Adjunctive Intravitreal Anti-vascular Endothelial Growth Factor and Moxifloxacin Therapy in Management of Intraocular Tubercular Granulomas.

PURPOSE: To report pre and post treatment levels of VEGF-A in the aqueous humour of patients with intraocular tubercular granulomas and study the effect of a combined intravitreal anti-VEGF bevacizumab and moxifloxacin therapy on their regression. METHODS: Aqueous samples of 10 consecutive patients with intraocular tubercular granulomas obtained before and after initiating treatment were subjected to ELISA for analysing intraocular VEGF-A levels. Intravitreal injections of bevacizumab and moxifloxacin were given weekly till complete regression of these granulomas. All patients received the usual four-drug ATT and oral corticosteroids. RESULTS: Mean baseline VEGF-A level was 1004.27±411.40 pg/ml (401.32-1688.95) that reduced significantly to 27.62±46.86 pg/ml (6.9-131.83) at the last injection. Meannumber of intravitreal injections was 3.1 (2-4). We found significant correlation of decreasing levels of aqueous VEGF-A with the clinical regression of these tubercular granulomas. CONCLUSIONS: Intraocular TB granulomas have high levels of VEGF-A. Weekly intravitreal injections of anti-VEGF bevacizumab with moxifloxacin as an adjunct to the standard care may cause prompt regression of tubercular granulomas. ABBREVIATIONS: TB: Tuberculosis; IOTB: Intraocular tuberculosis; VEGF: Vascular endothelial growth factor; RD: Retinal detachment; Mtb: Mycobacterium tuberculosis; ATT: Antitubercular therapy; AMD: Age-related macular degeneration; SRF: Subretinal fluid; ELISA: Enzyme immunosorbent assay; PCR: Polymerase chain reaction; ONH: Optic nerve head; MDR-TB: Multidrug-resistant tuberculosis; pg/ml: picogram/milliliter; ESR: Erythrocyte sedimentation rate; CECT: Contrast enhanced computed tomography; DNA: Deoxyribonucleic acid; RNA: Ribonucleic acid; BSL: Biosafety level; BCVA: Best corrected visual acuity; HM: Hand movements; KP: Keratic precipitates; PSC: Posterior subcapsular cataract; PS: Posterior synechiae; CRA: Chorio-retinal atrophy; IVMP: Intravenous methyl prednisolone; OCT: Optical coherence tomography; RPE: Retinal pigment epithelium; FFA: Fundus fluorescein angiography; ICG: Indocyanine angiography; RAP: Retinal arterial proliferans.

Potential effects of lowering the threshold of statistical significance in the field of chronic rhinosinusitis - A meta-research on published randomized controlled trials over last decade

Abstract Objective: To evaluate the impact of change in p-value threshold from 0.05 to 0.005, on published Randomized Controlled Trials (RCTs) over the last ten years in the field of chronic rhinosinusitis. Methods: A search of the PubMed database from 1st January 2011 to 31st December 2020 was conducted to include all RCTs that used p-value to determine the effects of an intervention. Data extracted included p-values, type of intervention, publishing journal with indexing, registration, funding, and multi- or single center status. The proportion of primary endpoints having p < 0.005 was determined first, followed by those with p > 0.005 but <0.05. Logistic regression analysis was used to determine if any trial characteristic was associated with reporting of significant p-values. Results: In total, 168 primary endpoints were identified from 123 RCTs. On analysis, 80 had a p-value <0.05, i.e., statistically significant on conventional parameter. Out of these, 53.75% had a p-value <0.005, which would retain significance under the proposed threshold, and the remaining 46.25% to be reclassified as ''suggestive''. None of the trial characteristics were contributing to reporting of conventional or proposed p-values on logistic regression analysis. Conclusion: Lowering the p-value threshold would render 46.25% of a decade of published RCTs results (in the field of CRS) to be reclassified as merely ''suggestive'' and not significant. Trial characteristics were not found contributing to reporting of p-value <0.005 or even <0.05. Level of evidence: II.

Does Femoral Intercondylar Notch Volume Differ in Anterior Cruciate Ligament-Injured Adult Patients Compared to the Uninjured?: A Meta-Analysis.

