Revisiting Global Health Security Measures in COVID 19 Pandemic

As the world has become a global village with increasing socio-economic interdependence, health, security and stability issues are imposing interrelated global impacts. Thus, activities supporting epidemic and pandemic preparedness are needed to minimize vulnerability to acute public health events. Coordination mechanisms must be pre-established for diagnostics, therapeutics and research as emergencies often lead to competition and shortage of resources. This paper attempts to discuss the available global health security measures at the time of COVID 19 pandemic

Proton pump inhibitors are associated with increased risk of development of chronic kidney disease

Background Acute interstitial nephritis secondary to proton pump inhibitors (PPIs) frequently goes undiagnosed due to its subacute clinical presentation, which may later present as chronic kidney disease (CKD). We investigated the association of PPI use with the development of CKD and death. Methods Two separate retrospective case–control study designs were employed with a prospective logistic regression analysis of data to evaluate the association of development of CKD and death with PPI use. The population included 99,269 patients who were seen in primary care VISN2 clinics from 4/2001 until 4/2008. For evaluation of the CKD outcome, 22,807 with preexisting CKD at the first observation in Veterans Affairs Health Care Upstate New York (VISN2) network data system were excluded. Data obtained included use of PPI (Yes/No), demographics, laboratory data, pre-PPI comorbidity variables. Results A total of 19,311/76,462 patients developed CKD. Of those who developed CKD 24.4 % were on PPI. Patients receiving PPI were less likely to have vascular disease, COPD, cancer and diabetes. Of the total of 99,269 patients analyzed for mortality outcome, 11,758 died. A prospective logistic analysis of case–control data showed higher odds for development of CKD (OR 1.10 95 % CI 1.05–1.16) and mortality (OR 1.76, 95 % CI 1.67–1.84) among patients taking PPIs versus those not on PPIs. Conclusions Use of proton pump inhibitors is associated with increased risk of development of CKD and death. With the large number of patients being treated with proton pump inhibitors, healthcare providers need to be better educated about the potential side effects of these medications

FUTURISTIC SCPOPE OF BIOMARKERS IN TUBERCULOSIS

ABSTRACTOne of the major causes of the mortality from single infectious agent, tuberculosis (TB) is prevalent worldwide. India has the highest number of TBcases in the world. It is the leading cause of death, because of its high mortality and morbidity because of the disease. Reason lies in the emergenceof multidrug-resistant TB strains, and the HIV infection, which reactivates the latent TB making it more severe. Moreover, failure to diagnose TBearly remains one of the primary hurdles in controlling of the disease. TB is a potentially hazardous infectious disease attacks various organs, mainlyaffecting lungs. The bacteria causing TB are spread from one person to another. Tiny droplets released into the air via coughs and sneezes lead to thepassage of infection. The disease is generally diagnosed by its symptoms, radiographic methods, and sputum smear microscopy and by cultivation ofthe Mycobacterium tuberculosis, which is considered as gold standard. Current advances in molecular biology and molecular epidemiology and a betterunderstanding of drug resistance in TB have given a new horizon to its rapid diagnosis. However, the cost-effective techniques, and their requirementfor sophisticated equipment and skilled personals have excluded their implementation on a routine basis, especially in low-income countries.Keywords: Biochemical markers, Tuberculosis, Microbiological tuberculosis

Comparison of Topical Oxygen with Vacuum Assisted Closure in Wound Healing in a Low Resource Setting

Background: The aim of this pilot study is to obtain preliminary results comparing topical oxygen therapy (TOT) and vacuum assisted closure (VAC)  in terms of its ability to accelerate wound healing.Methods: This non-randomised prospective study included patients with age 16-50 years, wound size ≥ 16cm2 and present below knee joint within  seven days of occurrence. Bates-Jensen wound assessment tool (BWAT) was used for evaluation at 8-day interval along with percent area reduction  at final follow up.Results: Mean number of cycles required in VAC and TOT group were 1.97 (range 1-3) and 2.1 (range 1-3) (each cycle of 5 days) per patient  respectively. Percent area reduction was significantly higher in the VAC group (34±9.7%) than TOT (11.3±3.8%) group at final follow up (p<0.05). TOT  patients had better improvement in epithelialization compared to VAC at last follow up. More extensive debridement was needed in patients of TOT  than VAC. There was no significant difference between final score in both groups.Conclusion: TOT appears to be comparable to well-established VAC in treatment of fresh traumatic wounds below the knee joint.  Further large scale,  multicentric and randomised studies comparing both these modalities of treatment should be the way forward.&nbsp

Treatment of femoral shaft fractures in young children by Ender’s nail: indications & complications

