Papers by keshav raj Sigdel
Clinical Case Reports, Oct 31, 2023
Rheumatology & autoimmunity, Jul 17, 2022
Wellcome open research, Oct 16, 2020
We report a case of an adult female with pulmonary tuberculosis who had biochemical evidence of l... more We report a case of an adult female with pulmonary tuberculosis who had biochemical evidence of liver injury during the presentation manifested as raised transaminases, but without clinically obvious pre-existing liver disease nor a history of hepatotoxic drug use. This is a fairly common scenario seen in tuberculosis endemic areas; however, this is an under reported condition in the literature and guidelines for its management has not been established. Many clinicians including the authors have treated such cases with modified liver friendly regimens in fear of increasing the hepatotoxicity with standard antitubercular drugs. However, the modified regimens may not be optimal in treating the underlying tuberculosis. In this report, we gave full dose standard drugs, and the liver injury resolved as evidenced by normalization of transaminases. Further research is required in this regard, but the presence of transaminitis with no obvious common underlying etiology may not warrant a modification of standard antitubercular regimen.
Wellcome open research, Jun 17, 2019
A 50 year old woman from Nepal had clinical features suggestive of meningitis. Cerebrospinal flui... more A 50 year old woman from Nepal had clinical features suggestive of meningitis. Cerebrospinal fluid (CSF) analysis was normal except for the presence of cryptococcal antigen. The inclusion of test for in Cryptococcus the CSF helped in making the diagnosis of cryptococcal meningitis in our patient who was apparently immunocompetent. Treatment with liposomal amphotericin B could not be started on time due to financial constraints. The patient had a stroke and further deteriorated. Liposomal amphotericin B is stocked by the government of Nepal for free supply to patients with visceral leishmaniasis, but the policy does not allow the drug to be dispensed for other infections. The family members of our patient acquired the drug within a few days from a government center using their political connections and following administering the treatment the patient improved. This case demonstrates the utility of considering cryptococcal meningitis as a differential diagnosis, and including tests for Cryptococcus when dealing with immunocompetent patients presenting with meningitis. It also demonstrates the effects of the sociopolitical situation on health care delivery in low-and middle-income countries (LMICs) such as Nepal.
International Immunopharmacology, Jun 1, 2014
IL-17 is a cytokine that produced by various type of cell. Previous studies have been shown that ... more IL-17 is a cytokine that produced by various type of cell. Previous studies have been shown that IL-17 plays a crit-20 ical role in the pathogenesis of different diseases. However, few studies have addressed the source and mecha-21 nism of IL-17 in the development of allograft rejection response. In this study, we present that the IL-17 22 expression reaches the strongest response at the early stage of cardiac allograft rejection, and was elevated earlier 23 than DC maturation. The IL-17 is predominantly produced by CD3 + T cells, whereas CD11c, CD11b, and NK1.1 24 positive cells rarely expressed IL-17. It is worth noting that blockade of endogenous IL-17 activity suppressed 25 DC maturation, decreased inflammatory cytokines and impaired Th1 immune response during acute allograft re-26 jection. Furthermore, adoptive transfer with DCs from IL-17-treated mice had a significant longer allograft surviv-27 al time and decreased number of IFN-γ produced by T cells. Consistently, in an in vitro experiment, recombinant 28 IL-17 significantly up-regulate co-stimulatory molecules of bone marrow derived dendritic cells (BMDCs), and IL-29 17-treated BMDCs show that an increased capacity to enhance T cell function was also observed. In conclusion, 30 our data provide clear evidence that the early elevated level of IL-17 contributes to allograft rejection through 31 modulating dendritic cell function.
Journal of immunology research, Feb 28, 2019
Journal of Patan Academy of Health Sciences, May 8, 2020
Introduction: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute... more Introduction: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and presents with fever, dry cough, fatigue, myalgia, and dyspnea. This study aims to is find out the understanding of COVID-19 among doctors at Patan Hospital.
Mediators of Inflammation, 2016
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by aberrant T ce... more Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by aberrant T cell immune response. Diffuse proliferative lupus nephritis (LN-IV) is the most common, severe, and active form of lupus nephritis. In this study, we investigated the production of Th1, Th2, and Th17 cytokines in prediction of active form of LN-IV. ProcartaPlex multiplex immunoassays panels were used for detection of serum Th1, Th2, and Th17 cytokines profiling. Th1 and Th17 cytokines (IL-18, IFN-, IL-12p70, IL-6, and IL-17A) were considerably expressed in the serum of lupus nephritis IV patients in comparison to the healthy control. However, only IL18 and IL6 were higher in class IV versus class III lupus nephritis. Importantly, the ratios of Th1/Th2 (IL-18/IL-4) and Th17/Th2 (IL-17A/IL-4) were significantly elevated in LN-IV when compared with LN-III, LN-V, and healthy controls. Consistently, the serum cytokines IL-18, IL-17A, and IFN-were markedly expressed in LN-IV patient glomeruli and interstitial tissue compared to other classes of LN by IHC. ROC further suggests that IL-18 was a potential marker for LN-IV. The data from our study suggests that the early detection and quantification of these cytokines may help in prediction of active form of LN-IV.
