A Randomised Controlled Trial Comparing Intratympanic Gentamicin with Methylprednisolone in Meniere's Disease with Good Hearing.

A randomized prospective parallel group trial was done to compare the efficacy of intratympanic low dose gentamicin with methylprednisolone in treating intractable unilateral Meniere's disease with serviceable hearing. STUDY DESIGN: Randomised prospective parallel group trial. SETTING: Tertiary care centre in South India. SUBJECTS AND METHODS: Forty patients with unilateral Meniere's disease and serviceable hearing with vertigo following 6 months of conservative therapy were enrolled between November 2018 and March 2020. Twenty patients were administered with one dose of intratympanic Gentamicin (40 mg/ml) and the other half were given intratympanic Methylprednisolone (40 mg/ml, 4 injections given on alternate days). Pure tone audiogram, speech discrimination score, number of vertigo episodes, dizziness handicap inventory, tinnitus handicap inventory and functional scores were compared before treatment, 3 months later and up to 24 months. There was no significant difference between the two treatments with regard to short term as well as long term DHI scores, THI scores, Functional level score and average pure tone audiogram of patients. In patients with unilateral Meniere's disease who have good hearing, one dose of Gentamicin had equivalent effect to that of four doses of Methylprednisolone in vertigo and tinnitus control, hearing preservation and quality of life.

Ileo-caecal doughnut bladder augmentation in children with exstrophy- epispadias complex- a study of 100 cases.

AIM: The small bladder in failed exstrophy needs to be augmented and also accommodate bladder neck surgery, ureteric re-implantations and a catheterizable channel. We present a novel method of ileocecal bladder augmentation providing a non-implanted, un-detached appendicular channel, rendered non refluxing by an ileal "fundoplication". The colonic segment could receive ureteric reimplantation when bladder plate is unsuitable. MATERIALS AND METHODS: Operative technique: Bilateral cephalo-trigonal reimplantation and bladder neck surgery is done. The ileocecal segment is isolated and arranged as a ring (doughnut) around the un-detached appendix which is made to pass behind the terminal ileum, through the ileal mesentery and then in front of the ileum as it exits as a catheterizable channel. The bowel segment is opened on the antimesenteric aspect except for the retro appendiceal ileal segment. The opened ileo-caecum is reconfigured as a de-tubularised augmentation pouch while the retro appendiceal ileal segment is wrapped around the appendix like a fundoplication. The colon segment may receive the ureteric reimplantation if required. CASE MATERIAL: 100 children (mean age 6.3 years) with failed exstrophy underwent doughnut augmentation (3 neobladders) in 2006-2021. Ninety eight were incontinent, with 30 open/dehisced bladder plate, 48 units were hydronephrotic (HUN), 105 ureters were refluxing (VUR) and eGFR was subnormal in 20 children. 79 children underwent YDL bladder neck plasty and 23 underwent bladder neck closure (primarily in 18). Three infants with HUN did not undergo bladder neck surgery. 126 ureters were reimplanted into the bladder, 44 into the colon segment while 30 were not reimplanted. RESULTS: 95 children are continent on CIC, which was gradually introduced starting with once or twice daily change of indwelling Mitrofanoff catheter leading to regular 3-4 hourly CIC as the child became confident. The appendicular channel was easily catheterizable without any leak in 95, had minor issues in 4 while one necrosed and replaced by a gastric tube. HUN recovered (25/48) or stabilized with a significant reduction in the grade of hydronephrosis (p = 0.001). VUR resolved in 90% of bladder reimplants, 85% of colonic reimplants and 70% of non-reimplanted ureters. In the 20 children with compromised renal function eGFR improved (71-106 ml/m2/min) significantly (p = 0.036) at follow up (mean 5 years). Urodynamics study (N = 33) showed a mean capacity of 95% of expected bladder capacity (EBC) with end filling pressure less than 25 cm of water (Mean end filling cystometric pressure = 15 cm of water). Complications included adhesive intestinal obstruction (N = 16) and bladder calculi (N = 12). CONCLUSION: The doughnut ileocecal augmentation provides a easily catheterizable, non-refluxing, appendicular channel, not requiring isolation of the appendix nor its reimplantation into the bladder. The colonic segment can provide a bed for ureteric reimplantation. Dryness with a good capacity bladder and preserved upper tract is achieved.

