Novel cryotherapy technique for pulpotomy in mature permanent teeth with symptomatic irreversible pulpitis- a randomized controlled trial.

OBJECTIVES: To assess the effect of cryotherapy on haemostasis, post-operative pain, and the outcome of full pulpotomy performed in mature permanent teeth with symptomatic irreversible pulpitis. MATERIALS AND METHODS: The study included sixty mature permanent mandibular molar teeth with symptomatic irreversible pulpitis and no periapical rarefaction. After coronal pulp tissue amputation, teeth were randomly allocated to one of two groups (n = 30 each). In group I (conventional pulpotomy), a sterile cotton pellet moistened with 2.5% NaOCl was used for haemostasis. In group II (cryotherapy), the pulp chamber was continuously lavaged with 2.50C normal saline solution for haemostasis using an indigenous portable cryotherapy irrigation unit. Following haemostasis, the pulp was capped with mineral trioxide aggregate and the tooth was restored with resin composite. The time taken to achieve haemostasis was recorded. Preoperative and 24, 48 and 72 h postoperative pain was measured using the Numerical Rating Scale. The pulpotomy outcome was assessed at the 12-month follow-up. Data were analyzed using Fischer's exact test, two-sample t-test, two-sample Wilcoxon rank-sum test, Friedman Test, and Wilcoxon Signed Rank Test. RESULTS: The cryotherapy group achieved haemostasis in less time (p < 0.05). There was a significant pain reduction at 24 and 48 h in the cryotherapy group when compared with the conventional pulpotomy group (P < 0.005). The overall success rate of pulpotomy after 12 months was 88% (n = 22) in both study groups(p < 0.05). CONCLUSIONS: Cryotherapy application reduces postoperative pain and has no adverse effect on the outcome of pulpotomy in permanent teeth with symptomatic irreversible pulpitis. CLINICAL RELEVANCE: The cryotherapy can be incorporated in pulpotomy protocol as an adjunct to minimize post-operative pain.

Comparative Evaluation of Topographic Parameters Using Three Different Topographers in Keratoconic and Cross-linked Keratoconic Corneas.

PURPOSE: To compare the parameters of three different topographic devices (Pentacam HR, Oculus Optikgeräte GmbH; Sirius, Costruzione Strumenti Oftalmici; and Cassini, i-Optics) in grading the severity of keratoconus in cross-linked and non-cross-linked eyes. METHODS: This was a prospective comparative interventional study done in a tertiary eye care center, wherein 114 eyes of 68 patients with keratoconus were divided into two groups: 62 eyes that were observed and 52 eyes that were cross-linked. All eyes were evaluated on all three topographers at baseline, 3-month follow-up, and 6-month follow-up. RESULTS: The Sirius showed significantly lower values of mean flat keratometry in comparison to the Pentacam HR (limits of agreement [LoA]: 1.75 to 3.51%) and Cassini (LoA: 1.75 to 3.51%). The mean steep keratometry values were higher for the Cassini in comparison to the Pentacam HR (LoA: 4.39 to 7.02%) and Sirius (LoA: 3.51 to 6.14%). The mean steep keratometry values of the Sirius were significantly lower than those of the Pentacam HR and in both the cross-linked and observation groups (LoA: 3.51 to 6.14%). The mean keratometry values were significantly higher in the Cassini compared to the Pentacam HR (LoA: 3.51 to 8.77%) and significantly lower in the Sirius in comparison to the Pentacam HR (LoA: 3.51 to 6.14%). The mean difference in astigmatism was also statistically significant between the three tomographers in both groups, with the Cassini showing higher values (LoA: 3.51 to 5.26%) and the Sirius lower values than the Pentacam HR (LoA: 5.26 to 6.14%). CONCLUSIONS: The authors conclude the three devices cannot be used interchangeably. The Cassini showed better agreement and correlation with the Pentacam HR in the staging of keratoconus, whereas the Sirius tended to underdiagnose and under-stage the disease. [J Refract Surg. 2024;40(4):e260-e269.].

Effect of volume of instillate on the diagnostic utility of bronchoalveolar lavage galactomannan in patients with suspected chronic pulmonary aspergillosis-A pilot study.

