Modified Nutrition Risk in Critically Ill Score, A Prognostic Marker of Morbidity and Mortality in Mechanically Ventilated Patients: A Prospective Observational Study

Background: Critically ill (CI) patients, especially those requiring mechanical ventilation (MV) are at a higher risk of malnutrition, which in turn is associated with increased hospitalization and excess mortality. The modified Nutrition Risk in Critically Ill (mNUTRIC) score, a predictor of mortality, has not been validated adequately in CI Indian patients. Thus, this study evaluated the mNUTRIC score as a prognostic marker of morbidity and mortality in CI patients requiring MV. Materials and methods: This prospective observational study was performed, between January 2018 and June 2019, in the intensive critical care unit (ICCU) of the medicine department of a tertiary care hospital. A total of 250 patients aged above 12 years, admitted in ICCU, and requiring MV for >48 hours were included. Based on the data collected, mNUTRIC score was calculated and patients were classified as at low (0–4) and high (5–9) nutritional risk. Mortality was the outcome variable. Results: More than a quarter of patients had a high mNUTRIC score (28.4%) and the overall mortality was 35.6%. A significantly greater proportion of non-survivors had a high mNUTRIC score (p-value<0.0001). Likewise, the mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, and mNUTRIC score (all p-values<0.0001) were significantly higher among the non-survivors than the survivors. On receiver operator characteristic (ROC) curve analysis, a cutoff value of >2 predicted mortality [area under the curve (AUC): 0.83; 95% confidence interval: 0.778–0.874] with a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 80.9, 76.4, 65.5, and 87.9%, respectively. Conclusion: At a cutoff of >2, mNUTRIC score had high sensitivity and specificity in the prediction of mortality.

The role of Ki‑67, p16, CD34, Bcl‑2, cyclooxygenase‑2 in the pathogenesis of proliferative verrucous leukoplakia.

CONTEXT: Proliferative verrucous leukoplakia (PVL) is a highly persistent and aggressive oral pre‑malignant lesion with an obscure etiopathogenesis and a malignant transformation rate of 85‑100%. AIMS: The aim of the present study is to assess the role of Ki‑67, p16, CD34, Bcl‑2, cyclooxygenase‑2 (COX‑2) in the spectrum of PVL to ascertain their role in its etiopathogenesis. SETTINGS AND DESIGN: A retrospective chart analysis was carried out on a series of seven confirmed cases of PVL, which were followed‑up for 2 years. SUBJECTS AND METHODS: Immunohistochemical appraisal of these cases was carried out by a panel of markers, related to cell proliferation, cell cycle regulation, angiogenesis, apoptosis and inflammation. The expression of these markers was correlated with patients’ clinicopathological profile. STATISTICAL ANALYSIS USED: The frequency distribution of the group data was analyzed. RESULTS: The latest labeling index of Ki‑67 in our cases ranged from 8.18 to 12.6. p16 was positive in 3/7 cases. Bcl‑2 expression was moderately positive in 2/7 cases. All cases were intensely positive for COX‑2 staining. Microvascular density assessed by CD34 staining ranged from 11 to 20/high power fields. One case which transformed into squamous cell carcinoma demonstrated increased Ki‑67, Bcl‑2, COX‑2, CD34 expression, but negative p16 and Bcl‑2 expression. CONCLUSIONS: Application of these markers in understanding the behavior of PVL suggests that an imbalance between the proliferation apoptosis dynamics of the lesion accompanied by an increase in inflammation and angiogenesis underlie the molecular pathogenesis of the PVL spectrum.

p53 immunoprofiling of potentially malignant oral disorders: A case series analysis.

Context: p53 tumor suppressor gene which is a frequent target for mutations in a high percentage of oral cancer is regarded as an early event in carcinogenesis. Aim: The role of p53 was assessed in potentially malignant oral disorders (PMOD) to ascertain its prognostic significance. Settings and Design: Retrospective case series analysis was carried out on 30 paraffin-embedded tissue blocks of confirmed oral leukoplakia with dysplasia. Materials and Methods: 10 cases of each of mild, moderate, and severe dysplasia were immunohistochemically analyzed for p53 expression. The intensity of staining, intracellular localization, and basal and/or suprabasal distribution were assessed. Statistics: The intensity of p53 staining and its distribution were analyzed by the Chi-square test. The intracellular localization of p53 in different grades of dysplasia was subjected to one way ANOVA. P<0.05 was considered significant. Results: 21/30 cases of epithelial dysplasia were positive for p53 immunopositivity. Intensity of p53 expression was strong in 12 cases and weak in 9 cases (P<0.05). p53 positivity was confined to basal cells in mild dysplasia, while severe dysplasia showed both basal and suprabasal staining (P<0.05). Nuclear and cytoplasmic staining between and within the groups were F=9.027 and F=6.465 respectively with high significance noted between mild dysplasia and severe dysplasia. Conclusions: Increased p53 expressivity and greater cellular localization with increase in the severity of dysplasia indicated a direct association between the degree of epithelial dysplasia and p53 accretion, which occurs as an early event in oral carcinogenesis.