Decreased femur tunnel widening after augmented suspensory fixation compared to suspensory fixation for single bundle hamstring ACL reconstruction.

Background: Tunnel widening after Anterior cruciate ligament (ACL) reconstruction using a hamstring graft is known to occur at follow-up. Our study aimed to investigate the effect of suspensory fixation augmentation using an interference screw on tunnel widening in single-bundle hamstring ACL reconstruction. Methods: 48 patients who had single bundle ACL reconstruction with femoral fixed loop fixation technique in 15 knees, and, fixed loop with augmented aperture (bio screw) fixation in 33 knees were analyzed. The width of the tunnel was measured using radiographs immediate post-op and at follow-up within 1 year. Computerized Tomogram (CT) measurements of the tunnels and functional scores were also done with overall follow-up for the fixed loop group being 21.33 months (Standard Deviation (SD)11.14) and the Augmentation group 9.12 months (SD 3.83). Results: Midpoint femur tunnel widening was reduced in the augmentation group, with measurements of 0.74 (SD 1.05) mm Antero Posterior (AP) and 1.01 (SD 1.04) mm in the Lateral view, compared to 1.54 (SD 1.48) mm AP and 1.79 (SD1.47 mm) in the Lateral for the fixed button group. The radiological widening was considerably less in the augmentation group with a p-value of 0.07. AP aperture widening in the augmentation group was 1.25(SD 1.10 mm), and 1.09(SD0.98) mm in the lateral view. The fixed button-only group measured 1.53 (SD1.30) mm in the AP, and 1.65 (SD 1.29) mm in the lateral view, both of which were not statistically significant. The follow-up Lysholm and International Knee Documentation Committee (IKDC) scores were similar for the 2 groups. Conclusion: Femoral tunnel midpoint and aperture widening were reduced with the fixed loop with aperture (bio screw) augmentation technique for hamstring grafts in single bundle ACL fixation within 1 year with comparable functional scores. Level of evidence: 4.

Thyroglossal Duct Cyst Carcinoma: Lessons from a 20-Case Series.

Aims and Objectives: Thyroglossal duct cyst (TDC) is a common congenital cyst with an incidence of about 7%. Thyroglossal duct cyst carcinoma (TDCC) is a rare sequel which arises from TDC and has an incidence of about 1%. As these are rare, they do not have well-defined management guidelines. The aim of this study was to analyse the clinical profile and pathological characteristics of patients with thyroglossal duct cyst carcinoma and to propose a protocol for their treatment and follow-up. Materials and Methods: A retrospective study was done from January 2000 to December 2019. All the clinical details, imaging characteristics, treatment and histopathology were analysed. Results: The mean age group in our study was 37.9 years with a female preponderance. The clinical features like rapid increase in size, fixity of the lump and lymph node metastasis were not very common. Seventy-five percent of our patients who underwent imaging had suspicious characteristics. Fifty-six percent of our patients had FNAC suggestive of TDCC. Fifty percent of our patients had concomitant thyroid carcinoma. None of our patients had distant metastasis at follow-up. Conclusions: TDCC is rare and a disease of young adulthood and usually has good prognosis. It may be a clinical surprise or a small lesion which can be detected with ultrasound and targeted FNAC. There is high rate of concomitant thyroid carcinoma and hence needs careful assessment. Sistrunk's procedure with total thyroidectomy either staged or simultaneously has good outcome and permits adjuvant treatment.

The clinico pathological features and survival in serous endometrial cancers.

