Comparison of Stressors Experienced by Patients and Nurses' Perception on the Patients' Stressors Admitted in ICU.

The study sought to compare the stressors experienced by patients and nurses' perception of the patients' stressors admitted in intensive care units (ICUs) of selected hospitals of Madurai (TN). Design used in this study was descriptive-comparative study design and purposive sampling technique was employed. The sample size consisted of 80, among these 40 were staff nurses working in ICU and 40 were patients who were admitted in ICU. The study was carried out by using Modified intensive care unit environmental stressors questionnaire (ICU-ESQ). This tool had 50 items, which are rated in a 4-point Likert-type scale. The items corresponded to stressors that are related to physical stressors (13 items), Psychological stressors (22 items) and the ICUEnvironment stressors (15 items). The data obtained were analysed by inferential statistics and descriptive statistics. The findings revealed that mean score of stressors experienced by patients was higher than the nurses mean score. The most stressful items ranked by patients and nurses were similarforfirst three items.

Role of microRNA in hydroxyurea mediated HbF induction in sickle cell anaemia patients.

Hydroxyurea (HU) is found to be beneficial in sickle cell anaemia (SCA) patients, due to its ability to increase foetal haemoglobin (HbF), however, patients show a variable response. Differences in HbF levels are attributed to many factors; but, the role of miRNA in HbF regulation is sparsely investigated. In this study, we evaluated the effect of miRNA expression on HbF induction in relation to hydroxyurea therapy in 30 normal controls, 30 SCA patients at baseline, 20 patients after 3 and 6 months of hydroxyurea (HU) therapy. HbF levels were measured by HPLC. Total RNA and miRNA were extracted from CD71+ erythroid cells and the expression was determined using Taqman probes. The mean HbF level increased 7.54 ± 2.44 fold, after 3 months of HU therapy. After the HU therapy 8 miRNAs were significantly up-regulated while 2 were down-regulated. The increase in miR-210, miR16-1, and miR-29a expression and decrease in miR-96 expression were strongly associated with the HU mediated HbF induction. Post HU therapy, decreased miR-96 expression negatively correlate with HbF and γ-globin gene while increased expression of miR-210, miR-16-1 and miR-29a post HU therapy positively corelate with HbF and γ-globin gene. Thus, suggest that miR-210, miR-16-1 and miR-29a are positive regulator of γ-globin gene and miR-96 is negative regulator of γ-globin gene. The study suggests the role of miR-210, miR16-1, miR-29a, and miR-96 in γ-globin gene regulation leading to HbF induction. Identification of the relevant protein targets might be useful for understanding the HU mediated HbF induction.

Correction to: Efficacy and Safety of Biosimilar Romiplostim Versus Innovator Romiplostim in Patients with Chronic Immune Thrombocytopenia.

[This corrects the article DOI: 10.1007/s12288-022-01602-5.].

Efficacy and Safety of Biosimilar Romiplostim Versus Innovator Romiplostim in Patients with Chronic Immune Thrombocytopenia.

Romiplostim is a Food and Drug Administration (FDA)-approved therapy for immune thrombocytopenia (ITP). Biosimilar is a biological product that has no clinical meaningful difference from an existing FDA-approved reference product. It has a potential of lowering health-care-related cost. Biosimilar of romiplostim can be made available to patients with ITP at a low cost and can be beneficial in providing the best therapy. Thus, the efficacy and safety of biosimilar romiplostim (ENZ110) was compared with innovator romiplostim (Nplate) with respect to platelet response in patients with chronic ITP. This was a prospective, multicenter, randomized, and double-blind clinical trial. Patients with chronic ITP, aged 18-65 years, were enrolled in a study and were randomized to receive either ENZ110 or Nplate in a 3:1 ratio for a treatment period of 12 weeks, respectively. After completion of the treatment period, the patients were followed-up for one week to evaluate the platelet response and to monitor the adverse events (AEs). Over the duration of 12 weeks, platelet response of > 50 × 109/L was achieved in 85.3% patients treated with ENZ110 and in 75.0% patients treated with Nplate in per protocol population. In intent-to-treat population, 83.8% patients with ENZ110 and 76.9% patients with Nplate achieved a platelet response of > 50 × 109/L. In the ENZ110 group, 111 AEs were recorded in 66.7% patients, while 18 AEs were reported in 61.5% patients in the Nplate group. The study demonstrated non-inferiority with comparable efficacy and safety between biosimilar romiplostim and innovator romiplostim in patients with chronic ITP. Trial registration number and date of registration: CTRI/2019/04/018614.