BACKGROUND: Stenotic femoral intercondylar notch is considered as a risk factor for anterior cruciate ligament (ACL) injury and three-dimensional notch volume is used as a marker for the injury. The primary purpose of this study was to assess the difference in notch volume between the ACL-injured and uninjured in men and women combined or stratified by sex. The secondary purpose was to assess the difference in notch volume between the ACL-intact men and women. METHODS: A search of PubMed/Medline, Scopus, Google Scholar, and Cochrane databases from inception to December 9, 2020, was conducted without restrictions using the following terms: ACL, notch, volume, notch volume, femoral notch volume, and intercondylar notch volume. Studies that compared the ACL-injured with uninjured controls were included. Independent extraction of articles by two authors using predefined data fields including study quality indicators was done. All pooled analyses were based on the inverse-variance weighted random effects model and mean difference was chosen as the effect measure. RESULTS: Nine studies (1,169 knees) qualified for overall analysis (both sexes combined) and significant heterogeneity was observed, which disappeared after pooling studies with age-sex matched controls and those without. Notch volume in the ACL-injured was 0.75 cm3 (95% confidence interval [CI], 0.53-0.96 cm3), which was smaller than that in the age- and sex-matched controls. Six studies qualified for analysis in men. Notch volume in the ACL-injured men was smaller, especially when non-contact ACL injury was considered (1.40 cm3; 95% CI, 1.08-1.73 cm3). Five studies qualified for analysis in women and ACL-injured women had smaller notch volume irrespective of the mechanism of injury (0.38 cm3; 95% CI, 0.18-0.59 cm3). Notch volume of the uninjured men was larger than that of the uninjured women (1.86 cm3; 95% CI, 1.54-2.18 cm3). CONCLUSIONS: ACL-injured adults have smaller notch volume than the age- and sex-matched controls. Non-contact ACL-injured males have smaller notch volume compared to ACL-intact males. ACL-injured females have smaller notch volume irrespective of the nature of injury. Men have higher notch volume than women. The quality of evidence is very low to low.

Factors affecting urinary outcome after delayed decompression in complete cauda equina syndrome: "A regression model study".

PURPOSE: To evaluate the recovery of urinary functions and the factors predicting urinary recovery, following delayed decompression in complete cauda equina syndrome (CESR) secondary to Lumbar disc herniation (LDH). METHODS: Retrospective study evaluated 19 cases of CESR due to single-level LDH, all presenting beyond 72 h. Mean delay in decompression was 11.16 ± 7.59 days and follow-up of 31.71 ± 13.90 months. Urinary outcomes were analysed on two scales, a 4-tier ordinal and a dichotomous scale. Logistic regression analysis was used for various predictors including delay in decompression, age, sex, radiation, level of LDH, motor deficits, type and severity of presentation. Time taken to full recovery was correlated with a delay in decompression. using Spearman-correlation. RESULTS: Optimal recovery was seen in 73.7% patients and time to full recovery was moderately correlated with a delay in decompression (r = 0.580, p = 0.030). For those with optimal bladder recovery, mean recovery time was 7.43 ± 5.33 months. Time to decompression and other evaluated factors were not found contributory to urinary outcomes on either scales. Three (15.8%) patients had excellent, 11 (57.9%) had good, while 3 (15.8%) and 2 (10.5%) had fair and poor outcomes respectively. CONCLUSIONS: Occurrence of CESR is not a point of no-return and complete recovery of urinary functions occur even after delayed decompression. Longer delay leads to slower recovery but it is not associated with the extent of recovery. Since time to decompression is positively correlated with time to full recovery, early surgery is still advised in the next available optimal operative setting. LEVEL OF EVIDENCE: IV.

Chronology of disc degeneration and facet joint arthritis in lumbar spine is variable - A CT based cross-sectional study.

BACKGROUND: The notion that disc degeneration (DD) always precedes facet joint arthritis (FJA) has held sway for many decades. However, it is not always the case. We hypothesized that DD is not always the first offender studied the prevalence of isolated DD and isolated FJA in the lumbar spine. METHODS: Inter-vertebral discs and bilateral facet joints of lumbar spines of 135 participants were graded. The participants were divided into one of the four categories. 'No degeneration,' 'Isolated disc degeneration without facet joint arthritis,' 'Combined disc degeneration and facet joint arthritis,' and 'Isolated facet joint arthritis without disc degeneration.' Multivariate logistic regression analysis was done to evaluate the predictive factors for spinal degeneration using FJA as a dependent variable while age, sex, BMI, smoking history, and DD as predictor variables. RESULTS: The majority of participants had isolated FJA 64 (47.4%). Combined DD and FJA were noted in 32 (23.7%), isolated DD in 8 (5.9%), while 31(23%) had no degeneration. Only age was found to be significantly contributing to the prediction model in multivariate analysis. CONCLUSION: Our study shows that spinal degeneration may begin either in the disc or in the facet joints depending upon the aetiological factors. It is a vicious circle that may be entered at any point, FJA or DD.

Notch Volume Measured on Magnetic Resonance Imaging Is Better Than 2-Dimensional Notch Parameters for Predicting Noncontact Anterior Cruciate Ligament Injury in Males.

