Evaluating the potential mediating role of ADAMTS13 activity in the relationship between obesity and the severity of COVID-19: A retrospective cohort study.

Obesity and low enzyme A disintegrin and metalloproteinase with thrombospondin type-1 motif-13 (ADAMTS13) activity have been linked to poor coronavirus disease 2019 (COVID-19). Given that obesity may influence ADAMTS13 activity, it is feasible; however, it remains unclear whether ADAMTS13 activity acts as a mediator between obesity and COVID-19 outcomes. We investigated the link between body mass index (BMI) and COVID-19 outcomes, using ADAMTS13 activity as a mediator. ADAMTS13 activity was measured in 86 hospitalized COVID-19 patients. BMI, ADAMTS13 activity, and COVID-19 outcomes were assessed. Obese patients had a high odds ratio for low ADAMTS13 levels. When different levels of ADAMTS13 activity were considered, the severity of COVID-19 in obese patients was 4.5 times that in the normal BMI group. Furthermore, increased coagulopathy indicators correlated with low ADAMTS13 activity. Patients with elevated ALT and AST levels showed a 3 to 4-fold increase in the chances of low ADAMTS13 activity (OR:3.19, 95% CI:1.22-8.90, P = .021; OR:2.17, 95% CI:0.91-5.27, P = .082, respectively). When ADAMTS13 activity was considered, obese patients had greater COVID-19 severity and slower viral clearance than those with normal BMI. Low ADAMTS13 activity and impaired liver function are associated with poor COVID-19 outcomes. These findings encourage researchers to use molecular component identification to study the effects of obesity on the von Willebrand factor (VWF)/ADAMTS13 axis, COVID-19 pathogenesis, and outcomes.

Comparison Between Fast-Track and Conventional Anesthesia for Children Undergoing Closure of Ventricular Septal Defects: A Systematic Review and Meta-Analysis.

Ventricular septal defect (VSD) is common in pediatric patients. This study aimed to evaluate the safety and effectiveness of using fast-track anesthesia and comparing it to traditional anesthesia, among children undergoing a transthoracic device closure for VSD. A systematic review following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. Relevant literature was identified through specific search terms in the Scopus, Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (Embase), Web of Science, The Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases. The inclusion criteria focused on observational studies that compared fast-track anesthesia with conventional anesthesia in pediatric VSD closure cases. Data extraction, quality assessment, and meta-analysis were performed using standard differences in means. Initially, 6,535 papers were identified, and subsequent screening of titles and abstracts led to the inclusion of four retrospective studies from a total of 51 studies. The analysis encompassed 477 patients, with 235 in the fast-track anesthesia group and 242 in the conventional anesthesia group. No statistically significant disparities were observed between the two groups concerning the operative duration and hemodynamic variations post-intubation or post-procedure (P >0.05). Nevertheless, the fast-track anesthesia group demonstrated significantly reduced healthcare expenses as well as shorter periods of mechanical ventilation, ICU stay, and overall hospitalization compared to conventional anesthesia (P <0.05). The use of fast-track anesthesia in combination with transthoracic device closure for VSD demonstrates a safe and effective approach for pediatric patients. This approach results in reduced healthcare costs (10,000 Renminbi (RMB)) and shorter durations of mechanical ventilation, ICU admission, and hospitalization compared to conventional anesthesia. Further clinical trials are necessary to confirm these results and assess long-term outcomes.

Interleukin-6 and the determinants of severe COVID-19: A retrospective cohort study.

