Browsing by Author "Kumar, Manoj"

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    Deficient functional wound closure as measured by elevated trans-epidermal water loss predicts chronic wound recurrence: An exploratory observational study
    (Springer Nature, 2024-10-09) Chattopadhyay, Debarati; Sinha, Mithun; Kapoor, Akshay; Kumar, Manoj; Singh, Kanhaiya; Mathew-Steiner, Shomita S.; Sen, Chandan K.; Surgery, School of Medicine
    A single-center, prospective, observational pilot study was performed to evaluate wound healing endpoint and recurrence by measuring transepidermal water loss (TEWL) post-closure at the site of wound repair. Patients with clinically-defined chronic wounds (such as pressure ulcers, diabetic ulcers, and trauma wounds) who visited the Plastic Surgery outpatient department or were in-patients at the All India Institute of Medical Sciences, Rishikesh, India, and were referred for chronic wound management, were enrolled. Non-invasive point-of-care TEWL measurements were obtained, from closed wound-site and contralateral healthy skin site, starting from confirmation of closure (post-closure, V0) continuing every 2 weeks for a maximum of five visits or until the wound recurred. Statistical analyses of the data involved logistic regression and likelihood ratio chi-square tests to assess differences in TEWL at visit 0 (V0) between the closed wound site and reference skin, with the TEWL score as the sole predictor of recurrence. Of the 72 subjects that completed the study, 44 (61%) showed no recurrence and 28 (39%) had wounds that recurred over a period of 12 weeks. A significant association was found between the V0 (post-closure) TEWL score and the odds of wound recurrence, both in univariate analysis (OR [95%CI] = 1.26[1.14,1.42] (p < 0.001) and after adjusting for covariates in multivariable analysis (OR [95%CI] = 1.34[1.19,1.61] (p < 0.001). The likelihood ratio chi-square analysis demonstrated that the V0 TEWL score is a significant universal predictor of recurrence across all wound types studied. Cases of closed wounds with subsequent recurrence showed an overall higher post-closure V0 TEWL score, compared to those who did not have a wound recurrence, across visits. The TEWL score cut-off value predictive of recurrence was 24.1 g.m-2.h-1 (AUC = 0.967). The outcome of this pilot study on a wide range of chronic wounds leads to the hypothesis that post-closure TEWL at the site of wound healing is a reliable biomarker of wound recurrence. It also raises the question whether the clinical endpoint of wound closure should include re-establishment of skin barrier function as additional criterion. The current standard of care wound closure endpoint calls for re-epithelialization of the wound with no discharge for two consecutive weeks disregarding the functional parameter of restoration of skin barrier function at the wound-site.
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    P-2109. Culture-Free Identification of Microbes in Seconds Directly from Clinical Samples using the MasSpec Pen Technology
    (Oxford University Press, 2025-01-29) Downey, Rachel; Kumar, Manoj; Kirkpatrick, Lindsey M.; Hauger, Sarmistha Bhaduri; Johnson, Coreen; Dunn, James; Jackobs, Faith; Keating, Michael; Eberlin, Livia; Pediatrics, School of Medicine
    Background: Broad spectrum antibiotics are often used empirically in cases of suspected invasive infection requiring surgical intervention while awaiting results of conventional testing (cultures and molecular tests). Rapid and accurate diagnosis of the etiologic pathogens is critical to allow for selection of targeted antibiotics and improve outcomes for patients. We present current results of a large, multi-center clinical study using the MasSpec Pen (MSPen) technology to characterize the metabolic profiles of clinically relevant microbes in culture isolates and apply the technology to culture-independent identification of infectious agents directly in clinical samples. Methods: The MSPen allows direct sample analysis using a solvent droplet followed by immediate mass spectrometry analysis, with total acquisition time of ∼15 seconds (fig 1). In this study 785 samples (635 isolates and 150 clinical specimens) were analyzed using this technology to create distinct metabolic profiles to differentiate bacterial pathogens. 80% of data were used as a training set to develop such profiles; 20 percent of data were used as a test set to identify bacterial infection. Results: We identified over 400 bacterial metabolites and lipids in 10 different microbial species and compiled a unique metabolic profile for each that was used to directly identify specific microbes in cultures and clinical specimens. Among culture isolates, our statistical classifiers were able to achieve 99% accuracy for Gram-typing, and 99% accuracy among 10 bacteria in the test set (fig 2). Using species-specific metabolites and lipids, we were able to identify Pseudomonas aeruginosa directly from 3 infected specimens and Staphylococcus epidermidis directly from infected bone. Conclusion: Our results show the incredible promise that direct MSPen analysis has for rapid, culture-independent identification of bacteria from patient tissues. We are working to build classifiers to differentiate bacteria by specific m/z values to improve identification in tissue samples.