Journal of Patan Academy of Health Sciences, Dec 30, 2022
Introduction: Any symptoms acquired after COVID-19 infection that persists beyond 12 weeks period... more Introduction: Any symptoms acquired after COVID-19 infection that persists beyond 12 weeks period and not explained by any other disease either already present or acquired after COVID-19 infection is termed as long COVID 19 by World Health Organisation. We tried to find out the prevalence of long COVID 19 in healthcare workers. Method: Questionnaire was made in google form based on COVID-19 Yorkshire Rehabilitation Screening Tool (COVID YRS Tool). Ethical approval was taken from IRC-PAHS. Data collected from all health care workers of PAHS from 2022/05/20 to 2022/07/20. Difference in Precovid and Postcovid status in different domains were compared by statistical tests. Result: The median age of our participants was 29 years. Prevalence of Long COVID 19 was 68.1%. 19 55.3% ha mild, 10.4% had moderate, 2.4% had severe symptoms. The most common symptom was fatigue (44%), anxiety (41%) and shortness of breath (36%). The COVID YRS Tool overall score was statically significant with p value <0.001. Pre COVID 19 and Post COVID 19, patients had statically significant in breathlessness, fatigue, nutrition, anxiety, usual activity, pain, anxiety and depression. Only 6% of our patients had severe COVID 19. Conclusion: People are still experiencing various symptoms after COVID 19 infection. Long COVID 19 has now been a health care problem. Long COVID 19 patients have multisystem involvement and multi-speciality team is needed for their management and rehabilitation.
Wellcome open research, Mar 26, 2019
A 50 year old woman from Nepal had clinical features suggestive of meningitis. Cerebrospinal flui... more A 50 year old woman from Nepal had clinical features suggestive of meningitis. Cerebrospinal fluid (CSF) analysis was normal except for the presence of cryptococcal antigen. The inclusion of test for in the CSF helped Cryptococcus in making the diagnosis of cryptococcal meningitis in our patient who was apparently immunocompetent. Treatment with liposomal amphotericin B could not be started on time due financial constraints. The patient had a stroke and further deteriorated. Liposomal amphotericin B is stocked by the government of Nepal for free supply to patients with visceral leishmaniasis, but the policy does not allow the drug to be dispensed for other infections. The family members of our patient acquired the drug within a few days from a government center using their political connections and following administering the treatment the patient improved. This case demonstrates the utility of considering cryptococcal meningitis as a differential diagnosis, and including tests for Cryptococcus when dealing with immunocompetent patients presenting with meningitis. It also demonstrates the effects of the sociopolitical situation on health care delivery in low-and middle-income countries (LMICs) such as Nepal.
Journal of Patan Academy of Health Sciences, Dec 31, 2021
Introduction: Coronavirus disease 2019 (COVID-19) caused by Severe acute respiratory syndrome cor... more Introduction: Coronavirus disease 2019 (COVID-19) caused by Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) may present with more severe symptoms in immunocompromised and elderly patients, including chronic myeloid leukemia (CML) patients. Method: From Jan 2020 to June 2021 all adult CML cohort receiving treatment from Patan Hospital, identified with COVID-19 infection were included in the study to analyze the severity of symptoms of COVID-19 in different age groups, phases of the CML, types of Tyrosine Kinase Inhibitor (TKI) used, and overall outcome. Ethical approval was obtained. Data were analyzed for association between variables by Fisher exact test using SPSS software. Result: Out of 882 CML cohort 23(2.60%) patients had COVID-19, more in the female population and in the younger age group, but the mortality was higher in the elderly age group which was statically significant. Regardless of symptoms, stages, different TKI used, about 92% recovered fully from COVID-19 infection. Conclusion: The incidence rate of COVID-19 infection in CML cohort patients, was 2.6%, and 92% recovered. Advanced stage of CML and elderly were had a more severe infection and higher mortality rate.
