Neelam Marwaha

Treatment With Platelet-Rich Plasma Is More Effective Than Placebo for Knee Osteoarthritis A Prospective, Double-Blind, Randomized Trial

Background: Specific growth factors have been proposed as therapeutic proteins for cartilage repair. Hypothesis: Platelet-rich plasma (PRP) provides symptomatic relief in early osteoarthritis (OA) of the knee. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 78 patients (156 knees) with bilateral OA were divided randomly into 3 groups. Group A (52 knees) received a single injection of PRP, group B (50 knees) received 2 injections of PRP 3 weeks apart, and group C (46 knees) received a single injection of normal saline. White blood cell (WBC)–filtered PRP with a platelet count 3 times that of baseline (PRP type 4B) was administered in all. All the groups were homogeneous and comparable in baseline characteristics. Clinical outcome was evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire before treatment and at 6 weeks, 3 months, and 6 months after treatment. They were also evaluated for pain by a visual analog scale, and overall satisfaction with the procedure and complications were noted. Results: Statistically significant improvement in all WOMAC parameters was noted in groups A and B within 2 to 3 weeks and lasting until the final follow-up at 6 months, with slight worsening at the 6-month follow-up. The mean WOMAC scores (pain, stiffness, physical function, and total score) for group A at baseline were 10.18, 3.12, 36.56, and 49.86, respectively, and at final follow-up were 5.00, 2.10, 20.08, and 27.18, respectively, showing significant improvement. Similar improvement was noted in group B (mean WOMAC scores at baseline: 10.62, 3.50, 39.10, and 53.20, respectively; mean WOMAC scores at final follow-up: 6.18, 1.88, 22.40, and 30.48, respectively). In group C, the mean WOMAC scores deteriorated from baseline (9.04, 2.70, 33.80, and 45.54, respectively) to final follow-up (10.87, 2.76, 39.46, and 53.09, respectively). The 3 groups were compared with each other, and no improvement was noted in group C as compared with groups A and B (P < .001). There was no difference between groups A and B, and there was no influence of age, sex, weight, or body mass index on the outcome. Knees with Ahlback grade 1 fared better than those with grade 2. Mild complications such as nausea and dizziness, which were of short duration, were observed in 6 patients (22.2%) in group A and 11 patients (44%) in group B. Conclusion: A single dose of WBC-filtered PRP in concentrations of 10 times the normal amount is as effective as 2 injections to alleviate symptoms in early knee OA. The results, however, deteriorate after 6 months. Both groups treated with PRP had better results than did the group injected with saline only.

Intravenous Autologous Bone Marrow Mononuclear Stem Cell Therapy for Ischemic Stroke: A Multicentric, Randomized Trial

Background and Purpose— Pilot studies have suggested benefit from intravenous administration of bone marrow mononuclear stem cells (BMSCs) in stroke. We explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke. Methods— This was a phase II, multicenter, parallel group, randomized trial with blinded outcome assessment that included 120 patients. Patients with subacute ischemic stroke were randomly assigned to the arm that received intravenous infusion of autologous BMSCs or to control arm. Coprimary clinical efficacy outcomes were Barthel Index score and modified Rankin scale at day 180. Secondary outcomes were change in infarct volume, National Institute of Health Stroke Scale (NIHSS) at day 90 and 180. Main safety outcomes were adverse events, any new area of 18fluorodeoxyglucose positron emission tomography uptake in any body part over 365 days. Results— Fifty-eight patients received a mean of 280.75 million BMSCs at median of 18.5 days after stroke onset. There was no significant difference between BMSCs arm and control arm in the Barthel Index score (63.1 versus 63.6; P=0.92), modified Rankin scale shift analysis (P=0.53) or score >3 (47.5% versus 49.2%; P=0.85), NIHSS score (6.3 versus 7.0; P=0.53), change in infarct volume (−11.1 versus −7.36; P=0.63) at day 180. Adverse events were also similar in the 2 arms, and no patient showed any new area of 18fluorodeoxyglucose uptake. Conclusions— With the methods used, results of this hitherto first randomized controlled trial indicate that intravenous infusion of BMSCs is safe, but there is no beneficial effect of treatment on stroke outcome. Clinical Trial Registration— URLs: http://ctri.nic.in/Clinicaltrials and http://www.clinicaltrials.gov. Unique identifiers: CTRI-ROVCTRI/2008/091/0004 and NCT0150177.

