Endoscopic vacuum therapy for nonhealing cavity with fistulous tract after peroral endoscopic myotomy for Zenker's diverticulum.

Video 1Endoscopic vacuum therapy for nonhealing cavity with fistulous tract after peroral endoscopic myotomy for Zenker diverticulum.

Relationship between long non-coding RNAs and Hippo signaling pathway in gastrointestinal cancers; molecular mechanisms and clinical significance.

Long non-coding RNAs (lncRNAs) play a significant biological role in the regulation of various cellular processes such as cell proliferation, differentiation, apoptosis and migration. In various malignancies, lncRNAs interplay with some main cancer-associated signaling pathways, including the Hippo signaling pathway to regulate the various cellular processes. It has been revealed that the cross-talking between lncRNAs and Hippo signaling pathway involves in gastrointestinal (GI) cancers development and progression. Considering the clinical significance of these lncRNAs, they have also been introduced as potential biomarkers in diagnostic, prognostic and therapeutic strategies in GI cancers. Herein, we review the mechanisms of lncRNA-mediated regulation of Hippo signaling pathway and focus on the corresponding molecular mechanisms and clinical significance of these non-coding RNAs in GI cancers.

Peptic ulcer characteristics in oral opium and non-opium user patients with upper gastrointestinal bleeding.

BACKGROUND/AIMS: Upper gastrointestinal bleeding (UGIB) is a frequent medical issue. The primary risk factors for bleeding peptic ulcers are Helicobacter pylori infection and non-steroidal anti-inflammatory drugs. The association between acute gastric/duodenal ulcer and opium use has been previously proposed; however, there is no available data on endoscopic findings of patients with acute UGIB who use opium. MATERIALS AND METHODS: In the present descriptive cross-sectional study, endoscopic data of 50 consecutive patients with oral opium use and 50 consecutive patients without any opium use who were admitted for UGIB were recorded. The size (5-10 mm, 11-20 mm, or more than 20 mm), number (single, double, or multiple), and location of the ulcers (esophagus, gastric corpus including the fundus and body, antrum, angulus, or duodenum) were examined by endoscopy in both groups. RESULTS: Three or more ulcers were observed in 46% and 16% of patients with oral opium use and without opium use, respectively (P-value = 0.001). The rate of giant ulcers (> 20 mm) was significantly higher in patients who used oral opium (40% vs. 12%; P-value = 0.007). Esophageal ulcers were also more common in oral opium users (30%) than non-users (8%) with UGIB (P-value = 0.01). Nevertheless, the location of the ulcers between the two groups generally was not statistically different. CONCLUSIONS: This study has demonstrated that multiple, large peptic ulcers in GIB are potential complications of oral opium use. This could aid the needed modifications in the treatment protocol for these patients.

Evaluation of tumor-educated platelet long non-coding RNAs (lncRNAs) as potential diagnostic biomarkers for colorectal cancer.

INTRODUCTION: Cancer-derived circulating components are increasingly considered as candidate sources for non-invasive diagnostic biomarkers. This study aimed to investigate the expression of tumor-educated platelet (TEP) long non-coding RNAs (lncRNAs) in colorectal cancer (CRC) patients and determine whether it could be served as a potential tool for CRC diagnosis. MATERIALS AND METHODS: Relative quantitative real-time PCR (qRT-PCR) was used to detect the expression levels of three cancer-related platelet-derived lncRNAs CCAT1, HOTTIP, and XIST in 75 CRC patients and 42 healthy controls. Quantitative data were analyzed by SPSS (IBM Corp., Armonk, NY, USA) for comparison of cancer and non-cancer individuals. The receiver operating characteristic (ROC) curve analysis was further performed to assess the diagnostic values of lncRNAs within the CRC patients. RESULTS: The expression levels of lncRNAs colon cancer associated transcript 1 (CCAT1) (P = 0.006) and HOXA transcript at the distal tip (HOTTIP) (P = 0.049), but not X-inactive specific transcript (XIST) (P = 0.12), were significantly upregulated in CRC patients compared to healthy individuals. However, there were no significant correlations between platelet lncRNAs and clinicopathological characteristics, including sex, age, tumor location, differentiation, and size (all at P > 0.05). The area under the ROC curve (AUC) of the lncRNA CCAT1 was 0.61 (sensitivity, 71%; specificity, 50%). CONCLUSION: TEP lncRNA CCAT1 is detectable in the circulation of CRC patients and could be considered as a potential diagnostic biomarker.

