Joint modeling of longitudinal and competing risks for assessing blood oxygen saturation and its association with survival outcomes in COVID-19 patients.

BACKGROUND: The objective of the present study is to evaluate the association between longitudinal and survival outcomes in the presence of competing risk events. To illustrate the application of joint modeling in clinical research, we assessed the blood oxygen saturation (SPO2) and its association with survival outcomes in coronavirus disease (COVID-19). MATERIALS AND METHODS: In this prospective cohort study, we followed 300 COVID-19 patients, who were diagnosed with severe COVID-19 in the Rohani Hospital in Babol, the north of Iran from October 22, 2020 to March 5, 2021, where death was the event of interest, surviving was the competing risk event and SPO2 was the longitudinal outcome. Joint modeling analyses were compared to separate analyses for these data. RESULT: The estimation of the association parameter in the joint modeling verified the association between longitudinal outcome SPO2 with survival outcome of death (Hazard Ratio (HR) = 0.33, P = 0.001) and the competing risk outcome of surviving (HR = 4.18, P < 0.001). Based on the joint modeling, longitudinal outcome (SPO2) decreased in hypertension patients (ß = -0.28, P = 0.581) and increased in those with a high level of SPO2 on admission (ß = 0.75, P = 0.03). Also, in the survival submodel in the joint model, the risk of death survival outcome increased in patients with diabetes comorbidity (HR = 4.38, P = 0.026). CONCLUSION: The association between longitudinal measurements of SPO2 and survival outcomes of COVID-19 confirms that SPO2 is an important indicator in this disease. Thus, the application of this joint model can provide useful clinical evidence in the different areas of medical sciences.

Survival rate of vaginal cancer in Asian countries: a systematic review and meta-analysis.

Introduction: Vaginal cancer is one of the major causes of mortality in women, which mostly takes place in low- and middle-income countries. Assessing the survival rate of vaginal cancer is essential to investigate the success rate of current treatments and screening tools. This study aims to determine the survival rate of vaginal cancer in Asia. Methods: This systematic review was carried out using four international databases, including Medline/Pubmed, ProQuest, Scopus, Web of Knowledge, and also Google Scholar. Articles were investigated up to the end of August 2021. The authors utilized the Newcastle-Ottawa Scale to evaluate the quality of the articles. Evaluating the papers for heterogeneity was performed using the Cochrane test and I² statistic. Meta-regression analysis was also applied based on the year of the study. Results: Three articles (13 records) fulfilled the inclusion criteria. Based on the random model, the overall 5-year survival rate was 74.63%. Also, the rates of survival in relation to the type of treatment including chemotherapy, radiotherapy, or other modalities, were 78.53, 78.44, and 68.54%, respectively. According to meta-regression analysis, no correlation was found between the survival rate and the year of the study. Conclusion: The vaginal cancer survival rate is lower in Asian countries compared to that of developed countries. Increasing patient survival rates in such countries is crucial by implementing newer diagnostic tools, advanced surgical techniques, and goal-oriented treatments. Early diagnosis in lower stages and educating the populations about risk factors and preventative measures are also necessary for raising the rate of survival.

Domestic Violence Against Women During the COVID-19 Pandemic and Its Relationship to Demographic and Family Factors: A Cross-Sectional Study in Iran.

