Itraconazole Improved Bronchial Wall Thickness in Severe Persistent Asthma: A Double-blind Placebo-controlled Randomized Clinical Trial.

The purpose of this study was to evaluate the effect of 8 months of treatment with itraconazole on airway wall thickness in patients with severe persistent asthma. It was a double-blind, randomized, placebo-controlled clinical trial (IRCT20091111002695N9). Seventy-five subjects with severe persistent asthma received itraconazole (100 mg), prednisolone (5 mg), or placebo twice a day for eight months in three treatment groups (n=25 in each group). The primary objective was to improve the right upper lobe apical segmental bronchus (RB1) wall thickness percentage measured by high-resolution computed tomography scan of the lungs. Other morphometric measurements of RB1, asthma control test (ACT) score, presence of wheezing, dyspnea severity, rate of asthma exacerbation, fractional exhaled nitric oxide (FeNO), and expiratory volume in 1 second (FEV1) were set as the secondary outcomes. Wall thickness percentage reduced significantly from 46% to 43.7% from pre- to post-treatment in the itraconazole-treated subjects. Similarly, lumen area and radius increased significantly in both the prednisolone and itraconazole groups. Itraconazole led to a significant improvement in wheezing, dyspnea severity, FEV1, ACT score, and FeNO. Although prednisolone was also effective in improving pulmonary function tests and ACT scores, it was associated with significantly more side effects than itraconazole. Long-term treatment with itraconazole resulted in a significant reduction in bronchial wall thickness and improvements in clinical findings and pulmonary function tests. Thus, itraconazole could be a helpful add-on treatment option for severe persistent asthma patients to achieve better disease control.

The Effects of Statins on Respiratory Symptoms and Pulmonary Fibrosis in COVID-19 Patients with Diabetes Mellitus: A Longitudinal Multicenter Study.

The aim of this prospective cohort study was to explore the effect of statins on long-term respiratory symptoms and pulmonary fibrosis in coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM). Patients were recruited from three tertiary hospitals, categorized into Statin or Non-statin groups, and assessed on days 0, 28, and 90 after symptoms onset to record the duration of symptoms. Pulmonary fibrosis was scored at baseline and follow-up time points by high-resolution computed tomography scans. Each group comprised 176 patients after propensity score matching. Data analysis revealed that the odds of having cough and dyspnea were significantly higher in the Non-statin group compared to the Statin group during the follow-up period. Overall, there was no significant difference in the change in pulmonary fibrosis score between groups. However, Non-statin patients with > 5 years of DM were more likely to exhibit a significantly higher fibrosis score during the follow-up period as compared to their peers in the Statin group. Our results suggest that the use of statins is associated with a lower risk of developing chronic cough and dyspnea in diabetic patients with COVID-19, and may reduce pulmonary fibrosis associated with COVID-19 in patients with long-term (> 5 years) DM.

PIWI interacting RNAs perspectives: a new avenues in future cancer investigations.

As a currently identified small non-coding RNAs (ncRNAs) category, the PIWI-interacting RNAs (piRNAs) are crucial mediators of cell biology. The human genome comprises over 30.000 piRNA genes. Although considered a new field in cancer research, the piRNA pathway is shown by the existing evidence as an active pathway in a variety of different types of cancers with critical impacts on main aspects of cancer progression. Among the regulatory molecules that contribute to maintaining the dynamics of cancer cells, the P-element Induced WImpy testis (PIWI) proteins and piRNAs, as new players, have not been broadly studied so far. Therefore, the identification of cancer-related piRNAs and the assessment of target genes of piRNAs may lead to better cancer prevention and therapy strategies. This review articleaimed to highlight the role and function of piRNAs based on existing data. Understanding the role of piRNA in cancer may provide perspectives on their applications as particular biomarker signature in diagnosis in early stage, prognosis and therapeutic strategies.

Clinical characteristics, gastrointestinal manifestations and outcomes of COVID-19 patients in Iran; does the location matters?

BACKGROUND: Coronavirus disease 2019 (COVID-19) started in Asia, and Iran was one of its first epicenters. AIM: To study the gastrointestinal (GI) symptoms and comorbidities associated with this pandemic in four different regions of Iran. METHODS: We analyzed data from severe acute respiratory syndrome coronavirus 2 positive patients evaluated at four hospitals of Iran (n = 91), including South (Shiraz), Southeast (Dezful), Rasht (North), and Northwest (Mashhad) between April and September 2020. Demographics, comorbidities and clinical findings including GI symptoms were collected. Statistical descriptive analysis and correlation analyses of symptoms, comorbidities, and mortality were performed. RESULTS: The average age of COVID-19 patients was 51.1 years, and 56% were male. Mortality rate was 17%. Cough with 84.6%, shortness of breath with 71.4%, fever with 52.7%, and loss of appetite with 43.9% were the main symptoms. Overall cardiac disease was the most common comorbidity with an average of 28.5% followed by hypertension (28.5%) and diabetes (25.2%). The highest comorbidity in North (Rasht) was diabetes (30%) and in South (Dezful) hypertension (37%). Shiraz leads cardiac disease with 43.4%. The most reported GI symptoms included nausea, diarrhea, vomiting, and abdominal pain, with 42.8%, 31.8%, 26.8%, and 12% prevalence, respectively. In addition, albumin, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase were elevated in 26.3%. CONCLUSION: Our results show hypertension and diabetes as the most common comorbidities, but their distribution was different in COVID-19 patients in the four studied regions of Iran. Nausea, diarrhea, and elevated liver enzymes were the most common GI symptoms. There was also a high mortality rate that was associated with high infection rates in Iran at the beginning of the pandemic.

