Sean McNish

Postoperative wound dehiscence: Predictors and associations

The Agency for Healthcare Research and Quality patient safety indicators (PSI) were developed as a metric of hospital complication rates. PSI‐14 measures postoperative wound dehiscence and specifically how often a surgical wound in the abdominal or pelvic area fails to heal after abdominopelvic surgery. Wound dehiscence is estimated to occur in 0.5–3.4% of abdominopelvic surgeries, and carries a mortality of up to 40%. Postoperative wound dehiscence has been adopted as a surrogate safety outcome measure as it impacts morbidity, length of stay, healthcare costs and readmission rates. Postoperative wound dehiscence cases from the Nationwide Inpatient Sample demonstrate 9.6% excess mortality, 9.4 days of excess hospitalization and

Chronic Leg Ulceration Associated with Polycythemia Vera Responding to Ruxolitinib (Jakafi)

40,323 in excess hospital charges relative to matched controls. The purpose of the current study was to investigate the associations between PSI‐14 and measurable medical and surgical comorbidities using the Explorys technology platform to query electronic health record data from a large hospital system serving a diverse patient population in the Washington, DC and Baltimore, MD metropolitan areas. The study population included 25,636 eligible patients who had undergone abdominopelvic surgery between January 1, 2008 and December 31, 2012. Of these cases, 786 (2.97%) had postoperative wound dehiscence. Patient‐associated comorbidities were strongly associated with PSI‐14, suggesting that this indicator may not solely be an indicator of hospital safety. There was a strong association between PSI‐14 and opioid use after surgery and this finding merits further investigation.

Electrochemical detection of Pseudomonas in wound exudate samples from patients with chronic wounds

We present the case of a 63-year-old white male with bilateral chronic leg ulcers due to polycythemia vera and hydroxyurea therapy who demonstrated dramatic healing of his wounds in response to ruxolitinib (Jakafi(®), Novartis), a novel Janus kinase-1 and -2 inhibitor. This patients wound had previously been refractory to multiple surgical interventions and immunosuppression. After the initiation of ruxolitinib, the patient underwent successful split-thickness skin grafting, with resultant healing of his wounds. He was stable without prednisone and other immunosuppressant therapy and had healed at 6 months. Ruxolitinib therapy could represent a novel option for patients who develop persistent inflammatory wounds in the setting of polycythemia vera and hydroxyurea therapy.

Relationship between opioid treatment and rate of healing in chronic wounds

In clinical practice, point‐of‐care diagnostic testing has progressed rapidly in the last decade. For the field of wound care, there is a compelling need to develop rapid alternatives for bacterial identification in the clinical setting, where it generally takes over 24 hours to receive a positive identification. Even new molecular and biochemical identification methods require an initial incubation period of several hours to obtain a sufficient number of cells prior to performing the analysis. Here we report the use of an inexpensive, disposable electrochemical sensor to detect pyocyanin, a unique, redox‐active quorum sensing molecule released by Pseudomonas aeruginosa, in wound fluid from patients with chronic wounds enrolled in the WE‐HEAL Study. By measuring the metabolite excreted by the cells, this electrochemical detection strategy eliminates sample preparation, takes less than a minute to complete, and requires only 7.5 μL of sample to complete the analysis. The electrochemical results were compared against 16S rRNA profiling using 454 pyrosequencing. Blind identification yielded 9 correct matches, 2 false negatives, and 3 false positives giving a sensitivity of 71% and specificity of 57% for detection of Pseudomonas. Ongoing enhancement and development of this approach with a view to develop a rapid point‐of‐care diagnostic tool is planned.

