The Effects of Curcumin Administration on Carotid Intima-Media Thickness and Pulse Wave Velocity in Diabetic Hemodialysis Patients: A Randomized, Double-Blinded, Placebo-Controlled Trial.

Background: Prior studies have reported that curcumin is inversely associated with reduced markers of atherosclerosis risk, including carotid intima-media thickness (CIMT). This study was designed to assess the effects of curcumin on CIMT and pulse wave velocity (PWV) in diabetic hemodialysis (HD) patients. Methods: This randomized, double-blinded, placebo-controlled trial was conducted on 39 diabetic HD patients. People were assigned to receive curcumin or placebo (starch) for 24 weeks. Individuals in the curcumin group (n = 26) received 80 mg/day. CIMT and PWV levels were taken at baseline and after 24 weeks of intervention. Results: After 24 weeks of intervention, curcumin intake did not affect mean levels of left (P = 0.83) and right (P = 0.47) CIMT and maximum levels of left (P = 0.84) and right (P = 0.11) CIMT, and PWV (P = 0.12) compared to the placebo. Furthermore, within-group difference demonstrated a significant reduction in mean levels of PWV (P = 0.01) in the curcumin group. We did not observe any significant change in C-reactive protein (CRP) concentrations after curcumin intake (P = 0.69). Conclusions: Curcumin intake did not affect mean levels of left and right CIMT and maximum levels of left and right CIMT, PWV, and CRP levels compared to the placebo. Additionally, within-group difference demonstrated a significant reduction in mean levels of PWV in the curcumin group.This trial was registered at www.irct.ir as http://www.irct.ir: IRCT20200527047584N1.

Chest CT in COVID-19 pneumonia: what are the findings in mid-term follow-up?

PURPOSE: The purposes of this study are to investigate mid-term chest computed tomography (CT) findings of coronavirus disease 2019 (COVID-19) pneumonia, assess the rate of complete resolution, and determine the individuals at risk for residual abnormalities. METHODS: Fifty-two cases of COVID-19 pneumonia with at least two chest CTs and mean 3-month interval between the initial and follow-up CT were enrolled in this retrospective study. Patients were categorized into two groups: complete resolution and residual disease on follow-up CT. Demographic, clinical, laboratory, and therapeutic data as well as initial and follow-up chest CT scans were compared and analyzed. RESULTS: Thirty patients (57.7%) demonstrate complete resolution of pulmonary findings, and 22 patients (42.3%) had residual disease on follow-up CT. The mean time interval between initial and follow-up CT was 91.3 ± 17.2 and 90.6 ± 14.3 days in the complete resolution and residual groups, respectively. The most common radiologic pattern in residual disease was ground-glass opacities (54.5%), followed by mixed ground-glass and subpleural parenchymal bands (31.8%), and pure parenchymal bands (13.7%). Compared to complete resolution group, patients with residual disease had higher CT severity score on initial exam (10.3 ± 5.4 vs. 7.3 ± 4.6, P value = 0.036), longer duration of hospitalization, higher rate of intensive care unit (ICU) admission, more underlying medical conditions, higher initial WBC count, and higher occurrence rate of leukocytosis in the hospitalization time period (all P values < 0.05). CONCLUSION: Extensive lung involvement on initial CT, ICU admission, long duration of hospitalization, presence of underlying medical conditions, high initial WBC count, and development of leukocytosis during the course of disease are associated with more prevalence of chronic lung sequela of COVID-19.

Current Understanding and Unknown Aspects of the Treatment of Granulomatosis with Polyangiitis (Wegener's Granulomatosis): Opportunities for Future Studies.

Granulomatosis with polyangiitis (GPA) is a rare and systemic autoimmune disease, causing necrotizing vasculitis of small arteries and veins. The majority of diagnosed patients with GPA have circulating anti-neutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3). Here, we have reviewed the last findings and uncertainties regarding the treatment of GPA. Between the available treatments, in addition to corticosteroids, cyclophosphamide (CYP) is effective for remission-induction, while it is associated with some serious side effects, such as infertility and increased risk of malignancies. On the other side, rituximab (RTX) seems a safer alternative option and as effective as CYP. It could be used as both remission-induction and maintenance therapy in GPA patients, especially in women of childbearing age. Pregnant patients, who must not be exposed to the CYP and RTX could be well-managed with intravenous immunoglobulin (IVIg). Co-trimoxazole, which is widely used to treat certain bacterial infections or as prophylaxis in immunosuppressed patients, could be effective in preventing disease relapse. In the meantime, 15- deoxyspergualin, plasma exchange are other therapeutic options with a low level of evidence. Regarding potential treatments, ofatumumab, ocrelizumab, belimumab, atacicept, tabalumab, abatacept (CTLA4-Ig), and Janus kinase inhibitors seem to be effective. Renal involvement, older age, the presence of baseline organ damage, delayed-diagnosis of disease, rising in creatinine level, and higher neutrophil/lymphocyte ratio is associated with poor outcomes. Optimum doses of medications, prediction of treatment response and disease relapse, explaining lack of response in some patients, treating children with GPA, and management of GPA during the pregnancy are controversial issues, which need further studies.

