Objective: The impact of thyroid hormones within normal range on muscle mass remains unknown. We examined the association between new onset of low muscle mass (LMM) and thyroid hormones among euthyroid men and women with three different definitions of LMM in prospective cohort study. Methods: We performed a cohort study of 198,069 Korean adults (mean age of 39.2 years), free of LMM at baseline, who participated in a repeated screening examination and were followed-up annually or biennially for up to 6.3 years. Thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxin (FT4) levels were measured by an electrochemiluminescent immunoassay. Muscle mass was assessed using a bioelectrical impedance analyzer. LMM was defined as the appendicular skeletal muscle mass (ASM) by body weight (ASM/weight, LMM-W), height squared (ASM/height2, LMM-H) and BMI (ASM/BMI, LMM-B) of one standard deviation below the sex-specific mean for young reference group. Results: During a median follow-up of 3.1 years (interquartile range, 2.0-4.1 years), new-onset LMM-W, LMM-H, and LMM-B occurred in 17,856 (incident rate, 27.8 per 1,000 person-years), 8,307 (incident rate, 13.4 per 1,000 person-years), and 13,990 participants (incident rate, 24.5 per 1,000 person-years) in each. In euthyroid men, FT4 was inversely and FT3 positively associated with incident LMM-W in a dose-response manner. TSH and FT4 had inverse dose-response relationship with incident LMM-B. Incident LMM-H of euthyroid men has no apparent associations with any thyroid hormones. Euthyroid women had no dose-response relationship between thyroid hormones and any definition of LMM. Conclusions: Among euthyroid men, FT4 had inverse dose-response association with new onset of LMM defined with weight (LMM-W) and BMI (LMM-B). Height squared LMM (LMM-H) had no apparent relationship with any thyroid hormones. Euthyroid women had no dose-responsive association between thyroid hormones and incident LMM. Key words: appendicular skeletal muscle mass, low muscle mass, thyroid hormones, Cohort study

Background: Whilst core curricula in neurology are nationally standardised, in real-world clinical practice, different approaches may be taken by individual consultants. In this study, we investigated: (1) variance in diagnostic and investigative practice, using a case-based analysis of inter-rater agreement; (2) potential importance of any differences in terms of patient care; (3) relationships between clinical experience, diagnostic certainty, diagnostic peer-agreement and investigative approach; (4) development of novel individualised metrics to facilitate appraisal. Methods: Four neurologists with 0-23 years’ experience at consultant level provided diagnosis, certainty (10-point Likert scale), and investigative approach for 200 consecutive general neurology outpatients seen by a newly qualified consultant. Diagnostic agreement was evaluated by percentage agreement. The potential importance of any diagnostic differences was assigned a score by the evaluating neurologist (6-point Likert scale). Associations between diagnostic agreement, certainty and investigative approach were assessed using Spearman correlation, logistic and ordinal regression, and reported as individualiszd metrics for each rater. Results: Diagnostic peer-agreement was 4/4, 3/4, 2/4 and 1/4 in 50%, 28%, 20% and 3% of cases, respectively. In 17%, differences in patient management were judged potentially important. Investigation rates were 42-73%. Mean diagnostic certainty ranged between 6.2/10 (SD 2.1) to 7.7/10 (SD 2.2) between least and most experienced consultants. Greater diagnostic certainty was associated with greater diagnostic peer-agreement (individual-rater regression coefficients 0.30-0.51, p<0.01) and lower odds of arranging investigations (individual-rater odds ratios 0.58-0.78, p<0.01). Conclusions: Variance in diagnostic and investigative practice between consultant neurologists exits and may result in differing management. Mean diagnostic certainty increased numerically with experience and was statistically associated with greater diagnostic peer-agreement and lower investigation rates. Metrics reflecting concordance with peers, and relationships to diagnostic confidence, could inform reflective practice.

Introduction. Locking the humanity in their homes, COVID-19 forced people to use the technology at hand to keep informed about the outbreak and to keep close to their loved ones. During this time, even if physical health is theoretically unaffected, keeping calm and sane can be challenging. The aim of this research was to evaluate whether exposure to COVID-19 information available in the digital space has a different impact on the mental condition of Romanian medical staff, compared to general population, particularly searching for depression and anxiety symptoms. Materials and methods. An online survey was conducted from April 6 to 16, 2020 within the Romanian users of Social Media platforms. The questionnaire assessed depression with the WHO-Five Well-Being Index, anxiety with the Generalized Anxiety Disorder Scale and Social Media exposure by asking how often the respondents saw COVID-19 related information on the most popular Social Media channels in Romania. Information about: gender, age, educational level, occupation, area of living and risk category was also collected. The risk categories were defined as no risk, medium risk, and medical staff. Results. Almost 90% of the 402 participants received daily through at least one Social Media channel information related to the COVID-19 outbreak. The Social Media Exposure significantly associated with the risk group only for Facebook and LinkedIn. However, exposure to information regarding COVID-19 was neither associated with anxiety nor depression. No significant association was identified neither between age class and self-assessed anxiety nor self-assessed depression. The self-assessment of depression was significantly more frequent as compared to self-assessment of anxiety. Conclusion. The results of this research are opposite to most of the already published literature. Depression and anxiety could not be correlated with the context of lockdown and excessive COVID-19-related information.

Aim: To evaluate risk factors associated with nocturia in patients with obstructive sleep apnea syndrome (OSAS). Materials and Methods: Patients diagnosed with OSAS by polysomnography (PSG) and over eighteen years old evaluated retrospectively between January and December 2019. The number of nocturia episodes was assessed in the 3-day bladder diary. We analyzed age, gender, body mass index (BMI), apnea-hypopnea index (AHI) scores and severity, hypertension, diabetes mellitus, smoking, heart diseases in all patients. Results: A total of 124 patients with the mean age of 49.9±11.6 years (range 25–81 years) was included in the study. Ninety-two (75.8%) patients had nocturia. The mean nocturia episode of patients with nocturia was 2.41.3. To determine the factors that affect the risk of nocturia, logistic regression analysis was performed. The results revealed that patient age and BMI were found as the most effective risk factors determining nocturia (p<0.05). The odds of patient age were 1.06 (95% CI 1.01-1.11, p=0.010) times higher for patients with nocturia. Every 1 unit increase in BMI increased the risk of nocturia by 1.12. 48 patients with nocturia underwent continuous positive airway pressure (CPAP) therapy or surgical treatment. The mean nocturia epi¬sodes of these patients were 2.3±1.4 before treatment and were 1.7±2.2 after treatment. There was a significant decrease in terms of nocturia episodes (p=0.032). Although there was a significant increase in the total daily urine volume after treatment, there was a statistically decrease in total night-time urine volume at night (p=0.016 and p=0.024, respectively). Conclusion Age and BMI were risk factors associated with nocturia in patients with OSAS.

