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Temporal changes in childhood cancer incidence and survival by stage at diagnosis in Australia, 2000-2017.
Youlden, DR, Baade, PD, Frazier, AL, Gupta, S, Gottardo, NG, Moore, AS, Aitken, JF
Acta oncologica (Stockholm, Sweden). 2023;(10):1256-1264
Abstract
BACKGROUND The Toronto Paediatric Cancer Stage Guidelines are a compendium of staging systems developed to facilitate collection of consistent and comparable data on stage at diagnosis for childhood cancers by cancer registries. MATERIAL AND METHODS This retrospective, observational cohort study investigated changes in stage-specific incidence and survival for children diagnosed between 2000-2008 compared to 2009-2017 using the population-based Australian Childhood Cancer Registry. Information on mortality for each patient was available to 31st December 2020. Shifts in incidence by stage were evaluated using chi-square tests, and differences in stage-specific five-year observed survival for all causes of death over time were assessed using flexible parametric models. RESULTS Stage was assigned according to the Toronto Guidelines for 96% (n = 7944) of the total study cohort (n = 8292). Changes in the distribution of incidence by stage between the two diagnosis periods were observed for retinoblastoma, with stage 0 increasing from 26% to 37% of cases (p = 0.02), and hepatoblastoma, with metastatic disease increasing from 22% to 39% of cases (p = 0.04). There were large gains in stage-specific survival over time for stage IV rhabdomyosarcoma (five-year adjusted mortality hazard ratio for 2009-2017 compared to 2000-2008 of 0.38, 95% CI 0.19-0.77; p = 0.01), stage M3 for medulloblastoma (HR = 0.41, 95% CI 0.21-0.79; p = 0.01) and metastatic neuroblastoma excluding stage MS (HR = 0.61, 95% CI 0.44-0.84; p < 0.01). CONCLUSION These results indicate that improvements in childhood cancer survival in Australia are most likely due to refined management rather than changes in stage at diagnosis, particularly for metastatic solid tumours. Wide international uptake of the Toronto Guidelines will allow comprehensive evaluation of differences in survival between countries.
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Systemic biomarkers of retinopathy of prematurity in preterm babies.
Sehgal, P, Narang, S, Chawla, D, Gupta, S, Jain, S, Sharma, U, Katoch, D, Kaur, J
International ophthalmology. 2023;(5):1751-1759
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Abstract
PURPOSE Retinopathy of prematurity (ROP) progression is an inter-play of various perinatal and neonatal angiogenic and inflammatory cytokines. A small subset of ROP progresses to ROP requiring treatment. The present study was conducted with the aim to determine whether levels of IL-6, IL-8 and VEGF in serum and urine at the time of first ROP screening visit could be a biomarker for the prediction of development of treatable ROP. METHOD Prospective single-center observational study of preterm babies screened for ROP. Blood and urine samples were collected as a part of routine sampling at initial ROP screening visit and stored at -80 °C for further processing. The babies were followed up and grouped into 'Group A' comprising of 35 babies who developed treatable ROP and 'Group B' comprising of 36 babies with regressed ROP or no ROP. The evaluation of blood and urine samples was done for IL6, IL8 and VEGF by solid-phase sandwich RayBio® Human ELISA kit. RESULTS The median serum values for IL-6, IL-8 and VEGF in Group A and Group B were 5.8 pg/ml (IQR 1.5,128.5) and 8.7 pg/ml (IQR 1.5,30.5), 55.9 pg/ml (IQR 28.0, 392.9) and 27.0 pg/ml (IQR 20.5,444.9) and 26.6 pg/ml (IQR 6.3, 39.4) and 30.0 pg/ml (IQR9.2,70.3), respectively. Group A had significantly increased levels of IL-8 (p < 0.05). However, AUROC curve for serum IL-8 demonstrated suboptimal discriminating ability. CONCLUSION Babies developing ROP requiring treatment had significantly increased levels of IL-8 in the serum at the time of initial screening. However, it could not serve as predictor for treatable ROP.
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Early cardiovascular involvement in dengue fever: A prospective study with two-dimensional speckle tracking echocardiography.
