Local intramuscular transplantation of autologous bone marrow mononuclear cells for critical lower limb ischaemia.

BACKGROUND: Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients, the disease progresses to critical limb ischaemia (CLI), also known as critical limb-threatening ischaemia. In a substantial number of individuals with CLI, no effective treatment options other than amputation are available, with around a quarter of these patients requiring a major amputation during the following year. This is the second update of a review first published in 2011. OBJECTIVES: To evaluate the benefits and harms of local intramuscular transplantation of autologous adult bone marrow mononuclear cells (BMMNCs) as a treatment for CLI. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 8 November 2021. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) of CLI in which participants were randomly allocated to intramuscular administration of autologous adult BMMNCs or control (either no intervention, conventional conservative therapy, or placebo). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes of interest were all-cause mortality, pain, and amputation. Our secondary outcomes were angiographic analysis, ankle-brachial index (ABI), pain-free walking distance, side effects and complications. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included four RCTs involving a total of 176 participants with a clinical diagnosis of CLI. Participants were randomised to receive either intramuscular cell implantation of BMMNCs or control. The control arms varied between studies, and included conventional therapy, diluted autologous peripheral blood, and saline. There was no clear evidence of an effect on mortality related to the administration of BMMNCs compared to control (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.15 to 6.63; 3 studies, 123 participants; very low-certainty evidence). All trials assessed changes in pain severity, but the trials used different forms of pain assessment tools, so we were unable to pool data. Three studies individually reported that no differences in pain reduction were observed between the BMMNC and control groups. One study reported that reduction in rest pain was greater in the BMMNC group compared to the control group (very low-certainty evidence). All four trials reported the rate of amputation at the end of the study period. We are uncertain if amputations were reduced in the BMMNC group compared to the control group, as a possible small effect (RR 0.52, 95% CI 0.27 to 0.99; 4 studies, 176 participants; very low-certainty evidence) was lost after undertaking sensitivity analysis (RR 0.52, 95% CI 0.19 to 1.39; 2 studies, 89 participants). None of the included studies reported any angiographic analysis. Ankle-brachial index was reported differently by each study, so we were not able to pool the data. Three studies reported no changes between groups, and one study reported greater improvement in ABI (as haemodynamic improvement) in the BMMNC group compared to the control group (very low-certainty evidence). One study reported pain-free walking distance, finding no clear difference between BMMNC and control groups (low-certainty evidence). We pooled the data for side effects reported during the follow-up, and this did not show any clear difference between BMMNC and control groups (RR 2.13, 95% CI 0.50 to 8.97; 4 studies, 176 participants; very low-certainty evidence). We downgraded the certainty of the evidence due to the concerns about risk of bias, imprecision, and inconsistency. AUTHORS' CONCLUSIONS: We identified a small number of studies that met our inclusion criteria, and these differed in the controls they used and how they measured important outcomes. Limited data from these trials provide very low- to low-certainty evidence, and we are unable to draw conclusions to support the use of local intramuscular transplantation of BMMNC for improving clinical outcomes in people with CLI. Evidence from larger RCTs is needed in order to provide adequate statistical power to assess the role of this procedure.

Comprehensive assessment of respiratory complications in patients with common variable immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by recurrent upper and lower respiratory tract infections and some noninfectious clinical complications. OBJECTIVE: To provide a detailed evaluation of respiratory presentations and complications in a cohort of Iranian patients with CVID. METHODS: A retrospective cohort study was conducted on 245 CVID patients who were recorded in the Iranian primary immunodeficiency disorders registry network. Respiratory manifestations were evaluated by reviewing clinical hospital records, immunologic findings, pulmonary function tests (PFT), and high-resolution computed tomography (HRCT) scans. RESULTS: Most of the patients (n = 208, 85.2%) had experienced at least 1 episode of acute respiratory manifestation, and pneumonia was observed in 31.6 % (n = 77) of cases as a first disease manifestation. During the follow-up, pneumonia, sinusitis, and otitis media were documented in 166 (68.6%), 125 (51.2%), and 103 (42.6%) cases, respectively. Abnormal PFT measurements were documented in 53.8% of patients. Among these patients, 21.5% showed restrictive changes, whereas 18.4% of patients showed an obstructive pattern. Bronchiectasis was the most frequent radiological finding, confirmed in 27.2% of patients. Patients with bronchiectasis were older at the time of immunodeficiency diagnosis (P < .001) and had longer diagnosis delay (P < .001) when compared with patients without bronchiectasis. CONCLUSION: This study highlights the importance of monitoring the respiratory tract system even in asymptomatic patients. Pulmonary function tests and CT scans are the most commonly used techniques aiming to identify these patients early, aiming to reduce the rate of long-term respiratory complications.

