The impact of piperine on the metabolic conditions of patients with NAFLD and early cirrhosis: a randomized double-blind controlled trial.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic dysfunction of the liver defined as an abnormal accumulation of fat within the liver without secondary triggers like alcohol consumption or viral hepatitis. Piperine, the bio-active ingredient of black pepper, can exert a significant function in treatment of individuals with NAFLDand early cirrhosis. We investigated the impact of piperine consumption with a duration of 12 weeks on patients with NAFLD and early cirrhosis compared toplacebo consumption. In a double-blind study, patients with NAFLD and early stage of cirrhosis were haphazardly distributed into case and control groups. They were prescribed a placebo and 5 mg of piperine for 12 weeks, respectively. The demographic and laboratory parameters of individuals were assessed as the baseline and after the duration of piperine intake. Piperine with a daily dosage of 5 mg could significantly decrease hepatic enzymes and glucose, and alleviate dyslipidemia in the case arm rather than the control arm. Moreover, HOMA levels and insulin resistance were reduced in case participants compared to the control counterparts. In the absence of approved medicinal intervention for patients with NAFLD, and regarding the favorable impact of piperine on NAFLD more studies on this subject are warranted.

Circulating glucagon-like peptide-1 level in patients with liver cirrhosis.

BACKGROUND: Glucagon-like peptide-1 (GLP-1), a gut-derived incretin hormone, plays a pivotal role in glucose-induced insulin secretion. Currently, the role of incretin hormones in the pathogenesis of cirrhosis is not clearly defined. This study aimed to investigate circulating levels of GLP-1 in liver cirrhosis and its association with the severity of liver disease. METHODS: A total of 80 participants including 39 patients with a definite diagnosis of liver cirrhosis and 41 healthy controls recruited in this cross-sectional study. Circulating levels of GLP-1 were determined using the ELISA method. The severity of liver cirrhosis was assessed according to the Child-Pugh, MELD (i), MELD-Na, MELD New, and UK end-stage liver disease score (UKELD) criteria. RESULTS: The mean age of patients and healthy subjects was 42.51 ± 12.80 and 42.07 ± 10.92 years, respectively (p value = .869). The mean MELD (i), MELD-Na, MELD New, UKELD, and Child-Pugh scores were 14.36 ± 4.26, 15.26 ± 4.81, 14.74 ± 4.66, 52.33 ± 3.82, and 7.28 ± 1.50, respectively. In this study, circulating levels of GLP-1 were statistically lower in cirrhotic patients compared with healthy controls (95.26 ± 17.15 vs 111.84 ± 38.14 pg/mL; p value = .017). CONCLUSION: Larger prospective studies are needed to explore the incretin effect in cirrhosis patients compared with healthy individuals.

Cold intolerance and associated factors: a population study.

Cold intolerance has been defined as a set of symptoms including pain, tingling, numbness, chills, stiffness, weakness, swelling or skin color changes on exposure to cold. Cold intolerance may have a profound effect on health-related quality of life. In this cross-sectional study, we investigated primarily the prevalence of cold intolerance and secondly associated factors in the general population of Tabriz. Simple random sampling of individuals aged ≥ 18 was performed from the population covered by Emamieh health center under the supervision of Tabriz University of Medical Sciences. A telephone interview was conducted with the participants by the general physician of that center. In participants with a positive response to each of two questions "I am oversensitive to cold" and "I experience pain or discomfort when exposed to cold" a Cold Intolerance Symptom Severity (CISS) questionnaire was filled. We used a cut off value 50 for defining cold intolerance. Of the 353 person who received telephone calls, 322 answered questions. Cold related symptoms and cold intolerance were reported in 144 (44.7%) and 38 (11.1%) persons, respectively. Cold intolerance was significantly more common in females and people with comorbidities. Cold intolerance led to a decrease in quality of job in 27 (8.4%) and a change in job in 6 (1.9%) persons. In conclusion, cold intolerance is a common problem in the general population of Tabriz.

