A Modular Communicative Leadless Pacing-Defibrillator System.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (ICD) is associated with fewer lead-related complications than a transvenous ICD; however, the subcutaneous ICD cannot provide bradycardia and antitachycardia pacing. Whether a modular pacing-defibrillator system comprising a leadless pacemaker in wireless communication with a subcutaneous ICD to provide antitachycardia and bradycardia pacing is safe remains unknown. METHODS: We conducted a multinational, single-group study that enrolled patients at risk for sudden death from ventricular arrhythmias and followed them for 6 months after implantation of a modular pacemaker-defibrillator system. The safety end point was freedom from leadless pacemaker-related major complications, evaluated against a performance goal of 86%. The two primary performance end points were successful communication between the pacemaker and the ICD (performance goal, 88%) and a pacing threshold of up to 2.0 V at a 0.4-msec pulse width (performance goal, 80%). RESULTS: We enrolled 293 patients, 162 of whom were in the 6-month end-point cohort and 151 of whom completed the 6-month follow-up period. The mean age of the patients was 60 years, 16.7% were women, and the mean (±SD) left ventricular ejection fraction was 33.1±12.6%. The percentage of patients who were free from leadless pacemaker-related major complications was 97.5%, which exceeded the prespecified performance goal. Wireless-device communication was successful in 98.8% of communication tests, which exceeded the prespecified goal. Of 151 patients, 147 (97.4%) had pacing thresholds of 2.0 V or less, which exceeded the prespecified goal. The percentage of episodes of arrhythmia that were successfully terminated by antitachycardia pacing was 61.3%, and there were no episodes for which antitachycardia pacing was not delivered owing to communication failure. Of 162 patients, 8 died (4.9%); none of the deaths were deemed to be related to arrhythmias or the implantation procedure. CONCLUSIONS: The leadless pacemaker in wireless communication with a subcutaneous ICD exceeded performance goals for freedom from major complications related to the leadless pacemaker, for communication between the leadless pacemaker and subcutaneous ICD, and for the percentage of patients with a pacing threshold up to 2.0 V at a 0.4-msec pulse width at 6 months. (Funded by Boston Scientific; MODULAR ATP ClinicalTrials.gov NCT04798768.).

Image-based non-invasive assessment of suction blister wounds for clinical safety and efficacy.

Recognising the need for objective imaging-based technologies to assess wound healing in clinical studies, the suction blister wound model offers an easily accessible wound model that creates reproducible epidermal wounds that heal without scarring. This study provides a comprehensive methodology for implementing and evaluating photography-based imaging techniques utilising the suction blister wound model. Our method encompasses a protocol for capturing consistent, high-quality photographs and procedures for quantifying these images via a visual wound healing score and a computer-assisted colour analysis of wound exudation and wound redness. We employed this methodology on 16 suction blister wounds used as controls in a clinical phase-1 trial. Our method enabled us to discern and quantify subtle differences between individual wounds concerning healing progress, erythema and wound exudation. The wound healing score exhibited a high inter-rater agreement. There was a robust correlation between the spectrophotometer-measured erythema index and photography-based wound redness, as well as between dressing protein content and photography-based dressing yellowness. In conclusion, this study equips researchers conducting clinical wound studies with reproducible methods that may support future wound research and aid in the development of new treatments.

Effect of mouth rinses on the stainability of monolithic lithium disilicate glass-ceramics with different surface treatments: An in vitro study.

