Hyperlipidemia and Platelet Parameters: Two Sides of the Same Coin.

INTRODUCTION:  Hyperlipidemia is a disorder in which lipid and cholesterol levels in the blood are elevated. Diabetes, coronary heart disease, obesity, and hypertension are commonly linked to hyperlipidemia. Despite this, hyperlipidemia is a widely neglected illness, owing to its asymptomatic nature, ignorance of aberrant lipid profiles on screening, and economic issues in poor countries such as India. Platelets have been shown to have a role in the thrombus consequences of atheromatous damage in hyperlipidemic individuals by initiating and propagating atherosclerotic plaques. Platelets with bigger diameters are thought to be more metabolically, enzymatically, and functionally agile than platelets with lower sizes. In steady-state operation, these bigger platelets release more thromboxane B2 than regular platelets. Platelets with bigger sizes are more hemostatically active and hence have a higher chance of forming a thrombus and thromboembolism. The aim of this study was to compare the values of key platelet parameters and platelet function in hyperlipidemic patients with normal age and sex-matched controls. MATERIAL AND METHODS:  A total of 100 individuals were included in this study, with 68 cases of hyperlipidemia and 32 controls having normal lipid profiles. Platelet volume indices (PVI) such as platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (P-LCR), plateletcrit (PCT), and platelet function (platelet aggregation with adenosine diphosphate, ADP) were compared between hyperlipidemia patients and age sex-matched controls with normal lipid profiles. RESULTS:  The cases had a statistically significant higher mean MPV (10.55 ± 1.81), PDW (14.93 ± 2.82), and P-LCR (30.97 ± 11.74) compared to mean MPV (9.35 ± 1.85), PDW (13.10 ± 2.60), and P-LCR (25.13 ± 12.23) of controls (p-value < 0.05). No significant difference was observed between the study group and control group with respect to mean PC and PCT (p-value > 0.05). In this study, there was a statistically significant increase noted in platelet aggregation percentage in hyperlipidemic patients than in the control group (42.03 ± 25.28 vs 31.25 ± 15.11) (p-value < 0.05). CONCLUSION:  To conclude, platelet parameters are a significant, easy, and cost-effective method for predicting future acute episodes in hyperlipidemic patients that should be utilized more widely. To avoid vascular events, these individuals may require higher antiplatelet dosages and more rigorous hyperlipidemia therapy.

Association of Serum Ferritin Levels with Microalbuminuria, Glycemic Control and Dyslipidemia.

As diabetes is on the rise worldwide, early screening and detection of its complications is crucial. The first clinical sign of renal dysfunction in diabetes is microalbuminuria. Ferritin may have a possible role in the development and prediction of microalbuminuria and other complications of diabetes by 3 possible mechanisms- 1) it is a marker of elevated body iron stores. 2) acts as acute-phase reactant and elevation reflects inflammation 3) Delayed clearance of glycosylated ferritin in patients with diabetes causes raised ferritin levels. In this premise, we studied the association between serum ferritin levels and microalbuminuria, glycemic control and dyslipidemia in type 2 diabetic patients. MATERIAL: A cross-sectional study was carried out at a tertiary hospital in northern India involving 152 patients of type 2 diabetes mellitus. Anthropometric measurements (weight, height), sample collection for basic laboratory parameters including complete blood count, kidney function tests, liver function tests, HbA1c, lipid profile, serum iron and ferritin levels, urinary albumin- creatinine ratio was done. A fundus examination was performed. Results were analyzed using descriptive statistics and making comparisons among various groups. Categorical data were summarized as proportions or percentages while discrete as mean. Chi-square test was used for testing associations. OBSERVATION: Mean serum ferritin levels were significantly higher in patients having microalbuminuria as against patients having normal urinary albumin- creatinine ratio (539 vs 292, p-value- 0.04). Patients having poor glycemic control (HbA1c > 7) had higher ferritin levels (p-value- 0.024). There was a near-significant association (p-value-0.06) between serum ferritin and triglyceride levels. More cases with raised serum ferritin had higher triglyceride levels. Patients having microalbuminuria had a higher prevalence of diabetic retinopathy (p-value- 0.003) and higher triglyceride levels (p-value- 0.041). CONCLUSION: Ferritin can act as a marker of diabetic nephropathy, poor glycemic control and dyslipidemia in type 2 diabetic patients. Our study, therefore, indicates that programs to prevent complications of diabetes would be more effective by placing greater emphasis on patients having higher ferritin levels.