Biomarkers for Transient Ischemic Attack: A Brief Perspective of Current Reports and Future Horizons.

Cerebrovascular disease is the leading cause of long-term disability in the world and the third-leading cause of death in the United States. The early diagnosis of transient ischemic attack (TIA) is of great importance for reducing the mortality and morbidity of cerebrovascular diseases. Patients with TIA have a high risk of early subsequent ischemic stroke and the development of permanent nervous system lesions. The diagnosis of TIA remains a clinical diagnosis that highly relies on the patient's medical history assessment. There is a growing list of biomarkers associated with different components of the ischemic cascade in the brain. In this review, we take a closer look at the biomarkers of TIA and their validity with a focus on the more clinically important ones using recent evidence of their reliability for practical usage.

Nasopharyngeal structure development in patients with cleft palate who underwent repair surgery.

OBJECTIVE: This study aimed to compare the developmental characteristics of bony nasopharyngeal (NP) in children with cleft palate (CP) and non-cleft subjects. METHODS: This study was conducted on 64 non-syndromic CP patients who underwent repair surgery and 23 non-cleft subjects as controls. Lateral cephalograms were performed on participants at rest in the natural head position. The X-coordinate and the Y-coordinate of three points on cephalograms were determined as Hormion (Ho), posterior maxillary point (PMP) and anterior point of the atlas (At) representing the anterior-posterior (AP) and vertical dimension of the NP. The linear dimension of the NP (i.e. Ho-At, Ho-PMP, At-PMP) and its area was also calculated. RESULTS: The bony structures of NP in the clef-affected subjects in isolated CP subgroup, had a significantly greater downward development in the maxillary region (PMP) (both with p = 0.001), more linear growth in cranial-maxillary (Ho-PMP) dimension (p = 0.017 and 0.004, respectively), and larger area (p = 0.017 and <0.001, respectively), when compared to normal subjects. There was no significant difference between either the unilateral cleft lip and palate (CLP) or bilateral CLP group with the control group regarding AP, vertical, and linear growth of the NP and its area (P > 0.05). CONCLUSIONS: Patients with repaired CP had downward deviated posterior maxilla, more linear growth in cranial-maxillary dimension and larger area compared to normal subjects. Among CP subtypes, a balanced growth was observed among repaired UCLP and BCLP patients, suggesting that with appropriate repaired surgery, normal development of the NP region could be expected in these subtypes.

Long-term side effects and lingering symptoms post COVID-19 recovery.

Since the Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), our understanding regarding the pathophysiology and clinical manifestations of this disease have been improving. However, we still have limited data on long-term effects and lingering symptoms of post COVID-19 recovery. Despite predilection of COVID-19 for lungs, multiple extra-pulmonary manifestations appear in multiple organs and biological systems and with continued infection and recovery worldwide. It is necessary that clinicians provide patients with previous SARS-CoV-2 infection with expectations of long-term effects during or after recovery from COVID-19. Herein, we review the long-term impact of COVID-19 on different organ systems reported from different clinical studies. Understanding risk factors and signs and symptoms of long-term consequences after recovery from COVID-19 will allow for proper follow-up and management of the disease post recovery.

NETosis in ischemic/reperfusion injuries: An organ-based review.

Neutrophil extracellular trap (NETosis), the web-like structures induced by neutrophil death, is an important inflammatory mechanism of the immune system leading to reactive oxygen species production/coagulopathy, endothelial dysfunction, atherosclerosis, and ischemia. NETosis exerts its role through different mechanisms such as triggering Toll-like receptors, inflammatory cytokines, platelet aggregation, neutrophil activation/infiltration, and vascular impairment. NETosis plays a key role in the prognosis of coronary artery disease, ischemic injury of kidney, lung, gastrointestinal tract and skeletal muscles. In this review, we explored the molecular mechanisms involved in NETosis, and ischemic/reperfusion injuries in body organs.