Cytokines, notably interleukin-6 (IL-6), increase considerably in patients with severe corona virus disease 2019 (COVID-19). This vigorous immune response may cause end-organ failure or death; hence, measuring IL-6 in the context of patient characteristics may help predict outcomes and encourage early comprehensive therapy. This study investigated the association between serum IL-6 levels, COVID-19 severity, and demographic, clinical, and biochemical characteristics. COVID-19 inpatients in NMC hospitals were investigated between November 2020 and November 2021. Several patient variables related to serum IL-6 and COVID-19 severity have been examined. The study included 374 COVID-19 inpatients, 235 of whom had severe disease with a median age of 51. The elderly had an increased risk of severe COVID-19 (73.8%) compared with young adults (71%), with higher white blood cells, D-dimer, Lactate dehydrogenase, creatinine, ferritin, prothrombin time, Procalcitonin, and fibrinogen levels (P < .001). C-reactive protein, troponin, intensive care unit admission, disease severity score, and mortality were significantly associated with higher serum IL-6 levels (P = .05) in the univariate analysis, but this significance disappeared in the multivariate analysis. IL-6, along with other demographic and clinical variables affected COVID-19 severity. These characteristics may predict patients at risk of severe disease and assist in establishing early comprehensive disease outcome strategies. Large-scale clinical research is needed to emphasize IL-6 and COVID-19.

Demystifying Ocular Syphilis - A Major Review.

Syphilis, caused by the spirochaete, Treponema pallidum, continues to be a public health challenge globally with its rates steadily increasing in the past few years. The disease is transmitted through small breaks in the skin during sexual contact, or via congenital transmission in utero, either across the placenta or by contact with an active genital lesion during delivery. Estimated 5.7-6 million new cases are detected every year worldwide in the 15-49 years age group. An increased incidence has been reported in most populations with particular clusters in special groups like men who have sex with men, female sex workers, and their male clients. Ocular syphilis has a varied presentation and is considered a great mimicker in all cases of uveitis. The laboratory diagnosis of syphilis is predominantly based on serological tests including TPHA and VDRL. Parenteral penicillin is the cornerstone of treatment for all stages of ocular syphilis.

Role of Swept source optical coherence tomography in management of acute Vogt-Koyanagi-Harada's disease.

Purpose: To evaluate the role of swept-source optical coherence tomography (SS-OCT) in the management of acute Vogt-Koyanagi-Harada's (VKH) disease. Methods: Retrospective analysis of SS-OCT images of acute VKH patients between January 2015 and February 2020 in a tertiary eye care hospital. Results: We studied 34 eyes of 17 patients with acute probable VKH disease. The mean age was 31.6 ± 10.4 years. Twelve patients were women. The mean follow-up was 17.1 ± 9.3 months. The mean visual acuity was 0.86 logMAR (Snellen equivalent: 6/45) at presentation and 0.18 logMAR (Snellen equivalent: 6/9) at the last follow-up. The mean subfoveal choroidal thickness (SFCT) was 784.97 microns at presentation, 431.40 microns at the first month of therapy, 453.94 microns at six months of therapy, and 405.83 microns at the last follow-up. Qualitative features noted on SS-OCT on presentation was subretinal fluid (SRF) in 29 (85%) eyes, subretinal hyperreflective dots in 34 (100%) eyes, subretinal septa in 33 (97%) eyes, RPE undulations in 21 (61.7%) eyes, posterior vitreous cells in 34 (100%) eyes, SRF around disc in 9 (26%) eyes, and disc swelling in 34 (100%) eyes. At the end of 1 year of follow-up, RPE undulations were absent in 30 eyes (88%) and disc swelling was notably absent in all 34 eyes (100%), though SRF around disc was noted in 4 eyes (11.7%) of 2 patients who had recurrences. Conclusion: SFCT, SRF around disc, RPE undulation, and disc swelling may be important indicators on SS-OCT to guide therapy and prognosticate recurrences in acute VKH.

Ultrasound biomicroscopy as a tool in the evaluation and management of ocular hypotony in uveitis.