Pathogenic and protective roles of cytokines in pemphigus: A systematic review.

Pemphigus is a rare and life-threatening group of blistering autoimmune diseases that affects the skin and mucous membranes. There are two major subtypes of pemphigus, including pemphigus vulgaris (PV) and pemphigus foliaceus (PF); each has different clinical manifestations. Pemphigus cannot be considered as a single disease and each patient may have a specific immunological profile. There are a lot of studies available regarding the role of different cytokines in the pathogenesis of pemphigus, although the data are not coherent between different studies. In this study, a systematic review from inception to December 25, 2019, through the MEDLINE/PubMed database had been performed to address several aspects of cytokines' roles in PV and PF. As a result, 57 studies from 352 initially found records, containing 26 cytokines had met the inclusion criteria. We found different pieces of evidence in favor of increased levels of TNF-α, TGF-ß, interleukin (IL)-8, IL-10, IL-12, IL-17, IL-21; while decreased levels of IL-2 and IL-23 in pemphigus patients. Regarding other cytokines, such as IFN-γ, IL-5, IL-15, IL-22, there are controversial results. Different studies suggested the association of TNF-α and IL-6 with disease activity and autoantibodies values. However, there is uncertainty regarding the role of IFN-γ, IL-2, IL-15, IL-27, and IL-33. Treatments with immunosuppressive agents may decrease IL-1, IL-6, IL-8, IFN-γ, IL-33, IL-17 levels. In conclusion, cytokines are deeply involved in PV and PF pathogenesis, and targeting specific cytokines may lead to development of more promising treatments for pemphigus.

Comparing the Efficacy and Safety of Treating Chronic Hepatitis B Infection during Pregnancy with Lamivudine, Telbivudine, and Tenofovir: A Meta-analysis.

Background and Aims: The perinatal transmission of hepatitis B virus (HBV) remains an important global health problem. Here, a systematic review and meta-analysis were conducted to evaluate the evidence regarding the efficacy and maternal/fetal safety of treating pregnant women with lamivudine, telbivudine (LdT), and tenofovir (TDF). Methods: A PubMed and Scopus search resulted in 1,076 records, which were reduced to 36, containing 7,717 pregnant women with chronic HBV infection and 7467 infants meeting the inclusion criteria. The latest search was in August 2019. Results: Treatment with LdT, but not lamivudine and TDF, could significantly reduce the hepatitis B virus surface antigen-positive rate (odds ratio (OR) = 0.37) in infants; it also led to higher rates of hepatitis B e antigen loss (OR = 12.14), hepatitis B e antigen seroconversion (OR = 8.93), and alanine aminotransferase normalization in mothers (OR = 1.49). Each of these treatments was able to significantly reduce HBV DNA positivity at birth (total OR = 0.19) and mother-to-child-transmission of HBV (total OR = 0.15), and to cause higher rates of HBV DNA suppression in mothers (total OR = 25.53). However, nucleos(t)ide analogues might also be involved in creatine kinase elevation (total OR = 7.48). In contrast, no significant association was found between nucleos(t)ide analogue therapy and preterm/premature births, congenital malformation, low birth weight, and abortion or fetal/infant death. The results suggested LdT's high capability of preventing mother-to-child-transmission. However, TDF failed to show significant associations to a reduced risk of mother-to-child-transmission, probably due to the low number of patients included. Conclusions: Although using either lamivudine, LdT, or TDF could lead to more favorable maternal/fetal outcomes, LdT seemed to show more potential in resolving certain infant- and maternal-related outcomes. More studies on the safety profile of such treatments are required.

A comprehensive review of rituximab therapy in rheumatoid arthritis patients.

Rituximab (RTX) is an approved treatment for rheumatoid arthritis (RA) patients that do not respond adequately to disease-modifying antirheumatic drugs. However, different new concerns, such as efficacy, optimum dose, safety issues, prediction of response to RTX, and pregnancy outcomes have attracted a lot of attention. The PubMed database was systematically reviewed for the last published articles, new findings, and controversial issues regarding RTX therapy in RA using "Rheumatoid arthritis" AND "rituximab" keywords, last updated on June 18, 2019. From 1812 initial recorders, 162 studies met the criteria. Regarding the optimum dose, low-dose RTX therapy (2 × 500 mg) seems as effective as standard dose (2 × 1000 mg), safer, and more cost-effective. The most common reported safety challenges included de novo infections, false negative serologic tests of viral infections, reactivation of chronic infections, interfering with vaccination outcome, and development of de novo psoriasis. Other less reported side effects are infusion reactions, nervous system disorders, and gastrointestinal disorders. Lower exposure to other biologics, presence of some serological markers (e.g., anti-RF, anti-CCP, IL-33, ESR), specific variations in FCGR3A, FCGR2A, TGFß1, IL6, IRF5, BAFF genes, and also EBV-positivity could be used to predict response to RTX. Although there is no evidence of the teratogenic effect of RTX, it is recommended that women do not expose themselves to RTX at least 6 months before the conception. Only a reversible reduction of B cell-count in the offspring may be the pregnancy-related outcome. Although RTX is an effective therapeutic option for RA, more studies on optimum doses, prevention of RTX-related side effects, prediction of RTX response, and safety during the pregnancy are required.

