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1.
Hepatocellular carcinoma tumour volume doubling time: a systematic review and meta-analysis.
Nathani, P, Gopal, P, Rich, N, Yopp, A, Yokoo, T, John, B, Marrero, J, Parikh, N, Singal, AG
Gut. 2021;(2):401-407
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Abstract
BACKGROUND Tumour growth patterns have important implications for surveillance intervals, prognostication and treatment decisions but have not been well described for hepatocellular carcinoma (HCC). The aim of our study was to characterise HCC doubling time and identify correlates for indolent and rapid growth patterns. METHODS We performed a systematic literature review of Medline and EMBASE databases from inception to December 2019 and national meeting abstracts from 2010 to 2018. We identified studies reporting HCC tumour growth or tumour volume doubling time (TVDT), without intervening treatment, and abstracted data to calculate TVDT and correlates of growth patterns (rapid defined as TVDT <3 months and indolent as TVDT >9 months). Pooled TVDT was calculated using a random-effects model. RESULTS We identified 20 studies, including 1374 HCC lesions in 1334 patients. The pooled TVDT was 4.6 months (95% CI 3.9 to 5.3 months I2=94%), with 35% classified as rapid, 27.4% intermediate and 37.6% indolent growth. In subgroup analysis, studies from Asia reported shorter TVDT than studies elsewhere (4.1 vs 5.8 months). The most consistent correlates of rapid tumour growth included hepatitis B aetiology, smaller tumour size (continuous), alpha fetoprotein doubling time and poor tumour differentiation. Studies were limited by small sample sizes, measurement bias and selection bias. CONCLUSION TVDT of HCC is approximately 4-5 months; however, there is heterogeneity in tumour growth patterns, including more aggressive patterns in Asian hepatitis B-predominant populations. Identifying correlates of tumour growth patterns is important to better individualise HCC prognostication and treatment decisions.
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Unusual Early Recovery of a Critical COVID-19 Patient After Administration of Intravenous Vitamin C.
Waqas Khan, HM, Parikh, N, Megala, SM, Predeteanu, GS
The American journal of case reports. 2020;21:e925521
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Plain language summary
Coronavirus disease (Covid-19) continues to spread globally and to date there are no proven treatments. Current treatment focuses on the management of the associated acute respiratory distress syndrome (ARDS). There are many studies demonstrating that in severe sepsis and ARDS; Vitamin C reduces systemic inflammation, prevents lung damage, reduces the duration of mechanical ventilation (MV) and the length of intensive care unit (ICU) stay in patients. This is a case report where a critically ill patient received high-dose Vitamin C intravenous (IV) infusions and recovered. A 74 year-old woman with Covid-19, developed ARDS and septic shock. Usual medications were given. She needed MV and deteriorated rapidly. On Day 7 she was administered Vitamin C (11g per 24 hours as a continuous IV infusion). Her clinical condition improved slowly after this. In this case, high dose IV Vitamin C was associated with fewer days on mechanical intervention, a shorter ICU stay and earlier recovery. These results show the importance of further investigation of IV Vitamin C to assess its efficacy in critically ill Covid-19 patients requiring mechanical ventilation and ICU care.
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) continues to spread, with confirmed cases now in more than 200 countries. Thus far there are no proven therapeutic options to treat COVID-19. We report a case of COVID-19 with acute respiratory distress syndrome who was treated with high-dose vitamin C infusion and was the first case to have early recovery from the disease at our institute. CASE REPORT A 74-year-old woman with no recent sick contacts or travel history presented with fever, cough, and shortness of breath. Her vital signs were normal except for oxygen saturation of 87% and bilateral rhonchi on lung auscultation. Chest radiography revealed air space opacity in the right upper lobe, suspicious for pneumonia. A nasopharyngeal swab for severe acute respiratory syndrome coronavirus-2 came back positive while the patient was in the airborne-isolation unit. Laboratory data showed lymphopenia and elevated lactate dehydrogenase, ferritin, and interleukin-6. The patient was initially started on oral hydroxychloroquine and azithromycin. On day 6, she developed ARDS and septic shock, for which mechanical ventilation and pressor support were started, along with infusion of high-dose intravenous vitamin C. The patient improved clinically and was able to be taken off mechanical ventilation within 5 days. CONCLUSIONS This report highlights the potential benefits of high-dose intravenous vitamin C in critically ill COVID-19 patients in terms of rapid recovery and shortened length of mechanical ventilation and ICU stay. Further studies will elaborate on the efficacy of intravenous vitamin C in critically ill COVID-19.
