Early hepatic artery thrombosis treatments and outcomes: aorto-hepatic arterial conduit interposition or revision of anastomosis?

BACKGROUND: Hepatic artery thrombosis (HAT) is one of the critical conditions after an orthotopic liver transplant (OLT) and leads to severe problems if not corrected promptly. However, multiple treatments have been proposed for HAT, in which surgical revascularization with either auto-hepatic conduit interposition (AHCI) or revision of the anastomosis is more familiar indeed indicated for some patients and in specific situations. In this study, we want to evaluate the success and outcomes of treating early HAT (E-HAT), which defines HAT within 30 days after OLT with either of the surgical revascularization techniques. METHOD: In this retrospective study, we collected information from the medical records of patients who underwent either of the surgical revascularization procedures for E-HAT after OLT. Patients who needed early retransplantation (RT) or died without surgical intervention for E-HAT were excluded. Demographic data, OLT surgery information, and data regarding E-HAT were gathered. The study outcomes were secondary management for E-HAT in case of improper inflow, biliary complications (BC), RT, and death. RESULTS: A total of 37 adult patients with E-HAT after OLT included in this study. These E-HATs were diagnosed within a mean of 4.6 ± 3.6 days after OLT. Two patients had their HA revised for the initial management of E-HAT; however, it changed to AHCI intraoperatively and finally needed RT. Two and nine patients from the AHCI and revision groups had re-thrombosis (12.5% vs. 47.3%, respectively, p = 0.03). RT was used to manage rethrombosis in all patients of AHCI and two patients of the revision group (22.2%). In comparison to the AHCI, revision group had statistically insignificant higher rates of BC (47.4% vs. 31.2%); however, RT for nonvascular etiologies (12.5% vs. 5.3%) and death (12.5% vs. 10.5%) were nonsignificantly higher in AHCI group. All patients with more than one HA exploration who were in the revision group had BC; however, 28.5% of patients with just one HA exploration experienced BC (p < 0.001). CONCLUSION: Arterial conduit interposition seems a better approach for the initial management of E-HAT in comparison to revision of the HA anastomosis due to the lower risk of re-thrombosis and the number of HA explorations; indeed, BC, RT, and death remain because they are somewhat related to the ischemic event of E-HAT than to a surgical treatment itself.

Sensitive detection of specific cell-free DNA in serum samples from sheep with cystic echinococcosis.

BACKGROUND: Developing more sensitive methods for the diagnosis of echinococcosis is essential. In this study PCR assay for sensitive detection of specific cell-free DNA (cfDNA) of Echinococcus granulosus sensu lato in the sera of the sheep naturally infected with echinococcosis was investigated. METHODS: To extract cfDNA from 35 infected sheep, the modified phenol-chloroform method was used for two different volumes (0.5 and 2 ml) of serum samples. From each extracted sample, two DNA volumes (5 and 10 µl) were amplified using both standard PCR and semi-nested PCR targeting NADH dehydrogenase subunit I. RESULTS: Standard and semi-nested PCR on 0.5 ml of serum samples detected Echinococcus DNA in 8 and 12 out of 35 sheep, respectively; however, using 2 ml of serum samples, they detected 24 and 27 samples. By increasing the volume of template DNA, the PCRs could detect 29 and 33 out of 35 samples. The results were confirmed by sequencing of randomly selected PCR amplicons and comparing them with GenBank databases. CONCLUSIONS: Larger volumes of serum for DNA extraction, greater volumes of DNA template for PCR, and employing a semi-nested PCR protocol, increased the sensitivity of PCR to 95%. This approach can also be applied to the diagnosis of echinococcosis in humans.

The efficacy of buprenorphine on moderate traumatic brain injury in the rat model.

