravaginal administration of a mixture of furazolidone and nifuroxime. It is important to consider possible cross-sensitivity of chemically related compounds even when they are administered by different routes.