PURPOSE: Chronic uveitis can lead to hypotony that may result in severe visual impairment. We highlight the use of ultrasound biomicroscopy (UBM) as an imaging tool to decide the modality of therapy and management of uveitic hypotony. METHODS: This was a retrospective hospital-based interventional case-series study that included a total of 36 eyes of 25 patients with uveitic hypotony seen between January 1997 and January 2020. RESULTS: Thirty-six eyes of 25 patients with uveitic ocular hypotony were included. Unilateral involvement was seen in 56%. The median age of presentation was 21 years with a median follow-up of 21.5 months. Anterior uveitis was noted in 13.88%, intermediate uveitis in 52.77%, and panuveitis in 33.33% eyes. UBM findings commonly noted were pars plana membranes, supraciliary effusion, blunted ciliary process, and ciliary body traction. Other findings included ciliochoroidal detachment and ciliary body edema. Moreover, 22.2% eyes were managed with medical therapy alone, whereas 77.8% eyes received both medical and surgical intervention based on UBM findings. Furthermore, 66.7% eyes showed improvement in intraocular pressure, 13.9% eyes maintained the same IOP, whereas 19.4% eyes had worsening of IOP at final follow-up. CONCLUSION: We found UBM as a useful imaging tool in evaluating and judiciously deciding the mode of management of uveitic hypotony.

Utility of Treponemal Testing from Aqueous Fluid in the Diagnosis of Ocular Syphilis in Patients with HIV/AIDS.

PURPOSE: Ocular syphilis is re-emerging globally especially in patients with human immunodeficiency virus (HIV). Atypical manifestations of ocular syphilis and/or other associated opportunistic infections often lead to a diagnostic dilemma. We evaluated the utility of aqueous humor (AH) Treponema pallidum hemagglutination assay (TPHA) titers in the diagnosis of ocular syphilis. METHODS: Retrospective case series of five HIV positive patients with positive syphilis serology in whom AH sampling was performed. All patients had ocular manifestations suspicious of infectious etiology. RESULTS: Panuveitis with/without retinitis was the commonest presentation. Along with blood investigations, polymerase chain reaction (PCR) testing from AH was done for Mycobacterium tuberculosis (MTB), Herpes Simplex Virus (HSV), Varicella Zoster Virus (VZV), Cytomegalovirus (CMV), and Toxoplasma gondii. In addition, serum antibody titers for Toxoplasma, rapid plasma reagin (RPR) and TPHA tests for syphilis were done. In patients with raised serum RPR/TPHA, aqueous TPHA titers were also assessed. Mean serum RPR titer was ≥ 1:32 and TPHA titer was ≥1:1280. Aqueous humor titers of TPHA was high in all patients (range ≥ 1:320 to ≥1:5120). Aqueous PCR was negative for all other infectious etiologies in four patients. In one patient, PCR-CMV was also positive, suggestive of a dual infection. Post-treatment with highly active antiretroviral therapy (HAART) and appropriate anti-syphilitic regime, complete resolution of lesions with corresponding fall in the serum RPR/TPHA titers were noted in all patients. CONCLUSIONS: Ocular syphilis with atypical presentations is usually diagnosed based on a positive syphilis serology and by excluding other infectious causes. In the present study, we have shown an excellent correlation between raised AH TPHA titers with serological values and the clinical presentation. Considering the ease of collection of AH in contrast to vitreous fluids, the AH-TPHA assay could potentially be a valuable tool in the diagnosis of ocular syphilis.

Histopathology and Molecular Biology Study of an Eyeball of a Case of Acute Retinal Necrosis.

PURPOSE: To report a histopathology and molecular biology study of an eyeball of a case of acute retinal necrosis (ARN). METHODS: Histopathology, immunohistochemistry and molecular biology of an enucleated globe of acute retinal necrosis 6 years after the onset of ARN. RESULTS: Histopathology showed persistence of chronic inflammatory cells with herpes virus inclusion body. Semi nested polymerase chain reaction showed varicella zoster virus. CONCLUSIONS: Chronic inflammatory cells and viral genome can be persistent even after 6 years after the onset of ARN.

Prognostication of the neurological outcome of tethered cord based on intraoperative neuromonitoring findings: how close can we get?

