Mismatch repair protein deficiency assessed by immunohistochemistry in sporadic colorectal carcinoma

Context: Globally, colorectal carcinoma (CRC) ranks the third most commonly diagnosed malignant disease, one of the leading causes of cancer deaths. Aims: To study the spectrum of clinicopathological characteristics of sporadic colorectal carcinoma and to assess mismatch repair gene deficiency by the expression pattern of the proteins assessed by immunohistochemistry. Setting and Design: Observational study conducted in a tertiary care hospital in West Bengal. Materials and Methods: Fifty-two surgically resected specimens of CRC received from January 2018 to May 2019 were studied for clinical, morphological, MSI status. Statistical Analysis Used: IBM SPSS 23. Results: A total of 50% of the cases belonged to younger and 50% to the older population, with male predominance being 53.8%. The most common histologic type was adenocarcinoma (88.5%). The majority was found to be well-differentiated carcinoma (50%). The majority cases were of the T3 stage accounting to 38.5%. A total of 24 out of 52 cases (46.15%) had an absent expression of at least one mismatch repair (MMR) protein. A significant correlation was found between the young age group and microsatellite instability (MSI) with a P value of 0.001. A significant association was found between MSI and tumor differentiation with P value of 0.018. A significant association was found between MSH6 and histological type with P value of 0.012. A significant association was found between MSI and tumor stage with P value of 0.032. Conclusions: This study shows a significantly higher number of sporadic colon cancers involving the young age group, and younger cases showed significant association with MSI. This alarming trend needs validation by studies involving larger populations and can be helpful prognostically as well as in formulating chemotherapeutic regimens.

Clinical Profile of MDR-TB patients with special reference to kanamycin induced ototoxicity in a tertiary care hospital of eastern India

Introduction: MDR-TB is defined as resistance to isoniazid and rifampicin, with or without resistance to other anti-TB drugs. Multidrug-resistant TB (MDR-TB) remains a public health crisis and a health security threat. Kanamycin, is an aminoglycoside antibiotic used to treat multi-drug resistant TB in the intensive phase. Objective: To analyze the patients of MDR-TB with respect to age, sex and presence of comorbidities like diabetes mellitus. Also to study the incidence of hearing impairments among patients of MDR-TB receiving injectable Kanamycin. Methods: 40 patients of MDR-TB diagnosed by sputum culture and drug susceptibility testing (DST) have been classified on the basis of age, sex and presence of diabetes mellitus. All have received injectable Kanamycin for 6months in their intensive phase (IP). Patients giving history of auditory impairments underwent pure tone audiometry (PTA) for detection of sensory neural hearing loss, if any. Result: Out of 40 patients of MDR-TB, 30 were males and the rest 10 were females. Age ranges from 12 to 70 years among which maximum patients fell in the age group of 21-30 years (12 patients). 16 patients were diabetic. After getting Kanamycin, 8 patients gave the history of auditory disturbances and only 1 patient found to have severe sensory neural hearing loss confirmed by pure tone audiometry. Conclusion: Prevalence of MDR-TB has been found more among males and in younger age group. Diabetes Mellitus play a major role here. Kanamycin induced hearing loss is not a very serious concern in our study.

Assessment of efficacy of Anti-IgE (Omalizumab) therapy in patients with severe allergic asthma in a tertiary care hospital of Eastern India

Introduction: Immunoglobulin E dependent mechanisms play an important role in the development of airway inflammation in allergic asthma. Atopic patients with severe asthma frequently have poorly controlled disease. Many have poor asthma control despite intensive treatment. Severe allergic asthma patients frequently treated with oral corticosteroids and therefore may develop serious side-effects. Anti-IgE antibody had been used in severe persistent allergic asthma in Western countries. However, its long-term efficacy in patients in India has not been reported. Objective: To assess the efficacy of anti IgE therapy in patients with severe allergic asthma. Method: 30 (16 male and 14 female) patients, with mean age of 49 having severe persistent allergic asthma, with recurrent exacerbations and on oral/IV steroids, received Omalizumab 150mg/300mg/450 mg for 1 year. Total dose of oral Steroids, use of rescue medications, changes in lung function (FEV1) were recorded at the baseline, 16 weeks & at end of the treatment (52 weeks) and then analyzed. Results: Significant reduction observed in total oral steroid use at 16 week & at 52 weeks. -10.5mg (p<0.003) & 22.5mg respectively. Use of rescue medications decreased by -7.90 puffs(p- <0.001) at 16 weeks and by -13.67 puffs (13.67 (p -<0.001) at 52 weeks. Improvements in lung Function (FEV1) observed with a tune of 700 ml. from Baseline after 52 weeks therapy. Conclusion: Use of anti-IgE antibody for 1 year is well tolerated and led to an overall significant improvement in patients with severe persistent allergic asthma.

