Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

BACKGROUND: The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19. METHODS: This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1. RESULTS: Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality. CONCLUSIONS: We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.

Colonic basidiobolomycosis in a patient with systemic lupus erythematosus (SLE).

BACKGROUND: Basidiobolus ranarum belongs to the Entomophthorales order and the Zygomycetes class. This fungus is an environmental saprophyte that can be found in soil and rotting vegetables.Primarily restricted to tropical regions including Asia, Africa, and South America. It might cause chronic inflammatory diseases, mostly affect subcutaneous tissue. Systemic infections involving the gastrointestinal tract are extremely rare. CASE PRESENTATION: Herein, we present a 44-year-old Persian man with the past medical history of lupus erythematosus with colicky abdominal pain started from three months before admission with many vomiting episodes, and a mass on the right lower quadrant, who had been thought initially to have an abdominal malignancy. The patient had vital signs were within normal ranges. His physical examination revealed tenderness and rebound tenderness on the right lower quadrant of the abdomen. A fixed mass 10 × 10 centimeter in diameter was palpated in the same quadrant. Laboratory, radiologic, colonoscopic examination was requested. The patient underwent laparotomy which revealed a mass in the terminal ileum and ascending colon with retroperitoneal adhesion and invasion to the right ureter behind it. Pathologic examination showed basidiobolomycosis infection in the specimen. CONCLUSION: Fungal infection should be among the differential diagnoses for adults present with abdominal mass in endemic regions of the world.

The effects of zinc supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial.

This study was performed to determine the effects of zinc supplementation on wound healing and metabolic status in patients with diabetic foot ulcer. The current randomized, double-blind, placebo-controlled trial was conducted among 60 patients (aged 40-85 years old) with grade 3 diabetic foot ulcer. Participants were randomly divided into two groups (30 participants in each group) to take either 220 mg zinc sulfate supplements containing 50 mg elemental zinc or placebo daily for 12 weeks. After the 12-week intervention, compared with the placebo, zinc supplementation was associated with significant reductions in ulcer length (-1.5 ± 0.7 vs. -0.9 ± 1.2 cm, p = 0.02) and width (-1.4 ± 0.8 vs. -0.8 ± 1.0 cm, p = 0.02). In addition, changes in fasting plasma glucose (-40.5 ± 71.0 vs. -3.9 ± 48.5 mg/dl, p = 0.02), serum insulin concentration (-8.0 ± 15.4 vs. +1.1 ± 10.3 µIU/ml, p = 0.009), homeostasis model of assessment-estimated insulin resistance (-3.9 ± 7.1 vs. +0.8 ± 5.9, p = 0.007), the quantitative insulin sensitivity check index (+0.01 ± 0.03 vs. -0.002 ± 0.02, p = 0.04) and HbA1c (-0.5 ± 0.8 vs. -0.1 ± 0.5%, p = 0.01) in the supplemented group were significantly different from the changes in these indicators in the placebo group. Additionally, significant increases in serum HDL-cholesterol (+4.1 ± 4.3 vs. +1.1 ± 5.1 mg/dl, p = 0.01), plasma total antioxidant capacity (+91.7 ± 213.9 vs. -111.9 ± 188.7 mmol/L, p < 0.01) and total glutathione (+68.1 ± 140.8 vs. -35.0 ± 136.1 µmol/L, p = 0.006), and significant decreases in high sensitivity C-reactive protein (-20.4 ± 24.6 vs. -6.8 ± 21.3 µg/ml, p = 0.02) and plasma malondialdehyde concentrations (-0.6 ± 0.9 vs. -0.2 ± 0.7 µmol/L, p = 0.03) were seen following supplementation with zinc compared with the placebo. Zinc supplementation for 12 weeks among diabetic foot ulcer patients had beneficial effects on parameters of ulcer size and metabolic profiles.

Concurrent peritoneal and pleural tuberculosis in an adult: A case report and literature review.

Background: The simultaneous involvement of the pleura and peritoneum with tuberculosis in the absence of pulmonary foci is an uncommon condition that may lead physicians to misdiagnose. Case Presentation: Herein, we present a Persian male adult who manifested with epigastric pain, weakness, and a history of pleuritic chest pain two months prior to admission. The findings of the physical examination included vital signs within the normal range, unilateral fine crackle in the lung, abdominal distension with positive shifting dullness, and fluid wave test. Analysis of the ascitic fluid revealed a Serum-ascites albumin gradient (SAAG) of less than 1.1g/dl, indicating a non-portal condition. The results of the acid-fast bacilli (AFB) staining as well as the TB polymerase chain reaction (PCR) test were negative. However, the adenosine deaminase (ADA) level was 44 IU/L. A chest CT scan revealed mediastinal lymph node enlargement and pleural thickening with loculated pleural effusion. Three acid-fast bacilli smear of morning sputum were sent, and all three were negative. An abdominopelvic CT scan showed multiple periaortic and mesenteric lymph nodes of varying sizes with mesenteric haziness and accumulation of effusion in the peritoneal cavity. Eventually, peritoneal biopsy, the gold standard, was performed, which revealed multiple granulomatous lesions and areas of caseous necrosis surrounded by Langerhans giant cells and epithelioid cells. Conclusion: It is worth noting that in cases of ascites and pleural thickening, especially in patients with poor socioeconomic status, simultaneous pleural and peritoneal TB should be considered, especially in third-world countries.

