An Efficacy and Safety Comparison of Regorafenib and Nivolumab in Unresectable Hepatocellular Cancer Patients: A Systematic Review.

OBJECTIVE: This systematic review aimed to compare the efficacy and safety of regorafenib and nivolumab, two FDA-approved second-line treatments for unresectable Hepatocellular Carcinoma (HCC). METHODS: Literature comparing the efficacy and safety of regorafenib and nivolumab in unresectable HCC patients was systematically searched across seven databases, including: PubMed, SCOPUS, Cochrane Database of Systematic Reviews, ScienceDirect, EBSCOhost, EMBASE, and ProQuest, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The search was done on April 2nd, 2023. Study quality and risk of bias were assessed using the Agency for Healthcare Research and Quality (AHRQ) and ROBINS-1 tools. The selected studies were included in the qualitative data synthesis. RESULTS: Three trials found that HCC patients taking nivolumab had statistically insignificantly longer OS, TTP, and progression-free survival than those on regorafenib. Nivolumab increased ORR, with largely partial responses, and mixed DCR, with little statistical significance. All three studies showed that nivolumab had fewer side effects and improved tolerance. DISCUSSION: Three retrospective cohort studies with a total of 383 regorafenib-receiving cohorts and 230 nivolumab-receiving cohorts were included in the qualitative analysis. Nivolumab was found to be superior in regards of longer overall survival, longer time to progression, higher objective response rate, and lower adverse event occurrence. However, statistical significance was not achieved in most of the parameters. CONCLUSIONS: The use of nivolumab is preferable as the second-line systemic therapy for unresectable HCC. More high-quality studies are urgently needed to generate quantitative analysis, and to encourage the formation of guidelines for second-line systemic therapy.

Examination of ejaculate fructose levels on male infertility patients at various times and centrifugation using semiautomatic method.

OBJECTIVE: Various factors, such as obstructive azoospermia, cause infertility in men. Biochemical examination of ejaculate, especially measurement of fructose, can be an additional investigation that can be used for this diagnosis in reproductive health. Examination of fructose is carried out after routine ejaculate analysis, resulting in prolonging the examination time so that it will affect the measurement of fructose level in the ejaculate and the accuracy of the diagnosis. This study aims to determine the best timing and procedure for measurement of fructose using a semiautomatic method. METHODS: This research is an analytic observational study conducted at Dr. Soetomo General Hospital, Surabaya. A total of 13 ejaculate samples from infertile male patients who met the inclusion criteria were evaluated. Each ejaculate was divided into eight aliquots that were examined for fructose using a semiautomated method after different intervals of time and centrifugation modalities. RESULTS: This study showed a significant difference in fructose levels when aliquots were centrifuged and examined immediately or after different interval of time (p=0.036). In addition, aliquots left standing for more than 60 minutes (p=0.012) and 120 minutes (p<0.001) before centrifugation, showed significantly lower levels compared to aliquots that were centrifuged and then immediately examined. CONCLUSIONS: We suggest that measuring fructose immediately after centrifugation is more reliable than measuring fructose left standing before or after centrifugation. Leaving the ejaculate standing will reduce the fructose level so that it does not resemble its real level.

Lay understanding and experience of sexual intercourse among couples with infertility undergoing an assisted reproduction technology program: A qualitative study.

Aim: To explore the perception and lay understanding of sexual intercourse and sexual life experiences among infertile couples before, during, and after undergoing an assisted reproduction technology (ART) program. Method: The participants of this descriptive qualitative study were Indonesian couples with infertility who underwent an ART program. Semi-structured interviews were conducted between September and December 2022, and the participants' responses were recorded. Data were analyzed using a step-by-step analysis based on Braun's qualitative analysis. The study was reported based on the Consolidated Criteria for Reporting a Qualitative Research (COREQ) Checklist. Results: Fifty participants were included, and five themes were developed before and two themes during or after the ART program. The couples' knowledge varied as they experienced sexual intercourse at different periods, such as before, during, and after the ART program. Many participants reported that ART affected their emotions and mood, leading to decreased desire to engage in sexual intercourse. However, some used sexual intercourse as a basis for creating optimism and confidence in having offspring. Furthermore, couples perceived that the purpose of sexual intercourse is not only to have offspring but also to improve communication, promote intimacy, and express affection. In contrast, some perceived the ART program as time consuming, preventing them from engaging in sexual activities. However, not all couples considered sexual activity solely as a means of procreation. They concluded that sexual behavior is not only determined by genetics. Conclusion: Couples who underwent the ART program regardless of its effectiveness were aware that sexual interaction is not only for having children but also for preserving harmony and familial connection.