STATEMENT OF PROBLEM: Mouth rinses have been reported to cause tooth surface discoloration. However, information regarding their effect on the stainability of monolithic glass-ceramics with different surface treatments is lacking. PURPOSE: The purpose of this in vitro study was to assess the effect of mouth rinses on the color change of milled and pressed monolithic lithium disilicate glass-ceramics with different surface treatments. MATERIAL AND METHODS: Fifty-six Ø12×1.5-mm disk specimens were fabricated using 2 different processing techniques: milling and pressing. Each group was subdivided into 2 subgroups according to surface treatments: glazed and polished. Specimens were then immersed in 2 different types of mouth rinse (n=7): chlorhexidine (CHX) and Listerine (LST). Color parameters were assessed using a digital spectrophotometer. Color difference (ΔE00) was calculated and compared with perceptibility (ΔE00=0.8) and acceptability (ΔE00=1.8) thresholds. The data were analyzed using ANOVA and Tukey post hoc tests (α=.05). RESULTS: The color difference (ΔE00) was significantly affected by the type of processing technique, surface treatment, and mouth rinse (P<.001) and their interaction (P=.008). All ΔE00 values were below the selected clinical acceptability threshold (ΔE00=1.8). Milled groups (ΔE00=1.13) showed greater discoloration than pressed groups (ΔE00=0.86). Glazed specimens (ΔE00=0.70) were more resistant to discoloration than polished specimens (ΔE00=1.28) and immersion in CHX (ΔE00=1.09) led to more discoloration than immersion in LST (ΔE00=0.89). CONCLUSIONS: The color of milled and pressed monolithic lithium disilicate glass-ceramics with different surface treatments was affected by using CHX and LST mouth rinses. Glazed lithium disilicate glass-ceramics showed less staining compared with those that were polished. Specimens immersed in CHX showed more discoloration than those immersed in LST.

Evaluation of the Diagnostic Accuracy of an Online Artificial Intelligence Application for Skin Disease Diagnosis.

Artificial intelligence (AI) algorithms for automated classification of skin diseases are available to the consumer market. Studies of their diagnostic accuracy are rare. We assessed the diagnostic accuracy of an open-access AI application (Skin Image Search™) for recognition of skin diseases. Clinical images including tumours, infective and inflammatory skin diseases were collected at the Department of Dermatology at the Sahlgrenska University Hospital and uploaded for classification by the online application. The AI algorithm classified the images giving 5 differential diagnoses, which were then compared to the diagnoses made clinically by the dermatologists and/or histologically. We included 521 images portraying 26 diagnoses. The diagnostic accuracy was 56.4% for the top 5 suggested diagnoses and 22.8% when only considering the most probable diagnosis. The level of diagnostic accuracy varied considerably for diagnostic groups. The online application demonstrated low diagnostic accuracy compared to a dermatologist evaluation and needs further development.

Clinical safety of an MRI conditional implantable cardioverter defibrillator system: A prospective Monocenter ICD-Magnetic resonance Imaging feasibility study (MIMI).

BACKGROUND: The aim of this study was to evaluate the safety and efficacy of the Lumax 740(®) Implantable Cardioverter Defibrillator (ICD) system in patients undergoing a defined 1.5 Tesla (T) MRI. MATERIALS AND METHODS: Between November 2013 and April 2014, eighteen patients (age range, 41-78 years; mean age, 64 years) implanted with a Lumax 740(®) ICD system for at least 6 weeks before an MRI were enrolled into this single-center feasibility study. The local ethics committee approved the study before patients gave written informed consent. Patients underwent defined MRI 1.5T of the brain and lower lumbar spine with three safety follow-up evaluations obtained during the 3-month study period. Data were analyzed descriptively. Study endpoints were the absence of either MRI and pacing system related serious adverse device effects (SADE), or of a ventricular pacing threshold increase >0.5V, or of an R-wave amplitude attenuation < 50%, or of an R-wave amplitude < 5.0 mV at 1-month follow-up. The assessment of safety and efficacy was supported by recording of all adverse events, changes in pacing threshold, R-wave sensing, pacing impedances and in battery status. RESULTS: Sixteen patients completed the MRI and the follow-up period. As no SADE occurred, the SADE free rate was 100%. Freedom from ventricular pacing threshold increase was 100% (16/16; 95%CI: 82.9%; 100.0%). There were no significant differences between baseline and follow-up measurements of sensing amplitudes (-0.58 ± 2.07 mV, P = 0.239, -0.41 ± 1.04 mV, P = 0.133, and -0.25 ± 1.36 mV, P = 0.724, for immediately after, 1 month and 3 months after MRI scan, respectively) and pacing thresholds (-0.047 ± 0.18 V, P = 0.317, -0.019 ± 0.11 V, P = 0.490, and 0.075 ± 0.19 V, P = 0.070, for immediately after, 1 month and 3 months after MRI scan, respectively). Lead impedances after the MRI scan were significantly lower as compared with baseline values (-22.8 ± 21.69 Ω, P = 0.001, -21.62 ± 39.71 Ω, P = 0.040, and -33.68 ± 57.73 Ω, P = 0.018, for immediately after, 1 month and 3 months after MRI scan, respectively). CONCLUSION: MRI scans in patients with MRI conditional ICD system (Lumax 740(®) ) are feasible and can be performed safely under defined conditions in a hospital setting.