BACKGROUND: During the COVID-19 pandemic, we have witnessed increased complaints from third parties about violent conditions through social media. This study aimed to determine the prevalence of domestic violence (DV) against women following exposure to the COVID-19 pandemic and its relevance to some related factors. MATERIALS AND METHODS: This study was conducted from July 2020 to May 2021 on married women of Babol, Iran. Eligible women entered into the study in a multi-stage cluster random sampling method. Data collection tools included demographic and family data, questionnaire HITS (Hurt, Insult, Threaten and Scream). Relationships were estimated using the Univariate and multivariate regression models.  Results: The mean age of 488 women and their spouses was 34.62 ± 9.14 and 38.74 ± 9.07, respectively. Of the total female participants, 37 (7.6%), 68 (13.9%), and 21 (4.3%) were victims of total violence, verbal abuse, and physical violence, respectively. Ninety-five women (19.5) had a history of coronavirus infection. Women who were satisfied with their income and husbands were university educated, their chances of DV were reduced by 72% (95% CI (0.09-0.85), OR = 0.28) and 67% (95% CI (0.11-0.92), OR = 0.33) respectively. Drug abuse by husbands increased the likelihood of DV by up to 4 times (OR = 4.00), and more contact with their husbands at home due to home quarantine was more than twice as likely to have DV (OR = 2.64).  Conclusion: Since the level of domestic violence was lower than before the coronavirus pandemic, it seems that most Iranian women were more under the support of their husbands during the coronavirus pandemic to endure the fear and panic caused by the pandemic. Women whose husbands had a university education and sufficient income had less domestic violence.

Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine: A Randomized Clinical Trial.

Importance: The protein-based SARS-CoV-2 vaccines FINLAY-FR-2 (Soberana 02) and FINLAY-FR-1A (Soberana Plus) showed good safety and immunogenicity in phase 1 and 2 trials, but the clinical efficacy of the vaccine remains unknown. Objective: To evaluate the efficacy and safety of a 2-dose regimen of FINLAY-FR-2 (cohort 1) and a 3-dose regimen of FINLAY-FR-2 with FINLAY-FR-1A (cohort 2) in Iranian adults. Design, Setting, and Participants: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial was conducted at 6 cities in cohort 1 and 2 cities in cohort 2. Participants included individuals aged 18 to 80 years without uncontrolled comorbidities, coagulation disorders, pregnancy or breastfeeding, recent immunoglobulin or immunosuppressive therapy, and clinical presentation or laboratory-confirmed COVID-19 on enrollment. The study was conducted from April 26 to September 25, 2021. Interventions: In cohort 1, 2 doses of FINLAY-FR-2 (n = 13 857) or placebo (n = 3462) were administered 28 days apart. In cohort 2, 2 doses of FINLAY-FR-2 plus 1 dose of FINLAY-FR-1A (n = 4340) or 3 placebo doses (n = 1081) were administered 28 days apart. Vaccinations were administered via intramuscular injection. Main Outcomes and Measures: The primary outcome was polymerase chain reaction-confirmed symptomatic COVID-19 infection at least 14 days after vaccination completion. Other outcomes were adverse events and severe COVID-19. Intention-to-treat analysis was performed. Results: In cohort 1 a total 17 319 individuals received 2 doses and in cohort 2 5521 received 3 doses of the vaccine or placebo. Cohort 1 comprised 60.1% men in the vaccine group and 59.1% men in the placebo group; cohort 2 included 59.8% men in the vaccine group and 59.9% in the placebo group. The mean (SD) age was 39.3 (11.9) years in cohort 1 and 39.7 (12.0) years in cohort 2, with no significant difference between the vaccine and placebo groups. The median follow-up time in cohort 1 was 100 (IQR, 96-106) days and, in cohort 2, 142 (137-148) days. In cohort 1, 461 (3.2%) cases of COVID-19 occurred in the vaccine group and 221 (6.1%) in the placebo group (vaccine efficacy: 49.7%; 95% CI, 40.8%-57.3%) vs 75 (1.6%) and 51 (4.3%) in cohort 2 (vaccine efficacy: 64.9%; 95% CI, 49.7%-59.5%). The incidence of serious adverse events was lower than 0.1%, with no vaccine-related deaths. Conclusions and Relevance: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of the efficacy and safety of FINLAY-FR-2 and FINLAY-FR-1A, 2 doses of FINLAY-FR-2 plus the third dose of FINLAY-FR-1A showed acceptable vaccine efficacy against symptomatic COVID-19 as well as COVID-19-related severe infections. Vaccination was generally safe and well tolerated. Therefore, Soberana may have utility as an option for mass vaccination of the population, especially in resource-limited settings, because of its storage condition and affordable price. Trial Registration: isrctn.org Identifier: IRCT20210303050558N1.