Outcome of Submucosal Inferior Turbinoplasty in Perennial Allergic Rhinitis.

Pharmacotherapy forms mainstay of treatment for allergic rhinitis, and has adverse effects associated with it. Topical steroid therapy is the preferred medication and considered best for long term prophylaxis but with limited compliance. Submucosal turbinoplasty reduces the duration of treatment in comparison to topical steroid which has to be taken daily for a long time. The aim was to evaluate the outcome of submucosal inferior turbinoplasty in patients with perennial allergic rhinitis. A prospective interventional study was performed on 35 patients diagnosed with perennial allergic rhinitis, diagnosed as per ARIA criteria from July 2016 to July 2018. The severity of the disease was assessed using mini RQLQ scoring system. The patients were then subjected to bilateral submucosal inferior turbinoplasty under endoscopic guidance under local anesthesia. 50% significant improvement (p value < 0.05) seen in symptoms were need to blow nose, sneezing, nasal obstruction, nasal discharge, watery eyes, need to rub eye, regular house work, recreational activities, sore eyes, tiredness, irritability and thirst. 100% improvement (p value < 0.05) seen in symptoms were sleep, need to blow nose, sneezing, nasal discharge, watery eyes, need to rub eye, recreational activities and irritability. Nasal obstruction was not severe in 17 (48.5%) patients giving a very good symptom relief and improving quality of life. This is due to reduction in the erectile tissue and roominess in the nasal cavity. All patients with allergic rhinitis with associated hypertrophied turbinates should invariably be given option of inferior turbinoplasty along with proper counselling regarding its advantages and disadvantages.

Histogram of States Based Assistive System for Speech Impairment Due to Neurological Disorders.

Assistive speech technology is a challenging task because of the impaired nature of dysarthric speech, such as breathy voice, strained speech, distorted vowels, and consonants. Learning compact and discriminative embeddings for dysarthric speech utterances is essential for impaired speech recognition. We propose a Histogram of States (HoS)-based approach that uses Deep Neural Network-Hidden Markov Model (DNN-HMM) to learn word lattice-based compact and discriminative embeddings. Best state sequence chosen from word lattice is used to represent dysarthric speech utterance. A discriminative model-based classifier is then used to recognize these embeddings. The performance of the proposed approach is evaluated using three datasets, namely 15 acoustically similar words, 100-common words datasets of the UA-SPEECH database, and a 50-words dataset of the TORGO database. The proposed HoS-based approach performs significantly better than the traditional Hidden Markov Model and DNN-HMM-based approaches for all three datasets. The discriminative ability and the compactness of the proposed HoS-based embeddings lead to the best accuracy of impaired speech recognition.

Mutation profile in Indian primary myelofibrosis patients and its clinical implications.

