Cerebral Palsy is a common and devastating neurological disorder, with no medical treatment apart from physiotherapy regimes to alleviate the functional disability. Regenerative medicine using stem cells has gained momentum in recent years as a possible strategy to repair the injured brain. Present study was undertaken in a open label series to evaluate the safety, feasibility and observe for any benefi cial effects of intra-arterial infusion of autologous bone marrow derived mononuclear cells in patients with cerebral palsy with moderate disability. Functional improvement was assessed using the motor power and spasticity scales, dystonia and abnormal movements scale and the activities of daily living scales by modifi ed Barthel Index and modifi ed Rankin Scores. Serial structural imaging with MRI and functional imaging with FDG-PET scans were done. Of the 30 patients injected with an average of 10-30 million cells into each carotid artery, improvements were observed in all clinical scales, and predominantly in the disability scores. No adverse events were noted on a 12 months follow up.

Background/Aims: Sigmoid esophagus and/or megaesophagus are considered as an advanced stage in the natural history of achalasia cardia. The role of peroral endoscopic myotomy (POEM) in these subset of patients is emerging. We performed a systematic review and metanalysis to study the efficacy of POEM in advanced achalasia cardia with sigmoid and megaesophagus. Methods: A literature search in PubMed and Embase was done from inception till August 3, 2021 to look for studies reporting exclusively on the role of POEM in advanced achalasia cardia with sigmoid and/or megaesophagus. The random effect method with inverse variance approach was used for the computation of pooled prevalence. For 2 groups’ analysis of continuous outcome standardized mean difference was used as the summary measure. Results: Eleven studies with 428 patients were included for analysis. The pooled technical and clinical success was 98.27% (95% CI, 96.19-99.22; I 2 = 0%) and 89.38% (95% CI, 84.49-92.86; I 2 = 26%) and on subgroup analysis into sigmoid and megaesophagus it was (98.06% [95% CI, 95.41-99.19; I 2 = 0%], 98.47% [95% CI, 92.72-99.69; I 2 = 0%] and 87.92% [95% CI, 80.68-92.70; I 2 = 37%], 88.36% [95% CI, 62.62-97.17; I 2 = 77%]) respectively. The clinical success at < 1 year and 1-3 year follow-up was 89.37% (95% CI, 82.82-93.61; I 2 = 0%) and 88.66% (95% CI, 81.65-91.22; I 2 = 46%) respectively. There was a significant reduction in the post-POEM scores with standardized mean difference for Eckardt score (4.81), for integrated relaxation pressure at 4 seconds (1.93), and for lower esophageal sphincter pressure (2.06). Conclusions POEM is an effective modality of treatment even in the subset of patients of advanced achalasia cardia with sigmoid and megae sophagus.

AIMTo study the effects of homocysteine and copper on type 5 phosphodiesterase (PDE5) expression in cavernosal vascular smooth muscle cells (CVSMCs) and to investigate superoxide (O(2)(.-)) derived from nicotinamide adenine dinucleotide phosphate oxidase as homocysteine and copper generate O(2)(.-), and O(2)(.-) upregulates PDE5 expression.

METHODSCVSMCs derived from rabbit penis were incubated with homocysteine or copper chloride with or without superoxide dismutase (SOD), catalase, sildenafil citrate, or apocynin (nicotinamide adenine dinucleotide phosphate inhibitor) for 16 h. The expression of PDE5 and of glyceraldehyde-3-phosphate dehydrogenase (internal standard) was assessed using Western blot analysis. In parallel, O(2)(.-) was measured spectrophotometrically.

RESULTSCuCl(2) alone (up to 10 micromol/L) and homocysteine alone (up to 100 micromol/L) had no effect on O(2)(.-) formation in CVSMCs compared to controls. In combination, however, homocysteine and CuCl(2) markedly increased O(2)(.-) formation, an effect blocked by SOD, catalase, apocynin, and sildenafil (1 micromol/L) when co-incubated over the same time course. PDE5 expression was also significantly increased in CVSMCs incubated with homocysteine and CuCl(2), compared to controls. This effect was also negated by 16-h co-incubation with SOD, catalase, apocynin and sildenafil.

CONCLUSIONThis represents a novel pathogenic mechanism underlying ED, and indicates that the therapeutic actions of prolonged sildenafil use are mediated in part through inhibition of this pathway.

Animals ; Blotting, Western ; Chelating Agents ; pharmacology ; Copper ; pharmacology ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; biosynthesis ; Data Interpretation, Statistical ; Gene Expression Regulation, Enzymologic ; drug effects ; Homocysteine ; pharmacology ; In Vitro Techniques ; Male ; Myocytes, Smooth Muscle ; drug effects ; enzymology ; NADPH Oxidases ; antagonists & inhibitors ; Penicillamine ; pharmacology ; Penis ; drug effects ; enzymology ; Phosphodiesterase Inhibitors ; pharmacology ; Piperazines ; pharmacology ; Purines ; pharmacology ; Rabbits ; Reactive Oxygen Species ; metabolism ; Sildenafil Citrate ; Sulfones ; pharmacology

Introduction:We assessed the role of the Pirani score in determining the number of casts and its ability to suggest requirement for tenotomy in the management of clubfoot by the Ponseti method. Materials and Methods:Prospective analysis of 66 (110 feet) cases of idiopathic clubfoot up to one year of age was done. Exclusion criteria included children more than one year of age at the start of treatment, non-idiopathic cases and previously treated or operated cases. Results: The initial Pirani score was (5.5±0.7) for the tenotomy group and the initial Pirani score was (3.3±1.6) for the non-tenotomy group. There was a significant difference between the initial Pirani score for the tenotomy and the nontenotomy group with t= -7.9, df= 64 p<0.0001. The tenotomy group had a significantly higher number of casts (four to seven) compared to non-tenotomy group (two to five) t=-10.4, df=64, p<0.0001. Spearman’s rank correlation coefficient was significant and confirmed positive correlation between the initial Pirani score and the number of casts required to correct the deformity (r = 0.931, p<0.0001). Conclusion: Initial high Pirani score suggests the need for greater number of casts to achieve correction and probable need for tenotomy. The number of casts required in achieving complete correction increases with increase in the initial Pirani score. The initial high hindfoot score (2.5-3) signifies the probable need of a minor surgical intervention of percutaneous tendoachilles tenotomy. Based on the initial Pirani score, parents can be informed about the probable duration of treatment and the need for tenotomy.

Methods: Among the patients who underwent TSA, 119 shoulders were retrospectively analyzed. Preoperative and postoperative clinical outcome data were collected. Linear regression analysis (univariate and multivariate) was conducted to evaluate the associations of clinical outcomes with age. Kaplan-Meier curves and Cox regression analyses were performed to evaluate implant survival. Results: At final follow-up, patients of all ages undergoing aTSA experienced significant and sustained improvements in all primary outcome measures compared with preoperative values. Based on multivariate analysis, age at the time of surgery was a significant predictor of postoperative outcomes. Excellent implant survival was observed over the course of this study, and Cox regression survival analysis indicated age and sex to not be associated with an increased risk of implant failure. Conclusions When controlling for sex and follow-up duration, older age was associated with significantly better patient-reported outcome measures. Despite this difference, we noted no significant effects on range of motion or implant survival.Level of evidence: IV.