BACKGROUND: Bronchoalveolar lavage (BAL) galactomannan (GM) is commonly used to diagnose Aspergillus-related lung diseases. However, unlike serum GM, which is measured in undiluted blood, BAL-GM is estimated using variable aliquots and cumulative volume of instillates during bronchoscopy. OBJECTIVE: Since different studies have reported varying diagnostic accuracy and cut-offs for BAL-GM in CPA, we hypothesized that the total volume of instillate and 'order/label' of aliquots significantly affects the BAL-GM values, which was evaluated as part of this study. PATIENTS & METHODS: We obtained 250 BAL samples from 50 patients (five from each) with suspected chronic pulmonary aspergillosis. BAL fluid was collected after instilling sequential volumes of 40 mL of normal saline each for the first four labels and a fifth label was prepared by mixing 1 mL from each of the previous labels. The GM level of each label was measured by PLATELIA™ ASPERGILLUS Ag enzyme immunoassay. This study measured the discordance, level of agreement, diagnostic characteristics (sensitivity, specificity and AUROC) and best cut-offs for BAL-GM in the different aliquots of lavage fluid. RESULTS: The study population, classified into CPA (28%) and non-CPA (72%) groups, based on ERS/ESCMID criteria (excluding BAL-GM) were not different with respect to clinico-radiological characteristics. The discordance of BAL-GM positivity (using a cut-off of >1) between the serial labels for the same patient ranged between 10% and 22%, while the discordance between classification using BAL-GM positivity (using a cut-off of ≥1) and clinic-radio-microbiological classification ranged between 18% and 30%. The level of agreement for serial labels was at best fair (<0.6 for all except one 'label'). The AUROC for the serial samples ranged between 0.595 and 0.702, with the '40 mL and the 'mix' samples performing the best. The best BAL-GM cut-off also showed significant variation between serial labels of varying dilutions (Range:1.01 - 4.26). INTERPRETATION: This study highlights the variation in BAL-GM measured and the 'positivity' between different 'labels' of aliquots of BAL, with the first aliquot and the mixed sample showing the best performances for diagnosis of CPA. Future studies should attempt to 'standardise' the instilled volume for BAL-GM estimation to standardise the diagnostic yield.

Efficacy of Bhramari pranayama and Om chanting on asthma control, quality of life, and airway inflammation in asthmatic children: an open-label randomized controlled trial.

OBJECTIVES: To explore the efficacy of combination of Bhramari pranayama and om chanting as an adjunct to standard pharmacological treatment on asthma control, quality of life, pulmonary function, and airway inflammation in asthmatic children. METHODS: Children (n = 110; 8-15 years) with uncontrolled or partly controlled asthma were recruited from the Pediatric Chest Clinic of All India Institute of Medical Sciences, New Delhi. Eligible participants were randomized to either home-based online Bhramari pranayama and om chanting plus standard treatment (YI + ST) group, or standard treatment (ST) alone group. Primary outcome measures were 12-week change in level of asthma symptom control; asthma control questionnaire (ACQ) score, spirometry indices, impulse oscillometry parameters, and pediatric asthma quality of life questionnaire (PAQLQ) score. Secondary outcome was a change in fractional exhaled nitric oxide (FeNO) levels at 12 weeks. Beginning from the enrollment, every participant was evaluated at 0, 2, 6, and 12 weeks. RESULTS: After 12 weeks of intervention, higher proportion (68.2%) of children were found to have controlled asthma symptoms in the YI + ST group as compared to ST group (38.5%) according to per protocol analysis (p = 0.03). When compared to ST group, children in YI + ST group showed significantly lower ACQ score, higher PAQLQ score and reduced FeNO levels. No significant changes were observed for the lung function parameters. CONCLUSION: Children practicing Bhramari pranayama and om chanting for 12 weeks have better asthma symptom control, quality of life, and reduced airway inflammation than those taking standard pharmacotherapy alone.

Thiopurines Have Sustained Long-term Effectiveness in Patients with Inflammatory Bowel Disease, Which is Independent of Disease Duration at Initiation: A Propensity Score Matched Analysis.

BACKGROUND AND AIMS: Thiopurines are viable option for the treatment of inflammatory bowel disease [IBD] in resource-limited countries. However, data on the effect of disease duration at thiopurines initiation on long-term effectiveness are limited. METHOD: We performed a propensity matched analysis of a retrospective cohort of patients with ulcerative colitis [UC] and Crohn's disease [CD]. Patients initiated on thiopurines early in the disease course [≤2 years] were compared with those started late [>2 years]. Effectiveness was defined as no requirement for hospitalisation, anti-tumour necrosis factor [TNF] agents, or surgery, and minimum steroid requirement [≤1 steroid course in 2 years] during follow-up. RESULTS: A total of 988 [UC: 720, CD: 268] patients were included (male: 665 [60.8%], median age: 40 [32-51] years, median follow-up: 40 [19-81] months). Overall effectiveness at 5 and 10 years was 79% and 72% in UC, and 69% and 63% in CD, respectively. After propensity score matching, there was no difference in 5- and 10-year effectiveness between early and late thiopurine initiation groups either for UC [81% and 80% vs 82% and 74%; p = 0.92] or CD [76% and 66% vs 72% and 51%, p = 0.32]. Male sex for UC (negative: hazard ratio [HR]: 0.67, 95% confidence interval [CI): 0.45-0.97; p = 0.03), and ileal involvement [positive: HR: 3.03, 95% CI: 1.32-6.71; p = 0.008], steroid-dependent disease [positive: HR: 2.70, 95% CI: 1.26-5.68; p = 0.01] and adverse events [negative: HR: 0.47, 95% CI:0.27-0.80; p = 0.005] for CD were predictors of thiopurine effectiveness. CONCLUSION: Thiopurines have sustained long-term effectiveness in both UC and CD. However, early thiopurine initiation had no better effect on long-term disease outcome compared with late initiation.