INTRODUCTION: Traumatic brain injury (TBI) is the leading cause of death, disability, and mental health disorders. A wide range of bioactive lipids, cytokines, and chemokines drives the inflammatory response. This study aimed to assess the efficacy of buprenorphine on moderate Trauma Brain Injury (mTBI) in rats. METHODS: In this study, 21 Wistar male rats weighing 230 ± 10 g were included. We trained cases by Morris water navigation task and mTBI induced by the pendulum. Then, buprenorphine treatment with 0.05 mg per kilogram of body weight continued from day 8 to 21. Finally, by Micro-Computed Tomography, behavioral evaluation by the Morris aqueous riddle test and biochemical factors of inflammation were assessed. RESULTS: Severe subdural inflammation was more in the treatment group than in the control group. The behavior of Rats showed that in the buprenorphine group, the mean duration of finding the platform increased compared to the control and Sham groups. However, the groups had no significant differences (P > 0.05). Biochemically, buprenorphine increased prolactin and decreased cortisol compared to the control and trauma groups (P < 0.05). CONCLUSION: These results suggest that buprenorphine causes fewer changes in behavioral functions in rats' models of mTBI and, because of their positive effect changes on inflammation biomarkers, biochemical behavioral tests, and CT scan images, could be ideal analgesic agents for pre-clinical responses after TBI.

The Impact of Rigid Cervical Collars on Outcome of Patients Who Underwent Posterior Cervical Laminectomy and Fusion: A Retrospective Comparative Study.

STUDY DESIGN: Retrospective cohort study. PURPOSE: This study aimed to investigate the cervical collar impact on the functional outcomes of patients after posterior cervical laminectomy and lateral mass screw fixation (PCLF) surgery. OVERVIEW OF LITERATURE: The safety and possible benefits of implementing rigid cervical collars subsequent to PCLF are insufficiently investigated. METHODS: Patients who underwent PCLF and received postoperative cervical collars from 2018 to 2020 were included in this retrospective cohort study. Their data were compared with an age- and sex-matched group of subjects who did not receive collars after PCLF during the same period. Pain intensity (using the Visual Analog Scale), Neck Disability Index, and quality of life (using 36-item Short Form Health Survey) of the patients were compared at baseline, 1, 3, 6, and 12 months postoperatively. RESULTS: A total of 36 patients who received cervical collars after surgery and 40 controls were included. At baseline and 1-month follow-up, there were no differences in pain intensity, functional status, and quality of life between the groups. However, at 3 months postoperatively, the quality of life of the subjects with no orthosis was higher than those who received cervical collars (p =0.01). At 6- and 12-month follow-up, there were no differences between the groups in pain intensity, functional status, and quality of life. CONCLUSIONS: No difference in the pain intensity and functional status of patients who used cervical collars and controls was shown in our study. Patients who did not wear cervical collars had a higher quality of life during the 3-month postoperative evaluation. Future prospective, well-controlled studies with longer follow-ups are needed to further investigate the effects of cervical orthosis on the clinical outcome of patients after PCLF.

Obstructed Descending Colon Mass Presented With Bochdalek Hernia: A Case Report.

The adult Bochdalek hernia is one of the right-sided diaphragmatic hernias that less than 30 cases reported until now. Here, we report a 64-year-old female patient who presented with dyspnea, abdominal pain, and nausea. Primary imaging showed a right-sided diaphragmatic hernia that contained the liver and right colon. At first, the patient underwent a right posterior thoracotomy, and the diaphragmatic defect was repaired. After 2 days, abdominal peritonitis happened then a midline laparotomy was performed. Finally, it was clear that the main problem was the obstructed and perforated descending colon mass that was presented with Bockdalek hernia. Unfortunately, the patient passed away 2 days after the operation. It should be considered that an increase in intra-abdominal pressure like the presence of obstructed colon mass can cause this rare hernia and It is important to determine the reason for the presentation of the symptomatic Bochdalek hernia in adult patients.

Effect of Topical Administration of Tranexamic Acid on Intraoperative and Postoperative Blood Loss during Posterior Cervical Laminectomy and Fusion Surgery: A Retrospective Study.

AIM: To assess the role of topical administration of tranexamic acid (TXA) on intraoperative and postoperative blood loss of patients undergoing posterior cervical laminectomy and lateral mass screw ?xation (PCLF) compared to a control group. MATERIAL AND METHODS: The data of 88 patients that underwent PCLF surgery, including 41 females and 47 males, were included in this retrospective study. Data elements including intraoperative blood loss (IBL), postoperative blood loss (PBL), amount of blood transfusion, surgical time, use of hemostatic agents, length of hospital stay, and time to return to work were extracted from medical records and compared between those who received topical TXA during surgery (irrigation of the surgical field with a solution of 3 g TXA in 100 ml normal saline) and an age- and sex-matched control group. RESULTS: There were 48 patients in the TXA group and 40 patients in the control group. There were no significant differences in the baseline measurements and the level of operation between the two groups. The results showed that IBL and PBL were significantly lower in the TXA group compared to the control group (p=0.03 and p < 0.01, respectively). There were no significant differences in the need for blood transfusion, surgical time, and hospital stay between the two groups (p > 0.05). Moreover, the use of hemostatic materials during surgery and the time to return to work were significantly lower in the topical TXA group (p=0.04 and p < 0.01, respectively). CONCLUSION: Topical TXA efficiently reduces intraoperative and postoperative bleeding in patients undergoing posterior cervical laminectomy and PCLF surgery. These results need further investigation in future studies to draw a definite conclusion.