Interferon-gamma (IFN-γ) is Elevated in Wound Exudate from Hidradenitis Suppurativa

Opioids are routinely used analgesics in patients with chronic wounds; however the impact of opioid exposure on wound healing is poorly understood. The purpose of this study was to investigate the association between opioid exposure and wound outcome in the Wound Etiology and Healing study. This longitudinal observational study was conducted on 450 subjects enrolled in the Wound Etiology and Healing biorepository. Data were collected prospectively including baseline characteristics, pain score, longitudinal opioid exposure, and total wound surface area (tWSA). Data were analyzed using static multivariate models, fixed‐effects mixed models, and time to event analysis. Using fixed‐effects models, opioid dose was significantly associated with tWSA after accounting for the effects of pain score and baseline co‐variates (p < 0.0001). For each 1‐unit increase in ln(opioid dose + 1) the ln(tWSA + 1) increased by 0.16 units (95% confidence interval 0.13–0.19, p < 0.0001). Visits where opioids were present had ln(tWSA + 1) 0.48 units larger (95% confidence interval 0.38–0.58, p < 0.0001) than visits with no opioid exposure. Using time‐to‐event analysis, patients who never received opioids healed faster than those who received opioids (log‐rank chi‐square 11.00, p = 0.0009). Using Cox regression analysis, patients with mean opioid dose ≥10 mg were significantly less likely to heal than those with no opioid (HR 0.67 [0.49–0.91], p = 0.011) after adjusting for wound size. Patients with opioid dose >0 to <10 mg had a similar hazard of not healing as those with no opioid exposure (HR 0.88 [0.65–1.19], p = 0.40). In conclusion, opioid analgesics are commonly prescribed to patients with chronic wounds; however, the data presented suggest that opioid exposure is associated with reduced likelihood of healing in patients with chronic wounds. Whether this is a causal relationship will require further study.

Impact of subspecialty elective exposures on outcomes on the American board of internal medicine certification examination

ABSTRACT Hidradenitis suppurativa (HS) is a chronic recurrent inflammatory disease of apocrine glands which affects 1–4% of young adults. The purpose of this study was to investigate inflammatory cytokines in effluent from HS lesions and to identify potential local drivers of inflammation in HS. Wound fluid specimens from HS patients (n = 8) and age-matched chronic wound patients (n = 8) were selected for analysis. The hidradenitis suppurativa score (HSS) was used to determine the extent of HS activity. Cytokine analysis was conducted using Meso Scale Discovery cytokine and proinflammatory panels. Interferon-gamma (IFN-γ) was significantly elevated in the HS effluent compared to chronic wounds (1418 ± 1501 pg/ml compared to 102.5 ± 138 pg/ml, p = 0.027). HS effluent also had significantly higher levels of tumor necrosis factor-β (TNF-β) (9.24 ± 7.22 pg/ml compared to 1.65 ± 2.14 pg/ml, p = 0.03). There was no significant difference in any other cytokines. There was no significant difference in demographics in the HS compared to chronic wound cohorts. Mean HSS in the HS cohort was 68.88 (SD ± 41.45). In this proof-of-concept pilot study, IFN-γ was significantly elevated in HS effluent. TNF-β/LT-α levels were also elevated in HS, although the levels were more modest. Further studies should focus on molecular drivers of tissue injury in HS and the relationship between HS effluent cytokine profile and disease activity.

Inherent Differences in Keratinocyte Function in Hidradenitis Suppurativa: Evidence for the Role of IL-22 in Disease Pathogenesis.

BackgroundThe American Board of Internal Medicine Certification Examination (ABIM-CE) is one of several methods used to assess medical knowledge, an Accreditation Council for Graduate Medical Education (ACGME) core competency for graduating internal medicine residents. With recent changes in graduate medical education program directors and internal medicine residents are seeking evidence to guide decisions regarding residency elective choices. Prior studies have shown that formalized elective curricula improve subspecialty ABIM-CE scores. The primary aim of this study was to evaluate whether the number of subspecialty elective exposures or the specific subspecialties which residents complete electives in impact ABIM-CE scores.MethodsABIM-CE scores, elective exposures and demographic characteristics were collected for MedStar Georgetown University Hospital internal medicine residents who were first-time takers of the ABIM-CE in 2006–2010 (n=152). Elective exposures were defined as a two-week period assigned to the respective subspecialty. ABIM-CE score was analyzed using the difference between the ABIM-CE score and the standardized passing score (delta-SPS). Subspecialty scores were analyzed using percentage of correct responses. Data was analyzed using GraphPad Prism version 5.00 for Windows.ResultsPaired elective exposure and ABIM-CE scores were available in 131 residents. There was no linear correlation between ABIM-CE mean delta-SPS and the total number of electives or the number of unique elective exposures. Residents with ≤14 elective exposures had higher ABIM-CE mean delta-SPS than those with ≥15 elective exposures (143.4 compared to 129.7, p=0.051). Repeated electives in individual subspecialties were not associated with significant difference in mean ABIM-CE delta-SPS.ConclusionsThis study did not demonstrate significant positive associations between individual subspecialty elective exposures and ABIM-CE mean delta-SPS score. Residents with ≤14 elective exposures had higher ABIM-CE mean delta-SPS than those with ≥15 elective exposures suggesting there may be an “ideal” number of elective exposures that supports improved ABIM-CE performance. Repeated elective exposures in an individual specialty did not correlate with overall or subspecialty ABIM-CE performance.