Trichorrhexis invaginata and ichthyosiform erythroderma in netherton syndrome.

Trichorrhexis invaginata and ichthyosiform erythroderma are pathognomic for Netherton Syndrome.

S100 Calcium-Binding Protein B and Glial Fibrillary Acidic Protein in Patients with Mild Traumatic Brain Injury.

OBJECTIVE: To examine the GFAP and S100B ability in prevention unnecessary brain Computed tomography (CT) scan in mild traumatic brain injury (mTBI) and compare them with the single extremity fracture in orthopedic patients. METHODS: In this prospective cohort study, two orthopedics patients' groups and mTBI patients were studied to assess the biomarkers' ability in prevention unnecessary brain CT scan at the emergency setting. There were 40 orthopedics' patients with single extremity fracture and 41 mTBI patients. Brain CT scans were done for all mTBI patients. RESULTS: Brain CT scans showed no intracranial traumatic lesions. The median levels for S100B in the mTBI group was 14.8 (4.4-335.9) ng/L, and in orthopedic patients' group was 13.3 (5-353.10) ng/L. Statistically significant differences were observed between both groups in S100B levels (p=0.006). The median Glial Fibrillary Acidic Protein (GFAP) levels in the mTBI patients' group were 600 (400-16300) and in the orthopedic patients' groups was 60 ng/L (300-14900). Statistically significant differences were observed between groups in GFAP (p=0.041). CONCLUSION: Our results showed that S100B and GFAP serum levels were significantly higher in patients with mTBI than in patients with a single limb fracture.

Scores based on neutrophil percentage and lactate dehydrogenase with or without oxygen saturation predict hospital mortality risk in severe COVID-19 patients.

BACKGROUND: Risk scores are needed to predict the risk of death in severe coronavirus disease 2019 (COVID-19) patients in the context of rapid disease progression. METHODS: Using data from China (training dataset, n = 96), prediction models were developed by logistic regression and then risk scores were established. Leave-one-out cross validation was used for internal validation and data from Iran (test dataset, n = 43) was used for external validation. RESULTS: A NSL model (area under the curve (AUC) 0.932) and a NL model (AUC 0.903) were developed based on neutrophil percentage and lactate dehydrogenase with and without oxygen saturation (SaO2) using the training dataset. AUCs of the NSL and NL models in the test dataset were 0.910 and 0.871, respectively. The risk scoring systems corresponding to these two models were established. The AUCs of the NSL and NL scores in the training dataset were 0.928 and 0.901, respectively. At the optimal cut-off value of NSL score, the sensitivity and specificity were 94% and 82%, respectively. The sensitivity and specificity of NL score were 94% and 75%, respectively. CONCLUSIONS: These scores may be used to predict the risk of death in severe COVID-19 patients and the NL score could be used in regions where patients' SaO2 cannot be tested.

Comparison of spirometry and impulse oscillometry in methacholine challenge test for the detection of airway hyperresponsiveness in adults.

INTRODUCTION: Airway hyper-responsiveness (AHR) is a characteristic feature of asthma. The aim of this study was to compare the impulse oscillometry (IOS) and spirometry to methacholine for AHR detection among individuals with clinically hyper-reactive airway disease suggestive of bronchial asthma and baseline spirometry were normal. MATERIALS AND METHODS: Adults with symptoms suggestive of AHR and normal baseline spirometry test were selected. The short protocol of methacholine challenge test (MCT) was performed for all subjects using IOS and spirometry simultaneously. The primary endpoint was to compare the methacholine dosage causing a 20% drop in forced expiratory volume in one second (FEV1), with methacholine dosage that causing 40% increasing the baseline respiratory resistance at 5 hertz (R5), as measured by IOS. RESULT: A total of 235 participants were analyzed, 184 (78.2%) had positive test results with R5, while 81 (34.4%) had positive MCT results with FEV1.The sensitivity and specificity of MCT with R5were 87.3%, 64.6%, and MCT with FEV1 were 39.1%, 85.4%, respectively. The area under the receiver operating characteristic (ROC) curve was greater at lower doses of MCT at R5, (AUROC: 0.653; p= 0.01). CONCLUSIONS: The results showed higher sensitivity, negative predictive value, and earlier response of the short protocol of MCT with IOS, compared to MCT with spirometry. Our study suggested the utility of IOS in addition to conventional spirometry as a method of choice in MCT for detection of AHR.