BACKGROUND Primary glomerulonephritis (PGN) has a significant part in non-diabetic kidney disease (NDKD) in diabetes mellitus (DM) patients. In our study, we compared the clinical, demographic, and laboratory features of patients with biopsy-proven diabetic nephropathy (DN) and PGN with type 2 DM METHODS In our retrospective study, type 2 DM patients who underwent kidney biopsy between 2011-2019 were included. Demographic, clinical, and laboratory characteristics of DN and PGN patients were compared. RESULTS Seventy patients with a mean age of 55.7 ± 9.4 and 43 (61.4%) males were included. 38 (54.3%) of the patients had DN, and 32 (45.7%) had PGN. In the PGN, membranous GN (20, 62.5%) was most common. In DN patients, diabetes duration was longer; complications such as retinopathy, neuropathy, hypertension, coronary artery disease, heart failure were more frequent. At the time of renal biopsy, blood sugar, HbA1C, blood pressure, serum albumin, and proteinuria values were similar in 2 groups. The pathological damage findings of kidney biopsy in DN patients were more severe. In the first year after kidney biopsy decrease in eGFR was higher in DN patients, whereas eGFR did not change in PGN patients. CONCLUSION In a diabetic patient, fasting blood sugar, hbA1C, serum albumin, and proteinuria did not differ in the differential diagnosis of DN and PGN, whereas complications of DM (retinopathy, neuropathy, hypertension, coronary artery disease) were more characteristic in differentiation. Detection of PGN in a diabetic patient is crucial for the success of the treatment, according to DN.

Background: Open living donor hepatectomy (OLDH) is a highly painful procedure. Advanced strategies for enhancing perioperative analgesia and accelerating recovery are needed for patients undergoing OLDH. This study evaluated the effects of intravenous infusion of dexmedetomidine (DEX) during OLDH on postoperative analgesia and recovery. Methods: This prospective, randomized, double-blinded, and placebo-controlled study included 34 patients randomized to a control group (group C) and a DEX group (group D). Utilization of intravenous patient-controlled analgesia (IV-PCA) pump, pain intensity, and postoperative recovery variables were recorded. Moreover, intraoperative anesthetic consumption, hemodynamic parameters, and fluid status were also recorded. Results: During the first 24 hours after surgery, patients in group D had a lower pain intensity. The cumulative numbers of IV-PCA pump presses and fentanyl consumption within 24 and 48 hours postoperatively in group C were significantly higher than in group D. The time to first IV-PCA attempt was prolonged in group D. In addition, faster flatus passage was observed in group D. Intraoperatively, fewer anesthetic agents were required in group D. Less fluctuation in hemodynamics and reduced bleeding were also found in group D. Conclusions: The present study revealed that the addition of intravenous infusion of DEX during OLDH provided several benefits in relieving postoperative pain and promoting recovery. Therefore, we concluded that intraoperative DEX infusion may play an important role in enhancing recovery of patients undergoing OLDH.

Abstract Background Differentiating viral from bacterial acute respiratory infections (ARIs) remains challenging, due to the non-specific clinical manifestations. The COVID-19 pandemic is putting extraordinary strain on healthcare resources. To date, molecular testing is available but has a long turnaround time and therefore cannot provide results at the point-of-care (POC) thereby exposing COVID-19/Non-COVID-19 patients to each other while awaiting diagnosis. Methods This observational study prospectively evaluated the utility of a triage strategy including FebriDx, a POC fingerstick blood test that differentiates viral from bacterial ARIs through simultaneous detection of Myxovirus-resistance protein A (MxA) and C-reactive protein (CRP), in rapidly determining viral cases requiring immediate isolation and confirmatory molecular testing, from non-infectious patients or bacterial infections requiring antibiotics. Results 75 consecutive patients were screened, 48 eligible cases were tested with FebriDx, 36 were confirmed viral infection and 35/36 had COVID-19. 31/35 COVID-19 cases tested positive for SARS-CoV-2 via rRT-PCR and (4/35) had a clinical diagnosis of probable COVID-19 based on symptoms, epidemiological history, and chest imaging (PPV 100% (35/35)). 13 cases were FebriDx viral negative and rRT-PCR was also negative. In one case, it was not possible to determine the exact cause of infection, although a viral infection could not be excluded. Including this patient, FebriDx NPV was 92.3% (12/13), exceeding the NPV of rRT-PCR a 68.3% (13/19), and diagnostic sensitivity was conservatively calculated at 97% (35/36) compared to 82.9% (29/35) for initial rRT-PCR. The diagnostic specificity of both FebriDx and rRT-PCR was 100%. Conclusions: FebriDx could be deployed as part of a reliable triage strategy for identifying possible COVID-19 patients with symptomatic ARI in the COVID-19 pandemic. Key words: Pandemic; COVID-19; SARS-CoV-2; pneumonia; viral; point of care; infection

