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Anti-PCSK9 Vaccines - An Emerging Therapeutic Innovative Game Changer in Dyslipidemia and Beyond
Mrinal Kanti Das,
Tapan Sinha,
Mahesh Kumar Chaudhary
Issue:
Volume 8, Issue 6, November 2020
Pages:
250-253
Received:
23 September 2020
Accepted:
15 October 2020
Published:
26 October 2020
Abstract: Proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) regulates the cholesterol metabolism by genetic mechanism mediating the LDL receptor degradation. Gain of the functions of the PCSK9 variants resulted in high level of LDL-cholesterol and loss of function in low level of the LDL-cholesterol level. The low level of LDL-cholesterol was associated with significant decrease in coronary artery disease. The genetic insight of lipid homeostasis and complex molecular biochemistry triggered a domain of active pharmacological research with prospect of introducing paradigm shift in primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in group of non-responders to anti-cholesterol treatment. The result has been the discovery of the PCSK9 inhibitors and vaccines. The former got the statutory approval by Federal Drug Administration (FDA) in conditions namely patients with heterozygous familial hypercholesterolemia (FH), individuals with ASCVD requiring further lowering of LDL-cholesterol levels. This has also important role in statin-intolerant patients. The various international guidelines have put the concept of the therapeutic approach in acute coronary syndrome (ACS) specially in high risk post-MI patients. However the present article will focus more on the PCSK9 vaccine and the encouraging evidences of its pleotropic effects in treatment of chronic clinical conditions and cancer. There are few challenges which need to be further explored especially considering the cost-benefit ratio. There is also the need of further research focusing on the expansion of the indications.
Abstract: Proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) regulates the cholesterol metabolism by genetic mechanism mediating the LDL receptor degradation. Gain of the functions of the PCSK9 variants resulted in high level of LDL-cholesterol and loss of function in low level of the LDL-cholesterol level. The low level of LDL-cholesterol...
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The Lag Time of Diagnosis of Axial Spondyloarthritis: A Bangladesh Perspective
Abu Tahir Muhammad Tanveer Hasan,
Muhammad Abdul Alim
Issue:
Volume 8, Issue 6, November 2020
Pages:
254-257
Received:
24 September 2020
Accepted:
15 October 2020
Published:
30 October 2020
Abstract: Background & Objective: The lag time of diagnosis of axial spondyloarthrits varies from country to country. The aim of this study was to find out the lag time of diagnosis of axial spondyloarthritis in Bangladesh based on the patients visiting the morning Rheumatology OPD of a tertiary-care hospital. Materials & Methods: This study was conducted in the Department of Rheumatology of Enam Medical College & Hospital, Savar, Dhaka, Bangladesh from October, 2018 to December, 2019. Ninety six patients with axial spondyloarthritis were recruited and they were enquired about their ages, places of residence, educational qualifications and duration of axial pain as well as peripheral pain. The participants also underwent estimation of ESR by Westergren method. Results: Mean age of the participants was 39.98 years. The mean and median lag times of diagnosis were 58.17 and 36 months respectively. The lag time of diagnosis followed a nonnormal (right-skewed) distribution. There was no significant difference between males and females (p≈0.921), between rural and urban participants (p≈0.221), between those with and without peripheral involvement (p≈0.387) as well as between those with and without elevated ESR according to Mann-Whitney U test. But the median lag time in those who were highly educated, ie. those who completed at least a bachelor degree was significantly (p≈0.016) shorter than that in those who were not highly educated. Conclusion: There is a considerable median delay in the diagnosis of axial spondyloarthritis in Bangladesh. Further research is required to identify the factors contributing to the delay so that those can be addressed to shorten the lag time.
Abstract: Background & Objective: The lag time of diagnosis of axial spondyloarthrits varies from country to country. The aim of this study was to find out the lag time of diagnosis of axial spondyloarthritis in Bangladesh based on the patients visiting the morning Rheumatology OPD of a tertiary-care hospital. Materials & Methods: This study was conducted in...