Concurrent chronic lymphocytic leukemia and COVID-19: A comprehensive review of epidemiological, diagnostic, and therapeutic challenges.

A comprehensive review of the literature on chronic lymphocytic leukemia (CLL) patients and recommendations regarding the evaluation and treatment of these patients was conducted. The overall prevalence of CLL and COVID-19 concurrence was found to be 0.6% (95%CI: 0.5% to 0.7%). Diagnostic interaction between CLL and COVID-19 remains a major challenge. Also, CLL patients have a lower rate of anti-SARS-CoV-2 IgG development. Evidences show the unacceptable therapeutic outcome in these patients. Although the CLL-COVID-19 occurrence is associated with adverse clinical consequences, no general and standard agreement has yet been presented for the management and treatment of this disease.

Comparison of losartan and amlodipine effects on the outcomes of patient with COVID-19 and primary hypertension: A randomised clinical trial.

BACKGROUND: Controversy exists regarding the drug selection in hypertension (HTN) management in patients with COVID-19. This study aimed to compare the effects of losartan and amlodipine in patients with primary HTN and COVID-19. METHODS: In this randomised clinical trial, hospitalised patients with COVID-19 and primary HTN were enrolled in the study. One arm received losartan, 25 mg, twice a day and the other arm received amlodipine, 5 mg per day for 2 weeks. The main outcomes were compare 30-day mortality rate and length of hospital stay. RESULTS: The mean age of patients treated with losartan (N = 41) and amlodipine (N = 39) was 67.3 ± 14.8 and 60.1 ± 17.3 years, respectively (P value = .068). The length of hospital stay in losartan and amlodipine groups was 4.57 ± 2.59 and 7.30 ± 8.70 days, respectively (P value = .085). Also, the length of ICU admission in losartan and amlodipine group was 7.13 ± 5.99 and 7.15 ± 9.95 days, respectively (P value = .994). The 30-day mortality was two and five patients in losartan and amlodipine groups, respectively (P value = .241). CONCLUSIONS: There was no priority in losartan or amlodipine administration in COVID-19 patients with primary HTN in decreasing mortality rate, hospital and ICU length stay. Further studies need to clarify the first-line anti-HTN medications in COVID-19.

GDF-15: Diagnostic, prognostic, and therapeutic significance in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the commonest primary malignant brain tumor and has a remarkably weak prognosis. According to the aggressive form of GBM, understanding the accurate molecular mechanism associated with GBM pathogenesis is essential. Growth differentiation factor 15 (GDF-15) belongs to transforming growth factor-ß superfamily with important roles to control biological processes. It affects cancer growth and progression, drug resistance, and metastasis. It also can promote stemness in many cancers, and also can stress reactions control, bone generation, hematopoietic growth, adipose tissue performance, and body growth, and contributes to cardiovascular disorders. The role GDF-15 to develop and progress cancer is complicated and remains unclear. GDF-15 possesses tumor suppressor properties, as well as an oncogenic effect. GDF-15 antitumorigenic and protumorigenic impacts on tumor development are linked to the cancer type and stage. However, the GDF-15 signaling and mechanism have not yet been completely identified because of no recognized cognate receptor.

Drug-drug interactions with candidate medications used for COVID-19 treatment: An overview.

