Effect of interferon-α on COVID-19 in-hospital mortality: a large-scale propensity score-matched study.

BACKGROUND:  Coronavirus infection can induce the production of inflammatory cytokines leading to acute respiratory distress syndrome (ARDS) and death. It is well-established that interferons (IFNs) are essential in regulating the immune response, thus their effects of IFNs on COVID-19 patients should be subject to investigation. This study aimed to investigate the effects of IFN-α alone or in combination with remdesivir in hospitalized COVID-19 patients. MATERIAL AND METHODS:  A multicentre, retrospective study was conducted on COVID-19 patients admitted to three hospitals in Tehran, Iran, from March 20, 2020, to March 18, 2021. The unadjusted and adjusted effects of IFN-α on COVID-19 outcomes were investigated through propensity score matching (PSM) to achieve a 1:1 balanced dataset. RESULTS: Among 4,782 patients, 3,764 were eligible for the study, including 1,704 patients (45.27%) receiving at least one treatment with IFN-α and 2,060 controls not receiving IFN-α. After PSM, 851 IFN-α patients and 851 controls were recruited in the PSM analysis with a median age of 60.8 (standard deviation [SD]: 16.2 and 60.9 [SD: 17.4]), respectively. The PSM results showed no significant difference between the survival curves of the IFN-α group and the control group (p=0.340). However, the unadjusted impact of IFN-α on the risk of mortality was statistically significant (p=0.043, hazard-ratio: 0.86; 95% confidence interval [CI]: 0.75-0.99). Also, the combination of IFN-α and remdesivir had no significant benefit (HR: 89, 95% CI: 0.74-1.34). CONCLUSION: Our findings indicate that subcutaneous administration of IFN-α, with or without remdesivir, does not have any significant impact on COVID-19 mortality and ICU admission. Future clinical trials considering the time, subtype, and form of IFN-α administration are warranted to investigate the potential therapeutic effects of IFN-α on COVID-19.

Predictors of postoperative pain six months after breast surgery.

Breast cancer, with a high prevalence and survival rate, leads to long-term complications. A major sequel is acute or chronic postoperative pain, and we investigated the possible relationship with clinical and psychological variables. Patients undergoing breast surgery filled out the loneliness (ULS-8) and depression (HADS) questionnaires. Patients rated their pain intensity with the Numerical Rating Scale (0-10, NRS) two days, seven days, and six months after surgery. Of 124 patients, the mean age was 45.86 years old, and the pain scores on the second and seventh postoperative days were 5.33 and 3.57, respectively. Sixth-month pain was significantly correlated with the acute scores with a mean of 3.27; and in the multivariate analysis, it was significantly associated with preoperative pain (p-value = 0.007), self-reported loneliness (p-value = 0.010), and adjuvant radiotherapy (p-value = 0.004). In conclusion, loneliness may be a risk factor for postoperative pain in breast surgery.

Sleep characteristics of middle-aged adults with non-alcoholic fatty liver disease: findings from the Shahrekord PERSIAN cohort study.

BACKGROUND: Several studies have reported short sleep duration in people with non-alcoholic fatty liver disease (NAFLD) but other sleep characteristics have been less studied. We aimed to assess the cross-sectional association of NAFLD with sleep duration and quality in an Iranian population sample. METHODS: We used data from 9,151 participants in the Shahrekord Prospective Epidemiological Research Studies in Iran (PERSIAN) Cohort Study, including 1,320 that were diagnosed with NAFLD. Log-binomial regression models sequentially adjusted for sociodemographic, lifestyle, clinical and biological variables were used to estimate relative risks (RR) and 95% confidence intervals (95% CI) for the association between NAFLD and sleep characteristics. RESULTS: Participants with NAFLD had shorter sleep duration, later wake-up time and bedtime, worse sleep efficiency, and more frequent daytime napping and use of sleeping pills, in age- and sex-adjusted models. After controlling for sociodemographic, lifestyle, clinical, and biological variables the associations remained strong for sleep efficiency (per 10%, RR = 0.92, 95%CI: 0.88-0.96) and use of sleeping pills (RR = 1.48, 95%CI: 1.17-1.88). The association between NAFLD and sleep efficiency was stronger in participants aged > 60 years (RR = 0.81, 0.70-0.93) and 40-60 years (RR = 0.87, 0.82-0.94), compared with those aged < 40 years (P-heterogeneity < 0.001). More frequent daytime napping in participants with NAFLD, compared with non-NAFLD, was observed in males but not females (P-heterogeneity = 0.007), and in those with body mass index (BMI) < 30 but not in obese participants (P-heterogeneity < 0.001). CONCLUSIONS: Diagnosis of NAFLD is associated with several poor sleep characteristics in middle-aged Iranians. Although longitudinal studies would help to clarify the direction of causality, our study shows that poor sleep is an important aspect of NAFLD.