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Hybrid Closed-Loop Insulin Delivery in Type 1 Diabetes During Supervised Outpatient Conditions.
Grosman, B, Ilany, J, Roy, A, Kurtz, N, Wu, D, Parikh, N, Voskanyan, G, Konvalina, N, Mylonas, C, Gottlieb, R, et al
Journal of diabetes science and technology. 2016;(3):708-13
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Abstract
BACKGROUND Efficacy and safety of the Medtronic Hybrid Closed-Loop (HCL) system were tested in subjects with type 1 diabetes in a supervised outpatient setting. METHODS The HCL system is a prototype research platform that includes a sensor-augmented insulin pump in communication with a control algorithm housed on an Android-based cellular device. Nine subjects with type 1 diabetes (5 female, mean age 53.3 years, mean A1C 7.2%) underwent 9 studies totaling 571 hours of closed-loop control using either default or personalized parameters. The system required meal announcements with estimates of carbohydrate (CHO) intake that were based on metabolic kitchen quantification (MK), dietician estimates (D), or subject estimates (Control). Postprandial glycemia was compared for MK, D, and Control meals. RESULTS The overall sensor glucose mean was 145 ± 43, the overall percentage time in the range 70-180 mg/dL was 80%, the overall percentage time <70 mg/dL was 0.79%. Compared to intervals of default parameter use (225 hours), intervals of personalized parameter use (346 hours), sensor glucose mean was 158 ± 49 and 137 ± 37 mg/dL (P < .001), respectively, and included more time in range (87% vs 68%) and less time below range (0.54% vs 1.18%). Most subjects underestimated the CHO content of meals, but postprandial glycemia was not significantly different between MK and matched Control meals (P = .16) or between D and matched Control meals (P = .76). There were no episodes of severe hypoglycemia. CONCLUSIONS The HCL system was efficacious and safe during this study. Personally adapted HCL parameters were associated with more time in range and less time below range than default parameters. Accurate estimates of meal CHO did not contribute to improved postprandial glycemia.
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Low-Cost High-Resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia: An International Trial.
Protano, MA, Xu, H, Wang, G, Polydorides, AD, Dawsey, SM, Cui, J, Xue, L, Zhang, F, Quang, T, Pierce, MC, et al
Gastroenterology. 2015;(2):321-329
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Abstract
BACKGROUND & AIMS Esophageal squamous cell neoplasia has a high mortality rate as a result of late detection. In high-risk regions such as China, screening is performed by Lugol's chromoendoscopy (LCE). LCE has low specificity, resulting in unnecessary tissue biopsy with a subsequent increase in procedure cost and risk. The purpose of this study was to evaluate the accuracy of a novel, low-cost, high-resolution microendoscope (HRME) as an adjunct to LCE. METHODS In this prospective trial, 147 consecutive high-risk patients were enrolled from 2 US and 2 Chinese tertiary centers. Three expert and 4 novice endoscopists performed white-light endoscopy followed by LCE and HRME. All optical images were compared with the gold standard of histopathology. RESULTS By using a per-biopsy analysis, the sensitivity of LCE vs LCE + HRME was 96% vs 91% (P = .0832), specificity was 48% vs 88% (P < .001), positive predictive value was 22% vs 45% (P < .0001), negative predictive value was 98% vs 98% (P = .3551), and overall accuracy was 57% vs 90% (P < .001), respectively. By using a per-patient analysis, the sensitivity of LCE vs LCE + HRME was 100% vs 95% (P = .16), specificity was 29% vs 79% (P < .001), positive predictive value was 32% vs 60%, 100% vs 98%, and accuracy was 47% vs 83% (P < .001). With the use of HRME, 136 biopsies (60%; 95% confidence interval, 53%-66%) could have been spared, and 55 patients (48%; 95% confidence interval, 38%-57%) could have been spared any biopsy. CONCLUSIONS In this trial, HRME improved the accuracy of LCE for esophageal squamous cell neoplasia screening and surveillance. HRME may be a cost-effective optical biopsy adjunct to LCE, potentially reducing unnecessary biopsies and facilitating real-time decision making in globally underserved regions. ClinicalTrials.gov, NCT 01384708.
