Randomized placebo-controlled trial of oral tannin supplementation on COVID-19 symptoms, gut dysbiosis and cytokine response.

The clinical study aim was to investigate whether a tannin-based dietary supplementation could improve the efficacy of standard-of-care treatment of hospitalized COVID-19 patients by restoring gut microbiota function. Adverse events and immunomodulation post-tannin supplementation were also investigated. A total of 124 patients receiving standard-of-care treatment were randomized to oral tannin-based supplement or placebo for a total of 14 days. Longitudinal blood and stool samples were collected for cytokine and 16S rDNA microbiome profiling, and results were compared with 53 healthy controls. Although oral tannin supplementation did not result in clinical improvement or significant gut microbiome shifts after 14-days, a reduction in the inflammatory state was evident and significantly correlated with microbiota modulation. Among cytokines measured, MIP-1α was significantly decreased with tannin treatment (p = 0.03) where it correlated positively with IL-1ß and TNF- α, and negatively with stool Bifidobacterium abundance.

Platelets modulate CD4+ T-cell function in COVID-19 through a PD-L1 dependent mechanism.

Severe COVID-19 is associated with a systemic inflammatory response and progressive CD4+ T-cell lymphopenia and dysfunction. We evaluated whether platelets might contribute to CD4+ T-cell dysfunction in COVID-19. We observed a high frequency of CD4+ T cell-platelet aggregates in COVID-19 inpatients that inversely correlated with lymphocyte counts. Platelets from COVID-19 inpatients but not from healthy donors (HD) inhibited the upregulation of CD25 expression and tumour necrosis factor (TNF)-α production by CD4+ T cells. In addition, interferon (IFN)-γ production was increased by platelets from HD but not from COVID-19 inpatients. A high expression of PD-L1 was found in platelets from COVID-19 patients to be inversely correlated with IFN-γ production by activated CD4+ T cells cocultured with platelets. We also found that a PD-L1-blocking antibody significantly restored platelets' ability to stimulate IFN-γ production by CD4+ T cells. Our study suggests that platelets might contribute to disease progression in COVID-19 not only by promoting thrombotic and inflammatory events, but also by affecting CD4+ T cells functionality.

Immunoglobulin G Immune Complexes May Contribute to Neutrophil Activation in the Course of Severe Coronavirus Disease 2019.

Severe coronavirus disease 2019 (COVID-19) is associated with an overactive inflammatory response mediated by macrophages. Here, we analyzed the phenotype and function of neutrophils in patients with COVID-19. We found that neutrophils from patients with severe COVID-19 express high levels of CD11b and CD66b, spontaneously produce CXCL8 and CCL2, and show a strong association with platelets. Production of CXCL8 correlated with plasma concentrations of lactate dehydrogenase and D-dimer. Whole blood assays revealed that neutrophils from patients with severe COVID-19 show a clear association with immunoglobulin G (IgG) immune complexes. Moreover, we found that sera from patients with severe disease contain high levels of immune complexes and activate neutrophils through a mechanism partially dependent on FcγRII (CD32). Interestingly, when integrated in immune complexes, anti-severe acute respiratory syndrome coronavirus 2 IgG antibodies from patients with severe COVID-19 displayed a higher proinflammatory profile compared with antibodies from patients with mild disease. Our study suggests that IgG immune complexes might promote the acquisition of an inflammatory signature by neutrophils, worsening the course of COVID-19.