Prevalence of Psychological Distress and Posttraumatic Stress Symptoms and Associated Factors in Hospitalized Iranian COVID-19 Patients.

Objectives: To investigate the prevalence of psychiatric symptoms/distress and posttraumatic stress (PTS) and associated factors among inpatients with COVID-19 before discharge from the hospital. Methods: This cross-sectional study was conducted in two teaching referral hospitals in Babol, Iran from July to November 2020. The subjects were inpatients diagnosed with COVID-19 who were clinically stable. Before their discharge from the hospital, the patients completed three questionnaires: demographic data, Brief Symptom Inventory, and Primary Care Post Traumatic Stress Disorder Screen for Diagnostic and Statistical Manual-5. Results: The subjects were 477 inpatients diagnosed with COVID-19 including 40 (8.4%) admitted to intensive care units. Their average age was 60.5±17.9 years; 53.9% were female. Most had symptoms of significant psychological distress (96.0%) and PTS (8.1%) prior to discharge. A higher level of education (-0.18; standard error (SE) = 0.05; p < 0.001) was a negative predictor of psychiatric distress. The admission to intensive care units (0.86; SE = 0.08; p< 0.001) was a positive predictor of psychiatric distress. Conclusions: Most COVID-19 inpatients suffered significant psychiatric distress and PTS symptoms before discharge. Appropriate mental health crisis interventions are recommended for COVID-19 patients during hospitalization.

A Multiple-Center, Retrospective Study of Characteristics and Outcomes of Hospitalized COVID-19 Patients with Cardiovascular Disease in North Iran.

Background: In this retrospective study, we investigated the outcomes and demographic characteristics of COVID-19 patients with and without a history of CVD. Methods: This large retrospective, multicenter study was performed on inpatients with suspected COVID-19 pneumonia who were admitted across four hospitals in Babol, Northern Iran.Demographic data, clinical data, and cycle threshold value (Ct) results of Real Time PCR were obtained. Then, participants were divided into two groups: (1) cases with CVDs, (2) cases without CVDs. Results: A total of 11097 suspected COVID-19 cases with a mean ± SD age of 53 ±25.3 (range: 0 to 99) years were involved in the present study. Out of whom 4599 (41.4%) had a positive RT-PCR result. Of those, 1558 (33.9%) had underlying CVD. Patients with CVD had significantly more co-morbidities such as hypertension, kidney disease, and diabetes. Moreover, 187 (12%) and 281 (9.2%) of patients with and without CVD died, respectively. Also, mortality rate was significantly high among the three groups of Ct value in patients with CVD, with the highest mortality in those with Ct between 10 and 20 (Group A = 19.9%). Conclusions: In summary, our results highlight that CVD is a major risk factor for hospitalization and the severe consequences of COVID-19. Death in CVD group is significantly higher compared to non-CVD. In addition, the results show that age-related diseases can be a serious risk factor for the severe consequences of COVID-19.

The global prevalence of methicillin-resistant Staphylococcus aureus colonization in residents of elderly care centers: a systematic review and meta-analysis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a difficult to treat infection, particularly in residents of elderly care centers (ECCs). Despite the substantial burden of MRSA, an inadequate number of studies have analyzed MRSA prevalence in ECCs. OBJECTIVES: We conducted a worldwide systematic review and meta-analysis on the prevalence and risk factors of MRSA in ECCs. METHODS: We searched MEDLINE/PubMed, EMBASE, Web of Science, and Scopus databases and the gray literature sources for all studies published between January 1980 and December 2022 on the prevalence of MRSA in ECCs. A random-effects model was utilized to estimate pooled prevalence rates at 95% confidence intervals (CI). Moreover, the data were analyzed based on World Health Organization-defined regions, income, and human development index levels. RESULTS: In total, 119 studies, including 164,717 participants from 29 countries, were found eligible for meta-analysis. The pooled global prevalence of MRSA was 14.69% (95% CI 12.39-17.15%; 16,793/164,717). Male gender [prevalence ratio (PR) = 1.55; 95% CI 1.47-1.64], previous MRSA infection (PR = 3.71; 95% CI 3.44-4.01), prior use of antibiotics (PR = 1.97; 95% CI 1.83-2.12), hospitalized within the previous year (PR = 1.32; 95% CI 1.20-1.45), have had any wound (PR = 2.38; 95% CI 2.23-2.55), have used urinary catheter (PR = 2.24; 95% CI 2.06-2.43), have used any medical device (PR = 1.78; 95% CI 1.66-1.91), and those with diabetes (PR = 1.55; CI 1.43-1.67) were more likely to be colonized by MRSA than other patients. CONCLUSION: Screening programs and preventive measures should target MRSA in ECCs due to the high global prevalence rates.

