Publications by authors named "Utsav Joshi"

18 Publications

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Disparity in Utilization of Multiagent Therapy for Acute Promyelocytic Leukemia in the United States.

Clin Lymphoma Myeloma Leuk 2021 Oct 25. Epub 2021 Oct 25.

Department of Internal Medicine, Division of Oncology and Hematology, University of Nebraska Medical Center, Omaha, NE; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE.

Background: Despite high rate of cure in acute promyelocytic leukemia (APL) in clinical trials, outcomes in real-world practice are dismal. We utilized National Cancer Database (NCDB) to explore utilization of multiagent therapy in APL and identify any disparities in treatment in real-world practices.

Patients And Methods: NCDB categorizes use of systemic chemotherapy into single agent versus multiagent therapy. Some patients received hormonal therapy, immunotherapy, and unknown therapy; details of these treatments could not be ascertained. We therefore used multiple logistic regression analysis to evaluate effects of covariates on the probability of multiagent therapy use in 6678 patients.

Results: Compared to patients >60 years, patients aged 0 to 18 years (hazard ratio[HR] 3.2, 95% confidence interval [CI] 1.8-5.5, P< .0001), 19 to 40 years (HR 1.6, 95% CI 1.03-2.54, P= .03), and 41 to 60 years (HR 1.6, 95% CI 1.3-1.9, P< .0001) were more likely to receive multiagent therapy. Patients with Charlson comorbidity index (CCI) of 0 (HR 1.6, 95% CI 1.2-2.3, P= .001) and CCI of 1 (HR 1.4, 95% CI 1.0-1.9, P= .04) had a higher likelihood of receiving multiagent therapy than patients with CCI ≥ 3. Patients treated at academic cancer centers, compared to those treated at community cancer center (HR 0.5, 95% CI 0.3-0.7, P= .001), comprehensive community cancer center (HR 0.7, 95% CI 0.6-0.8, P< .0001), and integrated network cancer center (HR 0.8, 95% CI 0.6-0.9, P= .02) were more likely to be treated with multiagent therapy. Compared to the patients with private insurance, those with Medicaid had increased likelihood (HR 1.2, 95% CI 1.0-1.4, P= .04) whereas uninsured patients had a lower likelihood of receiving multiagent therapy (HR 0.6, 95% CI 0.5-0.8, P= .0005).

Conclusion: To our knowledge, this study is the first and the largest scale analysis of treatment practices in APL in real-world practices. Our findings highlight significant disparities in treatment of APL based on age, insurance, and health-system factors.
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http://dx.doi.org/10.1016/j.clml.2021.10.010DOI Listing
October 2021

Adaptive Immune Responses Associated with the Central Nervous System Pathology of Gulf War Illness.

Neurosci Insights 2021 25;16:26331055211018458. Epub 2021 May 25.

Roskamp Institute, Sarasota, FL, USA.

Gulf War Illness is a multisymptomatic condition which affects 30% of veterans from the 1991 Gulf War. While there is evidence for a role of peripheral cellular and humoral adaptive immune responses in Gulf War Illness, a potential role of the adaptive immune system in the central nervous system pathology of this condition remains unknown. Furthermore, many of the clinical features of Gulf War Illness resembles those of autoimmune diseases, but the biological processes are likely different as the etiology of Gulf War Illness is linked to hazardous chemical exposures specific to the Gulf War theatre. This review discusses Gulf War chemical-induced maladaptive immune responses and a potential role of cellular and humoral immune responses that may be relevant to the central nervous system symptoms and pathology of Gulf War Illness. The discussion may stimulate investigations into adaptive immunity for developing novel therapies for Gulf War Illness.
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http://dx.doi.org/10.1177/26331055211018458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155779PMC
May 2021

Tuberculosis with Evans syndrome: A case report.

Clin Case Rep 2021 May 6;9(5):e04113. Epub 2021 May 6.

Department of Internal Medicine Institute of Medicine Tribhuvan University Teaching Hospital Kathmandu Nepal.

Evans syndrome and tuberculosis could be predisposing factors for one another, or there may be a common pathophysiological denominator for the co-occurrence. Further research is needed for a better understanding of pathophysiology and treatment.
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http://dx.doi.org/10.1002/ccr3.4113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122135PMC
May 2021

A late presenting left-sided congenital diaphragmatic hernia repair complicated by postoperative chylothorax: A case report.

Clin Case Rep 2021 Jan 11;9(1):350-354. Epub 2020 Nov 11.