Role of klotho and fibroblast growth factor 23 in arterial calcification, thickness, and stiffness: a meta-analysis of observational studies.

This meta-analysis was conducted to clarify the role of klotho and fibroblast growth factor 23 (FGF-23) in human arterial remodeling across recent studies, in terms of arterial calcification, thickness, and stiffness. A systematic literature search was conducted on five databases for articles up to December 2023. Arterial calcification, thickness, and stiffness were determined using the calcification score and artery affected, carotid intima-media thickness (CIMT), and pulse wave velocity (PWV), respectively. Sixty-two studies with a total of 27,459 individuals were included in this meta-analysis. Most studies involved chronic kidney disease patients. Study designs were mostly cross-sectional with only one case-control and nine cohorts. FGF-23 was positively correlated with arterial calcification (r = 0.446 [0.254-0.611], p < 0.0001 and aOR = 1.36 [1.09-1.69], p = 0.006), CIMT (r = 0.188 [0.02-0.354], p = 0.03), and PWV (r = 0.235 [0.159-0.310], p < 0.00001). By contrast, Klotho was inversely correlated with arterial calcification (r = - 0.388 [- 0.578 to - 0.159], p = 0.001) and CIMT (r = - 0.38 [- 0.53 to - 0.207], p < 0.00001). In conclusion, FGF-23 and Klotho were associated with arterial calcification, thickness, and stiffness, clarifying their role in arterial remodeling processes.

Inflammatory bowel disease (ulcerative colitis type) severity shows inverse correlation with semen parameters and testosterone levels.

ABSTRACT: Individuals with inflammatory bowel disease (IBD) have been reported to be at an increased risk of infertility and sexual dysfunction. Although the relationship between them remains unclear, IBD severity is suspected to affect hormone levels and fertility. To analyze the impact of IBD severity on semen parameters and sex hormone levels in ulcerative colitis-type IBD (UC-IBD), we conducted a cross-sectional study involving 120 patients with UC-IBD in Adam Malik General Hospital, Medan, Indonesia. The patients were classified into three groups based on the Mayo score for UC, followed by a comparison of various semen and hormone parameters among these groups. In addition to the cross-sectional analysis, a simple correlation test was conducted irrespective of the patient grouping. Sperm concentration, motility, and morphology were found to decline significantly with an increase in IBD severity. Without classifying patients with IBD into subgroups, the Mayo score showed negative correlations with sperm concentration (r = -0.375, P < 0.0001), rapid progressive motility (r = -0.660, P < 0.0001), free testosterone (r = -0.732, P < 0.0001), and total testosterone (r = -0.721, P < 0.0001), and positive correlations with immotile sperm (r = 0.660, P < 0.0001), abnormal morphology (r = 0.657, P < 0.0001), and sex hormone-binding globulin (SHBG; r = 0.278, P = 0.002). Sperm concentration, motility, and morphology declined significantly with the severity of IBD. This study suggests a significant negative impact of IBD severity on semen quality and sex hormones.

Microalbuminuria and mortality in individuals with coronary heart disease: A meta-analysis of a prospective study.