A randomized controlled trial to explore the safety and efficacy of irradiated buffy-coat granulocytes in pediatric patients with febrile neutropenia.

BACKGROUND: Transfusion of granulocytes obtained by apheresis is beneficial in febrile neutropenia (FN) but expensive and time-consuming. Buffy-coat-derived granulocytes could be an alternative. We studied the efficacy and safety of the administration of irradiated buffy-coat-derived granulocytes along with the standard of care in pediatric high-risk (HR) FN. METHODS: Sixty children ≤18 years with malignancy and chemotherapy-induced HR FN were randomized to either the granulocyte transfusion (GT) arm which received irradiated buffy-coat derived granulocyte transfusion along with the standard treatment or the standard treatment (ST) arm. RESULTS: Baseline characteristics, day-to-defervescence, antibiotic duration, hospital stay, and mortality were comparable between the groups. A significant difference was seen in days to achieve absolute neutrophil count (ANC) >500/mm3 in the 2 groups: 4.5 days (3-6.5) in the GT arm v/s 8 days (4-11) in the ST arm (P=0.01). CONCLUSION: Buffy-coat-derived granulocyte transfusion was safe and led to early hematological recovery but was not associated with survival benefits. Future studies with earlier initiation in the intended dose could be undertaken to generate more evidence.

A Cross-Sectional Survey of 505 Postpartum Women to Assess Lifestyle-Related Behaviour, Barriers, and Myths Affecting Postpartum Weight Retention and Its Management.

Background/Purpose: This study aims to assess lifestyle-related factors such as diet, physical activity and sleep along with common myths, beliefs, and barriers to a healthy lifestyle and resultant postpartum weight retention. It has also explored the association of the aforementioned factors with socio-demographic variables. Methods: A cross-sectional survey was conducted using a comprehensive pre-validated questionnaire on a convenience sample of postpartum women using a telephonic interview schedule. Results: A total of 505 postpartum women were recruited with median postpartum weight retention of 5 kg. More than half of the participants had incorrect dietary practices with less than one-tenth of women indulging in low/moderate-intensity physical activity. Postpartum women had poorer diet (p < 0.05) and sleep (p < 0.01) in the initial phase postpartum as compared to late postpartum. These women were also less physically active in the initial months and as the postpartum period progressed their physical activity also improved significantly (p < 0.001). Socio-demographic variables such as socio-economic status, education, and employment status were significantly associated with unhealthy lifestyle practices. Common barriers were lack of knowledge, time constraints, lack of childcare support and cultural myths and beliefs. Conclusion: The findings of the study will help in developing a comprehensive women-centric weight management module focusing on practical guidelines for lifestyle, breastfeeding and other confounding factors associated with postpartum weight management.

Can Whole-Body Magnetic Resonance Imaging Predict Relapse in Juvenile Idiopathic Arthritis? A Longitudinal Pilot Study.

OBJECTIVE: To determine the utility of whole-body magnetic resonance imaging (WB MRI) to predict relapse in children with juvenile idiopathic arthritis (JIA) in clinical remission. METHODS: Consecutive patients with JIA who fulfilled the Wallace criteria for remission were recruited into this longitudinal pilot study and underwent WB MRI. A radiological score was devised, incorporating synovitis, bone marrow edema, sacroiliitis, enthesitis, and bone erosions. Two readers independently scored the MR data sets. The same score was calculated for both knee joints individually and correlated with outcome for that joint. Score-based models incorporating clinical and laboratory variables were generated. Logistic regression analysis was done to determine predictors for relapse. Receiver operating characteristic curve was drawn for significant variables. RESULTS: Twenty-two children (median age, 12 years; interquartile range, 9.5-14.25 years) were included in the final analysis. At 24 months' follow-up, 15 joints in 5 children relapsed; knee was the most common site. Seven knee joints had disease relapse. On univariate analysis, synovitis and total score on WB MRI were significant predictors of relapse at follow-up, with odds ratios of 9.46 (bias-corrected 95% confidence interval, 3.07-29.13) and 2.8 (bias-corrected 95% confidence interval, 1.23-6.39) respectively. Two models, which included a higher number of joints involved at presentation and abrupt drug withdrawal strategy as predictor variables, were also statistically significant (odds ratio, approximately 1.9). On multivariate analysis of the predictors variables in models where p < 0.6, it was found that only synovitis score and total score were near statistical significance ( p = 0.06); no clinical or laboratory variables were significant. The areas under the receiver operating characteristic curve for relapse prediction were approximately 0.82, 0.87, 0.79, and 0.81 for synovitis score, total MRI score, and both models, respectively. CONCLUSION: Synovitis on WB MRI is the strongest independent predictor for disease relapse in children with JIA in remission.