Characterization of the mucosal microbiota in patients with nodular lymphoid hyperplasia with concurrent irritable bowel syndrome compared to healthy controls.

BACKGROUND: Nodular lymphoid hyperplasia (NLH) is known as a lymphoproliferative lesion in which multiple small nodules appear on the intestinal wall. It has been documented that patients who struggle with irritable bowel syndrome (IBS) are at greater risk of developing NLH. Here, we aimed to investigate the previously reported pathogens and the abundance of a selection of mucosal microbiota in IBS + NLH patients compared to IBS, and healthy controls. METHODS AND RESULTS: Terminal ileum biopsies were collected from 37 IBS + NLH, 37 IBS, and 29 healthy controls. Bacterial culture and PCR was performed to detect the presence of pathogens in biopsies. A qPCR assay was applied to assess the abundance of a selection of bacterial taxa. Totally, five bacterial isolates including two enteropathogenic and one enteroaggregative Escherichia coli (EPEC, EAEC), one enterotoxigenic Staphylococcus aureus (SEA), and one Yersinia enterocolitica strains were detected among the IBS + NLH cases. The relative abundance of Bacteroidetes and Streptococcus spp. in IBS + NLH patients was significantly less than IBS and healthy controls. Firmicutes, Pseudomonas spp., Haemophilus spp., and Campylobacter spp. were notably more abundant in IBS + NLH than in IBS patients. The abundance of Verrucomicrobia was higher in NLH + IBS than in healthy controls. Actinobacteria was also significantly more abundant among NLH + IBS patients than the controls. CONCLUSION: Our results demonstrated that mucosal microbiota composition in NLH + IBS patients slightly differs from that of IBS patients and healthy controls. Further research using large-scale cohorts are needed to enhance current understanding of the contribution of the mucosal microbiota to NLH pathogenesis with concurrent IBS.

Mortality among hospitalized COVID-19 patients during surges of SARS-CoV-2 alpha (B.1.1.7) and delta (B.1.617.2) variants.

The aim of this study was to evaluate the death proportion and death risk of COVID-19 hospitalized patients over time and in different surges of COVID-19. This multi-center observational study was conducted from March 21, 2021 to October 3, 2021 which included the alpha and delta SARS-CoV-2 surges occurred in April and August in Tehran, respectively. The risk of COVID-19 death was compared in different months of admission. A total of 270,624 patients with COVID-19, of whom 6.9% died, were admitted to hospitals in Tehran province. Compared to patients admitted in March, a higher risk of COVID-19 death was observed among patients admitted to the hospital in July (HR 1.28; 95% CI 1.17, 1.40), August (HR 1.40; 95% CI 1.28, 1.52), September (HR 1.37; 95% CI 1.25, 1.50) and October (HR 4.63; 95% CI 2.77, 7.74). The ICU death proportion was 36.8% (95% CI: 35.5, 38.1) in alpha surge and increased significantly to 39.8 (95% CI 38.6, 41.1) in delta surge. The risk of COVID-19 death was significantly higher in delta surge compared to alpha surge (HR 1.22; 95% CI 1.17, 1.27). Delta surge was associated with a higher risk of death compared to alpha surge. High number of hospitalizations, a shortage of hospital beds, ICU spaces and medical supplies, poor nutritional status of hospitalized patients, and lack of the intensivist physicians or specialized nurses in the ICU were factors that contributed to the high mortality rate in the delta surge in Iran.

Surface layer protein A from hypervirulent Clostridioides difficile ribotypes induce significant changes in the gene expression of tight junctions and inflammatory response in human intestinal epithelial cells.