Department of Pediatric Surgery Kanti children's Hospital Kathmandu Nepal.

Management of chylothorax after repair of late presenting congenital diaphragmatic hernia is debatable. Conservative management in the form of close monitoring of chylous output with nutritional support appears convincing to surgery.
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http://dx.doi.org/10.1002/ccr3.3528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813110PMC
January 2021

Mural cell dysfunction leads to altered cerebrovascular tau uptake following repetitive head trauma.

Neurobiol Dis 2021 03 28;150:105237. Epub 2020 Dec 28.

The Roskamp Institute, Sarasota, FL, USA; The Open University, Milton Keynes, UK; Bay Pines VA Healthcare System, Bay Pines, FL, USA. Electronic address:

A pathological characteristic of repetitive traumatic brain injury (TBI) is the deposition of hyperphosphorylated and aggregated tau species in the brain and increased levels of extracellular monomeric tau are believed to play a role in the pathogenesis of neurodegenerative tauopathies. The pathways by which extracellular tau is eliminated from the brain, however, remains elusive. The purpose of this study was to examine tau uptake by cerebrovascular cells and the effect of TBI on these processes. We found monomeric tau interacts with brain vascular mural cells (pericytes and smooth muscle cells) to a greater extent than other cerebrovascular cells, indicating mural cells may contribute to the elimination of extracellular tau, as previously described for other solutes such as beta-amyloid. Consistent with other neurodegenerative disorders, we observed a progressive decline in cerebrovascular mural cell markers up to 12 months post-injury in a mouse model of repetitive mild TBI (r-mTBI) and human TBI brain specimens, when compared to control. These changes appear to reflect mural cell degeneration and not cellular loss as no difference in the mural cell population was observed between r-mTBI and r-sham animals as determined through flow cytometry. Moreover, freshly isolated r-mTBI cerebrovessels showed reduced tau uptake at 6 and 12 months post-injury compared to r-sham animals, which may be the result of diminished cerebrovascular endocytosis, as caveolin-1 levels were significantly decreased in mouse r-mTBI and human TBI cerebrovessels compared to their respective controls. Further emphasizing the interaction between mural cells and tau, similar reductions in mural cell markers, tau uptake, and caveolin-1 were observed in cerebrovessels from transgenic mural cell-depleted animals. In conclusion, our studies indicate repeated injuries to the brain causes chronic mural cell degeneration, reducing the caveolar-mediated uptake of tau by these cells. Alterations in tau uptake by vascular mural cells may contribute to tau deposition in the brain following head trauma and could represent a novel therapeutic target for TBI or other neurodegenerative disorders.
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http://dx.doi.org/10.1016/j.nbd.2020.105237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170787PMC
March 2021

Clinical Characteristics and Management of the Hydatid Cyst of the Liver: A Study from a Tertiary Care Center in Nepal.

J Parasitol Res 2020 9;2020:8867744. Epub 2020 Sep 9.

Department of GI and General Surgery, Tribhuvan University Teaching Hospital, Institute of Medicine, Tribhuvan University, Maharajgunj, Kathmandu 44600, Nepal.

A hydatid cyst of the liver is a significant yet neglected public health problem in Nepal. The present study was carried out to evaluate the demographic characteristics, clinical presentations, and management of the patients of the hydatid cyst of the liver in the setting of a developing country. It was a retrospective, descriptive analysis of 53 patients admitted in the department of surgery with the diagnosis of hydatid cyst of the liver based on clinical manifestations, imaging studies, or serology between 2016 and 2019. The median age of the patients was 36 years, with the age group of 25-45 years being the most commonly affected (23, 43.4%). 58.5% of the patients were female. Abdominal pain (49, 92.5%) and a palpable liver (17, 32.1%) were the most common complaint and physical finding in our study population, respectively. Abdominal ultrasonography and computed tomography scan were the major imaging studies used to establish a diagnosis. A unilocular and anechoic cystic lesion was the most frequent imaging finding. The right lobe of the liver harbored the cysts in the maximum number of patients. Surgery was the preferred modality of treatment (23, 43.4%), with pericystectomy being the most common form of surgical intervention. The hydatid cyst of the liver is a common cause of morbidity in Nepal. Clinical evaluation supplemented by imaging studies is required for diagnosis, and surgery remains the treatment of choice in most cases. To explain the epidemiological pattern of the disease, multicentric studies involving a larger sample of patients should be conducted.
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http://dx.doi.org/10.1155/2020/8867744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499327PMC
September 2020

Pancreatic Tumors Complicating Pregnancy: A Concern for Fetomaternal Well Being.