BACKGROUND: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by abnormal proliferation of megakaryocytes, bone marrow fibrosis, and extramedullary hematopoiesis. We did mutation profile of 50 patients of PMF and tried to correlate it with initial clinical presentation of these patients. MATERIALS AND METHODS: All new and follow up patients who were diagnosed as PMF based on WHO 2016 definition of PMF were included. Mutation profile of these patients including JAK2 V617F, JAK2 exon 12, CALR and MPL mutations was done and all clinical, demographic and laboratory details were recorded. RESULTS: Total 50 patients were enrolled out of which 29 were males and 21 were females. Out of these patients, 32 (64%) were JAK2 positive, 13 (26%) were CALR positive, 1 (2%) were MPL positive and 4 (8%) were triple negative. As compared to JAK2+ve patients and triple negative group, CALR positive patients were younger, had lower total leucocyte count, larger spleen size, lower dynamic international prognostic scoring system (DIPSS) score and higher grade of fibrosis of marrow. CONCLUSION: This study depicts that incidence of JAK2 and CALR mutations in Indian PMF patients is fairly similar to that in rest of the world. CALR positive patients have better clinical parameters at presentation and have better prognosis as compared to JAK2 positive patients.

Glucose Phosphate Isomerase Deficiency: High Prevalence of p.Arg347His Mutation in Indian Population Associated with Severe Hereditary Non-Spherocytic Hemolytic Anemia Coupled with Neurological Dysfunction.

OBJECTIVES: Glucose-6-phosphate isomerase (GPI) deficiency is an autosomal recessive genetic disorder causing hereditary non-spherocytic hemolytic anemia (HNSHA) coupled with a neurological disorder. The aim of this study was to identify GPI genetic defects in a cohort of Indian patients with HNSHA coupled with neurological dysfunction. METHODS: Thirty-five patients were screened for GPI deficiency in the HNSHA patient group; some were having neurological dysfunction. Enzyme activity was measured by spectrophotometric method. The genetic study was done by single-stranded conformation polymorphism (SSCP) analysis, restriction fragment length polymorphism (RFLP) analysis by the restriction enzyme AciI for p.Arg347His (p.R347H) and confirmation by Sanger's sequencing. RESULTS: Out of 35 patients, 15 showed 35% to 70% loss of GPI activity, leading to neurological problems with HNSHA. Genetic analysis of PCR products of exon 12 of the GPI gene showed altered mobility on SSCP gel. Sanger's sequencing revealed a homozygous c1040G > A mutation predicting a p.Arg347His replacement which abolishes AciI restriction site. The molecular modeling analysis suggests p.Arg347 is involved in dimerization of the enzyme. Also, this mutation generates a more labile enzyme which alters its three-dimensional structure and function. CONCLUSIONS: This report describes the high prevalence of p.Arg347His pathogenic variant identified in Indian GPI deficient patients with hemolytic anemia and neuromuscular impairment. It suggests that neuromuscular impairment with hemolytic anemia cases could be investigated for p.Arg347His pathogenic variant causing GPI deficiency because of neuroleukin activity present in the GPI monomer which has neuroleukin action at the same active site and generates neuromuscular problems as well as hemolytic anemia.

Representation Learning Based Speech Assistive System for Persons With Dysarthria.

An assistive system for persons with vocal impairment due to dysarthria converts dysarthric speech to normal speech or text. Because of the articulatory deficits, dysarthric speech recognition needs a robust learning technique. Representation learning is significant for complex tasks such as dysarthric speech recognition. We focus on robust representation for dysarthric speech recognition that involves recognizing sequential patterns of varying length utterances. We propose a hybrid framework that uses a generative learning based data representation with a discriminative learning based classifier. In this hybrid framework, we propose to use Example Specific Hidden Markov Models (ESHMMs) to obtain log-likelihood scores for a dysarthric speech utterance to form fixed dimensional score vector representation. This representation is used as an input to discriminative classifier such as support vector machine.The performance of the proposed approach is evaluatedusingUA-Speechdatabase.The recognitionaccuracy is much better than the conventional hidden Markov model based approach and Deep Neural Network-Hidden Markov Model (DNN-HMM). The efficiency of the discriminative nature of score vector representation is proved for "very low" intelligibility words.

Can hydroxyurea serve as a free radical scavenger and reduce iron overload in ß-thalassemia patients?