Profile of tuberculous meningitis with or without HIV infection and the predicators of adverse outcome / Perfil de la meningitis tuberculosa con o sin infección por VIH y predictores de la evolución clínica adversa

OBJECTIVES: To compare the clinical, radiological and cerebrospinal fluid (CSF) findings, at hospital admission, among adult patients with tuberculous meningitis (TBM) with or without HIV infection and to identify the factors that predict adverse outcome at six months. METHODS: A total of 82 adult patients with TBM were included (40 HIV-positive and 42 HIV-negative). Several clinical (duration of illness, Glasgow Coma Scale score, presence of high temperature, headache, cranial nerve or sphincter abnormality, seizures and endocrine dysfunction), radiological (presence of hydrocephalus, cerebral infarction and oedema, meningeal enhancement, granuloma) and cerebrospinal fluid parameters (glucose, protein, lactate, lymphocytes, neutrophils and adenosine deaminase values) were recorded along with CD4 count in the peripheral blood. Statistical analysis was performed using the chi-square test. Individual variables were evaluated as prognostic factors for adverse outcome in both groups by calculating the relative risk of association for each. RESULTS: Temperature more than 38.33ºC was more common in the HIV-negative group while seizures, hydrocephalus, cerebral infarction and low CD4 count occurred significantly more commonly in the HIV-positive group. Hydrocephalus had strong association with severe neurological deficit and seizure with death in both the groups. CONCLUSION: Several clinical and laboratory features of TBM in patients who are HIV-positive are distinctly different from those without HIV infection; some of these have an association with the probability of adverse outcome.

OBJETIVOS: Comparar los hallazgos clínicos, radiológicos y del líquido cefalorraquídeo (LCR) entre pacientes adultos con meningitis tuberculosa (MTB) con o sin infección de VIH en su ingreso al hospital, e identificar los factores que predicen la evolución clínica adversa en seis meses. MÉTODOS: Un total de 82 pacientes adultos con MTB fueron incluidos (40 VIH positivos y 42 VIH negativos). Se registraron varios parámetros: clínicos (duración de la enfermedad, puntuación de la Escala de Coma de Glasgow, presencia de alta temperatura, dolor de cabeza, anormalidad del esfínter o nervio craneal, o anormalidad del esfínter, convulsiones y disfunción endocrina); radiológicos (la presencia de hidrocefalia, infarto cerebral, edema, realce meníngeo, granuloma); y del líquido (glucosa, proteína, lactato, linfocitos, neutrófilos, y valores de adenosina deaminasa), junto con un conteo de CD4 en la sangre periférica. Se realizó un análisis estadístico usando la prueba de chi-cuadrado. La variable individual se evaluó como factor pronóstico de la evolución clínica en ambos, calculando el riesgo relativo de asociación para cada uno. RESULTADOS: Una temperatura de más de 38.33ºC fue más común en el grupo VIH negativo, mientras que convulsiones, hidrocefalia, infarto cerebral, y bajo conteo de CD4 ocurrieron significativamente más normalmente en el grupo VIH positivo. La hidrocefalia estuvo fuertemente asociada con un déficit neurológico severo y la convulsión con la muerte en ambos grupos. CONCLUSIÓN: Varias características clínicas y de laboratorio del MTB en pacientes que son VIH positivos, difieren claramente de aquellos con infección por VIH. Algunas de estas características se hallan asociadas con la probabilidad de una evolución clínica adversa.

Alteration of timing of secretion of vascular endothelial growth factors is responsible for progression of diabetic retinopathy.

Diabetic retinopathy is one of the most common complications in diabetes mellitus due to persistent hyperglycaemia. Various biochemical mechanisms have been suggested to cause this complication. The authors' present study which included 100 patients of type-2 diabetes mellitus with different stages of diabetic retinopathy and without retinopathy shows that initiation of diabetic retinopathy is associated with increased anaerobic glycolysis and accelerated oxidative stress. Progression of this complication is guided by increased secretion of vascular endothelial growth factors. It is our assumption that increased secretion of vascular endothelial growth factors in early part of this disease e.g. before occurrence of morphological abnormality may modify this complication.

Scleredema of Buschke: a rare post-streptococcal complication.

A 19-year male presented with acute onset, gradually progressive symmetric indurations involving the skin over the face, neck, shoulders and upper part of chest following an upper respiratory tract infection. Detailed history and examination did not reveal evidence of Raynauds' phenomenon, nail changes, digital ulcers, pigmentation or any systemic involvement. Autoantibodies for systemic sclerosis were absent. Histopathology of skin biopsy documented scleredema. Antistreptolysin O (ASO) titer was elevated. We diagnosed a case of Scleredema adultorum of Buschke following a streptococcal throat infection. We report this case to highlight the importance of clinically differentiating this relatively benign, self-limiting disorder from systemic sclerosis.