Gupta, S, Gupta, M, Kashyap, JR, Arora, SK
Tropical doctor. 2022;(2):285-292
Abstract
Cardiac abnormalities in dengue infection have been conventionally identified by clinical manifestations. The primary objective of our prospective observational study was to assess true cardiovascular involvement and early myocarditis in 150 hospitalised, confirmed cases of dengue fever, through myocardial strain detection using two-dimensional speckle tracking echocardiography. Myocarditis was defined on the basis of European Society of Cardiology (ESC) 2013 criteria. Cardiac biomarkers, namely, creatine phosphokinase myocardial band was elevated in 28.6% and Troponin-T in 23.3% patients. Electrocardiography was abnormal in 64.6% while 6% patients had two-dimensional structural echocardiographic abnormalities. Myocardial dysfunction was suspected in 27.3% based on ESC criteria and strain analysis. The severe dengue group had lower longitudinal strain [-16.4 (6.3)] and circumferential strain [-15.7 (6.7)]. Two-dimensional speckle tracking echocardiography was found to be useful in improving the understanding of early myocardial mechanics in dengue fever.
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Use and Costs of Nonprescription Medications Among People With Spinal Cord Injury.
Gupta, S, Dhawan, J, McColl, MA, Smith, K, McColl, A
Archives of physical medicine and rehabilitation. 2022;(7):1279-1284
Abstract
OBJECTIVES The study objectives were to assess the prevalence of, and factors associated with the use and costs of nonprescription medications among people with spinal cord injury. DESIGN Observational design; a cross-sectional online survey. SETTING Community in Canada. PARTICIPANTS Individuals with spinal cord injury (N=160). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Not applicable. RESULTS A total of 160 individuals participated in this study. Of all study participants, 83% reported that they used at least 1 nonprescription medication over the last 12 months. On average, participants spent $52 per month on nonprescription medications. The average use and monthly expenditure did not differ significantly by age, sex, or injury parameters. Vitamins and minerals were most commonly used and constituted 62% of all nonprescription medications listed by the participants. Musculoskeletal issues were the most common health problems for which nonprescription medications were used. CONCLUSION Nonprescription medications are a common part of therapeutic drug regimens for people with spinal cord injuries and are purchased as an out-of-pocket expense. These products may or may not have established benefits. Knowledge about the use of nonprescription medications may help prescribers to improve drug safety, medication affordability, and quality of pharmacotherapy for patients with spinal cord injury.
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Panel of serum miRNAs as potential non-invasive biomarkers for pancreatic ductal adenocarcinoma.
Khan, IA, Rashid, S, Singh, N, Rashid, S, Singh, V, Gunjan, D, Das, P, Dash, NR, Pandey, RM, Chauhan, SS, et al
Scientific reports. 2021;(1):2824
Abstract
Early-stage diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to non-specific symptoms. Circulating miRNAs in body fluids have been emerging as potential non-invasive biomarkers for diagnosis of many cancers. Thus, this study aimed to assess a panel of miRNAs for their ability to differentiate PDAC from chronic pancreatitis (CP), a benign inflammatory condition of the pancreas. Next-generation sequencing was performed to identify miRNAs present in 60 FFPE tissue samples (27 PDAC, 23 CP and 10 normal pancreatic tissues). Four up-regulated miRNAs (miR-215-5p, miR-122-5p, miR-192-5p, and miR-181a-2-3p) and four down-regulated miRNAs (miR-30b-5p, miR-216b-5p, miR-320b, and miR-214-5p) in PDAC compared to CP were selected based on next-generation sequencing results. The levels of these 8 differentially expressed miRNAs were measured by qRT-PCR in 125 serum samples (50 PDAC, 50 CP, and 25 healthy controls (HC)). The results showed significant upregulation of miR-215-5p, miR-122-5p, and miR-192-5p in PDAC serum samples. In contrast, levels of miR-30b-5p and miR-320b were significantly lower in PDAC as compared to CP and HC. ROC analysis showed that these 5 miRNAs can distinguish PDAC from both CP and HC. Hence, this panel can serve as a non-invasive biomarker for the early detection of PDAC.
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Acute Kidney Injury and Electrolyte Abnormalities After Chimeric Antigen Receptor T-Cell (CAR-T) Therapy for Diffuse Large B-Cell Lymphoma.