The Utility of Galactomannan and Polymerase Chain Reaction Assays in Bronchoalveolar Lavage for Diagnosis of Chronic Pulmonary Aspergillosis.

The diagnosis of chronic pulmonary aspergillosis (CPA) is established by combined clinic-radio-microbiological criteria. Out of the different microbiological criteria, a positive serology for Aspergillus-specific IgG levels is the cornerstone of diagnosis. Alternatively, other microbiological evidence are sometimes sought viz., positive Aspergillus antigen (broncho-alveolar lavage fluid, i.e., BALF galactomannan ≥ 1.0), histopathological demonstration of the fungi following lung biopsy or resection, demonstration of hyaline septate hyphae in direct microscopy resembling Aspergillus spp. or its growth on a respiratory specimen. However, the exact roles of BALF- GM and the newer BALF-PCR have not been confirmed by studies till date. This study enrolled 210 patients with suspected CPA. Of the participants, 88 patients met the criteria for CPA, whereas 122 patients had an alternative diagnosis. The sensitivity-specificity of AsperGenius® PCR and "in-house" PCR were 52.27(36.69-67.54) %-33.78 (23.19-45.72) % and 36.36 (22.41-52.23) %-39.19 (28.04-51.23) % respectively. The sensitivity/specificity of BALF (> 1.0) and serum galactomannan (> 1.0) were 46.55% (33.34-60.13)/64.08% (54.03-73.3) and 29.82% (22.05-37.6)/86.84% (81.1-92.59) respectively. The optimal cut-off values for BALF-Galactomannan and serum galactomannan in diagnosing CPA were found to be 0.69 (sensitivity: 64%; specificity: 53%) and 0.458 (sensitivity: 67%; specificity: 64%) respectively. This results of this study suggests that Aspergillus PCR from BAL may not be a good "rule-in" test for diagnosing CPA. While the performances of GM in BAL and serum may be better than PCR, it should be best used in conjunction with other clinical, radiological, and other microbiological characteristics.

Childhood and Adolescent Sleep Awareness in Caregivers and Health Care Providers: A Community- and Hospital-Based Survey.

BACKGROUND: Sleep disorders are common in childhood and adolescence with mental and physical consequences needing appropriate intervention by caregivers and health care providers (HCPs). The objective of the study, conducted at a tertiary teaching hospital and public school in north India, was to develop validated questionnaires to evaluate childhood and adolescent sleep awareness in caregivers and HCPs. METHODS: The study participants (caregivers represented by parents of 2-18 year olds attending a public school and of those attending outpatient services at the study hospital and HCPs represented by medical interns and nursing graduates within 1 year of graduation) were enrolled after appropriate screening. RESULTS: Two separate questionnaires in English for caregivers (also translated in Hindi) and HCPs were applied on 313 caregivers and 175 HCPs (110 medical interns and 65 nursing graduates) and developed and validated with a Cronbach α of 0.73 and 0.74, respectively. The questionnaires covered three domains: sleep hygiene, sleep related health problems, and miscellaneous. Both group of respondents had >50% correct responses in sleep hygiene. The ĸ agreement between knowledge and practice of sleep hygiene in caregivers was 0.2. Poor response (<50% correct responses) was seen in sleep-related health problems in both groups of respondents implying knowledge deficit in various sleep disorders. The HCPs performed poorly on basic theoretical questions in miscellaneous domain. For consultation of sleep problems, most caregivers (48%) chose pediatricians. CONCLUSION: There is a need to strengthen undergraduate medical and nursing curriculum in sleep. Caregivers should be made aware of implications of unhealthy sleep.

Long-term effect of panretinal photocoagulation on optic nerve head parameters in diabetic retinopathy using Heidelberg retinal tomography III.