Early results of core decompression and autologous bone marrow mononuclear cells instillation in femoral head osteonecrosis: a randomized control study.

Fifty-one osteonecrotic hips in 40 patients were randomly divided into 2 treatment groups. Patients in group A (25 hips) were treated with core decompression, and those in group B (26 hips) received autologous bone marrow mononuclear cell instillation into the core tract after core decompression. Outcome between the 2 groups were compared clinically (Harris Hip score), radiographically (x-ray and magnetic resonance imaging), and by Kaplan-Meier hip survival analysis after 12 and 24 months of surgical intervention. The clinical score and mean hip survival were significantly better in group B than in group A (P < .05). Patients with adverse prognostic features at initial presentation, that is, poor Harris Hip score, x-ray changes, edema, and/or effusion on magnetic resonance imaging had significantly better clinical outcome and hip survival in group B than in group A.

Efficacy of Autologous Bone Marrow–Derived Stem Cell Transplantation in Patients With Type 2 Diabetes Mellitus

Progressive and inexorable beta-cell dysfunction is the hallmark of type 2 diabetes mellitus (T2DM) and beta-cell regeneration using stem cell therapy may prove to be an effective modality. A total of 10 patients (8 men) with T2DM for >5 years, failure of triple oral antidiabetic drugs, currently on insulin (> or = 0.7 U/kg/day) at least for 1 year, and glutamic acid decarboxylase antibody negative were included. Patients on stable doses of medications for past 3 months were recruited. Primary end points were reduction in insulin requirement by > or = 50% and improvement in glucagon-stimulated C-peptide levels at the end of 6 months of autologous bone marrow-derived stem cell transplantation (SCT), while secondary end points were a change in weight and HbA1c and lipid levels as compared to baseline. Seven patients were responders and showed a reduction in insulin requirement by 75% as compared to baseline. Mean duration to achieve the primary objective was 48 days. Three patients were able to discontinue insulin completely, although it was short-lived in one. Mean HbA1c reduction was 1% and 3 of the 7 responders had HbA1c value <7%. A significant weight loss of 5.5 kg was noted in the responders, whereas, nonresponders gained 2.2 kg of weight. However, weight loss did not correlate with reduction in insulin requirement (r = 0.68, P = 0.06). There was a significant improvement in both fasting and glucagon-stimulated C-peptide level in the group (P = 0.03) and responders (P = 0.03). HOMA-B increased significantly in the whole group (P = 0.02) and responders (P = 0.04) whereas, HOMA-IR did not change significantly (P = 0.74). Reduction in insulin doses correlated with stimulated C-peptide response at the baseline (r = 0.83, P = 0.047) and mononuclear cell count of infused stem cells (r = 0.57, P = 0.04). No serious adverse effects were noted. Our observations indicate that SCT is a safe and effective modality of treatment to improve beta-cell function in patients with T2DM. However, further large-scale studies are needed to substantiate these observations.

The molecular basis of β thalassaemia in Punjabi and Maharashtran Indians includes a multilocus aetiology involving triplicated α-globin loci

Summary We have analysed 201 β‐thalassaemia (β‐thal) genes from natives of the Punjab (156) and Maharashtra states of India and found the causative mutation in 200 of them. The most common β‐globin gene mutations differed significantly between these two groups and between these groups and Indian immigrants in the U.S.A. and the U.K. In the Punjabi Indians the IVS‐1, nt 1 (G–T) mutation accounted for nearly one‐quarter of β‐thal genes, whereas it was 5% or less in the other groups. Likewise, the cap+ 1 mutation was much more prevalent in the Punjabis, whereas the nonsense codon 15 allele had a higher frequency in the Maharashtrans of the Bombay region. The common IVS‐1, nt5 allele had a frequency of 60% of β‐thal genes in the Maharastrans, 35% in North American immigrants, and only 23% in the Punjabis. Two‐thirds of all β‐thal genes in Punjab were found in the merchant caste (Khatri‐Arora), whereas the menial caste (Shudra) was highly represented among those with β‐thal genes in Maharashtra. Two novel β‐globin alleles were each found once; a frameshift codon 55 (+ A) in Maharashtrans and a frameshift codons 47–48 (+ ATCT) in Punjabis.