Observations of hepatic encephalopathy profile in a tertiary care centre.

A study was conducted among 67 patients presenting with hepatic encephalopathy to establish the aetiological diagnosis and record the incidence of acute and chronic liver diseases. They all had undergone thorough clinical and laboratory evaluation. The factor precipitating encephalopathy was also identified. Among 67 patients 19 (28.4%) had acute liver disease and 48 (71.6%) had chronic liver disease. Majority of patients had grade 2 encephalopathy at presentation. Among the acute cases most common aetiology was acute viral hepatitis due to hepatitis B and E viruses whereas alcoholic liver disease was the most frequent cause of chronic liver disease. The most common precipitating factor was gastro-intestinal haemorrhage.

Correlation of lipid profile and carotid artery plaque as detected by Doppler ultrasound in ischaemic stroke patients--A hospital-based study.

Stroke is one of the leading causes of morbidity and mortality all over the world. Carotid plaque formation and intima media thickness can be a predictor of ischaemic stroke. In this regard studies from our country, are few and far between. This is a small hospital-based study to look in to this matter. We have assessed the intima media thickness of the common carotid as well as the internal and external carotid arteries by the ultrasound method. The lipid profiles were estimated and correlated with the intima media thickness. Results indicate that in the common as well as in the internal and external carotid arteries, the intima media thickness is a good predictor of ischaemic stroke. This thickness is also well correlated with the lipid levels in blood. Hence this non-invasive method can be used successfully to identify the high risk patients, prone to develop stroke.

Risk factor analysis in ischaemic stroke: a hospital-based study.

Stroke represents a major health burden in our country. Ischaemic stroke has got several risk factors associated with increased chance of atherosclerosis. A small hospital-based study was done to look into the risk factors associated with ischaemic stroke. Forty patients with CT-confirmed cerebral infarction were taken for the study and detailed history and clinical findings were obtained. Investigations like complete haemogram, fasting blood glucose, urea, creatinine, lipid profile, serum Lp(a), homocysteine, fibrinogen, ECG, chest x-ray, echocardiography, MRI/MRA where indicated, were done to identify the risk factors as well. Results indicated that hypertension was the most prevalent (87.5%) risk factor followed by ischaemic heart disease (35%) and diabetes. Dyslipidaemia was also found in a significant number of cases, mostly elevated LDL, low HDL and elevated Lp(a). Fibrinogen and homocysteine were of less significance.

Glycaemic consequences of HIV and highly active antiretroviral therapy: a pilot study and review of literature.

The metabolic consequences of HIV and AIDS are accentuated in the setting of highly active antiretroviral therapy. Peripheral lipodystrophy, central adiposity, hyperlipidaemia, insulin resistance and diabetes mellitus are frequent associations of protease inhibitor containing highly active antiretroviral therapy regimens. Ninety patients aged 25-50 years (males 52, females 38), seropositive for HIV 1 and 2 or both were selected to see the glycaemic profiles in asymptomatic early HIV disease with CD4 counts > 100/microl and to compare this with the glycaemic profile of (a) advanced HIV disease (CD4 counts < 200/microl), not on highly active antiretroviral therapy and (b) advanced HIV disease (CD4 counts < 200/microl), on uninterrupted non-protease inhibitor highly active antiretroviral therapy > 6 months. All the patients were grouped into 3: (1) Group A: CD4 counts > 500/microl (n=37), highly active antiretroviral therapy naive, (2) group B: CD4 counts < 200/microl (n=21), not on highly active antiretroviral therapy, and (3) group C: CD4 counts < 200/microl, receiving uninterrupted non-protease inhibitor based highly active antiretroviral therapy for > 6 months (n=32). The fasting blood glucose, glycosylated Hb (HbA1c) levels, were measured in all the patients in 3 groups and significance of difference between means was calculated among various groups. Body weight and waist-hip ratio were also measured. The results were analysed and compared with other studies.

Insulin in type 2 diabetes: promises to keep.

The concept which has evolved in the management of type 2 diabetes mellitus is early insulin therapy. In type 2 diabetes mellitus first phase insulin response is grossly impaired on eventually absent, overburdening phase 2 responses which obviously fail to compensate in the long run. Perpetuation of the age old practice to continue OHA while almost all beta-cells are exhausted is only buying time for starting insulin. Preservation of beta-cell function by early insulin therapy yields two important benefits: (1) Better glycaemic control at lower medication dose and (2) relative freedom from hypoglycaemia because of well preserved glucagon response. To ensure and to translate the proper action of insulin in the target organs we are now talking about designer insulins which are basically insulin analogues (short and long acting). So type 2 diabetes is a growing menace and is responsible for severe morbidity, mortality and poor quality of life. Good glycaemic control from the very beginning of diabetes has shown to favourably influence all of these and is accepted as a cardinal goal of proper diabetes care.