Armin Ahmed

Metabolic profiling in human lung injuries by high-resolution nuclear magnetic resonance spectroscopy of bronchoalveolar lavage fluid (BALF)

We present a method for identifying biomarkers in human lung injury. The method is based on high-resolution nuclear magnetic resonance (NMR) spectroscopy applied to bronchoalveolar lavage fluid (BALF) collected from lungs of critically ill patients. This biological fluid can be obtained by bronchoscopic and non-bronchoscopic methods. The type of lung injury in acute respiratory failure presenting as acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), continues to challenge critical care physicians. We characterize different metabolites in BAL fluid by non-bronchoscopic method (mBALF) for better diagnosis and understanding of ALI/ARDS by NMR spectroscopy. NMR spectra of mBALF collected from 30 patients (9 controls, 10 ARDS and 11 ALI) were analyzed for the identification of biomarkers. Statistical methods such as principal components analysis and partial least square discriminant analysis were carried out on 1H NMR spectrum of mBALF to identify biomarker responsible for separation among different lung injuries classes (ALI and ARDS) and normal lungs. The corresponding correlation of biomarkers with metabolic cycle has given insight into metabolism of lung injuries in critically ill patients. Our study shows statistically significant differentiation of various metabolites concentration in mBALF collected from lungs of ALI, ARDS and healthy control patients, making NMR spectroscopy as a possible new method of characterizing human lung injury.

Risk prediction for invasive candidiasis

Over past few years, treatment of invasive candidiasis (IC) has evolved from targeted therapy to prophylaxis, pre-emptive and empirical therapy. Numerous predisposing factors for IC have been grouped together in various combinations to design risk prediction models. These models in general have shown good negative predictive value, but poor positive predictive value. They are useful in selecting the population which is less likely to benefit from empirical antifungal therapy and thus prevent overuse of antifungal agents. Current article deals with various risk prediction models for IC and their external validation studies.

Hypocalcemia in acute pancreatitis revisited

Hypocalcemia is a frequent finding in acute pancreatitis. Severe hypocalcemia can present with neurological as well as cardiovascular manifestations. Correction of hypocalcemia by parenteral calcium infusion remains a controversial topic as intracellular calcium overload is the central mechanism of acinar cell injury in pancreatitis. The current article deals with the art and science of calcium correction in pancreatitis patients.

Invasive candidiasis in non neutropenic critically ill - need for region-specific management guidelines

Use of antifungal agents has increased over past few decades. A number of risk factors such as immunosuppression, broad spectrum antibiotics, dialysis, pancreatitis, surgery, etc., have been linked with the increased risk of invasive candidiasis. Though there are various guidelines available for the use of antifungal therapy, local/regional epidemiology plays an important role in determining the appropriate choice of agent in situations where the offending organism is not known (i.e. empirical, prophylactic or preemptive therapy). Developing countries like India need to generate their own epidemiological data to facilitate appropriate use of antifungal therapy. In this article, the authors have highlighted the need for region-specific policies/guidelines for treatment of invasive candidiasis. Currently available Indian literature on candidemia epidemiology has also been summarized here.

Invasive candidiasis in severe acute pancreatitis: Experience from a tertiary care teaching hospital

Background: Invasive candidiasis (IC) is associated with increased morbidity in severe acute pancreatitis (SAP). There is limited information regarding the predisposing factors, Candida species distribution and in vitro susceptibility. Methodology: Current data have been derived from a larger prospective nonintervention study conducted on 200 critically ill patients which was done to study the antifungal prescription practices, collect epidemiological data, and perform an external validation of risk prediction models for IC under senior research associateship program of Council of Scientific and Industrial Research New Delhi. Of these critically ill patients, thirty had SAP and were included for analysis. Results: There were 23 males and 7 females. Out of eight patients (27%) who developed IC, three had isolated candidemia, two had isolated deep-seated candidiasis while three had both candidemia and deep-seated candidiasis. SAP patients with IC had a longer duration of Intensive Care Unit stay, hospital stay, days on mechanical ventilation and duration of shock. Mortality was not different between SAP patients with or without IC. Conclusion: There is a high rate of Candida infection in SAP. More studies are needed to generate epidemiological data and develop antifungal stewardship in this subset of high-risk population.

Comments on "Candida glabrata candidemia; an emerging threat in critically ill patients"

Sir, The article “Candida glabrata candidemia; An emerging threat in critically ill patients” very well highlights the importance of this emerging species.[1] Due to delay in time to positivity for blood culture, empirical antifungal therapy is an important strategy in the management of invasive candidiasis, more so for C. glabrata infection. Appropriate empirical therapy requires identification of high risk group. In the present study, authors have reported broad spectrum antibiotic, mechanical ventilation, central venous catheter, diabetes mellitus and age >65 years as risk factors for C. glabrata candidemia. We agree with Chakrabartis view that due to lack of control group in the study, it is difficult to draw any inference regarding the risk factors.[2] At least two authors have attempted to develop risk model to predict C. glabrata candidemia. Tapia et al. studied 246 cases of candidemia, out of which 68 cases were due to C. glabrata.[3] Four factors independently associated with C. glabrata candidemia were absence of renal failure, <7 days in the hospital, abdominal surgery and fluconazole use. The model had moderately good discriminating ability between C.glabarata candidemia and non C. glabrata candidemia (c-statistic value 0.727 [95% confidence interval: 0.635-0.775]). Another risk prediction model was developed by Cohen et al. in a study including 48 C. glabrata candidemia patients and 106 had nonglabrata fungemia.[4] The model identified six factors independently associated with C. glabrata candidemia. These were age >60 years, recent abdominal surgery, interval from intensive care unit admission to first positive blood culture <7 days, recent use of cephalosporins, solid tumor, and absence of diabetes mellitus. The model had good discriminating ability (c-statistics value 0.89). These models require external validation before they can be generalized in different cohorts. Both above described models have identified gastro surgery as an independent risk factor for C. glabrata candidemia.[3,4] C. glabrata is a frequent gut colonizer in hospitalized patients and can disseminate to cause candidemia in susceptible host. It has been shown in animal model that gut of antibiotic-treated mice can act as a reservoir for C. glabrata. It would be enlightening if the authors can report the data regarding, nature of surgeries done in the surgical group. Hospitalized patients are frequently colonized with Candida. Risk of candidemia increases with increase in density of colonization and number of colonized sites.[5] The method used for identifying urine as the most common source of C. glabrata candidemia needs to be mentioned in the study. Authors have stated that candiduria is a useful indicator for systemic candidiasis, but it is unclear from the results that what were the other sites looked for. Interpreting the source of candidemia without studying different sites for colonization and typing the strain can give misleading results. Local epidemiology is important to guide empirical antifungal therapy. More studies are needed to identify the risk factors for C. glabrata infection and colonization as well as to conduct external validation of already existing risk models.