Background & Introduction: Serous cancers are a biologically aggressive variety of endometrial cancer (EC) with a high rate of recurrence and mortality among all the subtypes. Herein we describe our experience with serous endometrial cancer. Objective: This study was conducted to identify the clinicopathological characteristics, treatment modalities and survival outcomes in women diagnosed with serous endometrial malignancies. Methods: This was a retrospective descriptive analysis of data on patients diagnosed with serous endometrial tumours between January 2010 to September 2019 in our institute collected from electronic medical records. Descriptive statistics such as proportions, means and standard deviations and Cox regression hazards model on risk factors were performed. Survival was plotted by Kaplan-Meier curves. Results: During the study period, 32 (5.7%) patients out of 564 diagnosed cases of endometrial cancer had serous histology. The mean age at diagnosis was 62.5 years (SD 7.6) while mean BMI was 26.4 kg/m2 (SD 4.6). Staging laparotomy was done in 27(84%) of the patients. Advanced stages (III and IV) were detected in 16 patients (50%) at primary surgery.Adjuvant chemo therapy and radiation was received by 21(65.6%) patients therapy. Out of 32 patients, 13 (40%) developed recurrence while another 13 expired. Stage at diagnosis and type of adjuvant therapy were important factors in determining the outcome. Median recurrence free and overall survival was 22(95% CI 1.4-42) and 36 months (95% CI 10.1-61.8) respectively. Conclusion: Serous endometrial cancers are an intrusive subtype of EC. Comprehensive surgical staging with optimal cytoreduction should be aimed at. Adequate upfront molecular categorization of these tumors is mandated. Adjuvant therapy with chemotherapy and radiation is given in postoperative setting. Targeted therapies and immunotherapy could be considered in recurrences.

Novel patterns of expression and recruitment of new genes on the t-haplotype, a mouse selfish chromosome.

The t-haplotype of mice is a classical model for autosomal transmission distortion. A largely non-recombining variant of the proximal region of chromosome 17, it is transmitted to more than 90% of the progeny of heterozygous males through the disabling of sperm carrying a standard chromosome. While extensive genetic and functional work has shed light on individual genes involved in drive, much less is known about the evolution and function of the rest of its hundreds of genes. Here, we characterize the sequence and expression of dozens of t-specific transcripts and of their chromosome 17 homologues. Many genes showed reduced expression of the t-allele, but an equal number of genes showed increased expression of their t-copy, consistent with increased activity or a newly evolved function. Genes on the t-haplotype had a significantly higher non-synonymous substitution rate than their homologues on the standard chromosome, with several genes harbouring dN/dS ratios above 1. Finally, the t-haplotype has acquired at least two genes from other chromosomes, which show high and tissue-specific expression. These results provide a first overview of the gene content of this selfish element, and support a more dynamic evolutionary scenario than expected of a large genomic region with almost no recombination.

Comparing Intratympanic Gentamicin with Methylprednisolone in Meniere's Disease with Non-Serviceable Hearing.

Abstract: To compare the effectiveness of high dose fixed alternate day intratympanic gentamicin with methylprednisolone in the treatment of patients with unilateral, intractable Meniere's disease with poor hearing. Randomized single blind prospective parallel group trial in a tertiary referral centre. Twenty-two patients with definite unilateral Meniere's disease with average pure tone thresholds worse than 50 dB in the affected ear were enrolled. Eleven patients were treated with intratympanic buffered gentamicin and the other eleven were administered intratympanic methylprednisolone (both 4 injections, 40 mg/ml, on alternate days). Patients were assessed pre-intervention, 3 months post intervention and subsequently followed up for 2-4 years. Both groups of patients had significant control of vertigo, DHI scores and THI scores after treatment while the functional scores in the methylprednisolone group was not better than the pre- treatment scores in the long-term follow-up. 9 of 11(82%) patients in gentamicin group and 3 of 11(27%) patients in the methylprednisolone group achieved Class A vertigo control. The gentamicin group had better post intervention DHI scores (p = 0.016, 3 months and p = 0.046, long term) and Functional score (p = 0.014, 3 months and p = 0.05, long term). The hearing in both groups and THI scores, post intervention was similar between both groups. In patients with unilateral intractable MD with non-serviceable hearing, high fixed doses of both intratympanic gentamicin and methylprednisolone are effective in alleviating disease symptoms in long term follow-up. However, intratympanic gentamicin resulted in better control of vertigo, total DHI score and functional level scores than intratympanic methylprednisolone with no significant difference in hearing levels. Trail Registration Number: Clinical Trials Registry of India (CTRI- REF/2016/10/012363).