BACKGROUND: Surface layer protein A (SlpA), the primary outermost structure of Clostridioides difficile, plays an essential role in C. difficile pathogenesis, although its interaction with host intestinal cells are yet to be understood. The aim of this study was to investigate the effects of SlpA extracted from C. difficile on tight junction (TJ) proteins expression and induction of pro-inflammatory cytokines in human colon carcinoma cell line HT-29. SlpA was extracted from three toxigenic C. difficile clinical strains including RT126, RT001, RT084 as well as C. difficile ATCC 700057 as non-toxigenic strain. Cell viability was performed by MTT assay, and the mRNA expression of TJ proteins and inflammation-associated genes was determined using quantitative RT-PCR. Additionally, the secretion of IL-8, IL-1ß and TNF-α cytokines was measured by ELISA. RESULTS: C. difficile SlpA from selected RTs variably downregulated the expression level of TJs-assassinated genes and increased the expression level of TLR-4 and pro-inflammatory cytokines in HT-29 treated cells. SlpA from RT126 significantly (padj<0.05) decreased the gene expression level of claudins family and JAM-A and increased the secretion of IL-8, TNF-α and IL1-ß as compared to untreated cells. Moreover, only SlpA from RT001 could significantly induce the expression of IL-6 (padj<0.05). CONCLUSION: The results of the present study highlighted the importance of SlpA in the pathogenesis of CDI and C. difficile-induced inflammatory response in the gut. Further studies are required to unravel the significance of the observed results in promoting the intestinal inflammation and immune response induced by C. difficile SlpA from different RTs.

Epidemiology of COVID-19 in Tehran, Iran: A Cohort Study of Clinical Profile, Risk Factors, and Outcomes.

Background: The outbreak of coronavirus disease 2019 (COVID-19) dates back to December 2019 in China. Iran has been among the most prone countries to the virus. The aim of this study was to report demographics, clinical data, and their association with death and CFR. Methods: This observational cohort study was performed from 20th March 2020 to 18th March 2021 in three tertiary educational hospitals in Tehran, Iran. All patients were admitted based on the WHO, CDC, and Iran's National Guidelines. Their information was recorded in their medical files. Multivariable analysis was performed to assess demographics, clinical profile, outcomes of disease, and finding the predictors of death due to COVID-19. Results: Of all 5318 participants, the median age was 60.0 years, and 57.2% of patients were male. The most significant comorbidities were hypertension and diabetes mellitus. Cough, dyspnea, and fever were the most dominant symptoms. Results showed that ICU admission, elderly age, decreased consciousness, low BMI, HTN, IHD, CVA, dialysis, intubation, Alzheimer disease, blood injection, injection of platelets or FFP, and high number of comorbidities were associated with a higher risk of death related to COVID-19. The trend of CFR was increasing (WPC: 1.86) during weeks 25 to 51. Conclusions: Accurate detection of predictors of poor outcomes helps healthcare providers in stratifying patients, based on their risk factors and healthcare requirements to improve their survival chance.

Global pattern of trends in incidence, mortality, and mortality-to-incidence ratio rates related to liver cancer, 1990-2019: a longitudinal analysis based on the global burden of disease study.

BACKGROUND: Liver cancer (LC) is considered as one of the most dominant malignant tumors which ranked 4th and in terms of global mortality and incidence, respectively. This work aimed to investigate the global temporal trends in LC mortality-to-incidence ratio (MIR) and its components, with a particular focus on examining long-term effect of human development index (HDI) on these metrics in a 30-year follow-up. METHODS: The age-standardized LC incidence and mortality data were derived from the global burden of disease (GBD) study 2019. We first leveraged joinpoint piecewise linear regression analysis to ascertain time trends in LC incidence, mortality, and MIR complement [1-MIR] and the average annual percentage change (AAPC) of the rates over the period 1990-2019. Then, the association between the metrics and HDI was explored through longitudinal multilevel models (LMMs). RESULTS: The incidence rates paralleled the mortality rates worldwide and they had similar significant monotonic decrementing trends with AAPC values of - 1.10% (95% confidence interval (CI): - 1.40, - 0.90%) and - 1.40% (- 1.50, - 1.30%), respectively from 1990 to 2019. The [1-MIR] rates were around 0 and showed an increasing pattern from 1.70 to 8.10 per 100,000 people (AAPC, 4.90%) at the same period of time. Results from the LMMs displayed that the majority of the variation lies at the country level accounted for about 88% of the total variance. Moreover, our analysis supported that the HDI was negatively associated with either incidence or mortality over time (p < 0.05). CONCLUSIONS: Our findings highlighted that the global long-term temporal trends of LC incidence and mortality decreased slightly during 1990-2019 which may reflect improved therapeutic strategies and public health interventions. Besides, the low rates of [1-MIR] revealed the five-year relative survival rate was poor implying LC is diagnosed late in its development. Thereby, the policymakers' focus must be on early screening and detection of liver cancer.