Background: Treatment of femoral fractures in age group of 6 – 12 years is controversial. Operative treatment is becoming better accepted. Various modalities of fixation include plate osteosynthesis, External fixation; Antegrade locked nailing, and flexible intramedullary nailing.Methods: 60 children aged 6-12 years (Average age – 8.2 years) with 66 femoral diaphyseal fractures (61 closed and 05 open) in 60 patients were managed with closed Ender’s nailing. Pathological fractures due to unicameral bone cyst were evident in 5 patients. Femoral shaft fractures at the level proximal to distal three fifth with canal diameter of ≥ 6mm were included in the study. Out of 66 traumatic fractures 42 fractures had stable pattern and 19 had unstable fracture pattern. The results were evaluated clinically and radiologically.Results: All the 42 stable femoral fractures showed bridging callus in a mean time of 3.83 weeks (2.5 to 6.5 weeks). Full weight bearing was possible in a mean time of 4.19 weeks. Radiological union was seen in a mean time of 9.4 weeks. 34 fractures were evaluated by scanogram one year after injury and they revealed lengthening of 0.3cms. All the children returned to their previous level of activities. All the 19 unstable femoral fractures showed bridging callus in a mean time of 5.53 weeks (4 – 8 weeks). Full weight bearing was possible in a mean time of 6.21weeks. Radiological union was seen in a mean time of 12 weeks. 8 patients were readmitted for adjunctive procedures like nail impaction, traction and cast immobilization. 20% patients with unstable group had shortening of 1.3cms and 20% had external rotation of lower limb.Conclusions: Ender’s nailing is simple, cost-effective and minimally invasive procedure in 6-12 years of age. It offers stable fixation with rapid healing. There is prompt return of child to normal activity.

Renal Parameters in Mild, Moderate, and Chronic Cigarette Smokers

Objective: To explore the link between cigarette smoking and kidney function through renal parameter assessment.Methods: The present study was performed at the Department of Biochemistry Santosh Medical College, Ghaziabad, India, from September 2019 to April 2021. In this study, 140 subjects were included, out of which 35 were non-smokers, 35 smoked  <5 cigarette per day, 35 smoked 5-10 cigarette per day, and the remaining 35 smoked more than 10 cigarettes per day.Results: Blood urea, serum creatinine, urinary albumin, and uACR levels were found to increase significantly (p<0.001) in smokers as compared to non-smokers. These increases were higher among chronic cigarette smokers (p<0.001) as opposed to mild and moderate smokers. In contrast, serum uric acid, e-GFR, and urinary creatinine levels decreased significantly (p<0.001) in smokers when compared to non-smokers, with a higher decrease observed in chronic cigarette smokers (p<0.001) as opposed to the mild and moderate cigarette smokers.Conclusion: Alterations in urinary albumin, serum urea, serum creatinine, urinary creatinine, and e-GFR are associated with the risk of renal dysfunction

Radial club hand managed with ulnar osteotomy and centralization of hand: a case report and review

Radial club hand also called radial longitudinal deficiency or radial dyspasia is a preaxial longitudinal failure of formation. As the defect is preaxial it is often associated with thumb hypoplasia or anomaly of the radial aspect of the carpus. It is diagnosed clinically and on X-rays. It is frequently syndromic so it is a must to look for associated congenital anomalies by doing a through clinical examination. The frequency of this anomaly is between 1:50000 to 1:100000 live births. The incidence of all radial ray-deficient limbs, including hypoplastic thumbs alone, is approximately 1:30000. The radial deficiency is bilateral in 50% of the cases and the male:female is 3:2. It includes a wide spectrum of disorders that encompass an absent thumb or thumb hypoplasia, a thin first metacarpal and an absent radius. We report here a 1.5 years old child with isolated type IV radial club hand without any restricted range of motion in elbow managed with osteotomy of ulna and centralization of hand

BODIPY-Caged Photoactivated Inhibitors of Cathepsin B Flip the Light Switch on Cancer Cell Apoptosis

Acquired resistance to apoptotic agents is a long-standing challenge in cancer treatment. Cathepsin B (CTSB) is an enzyme which, among many essential functions, promotes apoptosis during cellular stress through regulation of intracelllular proteolytic networks on the minute timescale. Recent data indicate that CTSB inhibition may be a promising method to steer cells away from apoptotic death towards necrosis, a mechanism of cell death that can overcome resistance to apoptotic agents, stimulate an immune response and promote anti-tumor immunity. Unfortunately, rapid and selective intracellular inactivation of CTSB has not been possible. However, here we report on the synthesis and characterization of photochemical and biological properties of BODIPY-caged inhibitors of CTSB that are cell permeable, highly selective and activated rapidly upon exposure to visible light. Intriguingly, these compounds display tunable photophysical and biological properties based on substituents bound directly to boron. Me2BODIPY-caged compound 8 displays the dual-action capability of light-accelerated CTSB inhibition and singlet oxygen production from a singular molecular entitiy. The dual-action capacity of 8 leads to a rapid necrotic response in MDA-MB-231 triple negative breast cancer cells with high phototherapeutic indexes (\u3e30) and selectivity vs. non-cancerous cells that neither CTSB inhibition nor photosensitization gives alone. Our work confirms that singlet oxygen production and CTSB inactivation is highly synergistic and a promising method for killing cancer cells. Furthermore, our ability to trigger intracellular inactivation of CTSB with light will provide researchers with a powerful photochemical tool for probing biochemical processes on short timescales

A Comparison of Measured Creatinine Clearance versus Calculated Glomerular Filtration Rate for Assessment of Renal Function before Autologous and Allogeneic BMT