Can dressings soaked with polyhexanide reduce bacterial loads in full-thickness skin grafting? A randomized controlled trial.

BACKGROUND: Polyhexamethylene biguanide (PHMB)-based antiseptic solutions can reduce bacterial loads in different clinical settings and are believed to lower risk of infections. OBJECTIVE: We sought to assess the efficacy of a PHMB-based solution in lowering bacterial loads of full-thickness skin grafting wounds and the risk of surgical site infections (SSIs). METHODS: In this double-blinded clinical trial, 40 patients planned for facial full-thickness skin grafting were randomized 1:1 to receive tie-over dressings soaked with either PHMB-based solution or sterile water. Quantitative and qualitative bacterial analysis was performed on all wounds before surgery, at the end of surgery, and 7 days postoperatively. In addition, all patients were screened for nasal colonization of Staphylococcus aureus. RESULTS: Analysis of wounds showed no statistically significant difference in bacterial reductions between the groups. The SSI rates were significantly higher in the intervention group (8/20) than in the control group (2/20) (P = .028). Higher postoperative bacterial loads were a common finding in SSIs (P = .011). This was more frequent when S aureus was present postoperatively (P = .034), intraoperatively (P = .03), and in patients with intranasal S aureus colonization (P = .007). LIMITATIONS: Assessment of SSIs is largely subjective. In addition, this was a single-center study and the total number of participants was 40. CONCLUSION: Soaking tie-over dressings with PHMB solution in full-thickness skin grafting had no effect on postoperative bacterial loads and increased the risk of SSI development. The presence of S aureus intranasally and in wounds preoperatively and postoperatively increased postoperative bacterial loads, which in turn resulted in significantly more SSIs.

Influence of pseudo-resistance on the effect of renal denervation on 24-hour ambulatory blood pressure levels.

BACKGROUND: Renal denervation (RDN) is a promising treatment option in addition to medical antihypertensive treatment in patients suffering from resistant hypertension. Despite the growing interest in RDN, the negative result of the Symplicity HTN-3 trial led to a debate on the efficacy of RDN. METHODS: We systematically investigated the effects of RDN, evaluated by 24-hr ambulatory blood pressure measurements (ABPM), in a consecutive series of patients with resistant hypertension, which was defined by a mean office systolic blood pressure (SBP) >160 mm Hg (>150 mm Hg in patients with diabetes). Patients with a mean 24-hr SBP of less than 130 mm Hg at baseline were classified as pseudo-resistant, while all other patients were classified as true-resistant. After six months, we analyzed the response rates in true-resistant and in pseudo-resistant patients, respectively, by the means of 24-hr ABPM. Thereby, patients with a reduction of more than 5 mm Hg in 24-hr SBP were classified as responders. RESULTS: RDN was performed in 106 patients. By 24-hr ABPM, 20 patients (18.9%) were classified as pseudo-resistant patients. In this cohort, we only found two responders (response rate 10%) six months after RDN. By contrast, in true-resistant patients, the response rate was almost 60% and the mean BP reduction was -18.6/-9 mm Hg in 24-hr ABPM. CONCLUSIONS: We found a significant BP reduction in almost 60% of patients with true-resistant hypertension, but only in 10% in patients with pseudo-resistant hypertension. According to our results, patient selection seems to be crucial for acceptable response rates after RDN.