Clustering of Activated CD8 T Cells Around Malaria-Infected Hepatocytes Is Rapid and Is Driven by Antigen-Specific Cells.

Malaria, a disease caused by parasites of the Plasmodium genus, begins when Plasmodium-infected mosquitoes inject malaria sporozoites while searching for blood. Sporozoites migrate from the skin via blood to the liver, infect hepatocytes, and form liver stages which in mice 48 h later escape into blood and cause clinical malaria. Vaccine-induced activated or memory CD8 T cells are capable of locating and eliminating all liver stages in 48 h, thus preventing the blood-stage disease. However, the rules of how CD8 T cells are able to locate all liver stages within a relatively short time period remains poorly understood. We recently reported formation of clusters consisting of variable numbers of activated CD8 T cells around Plasmodium yoelii (Py)-infected hepatocytes. Using a combination of experimental data and mathematical models we now provide additional insights into mechanisms of formation of these clusters. First, we show that a model in which cluster formation is driven exclusively by T-cell-extrinsic factors, such as variability in "attractiveness" of different liver stages, cannot explain distribution of cluster sizes in different experimental conditions. In contrast, the model in which cluster formation is driven by the positive feedback loop (i.e., larger clusters attract more CD8 T cells) can accurately explain the available data. Second, while both Py-specific CD8 T cells and T cells of irrelevant specificity (non-specific CD8 T cells) are attracted to the clusters, we found no evidence that non-specific CD8 T cells play a role in cluster formation. Third and finally, mathematical modeling suggested that formation of clusters occurs rapidly, within few hours after adoptive transfer of CD8 T cells, thus illustrating high efficiency of CD8 T cells in locating their targets in complex peripheral organs, such as the liver. Taken together, our analysis provides novel insights into and attempts to discriminate between alternative mechanisms driving the formation of clusters of antigen-specific CD8 T cells in the liver.

Focused Parathyroidectomy Under Local Anesthesia - A Feasibility Study.

PURPOSE: We conducted this study to evaluate the feasibility, patient satisfaction, and cost of performing focused parathyroidectomy under local anesthesia (LA) and mild sedation, administered and monitored by a surgeon. MATERIALS AND METHODS: This was a prospective observational study of 30 patients with primary hyperparathyroidism (PHPT) undergoing a focused parathyroidectomy under LA and mild sedation at a single institution. The clinical features, gland weight, operating time, procedure time, postoperative pain scores, overall patient satisfaction, postoperative nausea and vomiting, analgesic requirements, complications, cost, and cure rates were documented. Data were analyzed using SPSS software version 17.0. RESULTS: In two patients (6.7%), the procedure had to be completed under general anesthesia (GA). Postoperative temporary hypocalcemia was witnessed in 14 of 30 (46.7%), but only 1 required intravenous calcium infusion. About 21 of 30 (75%) were completely satisfied with LA, whereas 25 of 30 (89%) were completely satisfied with surgical procedure. Furthermore, all patients were keen to recommend this procedure under LA to their friends and family. Comparing the cost between performing the procedure under LA with that under GA, a significant difference was witnessed (P = 0.001). Among the 26 patients reviewed at 6 months, all had a normal serum calcium and parathyroid hormone levels indicating 100% cure rate. CONCLUSION: Performing focused parathyroidectomy under LA is feasible; additionally, this method can significantly reduce the cost of the procedure (P = 0.001).

