Dermatologic manifestations of hereditary hemochromatosis: A systematic review.

Hereditary hemochromatosis (HH) is a genetic disorder leading to excessive iron absorption, impacting multiple organs, notably the skin, nails and mucosae. The objective of this study is to elucidate the dermatologic manifestations, associated symptoms, pathophysiology and management recommendations of HH. We searched five primary databases (PubMed, Embase, Cochrane Library, Scopus and Web of Science) up to April 2023. Non-English articles were included to minimize language bias. The studies were evaluated using Oxford Centre for Evidence-based Medicine standards, with adherence to PRISMA guidelines. Inaccessible articles were directly sourced from authors. Out of the initial 1582 publications from 1904 to 2023, 22 studies (19 in English, 2 in French and 1 in German) were selected. Most reports were from the USA, UK and France and were predominantly case reports, covering 148 patients with skin symptoms related to hereditary hemochromatosis. We collected data on the cutaneous findings and, when available, their histopathological features. The current study highlights the scope, variety and traits of dermatologic symptoms in hereditary hemochromatosis, pinpointing research gaps and areas for future exploration. Our review accentuates the diverse dermatological manifestations of hereditary hemochromatosis, notably hyperpigmentation, hypertrichosis and resistant pruritus, often linked to excessive iron deposition and subsequent impairment of skin cell function. We also found controversial evidence indicating that skin cancers seem to be associated with hereditary hemochromatosis. Porphyria cutanea tarda and hereditary hemochromatosis were frequently reported together. Given hereditary hemochromatosis's genetic nature, early identification in one individual can substantially guide familial care and preemptive interventions. Clinicians should prioritize hereditary hemochromatosis as a differential when patients present with specific dermatological symptoms, especially in sun-exposed regions. A rigorous assessment ensures accurate diagnosis, facilitating optimal management for both the patient and their family.

Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Irritable bowel syndrome (IBS) poses a significant challenge due to its poorly understood pathogenesis, substantial morbidity, and often inadequate treatment outcomes. The role of fecal microbiota transplantation (FMT) in managing IBS symptoms remains inconclusive. This systematic review and meta-analysis aimed to ascertain the effectiveness of FMT in relieving symptoms in IBS patients. A thorough search was executed on PubMed/Medline and Embase databases until 14 June 2023, including all studies on FMT use in IBS patients. We examined the efficiency of FMT in reducing patients' symptoms overall and in particular subgroups, classified by placebo preparation, FMT preparation, frequency, and route of administration. Among 1015 identified studies, seven met the inclusion criteria for the meta-analysis. The overall symptomatology of FMT-treated IBS patients did not significantly differ from the control group (Odds Ratio (OR) = 0.99, 95% Confidence Interval (CI) 0.39-2.5). Multiple doses of FMT compared with non-FMT placebo, or single-donor FMT therapy compared with autologous FMT placebo also showed no significant benefit (OR = 0.32, 95%CI (0.07-1.32), p = 0.11, and OR = 1.67, 95%CI (0.59-4.67), p = 0.32, respectively). However, a single dose of multiple-donor FMT administered via colonoscopy (lower gastrointestinal (GI) administration) significantly improved patient symptoms compared with autologous FMT placebo (OR = 2.54, 95%CI (1.20-5.37), p = 0.01, and OR = 2.2, 95%CI (1.20-4.03), p = 0.01, respectively). The studies included in the analysis showed a low risk of bias and no publication bias. In conclusion, lower GI administration of a single dose of multiple-donor FMT significantly alleviates patient complaints compared with the autologous FMT used as a placebo. The underlying mechanisms need to be better understood, and further experimental studies are desired to fill the current gaps.