The Association Between Low Levels of Vitamin D and Clinical Outcomes in Critically-Ill Children: A Systematic Review and Meta-Analysis.

Background: We conducted a meta-analysis to investigate the possible effects of vitamin D deficiency on clinical outcomes of critically-ill children.Methods: We searched Scopus-Embase and PubMed-Medline databases to find eligible observational articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations.Results: Seventeen articles (eighteen studies) involving 2987 critically ill patients met our inclusion criteria. Vitamin D deficiency was not associated with increased mortality. A significant association was only observed in very high developed countries between vitamin D deficiency and risk of sepsis [OR (95%CIs): 2.65 (1.30, 5.41)] and ventilation support requirement [OR (95%CIs): 1.35 (1.03, 1.77)].Conclusion: Our findings suggest that vitamin D deficiency is not associated with higher mortality among critically ill children but increases susceptibility to sepsis and the need for ventilator support in critical care settings.

The hyper IgM syndromes: Epidemiology, pathogenesis, clinical manifestations, diagnosis and management.

Hyper Immunoglobulin M syndrome (HIGM) is a rare primary immunodeficiency disorder characterized by low or absent levels of serum IgG, IgA, IgE and normal or increased levels of serum IgM. Various X-linked and autosomal recessive/dominant mutations have been reported as the underlying cause of the disease. Based on the underlying genetic defect, the affected patients present a variety of clinical manifestations including pulmonary and gastrointestinal complications, autoimmune disorders, hematologic abnormalities, lymphoproliferation and malignancies which could be controlled by multiple relevant therapeutic approaches. Herein, the epidemiology, pathogenesis, clinical manifestations, diagnosis, management, prognosis and treatment in patients with HIGM syndrome have been reviewed.

Candidiasis associated with very early onset inflammatory bowel disease: First IL10RB deficient case from the National Iranian Registry and review of the literature.

Defects in interleukin-10 (IL10) and interleukin-10 receptors (IL10R) are closely related to very early onset (infantile) inflammatory bowel disease (VEO-IBD). In the present study, we report a novel homozygous null mutation within interleukin-10 receptor B (IL10RB) gene in a child presenting with severe VEO-IBD. In accordance with previous reports, our patient manifested with chronic diarrhea, failure to thrive, intermittent fever and multiple anal ulcers associated with Candidiasis. Homozygous null mutation within IL10RB gene (c.92C > T, p.S31P) affecting the extracellular domain of protein was discovered in this patient. In conclusion, the diagnosis of IL-10R gene mutations should always be considered as a possible cause of refractory diarrhea and failure to thrive. Mutation analysis could help detect the genetic defects associated with these clinical manifestations and to determine the most appropriate treatment option for patients affected by this disease.

Respiratory Complications in Patients with Hyper IgM Syndrome.