Ischemic and Bleeding Profile of Patients on Dual Antiplatelet Therapy beyond 1 Year of Index Acute Coronary Syndrome / Percutaneous Intervention.

Dual antiplatelet treatment (DAPT) is the cornerstone of the management and prophylaxis of acute coronary syndrome (ACS). However, the associated risk of bleeding with the usage of DAPT and risk of thrombosis with stoppage of the drug makes it a challenging task to take appropriate decisions regarding the choice and duration of DAPT. The present study is aimed to tackle these challenges and to analyze whether prolonged dual antiplatelet therapy carries more risk of bleeding or a higher risk of thrombosis is present with discontinuation of the same. MATERIAL: In this study, a total of 235 cases of confirmed myocardial infarction, unstable angina, or those who underwent percutaneous intervention were included. After 1 year, the number of patients on DAPT, the type of antiplatelets they were using were observed, their ischemic risk was calculated using DAPT score, and bleeding risk was calculated using PRECISE-DAPT score. Bleeding events were assessed using BARC classification. OBSERVATION: Out of 235 patients, the majority of the patients were males (78.7%). Only 7.2% of the patients had bleeding since the start of the drugs. The majority (5% out of 7.2%) of bleeding episodes were clinically insignificant. 163 (69%) patients were on Dual antiplatelet therapy after 1 year. Out of which 115 were appropriately taking DAPT as per their DAPT score. Patients with high bleeding risk (PRECISE DAPT score ≥25) were 89, out of which 38 (53.2%) patients were taking SAPT, appropriate for their bleeding risk. While 112 (68.7%) were taking prolonged DAPT, appropriate for PRECISE-DAPT risk. CONCLUSION: The majority of patients remained on DAPT following discharge for more than 1 year after ACS. This suggests that treating physicians prioritizes ischemic risk reduction over bleeding risk in patients with ACS, according to the patient's risk profile.

Study of microalbuminuria in chronic obstructive pulmonary disease patients at tertiary care teaching hospital.

BACKGROUND: Hypoxemia-induced endothelial dysfunction leads to microalbuminuria. Microalbuminuria (MAB) has also been used as a parameter to assess the risk of cardiovascular events in an individual. The aim of this study was to observe the relationship of MAB in patients with chronic obstructive pulmonary disease (COPD) and to correlate MAB with different stages of COPD. MATERIALS AND METHODS: This cross sectional study included 140 patients with COPD selected according to GOLD guidelines based on COPD test assessment score and the number of exacerbations who had smoking pack years of more than 10 years. Urine albumin creatinine ratio (UACR) more than 30 mg/gm represents MAB. RESULTS: The UACR increases as the severity of groups of COPD increases with significant differences in UACR values among different COPD groups. Significant differences were seen among various groups of COPD when compared for different clinical parameters such as SPO2, PaO2, PaCO2, pH, and C-reactive protein (CRP). Pearson correlation analysis revealed that UACR was significantly inversely related with PaO2 (r = -0.514, P < 0.001), SPO2 (r = -0.397, P < 0.001) and FEV1 (r = -0.441, P < 0.001) and it was significantly positively correlated with PaCO2 (r = 0.675, P < 0.001). CONCLUSION: This study indicates that there is strong relationship of MAB in patients with COPD and the levels of MAB increase as the severity of COPD increases due to hypoxia and endothelial dysfunction. As MAB is a marker for cardiovascular risk, patients with COPD can be routinely evaluated for the urine test of MAB specially who are at increased risk for cardiovascular events.

Relative Prevalence and Outcome of Fetal Neural Tube Defect in a Developing Country.