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

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

BCG Vaccination and the Risk of Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

(1) Background: Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by progressive and irreversible autoimmune destruction of pancreatic beta cell islets, resulting in absolute insulin deficiency. To date, several epidemiologic and observational studies have evaluated the possible impact of BCG vaccination on T1D development, but the results are controversial. To elucidate this issue, we aimed to conduct a systematic review and meta-analysis of published cohort studies in this field. (2) Methods: A systematic search was performed for relevant studies published up to 20 September 2022 using Pubmed/Medline, Embase, and Scopus. Cohort studies, containing original information about the association between T1D and BCG vaccination, were included for further analysis. Pooled estimates and 95% confidence intervals (CI) for the risk ratio of T1D in BCG-vaccinated individuals compared to unvaccinated ones were assessed using the fixed effect model. (3) Results: Out of 630 potentially relevant articles, five cohort studies met the inclusion criteria. The total population of all included studies was 864,582. The overall pooled risk ratio of T1D development in BCG vaccinated and unvaccinated individuals was found to be 1.018 (95% CI 0.908-1.141, I2: 0%). (4) Conclusions: Our study revealed no protective or facilitative effect of prior BCG vaccination in T1D development.

Demographic, Epidemiologic, and Clinical Characteristics of Human Monkeypox Disease Pre- and Post-2022 Outbreaks: A Systematic Review and Meta-Analysis.

(1) Background: In early May 2022, an increasing number of human monkeypox (mpox) cases were reported in non-endemic disparate regions of the world, which raised concerns. Here, we provide a systematic review and meta-analysis of mpox-confirmed patients presented in peer-reviewed publications over the 10 years before and during the 2022 outbreak from demographic, epidemiological, and clinical perspectives. (2) Methods: A systematic search was performed for relevant studies published in Pubmed/Medline, Embase, Scopus, and Google Scholar from 1 January 2012 up to 15 February 2023. Pooled frequencies with 95% confidence intervals (CIs) were assessed using the random or fixed effect model due to the estimated heterogeneity of the true effect sizes. (3) Results: Out of 10,163 articles, 67 met the inclusion criteria, and 31 cross-sectional studies were included for meta-analysis. Animal-to-human transmission was dominant in pre-2022 cases (61.64%), but almost all post-2022 reported cases had a history of human contact, especially sexual contact. The pooled frequency of MSM individuals was 93.5% (95% CI 91.0-95.4, I2: 86.60%) and was reported only in post-2022 included studies. The male gender was predominant in both pre- and post-2022 outbreaks, and the mean age of confirmed cases was 29.92 years (5.77-41, SD: 9.38). The most common clinical manifestations were rash, fever, lymphadenopathy, and malaise/fatigue. Proctalgia/proctitis (16.6%, 95% CI 10.3-25.6, I2: 97.76) and anal/perianal lesions (39.8%, 95% CI 30.4-49.9, I2: 98.10) were the unprecedented clinical manifestations during the 2022 outbreak, which were not described before. Genitalia involvement was more common in post-2022 mpox patients (55.6%, 95% CI 51.7-59.4, I2: 88.11). (4) Conclusions: There are speculations about the possibility of changes in the pathogenic properties of the virus. It seems that post-2022 mpox cases experience a milder disease with fewer rashes and lower mortality rates. Moreover, the vast majority of post-2022 cases are managed on an outpatient basis. Our study could serve as a basis for ongoing investigations to identify the different aspects of previous mpox outbreaks and compare them with the current ones.

Diagnostic, Prognostic, and Therapeutic Roles of Gut Microbiota in COVID-19: A Comprehensive Systematic Review.