Study to Evaluate the Changes in Polycystic Ovarian Morphology after Naturopathic and Yogic Interventions.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the commonest endocrine disorders in women, with a prevalence ranging from 2.2% to 26% in India. Patients with PCOS face challenges including irregular menstrual cycles, hirsutism, acne, acanthosis nigricans, obesity and infertility. 9.13% of South Indian adolescent girls are estimated to suffer from PCOS. The efficacy of Yoga & Naturopathy (Y&N) in the management of polycystic ovarian syndrome requires to be investigated. Aims: The aim of the present study is to observe the morphological changes in polycystic ovaries of patients following 12 weeks of Y&N intervention. SETTINGS AND DESIGN: The study was conducted at the Government Yoga and Naturopathy Medical College and Hospital, Chennai, India. The study was a single blinded prospective, pre-post clinical trial. METHODS AND MATERIAL: Fifty PCOS patients of age between 18 and 35 years who satisfied the Rotterdam criteria were recruited for the study. According to their immediate participation in the study they were either allocated to the intervention group (n=25) or in the wait listed control group (n=25). The intervention group underwent Y&N therapy for 12 weeks. Change in polycystic ovarian morphology, anthropometric measurements and frequency of menstrual cycle were studied before and after the intervention. Results: Significant improvement was observed in the ovarian morphology (P<0.001) and the anthropometric measurements (P<0.001) between the two groups. CONCLUSIONS: The findings of the study indicate that Y&N interventions are efficient in bringing about beneficial changes in polycystic ovarian morphology. We speculate that a longer intervention might be required to regulate the frequency of menstrual cycle.

Complex History and Differentiation Patterns of the t-Haplotype, a Mouse Meiotic Driver.

The t-haplotype, a mouse meiotic driver found on chromosome 17, has been a model for autosomal segregation distortion for close to a century, but several questions remain regarding its biology and evolutionary history. A recently published set of population genomics resources for wild mice includes several individuals heterozygous for the t-haplotype, which we use to characterize this selfish element at the genomic and transcriptomic level. Our results show that large sections of the t-haplotype have been replaced by standard homologous sequences, possibly due to occasional events of recombination, and that this complicates the inference of its history. As expected for a long genomic segment of very low recombination, the t-haplotype carries an excess of fixed nonsynonymous mutations compared to the standard chromosome. This excess is stronger for regions that have not undergone recent recombination, suggesting that occasional gene flow between the t and the standard chromosome may provide a mechanism to regenerate coding sequences that have accumulated deleterious mutations. Finally, we find that t-complex genes with altered expression largely overlap with deleted or amplified regions, and that carrying a t-haplotype alters the testis expression of genes outside of the t-complex, providing new leads into the pathways involved in the biology of this segregation distorter.

Spectrum of pulmonary valve morphology and its relationship to pulmonary trunk in tetralogy of Fallot.

BACKGROUND: Tetralogy of Fallot (TOF) is a complex congenital heart disease with anatomic variations. Although the pulmonary valve in TOF is abnormal, it has not been studied well, especially on newer imaging modalities such as multidetector computed tomography (CT), which gives excellent anatomic detail. AIMS: The aim of this study was to assess the morphology of pulmonary valve in TOF on CT and evaluate its association with the degree of hypoplasia of infundibulum and pulmonary trunk. MATERIALS AND METHODS: The cardiac CT scans of 30 patients with TOF were reviewed to evaluate the morphology of the pulmonary valve, infundibulum, and pulmonary arteries. Fisher's exact test was performed to examine the association between pulmonary valve morphology and degree of hypoplasia of the infundibulum and pulmonary trunk. RESULTS: 16.7% of patients with TOF had pulmonary atresia. The prevalence of tricuspid, bicuspid, and absent valves were 10%, 53.3% and 6.7%, respectively. In another 13.3% of patients, although valve tissue was present, exact morphology could not be determined on CT. The commissures of 62.5% of the bicuspid valves were at 12 o'clock and 6 o'clock or slightly off the midline. There was statistically significant association between valve morphology and degree of infundibular hypoplasia (P < 0.001) and calibre of pulmonary trunk (P < 0.001). CONCLUSION: Morphological abnormality of the pulmonary valve is common in TOF. The most common type of pulmonary valve in TOF patients is bicuspid valve with commissures at 12 o'clock and 6 o'clock or slightly off the midline. Fewer cusps of the pulmonary valve are associated with a more severe degree of pulmonary artery hypoplasia.

Classification of T cell movement tracks allows for prediction of cell function.

