ITPA polymorphisms do not predict additional risk beyond TPMT and NUDT15 for thiopurine-induced cytopenia in inflammatory bowel disease.

INTRODUCTION AND AIM: Thiopurine-related leukopenia is associated with polymorphisms in the thiopurine methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X type motif 15 (NUDT15) genes. However, those polymorphisms explain only a fraction of thiopurine-related leukopenia. Our aim was to study the role of an inosine triphosphate pyrophosphatase (ITPA) polymorphism in patients with inflammatory bowel disease (IBD) and thiopurine-related leukopenia that was unexplained by the TPMT and NUDT15 polymorphisms. MATERIAL AND METHODS: We enrolled consecutive IBD patients on thiopurines (azathioprine or 6-mercaptopurine) from January 2019-March 2020, at a tertiary care center in North India. The presence of the ITPA (C.94C > A) polymorphism was evaluated in all patients, along with its association with thiopurine-related leukopenia. RESULTS: Of the 33 patients (from a total of 119 patients) that developed leukopenia, 8 had the TPMT (n = 1) or NUDT15 (n = 7) polymorphism. Of the remaining 111 patients, their mean age was 36.36 ±â€¯13.54 years and 57 (51.3%) were males. Twenty-five (21.01%) had unexplained leukopenia. The ITPA polymorphism was detected in 4 (16%) patients in the unexplained leukopenia group and 24 (27.9%) patients in the non-leukopenia group (p = 0.228). The odds ratio for predicting leukopenia with the ITPA polymorphism was 0.4921 (95% CI 0.1520-1.5830, p = 0.234). CONCLUSION: The ITPA (C.94C > A) polymorphism was frequently detected in the study population but was not predictive for leukopenia in patients with IBD on thiopurine therapy.

Evaluation of ultrasound airway assessment parameters in pregnant patients and their comparison with that of non-pregnant women: a prospective cohort study.

BACKGROUND: Clinical airway assessment parameters differ significantly between pregnant and non-pregnant patients, however literature comparing their ultrasound (US) airway parameters is limited. We planned a prospective cohort study to compare US-assessed airway parameters between pregnant and non-pregnant women. METHODS: We enrolled 82 pregnant females scheduled for elective cesarean section under neuraxial anesthesia and 80 age-matched non-pregnant females scheduled for elective surgery. Pre-operative clinical airway assessment was performed in both groups. The US airway assessment was done pre-operatively in non-pregnant and postoperatively in pregnant patients. Our primary objective was to compare US-assessed parameters, and secondary objectives included a comparison of clinical airway assessment parameters and investigating a relationship between a difficult airway (defined as a modified Mallampati grade (MMG) ≥ 3) and other airway assessment parameters. RESULTS: Among several US airway parameters, pregnant patients had significantly higher hyomental distance, anterior neck soft tissue thickness at the hyoid and vocal cord level, and oral cavity height, while the tongue thickness and mandibular condylar movements were significantly lower than in non-pregnant patients. Similarly, for the clinical airway assessment, pregnant patients had significantly higher MMG and upper lip bite test scores, mentohyoid distance, and neck circumference. Pregnancy, the ratio of pre-epiglottic space and epiglottis-to-vocal cords distance (Pre-E/E-VC), and hyoid bone visibility were independent predictors of a difficult airway. CONCLUSION: The US airway assessment parameters differ significantly between pregnant and non-pregnant patients. Pregnancy, hyoid bone visibility, and Pre-E/E-VC ratio were independent predictors of the difficult airway in female patients.

Increased fracture risk in Parkinson's disease - An exploration of mechanisms and consequences for fracture prediction with FRAX.