Removal of active-fixation coronary sinus leads using a mechanical rotation extraction device.

BACKGROUND: Active fixation coronary sinus (CS) leads are widely used in cardiac resynchronization therapy (CRT). Due to their low dislodgement rates they are an attractive option for implanters. However, extraction of active fixation leads is a complex procedure that bears potential fatal risks for patients. METHODS: We analyzed all patients undergoing StarFix® (Medtronic Inc., Minneapolis, MN, USA) extraction because of severe infection at our institution. Indication for extraction was severe device infection. Procedural outcomes as well as patient characteristics are reported. For removal of the leads a 9-Fr Evolution® (Cook Intravascular Inc., Leechburg, PA, USA) mechanical rotation extraction sheath was used. RESULTS: Between 2011 and 2014, six patients underwent extraction of StarFix® leads. One patient was female, whereas the others were males (mean age 64 ± 12 years). Implant duration was 46.5 ± 8.2 months before removal. All leads could be successfully extracted totally with the Evolution®. In one patient (16.6%) pericardial tamponade occurred immediately requiring surgical intervention. After establishment of cardiopulmonary bypass a 5-mm sharp cut in the lateral vein of the CS could be identified. It was fixed and the patient survived. On all leads, significant tissue growth between the fixation lobes could be observed. CONCLUSION: As illustrated by our cases, Attain StarFix® leads implanted years ago can be extracted with the help of a mechanical extraction sheath. However, this procedure bears potential risks and should only be performed with a cardiac surgery standby. If clinicians evaluate the implantation of Attain StarFix® leads in patients who are young or at high risk for device infection, they should be aware of these findings.

An electrical plasma surgery tool for device replacement--retrospective evaluation of complications and economic evaluation of costs and resource use.

BACKGROUND: Device replacements bear many potential risks for patients. Electrocautery should be used cautiously because of heating of the cautery tip which may lead to insulation melting. The PEAK PlasmaBlade™ (Medtronic Inc., Minneapolis, MN, USA) uses a novel technology to cut tissue. The objective of this study was to evaluate if this instrument is less destructive and can decrease complications and shorten procedure times. METHODS AND RESULTS: Two groups were compared: in group 1, surgery was done with scissors and conventional electrocautery, whereas the PEAK PlasmaBlade™ was used in group 2. Procedure time and complication rates were retrospectively investigated. Group 1 comprised 509 patients, while group 2 consisted of 102 patients. Procedure time in group 2 was significantly shorter with 28.4 ± 8.9 minutes than in group 1 with 47.5 ± 24.5 minutes (P < 0.001). The hospital stay was also reduced (2.1 ± 2.2 days versus 3.1 ± 2.4 days, P < 0.001). One major complication occurred in only 2.4% (two patients) of group 2 and in 6.9% (35 patients) of group 1. There were no damaged leads in group 2 compared to 5.7% in group 1 (P = 0.008). Cost analyses showed that the use of The PEAK PlasmaBlade™ instead of conventional electrocautery resulted in cost savings of €120/patient. CONCLUSION: Device replacement is associated with a notable complication risk. Our investigation showed that a new device for generator replacement resulted in significantly reduced procedure time and length of hospital stay while completely avoiding lead damage, which translated into considerable cost savings in a real world setting.

Surgical site infections in dermatologic surgery: etiology, pathogenesis, and current preventative measures.