Int Med Case Rep J 2020 8;13:255-259. Epub 2020 Jul 8.

Department of Obstetrics and Gynecology, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal.

Introduction: Hemoperitoneum resulting from the rupture of pancreatic tumors is a rare condition, especially during pregnancy.

Case Presentation: We report a case of a 21-year-old gravida 2, para 1, at 25+5 weeks of gestation, who presented to the hospital with severe epigastric pain and decreased fetal movement. Ultrasonography showed intrauterine fetal death, a retroperitoneal mass in the epigastric region, and hemoperitoneum. Computed tomography scan revealed a heterogeneously enhancing pancreatic mass suggestive of pancreatic neoplasm. However, the late diagnosis and the delay in treatment resulted in a deterioration of maternal status with eventual mortality.

Conclusion: Diagnostic difficulties occur because of the rarity of the condition and vague clinical presentations. In case of a pregnancy complicated by hemoperitoneum, prompt effort to stop the intraperitoneal bleeding is imperative.
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http://dx.doi.org/10.2147/IMCRJ.S263298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367919PMC
July 2020

Primary Duodenal Adenocarcinoma: Uncommon Tumor, Uncommon Presentation. A Case Report and Review of the Literature.

Int Med Case Rep J 2020 15;13:165-169. Epub 2020 May 15.

Department of GI and General Surgery, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal.

Introduction: The symptoms of primary duodenal adenocarcinoma, which is a rare but aggressive tumor, are vague and nonspecific and often result in a delayed diagnosis or misdiagnosis. This results in a tumor being diagnosed at an advanced stage when it becomes unresectable secondary to local and distant spread.

Case Presentation: A 64-year-old Nepalese female presented to our hospital with epigastric pain, anorexia, and significant weight loss that developed over two-and-a-half months. Upper gastrointestinal endoscopy showed an ulceroproliferative growth in the first part of the duodenum with no features of duodenal stenosis. Contrast-enhanced computed tomography of the abdomen revealed heterogeneously enhancing, circumferential, asymmetrical thickening in the first part of the duodenum and multiple liver metastases. Biopsy of the mass revealed features suggestive of moderately differentiated adenocarcinoma of the duodenum. She was managed with palliative care during her hospital stay. The unique presentation in our case was that the tumor did not cause stenosis and the patient could consume food till the last day of her life.

Conclusion: In patients with primary duodenal adenocarcinoma, the non-stenotic lesion is also a possibility. Clinicians should always maintain a high degree of suspicion to avoid the delay in diagnosis or misdiagnosis.
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http://dx.doi.org/10.2147/IMCRJ.S256107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237129PMC
May 2020

Targeting sirtuin activity with nicotinamide riboside reduces neuroinflammation in a GWI mouse model.

Neurotoxicology 2020 07 25;79:84-94. Epub 2020 Apr 25.

Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, 34243, United States; Open University, Milton Keynes, United Kingdom; James A. Haley Veterans' Hospital, Tampa, Florida, United States. Electronic address:

Gulf War Illness (GWI) affects 30% of veterans from the 1991 Gulf War (GW), who suffer from symptoms that reflect ongoing mitochondria dysfunction. Brain mitochondria bioenergetics dysfunction in GWI animal models corresponds with astroglia activation and neuroinflammation. In a pilot study of GW veterans (n = 43), we observed that blood nicotinamide adenine dinucleotide (NAD) and sirtuin 1 (Sirt1) protein levels were decreased in the blood of veterans with GWI compared to healthy GW veterans. Since nicotinamide riboside (NR)-mediated targeting of Sirt1 is shown to improve mitochondria function, we tested whether NR can restore brain bioenergetics and reduce neuroinflammation in a GWI mouse model. We administered a mouse diet supplemented with NR at 100μg/kg daily for 2-months to GWI and control mice (n = 27). During treatment, mice were assessed for fatigue-type behavior using the Forced Swim Test (FST), followed by euthanasia for biochemistry and immunohistochemistry analyses. Fatigue-type behavior was elevated in GWI mice compared to control mice and lower in GWI mice treated with NR compared to untreated GWI mice. Levels of plasma NAD and brain Sirt1 were low in untreated GWI mice, while GWI mice treated with NR had higher levels, similar to those of control mice. Deacetylation of the nuclear-factor κB (NFκB) p65 subunit and peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) was an increase in the brains of NR-treated GWI mice. This corresponded with a decrease in pro-inflammatory cytokines and lipid peroxidation and an increase in markers of mitochondrial bioenergetics in the brains of GWI mice. These findings suggest that targeting NR mediated Sirt1 activation restores brain bioenergetics and reduces inflammation in GWI mice. Further evaluation of NR in GWI is warranted to determine its potential efficacy in treating GWI.
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http://dx.doi.org/10.1016/j.neuro.2020.04.006DOI Listing
July 2020