Efficacy and safety of immune checkpoint inhibitors for patients with prostate cancer: a systematic review and meta-analysis.

Immunotherapy has revolutionized the treatment paradigm of many cancers, however, its effectiveness in prostate cancer patients is still under question. In the present systematic review and meta-analysis, we sought for assessing the efficacy and safety of Immune checkpoint inhibitors (ICIs) in patients with prostate cancer. PubMed, Scopus, Web of Science, and EMBASE databases were searched on Aguste 19, 2022. Thirty five studies met the eligibility criteria. The median overall survival (mOS) of all treatments was 14.1 months, with the longest and shortest mOS was seen among patients who received anti-CTLA-4 monotherapy and anti-PD-1/PD-L1+anti-CTLA-4 regimen at 24.9 and 9.2 months, respectively. Noteworthy, all types of adverse events had the lowest incidence in the anti-PD-1/PD-L1 monotherapy group. Considering the ICI monotherapy regimens, we found that fatigue, diarrhea, and infusion reaction had the highest incidence rates. Future studies evaluating the efficacy and safety of novel combination therapies with ICIs are warranted.

Predictive value of PD-L1 expression in response to immune checkpoint inhibitors for gastric cancer treatment: a systematic review and meta-analysis.

BACKGROUND: Which patients may benefit more from immune checkpoint inhibitors (ICIs) is still an important question. The present study aimed to investigate the role of the PD-L1 molecule in predicting the effectiveness of PD-1/PD-L1 inhibitors in gastric cancer patients. METHOD: We searched PubMed, Scopus, Web of Science, and EMBASE databases as of 25 March 202225 March 2022. RESULTS: Ten articles were included. When we used the TPS method for PD-L1 expression, none of the patients in tumor proportion score (TPS)≥1% and TPS < 1% groups took advantage of ICI therapy in terms of OS and PFS. However, gastric cancer patients with combined-positive score (CPS)≥1, CPS ≥ 5, and CPS ≥ 10 tumors represented superior OS for ICIs over the control agents, while their counterparts (i.e. patients with CPS < 1, CPS < 5, and CPS < 10 tumors) did not. In the subgroup analysis when patients with CPS ≥ 1 were selected, Nivolumab improved the OS and PFS remarkably by 26% and 25% when compared with control agents, respectively. However, Pembrolizumab significantly increased the rate of disease progression by 47% relative to the control medications. CONCLUSION: Among patients suffering from gastric cancer, considering PD-L1 CPS thresholds seems to be a more reliable predictive factor than TPS threshold for lower rate of mortality when PD-1/PD-L1 inhibitors are administered.

The effect of Trolox on the rabbit anal sphincterotomy repair.