The effects of Annual SZ drug on dynamic changes in lymphocytes and cytokines of COVID-19 patients: A randomized clinical trial.

BACKGROUND: The search for a potent anti-coronavirus therapy has remained an overwhelming task since the outbreak of COVID-19. Annual SZ is a novel formulation of artemisinin and its derivatives. We aim to investigate the effect of Annual SZ on clinical outcomes, cellular immune responses, and cytokine changes in COVID-19 patients. METHODS: This study included 80 COVID-19 hospitalized patients, which were randomly allocated into two groups (intervention and control). Both groups received standard supportive treatment. In addition, the intervention group (n = 40) received Annual SZ syrup, and the control group (n = 40) received a placebo. Dynamic changes in lymphocytes, cytokines, and clinical status were evaluated since hospital admission to 7 and 14 days after treatment. RESULTS: The dynamic count of total T lymphocytes and T lymphocyte subsets (CD4+ and CD8+) in the Annual SZ group was significantly higher than the placebo group (p < 0.05). In addition, Programmed Death 1 (PD-1) was significantly increased in the CD4+ and CD8+ T cells in the placebo group compared with the Annual SZ group (p < 0.05). Also, the CD4+/CD8+ ratio was not significantly different between the groups (p > 0.9). Moreover, IL-6 levels were significantly reduced (p < 0.05), while IL-4 and IFN-γ levels were not statistically different between the two groups (p > 0.05). CONCLUSION: This research indicated that the Annual SZ syrup significantly improved clinical status and lymphocyte frequency with less exhaustion of T lymphocytes and a reduction of inflammatory responses, which seems to be beneficial in the treatment process of COVID-19 patients.

Bell's palsy: a case report of unusual presentation in a patient with rhino-orbital cerebral mucormycosis.

BACKGROUND: Mucormycosis is a fungal infection caused by the Mucorales order of fungi. This fungus is commonly found in soil and can cause disease in immunocompromised patients. On the other hand, Bell's palsy is an idiopathic condition that results in the sudden onset of unilateral facial muscle weakness, affecting the facial nerve. CASE PRESENTATION: A 51-year-old Persian housewife with a history of poorly controlled diabetes mellitus presented with a splitting headache that had been ongoing for 1 week and an inability to close her left eye or make facial expressions on the left side of her face. The patient's vital signs were normal, but physical examination revealed a yellow-grey scar on the left side of her hard palate and Bell's palsy on the left side. A neurological examination showed that she could move both eyes but could not close her left eye, move up her left eyebrow, or smile. Further investigations were performed, including laboratory tests, radiologic imaging, and functional endoscopic sinus surgery. The patient underwent three rounds of debridement for bony erosion in the medial and posterior walls of the left maxillary sinus and the hard palate. Pathological examination confirmed mucormycosis infection in the hard palate and mucosa. CONCLUSION: Fungal infection must be considered a potential diagnosis for immunocompromised adults who exhibit symptoms of Bell's palsy.

Concurrent emphysematous cystitis and emphysematous pyelonephritis in a patient with extrarenal pelvis.

We report co-occurrence of emphysematous cystitis and emphysematous pyelonephritis (EC/EPN) in a 64-year-old female with poor-controlled diabetes mellitus (DM) that presented with flank pain, fever, and hematuria that turned out to have a bilateral extrarenal pelvis. On examination, she was feverish, and the costovertebral angle was tender. By considering herhemoglobin A1C, her DM was out of control. Inflammatory markers elevated. Renal function tests were impaired. Urine culture was positive for extended-spectrum beta-lactamase Escherichia coli. Computed tomography scans (CT) confirmed the presence of air in the bladder and renal pelvis in favor of EC and unilateral EPN. We planned to use conservative treatments. Promptly intravenous antibiotics started; thereafter, the renal pelvis was drained via percutaneous catheter, and the bladder was drained via foley catheter, as well. After 14 days of hospitalization, clinical status improved, urine culture got negative, and emphysema in follow-up CT images wholly regressed. To our knowledge, co-occurrence of emphysematous cystitis (EC) and emphysematous pyelonephritis (EPN) in a patient with an extra renal pelvis never happened. We tend to convey messages, including (1) the extrarenal pelvis may contribute to predisposing the patient to pyelonephritis if it is considerably large; (2) the conservative plan and observation was a successful experience in treating extrarenal pelvis patients with EC/EPN.

Late diagnosis of respiratory syncytial virus and influenza co-infection during coronavirus disease 2019 pandemic: a case report.