The impact of HIV on the risk of COVID-19 death among hospitalized patients.

BACKGROUND: Little is known about the association between Human Immunodeficiency Virus (HIV) infection and risk of death among hospitalized COVID-19 patients. We aimed to investigate this association using a multicenter study. MATERIAL AND METHODS: This multicenter study was conducted using the registry database of Coronavirus Control Operations Headquarter from March 21, 2021 to January 18, 2020 in the province of Tehran, Iran. The interest outcome was COVID-19 death among hospitalized patients living with and without HIV. The Cox regression models with robust standard error were used to estimate the association between HIV infection and risk of COVID-19 death. The subgroup and interaction analysis were also performed in this study. RESULTS: 326052 patients with COVID-19 were included in the study, of whom 127 (0.04%) were living with HIV. COVID-19 patients with HIV were more likely to be female, older, and to have symptoms such as fever, muscular pain, dyspnea and cough. The death proportion due to COVID-19 was 18 (14.17%) and 21595 (6.63%) among HIV and non-HIV patients, respectively. Patients living with HIV had lower mean survival time compared to those without HIV (26.49 vs. 15.31 days, P-value = 0.047). Crude risk of COVID-19 death was higher among HIV patients than in non-HIV group (hazard ratio[HR]: 1.60, 1.08-2.37). Compared to those without HIV, higher risk of COVID-19 death was observed among patients with HIV after adjusting for sex (1.60, 1.08-2.36), comorbidities (1.49, 1.01-2.19), cancer (1.59, 1.08-2.33), and PO2 (1.68, 1.12-2.50). However, the risk of COVID-19 death was similar in patients with and without HIV after adjusting for age (1.46, 0.98-2.16) and ward (1.30, 0.89-1.89). CONCLUSION: We found no strong evidence of association between HIV infection and higher risk of COVID-19 death among hospitalized patients. To determine the true impact of HIV on the risk of COVID-19 death, factors such as age, comorbidities, hospital ward, viral load, CD4 count, and antiretroviral treatment should be considered.

Assessing the association between subjective evaluation of space qualities and physiological responses through cinematic environments' emotion-eliciting stimuli.

Objectives: Human perception of the built environment affects emotional and physiological states. This research focused on the association between evaluating a space's visual qualities and physiological responses by mediating film contents to indicate the association between physiological indicators and assessing the quality of space in the presence of environmental stimuli. Method: Data collection was conducted using a psychological questionnaire and physiological indicators of heart rate (HR), blood pressure (BP), skin resistance level (SRL), and body temperature (BT) during the film screening. The ANOVA was conducted to compare different variables in the three films alongside linear regression to analyze the impact of variables on space quality. Spearman correlation coefficient analyses were performed to find the association between variables. Results: The descriptive statistics showed significant changes in psychological and physiological variables in films. Associations between the NAQ factor and physiological changes in HR, SBP, and DBP factors were significant. The results derived from the simple and multiple linear regressions depicted the significant impact of physiological factors on HR and BP on perceiving the quality of space. Conclusion: It was concluded that physiological changes caused by emotional arousal could be strongly associated with psychological assessments. Stimuli-affected video contents illustrating architectural spaces could efficiently extract the impact of physiological states and human cognitive responses to the space quality. Physiological characteristics related to the space appraisal could help realize the human-environment interaction in a multi-layered approach to the built environment and spatial cognition.