INTRODUCTION: Fecal incontinence (FI) is caused by external anal sphincter injury. Vitamin E is a potential strategy for anal sphincter muscle repair via its antioxidant, anti-inflammatory, anti-fibrotic, and protective properties against myocyte loss. Thus, we aimed to evaluate the water-soluble form of vitamin E efficacy in repairing anal sphincter muscle defects in rabbits. METHODS: Twenty-one male rabbits were equally assigned to the intact (without any intervention), control (sphincterotomy), and Trolox (sphincterotomy + Trolox administration) groups. Ninety days after sphincterotomy, the resting and squeeze pressures were evaluated by manometry, and the number of motor units in the sphincterotomy site was calculated by electromyography. Also, the amount of muscle and collagen in the injury site was investigated by Mallory's trichrome staining. RESULTS: Ninety days after the intervention, the resting and squeeze pressures in the intact and Trolox groups were significantly higher than in the control group (P = 0.001). Moreover, the total collagen percentage of the sphincterotomy site was significantly lower in the Trolox group than in the control group (P = 0.002), and the total muscle percentage was significantly higher in the Trolox group compared to the control group (P = 0.001). Also, the motor unit number was higher in the Trolox group than in the control group (P = 0.001). CONCLUSION: Trolox administration in the rabbit sphincterotomy model can decrease the amount of collagen and increase muscle, leading to improved anal sphincter electromyography and manometry results. Therefore, Trolox is a potential treatment strategy for FI.

Impact of Helicobacter pylori infection on the efficacy of immune checkpoint inhibitors for cancer treatment: a meta-analysis.

Aim: The present systematic review and meta-analysis was designed to assess the impact of Helicobacter pylori infection on the efficacy of immune checkpoint inhibitors (ICIs). Materials & methods: PubMed, Scopus, Web of Science and EMBASE databases were systematically searched up to 1 February 2023. Results: Three studies comprising 263 patients treated with ICIs were included. The results of pooled analysis showed that H. pylori infection was associated with reduced overall survival and progression-free survival. Furthermore, the rate of progressive disease after administration of ICIs was higher in H. pylori-positive patients relative to H. pylori-negative patients. Conclusion: H. pylori infection status is a novel potential response biomarker for predicting the efficacy of ICIs in different cancers.

Immune checkpoint inhibitors (ICIs) are a novel treatment modality for cancer patients. The efficacy of this kind of treatment can be affected by several factors. The present systematic review and meta-analysis was designed to evaluate the impact of infection by Helicobacter pylori on the outcomes of patients undergoing ICI therapy. Those patients who were affected by H. pylori had an increased rate of mortality and disease progression after ICI therapy relative to those who were not affected at the time of treatment. As a result, the findings highlight that H. pylori infection reduces the effectiveness of immunotherapy with ICIs.

Clinical efficacy and safety of bispecific antibodies for the treatment of solid tumors: a systematic review and meta-analysis.

INTRODUCTION: Immunotherapy is a promising and progressing treatment approach for cancer. Bispecific antibodies (BsAbs) are antibody constructs that can bind to two different epitopes. The dual-specificity of BsAbs improves their efficacy compared to monoclonal antibodies. AREAS COVERED: Although BsAbs have achieved excellent therapeutic effects in hematologic cancers, no systematic review with meta-analysis evaluated their efficacy in solid tumors. In the present systematic review and meta-analysis, we aimed to establish the clinical efficacy and safety of BsAbs in solid tumors. EXPERT OPINION: BsAbs are not associated with significantly better safety or efficacy outcomes than conventional therapies. BsAb was not associated with improvement in overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). However, BsAb increased the rate of stable disease (SD) significantly. Also, BsAb substantially increased the OS and PFS and resulted in a higher frequency of DCR for uveal melanoma. Furthermore, the safety analysis showed no obvious difference in the rate of any adverse events (AEs), grade ≥3 AEs, serious AEs, and AEs leading to treatment discontinuation in the intervention group compared to controls. Further high-quality randomized controlled trials on BsAbs in solid tumors are highly recommended.

The Autoimmune Manifestations in Patients with Genetic Defects in the B Cell Development and Differentiation Stages.