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The effects of extended release niacin on lipoprotein sub-particle concentrations in HIV-infected patients.
Lin, C, Grandinetti, A, Shikuma, C, Souza, S, Parikh, N, Nakamoto, B, Kallianpur, KJ, Chow, D
Hawai'i journal of medicine & public health : a journal of Asia Pacific Medicine & Public Health. 2013;(4):123-7
Abstract
With the advent of highly active antiretroviral therapy (HAART), Cardiovascular Disease (CVD) has emerged as the leading cause of death in Human Immunodeficiency Virus (HIV) infected patients. An atherogenic lipoprotein phenotype has been described in HIV- infected patients with a predominance of small, low density lipoprotein (SLDL) particles with accompanying elevated triglycerides and reduced high density lipoprotein cholesterol. This randomized controlled pilot study was conducted to evaluate the efficacy of Extended Release Niacin (ERN) in improving the lipid profile in HIV patients. A total of 17 HIV positive subjects on HAART therapy with High Density Lipoprotein Cholesterol (HDL) levels below 40mg/dl and Low Density Lipoprotein Cholesterol (LDL) below 130mg/dl were enrolled. Nine were randomized to be treated with ERN titrated from a starting level of 500mg/night and titrated to a level of 1500mg/night. Eight patients were assigned to the control arm. No placebo was used. Lipoprotein profiles of the subjects were analyzed at baseline and at the end of 12 weeks using Nuclear Magnetic Resonance (NMR) spectroscopy. At the end of 12 weeks, NMR spectroscopic analysis revealed a significant increase in overall LDL size (1.2% in ERN treated subjects vs 2.0% decrease in control patients, P=.04) and a decrease in small LDL particle concentration (17.0% in ERN treated subjects vs 21.4% increase in control patients, P=.03) in subjects receiving ERN as compared to those in the control group. Only 1 subject receiving ERN developed serious flushing which was attributed to an accidental overdose of the drug. This pilot study demonstrates that ERN therapy in HIV-infected patients with low HDL is safe and effective in improving the lipoprotein profile in these patients.
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Hepatocellular carcinoma in a noncirrhotic patient with HIV: a case report and review of the literature.
Parikh, N, Martel-Laferriere, V, Zhang, X, Dieterich, D, Fiel, MI, Perumalswami, P
Seminars in liver disease. 2012;(2):186-92
Abstract
A 59-year-old man with human immunodeficiency virus (HIV) was referred for persistently elevated liver enzyme activities. His HIV was well controlled on antiretroviral therapy and his viral load was undetectable. He had no history of chronic liver disease and had minimal alcohol intake. He was asymptomatic and his physical exam was unremarkable without any stigmata of liver disease. Beyond the elevations in alkaline phosphatase and gamma-glutamyl transferase, the rest of his laboratory work, including viral hepatitis serologies and serum α-fetoprotein, was within normal limits. A computed tomography (CT) scan revealed a mildly nodular liver but hepatic mass or ascites was not seen. He was subsequently followed every 3 to 6 months without any change in his clinical symptoms, laboratory values, or imaging tests. Two years after the original visit, the patient presented with acute onset of abdominal pain, an AFP of 15.8 ng/mL, and a 9-cm hepatic mass on imaging. Given his preserved liver function, he underwent right hepatic lobectomy. Histologic examination of the resected tissue was consistent with hepatocellular carcinoma (HCC). The uninvolved liver was noncirrhotic and unremarkable except for mild portal inflammation. As the vast majority of HIV patients who develop HCC have established chronic liver diseases such as hepatitis B and/or C along with cirrhosis, this case of HCC in an HIV patient without cirrhosis or viral hepatitis is rare. Although current screening guidelines recommend imaging only for patients with HIV and hepatitis B/C cirrhosis, closer monitoring may be important in HIV patients with even subtle liver dysfunction.
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Nonalcoholic fatty liver disease: pharmacologic and surgical options.