AIM: Microalbuminuria has been elevated as an outcome predictor in cardiovascular medicine. However, due to the small number of studies investigating the association of microalbuminuria and mortality in the coronary heart disease (CHD) population, the prognosis value of microalbuminuria in CHD remains under debate. The objective of this meta-analysis was to investigate the relationship between microalbuminuria and mortality in individuals with CHD. METHOD: A comprehensive literature search was performed using Pubmed, EuroPMC, Science Direct, and Google Scholar from 2000 to September 2022. Only prospective studies investigating microalbuminuria and mortality in CHD patients were selected. The pooled effect estimate was reported as risk ratio (RR). RESULTS: 5176 patients from eight prospective observational studies were included in this meta-analysis. Individuals with CHD have a greater overall risk of all-cause mortality (ACM) [rR = 2.07 (95% CI = 1.70-2.44); p = 0.0003; I2 = 0.0%] as well as cardiovascular mortality (CVM) [rR = 3.23 (95% CI = 2.06-4.39), p < 0.0001; I2 = 0.0%]. Subgroup analysis based on follow-up duration and a subset of CHD patients were similarly associated with an increased risk of ACM. CONCLUSION: This meta-analysis indicates that microalbuminuria is associated with a higher risk of mortality in individuals with CHD. Microalbuminuria can serve as a predictor of poor outcomes in CHD patients.

"Am I Masculine?" A metasynthesis of qualitative studies on traditional masculinity on infertility.

Background: The rate of infertility is increasing day by day. According to studies conducted worldwide, 30 million men are diagnosed with infertility. Cases of infertility are often associated with a failure to become male in society. Procreation and gender roles are often closely linked so that infertile men are often considered the second sex. Sometimes, this condition makes men question their masculinity. Methods: We performed a systematic review and metasynthesis with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline procedure on qualitative studies on ten databases exploring the experience of infertile men and their association with masculinity. Results: Twenty-four studies matched our question, and there are two major themes with eight subthemes that were obtained from the results of the metasynthesis of these studies. The impact of this gender issue is huge on men's health and their social interactions. As a result, gender issues provide a space for debate and a burden on men. Sometimes, men develop mental health problems. The topic of masculinity and infertility is at odds with feminism and is susceptible to the societal stigma that results from the hegemonic conception of masculinity. Interestingly, the men must accept reality and follow the treatment process for infertility, although it affects their psychological well-being. Conclusions: These findings provide insight for physicians, as treating infertility requires a multidisciplinary team that does not only address procreation issues. Social issues related to gender roles often bring patients into harmful and dangerous conditions. To address the gender issue in men globally in several dimensions, however, a large study in various populations is still required.

The interplay between neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, erectile dysfunction, and Peyronie's disease: A meta-analysis of observational studies.

INTRODUCTION: This study aims to investigate the relationship between Neutrophil- Lymphocyte Ratio (NLR), Platelet-Lymphocyte Ratio (PLR) with Erectile Dysfunction (ED) and Peyronie's disease (PD). METHODS: We conducted a meta-analysis of the observational study by searching for the appropriate keywords in eight databases. The risk of publication bias of the included studies was assessed by Egger's test and Kendall's t. The data extraction was carried out for each study and analysed using Revman 5.0. RESULTS: There were eleven eligible studies out of the 411 studies retrieved. Eight studies were conducted on cases of erectile dysfunction, and three studies on Peyronie's disease. There was a significant relationship between NLR, PLR and ED (SMD: 0.59, 95% CI: 0.33-0.85 and SMD: 0.64, 95% CI: 0.13-1.16, respectively). The same was also found for PD. The active phase of PD tended to have higher NLR (SMD: 0.68, 95% CI: 0.43-0.92) and PLR (SMD: 0.27, 95% CI: 0.06-0.49) compared to the chronic phase. No publication bias was found in both ED and PD studies. CONCLUSIONS: NLR and PLR indicate an ongoing inflammatory process in both ED and PD. These findings can be used as markers of treatment and prognosis of both diseases in sexual health care.

Semen and sex-steroid parameters among inflammatory bowel disease ulcerative colitis type according to rectal bleeding grade.