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Risk Factors and Impact of Diagnostic Delay in Patients with Inflammatory Bowel Disease in Bangladesh
Chanchal Kumar Ghosh,
S. M. Ali Hasan,
Md Abdur Rahim Miah
Issue:
Volume 8, Issue 6, November 2020
Pages:
258-262
Received:
14 October 2020
Accepted:
23 October 2020
Published:
30 October 2020
Abstract: Background and Aims: A delay in the diagnosis of inflammatory bowel disease (IBD) is a risk of developing complications and surgery. This study was done to evaluate the factors and impact of diagnostic delay on IBD patients in Bangladesh. Methods: This cross-sectional study was carried out in the Department of Gastroenterology of a tertiary care center in Bangladesh. Diagnostic delay was defined as the period from symptom onset to diagnosis of IBD. Results: Of the total 112 IBD patients 50 (44.6%) had Crohn’s disease CD and 62 (55.4%) had ulcerative colitis (UC). Males (67.9%) were predominant in the study. The median diagnostic delay was longer for patients with CD compared with patients with UC (median 24 versus 12 months; P-value 0.025). Rectal bleeding as presenting feature and male gender were negatively and positively associated with the longer diagnostic delay of IBD respectively (P-value <0.05). Of the patients with CD 14 (28%) had a history of IBD-related surgery and 7 (14%) had a history of perianal fistula. The presence of intestinal strictures, surgery, and perianal fistula at the time of diagnosis was significantly associated with long diagnostic delay for CD. Conclusion: Absence of rectal bleeding as presenting symptoms and also the male gender were the significant factors related to the longer diagnostic delay of IBD in our study. Long diagnostic delay is associated with an increased rate of complications in IBD, especially in CD.
Abstract: Background and Aims: A delay in the diagnosis of inflammatory bowel disease (IBD) is a risk of developing complications and surgery. This study was done to evaluate the factors and impact of diagnostic delay on IBD patients in Bangladesh. Methods: This cross-sectional study was carried out in the Department of Gastroenterology of a tertiary care ce...
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Contribution of Scanner in the Breast Cancer Extension Assessment in the Radiology Department of CNHU-HKM in Benin
Yekpe Ahouansou Patricia,
Adjadohoun Sonia,
Lokossou Symphorose,
Ngamo Gabriel,
Lokossou Andreas,
Kiki Miralda,
Akanni Djivèdé,
Biaou Olivier
Issue:
Volume 8, Issue 6, November 2020
Pages:
263-266
Received:
6 October 2020
Accepted:
27 October 2020
Published:
4 November 2020
Abstract: Objective: Breast cancer is the most common female cancer in the world. The prognosis depends on whether metastasis is present or not. The objective of this study was to provide an overview of the CT scan aspects identified during the evaluation of breast cancer extension in the Radiology department of the Teaching University Hospital of Hubert Koutoukou Maga (CNHU-HKM) in Cotonou in Benin. Materials and methods: It was a descriptive study with retrospective collection, conducted from January 1, 2018 to January 31, 2019 (13 months), in the Radiology department of CNHU-HKM. It focused on patients referred for a chest-abdominal-pelvic computed tomography (PET) scan, as part of an extension assessment for breast cancer. Results: During the period of the study, 40 chest-abdominal-pelvic CT scans were compiled, of which 38 (95%) were women and 02 men (5%), and among which 23 were metastatic, accountings for a prevalence of 57.5%. The average age was 51.22±16.33 with extremes of 30 and 83 years old. Among our patients, 32 (80%) had undergone a CT scan for an initial diagnostic of extension assessment, and 08 (20%) for the therapeutic response assessment. According to the TNM classification, T4 tumors accounted for 27.5% (11 cases). Lymph node involvement was found in 18 cases (43.90%), accounting for 12 (30%) of N1 and 6 (15%) of N3. The most commonly found metastatic sites were the lung in 25% followed by the pleura and the liver with equal percentages (10%). The metastases CT scan aspect was typically a carcinomatous lymphangitis appearance; fluid pleural effusions; hypodenses, hypovascular nodules hepatics; osteolytic or mixed bone damage and peritoneum, especially fluid effusion associated with peritoneal nodules. Conclusion: The frequency of breast cancer metastases is high in Benin. The most commonly found metastatic sites on scanner in descending order are the lungs, liver and bones.