PURPOSE: Hyper Immunoglobulin M (HIgM) syndrome is a heterogeneous group of primary immunodeficiency disorders, characterized by recurrent infections and associated with decreased serum IgG and IgA, but normal or increased IgM. The aim of the present study was to evaluate respiratory manifestations in patients with HIgM syndrome. METHODS: A total number of 62 patients, including 46 males and 16 females were included in the present study. To investigate the respiratory complications among HIgM patients, we evaluated the clinical hospital records, immunologic and molecular diagnostic assays, pulmonary function tests (PFT), and high-resolution computed tomography (HRCT) scans. RESULTS: Pneumonia was the most common respiratory manifestation (n = 35, 56.4%), followed by otitis media (45.1%), sinusitis (33.8%), and bronchiectasis (14.5%). 52.1% of the patients had abnormal PFT results, with a predominant restrictive pattern of changes. HRCT scans demonstrated abnormal findings in 85.7% of patients with found mutations. Ten cases had hilar lymphadenopathy and para-hilar infiltrates in their HRCT findings. Genetic diagnosis was confirmed in 29 HIgM patients (72.4% CD40 ligand (CD40L) and 24.1% activation-induced cytidine deaminase (AICDA/AID) deficiencies). Majority of patients with CD40L (71.4%) and AID (57.1%) deficiencies had missense mutations. Pneumonia and abnormal high-resolution computed tomography (HRCT) findings were more frequent among patients with CD40L mutation. Respiratory failure constituted the major cause of mortality (37.5%) with majority of cases occurring in CD40L-deficient patients (50%). CONCLUSIONS: Respiratory complications are common in patients with HIgM syndrome. A proper awareness of respiratory manifestations in patients with HIgM may result in improved management, reduced morbidity and mortality, and an improvement in the quality of life of the patients.

Clinical Manifestations, Immunological Characteristics and Genetic Analysis of Patients with Hyper-Immunoglobulin M Syndrome in Iran.

BACKGROUND: Hyper-immunoglobulin M (HIGM) syndrome is a rare heterogeneous group of primary immunodeficiency disorders characterized by low or absent serum levels of IgG and IgA along with normal or elevated serum levels of IgM. METHODS: Clinical and immunological data were collected from the 75 patients' medical records diagnosed in Children's Medical Center affiliated to Tehran University Medical Sciences and other Universities of Medical Sciences in Iran. Among 75 selected patients, 48 patients (64%) were analyzed genetically using targeted and whole-exome sequencing. RESULTS: The ratio of male to female was 2.9:1. The median age at the onset of the disease, time of diagnosis, and diagnostic delay were 10.5, 50, and 24 months, respectively. Pneumonia and lower respiratory tract infections (61.3%) were the most common complications. Responsible genes were identified in 35 patients (72.9%) out 48 genetically analyzed patients. Cluster of differentiation 40 ligand gene was the most mutated gene observed in 24 patients (68.5%) followed by activation-induced cytidine deaminase gene in 7 patients, lipopolysaccharide-responsive and beige-like anchor (1 patient), nuclear factor-kappa-B essential modulator (1 patient), phosphoinositide-3-kinase regulatory subunit 1 (1 patient), and nuclear factor kappa B subunit 1 (1 patient) genes. Nineteen (25.3%) patients died during the study period, and pneumonia was the major cause of death occurred in 6 (31.6%) patients. CONCLUSION: Physicians in our country should carefully pay attention to respiratory tract infections and pneumonia, particularly in patients with a positive family history. Further investigations are required for detection of new genes and pathways resulting in HIGM phenotype.

Single Nucleotide Polymorphisms of PTPN22 Gene in Iranian Patients with Ulcerative Colitis.

OBJECTIVES: Protein tyrosine phosphatase non-receptor type 22 gene (PTPN22) single-nucleotide polymorphisms (SNP) have been associated with a number of different autoimmune diseases. This study aimed to investigate the association of five polymorphisms of PTPN22 gene with susceptibility to ulcerative colitis (UC) in Iran. MATERIALS AND METHODS: A total of 67 patients diagnosed with UC (35 female and 32 male all under 18 years) and 93 healthy subjects were selected. The samples were genotyped for the, rs12760457, rs2476601, rs1310182, rs1217414, and rs33996649 in PTPN22 gene using real-time polymerase chain reaction (PCR) allelic discrimination TaqMan genotyping assays. RESULTS: The frequencies of the rs1310182 A and G alleles, and also the AA and GG genotypes were significantly different between the patient and the control groups (p < 0.05). The carriage of G allele of rs1310182 was significantly associated with increased risk of UC (OR (95% CI) = 1.17 (0.70-1.98), p < 0.001). Moreover, the genotype GG of SNP rs1310182 was significantly associated with UC (OR (95% CI) = 2.32 (1.13-4.76), p < 0.01). No association was found between other PTPN22 gene SNPs among UC patients. CONCLUSION: PTPN22 gene polymorphism in rs1310182 could play a crucial role in susceptibility to UC.