INTRODUCTION: Hypogonadism and inflammato-ry bowel disease (IBD) are often associated. This association may influence sexual and reproductive function in IBD, including sperm profile and sex steroid hormones. PATIENTS AND METHODS: This study included 59 IBD patients diagnosed with ulcerative colitis type IBD. Anamnesis was carried out regarding the history of the disease, along with a history of rectal bleeding. Evaluation proceeded with sperm and hormone examination if the patient agreed. RESULTS: Progressive motility sperm, immotile sperm, and normal sperm were found to be significantly different between the rectal bleeding groups. In grade 3 (more significant bleeding) progressive sperm (24.81 ± 5.85, p < 0.0001) and normal sperm (6.33 ± 12.56, p = 0.0003) rates tended to be lower, while immotile sperm tended to be higher (44.48 ± 11.21, p < 0.0001). Testosterone and free testosterone levels were also reported to be significantly different between groups, where grade 3 had lower levels 255.9 ± 30.08, p = 0.014 and 4.645 ± 0.5, p = 0.002 respectively. CONCLUSIONS: Our study shows that the degree of rectal bleeding influences sperm motility and morphology, as well as testosterone and free testosterone levels. These results can concern managing IBD patients to fulfill reproductive health care.

The sex life of male patients with cirrhosis and its organic factors: What we have got so far?

OBJECTIVE: The purpose of this study was to examine the sex lives of male cirrhotic patients organic factors affect them. METHOD: We did an observational study of 220 cirrhotic men's satisfaction with their sexual lives. Assessment of sex satisfaction was carried out using the New Sexual Satisfaction Scale. The frequency of intercourse and masturbation was estimated. Then, the levels of albumin, total bilirubin, vitamin D, and sex steroids were examined. Ascites and sarcopenia subgroups of our patients were stratified. RESULTS: Along with sex steroids, albumin, total bilirubin, and vitamin D all had an impact on how satisfying sex was (r = 0.22), (r = 0.24), and (r = -0.17) affected sex satisfaction. There were strong positive correlations between vitamin D (r = 0.33), albumin (r = 0.59), and free testosterone, along with a negative correlation between total bilirubin (r = -0.63) and free testosterone. An imbalance in sex steroid levels was observed, leading to decreased frequency of intercourse(p < 0.0001), weakened erections(p < 0.0001), and reduced quality of orgasm (p < 0.0001). Significant new sex behavior changes were found, such as an increase in masturbation. Physical limitations such as ascites and sarcopenia also impacted the decreasing sex life. CONCLUSION: The sex life of cirrhotic men is affected. The decrease in the frequency of intercourse and sexual satisfaction is noticeable in male patients and leads to increased masturbation. Free Testosterone, vitamin D, albumin, and bilirubin play role in their sex life. In addition, ascites and sarcopenia not only affect their sex life but also hamper the quality of their well-being.

The Association Between Lipid Serum and Semen Parameters: a Systematic Review.

Increased lipid levels sometimes not only affect sexual function but also are considered to harm semen quality. It is often a suspicion that elevated lipids are a factor in infertility. We conduct a systematic review. Articles that met the criteria were identified according to The Preferred Reporting Items for Systematic Review and Meta-analysis of recommendations in the PubMed, ProQuest, EBSCO, Web of Science Wiley Online, Springer Link, Scopus, and Science Direct databases with no time restriction for publication. Seven studies are eligible for qualitative analysis from nine studies that have the potential to be assessed. These studies measure the correlation of serum lipids (VLDL, HDL, LDL, triglycerides, total cholesterol, free cholesterol, phospholipids, free fatty acids) with semen parameters (concentration, motility, morphology, DNA fragmentation index). Although not all studies consistently report that lipids impact semen quality, this review suspects that lipids have a significant impact on sperm quality. This study implies that it is necessary to maintain lipid levels to maintain sperm quality and quality of life. However, further investigation with an observational cohort study design needs to be carried out to assess the effect of lipids on semen quality more precisely for the promotion of reproductive health care.

Association between serum midkine levels and tumor size in Indonesian hepatocellular carcinoma patients: a cross-sectional study.