Author Correction: Oleoylethanolamide treatment reduces neurobehavioral deficits and brain pathology in a mouse model of Gulf War Illness.

Sci Rep 2019 Jul 24;9(1):11011. Epub 2019 Jul 24.

Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, 34243, USA.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-019-46255-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650485PMC
July 2019

A permethrin metabolite is associated with adaptive immune responses in Gulf War Illness.

Brain Behav Immun 2019 10 17;81:545-559. Epub 2019 Jul 17.

Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, USA; Open University, Milton Keynes, UK; James A. Haley VA Hospital, Tampa, FL, USA. Electronic address:

Gulf War Illness (GWI), affecting 30% of veterans from the 1991 Gulf War (GW), is a multi-symptom illness with features similar to those of patients with autoimmune diseases. The objective of the current work is to determine if exposure to GW-related pesticides, such as permethrin (PER), activates peripheral and central nervous system (CNS) adaptive immune responses. In the current study, we focused on a PER metabolite, 3-phenoxybenzoic acid (3-PBA), as this is a common metabolite previously shown to form adducts with endogenous proteins. We observed the presence of 3-PBA and 3-PBA modified lysine of protein peptides in the brain, blood and liver of pyridostigmine bromide (PB) and  PER (PB+PER) exposed mice at acute and chronic post-exposure timepoints. We tested whether 3-PBA-haptenated albumin (3-PBA-albumin) can activate immune cells since it is known that chemically haptenated proteins can stimulate immune responses. We detected autoantibodies against 3-PBA-albumin in plasma from PB + PER exposed mice and veterans with GWI at chronic post-exposure timepoints. We also observed that in vitro treatment of blood with 3-PBA-albumin resulted in the activation of B- and T-helper lymphocytes and that these immune cells were also increased in blood of PB + PER exposed mice and veterans with GWI. These immune changes corresponded with elevated levels of infiltrating monocytes in the brain and blood of PB + PER exposed mice which coincided with alterations in the markers of blood-brain barrier disruption, brain macrophages and neuroinflammation. These studies suggest that pesticide exposure associated with GWI may have resulted in the activation of the peripheral and CNS adaptive immune responses, possibly contributing to an autoimmune-type phenotype in veterans with GWI.
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http://dx.doi.org/10.1016/j.bbi.2019.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155744PMC
October 2019

Oleoylethanolamide treatment reduces neurobehavioral deficits and brain pathology in a mouse model of Gulf War Illness.

Sci Rep 2018 08 27;8(1):12921. Epub 2018 Aug 27.

Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, 34243, USA.

There are nearly 250,000 Gulf War (GW) veterans who suffer from Gulf War Illness (GWI), a multi-symptom condition that remains untreatable. The main objective was to determine if targeting peroxisomal function could be of therapeutic value in GWI. We performed a pilot study that showed accumulation of very long chain fatty acids (VLCFA), which are metabolized in peroxisomes, in plasma from veterans with GWI. We then examined if targeting peroxisomal β-oxidation with oleoylethanolamide (OEA) restores these lipids to the normal levels and mitigates neuroinflammation and neurobehavioral deficits in a well-established mouse model of GWI. In GWI mice, treatment with OEA corresponded with cognitive benefits and reduced fatigue and disinhibition-like behavior in GWI mice. Biochemical and molecular analysis of the brain tissue showed reduced astroglia and microglia staining, decreased levels of chemokines and cytokines, and decreased NFκB phosphorylation. Treatment with OEA reduced accumulation of peroxisome specific VLCFA in the brains of GWI mice. These studies further support the translational value of targeting peroxisomes. We expect that OEA may be a potential therapy for treating neurobehavioral symptoms and the underlying lipid dysfunction and neuroinflammation associated with GWI. Oleoylethanolamide is available as a dietary supplement, making it appealing for human translational studies.
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http://dx.doi.org/10.1038/s41598-018-31242-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110778PMC
August 2018

Spontaneous cholecystocolic fistula: an uncommon complication of chronic cholecystitis.