Gupta, S, Seethapathy, H, Strohbehn, IA, Frigault, MJ, O'Donnell, EK, Jacobson, CA, Motwani, SS, Parikh, SM, Curhan, GC, Reynolds, KL, et al
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2020;(1):63-71
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Abstract
RATIONALE & OBJECTIVE Cytokine release syndrome is a well-known complication of chimeric antigen receptor T-cell (CAR-T) therapy and can lead to multiorgan dysfunction. However, the nephrotoxicity of CAR-T therapy is unknown. We aimed to characterize the occurrence, cause, and outcomes of acute kidney injury (AKI), along with the occurrence of electrolyte abnormalities, among adults with diffuse large B-cell lymphoma receiving CAR-T therapy. STUDY DESIGN Case series. SETTING & PARTICIPANTS We reviewed the course of 78 adults receiving CAR-T therapy with axicabtagene ciloleucel or tisagenlecleucel at 2 major cancer centers between October 2017 and February 2019. Baseline demographics, comorbid conditions, medications, and laboratory values were obtained from electronic health records. AKI was defined using KDIGO (Kidney Disease: Improving Global Outcomes) criteria. The cause, clinical course, and outcome of AKI events and electrolyte abnormalities in the first 30 days after CAR-T infusion were characterized using data contained in electronic health records. RESULTS Among 78 patients receiving CAR-T therapy, cytokine release syndrome occurred in 85%, of whom 62% were treated with tocilizumab. AKI occurred in 15 patients (19%): 8 had decreased kidney perfusion, 6 developed acute tubular necrosis, and 1 patient had urinary obstruction related to disease progression. Those with acute tubular necrosis and obstruction had the longest lengths of stay and highest 60-day mortality. Electrolyte abnormalities were common; hypophosphatemia, hypokalemia, and hyponatremia occurred in 75%, 56%, and 51% of patients, respectively. LIMITATIONS Small sample size; AKI adjudicated by retrospective chart review; lack of biopsy data. CONCLUSIONS In this case series of patients with diffuse large B-cell lymphoma receiving CAR-T therapy, AKI and electrolyte abnormalities occurred commonly in the context of cytokine release syndrome.
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Cross-sectional observational study evaluating the association between odontogenic cystic content and size.
Gupta, B, Gupta, S, Chaudhary, M, Raj, AT, Patil, S
Archives of oral biology. 2020;:104954
Abstract
OBJECTIVES To evaluate and correlate the cystic content and the size of odontogenic cysts. METHODS The study included 29 cases of odontogenic cysts reported in the Outpatient Department of Sharad Pawar Dental College. The cystic aspirate was analyzed for levels of sodium, potassium, calcium, chloride, total protein, globulin, albumin, and cholesterol. The sodium/potassium ratio was calculated. Pearson's correlation coefficient (ρ) was used to correlate the size of the cyst with the sodium/potassium ratio and other cystic contents. P < 0.05 was considered statistically significant. RESULTS A positive and statistically significant correlation (ρ = 0.625, p = 0.020) was noted between the sodium to potassium ratio and the size of the cyst. The correlation between the other cystic contents and the size of the cyst was not statistically significant (p > 0.05). CONCLUSION The sodium to potassium ratio is positively correlated with the radiographic size of cysts. A thorough analysis of cystic fluid components could provide valuable insights into the potential expansion of odontogenic cysts.
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Hyponatraemia in patients with community-acquired pneumonia; prevalence and aetiology, and natural history of SIAD.
Cuesta, M, Slattery, D, Goulden, EL, Gupta, S, Tatro, E, Sherlock, M, Tormey, W, O'Neill, S, Thompson, CJ
Clinical endocrinology. 2019;(5):744-752
Abstract
OBJECTIVE Hyponatraemia is common in community-acquired pneumonia (CAP) and is associated with increased mortality. The mechanism of hyponatraemia in CAP is not completely understood and treatment is therefore ill-defined. We aimed to define the causation of hyponatraemia in CAP. DESIGN Prospective, single-centre, observational study of all patients with CAP and hyponatraemia (≤ 130 mmol/L) during a 9-month period. PATIENTS The prevalence of each subtype of hyponatraemia, and the associated mortality, was determined in 143 admissions with CAP (Study 1). A sub-cohort of patients with SIAD (n = 10) was prospectively followed, to document the natural history of SIAD associated with CAP (Study 2). MEASUREMENTS In Study 2, blood and urine were collected on day 1, 3, 5 and 7 following admission for measurement of plasma vasopressin, sodium, osmolality and urine osmolality. RESULTS In study 1, 143/1723(8.3%) of CAP patients had hyponatraemia (≤130 mmol/L). About 66 had SIAD (46%), 60(42%) had hypovolaemic hyponatraemia (HON), 13(9%) had hypervolaemic hyponatraemia (HEN) and 4(3%) patients had hyponatraemia due to glucocorticoid hormone deficiency. Mortality was higher in the HEN than in the HON, SIAD or normonatraemic groups (P < 0.01). In Study 2, plasma sodium concentration normalized in 8/10 (80%) by day 7. Two patients with persistent hyponatraemia were discovered to have underlying bronchiectasis. CONCLUSIONS Hyponatraemia in CAP is most commonly secondary to SIAD or hypovolaemia. HEN is less common, but has worse prognosis. Prospective observation demonstrates that in SIAD, plasma AVP and sodium concentrations normalize with antimicrobials; failure of reversal of suggests underlying lung disease, such as bronchiectasis.