Evaluation of Time-Varying Biomarkers in Mortality Outcome in COVID-19: an Application of Extended Cox Regression Model.

Background: COVID-19 pandemic has created many challenges for clinicians. The monitoring trend for laboratory biomarkers is helpful to provide additional information to determine the role of those in the severity status and death outcome. Objective: This article aimed to evaluate the time-varying biomarkers by LOWESS Plot, check the proportional hazard assumption, and use to extended Cox model if it is violated. Methods: In the retrospective study, we evaluated a total of 1641 samples of confirmed patients with COVID-19 from October until March 2021 and referred them to the central hospital of Ayatollah Rohani Hospital affiliated with Babol University of medical sciences, Iran. We measured four biomarkers AST, LDH, NLR, and lymphocyte in over the hospitalization to find out the influence of those on the rate of death of COVID-19 patients. Results: The standard Cox model suggested that all biomarkers were prognostic factors of death (AST: HR=2.89, P<0.001, Lymphocyte: HR=2.60, P=0.004, LDH: HR=2.60, P=0.006, NLR: HR=1.80, P<0.001). The additional evaluation showed that the PH assumption was not met for the NLR biomarker. NLR biomarkers had a significant time-varying effect, and its effect increase over time (HR(t)=exp (0.234+0.261×log(t)), p=0.001). While the main effect of NLR did not show any significant effect on death outcome (HR=1.26, P=0.097). Conclusion: The reversal of results between the Cox PH model and the extended Cox model provides insight into the value of considering time-varying covariates in the analysis, which can lead to misleading results otherwise.

Serum soluble Fas ligand is a severity and mortality prognostic marker for COVID-19 patients.

Finding cytokine storm initiator factors associated with uncontrolled inflammatory immune response is necessary in COVID-19 patients. The aim was the identification of Fas/Fas Ligand (FasL) role in lung involvement and mortality of COVID-19 patients. In this case-control study, mild (outpatient), moderate (hospitalized), and severe (ICU) COVID-19 patients and healthy subjects were investigated. RNA isolated from PBMCs for cDNA synthesis and expression of mFas/mFasL mRNA was evaluated by RT-PCR. Serum sFas/sFasL protein by ELISA and severity of lung involvement by CT-scan were evaluated. Also, we docked Fas and FasL via Bioinformatics software (in silico) to predict the best-fit Fas/FasL complex and performed molecular dynamics simulation (MDS) in hyponatremia and fever (COVID-19 patients), and healthy conditions. mFasL expression was increased in moderate and severe COVID-19 patients compared to the control group. Moreover, mFas expression showed an inverse correlation with myalgia symptom in COVID-19 patients. Elevation of sFasL protein in serum was associated with reduced lung injury and mortality. Bioinformatics analysis confirmed that blood profile alterations of COVID-19 patients, such as fever and hyponatremia could affect Fas/FasL complex interactions. Our translational findings showed that decreased sFasL is associated with lung involvement; severity and mortality in COVID-19 patients. We think that sFasL is a mediator of neutrophilia and lymphopenia in COVID-19. However, additional investigation is suggested. This is the first report describing that the serum sFasL protein is a severity and mortality prognostic marker for the clinical management of COVID-19 patients.

One-year prevalence and the association between SARS-CoV-2 cycle threshold, comorbidity and outcomes in population of Babol, North of Iran (2020-2021).