The relative contributions of factors such as muscle strength, falls risk and low bone mineral density (BMD) to increased fracture risk in Parkinson's Disease (PD) were examined in an analysis of 5212 community-dwelling women age 75 years or more recruited to a randomised, double-blind, placebo-controlled study of the oral bisphosphonate, clodronate. Similar number of PD and non-PD subjects received treatment. Each participant had measurements of hip and forearm BMD, muscle strength (hand grip strength and maximum isometric quadriceps strength), ability in the sit-to-stand test, and postural stability. Incident radiographic and/or surgically verified fractures, and deaths, were recorded over an average follow-up of 3.8 years. A diagnosis of PD was made if it was self-reported and appropriate medication was recorded at the study entry. 47 of the women (0.9 %) had a diagnosis of PD at baseline. They were of similar age to those without PD, but reported higher disability scores and lower quality of life. While BMD at the forearm and hip regions was lower in PD, this only reached statistical significance at the femoral neck (0.61 ± 0.12 vs 0.65 ± 0.12 g/cm2, p = 0.037). Right hand grip strength was non-significantly lower in PD, but maximum right quadriceps strength was much reduced (96.9 ± 49.3 vs 126.3 ± 59.2 N, p = 0.003). Eleven (23.4 %) of the women with PD sustained 12 fractures, while 609 women (11.8 %) without PD sustained 742 osteoporotic fractures. The risk of osteoporotic fracture associated with PD was 2.24-fold higher in women with PD (Cox-regression HR 2.24, 95 % CI 1.23-4.06) and this remained high when adjusted for death as a competing risk (2.17, 95 % CI 1.17-4.01, p = 0.013). Following adjustment for femoral neck BMD, PD remained a significant predictor of fracture (HR 2.04, 1.12-3.70, p = 0.020). Entering PD as a risk variable using the rheumatoid arthritis input as a surrogate resulted in a reduction in PD as a FRAX-independent risk factor, particularly when BMD was included in FRAX (1.65, 95 % CI), but the relationship between PD and fracture risk appears to remain of clinical significance. The study suggests that PD may be an independent input in future iterations of FRAX, possibly due to non-skeletal components of risk such as reduced lower limb muscle strength. Introducing measures of muscle strength and performance in FRAX could also be considered.

Iron deficiency in proteinuric children with nephrotic syndrome: A cross-sectional pilot study.

Massive proteinuria in nephrotic syndrome causes depletion of various proteins. Iron deficiency can occur due to urinary loss of iron, transferrin, and soluble transferrin receptors. We conducted this cross-sectional study of 52 children with proteinuric nephrotic syndrome, aged 1-12 years (mean 7.1±2.7 years). Hemoglobin (Hb), RBC indices (MCV, MCH, MCHC), percentage of hypochromic RBCs (Hypo-He), reticulocyte hemoglobin content (Ret-He), and serum ferritin were examined. Seven (13%) patients had iron deficiency anemia and another 10 (19%) exhibited iron deficiency. A higher proportion of children with steroid-resistant disease had anemia than did steroid-sensitive children (P=0.076). Thus, children with nephrotic syndrome may have iron deficiency (32.7%), which needs to be screened.

Azathioprine induced pancreatitis, polyarthritis and panniculitis (PPP) syndrome in a patient with Crohn's disease.

Azathioprine and 6-mercaptopurine have been widely used for maintenance of remission in patients with inflammatory bowel disease. The use of thiopurines is associated with multiple adverse effects including dose dependent cytopenias or idiosyncratic reaction. We report about a case of azathioprine related pancreatitis associated with polyarthralgia and panniculitis. Pancreatitis, polyarthritis and panniculitis (PPP) syndrome is an uncommon phenomenon which may accompany a number of pancreatic diseases including acute or chronic pancreatitis or pancreatic malignancy. To the best of our knowledge, this is the first report of Azathioprine related PPP syndrome.

Audit of Quality and Quantity of Nucleic Acid Yield from Pediatric Acute Leukemia Cases Following a Bio-banking Initiative.