Natural tannin extracts supplementation for COVID-19 patients (TanCOVID): a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: This research aims to study the efficacy of tannins co-supplementation on disease duration, severity and clinical symptoms, microbiota composition and inflammatory mediators in SARS-CoV2 patients. TRIAL DESIGN: This is a prospective, double-blind, randomized, placebo-controlled, parallel-group trial to evaluate the efficacy of the administration of the dietary supplement ARBOX, a molecular blend of quebracho and chestnut tannins extract and Vit B12, in patients affected by COVID-19. PARTICIPANTS: 18 years of age or older, admitted to Hospital de Clinicas Jose de San Martin, Buenos Aires University (Argentina), meeting the definition of "COVID-19 confirmed case" ( https://www.argentina.gob.ar/salud/coronavirus-COVID-19/definicion-de-caso ). Inclusion Criteria Participants are eligible to be included in the study if the following criteria apply: 1. Any gender 2. ≥18 years old 3. Informed consent for participation in the study 4. Virological diagnosis of SARS-CoV-2 infection (real-time PCR) Exclusion Criteria Participants are excluded from the study if any of the following criteria apply: 1. Pregnant and lactating patients 2. Patients who cannot take oral therapy (with severe cognitive decline, assisted ventilation, or impaired consciousness) 3. Hypersensitivity to polyphenols 4. Patients already in ICU or requiring mechanical ventilation 5. Patients already enrolled in other clinical trials 6. Decline of consent INTERVENTION AND COMPARATOR: Experimental: TREATED ARM Participants will receive a supply of 28 -- 390 mg ARBOX capsules for 14 days. Patients will be supplemented with 2 capsules of ARBOX per day. Placebo Comparator: CONTROL ARM Participants will receive placebo supply for 14 days. The placebo will be administered with the identical dose as described for the test product. All trial participants will receive standard therapy, which includes: Antipyretics or Lopinavir / Ritonavir, Azithromycin and Hydroxychloroquine, as appropriate (treatment currently recommended by the department of Infectious Diseases of the Hospital de Clínicas that could undergo to modifications). In addition, if necessary: supplemental O2, non-invasive ventilation, antibiotic therapy. MAIN OUTCOMES: Primary Outcome Measures: Time to hospital discharge, defined as the time from first dose of ARBOX to hospital discharge [ Time Frame: Throughout the Study (Day 0 to Day 28) ] Secondary Outcome Measures: 28-day all-cause mortality [ Time Frame: Throughout the Study (Day 0 to Day 28) ]-proportion Invasive ventilation on day 28 [ Time Frame: Throughout the Study (Day 0 to Day 28) ]-proportion Level of inflammation parameters and cytokines [ Time Frame: day 1-14 ] -mean difference Difference in fecal intestinal microbiota composition and intestinal permeability [ Time Frame: day 1-14 ] Negativization of COVID-PCR at day 14 [ Time Frame: day 14 ]-proportion RANDOMIZATION: Potential study participants were screened for eligibility 24 hours prior to study randomization. Patients were randomly assigned via computer-generated random numbering (1:1) to receive standard treatment coupled with tannin or standard treatment plus placebo (control group). BLINDING (MASKING): Study personnel and participants are blinded to the treatment allocation, as both ARBOX and placebo were packed in identical containers. Thus, all the used capsules had identical appearance. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Considering an alpha error of 5%, a power of 80% a sample size of 70 patients per branch was estimated. 140 patients in total. TRIAL STATUS: The protocol version is number V2, dated May 23, 2020. The first patient, first visit was on June 12, 2020; the recruitment end date was October 6, 2020. The protocol was not submitted earlier because the enrollment of some patients took place after the closure of the recruitment on the clinicaltrials platform. In fact, due to the epidemiological conditions, due to the decrease of the cases in Argentina during the summer period, the recruitment stopped t before reaching the number of 140 patients (as indicated in the webpage). However, since there was a new increase in cases, the enrolment was resumed in order to reach the number of patients initially planned in the protocol. The final participant was recruited on February 14, 2021. TRIAL REGISTRATION: ClinicalTrials.gov, number: NCT04403646 , registered on May 27th, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

[Usefulness of gastric emptying scintigraphy for the evaluation and management of scleroderma related gastroparesis]. / Utilidad de la medición del vaciamiento gástrico por centellografía con 99mTc para la evaluacion y el manejo de la gastroparesia en la esclerodermia.

Scleroderma is a chronic autoimmune disease of unknown cause characterized by fibrotic skin and multiple organs involvement, including the gastrointestinal tract. It occurs mainly in women between 35 and 65 years of age. It is classified as limited or diffuse based on the extent of skin involvement. Gastrointestinal dysmotility is observed in up to 90% of patients with a diffuse and limited scleroderma. It may involve any segment of the gastrointestinal tract from the esophagus to the anus and is related to collagen deposition at the level of enteric and vascular smooth muscle. Gastroparesis is a condition characterized by abnormal gastric motility, delay gastric emptying, in the absence of a mechanical obstruction to outflow. Gastric scintigraphy with radiolabeled solid food is the gold standard for the diagnosis of gastroparesis. Two cases of patients with systemic scleroderma and severe gastroparesis are presented in order to discuss the diagnostic and therapeutic approach, emphasizing the utility of gastric emptying scintigraphy.

[Prolonged survival after local excision of a rectal leiomyosarcoma]. / Sobrevida prolongada luego de la resección local de un leiomiosarcoma de recto.

