Role of interferon therapy in severe COVID-19: the COVIFERON randomized controlled trial.

Type 1 Interferons (IFNs) have been associated with positive effects on Coronaviruses. Previous studies point towards the superior potency of IFNß compared to IFNα against viral infections. We conducted a three-armed, individually-randomized, open-label, controlled trial of IFNß1a and IFNß1b, comparing them against each other and a control group. Patients were randomly assigned in a 1:1:1 ratio to IFNß1a (subcutaneous injections of 12,000 IU on days 1, 3, 6), IFNß1b (subcutaneous injections of 8,000,000 IU on days 1, 3, 6), or the control group. All three arms orally received Lopinavir/Ritonavir (400 mg/100 mg twice a day for ten days) and a single dose of Hydroxychloroquine 400 mg on the first day. Our utilized primary outcome measure was Time To Clinical Improvement (TTCI) defined as the time from enrollment to discharge or a decline of two steps on the clinical seven-step ordinal scale, whichsoever came first. A total of 60 severely ill patients with positive RT-PCR and Chest CT scans underwent randomization (20 patients to each arm). In the Intention-To-Treat population, IFNß1a was associated with a significant difference against the control group, in the TTCI; (HR; 2.36, 95% CI 1.10-5.17, P-value = 0.031) while the IFNß1b indicated no significant difference compared with the control; HR; 1.42, (95% CI 0.63-3.16, P-value = 0.395). The median TTCI for both of the intervention groups was five days vs. seven days for the control group. The mortality was numerically lower in both of the intervention groups (20% in the IFNß1a group and 30% in the IFNß1b group vs. 45% in the control group). There were no significant differences between the three arms regarding the adverse events. In patients with laboratory-confirmed SARS-CoV-2 infection, as compared with the base therapeutic regiment, the benefit of a significant reduction in TTCI was observed in the IFNß1a arm. This finding needs further confirmation in larger studies.Trial Registration Number: ClinicalTrials.gov, NCT04343768. (Submitted: 08/04/2020; First Online: 13/04/2020) (Registration Number: NCT04343768).

Perinatal outcome in pregnancy with polyhydramnios in comparison with normal pregnancy in department of obstetrics at Shiraz University of Medical Sciences.

OBJECTIVE: Polyhydramnios can lead to maternal and fetal complication during pregnancy, so diagnosis and management can decrease some perinatal complications. STUDY DESIGN: One hundred and fourteen singleton pregnancies were diagnosed with idiopathic polyhydramnios in the department of obstetrics at Shiraz University of Medical Sciences between January 2000 and January 2011 and were compared with 114 normal pregnancies for their perinatal outcome. Variables include birth weight, admission to neonatal intensive care unit (NICU), meconium staining, respiratory distress, fetal death, neonatal death, low 1-min and 5-min APGAR score, primary cesarean section (C/S), preterm delivery (<37 weeks), postpartum bleeding, and placental abruption. RESULTS: Low birth weight (<2500 g), macrosoma (>4000 g), NICU admission, fetal distress, fetal death, lower 1-min and 5-min APGAR score, preterm delivery, and neonatal death were higher in the case group. However, meconium staining and malpresentation were equal between the two groups. Except for prematurity and 1-min and 5-min APGAR scores, there were no significant differences in other maternal or fetal outcomes considering the severity of polyhydramnios. CONCLUSION: Idiopathic polyhydramnios should be considered as a high-risk pregnancy that warrants close surveillance. More studies should be done to detect the best time and interval of fetal surveillance in these patients. Chromosomal and torch studies can determine the definite cause of polyhydramnios.

Hypothesis: ROBOPHERA, a phosphatase and tensin homolog-targeted antineoplastic therapy.

Phosphatase and tensin homolog (PTEN) is a protein that regulates cellular response to growth/antigrowth signals, cell survival, apoptosis, proliferation, angiogenesis, and cellular migration. Impairments in these processes are the main hallmarks of cancer, and reduced expression, activity, or stability of PTEN are among the most common etiologies of diverse types of sporadic cancers. Rosiglitazone (RO), bortezomib (BO), phosphatidylserine (PH), ethanol (E), and radiotherapy (RA) (ROBOPHERA) stimulate the expression and increase the activity of PTEN. Here, it is hypothesized that the synergistic effects of these medications on cancerous cells may stimulate differentiation of cancer stem cells toward non-stem-cancer cells, hinder progression and metastasis of the cancer, sensitize cancerous cells to antineoplastic therapies, and increase the efficacy and the rate of success of current treatments.

