Ozone as adjuvant support in the treatment of covid-19: a preliminary report of probiozovid trial

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jmv.26636.Rationale: The evaluation of new therapeutic resources against COVID-19 represents a priority in clinical research considering the minimal options currently available. Objectives: To evaluate the adjuvant use of systemic oxygen-ozone administration in the early control of disease progression in patients with COVID-19 pneumonia. Methods: PROBIOZOVID is an ongoing, interventional, randomized, prospective, double-arm trial enrolling patient with COVID-19 pneumonia. From a total of 85 patients screened, 28 were recruited. Patients were randomly divided into ozone- autohemotherapy group (14) and control group (14). The procedure consisted in a daily double-treatment with systemic Oxygen-Ozone administration for 7 days. All patients were treated with ad interim best available therapy. Measurements and Main Results: The primary outcome was delta in the number of patients requiring orotracheal-intubation despite treatment. Secondary outcome was the difference of mortality between the two groups. Moreover, haematological parameters were compared before and after treatment. No differences in the characteristics between groups were observed at baseline. As a preliminary report we have observed that one patient for each group needed intubation and was transferred to ITU. No deaths were observed at 7-14 days of follow up. Thirty-day mortality was 8,3% for ozone group and 10% for controls. Ozone therapy didn’t significantly influence inflammation markers, haematology profile and lymphocyte subpopulations of patients treated. Ozone therapy had an impact on the need for the ventilatory support, although didn’t reach statistical significance. Finally, no adverse events related to the use of ozone-autohemotherapy were reported. Conclusions: Preliminary results, although not showing statistically significant benefits of ozone on COVID-19, did not report any toxicity

Evidence of Uncoupling between Renal Dysfunction and Injury in Cardiorenal Syndrome: Insights from the BIONICS Study

Objective: The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF). Methods: In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF. Results: 26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF. Conclusions: In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153)

Ovarian carcinoma presenting with axillary lymph node metastasis: a case report

Ovarian cancer is usually limited to the abdomen and frequently remains confined. The occurrence of extrabdominal mestastases is unusual. In this report we describe a rare case of axillary involvement at initial presentation of ovarian cancer in a 48-year-old woman. The axillary mass was the only clinical abnormality. Cytological and histological findings, performed on axillary lymph nodes, showed the presence of psammoma bodies and specific immunohistochemical tumor markers (OC-125 and WTI), supporting the evidence of a metastatic axillary lymphadenopathy from ovarian cancer. Subsequently, chest and abdominopelvic computed tomography showed a right ovarian complex mass of 30 x 25 mm and biochemical tests showed high levels of CA 125. Surgical therapy was performed. Histology confirmed the diagnosis, evidencing a poorly differentiated serous-papillary carcinoma of the right ovary. In conclusion, cytological and histological findings can play a crucial role in suggesting the correct origin of a metastatic adenocarcinoma when the clinical presentation is atypical

Quadrantectomia e asportazione del linfonodo sentinella in anestesia locale in day hospital

Negli ultimi anni sono stati fatti grandi passi avanti per quanto riguarda sia la diagnostica sia la terapia del carcinoma della mammella. Ciò consente, nella maggior parte dei casi, di poter praticare una chirurgia conservativa. Con l’introduzione della tecnica del linfonodo sentinella, l’intervento chirurgico è stato notevolmente semplificato, tanto da poter essere eseguito in day surgery in anestesia locale. Scopo di questo lavoro è stato valutare se, dopo un attento studio del cavo ascellare con esame ecografico ed eventuale esame citologico, sia possibile dirimere tra linfonodi negativi e metastatici e valutare la fattibilità dell’intervento eseguito in anestesia locale, e quindi senza ricovero. Dal gennaio 2005 al gennaio 2007 54 pazienti, affette da carcinoma della mammella e che presentavano cavo ascellare negativo, sono state sottoposte a intervento chirurgico di quadrantectomia e asportazione del linfonodo sentinella in anestesia locale più eventuale sedazione. Otto di queste hanno presentato micrometastasi o cellule isolate nel linfonodo sentinella e, quindi, successivamente sono state sottoposte a linfoadenectomia. I nostri dati dimostrano che un attento studio del cavo ascellare consente sia di praticare la tecnica del linfonodo sentinella con buona probabilità di assenza di metastasi, sia di eseguire l’intervento in anestesia locale.Abstract In recent years, breast carcinoma diagnostics and therapy have evolved very considerably, allowing conservative surgery in most cases. These kinds of major operations have been greatly simplified since the introduction of the sentinel lymph node approach, with the possibility of a day surgery operation under local anaesthesia. The aim of this study, after thorough analysis of the axillary lymph nodes with ultrasound and cytological examinations, was to assess whether it would be possible to distinguish between negative and metastatic lymph nodes and whether the operation could be performed under local anaesthesia without hospitalisation. From January 2005 to January 2007, 54 breast carcinoma patients with negative axillary lymph nodes (after ultrasound examination) had a quadrantectomy and sentinel lymph node removal under local anaesthesia together with sedation where appropriate. Eight patients who presented micrometastases or isolated tumour cells in the sentinel lymph node underwent a subsequent lymphadenectomy. Our data show that, thanks to thorough analysis of the axillary cavity, it may be possible to use the sentinel lymph node approach with a good chance of the patient remaining free of distant metastases and of operating under local anaesthesia