PURPOSE: Primary B cell defects manifesting as predominantly antibody deficiencies result from variable inborn errors of the B cell lineage and their development, including impairments in early bone marrow development, class switch recombination (CSR), or terminal B cell differentiation. In this study, we aimed to investigate autoimmunity in monogenic patients with B cell development and differentiation defects. METHODS: Patients with known genetic defects in the B cell development and differentiation were recruited from the Iranian inborn errors of immunity registry. RESULTS: A total of 393 patients with a known genetic defect in the B cell development and differentiation (257 males; 65.4%) with a median age of 12 (6-20) years were enrolled in this study. After categorizing patients, 109 patients had intrinsic B cell defects. More than half of the patients had defects in one of the ATM (85 patients), BTK (76 patients), LRBA (34 patients), and DOCK8 (33 patients) genes. Fifteen patients (3.8%) showed autoimmune complications as their first manifestation. During the course of the disease, autoimmunity was reported in 81 (20.6%) patients at a median age of 4 (2-7) years, among which 65 patients had mixed intrinsic and extrinsic and 16 had intrinsic B cell defects. The comparison between patients with the mentioned four main gene defects showed that the patient group with LRBA defect had a significantly higher frequency of autoimmunity compared to those with other gene defects. Based on the B cell defect stage, 13% of patients with early B cell defect, 17% of patients with CSR defect, and 40% of patients who had terminal B cell defect presented at least one type of autoimmunity. CONCLUSION: Our results demonstrated that gene mutations involved in human B cell terminal stage development mainly LRBA gene defect have the highest association with autoimmunity.

Safety and efficacy of Elotuzumab combination therapy for patients with multiple myeloma: A systematic review and meta-analysis.

OBJECTIVE: We evaluate the efficacy and safety of Elotuzumab, an immunostimulatory monoclonal antibody, in combination with concomitant treatment regimens for multiple myeloma (MM) patients. RESEARCH DESIGN AND METHODS: PubMed, Scopus, Web of Science, and EMBASE databases were searched systematically up to 2 August 2022. RESULTS: Five randomized control trials with a total of 1,763 participants were included. Elotuzumab combination therapy improved PFS and OS by 14% (hazard ratio [HR] 0.86) and 20% (HR 0.80), respectively, relative to the non-Elotuzumab regimen. Adding Elotuzumab to Lenalidomide plus Dexamethasone regimen (HR 0.82) or Pomalidomide plus Dexamethasone regimen (HR 0.54) were considered to improve the PFS. Meanwhile, the risk of disease progression was only reduced for patients with relapsed/refractory MM (HR 0.70) but not for newly diagnosed/untreated MM (HR 0.93). Finally, the risk of serious adverse events (RR 1.12) and the risk of infection (RR 1.09) and cardiac disorders (RR 1.32) were higher for the experimental group compared to the control group. CONCLUSIONS: Our findings showed that Elotuzumab combination therapy prolonged OS and PFS compared to non-Elotuzumab treatments in patients with MM. However, further investigations are required to establish the most effective combination of the Elotuzumab regimen.

Determinants of Self-monitoring of Blood Glucose in Iranian Children and Adolescents with Type 1 Diabetes.