OBJECTIVES: To find out the relative prevalence of fetal neural tube defect (NTD) and its outcome in terms of survival at birth and beyond 2 years of age. METHODS: A 10-year prospective (2008-2018) observational study was performed, which included all prenatally detected fetal NTD. Two-year follow-up was done in cases of pregnancies resulting in live birth, in terms of their survival, physical morbidity and developmental delay. RESULTS: NTD was seen in 401/648 (62%) cases among the central nervous system malformations. More than half of the cases (54.1%) presented after 20 weeks of gestation, and 42.8% of the mothers were primiparous. Spina bifida was seen in 206 cases, anencephaly in 144, encephalocele in 43, whereas iniencephaly was seen in only eight cases. Associated anomalies were present in 51.2%. Only 19.0% cases were live-born, and merely 11% were alive beyond 2 years of age. Among types of spina bifida, lumbosacral meningomyocele was the most common (41.6%), whereas thoracic was the rarest (8.7%). After 2 years, physical disability was observed in more than half of the cases who survived. CONCLUSIONS: NTD is one of the commonest malformations with high mortality, and the physical and mental sub-normality is high among those who survive.

Assessment of subclinical atherosclerosis and endothelial dysfunction in chronic kidney disease by measurement of carotid intima media thickness and flow-mediated vasodilatation in North Indian population.

BACKGROUND: Chronic kidney disease (CKD) predisposes to accelerated atherosclerosis that is measured by carotid artery intima media thickness (CIMT) and brachial artery flow-mediated dilation (FMD). The aim of this study was to assess the noninvasive risk markers of subclinical atherosclerosis and endothelial dysfunction and their correlation with disease severity. METHODS AND RESULTS: This was a cross-sectional study conducted in 62 patients with CKD: 38 predialysis and 24 on hemodialysis and 50 age- and gender-matched controls. In both the patients and controls, high-sensitivity C-reactive protein (CRP) levels, %FMD, and CIMT were measured. Patients with CKD had increased CRP levels {[5.8 (1.0-6.0)] mg/L vs [1.0 (0.5-2.20)] mg/L; P < 0.001}; %FMD was significantly lower in patients on hemodialysis (5.51%) compared with stage IV (7.62%) and stage III (15.02%) and 17.95% in control subjects (P < 0.001); and CIMT values in hemodialysis patients (0.88 ± 0.06 mm) were significantly higher compared with stage IV (0.67 ± 0.10) and stage III (0.61 ± 0.12) (P < 0.001). Increased CIMT values were seen in patients with CKD (0.82 ± 0.21 mm) than in the healthy controls (0.55 ± 0.16 mm). In patients with CKD, a significant negative correlation was found between CRP levels and FMD responses (r = -0.315; P < 0.001), while a significant positive correlation was found between CRP and CIMT values (r = 0.327; P < 0.001). Compared with predialysis, hemodialysis subjects had significantly lower FMD and higher CRP and IMT values. CONCLUSION: CKD confers a higher inflammatory status when compared with apparently healthy general population. Abnormal FMD responses and CIMT values are more commonly found in dialysis patients. Our findings suggest that CIMT and FMD can be used as noninvasive markers for early risk assessment and stratification in various stages of CKD.

Clinical Characteristic and Risk Factors of Acute Kidney Injury among Dengue Viral Infections in Adults: A Retrospective Analysis.

Dengue is a growing public health problem in India, and acute kidney injury (AKI) is one of the least studied complications of dengue virus infection (DVI). This study was conducted to investigate the incidence, clinical characteristics, and risk factors for AKI in DVI. This was a retrospective study of patients with confirmed DVI presenting as dengue fever (DF) or dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) at our center over a period of 2 years. A total of 620 subjects fulfilling inclusion criteria were studied. Patients were divided into two cohorts (90 patients with AKI and 530 patients without AKI) to determine independent predictors of AKI. Among 620 patients, 454 (73.22%) had classical DF, 141 (22.74%) patients had DHF, and 25 (4.03%) patients had DSS. AKI was present in 90 (16.36%) patients; approximately one-third (31, 34.45%) had AKIN stage 1, 33 (36.66%) patients had AKIN stage 2, and 26 (28.88%) had AKIN stage 3. Among those with AKI, 14 patients expired and all had DHF/DSS. On multivariate logistic regression, AKI was associated with male gender [odds ratio (OR): 2.9], DHF (OR: 7.9), rhabdomyolysis (OR: 8.2), multiple-organ dysfunction (OR: 18.2), hypertension (OR: 0.7), diabetes mellitus (OR: 4.8), delayed hospitalization (OR: 2.2), and use of nephrotoxic drugs (OR: 2.86). In all, 320 patients (51.61%) had hospital stay >3 days. We found that AKI was an independent predictor for longer duration of hospital stay (OR: 7.2, 95% confidence interval: 4.8-10.7). AKI in DVI is associated with significant morbidity, mortality and longer hospital stay.