Leiomyosarcoma is a stromal tumor, originated from smooth muscle cells. The pathologic diagnosis represents a challenge in terms of differentiation from leiomyomas and gastrointestinal stromal tumors (GIST), defined by immunohistochemistry techniques. Its location in the rectum is extremely rare. So, management is not standardized. However, in the largest published series it was found that the abdominoperineal resection leads to better results in the prevention of local recurrence compared with local excision. We present here the case of a 44-year-old woman, whose first clinical manifestation of the disease was fever of prolonged course. A 5 cm leiomyosarcoma was diagnosed at 4 cm from the anal margin. A local transanal resection was performed. The patient is free of disease after 8 years.

[A case of melioidosis in Argentina]. / Un caso de melioidosis en la Argentina.

We describe a case of 17-year- old man native of Dominican Republic, with Hodgkin's lymphoma, who presented soft espontaneous draining nodules. In the clinical samples grew Burkholderia pseudomallei; the etiological agent of melioidosis. He received antimicrobial treatment with imipenem and amoxicillin/clavulanic with very good clinical evolution of the infectious process. Melioidosis diagnosis could be underestimated due to the low incidence of Burkholderia pseudomallei in our continent. The definitive diagnosis depends of the isolation and identification in the clinical sample.

Un caso de melioidosis en la Argentina / A case of melioidosis in Argentina

Se describe el caso de un varón de 17 años oriundo de República Dominicana, con antecedente de linfoma de Hodgkin, que presenta tumoraciones blandas con supuración espontánea. En sus cultivos desarrolló Burkholderia pseudomallei, agente etiológico de la melioidosis. El paciente recibió tratamiento antibiótico con imipenem y luego con amoxicilina-ácido clavulánico con muy buena evolución clínica del proceso infeccioso. En razón de la baja incidencia de Burkholderia pseudomallei en nuestro continente el diagnóstico de melioidosis pudo haber sido subestimado. Su diagnóstico definitivo depende del aislamiento e identificación del agente causal en la muestra clínica.

We describe a case of 17-year- old man native of Dominican Republic, with Hodgkin´s lymphoma, who presented soft espontaneous draining nodules. In the clinical samples grew Burkholderia pseudomallei; the etiological agent of melioidosis. He received antimicrobial treatment with imipenem and amoxicillin/clavulanic with very good clinical evolution of the infectious process. Melioidosis diagnosis could be underestimated due to the low incidence of Burkholderia pseudomallei in our continent. The definitive diagnosis depends of the isolation and identification in the clinical sample.

Criptococosis pulmonar diseminada y fulminante en paciente HIV negativo / Fulminant disseminated pulmonary crytococcosis in an HIV negative patient

La criptococosis pulmonar diseminada en pacientes HIV negativos es infrecuente, aunque otras causas de inmunocompromiso pueden facilitarla. Dada la potencial letalidad de este cuadro se requiere un alto nivel de sospecha clínica para instaurar el tratamiento adecuado en el momento oportuno. Se presenta el caso de una mujer de 84 años, con antecedente de neoplasia hematológica (AREBT) y tratamiento crónico con glucocorticoides que ingresa por un cuadro de disnea progresiva hasta CF IV y desarrolla posteriormente insuficiencia respiratoria, síndrome de distress respiratorio agudo y shock refractario falleciendo a las 48 horas. Posteriormente se obtuvo rescate de Criptococo neoformans en hemocultivos y el análisis anatomopatológico del material pulmonar obtenido postmortem fue compatible con daño alveolar difuso y criptococosis pulmonar.

Criptococosis pulmonar diseminada y fulminante en paciente HIV negativo / Fulminant disseminated pulmonary crytococcosis in an HIV negative patient

La criptococosis pulmonar diseminada en pacientes HIV negativos es infrecuente, aunque otras causas de inmunocompromiso pueden facilitarla. Dada la potencial letalidad de este cuadro se requiere un alto nivel de sospecha clínica para instaurar el tratamiento adecuado en el momento oportuno. Se presenta el caso de una mujer de 84 años, con antecedente de neoplasia hematológica (AREBT) y tratamiento crónico con glucocorticoides que ingresa por un cuadro de disnea progresiva hasta CF IV y desarrolla posteriormente insuficiencia respiratoria, síndrome de distress respiratorio agudo y shock refractario falleciendo a las 48 horas. Posteriormente se obtuvo rescate de Criptococo neoformans en hemocultivos y el análisis anatomopatológico del material pulmonar obtenido postmortem fue compatible con daño alveolar difuso y criptococosis pulmonar. (AU)