Background: Type 1 diabetes mellitus (T1DM) is a prevalent chronic disease among children and adolescents, necessitating effective self-monitoring of blood glucose (SMBG) levels. Understanding the determinants and factors influencing SMBG behavior is crucial for optimizing diabetes management in this population. Objectives: This study aimed to investigate the frequency of SMBG and identify the determinants influencing factors in children and adolescents with T1DM. Methods: This cross-sectional study was conducted in Tehran, Iran, and included 275 participants selected through simple random sampling from the Gabric Diabetes Education Association. The inclusion criteria comprised children and adolescents aged 3 - 18 years diagnosed with T1DM for at least 6 months who were using analog or neutral protamine Hagedorn (NPH) and regular insulin subcutaneously. Patients using insulin pumps were excluded. Data collection involved an online questionnaire covering demographic information (e.g., age, gender, educational status, and parental occupations) as well as clinical information (number of hypoglycemic episodes, hemoglobin A1C (HbA1C) levels, diabetes duration, insulin regimen, diabetes complications, glucose monitoring practices, hospitalizations, and behavioral characteristics). Statistical analyses, including descriptive statistics, correlation tests, and Poisson regressions, were performed using SPSS software (version 21). A significance level of P-value < 0.05 was considered statistically significant. Results: The participants had a mean age of 10.00 ± 3.77 years, with 54.2% being males. Most of the participants (87.3%) were schoolchildren, and the mean age of diagnosis was 6.56 ± 3.73 years, with a mean duration of 44.72 ± 36.32 months. Anthropometric investigations revealed mean height, weight, and body mass index (BMI) values of 136.69 ± 21.11 cm, 37.45 ± 15.51 kg, and 18.31 ± 3.55 kg/m2, respectively. The majority of participants (93.5%) used insulin pens, and the mean daily insulin dosage was 35.34 ± 22.20 IU. Parents reported consistent glucose level monitoring in 64.7% of cases. The mean HbA1c level was 7.91 ± 1.58%. Factors such as the price and availability of glucometer strips influenced glucose level monitoring. In univariate analysis, only age and HbA1C levels showed a negative correlation; however, parents' consistent checking showed a positive correlation with the frequency of daily, weekly, or monthly glucose checking. Conclusions: This study underscores the significance of SMBG in children and adolescents with T1DM. The findings emphasize the critical role of price and availability of glucometers and strips in achieving standard care for T1DM patients.

Autoimmunity in monogenic combined immune deficiencies with associated or syndromic features.

Background: Combined immune deficiencies (CIDs) with associated or syndromic features are a highly heterogeneous subgroup of inherited immune disorders. These patients represent specific clinical complications with an increased risk of autoimmune conditions. Methods: We analyzed data of monogenic patients with syndromic CIDs adopted from the Iranian inborn errors of immunity registry up to January 2022. A comprehensive comparison in terms of demographic, clinical, and immunological features was performed between patients with and without autoimmunity and also among four mutation groups with the most registered cases including ATM, STAT3 (AD-LOF), DNMT3B/ZBTB24, and WAS mutations. Results: A total of 137 patients with monogenic syndromic CIDs were included. Most commonly mutated genes were the ATM [80 (58.4%)] and STAT3 (AD-LOF) [19 (13.9%)], followed by DNMT3B [11 (8%)], and WAS [11 (8%)]. More than 18% of all patients with syndromic CIDs, including most DNMT3B/ZBTB24 mutations patients, were clinically diagnosed with antibody deficiencies before genetic evaluation. Patients with ATM and WAS mutations had the latest age of onset and the lowest age of diagnosis, respectively. Autoimmune disorders were diagnosed in 24 patients at a median age of 3.5 (2.6-6.0) years, 70.6% of which were diagnosed prior to the diagnosis of immunodeficiency. Lymphoproliferation, particularly hepatosplenomegaly, was significantly higher in patients with autoimmunity (p=0.004). Syndromic CID patients with autoimmunity had significantly lower IgG levels. Hematologic autoimmunity mainly immune thrombocytopenic purpura was the most frequent autoimmunity among major groups of ATM, STAT3 (AD-LOF), DNMT3B/ZBTB24, and WAS mutations, however ATM-mutated patients present more diversified involved organs including rheumatologic, gastrointestinal and dermatologic autoimmunity. Conclusion: About 18% of patients with monogenic syndromic CIDs developed autoimmunity, mainly in the form of hematological immune diseases. Autoimmunity could be an early-onset involvement with a potential diagnostic impact on suspicious cases of syndromic CIDs.

Prevalence of Asthma Symptoms in Children and Adolescents in Karaj, Iran: A Report from the Global Asthma Network Phase I Study.