Glycemic Gap Predicts in-Hospital Mortality in Diabetic Patients with Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: The relationship between admission hyperglycemia and intracerebral hemorrhage (ICH) outcome remains controversial. Glycemic gap (GG) is a superior indicator of glucose homeostatic response to physical stress compared to admission glucose levels. We aimed to evaluate the association between GG and in-hospital mortality in ICH. METHODS: We retrospectively identified consecutive patients hospitalized for spontaneous ICH at the 2 healthcare systems in the Twin Cities area, MN, between January 2008 and December 2017. Patients without glycosylated hemoglobin (HbA1c) test or those admitted beyond 24 hours post-ICH were excluded. Demographics, medical history, admission tests, and computed tomography data were recorded. GG was computed using admission glucose level minus HbA1c-derived average glucose. The association between GG and time to in-hospital mortality was evaluated by Cox regression analysis. Receiver operating characteristic (ROC) analysis with the DeLong test was used to evaluate the ability of GG to predict in-hospital death. RESULTS: Among 345 included subjects, 63 (25.7%) died during the hospital stay. Compared with survivors, non-survivors presented with a lower Glasgow coma scale score, larger hematoma volume, and higher white blood cells count, glucose, and GG levels at admission (p<0.001). GG remained an independent predictor of in-hospital mortality after adjusting for known ICH outcome predictors and potential confounders [adjusted hazard ratio: 1.09, 95% confidence interval (CI): 1.02-1.18, p = 0.018]. GG showed a good discriminative power (area under the ROC curve: 0.75, 95% CI: 0.68-0.82) in predicting in-hospital death and performed better than admission glucose levels in diabetic patients (p = 0.030 for DeLong test). CONCLUSIONS: Admission GG is associated with the risk of in-hospital mortality and can potentially represent a useful prognostic biomarker for ICH patients with diabetes.

Expression of Main Toll-Like Receptors in Patients with Different Types of Colorectal Polyps and Their Relationship with Gut Microbiota.

Abnormal activation of Toll-like receptor (TLRs) signaling can result in colon cancer development. The aim of this study was to investigate the expression of important TLRs in different histological types of colorectal polyps and evaluate their relationship with intestinal microbiota. The expression levels of TLR2, 3, 4, and 5 were analyzed in intestinal biopsy specimens of 21 hyperplastic polyp (HP), 16 sessile serrated adenoma (SSA), 29 tubular adenoma (TA), 21 villous/tubulovillous (VP/TVP) cases, and 31 normal controls. In addition, selected gut bacteria including Streptococcus bovis, Enterococcus faecalis, Enterotoxigenic Bacteroides fragilis (ETBF), Fusobacterium nucleatum, Porphyromonas spp., Lactobacillus spp., Roseburia spp., and Bifidobacterium spp. were quantified in fecal samples using absolute qRT PCR, and, finally, the association between TLRs and these gut microbiota- was evaluated by Spearman's correlation coefficient. Higher expression of TLR2 and TLR4 in VP/TVP and TA, and lower expression levels of TLR3 and TLR5 in all type of polyps were observed. The differences in TLR expression patterns was not only dependent on the histology, location, size, and dysplasia grade of polyps but also related to the intestinal microbiota patterns. TLR2 and TLR4 expression was directly associated with the F. nucleatum, E. faecalis, S. bovis, Porphyromonas, and inversely to Bifidobacterium, Lactobacillus, and Roseburia quantity. Furthermore, TLR3 and TLR5 expression was directly associated with Bifidobacterium, Roseburia, and Lactobacillus quantity. Our results suggest a possible critical role of TLRs during colorectal polyp progression. An abnormal regulation of TLRs in relation to gut microbial quantity may contribute to carcinogenesis.

Epidemiologic trend of mobile spine and sacrum chordoma: A National population-based study.

INTRODUCTION: Chordoma is a rare sarcoma of the axial skeleton. The incidence of this tumor is different between races. To understand the epidemiologic characteristic and due to rarity of this pathology, large number of cases should be evaluated through national data registries. MATERIALS AND METHODS: All pathologically confirmed cases of chordoma were derived from the Iran National Cancer Registry. Descriptive analysis was performed to extract age-standardized and age-specific incidence rates. Data regarding tumor location and chordoma subtypes were derived and analyzed. RESULTS: One hundred twenty-two cases of chordoma including 80 male and 42 female were identified. One hundred seven cases of nonotherwise specified chordoma, 14 chondroid chordoma, and one dedifferentiated chordoma were detected. The age-standardized incidence rate (ASIR) of chordoma was 0.28. Chordoma of the sacrum composed 67.2% of cases. The mean survival time was 4.5 years. CONCLUSION: Epidemiology characteristic of chordoma in Iran is similar to other studies; however, the total ASIR was lower and the incidence in sacrum is nearly twice respect to the mobile spine. While men affected by sacral chordoma in relatively older age, the female patients had higher mean age in case of mobile spine involvement. The survival rate of chordoma is significantly lower in comparison with other studies.