  Changes of serum IL-10, IL-1β, IL-6, MCP-1, TNF-α, IP-10 and IL-4 in COVID-19 patientsQingqing Lu1，Zhenhua Zhu2，Chaochao Tan3, Hui Zhou2，Yan Hu2，Ge Shen4，Pan Zhu4，Gang Yang4，Xiaobing Xie2△（1. Hunan University of Chinese Medicine, Changsha Hunan  Postal Code: 410208； 2. The First Hospital of Hunan University of Chinese Medicine, Changsha Hunan  Postal Code: 410007； 3. Hunan Provincial People’s Hospital, Changsha Hunan  Postal Code: 410005; 4.Loudi Center for Disease Control and Prevention，Loudi Hunan Postal Code: 417000）△ Correspondence author, E-mail：[email protected] Abstract: Background and purpose: Studies have shown that some cytokines in COVID-19 patients were elevated. This study aims to assess whether IL-10, IL-1β, IL-6, MCP-1, TNF-α, IP-10 and IL-4 serve as potential diagnostic biomarkers of COVID-19. Methods: The above serum cytokines in COVID-19 patients and non COVID-19 patients were detected by ELISA, SARS-CoV-2 IgM and IgG were detected by chemiluminescence method. Data were analyzed by independent-samples Mann-Whitney U-test, Levene T-test, T’-test or Spearman Correlation test as appropriate. Results: Serum levels of IL-10, IL-1β, MCP-1, TNF-α and IL-4 in COVID-19 patients were significantly higher than those in non-COVID-19 patients, while IL-6 were only significantly higher than in healthy people, IP-10 were significantly lower than in other diseases patients. AUCs of COVID-19 diagnosed by IL-10, IL-1β, IL-6, MCP-1, TNF-α, IP-10 and IL-4 were 0.735, 0.775, 0.595, 0.821, 0.848, 0.387 and 0.682, respectively. In COVID-19 patients’ serum, the levels of IL-10 and MCP-1 of male had noticeably higher than those of female, and all cytokines were significantly positively correlated with age, IL-1β and IL-4 were significantly negatively correlated with IgM, while IL-10, IL-1β, IL-6, TNF-α and IP-10 were significantly negatively correlated with IgG. IL-10 on 43-56 days were significantly lower than at 29-42 days, TNF-α at 15-42 days were significantly higher than at 0-14 days, IP-10 at 0-14 days were the highest, IL-4 at 29-42 days were significant higher than on 0-14 days. Conclusions: The detection of IL-10, IL-1 β, IL-6, MCP-1, TNF-α and IL-4 would assist the clinical study of COVID-19, and targeted inhibition of IP-10 in the early stage may be the key to future treatment of COVID-19.Keywords: cytokine; COVID-19; clinical value; course of disease;Q: What’s already known about this topic?A: Symptoms of COVID-19 patients, infection pathways of SARS-CoV-2, and the COVID-19 patients have higher cytokines.Q: What does this article add?A: What kinds of cytokines in COVID-19 patients were increased, whether they were potential diagnostic biomarkers of COVID-19 and offer prognostic insight upon initial presentation to help guide treatment, their relationship with age, gender，antibody concentration and course of the disease were also discussed.IntroductionNovel coronavirus (SARS-CoV-2) has high infectivity[1,2], the main methods for diagnosing it were nucleic acid detection and serological antibody detection [3]. Inflammatory factors are often increased in severe and critical patients [4], including interleukin (IL), colony-stimulating factor (CSF), chemokine, interferon (IFN), tumor necrosis factor (TNF), chemokine and growth factor (GF) [5]. Most of cytokines are produced by T lymphocytes, fibroblasts and mononuclear macrophages, and can in turn act on these cells, for example, IL-1β can activate vascular endothelial cells and lymphocytes, IL-6 can activate T lymphocytes and induce macrophage activation, MCP-1 can activate mononuclear macrophages, TNF-α can activate fibroblasts, IP-10 can recruit neutrophils and promote the secretion of multiple cytokines, thus, these cytokines could promote each other and jointly mediate inflammation; however, IL-10 can inhibit the inflammatory process. The early symptoms of Coronavirus disease 19 (COVID-19) patients were fever, dry cough and fatigue [6], but severe patients may develop even multiple organ failure [4], which may be related to the levels of cytokines [7-9]. In addition, overactivation of T cells was found in COVID-19 patients [10]. The production of cytokines is related to the individual immune function, so we assumed that the severity of COVID-19 can be predicted according to their levels. Our study aims to reveal the changes of serum levels in IL-10, IL-1β, IL-6, monocyte chemoattractant protein (MCP)-1, TNF-α, interferon-inducible protein (IP)-10 and IL-4 in COVID-19 patients, and assist clinical treatment of COVID-19. Materials and methods2.1 Specimens77 serum samples from male patients and 43 serum samples from female patients were collected from 48 COVID-19 patients in Loudi Center for Disease Control and Prevention, some of who were repeatedly sampled two to four times, and their ages ranged from 8 to 78 years old. The demographic and characteristics of the study participants have been showed in Table 1. Throat swab samples of these patients, including 2 dead patients and 17 asymptomatic infected patients, were detected by real-time PCR (test kits were purchased from Hunan Shengxiang Biotechnology Company), and the positive results of SARs-CoV-2 nucleic acid were confirmed. The COVID-19 is diagnosed according COVID-19 diagnosis and treatment guideline (Seventh Edition)[4]. Brief description is as follows: with epidemiological history and in line with the relevant clinical manifestations, as well as with new coronavirus etiology or serological evidence can be diagnosed. According COVID-19 diagnosis and treatment guideline (Seventh Edition), most of COVID-19 patients only received general treatment, including bed rest, timely effective oxygen therapy and antiviral treatment. Severe and critical patients generally need to be transferred to ICU for treatment including above treatment and timely organ function support treatment. The patients in this study received antiviral drugs such as interferon alpha, ritonavir, ribavirin and some traditional Chinese medicine, such as Qingfei Paidu decoction. In addition, we also collected the serum of non COVID-19 patients from The First Hospital of Hunan University of Chinese medicine. Among these patients, 53 patients suffered from the malignant tumor, hematological disease, rheumatic immune system disease and other diseases that increase the level of inflammatory factors, and 35 healthy people. All patients and their families had informed consent to the inclusion of the study and authorized to use their test results for the study. 2.2 Methods2.2.1 cytokine detectionThe 120 serum contents of IL-10, IL-1β, IL-6, MCP-1, TNF-α, IP-10 and IL-4 were detected by ELISA reader at 450 nm, the test kits and their standard were purchased from Beijing Human Diagnostics Company (double-antibody sandwich ELISA ), TECAN 200-8 were purchased from Shanghai TECAN Trading Company. Sensitivity: the minimal detectable concentrations for they were 0.0225, 0.0355, 0.0600, 0.0655, 0.0386, 0.0102 and 0.0180 pg/mL; specificity: when 50 ng / ml (100 ng / ml for IL-4) was used for specificity test, they did not react with common interfering cytokines and proteins. For statistical analysis: count the results which lower than the minimum detectable concentrations as half of the minimum detectable concentrations. A hole was added as a blank control. The samples whose OD value exceeds the linear range should be diluted before detection. The experiment was conducted in strict accordance with the instructions in the kit. All the reagents had their own standard. Both the repeatability (coefficient of variation between plates and within plates were less than 10%) and specificity were good. The kit has fixed value quality control and negative and positive control to ensure the accuracy of test results.2.2.2 SAS-COV-2 IgM and IgG antibody detectionThe serum samples of all cases were venous blood of 12 hours fasting without hemolysis or hyperlipidemia. The serum was obtained by centrifugation at 4000 RPM for 10 minutes, the contents of IgG and IgM in these serums were detected by magnetic particle chemiluminescence method, the SAS-COV-2 IgM and IgG test kits were purchased from Shenzhen Yahuilong Biotechnology Company, and 10.00AU/mL was taken as the positive judgment value, patients with results of 8-10AU/mL were retested 3-5 days later. Sensitivity and specificity were 98.5% and 100% when the cut-off value was 10.06 AU/mL; the HOOK effect would not appear when the antibody concentration was lower than 8000AU/mL. The experiment was carried out in strict accordance with the instructions in the kits. All the kits were provided with calibration information and quality control materials, and the repeatability (intra assay coefficient of variation was no more than 8%, and the inter assay coefficient of variation was no more than 15%) and specificity was good.2.2.3 Statistical analysisAll datas were processed by IBM SPSS statistic 21 and were drawn by GraphPad Prism 7. According to the characteristics of data distribution, independent-samples Mann-Whitney U-test was utilized to compare the serum levels of IL-10, IL-1 β, IL-6, MCP-1, TNF - α, IP-10 and IL-4 in different groups (COVID-19 patients, other diseases patients and healthy people) and course; Independent-samples Levene T-test or T’-test was utilized to compare COVID-19 patients in different genders; Spearman Correlation test was utilized to analyze the correlation between the levels of cytokines with ages, IgG and IgM. The difference was statistically significant with bilateral P-value < 0.05.3 Results3.1 Detection of IL-10, IL-1β, IL-6, MCP-1, TNF-α, IP-10 and IL-4 in serum samples of COVID-19 patients, other diseases patients and healthy people by ELISAAfter statistical analysis, as Figure 1 and Table 2 shows, it was found that the levels of IL-10, IL-1β, IL-6, MCP-1, TNF-α and IL-4 in the serum of COVID-19 patients were significantly higher than that in the serum of healthy people (PIL-10=0.000, PIL-1β==0.000,  PIL-6=0.000, PMCP-1=0.000, PTNF-α=0.000, PIL-4=0.002, respectively), while the serum levels of IP-10 between COVID-19 patients and healthy people were not significant different (P = 0.310); the serum levels of IL-10, IL-1β, MCP-1, TNF-α and IL-4 in COVID-19 patients were significantly higher than those in other diseases patients ( PIL-10=0.000, PIL-1β,=0.000, PMCP-1=0.000, PTNF-α=0.000, PIL-4=0.000, respectively), IP-10 in COVID-19 patients were significantly lower than those in other diseases patients (P=0.004), while the serum levels of IL-6 between COVID-19 patients and other diseases patients were not significant different (P = 0.078). In addition, IL-10, IL-6, MCP-1, and IL-4 in other diseases patients were significantly higher than those in healthy people (PIL-10=0.000, PIL-6,=0.000, PMCP-1=0.023, PIL-4=0.002, respectively), while the serum levels of IL-1β, TNF-α and IP-10 between COVID-19 patients and other diseases patients were not significant different (PIL-1β=0.453, PTNF-α=0.147, PIP-10=0.073, respectively).3.2 Diagnostic efficacy of detection of the IL-10, IL-1β, IL-6, MCP-1, TNF-α, IP-10 and IL-4 on COVID-19 by ELISA The abilities of prediction of IL-10, IL-1β, IL-6, MCP-1, TNF-α, IP-10 and IL-4 on COVID-19 were assessed by ROC curve, as Figure 2 shows, the COVID-19 patients were positive, and the other diseases patients and healthy people were negative, and select the tangent point with the largest Youden’s index as the cut-off value. When choose 2.621, 4.898, 1.730, 19.948, 0.110, 7.083 and 4.015 pg/mL respectively as their cut-off value, AUCs of COVID-19 diagnose by IL-10, IL-1β, IL-6, MCP-1, TNF-α, IP-10 and IL-4 were 0.735, 0.775, 0.595, 0.821, 0.848, 0.387 and 0.682, respectively, which means that IL-10, IL-1β, IL-6, MCP-1, TNF-α and IL-4 have potential diagnostic value for COVID-19, and TNF-α and MCP-1 have the best predictive effect. The sensitivities of diagnosis of TNF-α, MCP-1, IL-1β, IL-10, IL-4 and IL-6 were 81.2%, 84.6%, 63.2 %, 65.8 %, 67.5% and 72.6%, and the specificities of they were 93.0%, 69.8%, 95.3%, 89.5%, 100% and 64.0%; the sensitivity (parallel experiment) and specificity (series experiment) of combined diagnosis of TNF-α and MCP-1 were 97.1% and 97.9%, respectively. 3.3 The relationship between serum levels of IL-10, IL-1β, IL-6, MCP-1, TNF-α, IP-10 and IL-4 with gender and age in COVID-19 patients According to the statistical analysis, as Table 3 shows, it was found that the serum levels of IL-10 and MCP-1 in male COVID-19 patients were markebly higher than those in female patients (PIL-10=0.038, PMCP-1=0.031, respectively), while the differences of serum levels of IL-1β, IL-6, IP-10, TNF-α and IL-4 between male COVID-19 patients and female patients were not markebly significant (PIL-1β=0.611, PIL-6=0.354, PTNF-α=0.152, PIP-10=0.208, PIL-4=0.225, respectively).Ages of the owners of 7 serum samples were not clearly, the relationship between levels of cytokines and age in the other 113 serum samples of COVID-19 patients were show in Figure 3. According to the statistical analysis, the levels of all cytokines in COVID-19 patients were significant positively correlated with their ages (rIL-10=0.403, PIL-10=0.000; rIL-1β=0.200, PIL-1β=0.034; rIL-6=0.320, PIL-6=0.001; rMCP-1=0.431, PMCP-1=0.000; rTNF-α=0.246, PTNF-α=0.009; rIP-10=0.397, PIP-10=0.000; rIL-4=0.283, PIL-4=0.002, respectively).3.4 The relationship between serum levels of IL-10, IL-1β, IL-6, MCP-1, TNF-α, IP-10 and IL-4 and SAS-COV-2 IgM and IgG SARS-Cov-2 IgM and IgG concentrations in COVID-19 patientsThe correlation analysis of levels of IL-10, IL-1β, IL-6, MCP-1, TNF-α, IP-10, IL-4 and antibody concentration in serum samples of COVID-19 patients were shown in Figure 4. It was found that the levels of IL-1β and IL-4 in COVID-19 patients were negatively correlated with the level of IgM (rIL-1β=-0.206, PIL-1β=0.024; rIL-4=-0.208, PIL-4=0.023, respectively), while there were no significant correlation between the levels of IL-10, IL-6, MCP-1, TNF-α and IP-10 and the concentrations of IgM(PIL-10=0.416, PIL-6=0.056, PMCP-1=0.675, PTNF-α=0.301, PIP-10=0.622, respectively); the levels of IL-10, IL-1β, IL-6, TNF-α and IP-10 were negatively correlated with the level of IgG (rIL-10=-0.222, PIL-10=0.015; rIL-1β=-0.212, PIL-1β=0.020; rIL-6=-0.372, PIL-6=0.000; rTNF-α=-0.185, PTNF-α=0.043; rIP-10=-0.273, PIP-10=0.003, respectively), but there were no significant correlation between the levels of MCP-1 and IL-4 and the concentrations of IgG (PMCP-1=0.082, PIL-4=0.067, respectively).3.5 Changes in serum IL-10, IL-1β, IL-6, MCP-1, TNF-α, IP-10 and IL-4 in COVID-19 patients 47 serum are from patients who eventually died, or asymptomatic infected patients, 3 serum are from whose onset time are unknown, the other 70 serum were be divided into five groups according to the acquisition time from onset: a. 0-14 days, b. 15-28 days, c. 29-42 days, d. 43-56 days and e. 57-70 days. As it was shown in Table 4, IL-10 on 43-56 days were significant lower than those on 29-42 days (P=0.049), TNF-α on 15-42 days were significant higher than those on 0-14 days (Pab=0.030, Pac=0.027), IP-10 on 0-14 days were significant higher than those on 43-56 days, IP-10 on 0-14 days were highest and were significant higher than those on43-56 days (P=0.018), and IL-4 on 29-42 days were significant higher than those on 0-14 days (P=0.018).4 DiscussionWe measured the serum levels of these cytokines in COVID-19 patients and non COVID-19 patients by ELISA, the results showed that the serum levels of IL-10, IL-1β, MCP-1, TNF-α and IL-4 in COVID-19 patients were significantly higher than those in non COVID-19 patients, while IL-6 were only significantly higher than in healthy people, IP-10 in COVID-19 patients were significantly lower than those in other diseases patients. IL-10, IL-1β, IL-6, MCP-1, TNF-α and IL-4 have potential study value for COVID-19, and TNF-α and MCP-1 have the best predictive effect. It should be noted that the serum levels of IL-10 and MCP-1 in male COVID-19 patients were significantly higher than those in the female patients. The serum levels of all cytokines in patients were significantly positively correlated with age. IL-1β and IL-4 were significantly negatively correlated with IgM, while IL-10, IL-1β, IL-6, TNF-α and IP-10 were significantly negatively correlated with IgG. The continuous monitoring of the cured COVID-19 patients showed that the levels of TNF-α on 15-42 days were significant higher than those on 0-14 days, and IL-4 on 29-42 days were significant higher than those on 0-14 days, study shows that ICU patients had higher plasma levels of cytokines than non-ICU patients[1], which suggested that levels of cytokines may related to the severity of the disease, so we assume that the reason for this change is that the disease on 0-14 days is light; IL-10 on 43-56 days were significant lower than those on 29-42 days, which may because on 43-56 days, the immune system secreted more IL-10 to induce excessive apoptosis of immune cells in order to avoid damaging its normal tissues in the late stage of inflammation; IP-10 on 0-14 days were highest and were significant higher than those on 43-56 days, the finding that IP-10 rose sharply in the early stages of COVID-19 suggested that targeted inhibition of IP-10 in the early stage might be the key to future treatment of COVID-19. 5 ConclusionTo sum up, we found that the serum levels of IL-1β, MCP-1, IL-6 and IP-10 in patients with COVID-19 were rise, which was same as Severe Acute Respiratory Syndrome (SARS)[11-13], this similarity may be related to the fact that both SARS-CoV-2 and SARS viruses attack Angiotensin-Converting Enzyme 2 (ACE2)[14,15] and produce similar inflammatory processes; TNF-α in patients with COVID-19 were also rise, which was same as Middle East Respiratory Syndrome Coronavirus (MERS)[12,16,17]; what's interesting is that the level of IL-4 and IL-10 also rise in patients with COVID-19, which was different with the another two high pathogenic coronavirus diseases [11-13,16,17]. IL-10, IL-1 β, IL-6, MCP-1, TNF-α and IL-4 would assist the clinical study of COVID-19. In COVID-19 patients, the serum levels of all cytokines were significant positively correlated with age, the poor prognosis of the elderly may be related to this; some of they have relationships with the gender or antibody, the former may be related to the high level of ACE2 in  male reproductive system [18-20]; the levels of cytokines would change with the course of disease, and we assumed that targeted inhibition of IP-10 in the early stage may be the key to future treatment of COVID-19. Due to the limited number of samples and enrollment, neither the levels of cytokines between mild and severe patients, were be compared. It has been reported that there are high levels of Pro-inflammatory cytokines in severe COVID-19 patients serum [1,16,21]. To make it clear that whether the cytokine level can predict the course of disease development of COVID-19 patients, the follow-up research will continue.Data Availability Statements: The datas that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.REFERENCES [1] Chaolin Huang，Yeming Wang，Xingwang Li，Lili Ren，Jianping Zhao，Yi Hu，et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China [J]. Lancet, 2020; 395: 497-506.[2] Hongzhou Lu, Charles W. Stratton, Yi‐Wei Tang. Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle [J]. J Med Virol, 2020; 92: 401-402.[3] Yu Chen, Qianyun Liu, Deyin Guo. Emerging coronaviruses：genome structure，replication，and pathogenesis [J]. J Med Virol，2020; 92（4）：418-423.[4] The national health and Health Committee and the office of the State, Administration of traditional Chinese medicine (TCM).Diagnosis and Treatment Protocol for COVID-19 (Trial version 7)(state health office Medical Letter No.184 (2020). [EB/OL].(2020-03-04) [2020-03-05] http://www.nhc.gov.cn/yzygj/s7653p/202003/46c9294a7dfe4cef80dc7f5912eb1989.shtml.[5] Chousterman Benjamin G, Swirski Filip K, Weber Georg F. Cytokine storm and sepsis disease pathogenesis. [J]. Seminars in immunopathology,2017; 39(5):517-528.[6] Jasper Fuk-WooChan, Shuofeng Yuan, Kin-Hang Kok, Kelvin Kai-Wang To, Hin Chu, Jin Yang, et al. A familial cluster of pneumonia associated with the 2019 novel corona virus indicating person to person transmission: a study of a family cluster [J]. Lancet, 2020; 395: 514-523．[7] Shimabukuro-Vornhagen Alexander, Gödel Philipp, Subklewe Marion, Stemmler Hans Joachim, Schlößer Hans Anton, Schlaak Max, et al. Cytokine release syndrome. [J].Journal for immunotherapy of cancer,2018; 6(1):56-56.[8] Xue-Qin Meng, Xin-Hua Chen, Zayd Sahebally, Yu-Ning Xu, Sheng-Yong Yin, Li-Ming Wu, et al. Cytokines are early diagnostic biomarkers of graft-versus-host disease in liver recipients [J]. Hepatobiliary &amp; Pancreatic Diseases International,2017; 16(01):45-51.[9] Anne-Britt E Dekker, Pieta Krijnen, Inger B Schipper. Predictive value of cytokines for developing complications after polytrauma [J]. World Journal of Critical Care Medicine,2016; 5(03):187-200.[10] Zhe Xu, Lei Shi, Yijin Wang, Jiyuan Zhang, Lei Huang, Chao Zhang, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome [J]. Lancet Respir Med, 2020; 8(4)：420-422.[11] Channappanavar Rudragouda, Perlman Stanley. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. [J].Seminars in immunopathology, 2017; 39(5):529-539.[12] Kindler, E., V. Thiel, and F. Weber, Interaction of SARS and MERS Coronaviruses with the Antiviral Interferon Response[J]. Adv Virus Res, 2016. 96: 219-243.[13] Rudragouda Channappanavar, Anthony R. Fehr, Rahul Vijay, Matthias Mack, Jincun Zhao, David K. Meyerholz, et al. Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. Cell Host Microbe, 2016, 19(2): 181-193.[14] Yu Zhao, Zixian Zhao, Yujia Wang, Yueqing Zhou, Yu Ma, Wei Zuo. Single-cell RNA expression profiling of ACE2, the receptor of SARS-CoV-2 [J]. Am J Respir Crit Care Med, 2020, 202(5): 756-759. [15] Yushun Wan, Jian Shang, Rachel Graham, Ralph S. Baric, Fang Li. Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus [J]. Journal of virology, 2020; 94(7): e00127-20.[16] Kim Eu Suk, Choe Pyoeng Gyun, Park Wan Beom, Oh Hong Sang, Kim Eun Jung, Nam Eun Young, et al. Clinical Progression and Cytokine Profiles of Middle East Respiratory Syndrome Coronavirus Infection [J].Journal of Korean Medical Science,2016; 31(11):1717-1725. [17] Dianna L. Ng, Farida Al Hosani, M. Kelly Keating, Susan I. Gerber, Tara L. Jones, Maureen G. Metcalfe, et al. Clinicopathologic, immunohistochemical, and ultrastructural findings of a fatal case of Middle East respiratory syndrome coronavirus infection in the United Arab Emirates[J]. Am J Pathol. 2016; 186:652-658.[18] Zhenyu Fan, Liping Chen, Jun Li. Clinical Features of COVID-19-Related Liver Functional Abnormality [J]. Clinical Gastroenterology and Hepatology,2020; 18(7):1561-1566.[19] Caibin Fan, Kai Li, Yanhong Ding, Wei Lu Lu, Jianqing Wang. ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2019-nCoV Infection  [J/OL]. https://www.medrxiv.org/content/10.1101/2020.02.12.20022418v1, 2020-02-13.[20] Iziah E Sama, Alice Ravera, Bernadet T Santema, Harry van Goor, Jozine M ter Maaten,  John G F Cleland, et al. Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin–angiotensin–aldosterone inhibitors[J].Eur Heart J, 2020; 41(19):1810-1817.[21] Lingxi Guo, Dong Wei, Xinxin Zhang, Yurong Wu, Qingyun Li, Min Zhou. Clinical Features Predicting Mortality Risk in Patients With Viral Pneumonia: The MuLBSTA Score. [J]. Frontiers in microbiology,2019; 10:2752.AcknowledgementThe authors promise that all the data are from the clinical, and genuine and believable. The authors report no commercial associations that could be a conflict of interest. Novel Coronavirus Pneumonia Emergency Project of Hunan Province Science and Technology Department (2020SK3009, 2020SK3018, 2020SK3042) and the First-class Discipline Open Fund Project of Hunan University of Chinese Medicine (2018YXJS02) were received in support of this article.