  This study is a part of the Global Asthma Network (GAN) phase I project to assess asthma symptoms in children, adolescents, and their parents in Karaj, Iran. The present cross-sectional study was conducted in 2019-2020 in Karaj, Iran, in alignment with the goals of the GAN study, including assessing asthma prevalence, severity, and risk factors. In this study, 1500 students were selected using a multistage stratified cluster sampling method from 40 public and private schools in Karaj. The entire population of children aged 6-7 years or adolescents aged 13-14 years in a given school and their parents was considered the sample unit. The GAN core questionnaires were completed for students and parents. The results showed that the response rate was 89.6%. A total of 1326 children and adolescents, 572 children aged 6-7 years, and 754 aged 13-14 years and their parents were enrolled in the study. The prevalence of ever- and current wheezing was 24% and 13.8% among 6-7-year-olds, and 18.8% and 12.3% among 13-14-year-olds, respectively. In children aged 6-7 years, parental wheezing significantly increased the chances of children wheezing (odds ratio: 3.27; 95% confidence interval: 1.70, 6.310). The current study's findings showed that the prevalence of asthma symptoms among children and adolescents and their parents in Karaj, Iran, was mainly higher than the findings of studies conducted in other cities in Iran.

Immune checkpoint inhibitors plus chemotherapy versus chemotherapy alone as first-line therapy for advanced gastric and esophageal cancers: A systematic review and meta-analysis.

BACKGROUND: Esophageal, gastroesophageal, and gastric cancers are still among the leading causes of death worldwide. The introduction of immune checkpoint inhibitors (ICIs) has revolutionized the treatment strategy for several cancers. The combination of conventional chemotherapy with ICIs has been hypostatized to play a synergic effect over the chemotherapy alone regimen. Thus, the present systematic review and meta-analysis was conducted to compare the efficacy and safety of ICIs plus chemotherapy versus chemotherapy alone in patients suffering from advanced esophageal, gastroesophageal, and gastric cancers. METHODS: PubMed, Scopus, Web of Science, and EMBASE databases together with the conference abstracts of ASCO and ESMO were searched systematically up to March 25, 2022. The studies were selected in two steps, title/abstract and full-text screening. The primary outcome was set at the efficacy of ICIs plus chemotherapy relative to the chemotherapy alone in terms of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). The secondary outcome was the safety in terms of treatment-related adverse events (TRAEs) and immune-related AEs. RESULTS: A total of 11 publications involving 6,732 patients were included. First-line ICIs plus chemotherapy showed superior effect over chemotherapy alone in terms of OS (hazard ratio [HR] 0.76, 95 %CI 0.72-0.81), PFS (HR 0.68, 95 %CI 0.61-0.75), ORR (risk ratio [RR] 1.29, 95 %CI 1.20-1.40), and DCR (RR 1.06, 95 %CI 1.03-1.09). Significant predictors of OS benefit in combination therapy versus chemotherapy alone were PDL-1 combined positive score (CPS) ≥ 10 compared to CPS < 10 (p = 0.012), tumor proportion score (TPS) ≥ 1 % compared to TPS < 1 % (p = 0.016), and male gender compared to the females (p = 0.024). In the safety analysis, ICIs plus chemotherapy showed a higher rate of TRAEs in terms of any grade AEs (RR 1.02, 95 %CI 1.00-1.04), grade ≥ 3 AEs (RR 1.16, 95 %CI 1.06-1.26), serious AEs (RR 1.63, 95 %CI 1.44-1.85), and AEs led to treatment discontinuation (RR 1.51, 95 %CI 1.37-1.67). Furthermore, the rate of immune-related AEs of any grade (RR 2.18, 95 %CI 1.55-3.05) and immune-related grade ≥ 3 AEs (RR 2.76, 95 %CI 1.85-4.13) were also higher in ICI combination therapy group relative to chemotherapy alone group. CONCLUSION: Our findings demonstrated that first-line ICIs plus chemotherapy versus chemotherapy alone prolonged OS and PFS in patients with advanced esophagogastric cancers. Also, the rate of AEs was remarkably higher in the combination group. As a result, identifying methods to prevent AEs without affecting the efficacy of ICIs is highly warranted.

Heart Failure Status among Acute Ischemic Stroke Patients: A Hospital-Based Study.