BACKGROUND: Respiratory syncytial virus (RSV)-induced disease is one of the important causes of flu-like illness in older adults and can cause serious disease in those who are at high-risk medical conditions. During coronavirus disease 2019 (COVID-19) pandemic, because of overlapping symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection with other respiratory infections, diagnosing diseases based on clinical and radiological findings was challenging and could cause misdiagnosis. CASE PRESENTATION: An 87-year-old Persian man was admitted to the hospital due to loss of consciousness, respiratory distress, tachypnea, and oliguria. He had previously hospitalized because of cough, fever, loss of appetite, and fatigue. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) test was performed which was negative; however, based on ground glass opacity on his chest computed tomography (CT) scan and being on the outbreak of COVID-19, he fulfilled case definition of COVID-19; therefore, he received protocol's treatment (remdesivir) for COVID-19 and relatively recovered and discharged. In our center, we requested brain and chest CT scans, blood tests, and multiplex PCR. Multiplex PCR revealed co-infection of influenza virus and RSV. Although we had started pneumonia and sepsis treatment, old age, weak immune system and the delay in initiation of right antibiotic and antivirus therapy altogether led him to die. CONCLUSION: As a takeaway lesson of this case report, it is necessary to pay attention to viruses that show similar symptoms during future specific virus pandemics, especially in patients with old age and weak immune systems.

Bacterial endocarditis following COVID-19 infection: two case reports.

BACKGROUND: COVID-19, an emerging disease raised as a pandemic, urgently needed treatment choices. Some options have been confirmed as lifesaving treatments, but long-term complications must be clearly illustrated. Bacterial endocarditis is a less frequent disease among patients infected with SARS_COV_2 compared to other cardiac comorbidities in these patients. This case report discusses bacterial endocarditis as a potential adverse effect after administering tocilizumab, corticosteroids, and COVID-19 infection. CASE PRESENTATION: In the first case, a 51-year-old Iranian female housewife was admitted to the hospital with fever, weakness, and monoarthritis symptoms. The second case is a 63-year-old Iranian woman who is a housewife admitted with weakness, shortness of breath, and extreme sweating. Both cases tested positive for Polymerase chain reaction (PCR) less than one month ago and were treated with tocilizumab and corticosteroid. Both patients were suspected of infective endocarditis. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in the blood cultures of both patients. The diagnosis of endocarditis is confirmed for both cases. Cases are subjected to open-heart surgery, a mechanical valve is placed, and they are treated with medication. In subsequent visits, their condition was reported to be improving. CONCLUSION: Adjacent to cardiovascular inclusion as COVID-19 disease complications, secondary infection taken after the organisation of immunocompromising specialists can result in basic maladies and conditions counting infective endocarditis.

Brucellosis presenting with sepsis and cholestasis: A rare presentation of an endemic disease with review of the literature.

Brucellosis is a zoonotic disease endemic to the Middle East and Mediterranean basin. It has gained diagnostic challenge recently due to its increasingly non-specific and vague manifestations at presentation. Here, we report a 53-year-old man presenting with undulating fever and shaking chills and frequency, dysuria, hesitancy and malodorous urine. He had prior complicated urinary tract infection treated with intravenous antibiotics. Further evaluation revealed negative urine culture, intra-hepatic cholestasis due to underlying infection, elevated acute phase reactants and pancytopenia.The diagnosis of brucella was established as blood cultures grew Brucella melitensis and serum serology for Brucellosis returned positive. Following initiation of anti- brucella drugs, fever and laboratory abnormalities gradually returned to normal. Brucellosis should be always considered in the differential diagnosis of patients presenting with sepsis in endemic regions or when empiric antibiotic therapy fails to improve clinical and laboratory abnormalities. Diagnosis requires high level of suspicious based on the clinical history and constellation of symptoms.

Phenylketonuria in Iranian population: a study in institutions for mentally retarded in Isfahan.

Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene (12q22-q24) resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe) and production of the phenylketonuria (PKU) disease. To date there have been no reports on the molecular analysis of PKU in Iranian population. In this study, the states of the PKU disease in terms of prevalence and mutation spectrum among patients reside in the institutions for mentally retarded in Isfahan was investigated. In the first step, 611 out of 1541 patients with PKU phenotype or severe mental retardation were screened for the PKU disease using the Guthrie bacterial inhibition assay (GBIA) followed by HPLC. Among the patients screened 34 (5.56%) were found positive with abnormal serum Phe of above 7mg/dl. In the next step, the presence of 18 common mutations of the PAH gene in 26 of the patients with classical PKU (serum Phe above 20mg/dl) was investigated, using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Of the 52 independent mutant alleles that were analyzed, 34 (65.38%) were genotyped showing 8 mutations as follows: R252W (15.38%), Q232Q (13.46%), R261Q (7.69%), delL364 (7.69%), IVS10-11g>a (5.77%), L333F (5.77%), V245V (5.77%) and S67P (3.85%). The results from this study may serve as a reference to analyze the PKU mutations in other part of Iran, and to establish diagnostic tests for carrier detection and prenatal diagnosis of the PKU disease in Iranian population.