Now, we know that the first report of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was in December 2019 in Wuhan, China. In January, the existence of a disease caused by a virus with respiratory tropism for humans was announced, and in February it was already named SARS-Cov-2. The World Health Organization (WHO) 1 gave it the name of COVID-19, on February 11. One month later, WHO declared that the disease caused by this virus was already a pandemic (WHO, 2020)1. The virus started in China, then affected other Asian countries such as Japan, South Korea, etc., and later spread to Europe, then America.As this pandemic progresses, the reports of this six-month period show that this SARS-CoV-2 coronavirus not only targets the respiratory system, its effect on the cardiovascular, digestive, and renal apparatus has also been described. In addition, recent reports have described a set of neurological symptoms 2-4. Furthermore, the presence of this virus in the neurons and the capillary endothelium of the frontal cortex was seen in a patient who died of SARS-CoV-24. Moreover, other reports have shown its presence in the brainstem and in the cerebrospinal fluid (CSF) of other patients with SARS-CoV-2 5-6. Recent reports suggested that the cells with the expression of the angiotensin-converting enzyme 2 (ACE-2) may be a target for this coronavirus, since ACE 2 is a suggested cellular receptor for this coronavirus 4,7-8. Interestingly, various reports have demonstrated the presence of ACE-2, in both neurons and glial cells 7,9-11. Consequently, the evidence suggests that central nervous system (CNS) may be a target organ for this virus. It is known that the presence of this virus is responsible for the inflammatory process, which causes damage not only at the pulmonary level, but also at the cardiovascular, renal, and digestive system levels. All of these structures have a great regenerative capacity and thus reduce the damage in the long term. However, an inflammatory process at the CNS level could leave sequelae that, with age, could favor the early appearance of neurodegenerative processes, such as Alzheimer’s disease, Parkinson’s disease, vascular type dementia, multiple sclerosis etc., 12-13. Consequently, preventive measures should be taken to avoid the CNS from suffering future damage.Autopsy of patients with COVID-19 has shown that the brain tissue is hyperemic, edematous, and has degenerated neurons 2,7. However, it is necessary to know the percentage of cases in which there were changes in the nervous tissue caused by SARS-CoV-2, the types of modifications and the CNS regions most affected by COVID\sout-19. Data can help us know the impact on the brain tissue of this viral infection. In addition to supporting the neuroinvasive effect on the CNS and peripheral nervous system (PNS) of this coronavirus, there are the reported cases of meningitis, encephalitis, and Guillain-Barré syndrome associated with SARS-CoV-2 7,14-17.The clinical picture of SARS-CoV-2 is very wide, with symptoms and signs that involve the respiratory, cardiovascular, renal, digestive, and hepatic systems. However, there are also symptoms in which the CNS and PNS could be involved 2,3. Neurological manifestations have been classified as non-specific and specific by various authors2,15,18-20. Among the non-specific ones are headache, fatigue, dyspnea, etc. While the specific ones imply clear CNS or PNS affection data, such as loss of smell and reduction of taste and vision, neural pain, epileptic seizures, acute cerebrovascular disease, and deterioration of the state of consciousness have also been reported3,14,15,17,19,20.The way in which the SARS-CoV-2 can reach neurons and glial cells is through the blood crossing the blood-brain barrier or by retrograde transport through peripheral nerves. There is evidence for both hypotheses. At the beginning of the disease, patients with COVID-19 may have alterations or loss of smell and taste, probably because the virus may damage this pathway, which has been reported to recover, in some cases at the end of the disease and in others up to several weeks after the patient recovered 20. The virus can pass through the olfactory pathway, which enters the brain through the cribiform plate (transcribial route) 5,7,21. This route has been reported for other viruses, including SARS-CoV7,18,22. In addition, various reports have detected various viruses with respiratory tropism, including some coronaviruses, can reach the brain by retrograde transport, due to their neurotropic properties 5,7,21,22.Moreover, there is a percentage of patients who enter the ICU and require ventilatory assistance, since they do not breathe spontaneously7,21,23. Consequently, it is necessary to study whether this effect of COVID-19 is due to direct action on lung tissue or due to its neurotoxicity at the level of the brainstem, by affecting the respiratory center, which responds to changes in blood pH and CO2 levels 24.In summary, more studies are required to obtain additional information on the neurotoxic effects of COVID-19. However, with the aforementioned data, we can suggest that this coronavirus has neurotropic properties with neuroinvasive activity, which should be investigated, looking for therapeutic tools to reduce the damage that could be left at the nervous tissue level.ReferencesWorld Health Organization, Novel Coronavirus (2019-nCoV) Situation Report – 22, 2020Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Chang J, et al., Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol . 2020;77;1–9.Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, Collange O, et al., Neurologic Features in Severe SARS-CoV-2 Infection. N Engl J Med . 2020;382;2268-2270.Paniz-Mondolfi A, Bryce C, Grimes Z, Gordon RE, Reidy J, Lednicky J, Sordillo EM, Fowkes M. Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Med Virol . 2020;92;699-702.Bulfamante G, Chiumello D, Canevini MP, Priori A, Mazzanti M, Centanni S, Felisati G. First ultrastructural autoptic findings of SARS-Cov-2 in olfactory pathways and brainstem. Minerva Anestesiol . 2020.Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, Ueno M, et al., A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis . 2020;94;55-58.Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms. ACS Chem Neurosci . 2020;11;995-998.Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science . 2020;367;1444-1448.Yamagata R, Nemoto W, Nakagawasai O, Takahashi K, Tan-No K. Downregulation of spinal angiotensin converting enzyme 2 is involved in neuropathic pain associated with type 2 diabetes mellitus in mice.Biochem Pharmacol . 2020;174;113825.Mukerjee S, Gao H, Xu J, Sato R, Zsombok A, Lazartigues E. ACE2 and ADAM17 Interaction Regulates the Activity of Presympathetic Neurons.Hypertension. 2020;74;1181-1191.Kehoe PG, Al Mulhim N, Zetterberg H, Blennow K, Miners JS. Cerebrospinal Fluid Changes in the Renin-Angiotensin System in Alzheimer’s Disease. J Alzheimers Dis. 2019;72(2):525-535.Cairns DM, Rouleau N, Parker RN, Walsh KG, Gehrke L, Kaplan DL. A 3D human brain-like tissue model of herpes-induced Alzheimer’s disease.Sci Adv. 2020;6;eaay8828.. Flores G, Flores-Gómez GD, Gomez-Villalobos MJ. Neuronal changes after chronic high blood pressure in animal models and its implication for vascular dementia. Synapse. 2016;70;198-205.Dalakas MC. Guillain-Barré syndrome: The first documented COVID-19-triggered autoimmune neurologic disease: More to come with myositis in the offing. Neurol Neuroimmunol Neuroinflamm . 2020;7; e781.Faucher A, Rey PA, Aguadisch E, Degos B.Isolated post SARS-CoV-2 diplopia. J Neurol. 2020;1–2.Joob B, Wiwanitkit V. COVID-19 and Guillain-Barré syndrome. Rev Neurol (Paris), 2020.Wang L, Shen Y, Li M, Chuang H, Ye Y, Zhao H, Wang H. Clinical manifestations and evidence of neurological involvement in 2019 novel coronavirus SARS-CoV-2: a systematic review and meta-analysis. J Neurol . 2020;1–13.Asadi-Pooya AA, Simani L Central nervous system manifestations of COVID-19: A systematic review. J Neurol Sci . 413,116832..Kanwar D, Baig AM, Wasay M. Neurological manifestations of COVID-19. J Pak Med Assoc. 2020;70(Suppl 3), S101-S103.Kosugi EM, Lavinsky J, Romano FR, Fornazieri MA, Luz-Matsumoto GR, Lessa MM, Piltcher O, Sant’Anna GD. Incomplete and late recovery of sudden olfactory dysfunction in COVID-19. Braz J Otorhinolaryngol , 2020;S1808-8694, 30059-30068.Baig, A.M. Neurological manifestations in COVID-19 caused by SARS-CoV-2. CNS Neurosci Ther . 2020;26;499-501.Bohmwald K, Gálvez NMS, Ríos M, Kalergis AM. Neurologic Alterations Due to Respiratory Virus Infections. Front Cell Neurosci . 2018;12;386.Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients.J Med Virol . 2020;92;552-555.Guyenet PG, Bayliss DA. Neural Control of Breathing and CO2 Homeostasis. Neuron. 2015;87;946-961.