Cocaine Abuse: An Unusual Association.

Cocaine addiction is a common problem in the adolescent and the young adults, pharmacologic interventions to reverse the effects of which do not exist. Neurological complications of cocaine abuse, such as seizures, headache, ischemic or hemorrhagic stroke, or subarachnoid hemorrhage, can be disastrous as a result of uncontrolled vasoconstriction and vasculitic damage. The lone occurrence of subdural hematoma in the absence of any other intracranial hemorrhagic complication is rarely seen in patients of cocaine abuse. We wish to share our experience of one such patient who presented to us with an unusual combination of the widespread cerebral infarction and subdural hematoma.

Takotsubo cardiomyopathy.

Acute and rapidly reversible left ventricular dysfunction may be triggered by various emotional and physical insults. The most common precipitant being the death of a close family member but the other reported precipitants include court appearance, fear of a procedure, arguments and surprise parties and reunions. This entity is now well known as stress cardiomyopathy or Takotsubo cardiomyopathy. We report a case of rapidly reversible left ventricular dysfunction following attempted suicide by hanging.

Paraphenylenediamine poisoning.

Hair dye containing paraphenylenediamine (PPD) is widely used in India because of its free availability and low cost. PPD produces local as well as systemic toxic effects when applied topically and/or ingested. It is highly toxic when taken by mouth and the outcome depends mainly on the dose taken. Important clinical manifestations are angioedema leading to dysphasia and respiratory distress, rhabdomyolysis, intravascular hemolysis, acute renal failure and hepatic necrosis. Myocarditis or fatal arrhythmia may also occur in PPD poisoning. Mainstay of management is early recognition and supportive measures as there is no specific antidote. We hereby report a young female who presented to us with features of angioedema, cardiac manifestation and hepatic dysfunction after ingesting PPD, which was treated successfully. In the absence of laboratory facilities, clinical features like angioedema and chocolate brown-colored urine could be suggestive of PPD poisoning.

D-Limonene modulates inflammation, oxidative stress and Ras-ERK pathway to inhibit murine skin tumorigenesis.

D-Limonene, a common monoterepene has been shown to have antiproliferative, apoptosis-inducing and chemopreventive effects. In the present study, we have investigated the effects of D-limonene on the growth of 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor development. We found that D-limonene (50 and 100 mg/kg body weight) treatments to the mouse skin significantly reduced the TPA-induced (a) edema and hyperplasia (p < 0.001); (b) expression of cyclooxygenase-2; (c) ornithine decarboxylase activity (p < 0.001); and (d) [(3)H] thymidine incorporation into DNA (p < 0.001). In addition, treatment of D-limonene effectively restored the level of reduced glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, catalase and malondialdehyde production in TPA-treated mouse skin. In a two-stage skin tumorigenesis study, D-limonene significantly reduced the tumor burden (p < 0.005) and tumor incidence as compared to DMBA/TPA-treated mice. D-Limonene treatment also extended the latency period of tumor development from 4 to 9 weeks. D-Limonene treatment decreased the expression level of Ras, Raf and phosphorylation of extracellular signal-regulated protein kinase 1/2 in DMBA/TPA-induced tumors. A decrease in the expression of Bcl-2 and an increase in Bax expression were also observed in tumor tissues of mice treated with D-limonene. Taken together, our findings suggest that D-limonene may exert its chemopreventive activity through the inhibition of inflammation, oxidative stress and Ras-signaling as well as the induction of pro-apoptotic state during TPA-mediated promotion of DMBA-induced skin cancer in mouse model.

Falciparum malaria presenting as subdural hematoma.