BACKGROUND: Surgical site infections (SSIs) after dermatologic surgery continue to represent undesirable complications that affect patients in several aspects. The etiology and pathogenesis of SSIs are not completely understood, and as a result, current preventative measures are debatable. OBJECTIVE: To review and summarize the current available literature specific to SSIs in dermatologic surgery. The pathogenesis of SSIs, factors contributing to SSIs, current preventative guidelines, and evidence supporting their use are explored. METHODS: A review of the medical literature. RESULTS AND CONCLUSIONS: Most measures used to prevent SSIs in dermatologic surgery are based on studies of wounds in general surgery. Evidence specific to dermatologic surgery is scarce. More research related to the pathogenesis of SSIs is needed to establish effective preventative measures that are key to reducing incidences of SSIs.

Punch Biopsy Extraction With Fingers.

Punch biopsies are commonly used in dermatology for diagnosing skin diseases. Traditional methods involve the use of forceps, skin hooks, and scissors, which add to health care costs. The technique described here offers a cost-effective and efficient alternative for obtaining specimens.

[Leadless pacemakers : A "permanently" good solution?] / Sondenlose Herzschrittmacher : Eine "dauerhaft" gute Lösung?

The two currently available leadless pacemakers are highly effective and safe in the respective approval studies and also real-world registries. Compared to conventional pacemakers, there are lower long-term complication rates compared to conventional pacemaker systems (especially regarding lead dislocations and systemic infections). Increasing evidence (currently largely for the Micra™ [Medtronic, Minneapolis, MN, USA] device) shows that these advantages are also valid in the long-term. Leadless pacemakers can therefore be regarded a "permanently good solution", when appropriately implanted in suitable patients.

Study protocol for a phase 1, randomised, double-blind, placebo-controlled study to investigate the safety, tolerability and pharmacokinetics of ascending topical doses of TCP-25 applied to epidermal suction blister wounds in healthy male and female volunteers.

INTRODUCTION: TCP-25 gel is intended for use in treatment of wound infection and inflammation. Current local therapies for wounds have limited efficacy to prevent infections and there are no wound treatments available today that target the excessive inflammation that often hampers wound healing in both acute and chronic wounds. There is therefore a high medical need for new therapeutic alternatives. METHODS AND ANALYSIS: A randomised, double-blinded, first-in-human study was designed to evaluate the safety, tolerability and potential systemic exposure of three increasing doses of the TCP-25 gel applied topically on suction blister wounds in healthy adults. The dose-escalation will be divided into three sequential dose groups with eight subjects in each group (24 patients in total). Within each dose group, the subjects will receive four wounds, with two wounds on each thigh. Each subject will receive TCP-25 on one wound per thigh and placebo on one wound per thigh in a randomised double-blinded manner, with a reverse reciprocal position on each respective thigh, to a total of five doses over 8 days. An internal safety review committee will monitor emerging safety and plasma concentration data over the course of the study and must give a favourable recommendation prior to initiating the next dose group, which will receive placebo gel or a higher concentration of TCP-25 in exactly the same manner described above. ETHICS AND DISSEMINATION: The study will be performed in accordance with ethical principles consistent with the Declaration of Helsinki, ICH/GCPE6 (R2), European Union Clinical Trials Directive and applicable local regulatory requirements.This study is approved by the Swedish Medical Products Agency and the Swedish ethics committee under the registration number 2022-00527-01. The results of this study will be disseminated via publication to a peer-reviewed journal at the discretion of the Sponsor. TRIAL REGISTRATION NUMBER: NCT05378997.

Impact of pacing mode and different echocardiographic parameters on cardiac output (PADIAC).