Background: The incidence of liver cancer is increased worldwide with 75%-85% diagnosed as hepatocellular carcinoma (HCC). Current practice has low sensitivity limitations to diagnose the early stages of HCC, thus urging the need for a biomarker with higher sensitivity to detect HCC, specifically in the early stage. This study aimed to determine the association between midkine levels and progressiveness of hepatocellular carcinoma (HCC), according to tumor size, Barcelona Clinic Liver Cancer (BCLC), and presence of portal venous thrombosis. Methods: This cross-sectional study involved 100 patients in Adam Malik General Hospital diagnosed with HCC, collected with a consecutive sampling method, whose diagnoses were confirmed by findings of hypervascular on arterial phase imaging and portal vein or delayed phase washout triple-phase CT Scan. Samples are later categorized according to Barcelona Clinic Liver Cancer (BCLC) stages, tumor size, and presence of portal venous thrombosis. Blood samples were drawn to measure serum midkine using ELISA. Kruskal-Wallis and Mann-Whitney U tests were conducted to determine the difference of midkine levels based on tumor size, BCLC staging, and presence of portal venous thrombosis. Results: Serum midkine level shows a significant difference over tumor size (p=0.014), no significant difference found compared to BCLC stages and presence of portal venous thrombosis. Conclusion: Serum midkine levels are associated with the tumor size of HCC, thus helping physicians determine treatment plans.

Framing and understanding the whole aspect of oral sex from social and health perspectives: a narrative review.

Since thousands of years ago, oral sex has become part of sexual behavior among humans. Oral sex is considered taboo. Its taboo does not lie in the behavior, but its expression is deemed inappropriate. As technology becomes more sophisticated, human rights also stand out, leading to the disclosure of the practice in the 21 st century. The oral sex that is discussed on a large scale in media encourages people to express it as feedback whether within right or not. It all depends on the value of each people. We found that this sexual behavior is found everywhere regardless of religion, culture, and race. Pop culture influences this behavior so much, it can be seen from music, movies, and television programs that provoke oral sex. Many motivations underlying this behavior include getting sexual pleasure for the sake of living well-being. But it is undeniable that this behavior is still controversial. It could be at risk of causing disease and, on the other hand, is reported to provide many benefits.  According to our theory, oral sex is not a new behavior crossing boundaries. It is just an old behavior that surfaces because of the factors that support it. This behavior, which is still considered taboo, has its disadvantages such as sexually transmitted disease but has also benefits such as preventing preeclampsia.

A systematic review of retinoic acid in the journey of spermatogonium to spermatozoa: From basic to clinical application.

Background: Retinoic acid plays an essential role in testicular development and functions, especially spermatogenesis. We have reviewed the role of retinoic acid from basic (molecular) to clinical application. Methods: A search was conducted in the online database including PubMed, Google Scholar, and Scopus for English studies published in the last eight years about this issue. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in assessing the studies we are going to investigate. Results: Studies indicated that retinoic acid plays an essential role during pluripotent stem cell migration and lineage commitment, cell differentiation, apoptosis, stem cell number regulation, and maturation arrest in spermatogenic cells. Retinoic acid can also affect related protein expression and signaling pathways at different stages of spermatogenesis. Four studies have applied retinoic acid to humans, all of them in the single-arm observational study. The results look promising but need further research with more controlled study methods, randomization, and large samples. Conclusions: This current systematic review emphasizes a novel retinoic acid mechanism that has not been well described in the literature previously on its functions during the first seven days of spermatogenesis, leading to new directions or explanations of male infertility cause and treatments as a part of reproductive health care.

The Effect of Angiotensin Converting Enzyme (ACE) I/D Polymorphism on Atherosclerotic Cardiovascular Disease and Cardiovascular Mortality Risk in Non-Hemodialyzed Chronic Kidney Disease: The Mediating Role of Plasma ACE Level.