Information which can be harvested from a biological sample has greatly improved with advancements in diagnostic technologies. However, in developing countries, the awareness about usefulness of bio-banking concept is lacking and centres which do offer it, depend mainly on - 20 or - 80 °C for sample storage due to lack of sophisticated infrastructure like vapour phase nitrogen storage preservation. Hence in these resource constraint settings, timely audit of quality of nucleic acids extractable from samples stored is of utmost importance. In this study, we explore the effect of - 20 °C storage over nucleic acids (DNA/RNA) isolated from blood samples of 180 patients with various leukaemia's following a bio-banking initiative. We observed that the integrity and quality of both DNA and RNA were maintained in 70 and 80% samples respectively over time as reflected by their concentration measurements and inherent uniform expression of housekeeping gene GAPDH. Only 3.7% of the RNA samples and 4.2% of the DNA samples yielded very low concentrations despite minimizing processing and technical loss. In nutshell, audit of our biobank sample yield highlights that storage of blood samples at - 20 °C does not compromise the fidelity of nucleic acids for future diagnostic and research work in a resource constraint setting.

Favourable improvement in haematological parameters in response to oral iron and vitamin C combination in children with Iron Refractory Iron Deficiency Anemia (IRIDA) phenotype.

Treatment in IRIDA focuses on use of intravenous iron preparations to circumvent oral absorptive defect resulting from high levels of hepcidin due to TMPRSS6 gene variations. However, recent case reports and recommendations on atypical microcytic hypochromic anemias advocate use of oral iron and vitamin c trial before parenteral iron, as the same results in comparable improvement in haemoglobin. We prospectively evaluated our IRIDA cohort (n = 7) with oral iron and vitamin c dose over a period of 10 weeks and noted complete response in majority (6/7 = 86%) with >2 g/dL rise in Hb along with significant improvement of other iron related indices.

Hypoferremic State in Overweight and Obese Children.

Children with high body mass index (BMI) are at risk of iron deficiency. In present study, 71 children with overweight or obesity were screened for iron deficiency. Mean BMI, ferritin and plasma soluble transferrin receptor (sTrfR) levels were 26.1 kg/m2, 41.9 µg/L and 0.375 mg/L, respectively. Twenty (28%) children had anemia, and 44 (62%) had an underlying hypoferraemic state.

Liver failure determines the outcome in patients of acute-on-chronic liver failure (ACLF): comparison of APASL ACLF research consortium (AARC) and CLIF-SOFA models.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models. METHODS: A total of 1402 ACLF patients, enrolled in the APASL-ACLF Research Consortium (AARC) with 90-day follow-up, were analyzed. An ACLF score was developed in a derivation cohort (n = 480) and was validated (n = 922). RESULTS: The overall survival of ACLF patients at 28 days was 51.7%, with a median of 26.3 days. Five baseline variables, total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy, were found to be independent predictors of mortality, with AUROC in derivation and validation cohorts being 0.80 and 0.78, respectively. AARC-ACLF score (range 5-15) was found to be superior to MELD and CLIF SOFA scores in predicting mortality with an AUROC of 0.80. The point scores were categorized into grades of liver failure (Gr I: 5-7; II: 8-10; and III: 11-15 points) with 28-day cumulative mortalities of 12.7, 44.5 and 85.9%, respectively. The mortality risk could be dynamically calculated as, with each unit increase in AARC-ACLF score above 10, the risk increased by 20%. A score of ≥11 at baseline or persisting in the first week was often seen among nonsurvivors (p = 0.001). CONCLUSIONS: The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.

Lower Plasma Soluble Transferrin Receptor Range in Healthy Indian Pediatric Cohort as Compared to Asian and Western Data.

Soluble serum transferrin receptor is derived from erythroid transferrin receptor expressed on surface of developing erythroid cells. It can be detected in blood using sensitive ELISA methodology and blood levels reflect physiological iron dependent erythropoiesis state in bone marrow. Normal adult levels vary from 2 to 5 mg/l. However, pediatric studies are few and describe normal ranges to the tune of 1.0-3.0 mg/l, which are relatively lower than that of adults. In present study 40 healthy children (2-12 years) were evaluated to establish normal soluble transferrin receptor range. The mean transferrin receptor levels were 0.39 mg/l with a range of 0.17-2.1 mg/l. The levels were low as compared to mean levels described in other studies from West and our country (4.39 and 2.0 mg/l respectively). Since, no internationally standard method for reporting and testing for transferrin receptor levels are yet available, hence it is imperative to establish normal control ranges in different population cohorts, especially in pediatric age group, to better interpret their levels in diagnostic context.