Local intramuscular transplantation of autologous mononuclear cells for critical lower limb ischaemia.

BACKGROUND: Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients the disease progresses to critical limb ischaemia (CLI). In a substantial number of patients with CLI, no effective treatment option other than amputation is available and around a quarter of these patients will require a major amputation during the following year. This is an update of the review first published in 2011. OBJECTIVES: To determine the effectiveness and safety of local intramuscular transplantation of autologous adult bone marrow mononuclear cells (BMMNCs) as a treatment for critical limb ischaemia (CLI). SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched February 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 1). SELECTION CRITERIA: We included all randomised controlled trials of CLI in which participants were randomly allocated to intramuscular administration of autologous adult BMMNCs or control (either no intervention or conventional conservative therapy). We excluded studies on patients with intermittent claudication. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. Disagreements were resolved by consensus or by the third author. MAIN RESULTS: Only two small studies, with a combined total of 57 participants, met our inclusion criteria and were finally included. They were classified as having a moderate risk of bias with unclear issues regarding their methods, and according to the GRADE approach, the overall quality of the evidence would be considered as moderate. In one study the effects of intramuscular injections of BMMNCs in the ischaemic lower limbs of patients with CLI were compared with control (standard conservative treatment). No deaths were reported and no significant difference was observed between the two groups for either pain (P = 0.37) or the ankle brachial index (ABI) parameter. However, the treatment group showed a significantly smaller proportion of participants undergoing amputation compared with the control group (P = 0.026).In the other study, following subcutaneous injections of granulocyte colony-stimulating factor (G-CSF) for five days, peripheral blood derived mononuclear cells were collected and then transplanted by intramuscular injections into ischaemic lower limbs. The effects were compared with daily intravenous prostaglandin E1 injections (control group). No deaths were reported. Pain reduction was greater in the treatment group than in the control group (P < 0.001) as was increase in ABI (mean increase 0.13 versus 0.02, P < 0.01). The treatment group experienced a statistically significant increase in pain-free walking distance (PFWD) compared with the control group (mean increase 306.4 m versus 78.6 m, P = 0.007). A smaller proportion of participants underwent amputation in the treatment group compared with the control group (0% versus 36%, P = 0.007). AUTHORS' CONCLUSIONS: The data from the published trials suggest that there is insufficient evidence to support this treatment. These results were based on only two trials which had a very small number of participants. Therefore evidence from larger randomised controlled trials is needed in order to provide adequate statistical power to assess the role of intramuscular mononuclear cell implantation in patients with CLI.

Continuous Glucose Monitoring Metrics and Hemoglobin A1c Relationship in Patients with Type 2 Diabetes Treated by Hemodialysis.

Background:There is a need for accurate glycemic control metrics in patients with diabetes and end-stage kidney disease (ESKD). Hence, we assessed the relationship of continuous glucose monitoring (CGM) metrics and laboratory-measured hemoglobin A1c (HbA1c) in patients with type 2 diabetes (T2D) treated by hemodialysis. Methods: This prospective observational study included adults (age 18-80 years) with T2D (HbA1c 5%-12%), treated by hemodialysis (for at least 90 days). Participants used a Dexcom G6 Pro CGM for 10 days. Correlation analyses between CGM metrics [mean glucose, glucose management indicator (GMI), and time-in-range (TIR 70-180 mg/dL)] and HbA1c were performed. Results: Among 59 participants (mean age was 57.7 ± 9.3 years, 58% were female, 86% were non-Hispanic blacks), the CGM mean glucose level was 188.9 ± 45 mg/dL (95% CI: 177.2, 200.7), the mean HbA1c and GMI were 7.1% ± 1.3% and 7.8% ± 1.1%, respectively (difference 0.74% ± 0.95). GMI had a strong negative correlation with TIR 70-180 mg/dL (r = -0.96). The correlation between GMI and HbA1c (r = 0.68) was moderate. Up to 29% of participants had a discordance between HbA1c and GMI of <0.5%, with 22% having a discordance between 0.5% and 1%, and 49% having a discordance of >1%. Conclusions: In patients with diabetes and ESKD treated by hemodialysis, the GMI has a strong correlation with TIR, while HbA1c underestimated the average glucose and GMI. Given the limitations of HbA1c in this population, GMI or mean glucose and TIR may be considered as more appropriate glucose control markers.