The Effect of Topical Tranexamic Acid on Intraoperative Blood Loss in Patients Undergoing Posterior Lumbar Laminectomy and Discectomy: A Randomized, Double-Blind, Controlled Trial Study.

STUDY DESIGN: Randomized, double-blind, controlled trial study. PURPOSE: This study aimed to evaluate the safety and efficacy of topical tranexamic acid (TXA) on intraoperative blood loss (IBL) in patients that have degenerative lumbar canal stenosis and undergo posterior lumbar laminectomy and discectomy. OVERVIEW OF LITERATURE: The volume of IBL is directly proportional to potential surgical complications. Recent reports have shown that the topical use of antifibrinolytic drugs, such as TXA, during surgery might decrease IBL and improve patient outcomes. METHODS: A total of 104 patients with lumbar canal stenosis were enrolled in this randomized, double blinded clinical trial. Participants were randomized and divided into two groups: TXA (54 cases) and control (50 cases). In the TXA group, a TXA solution was used for washing and soaking, whereas, in the control group, irrigation of wound was with normal saline. IBL, pre- and postoperative coagulative studies, operation time, conventional hemostatic agent usage, systemic complications, and length of hospitalization were consecutively recorded. All participants were followed for an additional two months to gather data on their recovery status and time to return to work (RTW). RESULTS: At baseline, there was no difference in clinical or lab findings, between the groups. IBL and use of hemostatic agents were significantly decreased in TXA group, as compared to the control group (p=0.001 and p=0.011, respectively). Systemic complications, length of hospitalization, and RTW were not significantly different between groups (p=0.47, p=0.38, and p=0.08, respectively). CONCLUSIONS: This study showed that topical use of TXA during surgery may decrease IBL and minimize the use of hemostatic materials during posterior midline-approach laminectomy and discectomy, without increasing the potential for complications seen with intravenous TXA usage.

Epidemiology, Sociodemographic Factors and Comorbidity for Allergic Rhinitis, Asthma, and Rhinosinusitis Among 15 to 65-year-Old Iranian Patients.

Background: It is well established that upper and lower airways are often clumped together when diagnosing and treating a disease. This study was designed to determine the prevalence of upper and lower airway diseases and to assess the effect of sociodemographic factors on the prevalence and the comorbidity of these disorders. Methods: This cross-sectional population-based study included patients with ages ranging between 15 to 65 years, who were referred to allergy outpatient clinics in various provinces of Iran from April to September 2020. A modified global Allergy and Asthma European Network (GA2LEN) screening questionnaire was filled out by local allergists of the 12 selected provinces in Iran. Information about the patients and sociodemographic factors was also recorded. Statistical analysis was done by univariate statistical analyses and multiple logistic regressions in SPSS software Version 26. Results: Out of 4988 recruited patients, 1078 (21.6%) had the symptoms of allergic rhinitis (AR) and 285 (5.7%) met the criteria of asthma. The prevalence of acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) was 21.6 % and 22%, respectively. The highest prevalence of AR and ARS was in Tehran with the arateof of 33.9% each. Asthma was more prevalent in Khuzestan (14.2%) and CRS in Baluchestan (57.5%). Our analysis showed that the patients with asthma were most likely to have other allergic diseases as well-CRS (OR = 4.8; 95% CI, 2.02- 5.82), AR (OR= 2.5, 95% CI, 2.10-3), ARS (OR = 1.8; 95% CI, 2.10-3), followed by eczema (OR = 1.4; 95% CI, 1.13-1.67).We found that those individuals with CRS were most likely to have painkiller hypersensitivity (OR= 2.1; 95% CI, 1.21-3.83). Furthermore, smoking has been found more than 1.5 folds in patients with ARS. After adjusting variables, there was no correlation between education, occupation, and ethnicity with the studied diseases. Conclusion: Rhinosinusitis is a common condition among Iranian patients. This study confirmed that inflammation of the upper and lower airways can occur simultaneously. Gender, education, occupation, and ethnicity were found to be irrelevant in the development of either AR, asthma, ARS, or CRS.