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and plasma ACE levels may allow for the optimization of a preventive intervention to reduce cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. In this study, we aimed to analyze the association between ACE I/D polymorphism and cardiovascular mortality risk among non-hemodialyzed chronic kidney disease patients. This cross-sectional study examined 70 patients of Javanese ethnic origin with stable CKD who did not receive hemodialysis. ACE I/D polymorphisms, plasma ACE levels, atherosclerotic cardiovascular disease (ASCVD) risk, and cardiovascular mortality risk were investigated. As per our findings, the I allele was found to be more frequent (78.6) than the D allele (21.4), and the DD genotype was less frequent than the II genotype (4.3 vs. 61.4). The ACE I/D polymorphism had a significant direct positive effect on plasma ACE levels (path coefficient = 0.302, p = 0.021). Similarly, plasma ACE levels had a direct and significant positive effect on the risk of atherosclerotic cardiovascular disease (path coefficient = 0.410, p = 0.000). Moreover, atherosclerotic cardiovascular disease risk had a significant positive effect on cardiovascular mortality risk (path coefficient = 0.918, p = 0.000). The ACE I/D polymorphism had no direct effect on ASCVD and cardiovascular mortality risk. However, our findings show that the indirect effects of high plasma ACE levels may be a factor in the increased risk of ASCVD and cardiovascular mortality in Javanese CKD patients.

The Role of Plasma Interleukin-6 Levels on Atherosclerotic Cardiovascular Disease and Cardiovascular Mortality Risk Scores in Javanese Patients with Chronic Kidney Disease.

Interleukin-6 (IL-6) has been identified as an important pro-inflammatory factor involved in mediating the severity of chronic kidney disease (CKD). This study sought to determine the effect of plasma IL-6 levels on atherosclerotic cardiovascular disease (ASCVD) and cardiovascular mortality risk scores in Javanese CKD patients. We also analyzed the frequency of IL-6 G174C single nucleotide polymorphism (SNP) in the population. This study was a cross-sectional study involving seventy-three patients of Javanese ethnic origin with stable chronic kidney disease. We assessed the ASCVD risk score, cardiovascular mortality score, genotyping of IL-6 G174C SNP, and plasma IL-6 levels in these patients. The genotype distribution and allele frequencies of the IL-6 G174C SNP were predominated by the G genotype/allele (GG: 97.26%, GC: 1.37%, CC: 1.37%, G-allele: 97.95%, and C-allele: 2.05%). Despite the fact that plasma IL-6 levels did not directly affect cardiovascular mortality risk, further analysis revealed its direct effect on the ASCVD risk score (path coefficient = 0.184, p = 0.043, 95% CI = 0.018−0.380), which in turn affected cardiovascular mortality risk (path coefficient = 0.851, p = <0.01, 95% CI = 0.714−0.925). In conclusion, plasma IL-6 levels play important roles on ASCVD risk and cardiovascular mortality risk in Javanese patients with CKD.

Do Vitamin D receptor gene polymorphisms affect bone mass density in men?: A meta-analysis of observational studies.

The signs of aging in humans can often be detected through a decrease in bone mass density (BMD). The decrease in BMD as a risk of osteoporosis is often only seen in women, but not in men, even though men also have a risk of osteoporosis which can affect their well-being. We conducted study searches through databases such as PubMed, EBSCO, ProQuest, Willey Online, Science Direct, and SAGE. We performed analysis on four types of Vitamin D receptor polymorphisms: BsmI, ApaI, FokI, and TaqI from 14 potential studies involving men. We found that several genetic analysis models of BsmI and FokI significantly affected BMD in men: BB vs bb in whole body BMD (SMD = 0.43, 95% CI = [0.12-0.75], p = 0.0008, BB vs Bb in whole body BMD (SMD = -1.38, 95% CI = [-1.87 to 0.88], p < 0.00001), and FF+Ff vs ff spine BMD (SMD = 0.59, 95% CI = 0.13-1.05], p = 0.001), even after adjusting for comorbidities as confounding variables. The present meta-analysis showed that BsmI and FokI polymorphisms of the VDR gene were correlated with decreased BMD in men which may contribute to the aging process and well-being.

Stem cell therapy and diabetic erectile dysfunction: A critical review.