PURPOSE: The aim of this study was to evaluate the effect of panretinal photocoagulation (PRP) in diabetic retinopathy patients using Heidelberg retinal tomography III (HRT). SUBJECTS AND METHODS: A total of 90 eyes of 90 consecutive newly diagnosed patients with diabetic retinopathy (nonproliferative diabetic retinopathy, NPDR, Group I and proliferative, PDR, Group II) were recruited for the study. The eyes with PDR were subjected to PRP. The effect of PRP was measured on optic nerve head (ONH) parameters using HRT. RESULTS: Follow-up up to 4 years in both groups indicated that in Group II proliferative diabetic retinopathy (PDR) participants undergoing PRP, the ONH parameters showed a significant difference in cup area (P = 0.023), cup volume (P = 0.001), mean cup depth (P = 0.015), maximum cup depth (P < 0.001), mean retinal nerve fiber layer (RNFL) thickness (P < 0.001) at 1 year of follow-up, and remained significant in all at 4 years of follow-up, whereas there was no significant difference in any of the optic disc parameters in the participants of Group I belonging to NPDR group as compared to PDR group after 4 years. CONCLUSION: PRP affected the ONH morphology in the PDR group and the effect of this change should be interpreted with caution. This may require setting a new baseline for RNFL measurements using the HRT when documenting RNFL loss or glaucoma progression in patients who have undergone PRP.

Premeal almond load decreases postprandial glycaemia, adiposity and reversed prediabetes to normoglycemia: A randomized controlled trial.

BACKGROUND: Asian Indians show rapid conversion from prediabetes to type 2 diabetes (T2D). Novel dietary strategies are needed to arrest this progression, by targeting postprandial hyperglycaemia (PPHG). DESIGN: We conducted a free-living randomized controlled open-label parallel arm study to evaluate the effect of a premeal load of almonds (20 g) 30 min before major meals on anthropometric, glycaemic, and metabolic parameters over 3 months. Sixty-six participants with prediabetes in the age range of 18-60 yrs were recruited. The study was registered at clinicaltrials.gov (registration no. NCT04769726). RESULTS: Thirty participants in each arm completed the study. As per 'intention-to-treat' analysis, overall additional mean reductions were statistically significant for body weight, BMI, waist circumference (WC), subscapular and suprailiac skinfolds, and improved handgrip strength (Kg) (p < 0·001 for all) in the treatment arm vs. the control arm (after multiple adjustments). In the blood parameters, the additional mean reduction in the treatment arm vs. control arm was statistically significant for fasting and post-75 g oral glucose-load blood glucose, postprandial insulin, HOMA-IR, HbA1c, proinsulin, total cholesterol, and very low-density lipoprotein cholesterol (p < 0·001 for all). Most importantly, we observed a reversal to normoglycemic state (fasting blood glucose and 2 h post-OGTT glucose levels) in 23.3% (7 out of 30) of participants in the treatment arm which is comparable to that seen with Acarbose treatment (25%). CONCLUSION: Incorporation of 20 g of almonds, 30 min before each major meal leads to significant improvement in body weight, WC, glycemia (particularly PPHG), and insulin resistance and shows potential for reversal of prediabetes to normal glucose regulation over 3 months.

Biocompatible dressing for pediatric hypospadias repair.

PURPOSE: The search for an ideal Hypospadias repair dressing continues. We aimed to develop a hypoallergenic optimized biocompatible dressing (BD). METHOD: BD with a multi-layered structure of hydrophilic treated Polypropylene with three-layered technologies; Absorbent-spunlaced hydroentangled polyester/viscose blend, outer Polypropylene, Polyester, Acrylic, and Spandex, with super Absorbent Polymer and Acrylic adhesive. Wistar rat abdominal wound model was divided into two groups: control (normal gauze dressing with adhesive) and Study (BD). The physical properties and wound characteristics were compared. RESULTS: Average mass: thickness of BD was 626.7 ± 5.6 g m-2: 2.6 ± 0.015 mm. Absorption was 1425.2 ± 127.6%. Percentage desorption of solution A from dressings at 24:40 h was 1249 ± 150%:1417 ± 230%. BD was hydrophilic with no particles/residue after immersion and pH neutral. The average air permeability was 11.6 ± 1.6 cm3/cm2/sec. The tensile force was 200N-220N with an extension on the breaking point at 24 mm. BD was superior for ease of removability on Day 6 (p = 0.012) and sticking quality (p = 0.036), absorption (p = 0.036), ease of removability(p = 0.036), and sustenance (p = 0.030) on Day 10. BD dressing demonstrated better wound healing (p = 0.015) and decreased redness (p = 0.002) on Day 10. Histopathological healing was better with BD on Day 14(p = 0.025) and Day 20 (p = 0.034). CONCLUSION: BD demonstrated better desirable physical and wound healing qualities with less inflammation compared with control normal dressing.

Beneficial effects of premeal almond load on glucose profile on oral glucose tolerance and continuous glucose monitoring: randomized crossover trials in Asian Indians with prediabetes.

