Publications by authors named "M M Kumaraswamy"

30 Publications

Contribution of Streptococcus pyogenes M87 protein to innate immune resistance and virulence.

Microb Pathog 2022 Aug 17;169:105636. Epub 2022 Jun 17.

Department of Pediatrics, University of California at San Diego, La Jolla, CA, 92093, USA; Skaggs School of Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA, 92093, USA.

Streptococcus pyogenes is a pre-eminent human pathogen, and classified by the hypervariable sequence of the emm gene encoding the cell surface M protein. Among a diversity of M/emm types, the prevalence of the M/emm87 strain has been steadily increasing in invasive S. pyogenes infections. Although M protein is the major virulence factor for globally disseminated M/emm1 strain, it is unclear if or how the corresponding M protein of M/emm87 strain (M87 protein) functions as a virulence factor. Here, we use targeted mutagenesis to show that the M87 protein contributes to bacterial resistance to neutrophil and whole blood killing and promotes the release of mature IL-1β from macrophages. While deletion of emm87 did not influence epithelial cell adherence and nasal colonization, it significantly reduced S. pyogenes-induced mortality and bacterial loads in a murine systemic infection model. Our data suggest that emm87 is involved in pathogenesis by modulating the interaction between S. pyogenes and innate immune cells.
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http://dx.doi.org/10.1016/j.micpath.2022.105636DOI Listing
August 2022

Efficacy of pedicled anterolateral thigh flap for reconstruction of regional defects - a record analysis.

Acta Chir Plast 2022 ;64(1):6-11

Background: The anterolateral thigh (ALT) flap was described as the fasciocutaneous flap. It can be harvested as a pedicled and/or free flap. Majority of the free flaps are harvested as a fasciocutaneous flap. Their use in head and neck reconstruction and limb trauma is well established. Apart from these advantages, this flap has various applications which are less utilized. ALT flap can be used as a myocutaneous flap along with vastus lateralis muscle. When muscle and fasciocutaneous flaps are required, both can be harvested as a chimeric flap which can cover two different regions of the wound. Moreover, harvest of the pedicled flap procedure is less time-consuming than that of a free flap. Since it has a long vascular pedicle, when used as pedicled flap, it can reach up to the gluteal region. To evaluate these less applied advantages of pedicled ALT flap, our study was undertaken. This study aimed to evaluate the efficiency of ALT flap in terms of the surface area of coverage, arc of rotation and the advantages of including vastus lateralis muscle as part of the flap.

Methods: A retrospective record analysis of all pedicled ALT flap reconstruction of trochanteric, upper thigh, gluteal and flank regions from 2016 to 2018 was undertaken; 7 patients with 8 defects were included.

Results: All the flaps healed successfully. There was no major necrosis of the flap and minor complications like wound gapping were found in three patients.

Conclusion: The ALT-vastus lateralis flap dimensions can be very large and can be easily harvested in a very short time. Vastus lateralis muscle harvested can be used to fill the defect or can be used as chimera to cover the defect. The use of muscle over long standing infective pressure sores can sterilize the wound bed and help in preventing recurrence. The vascularity of this flap is robust and highly reliable. Even after a maximum arc of rotation (up to 170°) all the flaps survived without any major complications.
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http://dx.doi.org/10.48095/ccachp20226DOI Listing
April 2022

Moriarty's sign - predictor of skin graft take.

Acta Chir Plast 2021 ;63(4):166-170

Background: Resurfacing wound beds with split skin graft is the most common procedure in plastic surgery. Association of more pain in the donor site than in the recipient site has been used as a predictor of successful graft take by Stark in 1962 who termed it Moriartys sign.

Purpose: The aim of the study was: 1) to predict the successful take of skin graft by eliciting Moriartys sign; 2) to decide the day of first graft inspection based on Moriartys sign.

Methods: The authors hereby present a prospective study in 100 patients who underwent wound resurfacing with split thickness skin graft at the Department of Plastic Surgery in a tertiary care center between January 2014 and June 2015. The area with more pain, absence of pain or equivocal response at the graft donor site was recorded on the visual analog scale for 10 days.

Results: In this study, 80 patients had positive Moriartys sign, 12 patients had equivocal responses and 8 patients showed a negative sign. Patients with positive Moriartys sign underwent their first graft inspection on 10th postoperative day and showed 100% graft take. Twelve patients with equivocal response underwent first graft inspection on 5th day and had 70-80% graft take.  In 8 patients, with negative Moriartys sign first graft inspection done on 3rd day, the graft take was < 50%.