Drug-drug interaction (DDI) is a common clinical problem that has occurred as a result of the concomitant use of multiple drugs. DDI may occur in patients under treatment with medications used for coronavirus disease 2019 (COVID-19; i.e., chloroquine, lopinavir/ritonavir, ribavirin, tocilizumab, and remdesivir) and increase the risk of serious adverse reactions such as QT-prolongation, retinopathy, increased risk of infection, and hepatotoxicity. This review focuses on summarizing DDIs for candidate medications used for COVID-19 in order to minimize the adverse reactions.

Clinical characteristics and outcomes of pregnant women with COVID-19 and comparison with control patients: A systematic review and meta-analysis.

In a large-scale study, 128176 non-pregnant patients (228 studies) and 10000 pregnant patients (121 studies) confirmed COVID-19 cases included in this Meta-Analysis. The mean (confidence interval [CI]) of age and gestational age of admission (GA) in pregnant women was 33 (28-37) years old and 36 (34-37) weeks, respectively. Pregnant women show the same manifestations of COVID-19 as non-pregnant adult patients. Fever (pregnant: 75.5%; non-pregnant: 74%) and cough (pregnant: 48.5%; non-pregnant: 53.5%) are the most common symptoms in both groups followed by myalgia (26.5%) and chill (25%) in pregnant and dysgeusia (27%) and fatigue (26.5%) in non-pregnant patients. Pregnant women are less probable to show cough (odds ratio [OR] 0.7; 95% CI 0.67-0.75), fatigue (OR: 0.58; CI: 0.54-0.61), sore throat (OR: 0.66; CI: 0.61-0.7), headache (OR: 0.55; CI: 0.55-0.58) and diarrhea (OR: 0.46; CI: 0.4-0.51) than non-pregnant adult patients. The most common imaging found in pregnant women is ground-glass opacity (57%) and in non-pregnant patients is consolidation (76%). Pregnant women have higher proportion of leukocytosis (27% vs. 14%), thrombocytopenia (18% vs. 12.5%) and have lower proportion of raised C-reactive protein (52% vs. 81%) compared with non-pregnant patients. Leucopenia and lymphopenia are almost the same in both groups. The most common comorbidity in pregnant patients is diabetes (18%) and in non-pregnant patients is hypertension (21%). Case fatality rate (CFR) of non-pregnant hospitalized patients is 6.4% (4.4-8.5), and mortality due to all-cause for pregnant patients is 11.3% (9.6-13.3). Regarding the complications of pregnancy, postpartum hemorrhage (54.5% [7-94]), caesarean delivery (48% [42-54]), preterm labor (25% [4-74]) and preterm birth (21% [12-34]) are in turn the most prevalent complications. Comparing the pregnancy outcomes show that caesarean delivery (OR: 3; CI: 2-5), low birth weight (LBW) (OR: 9; CI: 2.4-30) and preterm birth (OR: 2.5; CI: 1.5-3.5) are more probable in pregnant woman with COVID-19 than pregnant women without COVID-19. The most prevalent neonatal complications are neonatal intensive care unit admission (43% [2-96]), fetal distress (30% [12-58]) and LBW (25% [16-37]). The rate of vertical transmission is 5.3% (1.3-16), and the rate of positive SARS-CoV-2 test for neonates born to mothers with COVID-19 is 8% (4-16). Overall, pregnant patients present with the similar clinical characteristics of COVID-19 when compared with the general population, but they may be more asymptomatic. Higher odds of caesarean delivery, LBW and preterm birth among pregnant patients with COVID-19 suggest a possible association between COVID-19 infection and pregnancy complications. Low risk of vertical transmission is present, and SARS-CoV-2 can be detected in all conception products, particularly placenta and breast milk. Interpretations of these results should be done cautiously due to the heterogeneity between studies; however, we believe our findings can guide the prenatal and postnatal considerations for COVID-19 pregnant patients.

Clinical and Demographical Characteristics of Cleft Lip and/or Palate in the Northwest of Iran: An Analysis of 1500 Patients.