BACKGROUND: Rapid conversion from prediabetes to diabetes and frequent postprandial hyperglycemia (PPHG) is seen in Asian Indians. These should be the target of dietary strategies. OBJECTIVES: We hypothesized that dietary intervention of preloading major meals with almonds in participants with prediabetes will decrease overall glycemia and PPHG. DESIGN: The study included two phases: (1) an oral glucose tolerance test (OGTT)-based crossover randomized control study, the effect of a single premeal almond load (20 g) given before OGTT was evaluated (n = 60, 30 each period). (2) The continuous glucose monitoring system (CGMS)-based study for 3 days including premeal almond load before three major meals was a free-living, open-labeled, crossover randomized control trial, where control and premeal almond load diets were compared for glycaemic control (n = 60, 30 in each period). The study was registered at clinicaltrials.gov (registration no. NCT04769726). RESULTS: In the OGTT-based study phase, the overall AUC for blood glucose, serum insulin, C-peptide, and plasma glucagon post-75 g oral glucose load was significantly lower for treatment vs. control diet (p < 0.001). Specifically, with the former diet, PPHG was significantly lower (18.05% in AUC on OGTT, 24.8% at 1-h, 28.9% at 2-h post OGTT, and 10.07% during CGMS). The CGMS data showed that premeal almond load significantly improved 24-glucose variability; SD of mean glucose concentration and mean of daily differences. Daily glycaemic control improved significantly as per the following: mean 24-h blood glucose concentration (M), time spent above 7.8 mmol/L of blood glucose, together with the corresponding AUC values. Premeal almond load significantly decreased following: overall hyperglycemia (glucose AUC), PPHG, peak 24-h glycaemia, and minimum glucose level during night. CONCLUSION: Incorporation of 20 g of almonds, 30 min before each major meal led to a significant decrease in PPHG (as revealed in OGTT-based study phase) and also improved insulin, C-peptide, glucagon levels, and improved glucose variability and glycemic parameters on CGMS in participants with prediabetes. CLINICAL TRIAL REGISTRY: The study was registered at clinicaltrials.gov (registration no. NCT04769726).

Safety, Efficacy, and Tolerability of Modified Atkins Diet in Persons With Drug-Resistant Epilepsy: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Modified Atkins diet (MAD) has emerged as an adjuvant therapy in drug-resistant epilepsy (DRE). Most studies are in children; there is limited evidence for DRE in adults. This study aimed to investigate whether MAD along with standard drug therapy (SDT) was indeed more effective than SDT alone in reducing seizure frequency and improving psychological outcomes at 6 months in adolescents and adults with DRE (nonsurgical). METHODS: A prospective randomized controlled trial was conducted at tertiary care referral center in India. Persons with DRE aged 10-55 years attending outpatient epilepsy clinics between August 2015 and April 2019, who had more than 2 seizures per month despite using at least 3 appropriate antiseizure medications (ASMs) at their maximum tolerated doses and had not been on any form of diet therapy for the past 1 year, were enrolled. Patients were assessed for the eligibility and randomly assigned to receive SDT plus MAD (intervention arm) or SDT alone (control arm). The primary outcome was >50% reduction in seizure frequency, and the secondary outcomes were quality of life (QOL), behavior, adverse events, and rate of withdrawal at 6 months. Intention-to-treat analysis was performed. RESULTS: A total of 243 patients were screened for eligibility; 160 patients (80 adults and 80 adolescents) were randomized to either the intervention or control arm. Demographic and clinical characteristics in both groups were comparable at baseline. At 6 months, >50% seizure reduction was seen in 26.2% in the intervention group vs 2.5% in the control group (95% CI 13.5-33.9; p < 0.001). Improvement in QOL was 52.1 ± 17.6 in the intervention group vs 42.5 ± 16.4 in the control group (mean difference, 9.6; 95% CI 4.3 to 14.9, p < 0.001). However, behavior scores could be performed in 49 patients, and improvement was seen in the intervention vs control group (65.6 ± 7.9 vs 71.4 ± 8.1, p = 0.015) at the end of the study. One patient had weight loss; 2 patients had diarrhea. DISCUSSION: The MAD group demonstrated improvement in all aspects (reduction in seizure frequency and behavioral problems) compared with the control group at the end of the study. MAD is an effective modality in controlling seizures; further research is required to assess its efficacy in terms of biomarkers along with descriptive metabolomics studies. TRIAL REGISTRATION INFORMATION: The clinical trial registry of India: CTRI/2015/07/006048. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the MAD increases the probability of seizure reduction in adolescents and adults with DRE.

CD34 negative HLA-DR negative acute myeloid leukaemia: A higher association with NPM1 and FLT3-ITD mutations.