Assessment of Glycemic Control by Continuous Glucose Monitoring, Hemoglobin A1c, Fructosamine, and Glycated Albumin in Patients With End-Stage Kidney Disease and Burnt-Out Diabetes.

OBJECTIVE: Patients with diabetes and end-stage kidney disease (ESKD) may experience "burnt-out diabetes," defined as having an HbA1c value <6.5% without antidiabetic therapy for >6 months. We aim to assess glycemic control by continuous glucose monitoring (Dexcom G6 CGM) metrics and glycemic markers in ESKD patients on hemodialysis with burnt-out diabetes. RESEARCH DESIGN AND METHODS: In this pilot prospective study, glycemic control was assessed by continuous glucose monitoring (CGM), HbA1c measures, and glycated albumin and fructosamine measurements in patients with burnt-out diabetes (n = 20) and without a history of diabetes (n = 20). RESULTS: Patients with burnt-out diabetes had higher CGM-measured daily glucose levels, lower percent time in the range 70-180 mg/dL, higher percent time above range (>250 mg/dL), and longer duration of hyperglycemia >180 mg/dL (hours/day) compared with patients without diabetes (all P < 0.01). HbA1c and fructosamine levels were similar; however, patients with burnt-out diabetes had higher levels of glycated albumin than did patients without diabetes. CONCLUSIONS: The use of CGM demonstrated that patients with burnt-out diabetes have significant undiagnosed hyperglycemia. CGM and glycated albumin provide better assessment of glycemic control than do values of HbA1c and fructosamine in patients with ESKD.

Continuous Glucose Monitoring-Guided Insulin Administration in Long-Term Care Facilities: A Randomized Clinical Trial.

OBJECTIVES: To evaluate the efficacy of real-time continuous glucose monitoring (rt-CGM) in adjusting insulin therapy in long-term care facilities (LTCF). DESIGN: Prospective randomized clinical trial. SETTINGS AND PARTICIPANTS: Insulin-treated patients with type 2 diabetes (T2D) admitted to LTCF. METHODS: Participants in the standard of care wore a blinded CGM with treatment adjusted based on point-of-care capillary glucose results before meals and bedtime (POC group). Participants in the intervention (CGM group) wore a Dexcom G6 CGM with treatment adjusted based on daily CGM profile. Treatment adjustment was performed by the LTCF medical team, with a duration of intervention up to 60 days. The primary endpoint was difference in time in range (TIR 70-180 mg/dL) between treatment groups. RESULTS: Among 100 participants (age 74.73 ± 11 years, 80% admitted for subacute rehabilitation and 20% for nursing home care), there were no significant differences in baseline clinical characteristics between groups, and CGM data were compared for a median of 17 days. There were no differences in TIR (53.38% ± 30.16% vs 48.81% ± 28.03%, P = .40), mean daily mean CGM glucose (184.10 ± 43.4 mg/dL vs 190.0 ± 45.82 mg/dL, P = .71), or the percentage of time below range (TBR) <70 mg/dL (0.83% ± 2.59% vs 1.18% ± 3.54%, P = .51), or TBR <54 mg/dL (0.23% ± 0.85% vs 0.56% ± 2.24%, P = .88) between rt-CGM and POC groups. CONCLUSIONS AND IMPLICATIONS: The use of rtCGM is safe and effective in guiding insulin therapy in patients with T2D in LTCF resulting in a similar improvement in glycemic control compared to POC-guided insulin adjustment.