Could "calprotectin" and "endocan" serve as "Troponin of Nephrologists"?

AKI, a serious, common and occasionally under-recognized condition, which is a significant contributor to the growing incidence of CKD and end-stage renal disease (ESRD). To date, the diagnosis of AKI is made by serial measurement of Cr and BUN which are late and imprecise markers of kidney injury. "Calprotectin" and "endocan" are two biomarkers that could reflect renal tubular injury and glomerular/endothelial-vascular damage, respectively. Measurement of urinary calprotectin could help the physicians to diagnose tubular degradation and differentiate prerenal AKI from intrinsic AKI. Serum level of endocan could signify endothelial damage. Herein it is hypothesized that calprotectin and endocan may help the clinicians to diagnose intrinsic AKI, earlier than rise of serum creatinine, differentiate AKI from acute presentation of CKD and also discriminate tubular injury from glomerular/vascular-endothelial injury, assess the prognosis and extent of renal damage and plan for appropriate therapy which may render these biomarkers as potentially applicable equivalents of Troponin in the field of nephrology.

Hypothesis: Fingolimod explores new horizons in treatment of lymphoma.

Lymphomas (Hodgkin's (10%) and non-Hodgkin's (90%) lymphomas) are a group of blood cell tumors arising from lymphocytes and lymphadenopathy is the most common primary presentation of the disease. In non-Hodgkin lymphomas, the prognosis is worse. As the disease initiates, neoplastic cells may spread to and involve other lymph nodes and extra nodal regions. The disease is staged based on desperation of neoplastic cells and the prognosis highly depends on the stage of the disease at the time of diagnosis. Fingolimod is an immunomodulating drug, approved for treating relapsing forms of multiple sclerosis. Fingolimod impairs migration of lymphocytes from lymph nodes and it is hypothesized that Fingolimod could alleviate and decrease disease burden of lymphoma as it sequesters malignant cells within involved lymph nodes and it decelerates progression of the disease, increases efficacy of other treatment options and it is synergistic with anti-VEGF medications, it is an anti-metastatic, anti-inflammatory, cytostatic/cytotoxic agent and it boosts function of immune system in deterioration of neoplastic cells. Therefore, the agent can be used not only to treat lymphoma, but also to control and prevent relapse of the disease in those who are remitted.

"Cystic fibrotics could survive cholera, choleraics could survive cystic fibrosis"; hypothesis that explores new horizons in treatment of cystic fibrosis.

Cystic fibrosis, the most common inherited disease of white population, is a disease of CFTR channels, in which mucosal function of many organs especially respiratory tract is impaired. Decreased mucociliary clearance and accumulation of mucus in airways facilitates colonization of infectious microorganisms, followed by infection. Following chronic infection, persistent inflammation ensues, which results in airway remodeling and deterioration of mucociliary clearance and result in a vicious cycle. Here, it is hypothesized that cholera toxin (CT) could ameliorate symptoms of cystic fibrosis as CT could dilute the thickened mucus, improve mucociliary clearance and alleviate airway obstruction. CT strengthens immunity of airway mucosa and it could attenuates bacterial growth and reduce persistency of infection. CT also modulates cellular immune response and it could decrease airway inflammation, hinder airway remodeling and prevent respiratory deterioration. Thereby it is hypothesized that CT could target and ameliorate many of pathophysiologic steps of the disease and it explores new horizons in treatment of CF.

Hypothesis: Pentoxifylline explores new horizons in treatment of preeclampsia.

Preeclampsia, the leading cause of maternal morbidity and perinatal mortality, initiates as inappropriate immune response to trophoblastic invasion impairs placentation and placental circulation. A poorly perfused placenta generates superoxide anions as well as anti-angiogenic factors and this series of events result in impairment of endothelial function, followed by maternal morbidities such as hypertension, kidney injury and proteinuria. Renal loss of anti-coagulant proteins and subsequent hyper-coagulable state along with endothelial dysfunction accelerates progression of the disease toward eclampsia. Since Pentoxifylline, a methyl-xanthine derivative known for enhancement of vascular endothelial function, down-regulation of many inflammatory cytokines increased during preeclampsia, improvement of placental circulation, reduction of ischemia-reperfusion injury, enhancement of vasodilatation and endothelial function, ameliorating proteinuria, inhibition of platelet aggregation and decreasing risk of preterm labor, which are all amongst morbidities of preeclampsia, here it is hypothesized that Pentoxifylline prevents development of preeclampsia and/or decelerate progression of the disease.