Nosocomial Outbreak of SARS-CoV-2 in a “Non-COVID-19” Hospital Ward: Virus Genome Sequencing as a Key Tool to Understand Cryptic Transmission

Dissemination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in healthcare institutions affects both patients and health-care workers (HCW), as well as the institutional capacity to provide essential health services. Here, we investigated an outbreak of SARS-CoV-2 in a “non-COVID-19” hospital ward unveiled by massive testing, which challenged the reconstruction of transmission chains. The contacts network during the 15-day period before the screening was investigated, and positive SARS-CoV-2 RNA samples were subjected to virus genome sequencing. Of the 245 tested individuals, 48 (21 patients and 27 HCWs) tested positive for SARS-CoV-2. HCWs were mostly asymptomatic, but the mortality among patients reached 57.1% (12/21). Phylogenetic reconstruction revealed that all cases were part of the same transmission chain. By combining contact tracing and genomic data, including analysis of emerging minor variants, we unveiled a scenario of silent SARS-CoV-2 dissemination, mostly driven by the close contact within the HCWs group and between HCWs and patients. This investigation triggered enhanced prevention and control measures, leading to more timely detection and containment of novel outbreaks. This study shows the benefit of combining genomic and epidemiological data for disclosing complex nosocomial outbreaks, and provides valuable data to prevent transmission of COVID-19 in healthcare facilities.     

Liver transplant recipients infected with SARS‐CoV‐2 in the early postoperative period: Lessons from a single center in the epicenter of the pandemic

The impact of coronavirus disease‐19 (COVID‐19) in liver recipients remains largely unknown. Most data derive from small retrospective series of patients transplanted years ago. We aimed to report a single‐center case series of five consecutive patients in the early postoperative period of deceased‐donor liver transplantation who developed nosocomial COVID‐19. Two patients presented important respiratory discomfort and eventually died. One was 69 years old and had severe coronary disease. She rapidly worsened after COVID‐19 diagnosis on 9th postoperative day. The other was 67 years old with non‐alcoholic steatohepatitis, who experienced prolonged postoperative course, complicated with cytomegalovirus infection and kidney failure. He was diagnosed on 36th postoperative day and remained on mechanical ventilation for 20 days, ultimately succumbing of secondary bacterial infection. The third, fourth, and fifth patients were diagnosed on 10th, 11th, and 18th postoperative day, respectively, and presented satisfactory clinical evolution. These last two patients were severely immunosuppressed, since one underwent steroid bolus for acute cellular rejection and another also used anti‐thymocyte globulin for treating steroid‐resistant rejection. Our novel experience highlights that COVID‐19 may negatively impact the postoperative course, especially in elder and obese patients with comorbidities, and draws attention to COVID‐19 nosocomial spread in the early postoperative period.     

Lipoprotein(a): Current Evidence for a Physiologic Role and the Effects of Nutraceutical Strategies

PurposeCardiovascular (CV) diseases account for most worldwide mortality, and a higher level of lipoprotein (Lp)-(a) is recognized as a prevalent contributing risk factor. However, there is no consensus regarding nutritional strategies for lowering Lp(a) concentration. Thus, the purposes of this literature review were to: (1) critically examine data concerning the effects of dietetic interventions and nutraceutical agents on Lp(a) level; and (2) review the feasibility and utility of their clinical use.MethodsA literature search was conducted for studies published between August 2018 and March 2019. The search was performed using the Cochrane, Medline, and Web of Science databases. In order to expand the research, there were no delimitations on the type or year of the studies. A total of 1932 articles were identified using this search procedure. After duplicates were eliminated, 740 abstracts of articles written in English were screened to identify those of highest relevance. In the final tally, a total of 152 full-text articles were included in this review.FindingsSeveral foods and decreases in saturated fat and ethanol intake, especially red wine intake, may lower Lp(a) concentration, but limits are necessary. Coffee and tea intake may decrease Lp(a) level; further investigation is crucial before they can be considered potent Lp(a)-lowering agents. Among supplementation strategies, only l-carnitine and coenzyme Q10 are promising clinical candidates to lower Lp(a) level. Since both l-carnitine and coenzyme Q10 supplementation are commonly used for CV support, they deserve further exploration regarding clinical applicability. In contrast, despite potential CV benefits, current research fails to justify use of higher intakes of vitamin C, soy isoflavones, garlic, and ω-3 for decreasing Lp(a) concentration.ImplicationsDefinitive long-term clinical trials are needed to confirm the effects of dietetic interventions and nutraceutical agents on Lp(a) concentration when anticipating improved CV outcomes.     