Abstract: Objective: Breast cancer is the most common female cancer in the world. The prognosis depends on whether metastasis is present or not. The objective of this study was to provide an overview of the CT scan aspects identified during the evaluation of breast cancer extension in the Radiology department of the Teaching University Hospital of Hubert Kou...
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Postural Instability in a Young Dyslexic Adult Improved by Hebbian Pulse-width Modulated Lighting
Albert Le Floch,
Samuel Henriat,
Rosane Fourage,
Guy Ropars
Issue:
Volume 8, Issue 6, November 2020
Pages:
267-273
Received:
14 October 2020
Accepted:
23 October 2020
Published:
4 November 2020
Abstract: Background: Postural stability is linked to vision in everyone, since when the eyes are closed stability decreases by a factor of 2 or more. However, in persons with dyslexia postural stability is often deficient even when the eyes are open, since they show deficits in motor as well as specific cognitive functions. In dyslexics we have shown that abnormal symmetry between retinal Maxwell’s centroid outlines occurs, perturbing the interhemispheric connections. We have also shown that pulse-width modulated lighting can compensate for this lack of asymmetry, improving the reading skills. Objective: As the postural stability and the vision are correlated, one may wonder if the excess of the postural instability recorded in a young adult with dyslexia can also be reduced by a pulse-width modulated light controlling the Hebbian synaptic plasticity. Method: Using a force platform we compared the postural responses of an observer without dyslexia with the responses of a subject with dyslexia, by measuring their respective standing postures with eyes open looking at a target in a room with either continuous or pulse lighting. Results: There was no effect of changing the lighting conditions on the postural control of the subject without dyslexia. However, we found that the postural stability of the subject with dyslexia which was actually impaired during continuous light, but was greatly improved when a 80 Hz pulsed light frequency was used. Importantly, the excursions of the surface area of the center of pressure on the force platform were reduced by a factor of 2.3. Conclusion: The postural instability in a dyslexic person can be improved by pulse-width modulated lighting.
Abstract: Background: Postural stability is linked to vision in everyone, since when the eyes are closed stability decreases by a factor of 2 or more. However, in persons with dyslexia postural stability is often deficient even when the eyes are open, since they show deficits in motor as well as specific cognitive functions. In dyslexics we have shown that a...
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Dyslipidemia and Atherosclerotic Cardiovascular Disease: Flash Back and Vision Ahead
Prabhash Chand Manoria,
Pankaj Manoria,
Rajesh Kumar Shrivastava,
Sharad Kumar Parashar
Issue:
Volume 8, Issue 6, November 2020
Pages:
274-278
Received:
23 September 2020
Accepted:
26 October 2020
Published:
16 November 2020
Abstract: Dyslipidemia is the most common modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD). There is unequivocal evidence that Low Density Lipoprotein Cholesterol (LDL-C) is the main culprit. Statins, ezetimibe, bempedoic acid and Proprotein Convertase Subtilisin/ Kexin Type 9 (PCSK9) inhibitors are used to target LDL-C. Statin is always utilized as the first line therapy and they decrease LDL-C by approximately 1 mmol/l (40 mg/dL). If the LDL goals are not achieved ezetimibe is used and this decreases LDL-C by 15-20%. Bempedoic acid can also be utilized to lower LDL-C before initiating PCSK9 inhibitors but this is not available in India as yet. PCSK9 inhibitors decrease LDL-C by 1 to 1.5 mmol/l (40-60 mg/dL) on top of all lipid lowering therapy and with this very low LDL-C level targets of < 55 or even < 40 mg/dL can be achieved in very high risk patient. After the LDL-C goal is achieved, non HDL-C is targeted if the triglycerides (TG) levels are above 200 mg/dL. Targeting HDL-C with drugs is not recommended because all trials of HDL-C elevating drugs on top of statins have been negative. The role of TG has a causal factor for ASCVD is still in the process of evolution. Icospent ethyl in REDUCE IT trial has shown reduction in ischemic cardiovascular events in patients with established CVD or diabetics with other risk factors on statins and elevated TG between 135-499 mg/dL. but the mechanism of benefit does not seem to be related to lowering of TG because the benefit was similar in subgroup of patients with TG > 150 <150 mg/dL. Inclisiran which blocks the synthesis of PCSK9 is emerging as very exciting molecule for the future. It decreases LDL-C by 50% which remains there for six months after a single injection of 300 mg.