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) emerged in late December 2019. Considering the important role of gut microbiota in maturation, regulation, and induction of the immune system and subsequent inflammatory processes, it seems that evaluating the composition of gut microbiota in COVID-19 patients compared with healthy individuals may have potential value as a diagnostic and/or prognostic biomarker for the disease. Also, therapeutic interventions affecting gut microbial flora may open new horizons in the treatment of COVID-19 patients and accelerating their recovery. Methods: A systematic search was conducted for relevant studies published from December 2019 to December 2021 using Pubmed/Medline, Embase, and Scopus. Articles containing the following keywords in titles or abstracts were selected: "SARS-CoV-2" or "COVID-19" or "Coronavirus Disease 19" and "gastrointestinal microbes" or "dysbiosis" or "gut microbiota" or "gut bacteria" or "gut microbes" or "gastrointestinal microbiota". Results: Out of 1,668 studies, 22 articles fulfilled the inclusion criteria and a total of 1,255 confirmed COVID-19 patients were examined. All included studies showed a significant association between COVID-19 and gut microbiota dysbiosis. The most alteration in bacterial composition of COVID-19 patients was depletion in genera Ruminococcus, Alistipes, Eubacterium, Bifidobacterium, Faecalibacterium, Roseburia, Fusicathenibacter, and Blautia and enrichment of Eggerthella, Bacteroides, Actinomyces, Clostridium, Streptococcus, Rothia, and Collinsella. Also, some gut microbiome alterations were associated with COVID-19 severity and poor prognosis including the increment of Bacteroides, Parabacteroides, Clostridium, Bifidobacterium, Ruminococcus, Campylobacter, Rothia, Corynebacterium, Megasphaera, Enterococcus, and Aspergillus spp. and the decrement of Roseburia, Eubacterium, Lachnospira, Faecalibacterium, and the Firmicutes/Bacteroidetes ratio. Conclusion: Our study showed a significant change of gut microbiome composition in COVID-19 patients compared with healthy individuals. This great extent of impact has proposed the gut microbiota as a potential diagnostic, prognostic, and therapeutic strategy for COVID-19. There is much evidence about this issue, and it is expected to be increased in near future.

Skin Manifestations in COVID-19 Patients: Are They Indicators for Disease Severity? A Systematic Review.

Introduction: Until now, there are several reports on cutaneous manifestations in COVID-19 patients. However, the link between skin manifestations and the severity of the disease remains debatable. We conducted a systematic review to evaluate the temporal relationship between different types of skin lesions and the severity of COVID-19. Methods: A systematic search was conducted for relevant studies published between January and July 2020 using Pubmed/Medline, Embase, and Web of knowledge. The following keywords were used: "SARS-CoV-2" or "COVID-19" or "new coronavirus" or "Wuhan Coronavirus" or "coronavirus disease 2019" and "skin disease" or "skin manifestation" or "cutaneous manifestation." Results: Out of 381 articles, 47 meet the inclusion criteria and a total of 1,847 patients with confirmed COVID-19 were examined. The overall frequency of cutaneous manifestations in COVID-19 patients was 5.95%. The maculopapular rash was the main reported skin involvement (37.3%) commonly occurred in middle-aged females with intermediate severity of the disease. Forty-eight percentage of the patients had a mild, 32% a moderate, and 20% a severe COVID-19 disease. The mild disease was mainly correlated with chilblain-like and urticaria-like lesions and patients with vascular lesions experienced a more severe disease. Seventy-two percentage of patients with chilblain-like lesions improved without any medication. The overall mortality rate was 4.5%. Patients with vascular lesions had the highest mortality rate (18.2%) and patients with urticaria-like lesions had the lowest mortality rate (2.2%). Conclusion: The mere occurrence of skin manifestations in COVID-19 patients is not an indicator for the disease severity, and it highly depends on the type of skin lesions. Chilblain-like and vascular lesions are the ends of a spectrum in which from chilblain-like to vascular lesions, the severity of the disease increases, and the patient's prognosis worsens. Those with vascular lesions should also be considered as high-priority patients for further medical care.

The prevalence of metabolic syndrome in cardiovascular patients in Iran: a systematic review and meta-analysis.