Granulocyte colony stimulating factor therapy for acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) is the leading cause of death in developed countries, and current treatment modalities have failed to regenerate the dead myocardium resulting from the ischemic damage. Stem cells have the potential to regenerate the damaged myocardium. These cells can be mobilized from the bone marrow by factors such as granulocyte colony stimulating factor (G-CSF). OBJECTIVES: To assess the effects of stem cell mobilization following granulocyte colony stimulating factor therapy in patients with acute myocardial infarction. SEARCH METHODS: We searched CENTRAL (The Cochrane Library Issue 4, 2010), MEDLINE (1950 to November week 3, 2010), EMBASE (1980 to 2010 week 48), BIOSIS Previews (1969 to 30 November 2010), ISI Science Citation Index Expanded (1970 to 4 December 2010) and ISI Conference Proceedings Citation Index - Science (1990 to 4 December 2010). We also checked reference lists of articles. SELECTION CRITERIA: We included randomized controlled trials including participants with a clinical diagnosis of AMI who were randomly allocated to the subcutaneous administration of G-CSF through a daily dose of 2.5, 5 or 10 microgram/kg for four to six days or placebo. No age or other restrictions were applied for the selection of patients. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data regarding the clinical efficacy and adverse outcomes. Disagreements were resolved by the third author. MAIN RESULTS: We included seven trials reported in 30 references in the review (354 participants). In all trials, G-CSF was compared with placebo preparations. Dosage of G-CSF varied among studies, ranging from 2.5 to 10 microgram/kg/day. Regarding overall risk of bias, data regarding the generation of randomization sequence and incomplete outcome data were at a low risk of bias; however, data regarding binding of personnel were not conclusive. The rate of mortality was not different between the two groups (RR 0.64, 95% CI 0.15 to 2.80, P = 0.55). Regarding safety, the limited amount of evidence is inadequate to reach any conclusions regarding the safety of G-CSF therapy. Moreover, the results did not show any beneficial effects of G-CSF in patients with AMI regarding left ventricular function parameters, including left ventricular ejection fraction (RR 3.41, 95% CI -0.61 to 7.44, P = 0.1), end systolic volume (RR -1.35, 95% CI -4.68 to 1.99, P = 0.43) and end diastolic volume (RR -4.08, 95% CI -8.28 to 0.12, P = 0.06). It should also be noted that the study was limited since the trials included lacked long enough follow up durations. AUTHORS' CONCLUSIONS: Limited evidence from small trials suggested a lack of benefit of G-CSF therapy in patients with AMI. Since data of the risk of bias regarding blinding of personnel were not conclusive, larger RCTs with appropriate power calculations and longer follow up durations are required in order to address current uncertainties regarding the clinical efficacy and therapy-related adverse events of G-CSF treatment.

A Randomized Controlled Trial Comparing the Efficacy and Safety of IDegLira Versus Basal-Bolus in Patients With Poorly Controlled Type 2 Diabetes and Very High HbA1c ≥9-15%: DUAL HIGH Trial.

OBJECTIVE: In participants with type 2 diabetes (T2D) and HbA1c >9.0-10.0%, guidelines recommend treatment with basal-bolus insulin. RESEARCH DESIGN AND METHODS: This randomized trial compared the efficacy and safety of insulin degludec and liraglutide (IDegLira) and basal-bolus among participants with high HbA1c ≥9.0-15.0%, previously treated with 2 or 3 oral agents and/or basal insulin, allocated (1:1) to basal-bolus (n = 73) or IDegLira (n = 72). The primary end point was noninferiority (0.4%) in HbA1c reduction between groups. RESULTS: Among 145 participants (HbA1c 10.8% ± 1.3), there was no statistically significant difference in HbA1c reduction (3.18% ± 2.29 vs. 3.00% ± 1.79, P = 0.65; estimated treatment difference (ETD) 0.18%, 95% CI -0.59, 0.94) between the IDegLira and basal-bolus groups. IDegLira resulted in significantly lower rates of hypoglycemia <70 mg/dL (26% vs. 48%, P = 0.008; odds ratio 0.39, 95% CI 0.19, 0.78), and less weight gain (1.24 ± 8.33 vs. 5.84 ± 6.18 kg, P = 0.001; ETD -4.60, 95% CI -7.33, -1.87). CONCLUSIONS: In participants with T2D and HbA1c ≥9.0-15.0%, IDegLira resulted in similar HbA1c reduction, less hypoglycemia, and less weight gain compared with the basal-bolus regimen.