AbstractCommon blood and marrow transplantation (BMT) eligibility criteria include a minimum glomerular filtration rate (GFR) that may vary by regimen intensity. GFR is often estimated by measurement of creatinine clearance in a 24-hour urine collection (24-hr CrCl), an inconvenient and error-prone method that overestimates GFR. The study objectives were to determine which of 6 GFR calculations: Cockroft-Gault (CG), modified CG (mCG), Modification of Diet in Renal Disease 1 (MDRD1), MDRD2, Jelliffe, and Wright, consistently underestimated measured 24-hr CrCl pre-BMT. We retrospectively analyzed 98 consecutive allogeneic (n = 48) or autologous (n = 50) adult BMT patients from January 2006 to April 2007. All 6 formulas were significantly (P < .001) correlated with 24-hr CrCl with R = 0.64 (Wright), 0.63 (CG), 0.61 (mCG), 0.61 (Jelliffe), 0.54 (MDRD2), and 0.50 (MDRD1). When compared to the measured 24-hr CrCl, MDRD2 consistently underestimated it in the highest proportion of patients (66%, P < .001), compared with MDRD1 (65%, P < .001), Jelliffe (61%, P = NS), mCG (55%, P = NS), Wright (34%, P < .001), and CG (34%, P = .001). Measured 24-hr CrCl, pre-BMT serum Cr, and all 6 equations were not predictive of renal regimen-related toxicity (RRT) post-BMT. The Wright and CG formulas are closest to, but overestimate 24-hr CrCl in 66% of patients. In comparison, MDRD2 consistently underestimates 24-hr CrCl in 66%. Although MDRD2 is the most conservative formula, all 6 formulas gave reasonable estimates of GFR and any of the 6 equations can replace the measured 24-hr CrCl. Larger analyses and transplantation of patients with GFR <50 mL/min may better define subgroups at risk for renal RRT

Urine tumor DNA detection of minimal residual disease in muscle-invasive bladder cancer treated with curative-intent radical cystectomy: A cohort study

BACKGROUND: The standard of care treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy, which is typically preceded by neoadjuvant chemotherapy. However, the inability to assess minimal residual disease (MRD) noninvasively limits our ability to offer bladder-sparing treatment. Here, we sought to develop a liquid biopsy solution via urine tumor DNA (utDNA) analysis. METHODS AND FINDINGS: We applied urine Cancer Personalized Profiling by Deep Sequencing (uCAPP-Seq), a targeted next-generation sequencing (NGS) method for detecting utDNA, to urine cell-free DNA (cfDNA) samples acquired between April 2019 and November 2020 on the day of curative-intent radical cystectomy from 42 patients with localized bladder cancer. The average age of patients was 69 years (range: 50 to 86), of whom 76% (32/42) were male, 64% (27/42) were smokers, and 76% (32/42) had a confirmed diagnosis of MIBC. Among MIBC patients, 59% (19/32) received neoadjuvant chemotherapy. utDNA variant calling was performed noninvasively without prior sequencing of tumor tissue. The overall utDNA level for each patient was represented by the non-silent mutation with the highest variant allele fraction after removing germline variants. Urine was similarly analyzed from 15 healthy adults. utDNA analysis revealed a median utDNA level of 0% in healthy adults and 2.4% in bladder cancer patients. When patients were classified as those who had residual disease detected in their surgical sample (n = 16) compared to those who achieved a pathologic complete response (pCR; n = 26), median utDNA levels were 4.3% vs. 0%, respectively (p = 0.002). Using an optimal utDNA threshold to define MRD detection, positive utDNA MRD detection was highly correlated with the absence of pCR (p \u3c 0.001) with a sensitivity of 81% and specificity of 81%. Leave-one-out cross-validation applied to the prediction of pathologic response based on utDNA MRD detection in our cohort yielded a highly significant accuracy of 81% (p = 0.007). Moreover, utDNA MRD-positive patients exhibited significantly worse progression-free survival (PFS; HR = 7.4; 95% CI: 1.4-38.9; p = 0.02) compared to utDNA MRD-negative patients. Concordance between urine- and tumor-derived mutations, determined in 5 MIBC patients, was 85%. Tumor mutational burden (TMB) in utDNA MRD-positive patients was inferred from the number of non-silent mutations detected in urine cfDNA by applying a linear relationship derived from The Cancer Genome Atlas (TCGA) whole exome sequencing of 409 MIBC tumors. We suggest that about 58% of these patients with high inferred TMB might have been candidates for treatment with early immune checkpoint blockade. Study limitations included an analysis restricted only to single-nucleotide variants (SNVs), survival differences diminished by surgery, and a low number of DNA damage response (DRR) mutations detected after neoadjuvant chemotherapy at the MRD time point. CONCLUSIONS: utDNA MRD detection prior to curative-intent radical cystectomy for bladder cancer correlated significantly with pathologic response, which may help select patients for bladder-sparing treatment. utDNA MRD detection also correlated significantly with PFS. Furthermore, utDNA can be used to noninvasively infer TMB, which could facilitate personalized immunotherapy for bladder cancer in the future