PURPOSE: To evaluate and compare intercondylar notch volume with other 2-dimensional notch parameters (measured on magnetic resonance imaging [MRI]) for prediction of noncontact anterior cruciate ligament (ACL) injury in males. METHODS: Retrospective case-control study in males based on MRI images. The case group consisted of 80 noncontact ACL-injured males and a control group of 80 age- and height-matched ACL-intact males. Inclusion criteria were 18 to 50 years old, full-thickness tear, MRI obtained within 1 year of injury, and ACL tear visually documented during arthroscopy. Multiligamentous, bilateral, or concomitant bony injuries were excluded. Notch volume and 2D parameters in both planes, including notch depth, notch width, intercondylar notch angle, notch-width index, and notch-shape index, were measured on MRI and compared. Slice interval was included in the formula for notch-volume assessment. Bivariate Pearson correlation between notch volume and 2D parameters was estimated. Multivariate conditional logistic regression analysis was used for predictor model. Receiver operating characteristic (ROC) curves were plotted. RESULTS: All MRIs had a standard slice thickness of 3 mm and slice interval of 0.3 mm. Notch volume (P < .001), notch angle in the axial plane (P = .001), and notch width in the coronal plane (P = .009) were significantly smaller in the ACL-injured group. Notch volume had inconsistent and negligible to low correlation with 2D parameters. Notch volume was the only significant contributor in the predictor model (P < .001). ROC curve showed that notch volume had highest area under the curve of 84.1% and optimal cutoff at 7.1550 cm3 (specificity, 88.7%; sensitivity, 65%). CONCLUSION: Significantly smaller intercondylar notch volume is associated with noncontact ACL injury in men and is the most important predictor for such an injury (optimal cutoff of 7.1550 cm3). Two-dimensional notch parameters are inconsistently associated with noncontact ACL injury in men, and none of the 2D parameters can be used as a surrogate for notch volume. Two-dimensional notch parameters fare poorly in predicting noncontact ACL injury in males. Notch volume measurement should include slice interval as a factor. LEVEL OF EVIDENCE: III, retrospective case-control study.

Correlation of vascular endothelial growth factor with the clinical regression of tubercular granuloma.

Tubercular granulomas are a common manifestation of intraocular tuberculosis. These are said to be hypoxic granulomas with increased expression of vascular endothelial growth factor (VEGF). Management of these granulomas includes a combination of antitubercular therapy (ATT) and oral corticosteroids. We report a case of tubercular granuloma with exudative retinal detachment which was treated with weekly intravitreal anti-VEGF and antibiotic injections along with ATT and corticosteroids. The VEGF levels measured paralleled with the clinical regression of the granuloma.

Role of Endoscopic Ultrasound in the Management of Tubercular Uveitis.

PURPOSE: To evaluate the role and safety of endoscopic ultrasound-guided fine-needle aspiration cytology (EUS-FNAC) in patients of tubercular uveitis. DESIGN: Interventional case series Methods: Thirty patients suspected of tubercular uveitis that underwent EUS-FNAC were enrolled in the study. The patient details recorded were age, gender, systemic history, ocular complaints and clinical manifestations. The details of the investigations - skin test, X-Ray chest, CECT (contrast enhanced computed tomography) of chest and findings on EUS-FNAC were also recorded. RESULTS: Thirty patients with suspected tubercular uveitis showed mediastinal lymphadenopathy on CECT-chest and underwent EUS-FNAC. A total of 27 patients showed tubercular lymphadenitis and three patients showed reactive lymphadenopathy. Ziehl-Neelsen (ZN) staining was positive for acid-fast bacilli in four cases and culture was positive in one case. There were no noted complications of EUS-FNAC. CONCLUSION: EUS-FNAC is a safe and efficacious procedure for confirming the diagnosis of tubercular uveitis and should be routinely employed wherever available.

Effects on auditory function of chronic exposure to electromagnetic fields from mobile phones.

The widespread use of mobile phones has given rise to apprehension regarding the possible hazardous health effects of high-frequency electromagnetic fields (EMFs) on auditory function. We conducted a study to investigate the effects of long-term (>4 yr) exposure to EMFs emitted by mobile phones on auditory function. Our study population was made up of 40 healthy medical students-31 men and 9 women, aged 20 to 30 years (mean 22.7). Of this group, 31 subjects typically held their phone to the right ear and 9 to the left ear; the non-phone-using ear served as each subject's control ear. The phone-using subjects were also split into two groups of 20 based on the duration of their daily phone use (≤60 min vs. >60 min). All subjects underwent pure-tone audiometry, speech audiometry, impedance audiometry, and brainstem evoked response audiometry (BERA), and comparisons were made between the phone-using ear and the control ear and between the shorter and longer duration of daily use. We found no statistically significant differences in high-frequency pure-tone average between the phone-using ears and the control ears (p = 0.69) or between the shorter- and longer-duration phone-using ears (p = 0.85). Moreover, statistical analysis of BERA findings revealed no significant differences between the phone-using ears and the control ears in terms of wave I-III, III-V, and I-V interpeak latencies (p = 0.59, 0.74 and 0.44, respectively). None of the subjects reported any subjective symptoms, such as headache, tinnitus, or sensations of burning or warmth behind, around, or on the phone-using ear. We conclude that the long-term exposure to EMFs from mobile phones does not affect auditory function.