Diabetic retinopathy in African-Americans with end-stage kidney disease: a cross-sectional study on prevalence and impact on quality of life.

INTRODUCTION: The prevalence, severity, and quality of life (QoL) impact of diabetic retinopathy (DR) among African-Americans (AAs) with end-stage kidney disease (ESKD) undergoing dialysis are unknown. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted on 93 AA adults with diabetes and ESKD. The diagnosis of DR was based on a review of medical records and/or a positive photograph with a portable hand-held device reviewed by both artificial intelligence software and a retinal specialist. QoL, physical disability social determinants of health (SDoHs) were assessed by standardized questionnaires. RESULTS: The prevalence of DR was 75%, with 33% of participants having mild, 9.6% moderate and 57.4% severe DR. A total of 43% had normal visual acuity; 45% had moderate visual impairment; and 12% had severe visual impairment. We found a high burden of disease, multiple SDoH challenges, and low QoL and general health among patients with ESKD. The presence of DR had no significant impact on physical health and QoL compared with participants without DR. CONCLUSIONS: DR is present in 75% of AA patients with diabetes and ESKD on haemodialysis. ESKD has a significant burden on general health and QoL; however, DR has a minor additional impact on the overall physical health and QoL in people with ESKD.

Anastomotic biliary stricture following liver transplantation and management analysis: 15 years of experience at a high-volume transplant center.

INTRODUCTION: The occurrence of anastomotic biliary stricture (BS) remains an essential issue following liver transplantation (LT). The present study aimed to compare our findings regarding the incidence of anastomotic BS to what is known. METHODS: The present study is a single-center, retrospective cohort study of a total number of 717 consecutive patients (426 men and 291 women) who had undergone LT from January 2001 to March 2016. Multivariable Cox regression analysis was conducted to evaluate the risk factors associated with anastomotic BS development. RESULTS: Post-transplant anastomotic BS developed in 70 patients (9.8%). In the Cox multivariate analysis (a stepwise forward conditional method), factors including biliary leak (hazard ratio [HR]: 6.61, 95% confidence interval [CI]: 3.08-17.58, p < 0.001), hepatic artery thrombosis (HR: 2.29, 95% CI: 1.03-5.88; p = 0.003), and acute rejection (HR: 2.18, 95% CI: 1.16-3.37; p = 0.006) were identified as independent risk factors for the development of anastomotic BS. Surgery in 6 cases (66.7%), followed by endoscopic retrograde cholangiopancreatography (ECRP) with a metal stent in 18 cases (62.1%), percutaneous transhepatic biliary drainage in 9 (20.9%), and ERCP with a single plastic stent in 8 (18.2%), had the highest effectiveness rates in the management of BS, respectively. CONCLUSIONS: Risk factors including biliary leak, hepatic artery thrombosis, and acute rejection were independently associated with an anastomotic BS. ERCP with a metal stent may be considered as an effective treatment procedure with a relatively low complication rate in the management of benign post-LT anastomotic BS.