Screening test for assessment of nutritional status in critically ill elderly patients

Sir, The article by Tripathy and Mishra.[1] on comparison of two screening tools for nutritional assessment in the critically ill elderly patient made for a very interesting read. Nutritional support in critically ill remains a topic of debate, and therefore, it is extremely important to stratify your patient for nutritional need. Nutritional screening in Intensive Care Unit (ICU) requires an understanding of two important points that are nutritional status at admission and severity of illness, and likely duration of organ support in the form of mechanical ventilation, vasopressor therapy. The severity of illness defines the catabolic stress and therefore, can be used to anticipate the expected loss of lean body mass. Nutritional scoring used in hospitalized patients cannot be generalized to ICU patients due to various reasons: Inappropriate assessment of weight due to fluid shifts Using body mass index as an indicator may mask the patients with sarcopenic obesity[2] Inclusion of catabolic stress in screening tool is absent Geriatric nutritional risk index (GNRI) uses albumin for assessment that is an acute phase reactant and should not be used in ICU patients. The methodology does not specify the method by which the ulnar length and knee length were measured. Who was the person who did the measurements? There is a possibility of bias if the person involved had a part in the data analysis and interpretation. The gold standard against which the two screening tools were compared is not described clearly. About 52.3% of patients were found to be “at risk” of malnutrition by this preset definition. In how many patients was the history of weight loss over last 6 months recorded. The gold standard should be able to detect 100% cases of at risk to malnutrition only then the comparison can be done.[3,4] The demographic of the patients is not described in details. It appears 70% of the patients had weight recorded, which is not reflected by the severity of illness, which was having a mean of 19. While comparing the two screening methods, the mortality is not described. How many patients died during the study period is not known. How was the patient classification according to GNRI? Did this classification have relation with mortality? The survival curve shows four patients who died. It is described for only Malnutrition Universal Screening Tool (MUST) no data for GNRI is given. We do not think conclusions should be drawn from the significant log rank when a number of events are so less. MUST/GNRI is for hospitalized patients using such tool for critically ill patients may oversimplify the assessment of nutritional status and we may miss the “high risk” or may include “low risk” patients, and over treat. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Nosocomial candiduria in chronic liver disease patients at a hepatobilliary center.

Sir, We read the article “Nosocomial candiduria in chronic liver disease patients at a hepatobiliary center”[1] with great interest. This article clearly highlights the importance of repeat sampling in patients who are reported as having candiduria. Candiduria can occur due to contamination, colonization (of the indwelling catheter or bladder), and infection (Candida cystitis or ascending pyelonephritis or renal candidiasis) as discussed in this article. Taking a repeat sample after insertion of fresh catheter eliminates the chances of contamination, but colonization can still be present without any clinical manifestation of disease.[2,3] Differentiation between the colonization and infection is difficult one and should be interpreted in the light of clinical features. Frequently, due to the presence of multiple co morbidities the line of demarcation between Candida colonization and infection is blurred, more so in critically ill patients. Pathogenesis of urinary tract and renal infections caused by Candida involves hematogenous spread as well ascending infection. When suspecting hematogenous spread various risk prediction scores (colonization index, Candida score) have been designed to guide therapy.[3,4] Candida colonization has been shown to be a risk factor for invasive candidiasis, but multiple site colonization and heavy colonization is considered more significant than single site colonization.[5] Candiduria represents single site colonization and should not trigger initiation of treatment unless other symptoms are also present. When suspecting ascending infection, one should look for predisposing factors like presence of stone or presence of obstruction, urinary drainage devices, prior surgical procedures, broad spectrum antibiotic use, old age, and diabetes mellitus. Infectious Disease Society of America 2009 guidelines recommends that asymptomatic candiduria should not be treated unless the patient is at high risk of invasive candidiasis (neutropenia, low birth weight, and patients who undergo urologic procedures).[6] The reason for treating asymptomatic candiduria in high risk patients is mainly prophylaxis. Chronic liver disease is a very broad terminology and includes various etiologies and stages of evolution in its natural history. Whether all chronic liver disease patients should be included in the high risk remains to be established. Currently, there is a paucity of literature regarding predisposition for invasive Candida infections among chronic liver disease patients. It would have been enlightening if the patient characteristics and stages/classification of liver disease were also mentioned in this study. The study also reports that 11 (3.5%) patients of candiduria evolved to candidemia. Though it is difficult to perform, genotypic identification is ideally required before one can say that species colonizing is the same as the species responsible for blood stream infection.