Nuclear displacement and fluorescence recovery after photobleaching (FRAP) assays to study division site placement and cytokinesis in fission yeast.

Cytokinesis is an essential cellular event that completes the cell division cycle. It begins with the assembly of an actomyosin contractile ring that undergoes constriction concomitant with the septum formation to divide the cell in two. Placement of the septum at the right position is important to ensure fidelity of the division process. In fission yeast, the medially placed nucleus is a major spatial cue to position the site of division. In this chapter, we describe a simple synthetic biology-based approach to displace the nucleus and study the consequence on division site positioning. We also describe how to perform fluorescence recovery after photobleaching to follow the dynamics of cytokinetic proteins at defined time points by live-cell microscopy.

Multiple pterygium syndrome: Challenge for anesthesiologist.

Multiple pterygium syndrome (MPS) is a very rare autosomal recessive disorder characterized by flexion of joint and digit contractures, skin webbing, cleft palate, deformity of the spine, and cervical spine fusion. Difficult airway is associated mainly due to micrognathia, retrognathia, webbing of the neck, and limitation of the mouth opening and neck extension. We are reporting a case of a 5-year-old female diagnosed with MPS and exhibiting a bilateral club foot and congenital vertical talus. The patient was posted for manipulation and above the knee casting under general anesthesia.

Inadvertent intrathecal injection of labetalol.

Labetalol is a combined α and ß adrenergic receptor blocker. It is used to treat hypertension, especially in pregnant patients. We report a case of a female patient who was given labetalol intrathecally in place of bupivacaine due to a similar appearance of ampoules which resulted in a drop in blood pressure and pulse rate. The patient responded to fluid resuscitation and there occurred no neurological sequelae.

Do traumatic lumbar punctures lead to greater relapses in acute lymphoblastic leukemia? Experience at a university hospital in India.

OBJECTIVE: The aim of the study was to evaluate the impact of traumatic lumbar puncture (TLP) at diagnosis of relapse in childhood acute lymphoblastic leukemia (ALL). Risk factors associated with TLP were assessed. MATERIALS AND METHODS: A retrospective analysis was performed from the records of children with ALL who were treated from January 2010 to December 2012. RESULTS: A total of 311 patients with median age of 5 years (range: 1-13) were treated for ALL. The cerebrospinal fluid analysis obtained from first LP revealed 275: Central nervous system 1 (CNS 1) (no blasts); 8: CNS 3 (blasts positive); and 28: TLP. Twenty-eight (9%) patients relapsed. Twelve (3.9%) had a CNS relapse. A TLP at diagnosis was not associated with an increased risk of systemic or CNS relapse (P = 0.298, 0.295). Three years event-free survival of patients with TLP and without atraumatic LP (ATLP) at diagnosis was 56 ± 5.2% and 51.8 ± 12.4%, (P = 0.520). Three years overall survival with TLP and ATLP was 73.3 ± 3.5% and 70.4 ± 12.5%, respectively, (P = 0.963). Median platelet count in patients with TLP was significantly lower than those without TLP (10,000/µL and 28,000/µL, P < 0.001). A receiver operating characteristic curve was constructed for predicting the risk of TLP based on platelet count. Area under the curve was 0.74 ± 0.05 (95% confidence interval 0.64-0.84). Platelet count < 23.5 × 109/L at the time of LP had 75% sensitivity and 64.4% specificity in predicting a TLP. CONCLUSIONS: Low platelet counts are significantly associated with risk of TLP. Traumatic LP at diagnosis was not associated with an increased risk of relapse.