Abstract: Dyslipidemia is the most common modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD). There is unequivocal evidence that Low Density Lipoprotein Cholesterol (LDL-C) is the main culprit. Statins, ezetimibe, bempedoic acid and Proprotein Convertase Subtilisin/ Kexin Type 9 (PCSK9) inhibitors are used to target LDL-C. Statin is al...
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Familial Hypercholesterolemia: Improving Outcomes with Newer Agents
Saumitra Ray,
Biswarup Sarkar
Issue:
Volume 8, Issue 6, November 2020
Pages:
279-284
Received:
23 September 2020
Accepted:
15 October 2020
Published:
16 November 2020
Abstract: Familial hypercholesterolemia (FH) is one of the commonest autosomal dominant genetic disorders which affects lipoprotein metabolism in the body, causing thereby severe hypercholesterolemia, mainly contributed by high level of low density lipoprotein cholesterol (LDLc). This causes polyvascular premature atherosclerosis with significant mortality, especially in the homozygous form (HoFH), where affected persons die in their teens. There are well developed diagnostic criteria for FH but the index of suspicion of the physician needs to be high to detect heterozygous FH. As the blood LDLc values are very high, even the highest doses of statins cannot bring down the levels to optimum. Life style management should also be rigorously implemented. Ezetimibe imparts some extra 10 to 15% reduction of LDLc on top of maximally tolerated dose of statins. PCSK9I agents are recently approved for FH. They reduce LDLc further by 30-50%. The small interfering RNA, inclisiran, reduces LDLc by almost 60% and has shown clinical benefit in FH patients. Many other newer agents are in the pipe line of development. In extreme cases, plasmapheresis is life saving, but difficult to adopt as a regular long term treatment. Often the absolute target of LDLc level is not achieved even with all available measures, and a more than 50% reduction from the baseline value is all that can be attained. Early diagnosis by screening of first degree relatives of the index case helps to attain long term clinical benefit.
Abstract: Familial hypercholesterolemia (FH) is one of the commonest autosomal dominant genetic disorders which affects lipoprotein metabolism in the body, causing thereby severe hypercholesterolemia, mainly contributed by high level of low density lipoprotein cholesterol (LDLc). This causes polyvascular premature atherosclerosis with significant mortality, ...