In this study, we hypothesize that hydroxyurea could provide an additional benefit as a free radical scavenger and/or iron chelator in ß-thalassemia patients with iron overload. Twenty-one ß-thalassemia intermedia patients who presented between 3 and 17 years but later required regular blood transfusions were enrolled for hydroxyurea therapy for a year. Fourteen patients responded to the therapy with hemoglobin levels maintained above 7.5 g/dl without transfusions. Hydroxyurea was discontinued after 6 months in seven patients who did not respond to the therapy and had to be continued on regular blood transfusions. We observed a statistically significant decrease in serum ferritin levels from 4194 ± 4850 ng/ml to 2129 ± 2380 ng/ml among the responders and from 2955 ± 2909 ng/ml to 2040 ± 2432 ng/ml among the non-responders and statistically significant decrease in labile iron pool from 18678.7 ± 10067.4 mean fluorescence intensity (MFI) to 14888.5 ± 5284.0 MFI among responders and from 17986.3 ± 9079.8 MFI to 15634.8 ± 8976.9 MFI among the non-responders after therapy. Phosphatidylserine externalization also showed a statistically significant decrease from 44.2 ± 22.2 MFI to 16.6 ± 6.7 MFI among the responders and from 46.9 ± 33.1 MFI to 39.8 ± 7.4 MFI among the non-responders along with a statistically significant decrease in the levels of reactive oxygen species from 72.8 ± 35.5 MFI to 29.0 ± 8.3 MFI among the responders and from 80.9 ± 41.4 MFI to 40.5 ± 15.8 MFI among the non-responders after therapy. A statistically significant increase in reduced glutathione levels was also observed from 430.8 ± 201.1 MFI to 715.5 ± 292.4 MFI among the responders and from 359.6 ± 165.6 MFI to 450.3 ± 279.5 MFI among the non-responders after therapy. This suggests the possible additional role of hydroxyurea as a free radical scavenger and/or iron chelator but requires a larger study for substantiation.

Paradoxical bleeding and thrombosis in a patient with afibrinogenemia and fibrinogen Mumbai mutation.

OBJECTIVES: Thrombosis is rarely reported in cases of afibrinogenemia and is generally associated with thrombophilia or replacement therapy. Often, it is difficult to predict whether the patients will bleed or whether they are exposed to the risk of thrombosis. METHODS: We report a patient with afibrinogenemia who presented with complete thrombosis of right hepatic, portal, and splenic veins and who described a lifelong history of bleeding. Direct sequencing of the three fibrinogen genes was performed to identify the mutation. RESULTS: DNA sequencing showed the presence of a homozygous for G8017A substitution in exon 8 of the fibrinogen ß-chain gene, resulting in a G434D missense mutation (Fibrinogen Mumbai). CONCLUSIONS: Presence of both bleeding and thrombotic manifestations in a patient with afibrinogenemia in the presence of other associated risk factors warrants a very careful individualized approach in the management of patients with afibrinogenemia.

Mutations in intron 1 and intron 22 inversion negative haemophilia A patients from Western India.