PURPOSE: To evaluate the correlation of intraoperative neuromonitoring (IONM) data in surgery for tethered cord syndrome (TCS) in children to the neurological outcome at 1-year follow-up. METHODS: 208 consecutive patients operated on for TCS, between January 2011 to February 2020, under electrophysiological monitoring in the Division of Paediatric Neurosurgery, AIMS, Kochi, India, were included. Their preoperative neurological, urological and orthopaedic status were compared with the postoperative status at 1 year follow-up. RESULTS: Our study prospectively collected the IONM data and retrospectively correlated it to the children's neurological outcome on follow-up. Out of 208 children, 28% (n = 59/208) had motor, 35% (n = 73/208) had bladder and 26% (n = 54/208) had bowel disturbances. Postsurgery, at one-year follow-up, 91% (n = 52/57) of the patients who had motor deficits had improvement, 82.3% (n = 51/62) of patients who had bladder deficits showed an improvement, and 88.8% (n = 48/54) with bowel deficits showed improvement. The monitorability for motor and sphincter potentials were 99.4% and 89.3%, respectively. Except for four patients (3 with bladder and 1 with motor worsening), all the patients who were monitorable with no deficits remained intact except for four patients, all the patients who had deficits and were monitorable improved after detethering (at 1 year). Clinical worsening corresponded to those who had a drop in amplitude of baseline TcMEP (n = 4). 18 events showed an increase in amplitude compared to the baseline TcMEP. These patients improved clinically on follow-up (at 1 year). CONCLUSIONS: IONM complements the preoperative clinical details in predicting immediate and long-term outcomes.

Human immunodeficiency virus and intraocular inflammation in the era of highly active anti retroviral therapy - An update.

Intraocular inflammation in patients with human immunodeficiency virus (HIV) infection is commonly due to infectious uveitis. Ocular lesions due to opportunistic infections (OI) are the most common and have been described extensively in the pre highly active antiretroviral therapy (HAART) era. Many eye lesions were classified as acquired immunodeficiency syndrome (AIDS) defining illnesses. HAART-associated improvement in immunity of the individual has changed the pattern of incidence of these hitherto reported known lesions leading to a marked reduction in the occurrence of ocular OI. Newer ocular lesions and newer ocular manifestations of known agents have been noted. Immune recovery uveitis (IRU), the new menace, which occurs as part of immune recovery inflammatory syndrome (IRIS) in the eye, can present with significant ocular inflammation and can pose a diagnostic and therapeutic challenge. Balancing the treatment of inflammation with the risk of reactivation of OI is a task by itself. Ocular involvement in the HAART era can be due to the adverse effects of some systemic drugs used in the management of HIV/AIDS. Drug-associated retinal toxicity and other ocular side effects are being increasingly reported. In this review, we discuss the ocular manifestations in HIV patients and its varied presentations following the introduction of HAART, drug-associated lesions, and the current treatment guidelines.

Tubercular panophthalmitis in a patient with human immunodeficiency virus infection: Proven clinicopathologically and by molecular diagnostic tests.

Ocular tuberculosis (OTB) in patients with human immunodeficiency virus (HIV) commonly presents as choroidal tubercles or granuloma. We report a rare presentation of OTB with hypopyon granulomatous uveitis in a patient with HIV on highly active antiretroviral therapy (HAART). Aqueous humor polymerase chain reaction (PCR) was positive for Mycobacterium tuberculosis (MTB). Antitubercular therapy (ATT) was initiated despite which it progressed to scleral abscess and panophthalmitis. Enucleation with ball implantation was done. Histopathology revealed caseating granuloma with numerous acid-fast bacilli (AFB) and real-time PCR showed increased copies of MTB genome. After a full course of ATT, he had stable ocular and systemic condition at final follow-up.

Coats-like response in tubercular subretinal abscess masquerading as melanoma as the initial manifestation of miliary tuberculosis.

Ocular neoplasia can masquerade as an inflammatory condition and vice-versa, which if untreated, can lead to loss of vision or even life. We present a young immunocompetent adult male referred to us as choroidal melanoma. He had a large atypical choroidal mass and exudative retinal detachment. He had no systemic complaints and ocular lesions were the first manifestation of disseminated disease. Aqueous polymerase chain reaction for Mycobacterium tuberculosis (MTB) was negative, but Mantoux, chest radiology, acid-fast bacilli, and caseation necrosis on pleural nodule histopathology confirmed tuberculosis (TB). While on antitubercular therapy, a rare "Coats'-like response" was noted which eventually resolved completely with treatment.