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Remdesivir Induced Liver Injury and Severe COVID-19 Infection
Chanchal Kumar Ghosh,
S. M. Ali Hasan,
Suman Dey
Issue:
Volume 8, Issue 6, November 2020
Pages:
285-288
Received:
4 November 2020
Accepted:
13 November 2020
Published:
23 November 2020
Abstract: Background and Aims: Remdesivir is identified as an effective therapeutic option in COVID-19, but its’ hepatic safety has not been well studied. So, we aimed to identify the pattern and severity of hepatotoxicity in remdesivir treated COVID-19 patients. Methods: This cross-sectional study was carried out at a dedicated COVID-19 unit of a university hospital in Dhaka, Bangladesh among severe COVID-19 cases. Alterations of liver functions were compared between the remdesivir and the non-remdesivir treated patients. Results: Out of 50 severe COVID-19 cases 25 had received remdesivir and 25 had received other supportive care without remdesivir. Median serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values were significantly higher in the remdesivir treated arm (p-value for AST <0.0001 and ALT <0.001). Grade-2 elevation of AST and ALT and grade-3 elevation of AST levels were significantly higher among the remdesivir treated group. No patients had significant bilirubin elevation (≥2.5 mg/dl) and only 1 patient had INR >1.5 in the remdesivir treated arm. Conclusion: Many of the patients with severe COVID-19 had mild to moderate aminotransferases elevation. If the elevation of liver enzymes occurs after the initiation of remdesivir, adverse drug reactions need to be considered and drug discontinuation may require if severe elevation occurs.
Abstract: Background and Aims: Remdesivir is identified as an effective therapeutic option in COVID-19, but its’ hepatic safety has not been well studied. So, we aimed to identify the pattern and severity of hepatotoxicity in remdesivir treated COVID-19 patients. Methods: This cross-sectional study was carried out at a dedicated COVID-19 unit of a university...
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A Brief Review for Clinicians of Iron Metabolism and the Safety, Efficacy, and Rationale for Use of Intravenous Iron Products
Marshall Patrick Stagg,
Jennifer Miatech,
Hailey Tarleton
Issue:
Volume 8, Issue 6, November 2020
Pages:
289-303
Received:
2 October 2020
Accepted:
17 October 2020
Published:
27 November 2020
Abstract: Iron is an abundant element that is essential for multiple biologic processes. Iron metabolism is not entirely understood, but since the discovery of hepcidin, much progress has been made especially in the last five years. This article is intended to enhance clinician understanding of iron metabolism which may inform decisions about parenteral iron use in iron-restricted erythropoiesis (IResE). This article briefly discusses intravenous (IV) iron utilization in iron deficiency, anemia of chronic inflammation (ACI), functional iron deficiency (FID), and anemia associated with chronic kidney disease, heart failure, pregnancy, inflammatory bowel disease and cancer. Oral iron therapy is valuable in mild to moderate pure iron deficiency. Intravenous iron is required when a prompt response is needed in severe pure iron deficiency. ACI is a hypoferremic state resulting from altered iron metabolism. In ACI, IV iron is needed to overcome the blocking effects of hepcidin on intestinal absorption. ESAs stimulate erythropoiesis increasing iron utilization. This surge in iron requirement can result in FID, especially when ESAs are used in patients with ACI. Intravenous iron is required to treat or avoid iron deficiency in FID when inflammation is present. Parenteral iron maximizes ESA response and can make using erythropoiesis-stimulating agents (ESAs) safer by being ESA sparing. The complex and seemingly ubiquitous nature of iron in humans and the inadequate methods of assessment of iron status in inflammatory states means clinical and laboratory monitoring and individualization of care remain essential. The decision to administer intravenous iron is complex as it often lacks robust consensus guidelines; despite this we can expect utilization of these products to increase as they are safe, effective and necessary.
Abstract: Iron is an abundant element that is essential for multiple biologic processes. Iron metabolism is not entirely understood, but since the discovery of hepcidin, much progress has been made especially in the last five years. This article is intended to enhance clinician understanding of iron metabolism which may inform decisions about parenteral iron...