Background: The present study aimed to investigate the one-year prevalence of SARS-CoV-2, common comorbidities and demographic information among negative- and positive rRT-PCR in health care workers (HCW), hospitalized and outpatients. Also, the association between SARS-CoV-2 cycle threshold (Ct) and the outcomes of patients were analyzed in Babol, northern Iran. Methods: This large retrospective cross-sectional study was performed between March 2020 and March 2021. The records of 19232 hospitalized, outpatients and HCW suspected to COVID-19 were collected from teaching hospitals in the North of Iran. Results: Out of the 19232 suspected to COVID-19 patients, 7251 (37.7%) had a positive rRT-PCR result; 652 (9%), 4599 (63.4%) and 2000 (27.6%) of those were categorized as HCW, hospitalized and outpatients, respectively. Moreover, between the hospitalized and the outpatient group, 10.2 and 0.8% cases died, whereas no death cases were reported in the HCW. Furthermore, it seems that death rate was significantly different between the three groups of Ct value, the highest mortality in those with Ct between 21 and 30 (group B=7.6%) and the lowest in the group with the highest Ct (between 31 and 40 = 5.5%) (p<0.001). Conclusion: In summary, 37.7% of cases were positive for SARS-CoV-2; of which, 63.4, 27.6 and 9% were hospitalized, outpatients and HCW, respectively. With regard to the mortality rate in hospitalized patients and the significant association with Ct under 20 and 30, it seems that the early detection and the initial quantification of SARS-CoV-2 in the first week of the conflict and therapeutic considerations to reduce the relative load can reduce the mortality rate.

The survival rate of liver transplantation in children: a systematic review and meta-analysis.

Liver transplantation is a life-saving treatment for children who are in liver failure. The survival rate index is used to assess the success rate of liver transplantation. The study aimed to assess the survival rate of liver transplantation in children. We searched 5 international databases in this study, including Medline/PubMed, ProQuest, Scopus, Web of Knowledge, and Google Scholar, for published articles by the end of 2020. Also, meta-regression analysis was performed based on the year of the study, and subgroup analysis was performed according to continents. A total of 425 titles were reviewed. Based on the results, 96 articles were entered in the meta-analysis. Established on the random-effect model, the survival rates of 1, 3, 5, and 10 years of transplantation were 86.62%, 77.74%, 73.95%, and 68.60%, respectively. Also, based on the meta-regression results, there was a relationship between the year of the study and the survival rate, as the study year gets more recent, the survival rate is increased. This study can provide documented and comprehensive evidence which can be the basis of many policies and decisions in various sectors of health development, including evaluating treatment options and health interventions in transplantation.

A Large Retrospective Study of Epidemiological Characteristics of COVID-19 Patients in the North of Iran: Association between SARS-CoV-2 RT-PCR Ct Values with Demographic Data.

Objectives: To avoid worsening from mild, moderate, and severe diseases and to reduce mortality, it is necessary to identify the subpopulation that is more vulnerable to the development of COVID-19 unfavorable consequences. This study aims to investigate the demographic information, prevalence rates of common comorbidities among negative and positive real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) patients, and the association between SARS-CoV-2 cycle threshold (Ct) at hospital admission, demographic data, and outcomes of the patients in a large population in Northern Iran. Methods: This large retrospective cross-sectional study was performed from 7 March to 20 December 2020. Demographic data, including gender, age, underlying diseases, clinical outcomes, and Ct values, were obtained from 8,318 cases suspected of COVID-19, who were admitted to four teaching hospitals affiliated to Babol University of Medical Sciences (MUBABOL), in the north of Iran. Results: Since 7 March 2020, the data were collected from 8,318 cases suspected of COVID-19 (48.5% female and 51.5% male) with a mean age of 53 ± 25.3 years. Among 8,318 suspected COVID-19 patients, 3,250 (39.1%) had a positive rRT-PCR result; 1,632 (50.2%) patients were male and 335 (10.3%) patients died during their hospital stay. The distribution of positive rRT-PCR revealed that most patients (464 (75.7%)) had a Ct between 21 and 30 (Group B). Conclusion: Elderly patients, lower Ct, patients having at least one comorbidity, and male cases were significantly associated with increased risk for COVID-19-related mortality. Moreover, mortality was significantly higher in patients with diabetes, kidney disease, and respiratory disease.