Comparing early and late treatments with rituximab in pemphigus vulgaris: which one is better?

During the last decade, successfully treatment of patients diagnosed with pemphigus vulgaris (PV) with rituximab (RTX) was reported by several authors. The present study has been designed to compare the clinical outcomes and RTX-related side effects between the two groups of early treated (≤ 6 months) and lately treated PV (> 6 months) patients with RTX. We did a retrospective study between Oct 2014 and Jun 2016 to compare the short-term efficacy and safety of RTX in PV diagnosed patients. The primary and secondary endpoints were complete/partial remission of disease and safely tapering of corticosteroids without disease relapse, respectively. Among the 250 RTX exposed PV patients in the selected period, 107 were successfully followed for the mean 19.71 ± 16.78 months. Twenty-four and eighty three have categorized as the early (≤ 6 months after diagnosis) or lately (> 6 months after diagnosis) RTX-treated patients, respectively. A higher rate of complete remission, longer time lasting remission phase, and a lower number of adjuvants were associated with early RTX treatment. Early treatment with RTX might be associated with improvement of clinical effects, but does not seems to be safer than lately RTX therapy. Those in the early treated group may not only have a higher chance to achieve complete remission, but also experience a longer time of disease remission with lower cumulative doses of adjuvant therapy.

Nucleoside/nucleotide analogues in the treatment of chronic hepatitis B infection during pregnancy: a systematic review.

BACKGROUND: Women of childbearing age who have developed chronic hepatitis B (CHB) infection, especially HBeAg-positive highly viraemic pregnant women, are largely responsible for the familial transmission of the infection. Therefore, choosing the most effective and safest antiviral medications to manage pregnant CHB patients is of crucial importance. MATERIALS AND METHODS: The PubMed and Scopus databases were searched through September 2017, for all the journal articles possessing original results regarding treatment of CHB pregnant women with any nucleos(t)ide analogue (NA) therapies, including lamivudine (LAM), adefovir (ADV), entecavir (ETV), telbivudine (LdT), and tenofovir (TDF). RESULTS: After the primary search, 882 studies were recognized, and updating the searching results, 41 journal articles with original data were investigated, involving 3874 newborn infants from mothers with CHB, and their mothers completed follow-up until the delivery. The most important basic data and results regarding the efficacy of drugs, the rate of vertical transmission, safety issues associated with pairs of mothers and infants, median levels of HBV DNA, breastfeeding data, and rate of rate of vaccination success were collected. Moreover, possible key conclusion, recommendations, and learned lessons were discussed. Among the evaluated NAs, all LAM was efficient and safe. LdT was found to be very effective but had some safety concerns. In contrast, TDF had the advantages of both effectiveness and safety. CONCLUSION: According to data in the literature, initiation of TDF at the trimester of pregnancy in combination with immunoprophylaxis to prevent mother-to-child transmission (MTCT) of CHB infection is strongly recommended as well as successful immunization of CHB pregnant women by anti-HBV vaccines.

Toward cure chronic hepatitis B infection and hepatocellular carcinoma prevention: Lessons learned from nucleos(t)ide analogues therapy.

Nucleos(t)ide analogues (NAs) could successfully suppress hepatitis B virus (HBV) replication in patients with chronic hepatitis B (CHB). However, due to probable development of drug resistance or low/delayed response, these treatments may not be satisfactory. In addition to the HBV DNA polymerase inhibiting activity, these drugs could lead to changes in cytokines profiles. It is important to monitor these changes so that they could be used as target of treatment. Evaluating the previously reported immune responses due to NAs treatments, it was concluded that interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin-4 (IL-4), and IL-12 increase after the treatment. This will be followed by the improved capacity of immune cells for eliminating HBV. In contrast, regulatory responses including IL-10 and transforming growth factor-beta (TGF-ß) significantly decreased as the result of NAs therapy. Unexpectedly, T helper (Th) 17-associated cytokines also decreased significantly. These results could be used to employ the new strategies to suppress viral replication, minimize HBV DNA levels, inducing hepatitis B e antigen (HBeAg) seroconversion or even hepatitis B surface antigen (HBsAg) seroclearance. In order to accomplish these goals, extended treatment with high dose of both IL-12 and IFN in combination with high barrier to resistance NA might significantly improve the HBsAg seroclearance rate. Considering the danger of emerging aberrant immune responses, determining the optimum dosage as well as close monitoring of patients during the treatment is strongly advised. In order to make HBV immunotherapy practical, further studies are needed to confirm these results.