Proliferation and cytogenetic analysis of hairy cell leukemia upon stimulation via the CD40 antigen

Using the CD40 system, in vitro proliferation of hairy cell leukemia (HCL) was examined in 43 patients. In this culture system, cells were stimulated by interleukin-4 (IL-4) and anti-CD40 monoclonal antibodies (MoAbs) that were added in soluble form or were cross-linked via their Fc part using Fc gamma RII-transfected mouse fibroblast cells. Proliferation was induced and confirmed by 3H-thymidine incorporation in 14 cases and by the presence of metaphases in 42 cases. 3H-thymidine incorporation showed a heterogeneous pattern: cross-linking of anti- CD40 gave the highest proliferation in 8 cases; in 11 cases, stimulation with anti-CD40 MoAbs alone, without cross-linking also resulted in proliferation; the addition of IL-4 further enhanced 3H- thymidine incorporation in 5 cases, but suppressed this phenomenon in 5 other cases. The CD40 system proved to be very effective in obtaining cytogenetic data. With a success rate of 42 of 43 patients tested, we found clonal abnormalities in 8 cases (19%) and nonclonal abnormalities with involvement of one or two abnormal metaphases in another 7 cases. The chromosomes most frequently involved in the abnormal karyotypes, both structurally and numerically, were chromosomes 5, 7, and 14. By fluorescence-activated cell-sorting analysis of the cultured cells, and by immunophenotypic analysis of metaphase spreads, T-cell growth could be excluded and the HCL-lineage confirmed. Stimulation via the CD40 antigen is an excellent tool for growing hairy cell leukemia cells.     

Experimental dilatation of the cecum and colon in rats. IV. Evaluation of a model produced by the use of lactose in the food of animals in the chronic phase of infection by the Colombia strain of T. cruzi

Female Wistar albino rats (30 day of age) were inoculated three times in intervals of 7 days with 1 x 10(7) epimastigote forms of T. cruzi and challenged 30 days after the last inoculation with 1 x 10(5) trypomastigote forms of the Colombia strain of T. cruzi. Rats of the same sex and age were used as controls. One-hundred-fifty days after inoculation the animals were allocated into 4 groups: Group I (control), divided into subgroup L (fed lactose for 4 weeks) and subgroup S (fed saccharose for 4 weeks); Group II (inoculated), divided into subgroup L (fed lactose for 4 weeks) and subgroup S (fed saccharose for 4 weeks); Group III (control), divided into subgroup L-S (fed lactose for 4 weeks and saccharose for the following 4 weeks) and subgroup S (fed saccharose for 8 weeks); and Group IV (inoculated), divided into subgroup L-S (fed lactose for 4 weeks and saccharose for the following 4 weeks) and subgroup S (fed saccharose for 8 weeks). The disaccharide (lactose or saccharose) was added to a standard laboratory diet, 25 g/100 g of the final weight of the diet. At the end of the experimental periods the animals were sacrificed in light ether anesthesia. The volume of the large intestine was measured, and the weights of the cecum and colon were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia

A phase I clinical trial was initiated to treat patients with stage IV B-derived chronic lymphocytic leukemia (CLL) with the IgG2a murine monoclonal antibody T101. This antibody binds to a 65,000-mol wt (T65) antigen found on normal T lymphocytes, malignant T lymphocytes, and B- derived CLL cells. All of the patients had a histologically confirmed diagnosis of advanced B-derived CLL and were refractory to standard therapy, and more than 50% of their leukemia cells reacted with the T101 antibody in vitro. The patients received T101 antibody two times per week, over two to 50 hours by intravenous administration in 100 mL of normal saline containing 5% human albumin. Twelve patients were treated with a fixed dosage of 1, 10, 50, or 100 mg, and one patient was treated with 140 mg of antibody. It was demonstrated that patients given two-hour infusions of 50 mg developed pulmonary toxicity, with shortness of breath and chest tightness. This toxicity was eliminated when infusions of 50 or 100 mg of T101 were prolonged to 50 hours. All dose levels caused a rapid but transient decrease in circulating leukemia cell counts. In vivo binding to circulating and bone marrow leukemia cells was demonstrated at all dose levels with increased binding at higher dosages. Antimurine antibody responses were not demonstrated in any patients at any time during treatment. Circulating free murine antibody was demonstrated in the serum of only the two patients treated with 100 mg of antibody as a 50-hour infusion and the patient treated with 140 mg of antibody over 30 hours. Antigenic modulation was demonstrated in patients treated at all dose levels but was particularly apparent in patients treated with prolonged infusions of 50 and 100 mg of antibody. We were also able to demonstrate antigenic modulation in lymph node cells, which strongly suggests in vivo labeling of these cells. Overall, T101 antibody alone appears to have a very limited therapeutic value for patients with CLL. The observations of in vivo labeling of tumor cells, antigenic modulation, antibody pharmacokinetics, toxicity, and antimurine antibody formation may be used in the future for more effective therapy when drugs or toxins are conjugated to the antibody.