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Fluorescence spectroscopic study on malignant and premalignant oral mucosa of patients undergoing treatment: An observational prospective study.
Kanchwala, N, Kumar, N, Gupta, S, Lokhandwala, H
International journal of surgery (London, England). 2018;:87-91
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BACKGROUND To evaluate the changes of oral mucosa in malignancy and pre-malignant oral conditions using fluorescence spectroscopy during various phases of treatment. MATERIAL AND METHODS The study involved patients of squamous cell carcinoma of the oral cavity and the premalignant lesions coming for the follow up/post-operative radiotherapy. The autofluorescence spectra were recorded in vivo using a Nitrogen laser based fluorimeter. Three sites of each patient were examined-right & the left buccal mucosa and the tongue. For a given pathology, spectra from all the individuals were grouped and mean spectra after different radiation cycles were compared. The quantitative analysis of the spectra involved extraction of diagnostically relevant spectral information through Maximum Representation and Discrimination Feature. RESULTS As different patients had different response to the radiation, it was difficult to visualize any particular trend with increased number of radiation cycles. However, for a given pathology and an individual, when mean spectra after different radiation cycles and surgery were compared, the observation was: Intensity of the 460 nm fluorescence band for each pathology was increased with the number of radiation cycle. That had indicated tissue was being reverted back to its grossly normal features. As 460 nm fluorescence spike was a standard spectra for normal mucosa. CONCLUSION The results strengthened the hypothesis that fluorescence spectroscopy has considerable potential for use as a tool to evaluate the response to treatment in oral malignancy. These spectra of radiotherapy and surgically treated patients can be used as standards for treated patients in further studies.
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The contribution of undiagnosed adrenal insufficiency to euvolaemic hyponatraemia: results of a large prospective single-centre study.
Cuesta, M, Garrahy, A, Slattery, D, Gupta, S, Hannon, AM, Forde, H, McGurren, K, Sherlock, M, Tormey, W, Thompson, CJ
Clinical endocrinology. 2016;(6):836-844
Abstract
OBJECTIVE The syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of hyponatraemia. Data on SIAD are mainly derived from retrospective studies, often with poor ascertainment of the minimum criteria for the correct diagnosis. Reliable data on the incidence of adrenal failure in SIAD are therefore unavailable. The aim of the study was to describe the aetiology of SIAD and in particular to define the prevalence of undiagnosed adrenal insufficiency. DESIGN Prospective, single centre, noninterventional, observational study of patients admitted to Beaumont Hospital with euvolaemic hyponatraemia (plasma sodium ≤ 130 mmol/l) between January 1st and October 1st 2015. PATIENTS A total of 1323 admissions with hyponatraemia were prospectively evaluated; 576 had euvolaemic hyponatraemia, with 573 (43·4%) initially classified as SIAD. MAIN OUTCOME MEASURES (i) Aetiology of SIAD, defined by diagnostic criteria; (ii) Incidence of adrenal insufficiency. RESULTS Central nervous system diseases were the commonest cause of SIAD (n = 148, 26%) followed by pulmonary diseases (n = 111, 19%), malignancy (n = 105, 18%) and drugs (n = 47, 8%). A total of 22 patients (3·8%), initially diagnosed as SIAD, were reclassified as secondary adrenal insufficiency on the basis of cortisol measurements and clinical presentation; 9/22 cases had undiagnosed hypopituitarism; 13/22 patients had secondary adrenal insufficiency due to exogenous steroid administration. CONCLUSIONS In a large, prospective and well-defined cohort of euvolaemic hyponatraemia, undiagnosed secondary adrenal insufficiency co-occurred in 3·8% of cases initially diagnosed as SIAD. Undiagnosed pituitary disease was responsible for 1·5% of cases presenting as euvolaemic hyponatraemia.