BACKGROUND: Cardiovascular disease is the cause of more than 50% of mortalities globally, and this rate has grown by 8.6% since the 60 s. One of the risk factors associated with cardiovascular disease and its resulting mortality rate is the metabolic syndrome. Different studies have reported inconsistent rates for the metabolic syndrome. However, no comprehensive study has been conducted to combine the results of existing studies. Thus, the present study was performed with the aim of determining the prevalence of metabolic syndrome among cardiovascular patients in Iran through a systematic review and meta-analysis. METHOD: In this review study, the Scientific Information Database, Google Scholar, Science Direct, Scopus, PubMed, and Web of Science (ISI), databases were searched from January 2005 and until May 2020, to identify and extract related articles. To conduct the analysis, a random effects model was used, and the heterogeneity of the studies was examined using the I2 index. Data analysis was performed within Comprehensive Meta-Analysis (version 2) software. RESULTS: The prevalence of metabolic syndrome in cardiovascular patients in Iran in the 27 papers examined with a sample size of 44,735 patients was 34.2% (95% CI: 26.8-42.6%). A sensitivity analysis was performed to ensure the stability of the results, these results show that by omitting the prevalence from each study, the overall prevalence (34.2%) does not change significantly. the highest prevalence of metabolic syndrome in studies conducted in the period between 2015 and 2020, and this was reported as 55.3 (95% CI: 47.9-62.3) and the highest prevalence of metabolic syndrome in studies conducted in the methods of diagnosis IDF, and the rate was reported as 48 (95% CI: 36.5-59.8). based on meta-regression as the year of research increased, the prevalence of metabolic syndrome in cardiovascular patients in Iran also increased. However, with the increase in sample size, this prevalence decreased (p < 0.05). CONCLUSIONS: The results of this study indicate that metabolic syndrome is high in cardiovascular patients in Iran. Accordingly, by understanding its etiology and supervision at all levels, suitable solutions could be offered by providing feedback to hospitals.

The effect of unilateral and bilateral laparoscopic surgery for endometriosis on Anti-Mullerian Hormone (AMH) level after 3 and 6 months: a systematic review and meta-analysis.

BACKGROUND: Endometriosis is one of the most common causes of infertility. The causes of the disease and its definitive treatments are still unclear. Moreover, Anti-Mullerian Hormone (AMH) is a glycoprotein dimer that is a member of the transient growth factors family. This research work aimed to identify the effect of unilateral and bilateral laparoscopic surgery for endometriosis on AMH levels after 3 months, and 6 months, using meta-analysis. METHODS: In this study, the articles published in national and international databases of SID, MagIran, IranMedex, IranDoc, Cochrane, Embase, Science Direct, Scopus, PubMed, and Web of Science (ISI) were searched to find electronically published studies between 2010 and 2019. The heterogeneous index between studies was determined using the I2 index. RESULTS: In this meta-analysis and systematic review, 19 articles were eligible for inclusion in the study. The standardized mean difference was obtained in examining of unilateral laparoscopic surgery for endometriosis (before intervention 2.8 ± 0.11, and after 3 months 2.05 ± 0.13; and before intervention 3.1 ± 0.46 and after 6 months 2.08 ± 0.31), and in examining bilateral laparoscopic surgery for endometriosis examination (before intervention 2.0 ± 08.08, and after 3 months 1.1 ± 0.1; and before intervention 2.9 ± 0.23 and after 6 months 1.4 ± 0.19). CONCLUSION: The results of this study demonstrate that unilateral and bilateral laparoscopic surgery for endometriosis is effective on AMH levels, and the level decreases in both comparisons.

Olfactory and gustatory dysfunction in COVID-19 patients: A meta-analysis study.