How to advocate for the inclusion of chronic kidney disease in a national noncommunicable chronic disease program.

Many countries are developing or refining national strategies for noncommunicable chronic disease (NCD) prevention and control. Chronic kidney disease (CKD) is a cause and consequence of other NCDs; CKD acts as a risk multiplier for all four key NCDs as specified by the World Health Organization; CKD is associated with high health-care costs; CKD is readily identifiable; and treatment of CKD is cost-effective and improves outcomes. These observations argue in favor of including CKD in national NCD programs. The purpose of this article is to outline key steps in advocating for the inclusion of CKD in national NCD strategies.

Multifocal cysticercosis with optical coherence tomography findings in a child.

We herein report a case with multifocal cysticercosis--sub-conjunctival cysticercus cyst, sub-retinal cysticercosis, and neurocysticercosis in a child. The optical coherence tomography (OCT) findings of the sub-retinal cysticercus cyst are reported. He was treated with anti-helminthic drugs and oral prednisolone followed by surgical removal of the sub-retinal cyst. He subsequently underwent silicone oil removal with lens aspiration and intraocular lens implantation maintaining stable vision.

Serum adiponectin and cardiovascular risk in chronic kidney disease and kidney transplantation.

BACKGROUND: Serum adiponectin is inversely linked to obesity, impaired glucose homeostasis, dyslipidemia and hypertension and has been suggested as a possible marker of cardiovascular (CV) disease in the general population. However, its role in chronic kidney disease and following renal transplantation is not well established. METHODS: This study examined the relationship of adiponectin with CV risk factors and kidney function in patients with predialysis chronic kidney disease (CKD) (n=33) and those who had undergone a renal transplantation (n=43). Serum adiponectin was measured using ELISA. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) study formula. Associations of adiponectin with clinical and laboratory parameters were tested. RESULTS: Mean age of the population was 37 +/- 11 years, 83% were men, 18% had diabetes and mean GFR was 48 +/- 29 ml/min per 1.73 m2. Adiponectin levels inversely related with eGFR (p=0.021), body mass index (BMI) (p=0.024), waist circumference (p=0.018) and hemoglobin (p=0.004), and directly related with high-sensitivity C-reactive protein (hsCRP) (p=0.019). It did not correlate with blood pressure, lipids, fasting glucose or smoking. On multivariate analysis, eGFR (beta=-0.360, p=0.002) and BMI (beta=-0.346, p=0.003) were independent determinants of adiponectin, adjusted for age, sex, lipids, diabetes, hypertension and transplant status. Renal transplant patients had lower CV risk, however adiponectin was similar to CKD patients (22 +/- 17 vs. 23 +/- 21; p=0.8). Adiponectin was inversely related to eGFR (p=0.003). CONCLUSION: This is the first study showing that serum adiponectin is a poor predictor of cardiovascular risk in both the CKD and renal transplant population. Serum adiponectin levels are influenced by renal function. Adiponectin levels increased with decreasing kidney function in CKD renal transplant recipients. Despite better CV risk profile, transplant patients had similar adiponectin levels to those of CKD patients. We conclude that adiponectin levels do not reflect the high CV risk in CKD.

Endostatin is a potential inhibitor of Wnt signaling.

Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. To gain insight into ES-mediated signaling, we studied the effects of ES RNA on Xenopus embryogenesis and observed developmental abnormalities consistent with impaired Wnt signaling. ES RNA blocked the axis duplication induced by beta-catenin, partially suppressed Wnt-dependent transcription, and stimulated degradation of both wild-type and "stabilized" forms of beta-catenin, the latter suggesting that ES signaling does not involve glycogen synthase kinase 3. Moreover, ES uses a pathway independent of the Siah1 protein in targeting beta-catenin for proteasome-mediated degradation. ES failed to suppress the effects of T cell-specific factor (TCF)-VP16 (TVP), a constitutive downstream transcriptional activator that acts independently of beta-catenin. Importantly, these data were replicated in endothelial cells and also in the DLD-1 colon carcinoma cells with the mutated adenomatous polyposis coli protein. Finally, suppression of endothelial cell migration and inhibition of cell cycle by ES were reversed by TVP. Though high levels of ES were used in both the Xenopus and endothelial cell studies and the effects on beta-catenin signaling were modest, these data argue that at pharmacological concentrations ES may impinge on Wnt signaling and promote beta-catenin degradation.