INTRODUCTION: CD34 and HLA-DR negativity is often used as a characteristic immunophenotypic feature of acute promyelocytic leukaemia (APL) that differentiates APL from other subtypes of acute myeloid leukaemia (AML). However, other subtypes of AML, without expression of CD34 and HLA-DR antigens, have also been reported. METHODS: We analysed the HLA-DR negative de novo non-APL AML cases by dividing HLA-DR negative non-APL group into 2 sub-groups based on CD34 expression and compared the characteristics of CD34 negative HLA-DR negative with CD34 positive HLA-DR negative non-APL AML cases with respect to morphologic, immunophenotypic, molecular and clinical parameters. RESULTS: There were 70 cases (8.54%) which were CD34 negative HLA-DR negative and 52 cases (6.34%) were CD34 positive HLA-DR negative. The median age at diagnosis was higher in CD34 negative HLA-DR negative AML than in CD34 positive HLA-DR negative AML group (38 years vs. 12 years, p < 0.001). DIC rate was higher in CD34 negative HLA-DR negative group than the other group (p < 0.001). Median total leucocyte count was higher with higher blast count in peripheral blood and bone marrow in CD34 negative HLA-DR negative AML cases than the other group (p < 0.05). CD34 negative HLA-DR negative AML was more associated with normal karyotype (96.2% vs. 38.5%; p < 0.001), NPM1 mutation (67.8% vs. 8.3%; p < 0.001) and FLT-ITD mutation (37.3% vs. 13.9%; p < 0.05). In CD34 negative HLA-DR negative group, 16 cases had co-occurrence of NPM1 and FLT3-ITD mutations, whereas no case of CD34 positive HLA-DR negative group had such dual mutation positivity. There was poor median overall survival [3.8 months (95%CI: 2.3-7.8 months) vs. 20.4 months (95% CI: 12.8-25.7 months); p = 0.0148] in CD34 positive HLA-DR negative AML than CD34 negative HLA-DR negative AML cases. CONCLUSION: We found that the CD34 negative HLADR negative non APL AML is highly associated with NPM1 and FLT3-ITD mutation, older age at diagnosis, DIC, higher total leucocyte count, higher blast counts and normal karyotype in comparison to CD34 positive HLA-DR negative AML group. Co-occurrence of NPM1 and FLT3-ITD mutation was also exclusively seen in CD34 negative HLA-DR negative group. There was poor overall survival in CD34 positive HLA-DR negative AML than CD34 negative HLA-DR negative AML cases.

Genetic polymorphism of fatty acid binding protein-2 in hyperlipidemic Asian Indians in North India.

BACKGROUND: Fatty acid binding protein-2 (FABP-2) is involved in the metabolism of lipids in the intestine. FABP-2 Ala54Thr polymorphism involves a transition of G to A at codon 54 of FABP-2, resulting in an amino acid substitution Ala54 to Thr54 and is associated with elevated fasting triglycerides in some hyperlipidemic populations. In current genome builds and gene databases the variant of the Ala54Thr FABP-2 (rs 1 799 883) is annotated as c.163A>G (p. Thr55Ala). AIM AND OBJECTIVE: The status of this polymorphism in hyperlipidemic Asian Indians from North India has not been investigated. This study was aimed to evaluate the distribution of the polymorphic variants of the Ala54Thr FABP-2 and their association with lipids in hyperlipidemic subjects. METHODS: Ala54Thr FABP-2 polymorphism in both hyperlipidemic (n = 210) and normolipidemic (n = 342) subjects was assessed by PCR-RFLP. RESULTS: Ala54Thr genotypes and alleles distribution did not differ between the hyperlipidemic and normolipidemic groups. The heterozygous genotype FABP-2 Ala/Thr was significantly associated with higher levels of triglycerides and very low-density lipoproteins as compared to the homozygous variant (Thr/Thr) genotype and the wild type homozygous (Ala/Ala) genotype. CONCLUSIONS: The heterozygous genotype FABP-2 Ala54Thr is a risk factor for the development of hypertriglyceridemia and increased levels of VLDL-c in Asian Indians from North India.

Negative Emotions, Triggers, and Coping Strategies Among Postpartum Indian Women During Second Wave of COVID-19 Pandemic: Lessons for the Subsequent Waves and Beyond.

Introduction: The study aimed to evaluate COVID-19 associated psychological distress among pregnant and postpartum women during the second wave of COVID-19 in India. Methods: A cross-sectional survey was done using a pre-validated tool involving 491 participants attending a tertiary-care hospital during the second wave of COVID-19 in India. Results: Three-fourths of participants experienced negative emotions such as fear and various features of depression. Participants (75%) reported COVID-related news on TV/Radio/Newspapers including social media as the major trigger for these negative emotions. Loss of social support mainly affected postpartum women (p < 0.001) and working women (p < 0.001). Inability to access healthcare services had negative associations with age (p < 0.001), education (p < 0.001), and socioeconomic class (p < 0.001). Various coping strategies being followed by participants included watching TV/Videos or reading books (93%), resorting to social media (77%), spending more time praying and meditating (86%), and engaging in hobbies (56%). Conclusion: During the second wave, the COVID-19 pandemic had a significantly high negative impact on the psychological and social well-being of pregnant and postpartum women. Hence, it is important to initiate appropriate preventive and corrective steps by the policymakers for any future waves of the pandemic.