Effect of azithromycin on bronchial wall thickness in severe persistent asthma: A double-blind placebo-controlled randomized clinical trial.

BACKGROUND: Azithromycin reduced airway remodeling in animal models of asthma. However, its effect on human subjects has not been studied yet. This study aimed to investigate the effect of long-term treatment with azithromycin on airways wall thickness in patients with severe persistent asthma. METHODS: In this randomized, double-blind, placebo-controlled clinical trial, patients with severe persistent asthma received azithromycin (250 mg, BID, three days a week), prednisolone (5 mg, BID), or placebo for eight months in three separate groups in addition to the standard therapy. The improvement in right upper lobe apical segmental bronchus (RB1) wall thickness obtained by high resolution computed tomography was set as the primary outcome. Secondary outcomes included: cough severity, dyspnea severity, asthma control test (ACT) score, asthma exacerbation rate, pulmonary function tests, and fractional exhaled nitric oxide (FENO). RESULTS: Seventy-eight out of ninety randomized subjects completed eight months of treatment with azithromycin (n = 25), prednisolone (n = 27), or placebo (n = 26). Bronchial wall thickness percentage did not change significantly in any of the groups. However, the inner radius and lumen area of azithromycin and prednisolone-treated subjects increased significantly (p < 0.05 for both). Azithromycin also significantly improved the dyspnea severity, ACT score, FENO, and FEV1, FEF25-75, and FEV1/FVC (p < 0.05 for all). Cough severity or asthma exacerbation rate did not change significantly after eight months of treatment with azithromycin. CONCLUSION: Long-term treatment with azithromycin increased lumen radius and lumen area in patients with severe persistent asthma. However, there was no significant change in wall thickness in any of the treatment groups. TRIAL REGISTRATION: IRCT.com (IRCT20091111002695N8).

Statins in patients with COVID-19: a retrospective cohort study in Iranian COVID-19 patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has profoundly affected the lives of millions of people. To date, there is no approved vaccine or specific drug to prevent or treat COVID-19, while the infection is globally spreading at an alarming rate. Because the development of effective vaccines or novel drugs could take several months (if not years), repurposing existing drugs is considered a more efficient strategy that could save lives now. Statins constitute a class of lipid-lowering drugs with proven safety profiles and various known beneficial pleiotropic effects. Our previous investigations showed that statins have antiviral effects and are involved in the process of wound healing in the lung. This triggered us to evaluate if statin use reduces mortality in COVID-19 patients. RESULTS: After initial recruitment of 459 patients with COVID-19 (Shiraz province, Iran) and careful consideration of the exclusion criteria, a total of 150 patients, of which 75 received statins, were included in our retrospective study. Cox proportional-hazards regression models were used to estimate the association between statin use and rate of death. After propensity score matching, we found that statin use appeared to be associated with a lower risk of morbidity [HR = 0.85, 95% CI = (0.02, 3.93), P = 0.762] and lower risk of death [(HR = 0.76; 95% CI = (0.16, 3.72), P = 0.735)]; however, these associations did not reach statistical significance. Furthermore, statin use reduced the chance of being subjected to mechanical ventilation [OR = 0.96, 95% CI = (0.61-2.99), P = 0.942] and patients on statins showed a more normal computed tomography (CT) scan result [OR = 0.41, 95% CI = (0.07-2.33), P = 0.312]. CONCLUSIONS: Although we could not demonstrate a significant association between statin use and a reduction in mortality in patients with COVID19, we do feel that our results are promising and of clinical relevance and warrant the need for prospective randomized controlled trials and extensive retrospective studies to further evaluate and validate the potential beneficial effects of statin treatment on clinical symptoms and mortality rates associated with COVID-19.

Neurological disorders caused by two cerebral alveolar hydatid cysts in an old woman: a rare case report.

Alveolar hydatid disease, caused by Echinococcus multilocularis, is a life-threatening infectious disease which primarily occurs in the liver. Intracranial hydatid disease is a rare presentation with reported incidence of ~1% of all cases. Here we reported a 60-year-old woman, with the past history of hydatid cysts in her liver, who was presented to us with progressive symptoms consist of headaches, diminished vision, cognitive disorders and delusion. She was disoriented in time, space and person. Bilateral mild papilledema and exaggerated reflexes were observed. Magnetic resonance imaging of the brain revealed two intra-axial multilucular cystic masses in the fronto-pareital and parieto-occipital regions. The patient underwent two operations and the lesions were removed without any rupture. Medical therapy with Albendazole was started. Neurological symptoms disappeared a few weeks after the surgeries. Although multiple alveolar hydatid cysts are extremely rare, they should be considered in the differential diagnosis of intracranial cystic lesions.