Erectile dysfunction (ED) has been identified as one of the most frequent chronic complications of diabetes mellitus (DM). The prevalence of ED is estimated to be about 67.4% in all DM cases worldwide. The pathophysiological process leading to ED involves endothelial, neurological, hormonal, and psychological factors. In DM, endothelial and neurological factors play a crucial role. Damages in the blood vessels and erectile tissue due to insulin resistance are the hallmark of ED in DM. The current treatments for ED include phosphodiesterase-5 inhibitors and penile prosthesis surgery. However, these treatments are limited in terms of just relieving the symptoms, but not resolving the cause of the problem. The use of stem cells for treating ED is currently being studied mostly in experimental animals. The stem cells used are derived from adipose tissue, bone, or human urine. Most of the studies observed an improvement in erectile quality in the experimental animals as well as an improvement in erectile tissue. However, research on stem cell therapy for ED in humans remains to be limited. Nevertheless, significant findings from studies using animal models indicate a potential use of stem cells in the treatment of ED.

Initial study on TMPRSS2 p.Val160Met genetic variant in COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global health problem that causes millions of deaths worldwide. The clinical manifestation of COVID-19 widely varies from asymptomatic infection to severe pneumonia and systemic inflammatory disease. It is thought that host genetic variability may affect the host's response to the virus infection and thus cause severity of the disease. The SARS-CoV-2 virus requires interaction with its receptor complex in the host cells before infection. The transmembrane protease serine 2 (TMPRSS2) has been identified as one of the key molecules involved in SARS-CoV-2 virus receptor binding and cell invasion. Therefore, in this study, we investigated the correlation between a genetic variant within the human TMPRSS2 gene and COVID-19 severity and viral load. RESULTS: We genotyped 95 patients with COVID-19 hospitalised in Dr Soetomo General Hospital and Indrapura Field Hospital (Surabaya, Indonesia) for the TMPRSS2 p.Val160Met polymorphism. Polymorphism was detected using a TaqMan assay. We then analysed the association between the presence of the genetic variant and disease severity and viral load. We did not observe any correlation between the presence of TMPRSS2 genetic variant and the severity of the disease. However, we identified a significant association between the p.Val160Met polymorphism and the SARS-CoV-2 viral load, as estimated by the Ct value of the diagnostic nucleic acid amplification test. Furthermore, we observed a trend of association between the presence of the C allele and the mortality rate in patients with severe COVID-19. CONCLUSION: Our data indicate a possible association between TMPRSS2 p.Val160Met polymorphism and SARS-CoV-2 infectivity and the outcome of COVID-19.

Inflammatory laboratory findings associated with severe illness among hospitalized individuals with COVID-19 in Medan, Indonesia: a cross-sectional study.

Background: Coronavirus disease (COVID-19) is still a global health problem. COVID-19 patients with severe pneumonia have a higher risk for critical illness, mostly complicated by acute respiratory distress syndrome. The inflammatory response is critical, and the cytokine storm increases severity of COVID-19. Many factors could be associated with a cytokine storm but these are incompletely understood. The aim of this study is to present characteristics of patients with COVID-19 and explore the clinical and inflammatory parameters of severe and critically ill COVID-19 patients in the intensive care unit (ICU). Method: The cross-sectional study was conducted in all severe COVID-19 patients admitted to the ICU. Peripheral blood was taken for laboratory examination within 24 hours of admission. Hematologic parameters, serum electrolyte, renal function, liver function, pancreas enzyme, D-dimer, inflammatory cytokines interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, monocyte chemoattractant protein-1 (MCP-1), and C-reactive protein (CRP) were assessed in this study. Comparison analyses were done between sex, comorbidity existed, body mass index (BMI), and vaccination status. Results: A total of 80 subjects were included in the study. The most frequent comorbidities found among the subjects were obesity (36.35%) and diabetes (22.5%). Only 13.75% of subjects were vaccinated. Laboratory results indicated leukocytosis and neutrophilia, with neutrophil-lymphocyte-ratio (NLR) of 7. The mean inflammatory findings (IL-6, IL-10, TNF-alpha, IFN-gamma, MCP-1), D-dimer, CRP, and lipase increased. Lipase levels were higher in men (p=0.003) and in comorbidity groups. No significant differences found with different BMI groups. Lipase, IL-6, and MCP-1 levels were significantly higher (p=0.019, <0.0001, and 0.03, respectively) in the non-vaccinated group. Conclusions: Most patients with severe COVID-19 have comorbidities and increased inflammatory markers.