Adverse reactions in a large cohort of patients with inborn errors of immunity receiving intravenous immunoglobulin.

BACKGROUND: Intravenous immunoglobulins (IVIg) are the major treatment in inborn errors of immunity (IEI) disorders; However, IVIg infusions show some adverse effects. We aimed to assess the adverse reactions of IVIg infusions. METHODS: Data of IVIg infusions in IEI patients were collected from 2011 to 2021. Totally, 363 IEI patients received IVIg regularly in Iran entered the study. The adverse reactions are classified regarding their severity and chronicity. RESULTS: 22,667 IVIg infusions were performed in the study. 157 patients (43.2%) and 1349 (5.9%) infusions were associated with at least one type of adverse reaction. The highest rates of adverse reactions were seen in severe combined immunodeficiency. Myalgia, chills, headache, fever, and hypotension were the most frequent adverse effects of IVIg. CONCLUSION: The reactions affect almost half of the patients mainly in the first infusions which necessitate the close observation of IEI patients receiving IVIg.

Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity.

BACKGROUND: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunologic, and molecular data of monogenic IEI patients with and without autoimmune manifestations. METHODS: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data. RESULTS: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1%) were born to consanguineous parents. At the time of the study, 330 individuals (75.7%) were alive and 106 (24.3%) were deceased. Autoimmunity was reported in 92 (20.0%) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5%) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4%). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0%), ATM (in 13 patients, 14.0%), and BTK (in 9 patients, 10.0%) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100%), 3 of 3 AIRE (100%), and 21 of 30 LRBA (70.0%) mutated genes had the highest prevalence of autoimmunity. CONCLUSIONS: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders, especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease.

Effect of misoprostol with and without letrozole on the induction of abortion for women with first-trimester missed abortion.

OBJECTIVE: To determine whether addition of letrozole to a misoprostol-based abortion regimen can increase the rate of complete abortion. METHODS: The randomized, placebo-controlled, double-blind trial enrolled women with missed abortion in the first trimester of pregnancy attending Sadooghi Hospital, Isfahan, Iran, from 2016 to 2018. The women were randomly assigned to the study group, which received 10 mg of letrozole daily for 3 days, followed by two doses of 800 µg of vaginal misoprostol at a 4-hour interval, or the control group, which received a placebo, followed by the same dose of misoprostol. Sonography was performed to check the abortion status. RESULTS: In total, 120 women completed the study: 60 in the misoprostol plus letrozole group, and 60 in the misoprostol only group. Complete abortion was documented for 93 (77.5%) women: 48 (80.0%) in the misoprostol plus letrozole group and 45 (75.0%) in the misoprostol only group (P=0.80). The mean duration of induction in the misoprostol plus letrozole and misoprostol only groups was 7.35 ± 3.54 hours and 8.2 ± 3.8 4hours, respectively (P=0.21). CONCLUSION: Administration of misoprostol alone was found to be as effective as the administration of misoprostol plus letrozole for first-trimester missed abortion.

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity.

BACKGROUND: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. METHODS: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. RESULTS: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. CONCLUSION: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity.

Preventive Effect of Dexamethasone Therapy on the Transient Hypoparathyroidism through Total Thyroidectomy.

INTRODUCTION: This study aimed to investigate whether pre-operative dexamethasone could ameliorate transient hypoparathyroidism outcome through total thyroidectomy. MATERIALS AND METHODS: This randomized clinical trial study was conducted on 128 patients underwent total thyroidectomy from March 2014 to April 2015. Patients were randomly assigned to two groups of experimental receiving 8 mg IV of intravenous dexamethasone (n=45) 45 min before skin incision treatment and control (n=83). After the surgery, all patients were evaluated for clinical and laboratory hypocalcaemia. RESULTS: Post-operative transient biochemical hypoparathyroidism and hypocalcaemia did not occur more often in the control group, compared to the dexamethasone group while controlling for the baseline variables. However, there was a significant difference in phosphorus level between the dexamethasone and control groups (P=0.028). A total of 50 (39.1%) patients developed hypocalcaemia after surgery. Moreover, post-operative symptomatic hypocalcemia occurred more frequently in the control group (68%) compared to the dexamethasone group (32%); however, this difference was not statistically significant (P=0.54). CONCLUSION: The pre-operative administration of dexamethasone reduced post-operative hypocalcemia rate. It is essential to conduct future studies with validated means for better results.

Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort.

BACKGROUND: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses. OBJECTIVE: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings. METHODS: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID. RESULTS: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 µ heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with µ heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with µ heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008). CONCLUSIONS: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment.

Comparison of Surgical Outcome Between Diabetic Versus Nondiabetic Patients After Lumbar Fusion.

BACKGROUND: The prevalence of diabetes mellitus (DM) is increasing worldwide. Thereby, an increasing rate of patients with DM are subjecting to spine surgery. Reviewing the literature, a higher rate of surgery-related complications is reported in DM patients. There is no prospective study comparing the outcomes of lumbar fusion surgery in patients with and without DM. We aimed to investigate whether DM is associated with worse patient-reported outcomes, lower fusion rate, and higher complication rate in subjects undergoing spinal lumbar fusion surgery. METHODS: Forty-eight subjects with DM (DM group) and 48 controls (control group) were recruited. Data regarding age, duration of diabetes, comorbidities, fasting blood sugar, HbA1c, insulin dependence, duration of operation and the volume of bleeding, and the number of infused packed cell were recorded for all patients. Pain and functional status of the patients using the visual analogue scale (VAS) and Oswestry Disability Index (ODI) were measured before operation and 2 weeks, 6 months, and 1 year after lumbar spinal fusion surgery. Using lumbar computed tomography scan and anteroposterior and lateral x-ray 1 year after the surgery, fusion was assessed. RESULTS: Fusion rate after 1 year was 78% in the control group and 53% in the DM group (P = .02). Patients with DM had higher VAS scores comparing to controls 1 year after the operation, but the difference was not significant (P = .07). However, comparing the functional status of the subjects, significantly higher ODI scores were found among DM patients comparing to controls (P = .002). CONCLUSION: Rate of fusion among diabetic patients who undergo lumbar spinal fusion surgery is lower than healthy controls. Spine surgeons should consider this to provide the best possible facilities during the surgery to increase the fusion rate in these patients.

Fourth Update on the Iranian National Registry of Primary Immunodeficiencies: Integration of Molecular Diagnosis.

BACKGROUND: The number of inherited diseases and the spectrum of clinical manifestations of primary immunodeficiency disorders (PIDs) are ever-expanding. Molecular diagnosis using genomic approaches should be performed for all PID patients since it provides a resource to improve the management and to estimate the prognosis of patients with these rare immune disorders. METHOD: The current update of Iranian PID registry (IPIDR) contains the clinical phenotype of newly registered patients during last 5 years (2013-2018) and the result of molecular diagnosis in patients enrolled for targeted and next-generation sequencing. RESULTS: Considering the newly diagnosed patients (n = 1395), the total number of registered PID patients reached 3056 (1852 male and 1204 female) from 31 medical centers. The predominantly antibody deficiency was the most common subcategory of PID (29.5%). The putative causative genetic defect was identified in 1014 patients (33.1%) and an autosomal recessive pattern was found in 79.3% of these patients. Among the genetically different categories of PID patients, the diagnostic rate was highest in defects in immune dysregulation and lowest in predominantly antibody deficiencies and mutations in the MEFV gene were the most frequent genetic disorder in our cohort. CONCLUSIONS: During a 20-year registration of Iranian PID patients, significant changes have been observed by increasing the awareness of the medical community, national PID network establishment, improving therapeutic facilities, and recently by inclusion of the molecular diagnosis. The current collective study of PID phenotypes and genotypes provides a major source for ethnic surveillance, newborn screening, and genetic consultation for prenatal and preimplantation genetic diagnosis.

Clinical, immunologic, and genetic spectrum of 696 patients with combined immunodeficiency.