OBJECTIVE: Orofacial clefts (OFCs) can occur as an isolated defect or as a manifestation of other syndromes. The current study aimed to evaluate demographic characteristics and distribution of different types of accompanying anomalies for OFCs in the northwest of Iran. DESIGN: A retrospective cohort study. SETTING: Tertiary pediatric hospital. PATIENTS AND PARTICIPANTS: This study was conducted on 1500 cleft lip and/or palate patients born between July 2010 and June 2020 in the northwest of Iran. MAIN OUTCOME MEASURES: Demographic and clinical characteristics of the children with OFCs including familial history, accompanying anomalies and syndromes, maternal passive smoking, mothers' and fathers' age, consanguineous marriage, and birth order. RESULTS: Among 1500 patients, 441 had cleft lip, 615 had cleft palate, and 444 had cleft lip and palate. The positive family history of OFCs was found to be 20.9% to 25.4% depending on the cleft type. Accompanying anomalies were identified in 29.8% of cases. Cardiac, facial, and ear abnormalities were the most common types. Also, 2.9% were identified with syndromes and sequences. These included Pierre Robin Sequence, Velo-cardio-facial syndrome, and Down syndrome most frequently. CONCLUSION: These findings may provide references for appropriate resources to establish and direct counseling and primary preventive projects in the northwest of Iran.

Fluconazole prophylaxis against invasive candidiasis in very low and extremely low birth weight preterm neonates: a systematic review and meta-analysis.

BACKGROUND: Evidence shows that fluconazole prophylaxis is an effective treatment against invasive fungal infections in preterm neonates, however, the most efficient schedule of fluconazole prophylaxis for the colonization and mortality of invasive candidiasis (IC) is unknown. PURPOSE: This systematic review and meta-analysis aimed to assess the efficiency of different prophylactic fluconazole schedules in controlling IC colonization, infection, and mortality in very low birth weight (VLBW) and extremely low birth weight (ELBW) infants in neonatal intensive care units. METHODS: We searched the PubMed, Scopus, Embase, and Cochrane databases using the keywords "candida," "invasive candidiasis," "IC," "fluconazole prophylaxis," "preterm infants," "very low birth weight infants," "VLBW," "extremely low birth weight," and "ELBW." RESULTS: Mortality was significantly decreased in a metaanalysis of studies using different fluconazole prophylaxis regimens. The meta-analysis also indicated a significant decrease in the incidence of IC-associated mortality in ELBW infants using the same fluconazole prophylaxis schedules. CONCLUSION: Future studies should explore the effectiveness of other different fluconazole prophylaxis schedules on IC colonization, infection, and mortality.

Role of circulatory leukocyte based indices in short-term mortality of patients with heart failure with reduced ejection fraction.

BACKGROUND: Pro-inflammatory signaling is mediated by a variety of inflammatory mediators which can cause myocardial apoptosis, hypertrophia, and fibrosis, and also ultimately lead to adverse cardiac remodeling. This study aimed to assess the role of circulating leukocyte-based indices in predicting the short-term mortality in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: In a retrospective study, patients with HFrEF admitted to a tertiary referral center between January 2016 and January 2017 were recruited to this study. The association between neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dLNR = neutrophils/(leukocytes-neutrophils)), monocyte/granulocyte to lymphocyte ratio (MGLR = (white cell count-lymphocyte count) to lymphocyte count), platelet to lymphocyte ratio (PLR) and six-months mortality of patients were assessed. RESULTS: A total of 197 patients with HFrEF were enrolled in the study. NLR (P<0.001), dNLR (P<0.001), MGLR (P<0.001), PLR (P=0.006) and LVEF (P=0.042) showed significant difference between survived and died patients. In the Cox multivariate analysis we did not find NLR, dLNR, MGLR or PLR as an independent predictor of short-term mortality in HFrEF patients. CONCLUSIONS: Although High NLR, PLR, MGLR and dNLR was associated with short-term mortality, it failed to independently predict the prognosis of HFrEF patients.