Clin Case Rep 2017 11 29;5(11):1878-1881. Epub 2017 Sep 29.

Department of Surgery Institute of Medicine Tribhuvan University Kathmandu Nepal.

Cholecystocolic fistula, a rare complication of long-standing gallstone disease, is a diagnostic challenge owing to nonspecific clinical presentation and lack of accurate preprocedural diagnostic modalities. In case of incidental discovery of the fistula during the surgical procedure, excision of the fistula with repair of the colonic defect is imperative.
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http://dx.doi.org/10.1002/ccr3.1215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676273PMC
November 2017

Neuromyelitis Optica in a Nepalese Man.

Case Rep Neurol Med 2017 8;2017:8596781. Epub 2017 Aug 8.

Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, Nepal.

Background: Neuromyelitis optica is a severely disabling inflammatory disorder of the central nervous system of autoimmune etiology that mainly affects the optic nerves and spinal cord. Here, we present a case report detailing a patient with tingling and weakness of right upper and lower limbs who was neuromyelitis optica immunoglobulin G-positive.

Case Presentation: A 46-year-old Nepalese man presented to the hospital with a history of tingling and weakness of right upper and lower limbs that developed over a period of two months. Clinical evaluation showed diminished power across all major muscle groups in the right upper and lower limbs. Magnetic resonance imaging of his cervical spine showed T1 iso- to hypointense signal and T2 hyperintense signal in central cervical spinal cord from first to sixth cervical level, probably suggestive of myelitis or demyelination. The patient was immediately started on intravenous methylprednisolone. The diagnosis of neuromyelitis optica was later confirmed with strongly positive neuromyelitis optica immunoglobulin G.

Conclusion: In resource limited setting, in the absence of tests for neuromyelitis optica immunoglobulin G, treatment was started and the patient's condition started to get better. Hence, early initiation of aggressive immunosuppressive treatment is essential in such cases.
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http://dx.doi.org/10.1155/2017/8596781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591917PMC
August 2017

Assessment of quality of life in patients undergoing hemodialysis using WHOQOL-BREF questionnaire: a multicenter study.

Int J Nephrol Renovasc Dis 2017 19;10:195-203. Epub 2017 Jul 19.

Department of Internal Medicine, Tribhuvan University, Institute of Medicine, Maharajgunj, Kathmandu, Nepal.

Background: Assessment of quality of life (QOL) of patients with end-stage renal disease has become increasingly important, both in order to evaluate the influence of the disease on patients and the type of renal replacement therapy they require. Therefore, in this study, we aimed to assess QOL in patients undergoing hemodialysis and evaluated the effects of various sociodemographic factors affecting QOL of such patients in Nepal.

Methods: A cross-sectional study was conducted among 150 patients with chronic kidney disease undergoing hemodialysis at two major centers in Nepal. Demographic data including age, sex, ethnicity, educational status, marital status, employment, income, duration of illness, and duration on hemodialysis were collected. QOL was assessed using the World Health Organization Quality of life (WHOQOL-BREF) questionnaire. Four domains (physical, psychological, social, and environmental) and two items (overall perception of QOL and health) of the WHOQOL-BREF were the primary end points of this study. Bivariate relationship between sociodemographic factors and QOL scores were analyzed using independent samples -test and one-way analysis of variance. Multiple linear regression analysis was performed to determine independent predictors of QOL.

Results: Following QOL scores were recorded: environmental domain (53.17±15.59), psychological domain (51.23±18.61), social domain (49.86±21.64), and physical domain (45.93±16.90). Older age was associated with a better QOL score in the social domain (=0.005), and employed patients scored better in the environmental domain (=0.019). Unemployed patients and those of the Terai/Madhesi ethnic group had significantly low scores in overall perception of health (<0.05) as compared to other groups. Low income status and increased duration on hemodialysis were found to be the only independent negative predictors of QOL in patients with hemodialysis (<0.05).

Conclusion: Patients with chronic kidney disease on dialysis had overall low QOL scores in all four domains. Age, ethnicity, employment status, income, and duration on hemodialysis affected one or more domains of QOL in such patients. Low income status and increased duration on hemodialysis were the only independent negative predictors of QOL of patients on maintenance hemodialysis.
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http://dx.doi.org/10.2147/IJNRD.S136522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529382PMC
July 2017

Pancreatic pseudocyst or mucinous cystadenocarcinoma of pancreas? A diagnostic dilemma.