Introduction: Dental caries is an infectious disease with predominantly of cariogenic bacteria such as Streptococcus mutans (S. mutans). Xylitol is considered as one of the effective agents that can limit this dental infection. In this randomized, placebo-controlled trial, we aimed to evaluate the potential reflection of short-term xylitol consumption on pro-inflammatory cytokines (TNF-, IL-6 and IL-8) and S. mutans counts by ELISA and qPCR (Quantitative real-time PCR), respectively. Methods: In this study, 154 participants were assigned to two groups, control and xylitol. Dental examination, saliva and swab samples were done at baseline and at 3-week for clinical and microbiological assessment. Results: In xylitol group at the end of 3-week, gingival and plaque index scores were significantly decreased with respect to baseline values (p<0.001 and p<0.05, respectively). The salivary concentration of TNF-, IL-6 and IL-8 were statistically declined at 3-week, more so than those at baseline in xylitol group (p<0.001). S. mutans expression was reduced about 5-fold at 3-week use of xylitol and it was a statistically significant difference compared to baseline (p<0.001). Conclusion: Intriguingly, even short-term consumption of xylitol might play a favorable role in maintaining the oral health status, possibly as a result of decreasing the release of pro-inflammatory cytokines and the counts of S. mutans. Nonetheless, this investigation warrants further endorsement.