COVID-19, caused by a novel coronavirus, is a persistent global pandemic. It is crucial to examine existing reports to effectively summarize and characterize its clinical course. We used a large-scale meta-analysis to establish prevalence rates for loss of olfaction and gustation in COVID-19 positive patients. PubMed/Medline, Embase, and Web of Sciences were searched for articles published until April 30, 2020. Furthermore, to avoid missing papers, more searches were carried out in the reference lists of covered studies. Articles that mentioned olfactory and/or gustatory disorder in patients with COVID-19 were included for further analysis. Articles that did not report the aforementioned information were excluded. Duplicated articles, reviews, and meta-analysis were excluded as well. The quality of the references was assessed according to the checklist provided by JBI (Joanna Briggs Institute). We used independent extraction of data by multiple observers. The pooled frequency with 95% confidence intervals (CI) was assessed using random effect model. The main outcome measures reported were the pooled frequency of olfaction and pooled frequency of gustation disorder in patients with COVID-19 calculated using a random effect model weighted by the study population. The 15 included studies had 3,739 participants which all had confirmed COVID-19. Olfactory and gustatory disorders were assessed and a total number of 1,354 and 1,729 were reported to have taste or smell impairment, respectively. The estimated rate of taste disorder in patients with COVID-19 was 49.0% [95% confidence interval (CI) 34.0-64.0, I2: 96%] (Figure 2). The estimated rate of olfactory disorder in patients with COVID-19 was 61.0% (95% CI 44.0%-75.0%). Our meta-analysis demonstrated high rates of taste (49.0%) and smell (61.0%) disorders in patients with confirmed COVID-19. Results increase the power of recent reports-loss of olfactory and loss of gustation should now routinely be considered in the setting of COVID-19 infection.

COVID-19 Clinical Characteristics, and Sex-Specific Risk of Mortality: Systematic Review and Meta-Analysis.

Background: The rapidly evolving coronavirus disease 2019 (COVID-19), was declared a pandemic by the World Health Organization on March 11, 2020. It was first detected in the Wuhan city of China and has spread globally resulting in a substantial health and economic crisis in many countries. Observational studies have partially identified different aspects of this disease. There have been no published systematic reviews that combine clinical, laboratory, epidemiologic, and mortality findings. Also, the effect of gender on the outcomes of COVID-19 has not been well-defined. Methods: We reviewed the scientific literature published from January 1, 2019 to May 29, 2020. Statistical analyses were performed with STATA (version 14, IC; Stata Corporation, College Station, TX, USA). The pooled frequency with 95% confidence intervals (CI) was assessed using random effect model. P < 0.05 was considered a statistically significant publication bias. Results: Out of 1,223 studies, 34 satisfied the inclusion criteria. A total of 5,057 patients with a mean age of 49 years were evaluated. Fever (83.0%, CI 77.5-87.6) and cough (65.2%, CI 58.6-71.2) were the most common symptoms. The most prevalent comorbidities were hypertension (18.5%, CI 12.7-24.4) and Cardiovascular disease (14.9%, CI 6.0-23.8). Among the laboratory abnormalities, elevated C-Reactive Protein (CRP) (72.0%, CI 54.3-84.6) and lymphopenia (50.1%, CI 38.0-62.4) were the most common. Bilateral ground-glass opacities (66.0%, CI 51.1-78.0) was the most common CT scan presentation. The pooled mortality rate was 6.6%, with males having significantly higher mortality compared to females (OR 3.4; 95% CI 1.2-9.1, P = 0.01). Conclusion: COVID-19 has caused a significant number of hospitalization and mortality worldwide. Mortality associated with COVID-19 was higher in our study compared to the previous reports from China. The mortality was significantly higher among the hospitalized male group. Further studies are required to evaluate the effect of different variables resulting in sex disparity in COVID-19 mortality.

Clinical Features, Diagnosis, and Treatment of COVID-19 in Hospitalized Patients: A Systematic Review of Case Reports and Case Series.