Despite increased awareness and diagnostic facilities, 70-80% of the haemophilia A (HA) patients still remain undiagnosed in India. Very little data is available on prevalent mutations in HA from this country. We report fifty mutations in seventy one Indian HA patients, of which twenty were novel. Ten novel missense mutations [p.Leu11Pro (p.Leu-8Pro), p.Tyr155Ser (p.Tyr136Ser), p.Ile405Thr (p.Ile386Thr), p.Gly582Val (p.Gly563Val) p.Thr696Ile (p.Thr677Ile), p.Tyr737Cys (p.Tyr718Cys), p.Pro1999Arg (p.Pro1980Arg), p.Ser2082Thr (p.Ser2063Thr), p.Leu2197Trp (p.Leu2178Trp), p.Asp2317Glu (p.Asp2298Glu)] two nonsense [p.Lys396* (p.Lys377*), p.Ser2205* (p.Ser2186*)], one insertion [p.Glu1268_Asp1269ins (p.Glu1249_Asp1250)] and seven deletions [p.Leu882del (p.Leu863del), p.Met701del (p.Met682del), p.Leu1223del (p.Leu1204del), p.Trp1961_Tyr1962del (p.Trp1942_Tyr1943del) p.Glu1988del (p.Glu1969del), p.His1841del (p.His1822del), p.Ser2205del (p.Ser2186del)] were identified. Double mutations (p.Asp2317Glu; p.Thr696Ile) were observed in a moderate HA case. Mutations [p. Arg612Cys (p.Arg593Cys), p.Arg2326Gln (p.Arg2307Gln)] known to be predisposing to inhibitors to factor VIII (FVIII) were identified in two patients. 4.6% of the cases were found to be cross reacting material positive (CRM+ve). A wide heterogeneity in the nature of mutations was seen in the present study which has been successfully used for carrier detection and antenatal diagnosis in 10 families affected with severe to moderate HA.

Down-regulation of miR-199b associated with imatinib drug resistance in 9q34.1 deleted BCR/ABL positive CML patients.

Chronic myeloid leukemia (CML) occurs due to t(9,22) (q34;q11) and molecularly BCR/ABL gene fusion. About 15-18% Philadelphia positive CML patients have gene deletions around the translocation breakpoints on 9q34.1. The microRNAs (miRNAs), namely miR-219-2 and miR-199b, centromeric to the ABL1 gene are frequently lost in CML patients. We have designed a study to determine miR-219-2 and miR-199b expression levels which would help to understand the prognosis of imatinib therapy. A total of 150 CML patients were analyzed to identify 9q deletion. Fluorescent in-situ hybridization (FISH) was performed using BCR/ABL dual color, dual fusion probe to study the signal pattern and BAC probes for miR-199b and miR-219-2 (RP11-339B21 and RP11-395P17) to study the miRNA deletions. The expression level of miRNA was analyzed by real-time polymerase chain reaction (RT-PCR). FISH analysis revealed 9q34.1 deletion in 34 (23%) CML patients. The deletions were not detected using BAC probes for miRNAs in 9q deleted patients. The expression analysis showed down-regulation of miR-199b and miR-219-2 in the 9q deleted patients (34 CML) as compared to a pool of patients without deletion. However, miR-199b (9q34.11) was significantly (p=0.001) down-regulated compared to miR-219-2. The follow-up study showed that the miR-199b was found to be strongly associated with imatinib resistance, as 44.11% patients showed resistance to imatinib therapy. Hence, the deletion in 9q34.1 region (ABL) plays an important role in disease pathogenesis. Eventually, miRNAs can provide new therapeutic strategies and can be used as a prognostic indicator.

Hemophagocytic lymphohistiocytosis in a 19 year old critically ill patient.

Haemophagocytic lymphohistiocytosis (HLH) describes a clinical syndrome of hyperinflammation resulting in an uncontrolled and ineffective immune response. It presents with a clinical picture of likely sepsis, i.e., fever, laboratory evidence of inflammatory response, coagulopathy and thrombocytopaenia should be appropriately investigated and managed for sepsis, but the possible diagnosis of HLH should be borne in mind. Awareness of the clinical symptoms and of diagnostic criteria for HLH is crucial to starting immunosuppressive/immunomodulatory and cytotoxic drugs in time. We present a case of HLH in a 19 year old male who presented with fever, neurological symptoms, cytopaenias, laboratory markers of inflammation and bone marrow aspirate showed hemophagocytosis.

Fusion of complex odontome with permanent mandibular molar.

Odontomas are malformation of the dental tissue, arising during normal tooth development. They are usually asymptomatic, but often associated with tooth eruption disturbance. This article reports a case of complex odontome in a 23-year-male, which hampered the eruption of mandibular right second molar as well devitalization of first molar.