Background: Pharmacogenomics (PG) is a modern tool of personalizing treatment protocols to improve the efficacy and safety of drug prescriptions. These benefits are offset by a slow uptake in clinical application due to a host of physician factors, patient factors, and/or health system factors. Our study, thus, aimed to determine the knowledge, attitude, future expectations, and perceived barriers of medical students and physicians in Jordan regarding PG testing. Methods: A descriptive, cross-sectional study was conducted between February-August 2019. Physicians and senior medical students from academic and non-academic institutions in North Jordan (n=424) were surveyed. A structured, self-administered questionnaire was designed and piloted for the purpose of the study. A scoring system for each dimension assessed was calculated and presented using means. Mean scores were compared by sociodemographic and professional variables. Results: The response rate was 70.7%. The mean total PG knowledge score (±SD) was 5.42 (±1.51) out of 10, with a significantly higher mean among respondents aged ≥30 years (5.21 ± 1.62) compared to those <30 years-old (5.54 ± 1.43; p= 0.03). The mean total PG attitude score was 21.18 (±2.58) out of 24, with significant differences by seniority levels evident (p= 0.03). The future expectations of PG among our sample were high, with a mean score of 10.44 (±1.64) out of 12. The top three perceived barriers in applying PG were the high cost, lack of clinical guidelines, and limited knowledge and awareness. Conclusion: Physicians and medical students in Jordan have low overall knowledge, albeit strongly positive attitude and future expectations toward PG, despite the perceived high cost and lack of clinical guidelines. Thus, we strongly recommend adopting a comprehensive educational strategy that aims to integrate PG concepts into medical curricula, and promote the culture of continuous medical education about PG among practitioners.