Background: Since heart failure (HF) and ischemic stroke have common risk factors, their concurrent occurrence is likely. Strokes in HF patients could be life-threatening and lead to severe disabilities, longer hospitalization time, and mortality. The present study aims to investigate the prevalence of HF and its severity based on ejection fraction (EF) in patients with acute ischemic stroke. Methods: The present cross-sectional study included acute ischemic stroke patients admitted to Shahid Rajaei hospital in Karaj in 2020-2021. The diagnosis of HF was based on transthoracic echocardiography within 48 hours of symptom onset, and HF was classified into two groups: 41-49% as mildly reduced EF (HFmrEF) and ≤40% as reduced EF (HFrEF). Patients who did not complete cardiac studies were excluded. Results: 257 acute ischemic stroke patients (62.6% male) were included. Among stroke patients, the prevalence of HF, including HFrEF and HFmrEF, was 30.0% (95% CI: 21.4-38.6). HFmrEF and HFrEF was diagnosed in 32 (12.5%) and 45 (17.5%) patients, respectively. HF was significantly associated with older age, hypertension, past myocardial infarction (MI), and arrhythmia. A history of previous MI significantly increased the odds of heart failure (OR: 3.25, 95% CI: 1.82-5.81). Conclusion: There is a high prevalence of HF among acute ischemic stroke patients. Older patients with a history of hypertension and previous MI are at higher risk. Since patients with HF have a higher mortality and morbidity rate after experiencing an ischemic stroke, close cooperation between the neurology and cardiology specialists for providing advanced care for survivors is required.

Associated factors to insulin adherence in type 1 diabetes in Tehran and Karaj, Iran.

Purpose: Type 1 diabetes mellitus (T1DM) is a chronic metabolic disorder, and its prevalence and incidence are increasing globally. Insulin therapy is the basis of T1DM management that can prevent numerous complications. Identifying and resolving the factors involved in patients' non-adherence can reduce complications, mortality, and economic burden. Methods: In this cross-sectional study, a sample of patients with T1DM were included from Alborz and Tehran cities of Iran in 2020. Patients filled the questionnaires consisting of sociodemographic and diabetes characteristics, weight and height measurements, 8-item Morisky Medication Adherence Scale (MMAS), and barriers to insulin therapy. Patients with < six scores of MMAS were considered to have low adherence, while ≥ 6 scores showed moderate/high adherence. Data were analyzed using SPSS, and a P-value of less than 0.05 was considered statistically significant. Results: 189 patients with T1DM with a mean (± SD) age of 17.95 (± 10.98) years were enrolled in the study, and 73.5% of patients had moderate/high adherence to insulin therapy. Younger age and owning insurance were significantly associated with being classified in the higher adherence group. The barriers that were significantly associated with non-adherence were forgetting to buy, physician inaccessibility, cost, exhaustion from the long-term injection, forgetfulness, injection site reaction, and rebellion against parents in the < 20 years age group. The main barriers in ≥ 20 years age group were forgetting to buy and insufficient injection instruction. Conclusion: The identified barriers to insulin injection would be helpful for policymakers and clinicians to increase insulin adherence among patients with T1DM. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01105-0.

The clinical, molecular, and therapeutic features of patients with IL10/IL10R deficiency: a systematic review.