A randomized comparative trial evaluating the safety and efficacy of liposomal amphotericin B (Fungisome) versus conventional amphotericin B in the empirical treatment of febrile neutropenia in India.

BACKGROUND: In patients with persistent fever and netropenia, amphotericin B is administered empirically for early treatment and prevention of systemic fungal infections. Despite this treatment, there are chances of breakthrough fungal infections and drug is also toxic. MATERIALS AND METHODS: A multicentric, randomized, controlled clinical trial was conducted to compare liposomal amphotericin B two doses with conventional amphotericin B as empirical antifungal therapy. RESULTS: The average body weight of patients was 26.4 ± 14.8 (n=22), 32.9 ± 19.4 (n=23) and 37.9 ± 20.0 (n=20) kg in 1 mg, 3 mg Fungisome (liposomal amphotericin B) and 1 mg/kg/day conventional amphotericin B group, respectively. The mean age was 16.2 ± 13.4, 16.0 ± 10.9 and 22.7 ± 16.2 yrs in 1 and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional AMP B group, respectively. The average duration of treatment with 1 mg and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional amphotericin B was 17 ± 9.8, 16.2 ± 8.3, and 14.7 ± 10.7 days, respectively. The time to resolve fever was 13.3 ± 10.2, 10.9 ± 7.1, 10.1 ± 6.7 days, and for absolute neutrophil count (ANC) to be above 500 cells per microliter, it took 13.4 ± 9.6, 10.6 ± 7.6 and 7.3 ± 3.4 days, respectively. Liposomal formulations were well-tolerated compared to conventional amphotericin B. CONCLUSIONS: This small randomized study showed that the indigenous liposomal formulation Fungisome appears to be equally efficacious and safer than conventional amphotericin B. Also, the lower dose Fungisome (1 mg/kg/day) appears to be equally efficacious and was well-tolerated as compared to higher dose Fungisome (3 mg/kg/day). Treatment cost would be a major factor for limiting use of higher dose of Fungisome.

Nerve growth factor promotes endothelial progenitor cell-mediated angiogenic responses.

PURPOSE: In response to ischemia, retinal neuronal cells express nerve growth factor (NGF), which can be proangiogenic. Endothelial progenitor cells (EPCs) can participate with the resident vasculature to promote angiogenesis. We postulated that NGF may stimulate CD34⁺ EPCs to convert to an angiogenic phenotype. METHODS: Human CD34⁺ cells and human retinal endothelial cells (HRECs) were used to examine the effect of NGF on key steps associated with neovascularization. CD34⁺ cells and HRECs were stimulated with NGF (1 to 4 pM) for 24, 48, and 72 hours. Cell migration was measured using a modified Boyden chamber assay. Expression of the receptor for the cytokine stromal derived growth factor 1 (SDF-1), CXCR-4, was assessed by flow cytometry. In vitro angiogenesis was tested using a three-dimensional (3D) extracellular matrix with HRECs/CD34⁺ cell cocultures. NGF receptor activation was assessed by western analysis. RESULTS: NGF promoted proliferation of CD34⁺ cells but not HRECs. Pretreatment of CD34⁺ cells with NGF increased CXCR-4 expression in CD34⁺ cells, resulting in enhanced migration to SDF-1 (P < 0.0001). The enhanced tubule-forming effect of NGF in HRECs was further potentiated by coculture with NGF-pretreated CD34⁺ cells (P < 0.01). The beneficial effect of NGF was blocked (P < 0.0001) by the ERK inhibitor PD98059. In both CD34⁺ and HRECs, NGF increased phosphorylation of neurotrophic tyrosine kinase receptor type 1 (TrkA) receptor by ERK1 activation (P < 0.01). CONCLUSIONS: Our in vitro results suggest that NGF released from ischemic nerves in vivo may contribute to the "angiogenic switch" by stimulating the angiogenic behavior of CD34⁺ cells while minimally affecting resident retinal endothelial cells.