Prognostic accuracy of inflammatory markers in predicting risk of ICU admission for COVID-19: application of time-dependent receiver operating characteristic curves.

OBJECTIVE: Intensive care unit (ICU) admission occurs at different times during hospitalization among patients with COVID-19. We aimed to evaluate the time-dependent receive operating characteristic (ROC) curve and area under the ROC curve, AUC(t), and accuracy of baseline levels of inflammatory markers C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) in predicting time to an ICU admission event in patients with severe COVID-19 infection. METHODS: In this observational study, we evaluated 724 patients with confirmed severe COVID-19 referred to Ayatollah Rohani Hospital, affiliated with Babol University of Medical Sciences, Iran. RESULTS: The AUC(t) of CRP and NLR reached 0.741 (95% confidence interval [CI]: 0.661-0.820) and 0.690 (95% CI: 0.607-0.772), respectively, in the first 3 days after hospital admission. The optimal cutoff values of CRP and NLR for stratification of ICU admission outcomes in patients with severe COVID-19 were 78 mg/L and 5.13, respectively. The risk of ICU admission was significantly greater for patients with these cutoff values (CRP hazard ratio = 2.98; 95% CI: 1.58-5.62; NLR hazard ratio = 2.90; 95% CI: 1.45-5.77). CONCLUSIONS: Using time-dependent ROC curves, CRP and NLR values at hospital admission were important predictors of ICU admission. This approach is more efficient than using standard ROC curves.

The association of decreased HLA-G+ immune cell frequencies with critical COVID-19 patients.

INTRODUCTION: COVID-19 (coronavirus disease-2019) is an infectious disease caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Immune dysregulation causes inflammation and massive production of inflammatory mediators that worsen the patients' status. Here, regulatory immune cells may ameliorate inflammation and improve the severity of the disease. MATERIALS AND METHODS: A total of 76 participants were enrolled in this study and divided into 3 groups as follows: patients with moderate/severe COVID-19 (n = 25), patients with critical COVID-19 (n = 26), and healthy controls (n = 25). After blood collection, peripheral blood mononuclear cells (PBMCs) were isolated and stained by FITC-conjugated anti-CD4 monoclonal antibodies (mABs), PE-conjugated anti-HLA-G mABs, PerCPCy5.5-conjugated anti-CD14 mABs, and APC-conjugated anti-CD8 mABs. RESULTS: Critical COVID-19 patients had a significantly lower frequency of CD4+ HLA-G+ T lymphocytes compared with moderate/severe COVID-19 patients (p value < 0.001; SMD, -1.27; 95% CI [-1.86, -0.66]) and healthy controls (p value < 0.05; SMD, -0.69; 95% CI [-1.25, -0.12]). Critical COVID-19 patients had a significantly lower frequency of CD14+ HLA-G+ monocytes compared with moderate/severe COVID-19 patients (p value < 0.001; SMD, -2.09; 95% CI [-2.77, -1.41]) and healthy controls (p value < 0.05; SMD, -0.83; 95% CI [-1.40, -0.25]). However, there was no difference between the groups regarding the frequency of CD8+ HLA-G+ T lymphocytes. CONCLUSION: The increased amount of immunomodulatory HLA-G+ cells may reduce the severity of the disease in moderate/severe COVID-19 patients compared with critical COVID-19 patients.

Optimal cut points of N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) in patients with COVID-19.