A PROSPECTIVE, BLINDED STUDY OF BIOIMPEDANCE VECTOR ANALYSIS AND BIOMARKER TESTING FOR THE PREDICTION OF WORSENING RENAL FUNCTION IN CONSECUTIVE PATIENTS WITH ACUTELY DECOMPENSATED HEART FAILURE: PRIMARY RESULTS OF THE BIOMONITORING AND CARDIORENAL SYNDROME IN HEART FAILURE (BIONICS-HF) TRIAL

Background . Worsening renal function (WRF) commonly affects patients with acutely decompensated heart failure (ADHF), and is associated with significant morbidity and mortality. The ability to predict WRF is limited. .Methods . In a prospective, blinded international study, 101 consecutive emergency department patients with ADHF were evaluated with bioimpedance vector analysis (BIVA), and blood was tested for blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), amino-terminal pro-B type natriuretic peptide (NT-proBNP), BNP, ST2, and neutrophil gelatinase associated lipocalin (NGAL). The primary endpoint was in-hospital WRF (defined as rise in creatinine by >0.3 mg/dL or >25% from baseline). The secondary endpoint was a composite of in-hospital .Results . 26% developed WRF and 8% died. Baseline characteristics of subjects developing WRF were generally similar to those who did not, including similar initial diuretic dose. Results for BIVA, BUN, creatinine, eGFR or ST2 were not associated with either endpoint, while NT-proBNP (4846 vs 3024 pg/mL; p =.04), BNP (609 vs 435 pg/mL; P =.05) and NGAL (234 vs 174 pg/mL; P =.05) were each associated with WRF, and were most prognostic when used in combination (FIGURE). NT-proBNP, BNP and NGAL were similarly predictive of the secondary endpoint (P =.01). .Conclusions . In patients with ADHF, the combination of NT-proBNP/BNP and NGAL at presentation predicts impending WRF and WRF/in-hospital death

Evidence of Uncoupling between Renal Dysfunction and Injury in Cardiorenal Syndrome: Insights from the BIONICS Study.

OBJECTIVE: The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF). METHODS: In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF. RESULTS: 26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF. CONCLUSIONS: In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153)

YAP\u2013TEAD1 control of cytoskeleton dynamics and intracellular tension guides human pluripotent stem cell mesoderm specification

The tight regulation of cytoskeleton dynamics is required for a number of cellular processes, including migration, division and differentiation. YAP\u2013TEAD respond to cell\u2013cell interaction and to substrate mechanics and, among their downstream effects, prompt focal adhesion (FA) gene transcription, thus contributing to FA-cytoskeleton stability. This activity is key to the definition of adult cell mechanical properties and function. Its regulation and role in pluripotent stem cells are poorly understood. Human PSCs display a sustained basal YAP-driven transcriptional activity despite they grow in very dense colonies, indicating these cells are insensitive to contact inhibition. PSC inability to perceive cell\u2013cell interactions can be restored by tampering with Tankyrase enzyme, thus favouring AMOT inhibition of YAP function. YAP\u2013TEAD complex is promptly inactivated when germ layers are specified, and this event is needed to adjust PSC mechanical properties in response to physiological substrate stiffness. By providing evidence that YAP\u2013TEAD1 complex targets key genes encoding for proteins involved in cytoskeleton dynamics, we suggest that substrate mechanics can direct PSC specification by influencing cytoskeleton arrangement and intracellular tension. We propose an aberrant activation of YAP\u2013TEAD1 axis alters PSC potency by inhibiting cytoskeleton dynamics, thus paralyzing the changes in shape requested for the acquisition of the given phenotype

Evidence of uncoupling between renal dysfunction and injury in cardiorenal syndrome: insights from the BIONICS study.

ObjectiveThe objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF).MethodsIn a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF.Results26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF.ConclusionsIn ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153)