Introduction and Objectives There are no cardiovascular risk prediction models developed in South Asian cohorts. Therefore, different risk models not validated in South Asians are being used. We aimed to compare cardiovascular risk predictions of Framingham risk score (FRS) and World health organization/International society of hypertension (WHO/ISH) charts for agreement in a sample of South Asians. Methods 10-year cardiovascular risk predictions of patients without previous cardiovascular diseases attending a non-communicable disease clinic were calculated using FRS (with BMI and with cholesterol) and WHO/ISH charts (with and without cholesterol). Patients were categorized into low(<20% ) and high(≥20%) cardiovascular risk groups on risk predictions. Agreement in risk categorisation with different prediction models was compared using Cohen’s kappa coefficient(κ). Results 169 patients (females 130(81.1%)) mean age 65 ±6.9 years were studied. 80(47.3%), 62(36.7%), 18(10.7%), and 16(9.5%) were predicted high-risk by FRS BMI-based, FRS cholesterol-based, WHO/ISH without-cholesterol and WHO/ISH with-cholesterol models, respectively. Agreement between the two FRS models (κ = 0.736, p<0.0001) and the two WHO/ISH models (κ = 0.804, p<0.0001) in stratifying patients into high and low-risk groups, were “good”. However, the agreements between, FRS BMI-based and WHO/ISH without-cholesterol models (κ = 0.234, p<0.0001) and FRS cholesterol-based and WHO/ISH with-cholesterol models (κ = 0.306, p<0.0001) were only “fair”. Conclusion Cardiovascular risk predictions of FRS were higher than WHO/ISH charts and the agreement in risk stratification was not satisfactory in Sri Lankans. Therefore, different cardiovascular risk prediction models should not be used interchangeably in the follow-up of South Asians.

The goal of this study was to assess the clinical effectiveness and safety profile of the COVID-19 treatment protocol (containing both hydroxychloroquine (HCQ) and azithromycin) in an Iraqi specialized hospital. Methods: This prospective study used a pre- and post-intervention design without a comparison group. The intervention was routine Ministry of Health (MOH) approved management of COVID-19 for all patients. The study was conducted in a public healthcare setting in Baghdad, Iraq from March 1st to May 25, 2020. The study outcome measures included the changes in clinical and biochemical parameters during the hospitalization period. Paired t-test and Chi-square test were used to compare the measures of vital signs, lab tests and symptoms before and after treatment. Results: The study included 161 patients who were admitted with positive RT-PCR and clinical symptoms of COVID-19. In terms of severity, 53 (32.9%) patients had mild condition, 47 (29.2%) had moderate condition, 35 (21.7%) had severe condition, and 26 (16.1%) had critical condition. Most patients (84.5%) recovered and were discharged without symptoms after testing negative with RT-PCR, while 11 (6.8%) patients died during the study period. The signs and symptoms of COVID-19 were reduced significantly in response to therapy regimen containing HCQ and azithromycin. The most common reported side effects were stomach pain, hypoglycemia, dizziness, itching, skin rash, QT prolongation, arrhythmia, and conjunctivitis. Conclusions: This natural trial showed that COVID-19 regimen containing both HCQ and azithromycin can be helpful to promote recovery of most patients and reduced their signs and symptoms significantly. It also shows some manageable side effects mostly those related to heart rhythm. In the absence of FDA-approved medications to treat COVID-19, the repurposing of HCQ and azithromycin to control the disease signs and symptoms can be useful.