Tubercular subretinal abscess in a pediatric intermediate uveitis patient on methotrexate.

Pediatric intermediate uveitis (IU), usually idiopathic, can also be associated with tuberculosis (TB) and sarcoidosis. A 14-year-old girl was diagnosed with idiopathic IU after ruling out TB and sarcoid. She was treated with oral steroids and methotrexate (MTX) with good inflammation control. One year later, she presented with subretinal (SR) abscess. Lab tests were still negative but aqueous polymerase chain reaction confirmed TB. With antituberculosis treatment, complete resolution of the lesion was noted. The likelihood of a change in phenotype of ocular TB, from an IU to TB SR abscess or a possible reactivation of latent TB due to MTX are discussed.

Metabolomic Markers of Essential Fatty Acids, Carnitine, and Cholesterol Metabolism in Adults and Adolescents with Phenylketonuria.

Background: Individuals with phenylketonuria (PKU) have a risk of cognitive impairment and inflammation. Many follow a low-phenylalanine (low-Phe) diet devoid of animal protein in combination with medical foods (MFs). Objective: To assess lipid metabolism in participants with PKU consuming amino acid MFs (AA-MFs) or glycomacropeptide MFs (GMP-MFs), we conducted fatty acid and metabolomics analyses. Methods: We used subsets of fasting plasma and urine samples from our randomized crossover trial in which participants with early-treated classical and variant (milder) PKU consumed a low-Phe diet combined with AA-MFs or GMP-MFs for 3 wk each. Fatty acid profiles of red blood cell (RBC) membranes were determined for 25 adults (aged 18-49 y) with PKU and 143 control participants. Metabolomics analyses of plasma and urine samples were conducted by Metabolon for 9-10 adolescent and adult participants with PKU and for 15 control participants. Results: RBC fatty acid profiles were not significantly different with AA-MFs or GMP-MFs. PKU participants showed higher total n-6:n-3 (ω-6:ω-3) fatty acids (mean ± SD percentages of total fatty acids: AA-MF = 5.45% ± 1.07%; controls = 4.33%; P < 0.001) and lower docosahexaenoic acid (DHA; AA-MF = 3.21% ± 0.98%; controls = 3.70% ± 1.01%; P = 0.02) and eicosapentaenoic acid (AA-MF = 0.33% ± 0.12%; controls = 0.60% ± 0.43%; P < 0.001) in RBCs than did control participants. Despite higher carnitine intake from AA-MFs than GMP-MFs (mean ± SE intake: AA-MFs = 58.6 ± 5.3 mg/d; GMP-MFs = 0.3 ± 0.01 mg/d; P < 0.001), plasma concentrations of carnitine were similar and not different from those in the control group (AA-MF compared with GMP-MF, P = 0.73). AA-MFs resulted in higher urinary excretion of trimethylamine N-oxide (TMAO), which is synthesized by bacteria from carnitine, compared with GMP-MFs (mean ± SE scaled intensity-TMAO: AA-MFs = 1.2 ± 0.1, GMP-MFs = 0.9 ± 0.1; P = 0.005). Plasma deoxycarnitine was lower in PKU participants than in control participants, suggesting reduced carnitine biosynthesis in PKU (AA-MF = 0.9 ± 0.1; GMP-MF = 1.0 ± 0.1; controls = 1.3 ± 0.1; AA-MF compared with controls, P = 0.01; GMP-MF compared with controls, P = 0.04). Conclusions: Supplementation with DHA is needed in PKU. Carnitine supplementation of AA-MFs shows reduced bioavailability due, in part, to bacterial degradation to TMAO, whereas the bioavailability of carnitine is greater with prebiotic GMP-MFs. This trial was registered at www.clinicaltrials.gov as NCT01428258.