Phenotype frequencies of blood group systems (Rh, Kell, Kidd, Duffy, MNS, P, Lewis, and Lutheran) in north Indian blood donors

BACKGROUND We here report the first study of antigen and phenotype frequencies of various blood group systems by gel technology in north Indian blood donors. STUDY DESIGN AND METHODS A total of 1240 regular repeat voluntary north Indian blood donors of O blood group were included for red cell antigen typing of Rh (D, C, E, c, e) and Kell (K) blood group systems. Out of these, 317 donors were randomly selected for typing of other blood group antigens: Jk(a), Jk(b), k, Kp(a), Kp(b), Fy(a), Fy(b), M, N, S, s, Le(a), Le(b), P(1), Lu(a), Lu(b) and Xg(a). Calculations of antigen and phenotypes frequencies were expressed as percentages and for allele frequencies under the standard assumption of Hardy-Weinberg equilibrium. RESULTS Out of 1240 O group blood donors, 93.39% were Rh D and 5.56% were K positive. Amongst Rh antigens, e was the most common (98.3%) followed by D, C (84.76%), c (52.82%) and E (17.9%) with DCe/DCe (R(1)R(1), 43.8%) being the most common phenotype. In Kell blood group system, we found k antigen to be 100% and a rare phenotype Kp (a+b+) was found in 0.95% of the donors. For Kidd and Duffy blood group systems, Jk (a+b+) and Fy (a+b-) were the most common phenotypes (49.21% and 43.85%, respectively). In the MNS blood group system, M+N+S+s+ (19.55%) was the most common whereas M-N+S+s- (1.26%) was least common phenotype found. We found rare Lu (a+b+) and Lu (a-b-) phenotypes in 0.95% and 3.15% of the donors, respectively. Xg(a) antigen was seen in 86.67% and 62.6% of female and male donors, respectively. CONCLUSIONS Knowledge of red cell antigen phenotype frequencies in a population is helpful in terms of their ethnic distribution, in creating a donor data bank for preparation of indigenous cell panels, and providing antigen negative compatible blood to patients with multiple alloantibodies.

Autologous bone marrow-derived stem cells in amyotrophic lateral sclerosis: a pilot study.

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no effective treatment. Stem cell therapy may be one of the promising treatment options for such patients. AIM To assess the feasibility, efficacy and safety of autologous bone marrow-derived stem cells in patients of ALS. SETTINGS AND DESIGN We conducted an open-label pilot study of autologous bone marrow-derived stem cells in patients with ALS attending the Neurology Clinic of a tertiary care referral centre. MATERIALS AND METHODS Ten patients with ALS with mean revised ALS Functional Rating Scale (ALSFRS-R) score of 30.2 (± 10.58) at baseline received intrathecal autologous bone marrow-derived stem cells. Primary end point was improvement in the ALSFRS-R score at 90, 180, 270 and 365 days post therapy. Secondary endpoints included ALSFRS-R subscores, time to 4-point deterioration, median survival and reported adverse events. Paired t-test was used to compare changes in ALSFRS-R from baseline and Kaplan-Meier analysis was used for survival calculations. RESULTS There was no significant deterioration in ALSFRS-R composite score from baseline at one-year follow-up (P=0.090). The median survival post procedure was 18.0 months and median time to 4-point deterioration was 16.7 months. No significant adverse events were reported. CONCLUSION Autologous bone marrow-derived stem cell therapy is safe and feasible in patients of ALS. Short-term follow-up of ALSFRS-R scores suggests a trend towards stabilization of disease. However, the benefit needs to be confirmed in the long-term follow-up period.