Falciparum malaria is a common disease in tropical countries associated with myriad of complications that can be life-threatening. We hereby report an 85 year old male who was suffering from falciparum malaria and presented with subdural hematoma, an unusual complication of central nervous system secondary to severe thrombocytopenia.

Sturge Weber syndrome.

Sturge Weber Syndrome also called as encephalotrigeminal angiomatosis is a sporadically occurring neurocutaneous syndrome, characterized by vascular malformation with capillary venous angiomas that involve face, choroid of eye and leptomeninges with resulting neurological and orbital manifestations. We hereby report a young unmarried girl who diagnosed as a case of SWS on the basis of Port wine stain since birth, past history of seizures since the age of four years and at this time presented with status epilepticus, mental retardation (I.Q.--30 to 35), EEG abnormality and characteristic imaging findings. This may be a common condition for paediatrician and neurologist but as a physician we usually do not see it that often.

Epigallocatechin-3-gallate inhibits paracrine and autocrine hepatocyte growth factor/scatter factor-induced tumor cell migration and invasion.

Aberrant activation of hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, Met, is involved in the development and progression of many human cancers. In the cell-based screening assay, (-)epigallocatechin-3-gallate (EGCG) inhibited HGF/SF-Met signaling as indicated by its inhibitory activity on HGF/SF-induced cell scattering and uPA activation (IC50=15.8 microgram/ml). Further analysis revealed that EGCG at low doses specifically inhibited HGF/SF-induced tyrosine phosphorylation of Met but not epidermal growth factor (EGF)-induced phosphorylation of EGF receptor (EGFR). On the other hand, high-dose EGCG decreased both Met and EGFR proteins. We also found that EGCG did not act on the intracellular portion of Met receptor tyrosine kinase, i.e., it inhibited InlB-dependent activation of Met but not NGF-induced activation of Trk-Met hybrid receptor. This inhibition decreased HGF-induced migration and invasion by parental or HGF/SF-transfected B16F10 melanoma cells in vitro in either a paracrine or autocrine manner. Furthermore, EGCG inhibited the invasion/metastasis of HGF/SF-transfected B16F10 melanoma cells in mice. Our data suggest the possible use of EGCG in human cancers associated with dysregulated paracrine or autocrine HGF/SF-Met signaling.

Abdominal angina: an unusual presentation of Takayasu's arteritis.

Takayasu's arteritis (TA) is an idiopathic large vessel vasculitis of young adults that affects the aorta and its major branches. The authors hereby present a case of TA that presented with abdominal aorta thrombosis. She was put on low-molecular weight heparin, antiplatelets, corticosteroids, cyclophosphamide along with haematinics and was referred to Department of Cardiothoracic and Vascular Surgery for further management.

Recurrent lower motor neuron type facial palsy: an unusual manifestation of SLE.

Facial nerve palsy is the most common cause of mononeuropathy in the humans, Bell's palsy being the commonest cause of that. Cranial neuropathy, particularly facial is a rare event in systemic lupus erythematosus (SLE). The authors hereby report on a 20-year-old female patient who had recurrent lower motor neuron type facial palsy and on subsequent workup she was diagnosed as a case of SLE. She was put on oral prednisolone to which she showed gradual response. The authors believe that this is the first case report of SLE presenting as recurrent facial palsy.

Disseminated tuberculosis: interesting hematological observations.

Disseminated tuberculosis can present in various ways including prolonged fever / pyrexia of unknown origin, hepatosplenomegaly, lymphadenopathy, meningitis and rarely extreme forms of hematological abnormalities such as pancytopenia and leukemoid reaction. We hereby report a case who presented with short history of fever, associated with vomiting and altered sensorium. He also had evidence of meningitis on neuroimaging with equivocal CSF finding. During his stay, he showed a spectrum of interesting hematological findings, including severe pancytopenia on peripheral smear, hemophagocytosis, epithelioid cell granuloma with Langhans' giant cells and focal necrosis consistent with tuberculosis on bone marrow examination. He showed an excellent clinical as well as hematological response to four drug antitubercular treatment (RHZE). The report highlights the significance of hematological picture in final confirmation of tuberculosis which may otherwise be passed off as nutritional or other unrelated causes.