Parikh, N, Ahmad, J
Gastroenterology clinics of North America. 2011;(3):541-59
Abstract
The last decade has seen many studies examining the prevalence and natural history of NAFLD in the United States and it is clear that this disease is likely to be an important cause of liver-related morbidity in the future. Several pharmacologic therapies have shown some promise; currently, vitamin E and insulin-sensitizing agents such as pioglitazone can be considered in appropriate cases. Conservative measures to promote weight loss still have a role to play, but the obesity epidemic in the Western World has reached such proportions that bariatric surgery is proving to be an attractive option for patients with a BMI greater than 35 to 40 kg/m2. Well-designed prospective studies are required to ensure that all of these therapies are safe and effective in the long term. Newer agents will likely be investigated as the pathogenesis of NAFLD and fibrosis progression in NASH are further elucidated.
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Classical and emerging roles of vitamin D in hepatitis C virus infection.
Gutierrez, JA, Parikh, N, Branch, AD
Seminars in liver disease. 2011;(4):387-98
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Abstract
According to the Institute of Medicine, the risk of clinically significant vitamin D deficiency increases at 25-hydroxyvitamin D levels below 20 ng/mL. By this standard, most cirrhotic hepatitis C virus- (HCV-) positive patients and many noncirrhotic patients are vitamin D-deficient. The high prevalence of vitamin D deficiency among HCV patients is a cause for concern for several specific reasons. Classic studies established the importance of vitamin D and calcium in maintaining bone. Vitamin D's beneficial effects on bone are likely to be vital for HCV-infected patients because these individuals have a high prevalence of low bone mineral density. Many pharmaceutical agents reduce bone density and exposure to these drugs may increase bone disease in HCV-positive patients. Bone loss occurs following liver transplantation and bone density is often low in patients with HIV/HCV co-infection who are on combination antiretroviral therapy. Some evidence suggests that ribavirin reduces bone density, underscoring the special need to monitor vitamin D in patients receiving HCV treatment and to prescribe supplements, as appropriate. In addition to its role in calcium metabolism, vitamin D is also an immune modulator that reduces inflammation while enhancing protective immune responses. Higher vitamin D levels are associated with less liver fibrosis and less inflammation in HCV patients. Recent studies show that low vitamin D levels are associated with treatment failure among HCV-infected patients receiving pegylated-interferon and ribavirin. If confirmed, these findings will provide an additional reason to ensure adequate levels of vitamin D. Information about how to monitor vitamin D status and how to use vitamin D supplements most effectively in HCV-infected patients is provided.
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Liver x receptors: a potential therapeutic target for modulating the atherosclerotic process.
Parikh, N, Frishman, WH
Cardiology in review. 2010;(6):269-74
Abstract
Liver X receptors (LXRs) are nuclear receptors that play a major role in the expression of genes which are involved in lipid metabolism. LXRs are part of the superfamily of steroid receptors that work to deliver metabolic signals on the transcriptional level to either suppress or activate target genes. LXRs, once ligand-activated, work by forming heterodimers with the retinoid X receptor, after which they act as transcription factors by binding to the promoter region of deoxyribonucleic acid sequences, thereby affecting gene expression. Specifically, LXR has been shown to be involved with genes that help in the modulation of lipid metabolism, therein having a significant effect on the development or propagation of atherosclerosis. This review paper will discuss the overall function of LXRs and their role in lipid metabolism, and will help identify possible therapeutic modulators of LXRs that can be used for the prevention and treatment of atherosclerosis.
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The safety of drugs used in acid-related disorders and functional gastrointestinal disorders.
Parikh, N, Howden, CW
Gastroenterology clinics of North America. 2010;(3):529-42
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Abstract
Medicines are frequently used in the management of acid-related disorders and functional gastrointestinal disorders. With the exception of complicated peptic ulcer disease, these disorders are not associated with appreciable mortality. Drug treatments have consequently been held to the highest standards of safety. Some medicines have been withdrawn or restricted based on assessments and perceptions of risk. However, the risk of serious toxicity is low for most of the agents discussed in this article. Assessments are made of the safety and adverse-event profiles of certain drug classes and, where appropriate, individual medicines. For conditions with a low risk of mortality or serious morbidity, clinicians need to balance the risks of potential adverse events with the anticipated benefits of a successful outcome of specific drug treatment.