Interleukin10 (IL10) and IL10 receptor (IL10R) deficiencies are monogenic inborn errors of immunity (IEI) causing early-onset inflammatory bowel diseases (IBD). In this report, we systematically reviewed articles that included related keywords using PubMed, Web of Science, and Scopus databases. The articles were screened for eligibility criteria before data extraction. We assessed 286 patients (44.5% female) with IL10 and/or IL10R deficiencies who were predominantly from China (40.7%), Italy (13.9%), and South Korea (8.5%). The median age of onset was 1.0 (0.3-4.0) months with a median age of genetic diagnosis at 16.0 (7.4-81.0) months. Consanguinity was reported in all evaluable patients with IL10 deficiency and in 38.2% of patients with IL10R deficiency (22.9% of patients with IL10RA, and 79.4% of patients with IL10RB deficiency). The most prevalent mutations in IL10RA were c.301C>T (p.R101W) and c.537G>A (p.T179T), those in IL10RB were c.139A>G (p.K47E) and c.611G>A (p.W204X). Auto-inflammation and enteropathy were present in all cases. The first presentation of both groups was protracted diarrhea (45.7%), bloody diarrhea (17.8%), and colitis (15.5%). Patients with IL10R deficiency had a high frequency of dermatologic manifestations (50.5%) and failure to thrive (60.5%), while IL10-deficient patients lacked those complications. In the majority of patients, the basic immunologic parameters were in normal ranges. Of the entire publications, 30.7% underwent hemopoietic stem cell transplantation, 57.5% surgery, and 86.6% immunosuppressive treatment. The 10-year survival rate was higher in patients with IL10 deficiency than in patients with IL10R deficiency. In conclusion, IL10/IL10R deficiency predominantly presents with treatment-resistant, early-onset IBD within the first months of life. We detected no clear correlation between the phenotype of patients carrying the same variant. The high prevalence of distinct clinical manifestations reported in IL10RA- and IL10RB-deficient patients might be attributable to the interactions between the target tissue and cytokines other than IL10 capable of binding to IL10RB. These results gain translational significance by contributing to earlier diagnosis, adequate therapy, and avoiding delay in the diagnosis and unfavorable outcomes.

Cytokine-induced killer cells mediated pathways in the treatment of colorectal cancer.

Cytokine-induced killer (CIK) cell therapy is a type of adoptive immunotherapy that due to its high proliferation rate and anti-tumor characteristics, is being investigated to treat various solid tumors. Since advanced colorectal cancer (CRC) has high mortality and poor survival rates, and the efficacy of chemotherapy and radiotherapy is limited in treatment, the application of CIK cell therapy in CRC has been evaluated in numerous studies. This review aims to summarize the clinical studies that investigated the safety and clinical efficacy of CIK cell therapy in CRC. Therefore, 1,969 enrolled CRC patients in the clinical trials, of which 842 patients received CIK cells in combination with chemotherapy with or without dendritic cell (DC) infusions, were included in the present review. Furthermore, the signaling pathways involved in CIK cell therapy and novel methods for improving migration abilities are discussed. Video abstract.

Clinical, immunological, and genetic features in 938 patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED): a systematic review.

Background: Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare inborn immune error characterized by a triad of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism (HP), and adrenal insufficiency (ADI).Methods: Literature search was conducted in PubMed, Web of Science, and Scopus databases using related keywords, and included studies were systematically evaluated.Results: We reviewed 938 APECED patients and the classic triad of APECED was detected in 57.3% (460 of 803) of patients. CMC (82.5%) was reported as the earliest, HP (84.2%) as the most prevalent, and ADI (72.2%) as the latest presentation within the classic triad. A broad spectrum of non-triad involvements has also been reported; mainly included ectodermal dystrophy (64.5%), infections (58.7%), gastrointestinal disorders (52.0%), gonadal failure (42.0%), neurologic involvements (36.4%), and ocular manifestations (34.3%). A significant positive correlation was detected between certain tissue-specific autoantibodies and particular manifestations including ADI and HP. Neutralizing autoantibodies were detected in at least 60.0% of patients. Nonsense and/or frameshift insertion-deletion mutations were detected in 73.8% of patients with CMC, 70.9% of patients with HP, and 74.6% of patients with primary ADI.Conclusion: Besides penetrance diversity, our review revealed a diverse affected ethnicity (mainly from Italy followed by Finland and Ireland). APECED can initially present in adolescence as 5.2% of the patients were older than 18 years at the disease onset. According to the variety of clinical conditions, which in the majority of patients appear gradually over time, clinical management deserves a separate analysis.