Introduction: The extent of the hemodynamic benefit from AV-synchronous pacing in patients with sinus rhythm and AV block is not completely understood. Thus, we systematically investigated the association of an array of echocardiographic and epidemiological parameters with the change in cardiac output depending on the stimulation mode (AV-synchronous or AV-asynchronous pacing). Methods: Patients in sinus rhythm after previous dual chamber pacemaker implantation underwent a thorough basic echocardiographic assessment of diastolic and systolic left ventricular function, and atrial function (26 echo parameters, including novel speckle tracking strain measurements). Then, stroke volume was measured with AV-synchronous (DDD) and AV-asynchronous (VVI) pacing. Each patient represented their own control, and the sequence of stroke volume measurements was randomized. Results: In this prospective single-center study (NCT04068233, registration August 22nd 2019), we recruited 40 individuals. The stroke volume was higher in all patients when applying AV-synchronous DDD pacing [median increase 12.8 ml (16.9%), P < 0.001]. No echo parameter under investigation was associated with the extent of stroke volume increase in a linear regression model. Of all epidemiological variables, a history of acute myocardial infarction (AMI) was associated with an attenuated stroke volume gain in a univariate and a multivariate regression model that adjusted for confounders. A- and S-wave velocities were reduced in the AMI group. Discussion: In our cohort of patients, each subject benefited from AV-synchronous DDD pacing. No single echo parameter could predict the amount of stroke volume increase. The beneficial effect of AV-synchronous pacing on stroke volume was attenuated after prior acute myocardial infarction.ClinicalTrials.gov identifier (NCT number): NCT04068233.

A descriptive study of bacterial load of full-thickness surgical wounds in dermatologic surgery.

BACKGROUND: Surgical site infections (SSIs) after dermatologic surgery cause pain, prolong healing, result in unaesthetic complications, and lead to excessive use of antibiotics. The pathogenesis of wound infections is complex and is dependent on bacterial load and diversity, among several factors. OBJECTIVE: To investigate bacterial dynamics at dermatosurgical sites at different time intervals and assess the correlation with postoperative outcomes and to examine different endo- and exogenous factors that may contribute to SSIs. METHODS: Eighteen patients undergoing skin grafting of the face were studied. The following SSI-related factors were registered: age and sex of the patient, ulceration of the lesion, diabetes, immunosuppressive therapy, smoking, anticoagulative therapy, and use of antibiotic prophylaxis. Wounds from each patient were swabbed preoperatively, intraoperatively, and postoperatively. The bacterial composition of the swabs was then analyzed quantitatively and qualitatively. RESULTS: Sixteen of 18 surgical sites contained varying quantities of surface-associated bacteria. Coagulase-negative staphylococci and Propionibacterium acnes were the predominant bacteria isolated at all times. Intraoperative analysis was not predictive of SSIs. Use of antibiotic prophylaxis was the only registered SSI-related factor that showed significant variation in bacterial load between pre- and postoperative samples. Postoperative bacterial load was found to be lower than preoperative load in patients who received antibiotics. This was in contrast to patients who did not receive antibiotics, who had significantly higher postoperative levels (p=.02). The presence of high postoperative bacterial loads, regardless of the bacterial species isolated, showed a statistically significant positive correlation with a complicated postoperative outcome (p≤.001). CONCLUSIONS: This study provides novel insights into the bacterial dynamics of dermatologic surgery-induced wounds and the variation of this over time. The results highlight the potential relevance of quantifying bacterial loads, as well as determining specific types of bacteria, in dermatologic surgery.

Distant Resolution of Actinic Keratosis following Cryosurgery: An Unusual Phenomenon.

Early after the introduction of cryosurgery to clinical practice, there were reports of metastasis regressing after cryosurgery of a primary tumour, mainly prostate and breast cancer, suggesting a systemic immunological effect to a local reaction. Colleagues within dermatology have occasionally experienced similar systemic effects following cryosurgery. However, published reports of such cases are lacking. In this case, we report a photographed distant resolution of an actinic keratosis (AK) on 68-year-old woman's arm following cryosurgery of another AK on the same arm.

Method development and characterisation of the low-molecular-weight peptidome of human wound fluids.