Safety and efficacy of autologous mesenchymal stromal cells transplantation in patients undergoing living donor kidney transplantation: A pilot study

This pilot study assesses the safety and feasibility of autologous mesenchymal stromal cell (MSC) transplantation in four patients that underwent living donor renal transplantation, and the effect on the immunophenotype and functionality of peripheral T lymphocytes following transplantation.

Prevalence of coeliac disease in healthy blood donors: A study from north India

BACKGROUND Blood donor screening can help predict prevalence of coeliac disease in population. METHODS Between December 2010 and June 2011, healthy blood donors were screened using anti-tissue glutaminase antibodies. Those positive underwent duodenoscopy. Their age, gender, body mass index and haemoglobin and histological changes were recorded. RESULTS Of the 1610 blood donors screened, 1581 (98.2%) were males. The mean age of donors was 31.51 ± 9.66 years and the mean body mass index was 22.12 ± 4.24 kg/m(2). Nine (0.56%) men were seropositive. Endoscopic features included reduced fold height (9), scalloping (8), grooving (7) and mosaic mucosal pattern (3). Eight had Marsh IIIa changes whilst one had IIIb change. The prevalence of coeliac disease was 1:179 (0.56%, 95% confidence interval 1/366-1/91, 0.27-1.1%). None of the 9 patients had any symptoms. Their mean haemoglobin and body-mass index was similar to rest of the cohort. CONCLUSION The prevalence of coeliac disease amongst apparently healthy blood donors was 1:179 (0.56%).

Efficacy and Safety of Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients with Type 2 Diabetes Mellitus: A Randomized Placebo-Controlled Study

There is a growing interest in cell-based therapies in T2DM as β-cell failure is progressive and inexorable with the advancing duration of disease. This prospective, randomized, single-blinded placebo-controlled study evaluates the efficacy and safety of autologous bone marrow-derived stem cell transplantation (ABMSCT) in T2DM. Twenty-one patients with triple oral antidiabetic drug failure and requiring insulin ≥0.4 IU per kg per day with HbA1c <7.5% were randomly assigned to an intervention (n = 11) and control group (n = 10) and followed for 12 months. Patients in the intervention group received ABMSCT through a targeted approach, and after 12 weeks, a second dose of stem cells was administered through the antecubital vein after mobilization with G-CSF, while the control group underwent a sham procedure. The primary end point was a reduction in insulin requirement by ≥50% from baseline while maintaining HbA1c <7%. Nine out of the 11 (82%) patients in the intervention group achieved the primary end point, whereas none of the patients in the control group did over the study period (p = 0.002). The insulin requirement decreased by 66.7% in the intervention group from 42.0 (31.0-64.0) IU per day to 14.0 (0.0-30.0) IU per day (p = 0.011), while in controls it decreased by 32.1% from 40.5 (31.8-44.3) IU per day to 27.5 (23.5-33.3) IU per day (p = 0.008) at 12 months. The reduction in insulin requirement was significantly more in the intervention group compared to controls at both 6 (p = 0.001) and 12 months (p = 0.004). There was a modest but nonsignificant increase in HbA1c (%) in cases from 6.9% (6.4-7.2%) to 7.1% (6.6-7.5%) as well as in controls from 6.9% (6.2-7.0%) to 7.0% (6.9-7.5%). Ten out of 11 (91%) patients could maintain HbA1c <7% in the intervention group, whereas 6 out of 10 did (60%) in the control group (p = 0.167). The glucagon-stimulated C-peptide significantly increased in treated cases compared to controls (p = 0.036). The decrease in insulin requirement positively correlated with stimulated C-peptide (r = 0.8, p = 0.001). In conclusion, ABMSCT results in a significant decrease in the insulin dose requirement along with an improvement in the stimulated C-peptide levels in T2DM. However, a greater number of patients with a longer duration of follow-up are required to substantiate these observations.