Effectiveness of dietary interventions on cardio-metabolic risk factors in patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Dietary modification is considered as one of the main strategies in the management of nonalcoholic fatty liver disease (NAFLD). The objective of this study was to systematically investigate the effect of dietary interventions on the cardio-metabolic risk factors, including lipid profile and insulin resistance in this population. METHODS: We searched electronic databases of PubMed and Scopus until January 2020 and included randomized controlled trials that compared the effect of dietary modifications vs. control on lipid profile and insulin resistance in patients with NAFLD. The random-effect analysis was performed to calculate pooled weighted mean differences (WMD). RESULTS: Our finding showed that serum triglycerides (TG) (n=5, WMD -38.50 mg/dL, 95% confidence interval [CI] -61.68 to -15.31; P=0.001) and total cholesterol (TC) (n=4, WMD -18.70 mg/dL, 95%CI -34.85 to -2.53; P=0.023) decrease following diet intervention along with marginally significant weight reduction (n=5, WMD -3.61 mg/dL, 95%CI -7.25 to 0.04; P=0.053). There was no change in the homeostatic model assessment for insulin resistance, high- and low-density lipoprotein (LDL) levels (P>0.05). Subgroup analysis revealed that Mediterranean diet reduced TG (n=2, WMD -57.52 mg/dL, 95%CI -75.73 to -39.31; P<0.001) and weight (n=2, WMD -7.59 Kg, 95%CI -13.53 to -1.66; P=0.012), and also increased LDL level (n=2, WMD 29.73 mg/dL, 95%CI 13.82-45.65; P<0.001). However, standard hypocaloric diet improved TC (n=2, WMD -23.20 mg/dL, 95%CI -36.96 to -9.44; P=0.001) and LDL (n=2, WMD -16.82 mg/dL, 95%CI -29.44 to -4.19; P=0.009). CONCLUSION: Dietary modifications may improve serum TG, TC, and obesity in NAFLD.

A Pilot Randomized, Clinical Trial of the Anti-pruritus Effect of Melatonin in Patients with Chronic Liver Disease.

Pruritus is one of the disturbing complications induced by chronic liver disease (CLD), bearing a negative impact on patient quality of life and potentially resulting in early liver transplants. Given the main role of the autotaxin enzyme in pruritus induced by CLD and the suppressive effects of melatonin on the expression of the autotaxin gene, this study was designed to evaluate the antipruritic effect of melatonin in patients with CLD. A double-blind, cross-over, randomized, placebo-controlled pilot trial was conducted on patients with CLD -induced pruritis. Patients were randomly assigned to two groups where they received melatonin 10-mg at night or placebo for 2 weeks. After a 2-week washout period, patients were then crossed over to the other group. The Visual Analog Scale (VAS) and the 12-Item Pruritus Severity Score (12-PSS) were used to assess patient response to therapy as the co-primary outcomes, while liver function tests were assayed too. Forty patients completed the study. The VAS score showed alleviation of 3.21 ± 2.24 (in pruritus) with melatonin (p-value <0.05). The study goal (a reduction of at least 20% in VAS) was achieved in 33 (82%) of study participants. In patients who received melatonin, the 12-PSS and Body Surface Area (BSA) affected by pruritus decreased on average 46.57% and 51.71%, respectively, with mood, sleep pattern and daily activity levels also demonstrating significant improvement (p-value < 0.05). Melatonin was found to be effective for managing pruritus in patients with CLD.

Prognostic Factors Associated with Survival in Patients Infected with COVID-19: A Retrospective Study on 214 Patients from Iran.

BACKGROUND: Decision-making on allocating scarce medical resources is crucial in the context of a strong health system reaction to the coronavirus disease 2019 (COVID-19) pandemic. Therefore, understanding the risk factors related to a high mortality rate can enable the physicians for a better decision-making process. METHODS: Information was collected regarding clinical, demographic, and epidemiological features of the definite COVID-19 cases. Through Cox regression and statistical analysis, the risk factors related to mortality were determined. The Kaplan-Meier curve was used to estimate survival function and measure the mean length of living time in the patients. RESULTS: Among about 3000 patients admitted in the Taleghani hospital as outpatients with suspicious signs and symptoms of COVID-19 in 2 months, 214 people were confirmed positive for this virus using the polymerase chain reaction (PCR) technique. Median time to death was 30 days. In this population, 24.29% of the patients died and 24.76% of them were admitted to the ICU (intensive care unit) during hospitalization. The results of Multivariate Cox regression Analysis showed that factors including age (HR, 1.031; 95% CI, 1.001-1.062; P value=0.04), and C-reactive protein (CRP) (HR, 1.007; 95% CI, 1.000-1.015; P value=0.04) could independently predict mortality. Furthermore, the results showed that age above 59 years directly increased mortality rate and decreased survival among our study population. CONCLUSION: Predictor factors play an important role in decisions on public health policy-making. Our findings suggested that advanced age and CRP were independent mortality rate predictors in the admitted patients.