BACKGROUND: COVID19 patients may suffer from multiple cardiovascular complications. Recently, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) was a potentially independent risk factor for COVID-19 in-hospital death. The present study aimed to find new optimal cut points for NT-proBNP across censored survival failure time outcomes in hospitalized COVID-19 patients. RESULTS: This cohort study was conducted on 272 patients with COVID-19 whose initial records were recorded from March 2020 to July 2020. Demographic characteristics, clinical examinations, and laboratory measurements were collected at the beginning of the admission registered in the patient record system located in the hospital. We used the maximally selected rank statistics to determine the optimal cut points for NT-proBNP (the most significant split based on the standardized log-rank test). Survival time was defined as the days from hospital admission to discharge day. In this cohort study, two optimal cut points for NT-proBNP were 331 (pg/mL) and 11,126 (pg/mL) based on a survival model. The adjusted HR of NT-proBNP for in-hospital death was 3.41 (95% CI: 1.22-9.51, P = 0.02) for medium against low category, and 3.84 (95% CI: 1.30-11.57, P = 0.01) for high in comparison with low group. CONCLUSIONS: We reported a dramatically increased concentration of NT-proBNP among COVID-19 patients without heart failure in both severe and non-severe cases. Moreover, our study showed that a high level of NT-proBNP was highly associated with the prolonged survival time of patients with COVID-19. NT-proBNP is a strong prognostic indicator of in-hospital death in the second week of admission.

Ten-year data analysis of digestive system malignancies in Babol, North of Iran: 2008-2017.

BACKGROUND: Unlike some regions of the world where digestive system cancers are not considered as important health problems, these neoplasms are among the most common malignancies in the northern region of Iran. METHODS: This observational analytical study was carried out based on data collected by the Cancer Registration Center affiliated to the Vice Chancellery for Health of Babol University of Medical Sciences, North of Iran, during 2008-2017. Crude incidence rate (CR), and age-standardized incidence rate (ASR) have been calculated for different GI cancers, based on the primary involved site; and have been compared in different years, patients' age, gender and place of residence. RESULTS: Totally, 4332 records were related to digestive system cancers. Mean age of patients was 63.48±14.73 years; men (2743; 63.3%) were more affected than women (1589; 36.7%) (p<0.001). The most incident malignancies of digestive system were from stomach, colorectal and esophagus in men; and colorectal, stomach and esophagus in women, respectively. These three cancers accounted for 3725 (85.98%) of total GI malignancies. The mean age of patients in various types of GI cancers was statistically different (p<0.001). Age- standardized incidence rate showed different values in different years; from 521.40 (95% CI: 462.79-580.00) in year 2016 to 1834.33 (95% CI: 1637.36-2031.29) in year 2008. CONCLUSION: Gastric, esophageal and colorectal cancers were the most prevalent digestive system malignancies in Babol, North of Iran, and accounted for about 86% of all GI tract cancers. A considerable variation has been found in incident gastrointestinal cancers in different years.

Neonatal Outcomes in Pregnant Women Infected with COVID-19 in Babol, North of Iran: A Retrospective Study with Short-Term Follow-Up.

During the coronavirus disease 2019 (COVID-19) pandemic, the number of pregnant women and neonates suffering from COVID-19 increased. However, there is a lack of evidence on clinical characteristics and neonatal outcomes in pregnant women with COVID-19. We evaluated short-term outcomes (4 weeks postdischarge) and symptoms in neonates born to mothers infected with COVID-19. In this retrospective cohort study, we included all neonates born to pregnant women with COVID-19 admitted to Ayatollah Rohani Hospital, Babol, Iran, from February 10 to May 20, 2020. Clinical features, treatments, and neonatal outcomes were measured. Eight neonates were included in the current study. The mean gestational age and birth weight of newborns were 37 ± 3.19 weeks (30₊6-40) and 3077.50 ± 697.64 gr (1720-3900), respectively. Apgar score of the first and fifth minutes in all neonates was ≥8 and ≥9 out of 10, respectively. The most clinical presentations in symptomatic neonates were respiratory distress, tachypnea, vomiting, and feeding intolerance. This manifestation and high levels of serum C-reactive protein (CRP) in three infants are common in neonatal sepsis. The blood culture in all of them was negative. They have been successfully treated with our standard treatment. Our pregnant women showed a pattern of clinical characteristics and laboratory results similar to those described for nonpregnant COVID-19 infection. This study found no evidence of intrauterine or peripartum transmission of COVID-19 from mother to her child. Furthermore, the long-term outcomes of neonates need more study.