Using a unique combination of visual, statistical, and data mining methods, we tested the hypothesis that an immune cell's movement pattern can convey key information about the cell's function, antigen specificity, and environment. We applied clustering, statistical tests, and a support vector machine (SVM) to assess our ability to classify different datasets of imaged flouresently labelled T cells in mouse liver. We additionally saw clusters of different movement patterns of T cells of identical antigenic specificity. We found that the movement patterns of T cells specific and non-specific for malaria parasites are differentiable with 72% accuracy, and that specific cells have a higher tendency to move towards the parasite than non-specific cells. Movements of antigen-specific T cells in uninfected mice vs. infected mice were differentiable with 69.8% accuracy. We additionally saw clusters of different movement patterns of T cells of identical antigenic specificity. We concluded that our combination of methods has the potential to advance the understanding of cell movements in vivo.

In vivo imaging of CD8+ T cell-mediated elimination of malaria liver stages.

CD8(+) T cells are specialized cells of the adaptive immune system capable of finding and eliminating pathogen-infected cells. To date it has not been possible to observe the destruction of any pathogen by CD8(+) T cells in vivo. Here we demonstrate a technique for imaging the killing of liver-stage malaria parasites by CD8(+) T cells bearing a transgenic T cell receptor specific for a parasite epitope. We report several features that have not been described by in vitro analysis of the process, chiefly the formation of large clusters of effector CD8(+) T cells around infected hepatocytes. The formation of clusters requires antigen-specific CD8(+) T cells and signaling by G protein-coupled receptors, although CD8(+) T cells of unrelated specificity are also recruited to clusters. By combining mathematical modeling and data analysis, we suggest that formation of clusters is mainly driven by enhanced recruitment of T cells into larger clusters. We further show various death phenotypes of the parasite, which typically follow prolonged interactions between infected hepatocytes and CD8(+) T cells. These findings stress the need for intravital imaging for dissecting the fine mechanisms of pathogen recognition and killing by CD8(+) T cells.

Antiirritant properties of polyols and amino acids.

BACKGROUND: Antiirritants are used in cosmetic products to prevent or to treat skin irritations that arise during daily life. Data were published earlier on the efficacy of the best-known humectant, glycerol, in reducing irritation. OBJECTIVE: The aim of the present study was to examine the effects of different polyols (including glycerol, xylitol, and mannitol) and the amino acids taurine and glycine on sodium lauryl sulfate (SLS)-induced skin irritation. METHODS: Healthy adult volunteers were patch-tested with 0.1% SLS in the presence or absence of one or another polyol or amino acid. Skin reactions were evaluated via measurements of transepidermal water loss (TEWL). RESULTS: Glycerol and xylitol significantly suppressed the SLS-induced increase in TEWL, whereas mannitol had no effect on the SLS-induced skin irritation. Taurine also inhibited the SLS-induced increase in TEWL, but glycine was not effective in reducing the SLS-induced irritative response. CONCLUSION: Similar to the action of the well-known antiirritant glycerol, SLS-induced skin irritation is suppressed by xylitol and taurine. These results suggest that these agents might also be effective in preventing irritative dermatitis.

Necrolytic migratory erythema.

BACKGROUND: Necrolytic migratory erythema is considered to be a paraneoplastic dermatosis. The classical symptoms are associated with alpha-cell pancreatic islet cell tumor or 'glucagonoma'. Generally, extracutaneous hallmarks of this disease include weight loss, diabetes, anaemia and diarrhoea. OBSERVATION: We report a case of a 39-year-old woman with a 3-year history of recalcitrant psoriasiform eruption, who had no other associated symptoms on routine examination. Histologic examinations suggested necrolytic migratory erythema. Abdominal computer tomography was performed, which revealed a tumor in the tail of the pancreas. After distal resection of the pancreas her skin symptoms resolved in a few days time. Histology was consistent with glucagonoma. She is clinically well and symptomless and no signs of metastasis after 4 years. CONCLUSIONS: It is infrequent to have only necrolytic migratory erythema, hyperglucagonaemia and islet-cell tumor but no other extracutaneous symptoms in glucagonoma syndrome. To our knowledge, ours is the second such case reported in the literature. Skin symptoms are important, often they are the clue to the diagnosis of glucagonoma syndrome.