Background Atopic dermatitis (AD) is the chronic inflammatory disorder that affects both in childhood and adulthood. Mounting evidence indicates that gut dysbiosis contributes to AD via the gut-skin axis. Constipation can result in alteration of the gut microflora. The clinical impact of constipation on AD has not been researched. Therefore, we aim to assess the risk of AD in constipated patients by the population-based cohort study. Methods We collected 87015 constipated people and 87015 people without constipation between 1999 and 2013 from the Taiwanese National Health Insurance Research Database. Propensity score analysis was administrated to match age, gender, comorbidities, and medications at a ratio of 1:1. Multiple Cox regression analysis was utilized to evaluate the adjusted hazard ratio of AD. In addition, sensitivity tests and a stratified analysis were conducted. Results The incidence of AD was 4.7 per 1,000 person-years in the constipation group, which was higher than the rate of 2.2 per 1,000 person-years observed in the non-constipation group. After adjustment for age, gender, comorbidities, corticosteroids, and antihistamine, constipated people had a 2.11-fold greater risk of AD compared to those without constipation (adjusted hazard ratio [aHR]: 2.11 (95% C.I. 1.98-2.24). Moreover, constipated people had a higher likelihood of AD, regardless of gender, comorbidities, as well as the usage of corticosteroids, and antihistamines. Conclusion Constipation is associated with a significantly risk factor of AD. Clinicians should be careful of the possibility of AD in constipated people. Further study is warranted to investigate the possible pathological mechanisms of this relationship.

Purpose: Some patients who undergo robot-assisted laparoscopic radical prostatectomy (RARP) continue to experience long-term urinary incontinence (UI). This study aimed to evaluate easily obtainable factors that can predict long-term UI following RARP. Materials and Methods: A total of 315 patients who underwent RARP for localized prostatic cancer were analyzed. We separated the patients into two groups, namely, the Continence group and the Incontinence group, according to the presence or absence of UI at 12 months after surgery, and we compared the patients’ characteristics and operative data to identify clinical signs associated with long-term UI. Additionally, correlations between these factors and postoperative urethral function were evaluated. Urinary continence was defined as both the use of 0 pads/per day and <2 g of urine lost using the 24-h pad weight test. Results: Of 315 patients, 250 (79.4%) achieved urinary continence and 65 (20.6%) had UI. Age, storage-related lower urinary tract symptoms before surgery, nerve-sparing surgery, and the 24-h urine loss immediately after urethral catheter removal significantly affected long-term UI after RARP. Multivariate logistic regression analyses revealed that the 24-h urine loss after catheter removal was a significant predictor of long-term UI. Receiver operating characteristic curve analysis identified a urine loss of 330 g/day as the optimal cutoff value, which yielded 92% sensitivity and 84% specificity, and it showed significant correlations with postoperative urethral function and the time to recover urinary continence. Conclusion: The 24-h urine loss immediately after urethral catheter removal may be the most reliable and useful predictor of long-term UI following RARP.

Purpose: To evaluate the effect of partial nephrectomy on renal function and to identify predictors of estimated glomerular filtration rate (eGFR) at six months after partial nephrectomy. Methods: Medical data of 154 consecutive patients who underwent partial nephrectomy for a renal mass between January 2015 and March 2020 were retrospectively analyzed. The primary outcome measure was eGFR at six months postoperatively. A non-linear regression analysis was performed to examine the association between primary outcome measure and candidate predictors. Results: Of the patients, 66 (42.9%) were females and 88 (57.1%) were males with a median age of 60 (range, 50 to 67) years. The median baseline eGFR was 90.40 (range, 74.96 to 102.97) mL/min/1.73 m2, while the median eGFR at six months was 77.12 (range, 61.06 to 91.93) mL/min/1.73 m2 (p<0.001). Baseline eGFR (=22.691, 95%CI: 18.821 to 26.460, when baseline eGFR levels change from 74.97 ml/min/1.73 m2 to 102.68 ml/min/1.73 m2, p<0.001) was found to be directly associated with the postoperative eGFR levels at six months. In contrary, advanced tumor size (=-3.168, 95%CI: -5.332 to -1.005, when tumor size levels change from 3 to 6 cm, p<0.001) and presence of hypertension ( = -3.479, 95%CI: -6.956 to -0.0031, p=0.049) were also found to be inversely associated with the postoperative eGFR levels at six months. Conclusion: Baseline eGFR values, tumor size, and presence of hypertension are significant predictors of eGFR values in the mid-term in patients undergoing partial nephrectomy.

Background: The relationship between socioeconomic status (SES) and the prognosis of HF with reduced (HFrEF) vs. preserved (HFpEF) ejection fraction remains unsettled. Objective: To analyze the relationship between SES and the prognosis of patients with incident HFrEF and HFpEF. Methods: Prospective study over 15 years (2003-2017) on 9658 patients diagnosed with HF. Main outcomes were mortality and hospitalizations for HF. The independent relationship between SES and the prognosis, stratifying patients for cardiovascular co-morbidity after propensity score-matching was analyzed. Results: After matching 7116 patients, during a median follow-up of 8.11 years, 5616 patients died (78.9%) and 5549 patients were hospitalized (78.0%). High income level was associated with a lower all-cause mortality (RR for HF patients [95% CI]: 0.86 [0.80-0.92], RR for HFrEF: 0.88 [0.82-0.95] and RR for HFpEF: 0.82 [0.75-0.90], P <0.001 in all cases), and cardiovascular mortality (RR for HF: 0.84 [0.76-0.92], RR for HFrEF: 0.87 [0.81-0.93] and RR for HFpEF: 0.88 [0.77-0.88], P <0.001 in all cases), less hospitalizations (RR for HF: 0.70 [0.65-0.78], RR for HFrEF: 0.78 [0.68-0.88] and RR for HFpEF: 0.61 [0.55-0.68], P <0.001 in all cases), and less 30-day readmissions (RR for HF: 0.67 [0.59-0.75], RR for HFrEF: 0.71 [0.63-0.79] and RR for HFpEF: 0.61 [0.55-0.69], P <0.001 in all cases), after adjustment for comorbidities, and other potential confounders. Analyses of recurrent hospitalizations gave larger SES benefits than time-to-first-event analyses. Conclusions: In this propensity-matched study, a high net annual household income is associated with an improved prognosis of patients with incident HFrEF and HFpEF.

Background: The liberal administration of hydroxychloroquine-sulphate (HCQ) to COVID-19 patients has raised concern regarding the risk of QTc prolongation and cardiac arrhythmias, particularly when prescribed with azithromycin. We evaluated the incidence of QTc prolongation among moderately and severely ill COVID-19 patients treated with HCQ and of the existence of concomitant alternative causes. Methods: All COVID-19 patients treated with HCQ (between Mar 1 and Apr 14, 2020) in a tertiary medical center were included. Clinical characteristics and relevant risk factors were collected from the electronic medical records. Individual patient QTc intervals were determined before and after treatment with HCQ. The primary outcome measure sought was a composite endpoint comprised of either an increase ≥ 60 milliseconds (ms) in the QTc interval compared with pretreatment QTc, and/or a maximal QTc interval >500 ms. Results: Ninety patients were included. Median age was 65 years (IQR 55-75) and 57 (63%) were male. Thirty-nine patients (43%) were severely or critically ill. Hypertension and obesity were common (n=23 each, 26%). QTc prolongation evolved in fourteen patients (16%). Age > 65 years, congestive heart failure, severity of disease, C-reactive protein level, hypokalemia and furosemide treatment, were all associated with QTc prolongation. Adjusted analysis showed that QTc prolongation was five times more likely with hypokalemia [OR 5, (95% CI, 1.3-20)], and three times more likely with furosemide treatment [OR 3 (95% CI, 1.01-13.7)]. Conclusion: In patients treated with HCQ, QTc prolongation was associated with the presence of traditional risk factors such as hypokalemia and furosemide treatment.