C-Reactive Protein as a Prognostic Indicator in COVID-19 Patients.

While some biomolecules have been explored to identify potential biomarkers for the prognosis of COVID-19 patients, there is no reliable prognostic indicator of the disease progression and severity. We aimed to evaluate the ability of the C-reactive protein (CRP) to predict COVID-19 infection outcome. This retrospective study was conducted on 429 patients diagnosed with COVID-19 between March 30, 2020, and April 30, 2020. The study population was divided into severe (n = 175) and nonsevere cases (n = 254). Data on demographic characteristics, clinical features, and laboratory findings on admission were collected. The proportion of patients with increased CRP levels was significantly higher in severe cases than in nonsevere patients. Analysis of the receiver operating characteristic (ROC) curve found that CRP could be used as an independent factor in predicting the severity of COVID-19. Also, patients with CRP >64.75 mg/L were more likely to have severe complications. In conclusion, CRP serum levels can predict the severity and progression of illness in patients with COVID-19.

Linkage of Lambda Interferons in Protection Against Severe COVID-19.

The most recently discovered interferon (IFN) family, type III IFNs or lambda IFNs (IFN-λs) are caused by viral infection and act in mucosal barriers, such as the respiratory tract. In this study, we assessed the serum levels of IFN-λs in new coronavirus disease-2019 (COVID-19) patients. Sixty-four COVID-19 patients were enrolled in this study. All cases were divided into the intensive care unit (ICU) and non-ICU groups according to their symptoms. Fourteen samples of healthy controls were also included. The serum levels of IFN-λ1 and IFN-λ2 were analyzed by specific enzyme-linked immunosorbent assay (ELISA) kits. The concentrations of IFN-λ1 and IFN-λ2 induced in the serum of non-ICU patients (836.7 ± 284.6 and 798.8 ± 301.5 pg/mL, respectively) were higher than found in ICU patients (81.57 ± 34.25 and 48.32 ± 28.13 pg/mL, respectively) (P = 0.004 and P = 0.006, respectively) and healthy controls (85.57 ± 33.63 and 65.82 ± 21.26 pg/mL, respectively) (P = 0.03 and P = 0.04, respectively). Meanwhile, no significant differences were found in the concentration of both cytokines between the ICU patients and healthy controls. We conclude that higher levels of IFN-λs are associated with decreased clinical manifestations in COVID-19 patients. These cytokines could be a promising therapeutic agent to avoid the overwhelming consequences of COVID-19.

Reduced frequency of T helper 17 and T helper 1 cells and their association with critical coronavirus disease 2019.

There is very little knowledge about the immune responses, particularly cellular immunity to coronavirus disease 2019 (COVID-19). The main objective of this study was to evaluate the frequency of T helper (Th) cell subtypes, including Th1, Th17, and Treg cells, in moderate-to-severe and critical COVID-19 patients compared to healthy controls. Twenty-nine moderate-to-severe and 13 critical patients confirmed for COVID-19, and 15 healthy subjects were included in this study. Interferon-γ (IFN-γ)-producing Th1 and interleukin-17A-producing Th17 and Treg cells in peripheral blood were measured with flow cytometry. The frequency of Th1 and Th17 was significantly decreased in critical patients compared to healthy subjects (aMD: -2.76 and - 2.34) and moderate-to-severe patients (aMD: -1.89 and - 1.89), respectively (p < 0.05). Differences were not significant between moderate-to-severe patients and healthy subjects for both Th1 (p = 0.358) and Th17 (p = 0.535), respectively. In contrast, significant difference was not observed between study subjects regarding the frequency of Treg cells. Patients with critical COVID-19 had a markedly lower Th1/Treg and Th17/Treg ratios compared with the controls and moderate-to-severe cases. Our study showed a dysregulated balance of Th1 and Th17 cells and its relation to the severity of COVID-19.