Clinico-Hematological Profile of Acute Myeloid Leukemia: Experience From a Tertiary Care Cancer Center in North India.

INTRODUCTION: Complete diagnosis of acute myeloid leukemia (AML) requires knowledge of clinical information combined with morphologic evaluation, immunophenotyping, karyotyping, and molecular genetic testing. The study intends to evaluate the demographic profile, clinical workup, and investigation, including flow cytometric immunophenotyping, in adult and pediatric age groups of AML. MATERIALS AND METHODS: This is a retrospective study of AML patients treated between January 2017 and December 2021. Clinical and demographic characteristics and investigation findings were recorded from case files and the hematology database. RESULT: A total of 896 cases of AML were registered during the given period, of which 819 cases were de-novo AML. Among those 819 cases, more than two-thirds of cases, i.e., 78.9% (N = 646), received induction chemotherapy. A significantly higher male-to-female ratio was observed (1.5:1). The median age was 22 years. The median time for diagnosis was three days and the median time for treatment intervention was four days. There were significant differences in the Eastern Cooperative Oncology Group (ECOG) performance status scores between pediatric and adult AML patients. Pediatric AML patients presented with better ECOG performance scores (ECOG performance scores 0 and 1) than adult patients (74.76% vs. 43.14%, p < 0.001). Further comparing adult vs. pediatric AML patients, normal karyotype (60.56% vs. 31.93%, p < 0.001) and NPM1 (22.25% vs. 6.72%, p < 0.001) and FLT3-ITD mutations (20.28% vs. 7.98%, p<0.001) were more common in the adult group, whereas AML-ETO (40.76% vs. 16.34%, p < 0.001) was more common in the pediatric group. CONCLUSION: The study highlights the presenting age is lower than global figures. The median time for initial diagnosis and the start of treatment is within the acceptable norms. Normal karyotype and NPM1 and FLT3 mutations were common in adult AML patients, whereas AML-ETO was more common in the pediatric cohort. These findings will help plan prospective studies and see the correlation with treatment outcomes. The laboratory workup practice currently complies with the standard guidelines at our center.

Interleukin-33 Induces Neutrophil Extracellular Trap (NET) Formation and Macrophage Necroptosis via Enhancing Oxidative Stress and Secretion of Proatherogenic Factors in Advanced Atherosclerosis.

Interleukin-33 (IL-33) acts as an 'alarmin', and its role has been demonstrated in driving immune regulation and inflammation in many human diseases. However, the precise mechanism of action of IL-33 in regulating neutrophil and macrophage functioning is not defined in advanced atherosclerosis (aAT) patients. Further, the role of IL-33 in neutrophil extracellular trap (NET) formation in aAT and its consequent effect on macrophage function is not known. In the present study, we recruited n = 52 aAT patients and n = 52 control subjects. The neutrophils were isolated from both groups via ficoll/percoll-based density gradient centrifugation. The effect of IL-33 on the NET formation ability of the neutrophils was determined in both groups. Monocytes, isolated via a positive selection method, were used to differentiate them into macrophages from each of the study subjects and were challenged by IL-33-primed NETs, followed by the measurement of oxidative stress by calorimetric assay and the expression of the proinflammatory molecules by quantitative PCR (qPCR). Transcript and protein expression was determined by qPCR and immunofluorescence/ELISA, respectively. The increased expression of IL-33R (ST-2) was observed in the neutrophils, along with an increased serum concentration of IL-33 in aAT compared to the controls. IL-33 exacerbates NET formation via specifically upregulating CD16 expression in aAT. IL-33-primed NETs/neutrophils increased the cellular oxidative stress levels in the macrophages, leading to enhanced macrophage necroptosis and the release of atherogenic factors and matrix metalloproteinases (MMPs) in aAT compared to the controls. These findings suggested a pathogenic effect of the IL-33/ST-2 pathway in aAT patients by exacerbating NET formation and macrophage necroptosis, thereby facilitating the release of inflammatory factors and the release of MMPs that may be critical for the destabilization/rupture of atherosclerotic plaques in aAT. Targeting the IL-33/ST-2-NETs axis may be a promising therapeutic target for preventing plaque instability/rupture and its adverse complications in aAT.