Introduction: The 2019 novel coronavirus (COVID-19) has been declared a public health emergency worldwide. The objective of this systematic review was to characterize the clinical, diagnostic, and treatment characteristics of hospitalized patients presenting with COVID-19. Methods: We conducted a structured search using PubMed/Medline, Embase, and Web of Science to collect both case reports and case series on COVID-19 published up to April 24, 2020. There were no restrictions regarding publication language. Results: Eighty articles were included analyzing a total of 417 patients with a mean age of 48 years. The most common presenting symptom in patients who tested positive for COVID-19 was fever, reported in up to 62% of patients from 82% of the analyzed studies. Other symptoms including rhinorrhea, dizziness, and chills were less frequently reported. Additionally, in studies that reported C-reactive protein (CRP) measurements, a large majority of patients displayed an elevated CRP (60%). Progression to acute respiratory distress syndrome (ARDS) was the most common complication of patients testing positive for COVID-19 (21%). CT images displayed ground-glass opacification (GGO) patterns (80%) as well as bilateral lung involvement (69%). The most commonly used antiviral treatment modalities included, lopinavir (HIV protease inhibitor), arbidiol hydrochloride (influenza fusion inhibitor), and oseltamivir (neuraminidase inhibitor). Conclusions: Development of ARDS may play a role in estimating disease progression and mortality risk. Early detection of elevations in serum CRP, combined with a clinical COVID-19 symptom presentation may be used as a surrogate marker for the presence and severity of the disease. There is a paucity of data surrounding the efficacy of treatments. There is currently not a well-established gold standard therapy for the treatment of diagnosed COVID-19. Further prospective investigations are necessary.

Is there any association between gut microbiota and type 1 diabetes? A systematic review.

INTRODUCTION: Type 1 diabetes (T1D) is the second most common autoimmune disease among children. There is evidence suggesting that dysbiosis of some gut colonizing bacteria are associated with the pathogenesis of T1D. However, these studies are still controversial and a systematic review was conducted to evaluate the association between gut microbiota and T1D. METHODS: A systematic search was carried out in Medline (Via Pubmed) and Embase from January 2000 to January 2019 for all original cross-sectional, cohort, case-control or nested case-control studies investigating the association between gut microbiota and T1D. RESULTS: Of 568 articles identified, 26 studies met the inclusion criteria. The total population study of these articles consists of 2600 children (under 18 years old) and 189 adults. Among the included studies, 24 articles confirmed the association between gut microbiota dysbiosis and T1D. The most common bacterial alterations in T1D patients included Bacteroides spp., Streptococcus spp., Clostridium spp., Bifidobacterium spp., Prevotella spp., Staphylococcus spp., Blautia spp., Faecalibacterium spp., Roseburia spp., and Lactobacillus spp. CONCLUSION: Our study showed a significant association between alterations in intestinal microbial composition and T1D; however, in some articles, it is not clear which one happens first. Investigation of altered gut microbiota can help in the early detection of T1D before seropositivity. Targeted microbiome modulation can be a novel potential therapeutic strategy.

The Effects of Glyceryl Trinitrate Patch on the Treatment of Preterm Labor: A Single-blind Randomized Clinical Trial.

BACKGROUND: Preterm labor (PTL) is one of the main causes of neonatal mortality and morbidity. PTL leads to serious complications especially in the gestational age prior to 24-26 weeks. The aim of this study was to investigate the effect of glyceryl trinitrate (GTN) patch on the treatment and complications of PTL. METHODS: In this clinical trial, 84 singleton pregnant women with gestational age of 27-35 weeks were surveyed. PTL was clinically diagnosed and the patients were randomly divided into two groups who were treated with GTN or placebo for 48 hr. The consequences, complications and changes in some parameters in both groups were compared. Data were analyzed with chi square test, paired and unpaired t tests by SPSS software and p<0.05 was considered significant. RESULTS: No significant difference was observed between two groups in terms of successful tocolysis, receiving full dose of corticosteroids and the mean prolongation of the pregnancy. However, delivery times in patients who delivered during the hospitalization were 31±4.4 and 18.3±2.2 hr (p=0.01), respectively. Headache was more severe in control group (p=0.007). The systolic and mean arterial blood pressure decrease (p<0.001) and maternal heart rate increase (p=0.01) were significant in GTN group. The changes of vital signs were not significant in placebo group. CONCLUSION: The effect of GTN in the treatment of PTL is similar to the placebo without any serious complication. However, GTN delays the delivery time in delivery during the primary hospitalization. Thus, further studies with larger sample size are needed to evaluate the exact effects of GTN on PTL.