Review article: High-throughput screening: the hits and leads of drug discovery- an overview.

The mechanism-based approach which corresponds to the target-based approach screens for compounds with a specific mode of action. The highly effective nature of high-throughput screening (HTS) for identification of highly target specific compounds is attributed to its precise focus on single mechanism. This logical development of receptor technology is closely connected with the changes in strategy of chemical synthesis. The vast number of compounds produced by combinatorial chemistry and the possibility of testing many compounds, including natural products, in a short period of time by HTS attracted attention of many workers. Various detection techniques like fluorescence resonance energy transfer (FRET), Homogeneous time resolved fluorescence (HTRF), etc are available, and the screening of more than 100,000 samples per day is possible. With the introduction of robotics, automation and miniaturization techniques, it became feasible to screen 50,000 compounds a day with complex work-stations. High-throughput screening methods are also used to characterize metabolic and pharmacokinetic data about new drugs. With the use of Cassette dosing techniques even the pharmacokinetic data can be assessed for large number of drug candidates, though not free of drawbacks, yet an effective technique to further increase the drug discovery and development rate. The objective of this article is to give an overview to the High-Throughput screening methodologies used in industries as well as in academic research programmes.

Detection of -Lactamases in nosocomial gram negative clinical isolates.

-lactamases represent the most common mechanism of -lactam resistance. Extended spectrum -lactamases (ESBLs) represent a major group of -lactamses currently being identified worldwide in large numbers along with inducible AmpC -lactamases and derepressed mutants. The present study was done to detect -lactamase production in clinical isolates by rearranging routine discs used in reporting susceptibility to specifically assess ESBLs, AmpC -lactamases (both inducible and hyperproducers i.e., derepressed mutants). A total of 286 clinical isolates were studied using a novel predictor disc approximation method to detect the above mechanisms of resistance with careful use and placement of antimicrobial discs. Of the 286 isolates, 151(53%) were ESBL producers of which 131(46%) were also derepressed mutants while remaining 20(7%) were plain ESBL producers. Forty (14%) were plain derepressed mutants. Inducible AmpC -lactamase production was detected in 19(7%) of the isolates. The commonest ESBL producers were E.coli and K. pneumoniae. The high incidence of -lactamase production due to multiple mechanisms in clinical isolates is alarming and urgent action needs to be taken from both a therapeutic and infection control perspective.

Fistulization of hepatic hydatid cyst into duodenum.

Though rupture of hepatic hydatid cyst is not uncommon, fistulization into the gut following rupture is rare. We report a case in whom a hepatic hydatid cyst ruptured into the first part of the duodenum.

Current status of filariasis in Chavakad taluk, Trichur district, Kerala.

A sample survey using parasitological, clinical and entomological indicators was carried out in all the 18 administrative units of Chavakad taluk, Trichur district, Kerala, India to assess the current filariasis situation. Cluster sampling procedure was followed to screen individuals. Both Wuchereria bancrofti and Brugia malayi species were found to be prevalent in this taluk. Microfilaria (mf) carriers with W. bancrofti were detected in eight areas while B. malayi was recorded only from one area. The two species were found to co-exist in another area. The highest infection rate registered for W. bancrofti was 1.51 while it was 0.3 for B. malayi. Infection due to W. bancrofti constituted 87.88% of the total 33 microfilaria cases. Prevalence of B. malayi was very low. Cases with clinical manifestation of filariasis were recorded in all the four areas surveyed. The present trend in the prevalence of infection (mf) and disease showed a decline in both the species when compared to earlier surveys of 1960s. At least 11 areas are still endemic for filariasis in this taluk. Although prevalence of mf was recorded for the first time in one of the areas viz., Elavalli, the rate was only 0.16%. Entomological surveys revealed the presence of 14 mosquito species, of which Culex quinquefasciatus contributed 84.85% and Mansonia 0.77%. While C. quinquefasciatus was recorded in all the 18 areas, Mansonia spp were found only in 8 areas. Only C. quinquefasciatus was found to harbour different developmental stages of W. bancrofti, with overall infection and infectivity rates of 1.94 and 0.97 respectively. The possible reason for the decline in vector density and infection in man are postulated.

Myiasis in filarial lymphoedema due to Chrysomyia bezziana.

In patients with filarial lymphoedema of the limbs, infestation by maggots is extremely rare. We saw three patients with lymphoedema who harboured Chrysomyia bezziana in leg ulcers and in one of them 128 maggots were recovered. A course of local dressing, antibiotics and anti-inflammatory drugs resulted in healing of the wounds. Ulcers in patients with lymphoedema should be carefully tended with cleaning and dressing otherwise myiasis may supervene.