Wellcome open research, Jun 16, 2022
Paraquat (1, 1′-dimethyl-4,4′-bipyridinium) is a commonly used herbicide that is highly toxic whe... more Paraquat (1, 1′-dimethyl-4,4′-bipyridinium) is a commonly used herbicide that is highly toxic when ingested. Ingestion of toxic doses of paraquat has serious complications on the lungs, gastrointestinal tract, kidney, liver, and other organs. Due to its inherent toxicity and the lack of a specific antidote, it has a high case fatality rate. Despite being restricted to commercially licensed users in Nepal, it is a common herbicide causing both intentional and accidental poisoning. Although there have been numerous anecdotal cases of paraquat poisoning in Nepal, no reports have been published in the literature.. We report a case of a 30-year old female, who developed gastrointestinal symptoms like vomiting, diarrhoea and odynophagia, renal and liver injury after accidental ingestion of 10ml of 20% paraquat. Symptoms and organ involvement subsided with timely and appropriate supportive management.
Wellcome open research, Aug 1, 2019
Ayurvedic medicine, a traditional system of medicine practiced in the Indian subcontinent is cons... more Ayurvedic medicine, a traditional system of medicine practiced in the Indian subcontinent is considered to be devoid of adverse effects. We report three cases which highlight the possibility of adverse events related with the use ofwith the use of ayurvedic products. A 35 years old woman with hepatitis took ayurvedic powder medicine and with swarnabhasma (gold salt)s and had her liver injury worsened, possibly due to alkaloids, and developed nephrotic syndrome, possibly due to and gold salt. A 57 years old hypertensive man was taking ayurvedic medicine containing reserpine which had long been withdrawn from the allopathic system of medicine due to wide range of side effects. A 47 years old woman with rheumatoid arthritis was taking an unknown tablet containing a steroid as an adulterant for 2 years and developed side effects typical of steroid excess. We like to highlight the fact that ayurvedic medicines do have propensity to may cause adverse effects due to adulterations or inherent constituents like alkaloids, and hence are may not always be completely safe.
Wellcome open research, Jan 22, 2019
We report two cases which highlight the fact how poor communication leads to dangerously poor hea... more We report two cases which highlight the fact how poor communication leads to dangerously poor health outcome. We present the case of a 50-year-old woman recently diagnosed with rheumatoid arthritis from Southern Nepal presented to Patan hospital with multiple episodes of vomiting and oral ulcers following the intake of methotrexate every day for 11 days, who was managed in the intensive care unit. Similarly, we present a 40-year-old man with ileo-caecal tuberculosis who was prescribed with anti-tubercular therapy (ATT) and prednisolone, who failed to take ATT due to poor communication and presented to Patan Hospital with features of disseminated tuberculosis following intake of 2 weeks of prednisolone alone. These were events that could have been easily prevented with proper communication skills. Improvement of communication between doctors and patients is paramount so that life-threatening events like these could be avoided.
Wellcome open research, Aug 22, 2022
Isoniazid is an anti-tuberculosis medication that is extensively used for treatment and preventio... more Isoniazid is an anti-tuberculosis medication that is extensively used for treatment and prevention of tuberculosis. Acute isoniazid poisoning is characterized by a clinical triad of recurrent seizures, raised anion gap metabolic acidosis and coma. The seizures are unresponsive to standard anticonvulsant drugs, instead requiring pyridoxine administered in a dose equal to the amount of isoniazid consumed. Due to the high incidence of tuberculosis in low-income countries like Nepal, isoniazid intoxication should be considered in any patient who present with such unresponsive seizures and coma. We report a case of a 31 years old woman from Nepal, who intentionally ingested 12 grams of isoniazid and presented with generalized tonic-clonic seizures. She was successfully managed with 10 grams of pyridoxine along with other supportive management, including sodium bicarbonate for metabolic acidosis and mechanical ventilation. Doctors working in low-income countries, like Nepal, where tuberculosis is endemic, should be well acquainted with presentations and management of isoniazid intoxication.
Frontiers in Immunology, Jun 27, 2022
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by multiarticular, symm... more Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by multiarticular, symmetrical and invasive arthritis resulting from immune system abnormalities involving T and B lymphocytes. Although significant progress has been made in the understanding of RA pathogenesis, the underlying mechanisms are not fully understood. Recent studies suggest that NLRP3 inflammasome, a regulator of inflammation, might play an important role in the development of RA. There have been increasing clinical and pre-clinical evidence showing the treatment of NLRP3/IL-1b in inflammatory diseases. To provide a foundation for the development of therapeutic strategies, we will briefly summarize the roles of NLRP3 inflammasome in RA and explore its potential clinical treatment.