Clin Case Rep 2017 Apr 6;5(4):501-504. Epub 2017 Mar 6.

Department of Radiology Institute of Medicine Kathmandu Nepal.

Pancreatic cystic neoplasm is difficult to distinguish from pseudocyst as clinical and radiological evidences may not be sufficient to make an accurate diagnosis. This may result in misdiagnosis with inappropriate management. Hence, every effort should be made for their distinction to avoid internal drainage procedures for neoplasms instead of extirpation.
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http://dx.doi.org/10.1002/ccr3.887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378858PMC
April 2017

Hepatitis B virus induced cytoplasmic antineutrophil cytoplasmic antibody-mediated vasculitis causing subarachnoid hemorrhage, acute transverse myelitis, and nephropathy: a case report.

J Med Case Rep 2017 Apr 3;11(1):91. Epub 2017 Apr 3.

Tribhuvan University, Institute of Medicine, Maharajgunj Medical Campus, Kathmandu, Nepal.

Background: Transverse myelitis, subarachnoid hemorrhage, and nephropathy are established but rare complications of hepatitis B virus infection that can potentially be triggered by an antibody-mediated vasculitis as a result of a viral infection. The following is a case report detailing a patient presenting with all three of the above presentations who is cytoplasmic antineutrophil cytoplasmic antibody-positive and a chronic carrier of hepatitis B.

Case Presentation: A 33-year-old Nepalese man presented to our hospital with headache, swelling of his body, paraplegia, and back pain that developed over a period of 10 days. Laboratory studies showed proteinuria and elevated levels of serum urea and creatinine. Viral serology was suggestive of chronic inactive hepatitis B carrier state. A computed tomography scan of his head revealed features suggestive of subarachnoid hemorrhage. Magnetic resonance imaging of his dorsal spine showed diffuse T2 high signal intensity within his spinal cord extending from second to 12th thoracic vertebral level which was suggestive of transverse myelitis. The origin of these symptoms was attributed to immune complex-mediated vasculitis after serum analysis for cytoplasmic antineutrophil cytoplasmic antibody came out positive. He was managed with steroids administered orally and intravenously and entecavir administered orally.

Conclusion: This case highlights the possibility of a hepatitis B virus-induced vasculitis as the cause of subarachnoid hemorrhage, transverse myelitis, and nephropathy.
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http://dx.doi.org/10.1186/s13256-017-1255-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376690PMC
April 2017

Translational potential of long-term decreases in mitochondrial lipids in a mouse model of Gulf War Illness.

Toxicology 2016 Nov 29;372:22-33. Epub 2016 Oct 29.

Roskamp Institute, Sarasota, FL, USA; James A. Haley VA Hospital, Tampa, FL, USA; Open University, Milton Keynes, UK.

Gulf War Illness (GWI) affects 25% of veterans from the 1990-1991 Gulf War (GW) and is accompanied by damage to the brain regions involved in memory processing. After twenty-five years, the chronic pathobiology of GWI is still unexplained. To address this problem, we examined the long-term consequences of GW exposures in an established GWI mouse model to identify biological processes that are relevant to the chronic symptoms of GWI. Three-month old male C57BL6 mice were exposed for 10days to GW agents (pyridostigmine bromide and permethrin). Barnes Maze testing conducted at 15- and 16-months post-exposure revealed learning and memory impairment. Immunohistochemical analyses showed astroglia and microglia activation in the hippocampi of exposed mice. Proteomic studies identified perturbation of mitochondria function and metabolomics data showed decreases in the Krebs cycle compounds, lactate, β-hydroxybutyrate and glycerol-3 phosphate in the brains of exposed mice. Lipidomics data showed decreases in fatty acids, acylcarnitines and phospholipids, including cardiolipins in the brains of exposed mice. Pilot biomarker studies showed that plasma from exposed mice and veterans with GWI had increases in odd-chain, and decreases in long-chain, acylcarnitines compared to their respective controls. Very long-chain acylcarnitines were decreased in veterans with GWI compared to controls. These studies suggest that mitochondrial lipid disturbances might be associated with GWI and that further investigation is required to determine its role in the pathophysiology of this illness. Targeting mitochondrial function may provide effective therapies for GWI, and that lipid abnormalities could serve as biomarkers of GWI.
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http://dx.doi.org/10.1016/j.tox.2016.10.012DOI Listing
November 2016
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