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Biological Incorporation of Lyophilized Radiation Sterilized Bone Allograft and Mixed Bone Graft for the Management of Cysts and Cyst Like Lesions in Bone
Nakul Kumar Datta,
Krishna Priya Das,
Mohammad Mamun Mia
Issue:
Volume 8, Issue 6, November 2020
Pages:
304-311
Received:
31 October 2020
Accepted:
16 November 2020
Published:
4 December 2020
Abstract: Cystic lesions include Simple bone cyst and Aneurysmal bone cyst, and among cyst like lesions studied Giant cell tumor, fibrous dysplasia and Non-ossifying fibroma. This prospective interventional study was conducted in the Department of orthopaedic surgery Bangubandhu Sheikh Mujib Mdical university (BSMMU) and Biomedical research division, Atomic energy centre Savar, Dhaka Bangladesh from January 2004 to December 2019. Out of 155 Cysts and cysts like lesions were operated, among which cystic lesions were 73 (47.10%), among cystic lesions SBC was 51 (69.86%), and ABC-22 (30.14%) and cyst like lesions were 82 (52.90%), among cyst like lesions GCT was 68 (82.92%), FD was 12 (14.63%) & NOF was 2 (2.43%). All cases were operated by thorough curettage and cavity filled with Lyophilized radiation sterilized bone allograft impregnated with autogenous bone marrow for children and mixed bone graft in adult. Clinical and radiological evaluation was done in all cases in which 61 (83.56%) out of 73 cystic lesions were healed and 12 (16.44%) lesions were recurred, on the other hand 58 (70.73%) out of 82 cyst like lesions were healed and 24 (29.27%) lesions were recurred. Out of 155 cysts and cyst like lesions 119 (76.78%) were healed / satisfactory and 36 (23.22%) were recurred. Follow up period were 9 month to 15 years. P value is <.001. Main aims to evaluate the complete healing of cystic and cyst like lesions of bone with in corporation of allograft. Bone marrow impregnated Lyophilized radiation sterilized bone allograft and mixed bone graft is useful graft material for healing of the lesional area and restoring structural integrity as well as function for management of cysts and cyst like lesions in bone.
Abstract: Cystic lesions include Simple bone cyst and Aneurysmal bone cyst, and among cyst like lesions studied Giant cell tumor, fibrous dysplasia and Non-ossifying fibroma. This prospective interventional study was conducted in the Department of orthopaedic surgery Bangubandhu Sheikh Mujib Mdical university (BSMMU) and Biomedical research division, Atomic ...
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Acquired Hemophilia B Through Liver Transplantation: A Case Report and Literature Review
Christine Jane Kurian,
Douglass Alan Drelich,
Sanaa Rizk
Issue:
Volume 8, Issue 6, November 2020
Pages:
312-315
Received:
4 October 2020
Accepted:
28 October 2020
Published:
16 December 2020
Abstract: Hemophilia B, also called Christmas disease, is an X-linked inherited bleeding disorder that predominantly affects males, and it is caused by deficiency of coagulation factor IX. Factor IX is a coagulation factor produced in the liver. Liver transplantation from hemophilia B donors is neither widely documented nor performed due to presumed risk of developing increased bleeding tendency in the recipient due to potential acquired factor IX deficiency. In this review, we present a case of liver and kidney transplantation from a donor with mild hemophilia B to a recipient with no history of hemophilia B and literature review. This is a relatively rare situation with only two other prior case reports of acquired Hemophilia B through liver transplantation noted in 2015. The 2 cases presented in the literature lead to acquired hemophilia B in liver transplant recipients since donors were not screened due to mild disease and low suspicion level. In our case, the donor was known to have mild Hemophilia B and the recipient had a rapid decline – thus it is imperative to weigh risks and benefits of transplantation from this donor population. While those individuals with mild hemophilia B disease (and low bleeding burden) should be considered as an alternative donor for liver transplantation, appropriate counseling should be done with the recipient about possible bleeding risks and OLT should only occur after patient consent. A multidisciplinary approach should involve hematology in case factor replacement therapy is needed post transplantation and for long term follow up.
Abstract: Hemophilia B, also called Christmas disease, is an X-linked inherited bleeding disorder that predominantly affects males, and it is caused by deficiency of coagulation factor IX. Factor IX is a coagulation factor produced in the liver. Liver transplantation from hemophilia B donors is neither widely documented nor performed due to presumed risk of ...
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