Conclusion: The study demonstrates that Moriartys sign is a reliable clinical predictor of split thickness skin graft take and may be useful as a guide to determine the day of first graft inspection. It is an effective method even for junior members of the surgical and nursing team to monitor parameters in relation to this sign. It can be practiced in a smaller group of hospitals, too. Hence, the authors recommend to integrate this clinical assessment in routine practice.
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http://dx.doi.org/10.48095/ccachp2021166DOI Listing
January 2022

Bacterial Membrane-Derived Vesicles Attenuate Vancomycin Activity against Methicillin-Resistant .

Microorganisms 2021 Sep 29;9(10). Epub 2021 Sep 29.

Research Group for Host-Microbe Interactions, UiT-The Arctic University of Norway, 9037 Tromsø, Norway.

Methicillin-resistant (MRSA) has evolved numerous antimicrobial resistance mechanisms and is identified as a serious public health threat by the World Health Organization and U.S. Centers for Disease Control and Prevention. The glycopeptide vancomycin (VAN) remains a cornerstone of therapy for severe MRSA infections despite increasing reports of therapeutic failure in hospitalized patients with bacteremia or pneumonia. Recently, the role of released bacterial-derived membrane vesicles (MVs) in antibiotic resistance has garnered attention. Here we examined the effect of exogenous MRSA-derived MVs on VAN activity against MRSA in vitro, using minimum inhibitory concentration and checkerboard assays, and ex vivo, incorporating components of host innate immunity such as neutrophils and serum complement present in blood. Additionally, the proteome of MVs from VAN-exposed MRSA was characterized to determine if protein expression was altered. The presence of MVs increased the VAN MIC against MRSA to values where clinical failure is commonly observed. Furthermore, the presence of MVs increased survival of MRSA pre-treated with sub-MIC concentrations of VAN in whole blood and upon exposure to human neutrophils but not human serum. Unbiased proteomic analysis also showed an elevated expression of MV proteins associated with antibiotic resistance (e.g., ) or proteins that are functionally linked to cell membrane/wall metabolism. Together, our findings indicate MRSA-derived MVs are capable of lowering susceptibility of the pathogen to VAN, whole-blood- and neutrophil-mediated killing, a new pharmacodynamic consideration for a drug increasingly linked to clinical treatment failures.
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http://dx.doi.org/10.3390/microorganisms9102055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539228PMC
September 2021

Free tensor fascia lata flap - a reliable and easy to harvest flap for reconstruction.

Acta Chir Plast 2021 ;63(2):57-63

Background: Flaps are the essence of reconstructive surgery. The ability to successfully design, execute and manage the flaps makes plastic surgery an outstanding speciality. The choice of flap is mainly guided by the type of the defect. However, certain factors like technique feasibility, duration of the surgery and patient factors do have a role in decision making. The primary type of free flap (whether a muscle or a fasciocutaneous flap) is dictated by the defect or the wound characteristics. However, the choice of flap depends on various factors like the component of flap, pedicle length required, the ease of harvest and donor site morbidity. Tensor fascia lata (TFL) is one myocutaneous flap, which has well developed components other than a muscle.

Materials And Methods: The patients admitted to a tertiary care hospital with the diagnosis of composite tissue defect in any region of the body were enrolled for this study from November 2016 to November 2018. Patients undergoing free TFL flap reconstruction are studied. The duration of flap harvest, the anatomical site of pedicle, flap outcome and the need of secondary surgery were analysed.

Results: Totally 14 patients were reconstructed with a free TFL flap. The anatomic location of the defect was more frequent on lower limbs - 8 cases (58%), followed by the upper limb and the head and neck area (3 cases, each 21%). The mean flap harvest time was -62.07 (45-80) min. The mean size of pedicle entry was 8.7 cm from the anterior superior iliac spine. Out of the 14 flaps, there were 10 (71%) flaps successful completely and 4 (29%) of them had partial loss.

Conclusion: A free TFL flap harvest time is very short compared to any other flaps and hence makes it the flap of choice in patients who are critical and cannot withstand long operating time.
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http://dx.doi.org/10.48095/ccachp202157DOI Listing
August 2021
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