BACKGROUND: Combined immunodeficiencies (CIDs) are diseases of defective adaptive immunity with diverse clinical phenotypes. Although CIDs are more prevalent in the Middle East than Western countries, the resources for genetic diagnosis are limited. OBJECTIVES: This study aims to characterize the categories of patients with CIDs in Iran clinically and genetically. METHODS: Clinical and laboratory data were obtained from 696 patients with CIDs. Patients were subdivided into those with syndromic (344 patients) and nonsyndromic (352 patients) CIDs. Targeted DNA sequencing was performed on 243 (34.9%) patients. RESULTS: The overall diagnostic yield of the 243 sequenced patients was 77.8% (189 patients). The clinical diagnosis of hyper-IgE syndrome (P < .001), onset of disease at greater than 5 years (P = .02), and absence of multiple affected family members (P = .04) were significantly more frequent in the patients without a genetic diagnosis. An autosomal recessive disease was found in 62.9% of patients, reflecting the high rate of consanguinity in this cohort. Mutations impairing VDJ recombination and DNA repair were the most common underlying causes of CIDs. However, in patients with syndromic CIDs, autosomal recessive mutations in ataxia-telangiectasia mutated (ATM), autosomal dominant mutations in signal transducer and activator of transcription 3 (STAT3), and microdeletions in 22q11.21 were the most commonly affected genomic loci. Patients with syndromic CIDs had a significantly lower 5-year survival rate rather than those with nonsyndromic CIDs. CONCLUSIONS: This study provides proof of principle for the application of targeted next-generation sequencing panels in countries with limited diagnostic resources. The effect of genetic diagnosis on clinical care requires continued improvements in therapeutic resources for these patients.

Area under the curve during OGTT in first-degree relatives of diabetic patients as an efficient indicator of future risk of type 2 diabetes and prediabetes.

OBJECTIVE: To establish whether the area under the curve of an OGTT has a predictive role in identifying prediabetic and diabetic subjects among first-degree relatives (FDR) of patients with diabetes mellitus type 2 (DM). DESIGN, PATIENTS AND MEASUREMENTS: In a population-based cohort study, 766 FDR of diabetic patients with a normal glucose tolerance test (NGT) completed a 2-hour OGTT. They were followed up for 7 years and classified according to the American Diabetes Association criteria into: NGT, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and DM. Relative risk (RR) and 95% confidence intervals (95%CI) were calculated based on logistic regression. Receiver operator characteristic (ROC) analysis along with AUC at different intervals and at time points during the OGTT was used to evaluate the risk of prediabetes and diabetes. RESULTS: Twenty-three subjects (3%) developed type 2 DM, 118 (29.3%) IFG, 81 (11.5%) IGT and 544 (71%) subjects remained NGT. AUC and mean difference of glucose in all high-risk groups demonstrated significant differences in both intervals and time points when compared to the NGT group. The cut-off values during OGTT to predict prediabetes and diabetes was determined as blood glucose more than 7.2 and 7.8 mmol/L at 30 and 60 minutes, respectively. The time point 60 has the highest predictive role for the development of diabetes, alone, and improved the performance of a prediction model containing multiple important clinical risk factors. CONCLUSION: The data suggest that the glycaemic response to an OGTT may predict the risk of development of diabetes in first-degree relatives of DM patients.

Thyroid function test in diabetic ketoacidosis.

BACKGROUND: Metabolism of thyroid hormones is influenced by acute systemic illnesses including diabetic ketoacidosis. In these cases T3 level is usually decreased and this condition is called "low T3 syndrome" which is usually reversed by treating the under lying Disease. OBJECTIVES: thyroid function test analysis before and after diabetic ketoacidosis treatment. METHOD: In this cross sectional study thyroid function tests were analyzed in 16 diabetic ketoacidosis patients according to American diabetic association before and after insulin therapy. RESULT: mean triiodothyronine (T3) level before and after ketoacidosis treatment were 63.2±28.2ng/dl/and 78.5±26.2ng/dl (P. value 0.00) respectively and the mean thyroxin level (T4) before and after ketoacidosis were 3.18±1.4ng/dl and 5.17±2.4ng/dl (P. value=0.00) .Mean thyrotropin (TSH) level and triiodothyronine uptake (T3RU) before and after treatment showed no significant difference. CONCLUSION: Diabetic ketoacidosis is a sever systemic disease which along with reduction in T3 level, T4 level is also decreased and TSH level is normal. The changes in Thyroid hormones are reversed to normal after treatment of ketoacidosis so it is recommended in interpreting results of TFT in these patients we should consider these facts and thyroid function test should be repeated after treatment.