Rheumatology & autoimmunity, Jul 17, 2022
Rheumatology, 2016
Objectives: The role of bone disease in spondyloarthropathy (SpA) remains of great interest with ... more Objectives: The role of bone disease in spondyloarthropathy (SpA) remains of great interest with evidence of an increased risk of bone fragility and fracture. The effects of lifestyle factors such as sun light exposure and vitamin D deficiency on SpA remain uncertain. The study was to examine those factors on skeletal integrity in axial spondyloarthropathy (axSpA) patients associated with sub-clinical osteomalacia. Material and Methods: 95 axSpA patients and 74 healthy controls in the same season were enrolled. ASASendorsed disease activity score (ASDAS), 25-hydroxyvitamin D, parathyroid hormone (PTH), bone turnover biomarkers procollagen type 1 N-terminal peptide (PINP) and osteocalcin(OC), serum C-telopeptides of type I collagen (sCTX), serum alkaline phosphatase (sALP), adjusted calcium, C-reactive protein, bone minimal density (BMD) of total proximal femur and lumbar spine were measured. Questionnaires on daily sun exposure time and other factors were ascertained. Results: axSpA patients were with significantly decreased vitamin D and raised sALP levels than controls (p<0.001). 74% of axSpA patients had vitamin D deficiency. Their vitamin D levels were inversely related to the disease duration (r=-0.234, p<0.05) but positively to daily sunlight exposure time and calcium (r=0.064, p<0.001, respectively). axSpA patients had significantly higher bone turnover biomarkers sCTX and OC (p<0.05), and significantly lower femoral neck T and Z scores in BMD than controls (p=0.000). Conclusion: Vitamin D insufficiency exist in most (74%) of axSpA patients. axSpA patients exhibited significantly lower vitamin D and raised ALP levels, and with significantly higher bone turnover biomarkers and low BMD than controls, which indicated that subclinical biochemical osteomalacia associated with most axSpA patients.
Kathmandu University Medical Journal, May 1, 2013
Eosinophilic fasciitis is a rare systemic disease characterized by inflammatory thickening of the... more Eosinophilic fasciitis is a rare systemic disease characterized by inflammatory thickening of the skin and underlying fascia, peripheral eosinophilia, elevated inflammatory markers and typical biopsy findings. Internal organ involvement is rare unlike in other fibrosing disorders. Though this is usually a benign disease, it is often difficult to diagnose and the course may also be variable. Glucocorticoids are the mainstay of therapy, but in many cases steroid sparing immunosuppressive drugs are required particularly if the diseases has protracted course. The author reports a typical case of this rare disorder which could well be a first report from Nepal.
The Lancet Regional Health - Western Pacific, Oct 1, 2021
Background: Clinical remission is an attainable goal for Rheumatoid Arthritis (RA). However, data... more Background: Clinical remission is an attainable goal for Rheumatoid Arthritis (RA). However, data on RA remission rates in Asia-Pacific region are lacking. We conducted a cross-sectional study to evaluate the clinical remission status and the associated factors in RA patients in Asia-Pacific region. Methods: RA patients receiving standard care were enrolled consecutively from 17 sites in 11 countries. Data were collected on-site by rheumatologists with a standardized case-report form. Remission was analyzed by different definitions including disease activity score using 28 joints (DAS28) based on ESR and CRP, clinical disease activity index (CDAI), simplified disease activity index (SDAI), Boolean remission definition, and clinical deep remission (CliDR). Logistic regression was used to determine associated factors of remission. Findings: A total of 2010 RA patients was included in the study, the overall remission rates were 62·31% (DAS28-CRP), 35·51% (DAS28-ESR), 30·78% (CDAI), 26·50% (SDAI), 24·71% (Boolean), and 17·06% (CliDR), respectively, and varied from sites to sites in the 11 countries. Biological disease-modifying antirheumatic drugs (bDMARDs) prescription rate was low (16·9%). Compared to patients in non-remission, patients in remission had higher rates of csDMARDs monotherapy, bDMARDs usage and lower rates of GC usage. The favorable factors were male sex, younger age, fewer comorbidities, less extra-articular manifestations (EAM), and use of bDMARDs, while treatment with GC was negatively associated with remission. Interpretation: Remission rates were low and varied in the Asia-Pacific region. Treatment with bDMARDs and less GC usage were related to higher remission rate. There is an unmet need for RA remission in the Asia-Pacific region. Funding Information: Beijing Municipal Science and Technology Project (Z191100006619110), Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Peking-Tsinghua Center for Life Sciences. Declaration of Interests: None. Ethics Approval Statement: The study was approved by the ethics committee of each center.
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Papers by keshav raj Sigdel