The normal wound healing process is characterised by proteolytic events, whereas infection results in dysfunctional activations by endogenous and bacterial proteases. Peptides, downstream reporters of these proteolytic actions, could therefore serve as a promising tool for diagnosis of wounds. Using mass-spectrometry analyses, we here for the first time characterise the peptidome of human wound fluids. Sterile post-surgical wound fluids were found to contain a high degree of peptides in comparison to human plasma. Analyses of the peptidome from uninfected healing wounds and Staphylococcus aureus -infected wounds identify unique peptide patterns of various proteins, including coagulation and complement factors, proteases, and antiproteinases. Together, the work defines a workflow for analysis of peptides derived from wound fluids and demonstrates a proof-of-concept that such fluids can be used for analysis of qualitative differences of peptide patterns from larger patient cohorts, providing potential biomarkers for wound healing and infection.

Infected wounds and burns represent a serious risk to patients: they can delay healing and, if left untreated, can lead to generalised infection or sepsis, organ failure and death. Wounds and burns get infected when harmful micro-organisms, such as bacteria, enter the wound. Predicting the risk of infections, and detecting them early, could reduce their impact and make treating them easier. A way to distinguish between healing and infected wounds is to study how proteins are broken down in each situation. Proteases are the enzymes that break down proteins, and they are different in healing wounds and infected wounds that are failing to heal. This is because, while the body produces proteases, the bacteria that cause infection do so too. Each protease breaks down proteins in a specific way, resulting in a different set of protein fragments, known as peptides. Together, all the peptides in a wound are referred to as the wound's 'peptidome'. Studying the peptidome of a wound could show whether it is infected, and even what type of bacteria might be responsible, which could help identify suitable treatments. Van der Plas et al. used a technique called mass spectrometry to study the peptidome of wounds after surgery. Sterile post-surgical wounds showed high levels of peptides compared to plasma, the liquid component of blood, with up to 4,300 different peptides. Comparing healing wounds to ones infected with the bacterium Staphylococcus aureus revealed that infected wounds contained peptides from about 150 proteins not found in uninfected wounds, while peptides from 90 proteins were unique to uninfected wounds. The peptides exclusive to uninfected wounds included some linked to antimicrobial activity and immune system activity. Van der Plas et al.'s results suggest that analysing the peptidome may be an approach to tracking the healing status of wounds, making it easier to detect infection before symptoms are apparent. The next step will be to study more wounds and identify the reliable peptide markers to use them for diagnostic tests.

Bioinformatic Analysis of the Wound Peptidome Reveals Potential Biomarkers and Antimicrobial Peptides.

Wound infection is a common and serious medical condition with an unmet need for improved diagnostic tools. A peptidomic approach, aided by mass spectrometry and bioinformatics, could provide novel means of identifying new peptide biomarkers for wound healing and infection assessment. Wound fluid is suitable for peptidomic analysis since it is both intimately tied to the wound environment and is readily available. In this study we investigate the peptidomes of wound fluids derived from surgical drainages following mastectomy and from wound dressings following facial skin grafting. By applying sorting algorithms and open source third party software to peptidomic label free tandem mass spectrometry data we provide an unbiased general methodology for analyzing and differentiating between peptidomes. We show that the wound fluid peptidomes of patients are highly individualized. However, differences emerge when grouping the patients depending on wound type. Furthermore, the abundance of peptides originating from documented antimicrobial regions of hemoglobin in infected wounds may contribute to an antimicrobial wound environment, as determined by in silico analysis. We validate our findings by compiling literature on peptide biomarkers and peptides of physiological significance and cross checking the results against our dataset, demonstrating that well-documented peptides of immunological significance are abundant in infected wounds, and originate from certain distinct regions in proteins such as hemoglobin and fibrinogen. Ultimately, we have demonstrated the power using sorting algorithms and open source software to help yield insights and visualize peptidomic data.