Late failure of a split-thickness skin graft in the setting of homozygous factor V Leiden mutation: a case report and correlative animal model from the Wound Etiology and Healing (WE-HEAL) study.

ABSTRACT Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease of apocrine gland-bearing skin which affects approximately 1–4% of the population. Defective keratinocyte function has been postulated to play a role in HS pathogenesis. Using an in vitro scratch assay, differences between normal, HS, and chronic wound (CW) keratinocytes were evaluated. Normal keratinocytes exhibited faster scratch closure than HS or CW, with normal samples showing 93.8% closure at 96 hours compared to 80.8% in HS (p = 0.016) and 71.5% in CW (p = 0.0012). The keratinocyte viability was similar in normal and HS (91.12 ± 6.03% and 86.55 ± 3.28%, respectively, p = 0.1583), but reduced in CW (72.34 ± 13.12%, p = 0.0138). Furthermore, apoptosis measured by annexin V/propidium iodide, was higher in CW keratinocytes (32.10 ± 7.29% double negative cells compared to 68.67 ± 10.37% in normal and 55.10 ± 9.46% in HS, p = 0.0075). Normal keratinocytes exhibited a significantly higher level of IL-1α (352.83 ± 42.79 pg/ml) compared to HS (169.96 ± 61.62 pg/ml) and CW (128.23 ± 96.61 pg/ml, p = 0.004). HS keratinocytes exhibited significantly lower amounts of IL-22 (8.01 pg/ml) compared to normal (30.24 ± 10.09 pg/ml) and CW (22.20 ± 4.33 pg/ml, p = 0.0008), suggesting that defects in IL-22 signaling may play a role in HS pathogenesis. These findings support intrinsic differences in keratinocyte function in HS which cannot be attributed to reduced keratinocyte viability or increased apoptosis.

Utility of a human–mouse xenograft model and in vivo near-infrared fluorescent imaging for studying wound healing

We present the case of a 53‐year‐old Caucasian male smoker with remote history of left lower extremity deep venous thrombosis (DVT) and a strong family history of thrombosis, who presented to the Center for Wound Healing at MedStar Georgetown University Hospital with spontaneous left leg ulceration. Prothrombotic evaluation showed homozygosity for the factor V Leiden (FVL) mutation. Therapeutic anticoagulation was commenced with warfarin (Coumadin®) and the patient underwent successful debridement and Apligraf® followed by split‐thickness skin graft (STSG) of two wounds. He had an uneventful postoperative course and on the 27th postoperative day the grafts were 95% intact. However, by postoperative day 41 there was 10% graft loss, and over the subsequent 2 weeks both grafts necrosed. On further questioning, it transpired that the patient had discontinued his warfarin on postoperative day 37 because he thought that it was no longer necessary. The patient is enrolled in the Wound Etiology and Healing (WE‐HEAL) study, and at the time of the original graft, residual skin fragments from the STSG were transplanted onto a nude mouse for development of an animal model of wound healing. The mouse graft was successful and was harvested at postoperative day 87 for pathological examination. We review the mechanisms by which prothrombotic states, particularly FVL mutation, can contribute to skin graft failure and delayed wound healing. This case highlights the importance of considering prothrombotic conditions in patients with spontaneous leg ulcerations and the impact of therapeutic anticoagulation on healing. It further allows us to demonstrate the efficacy of the animal model in which residual fragments of STSG tissue are utilised for transplant onto nude mice for manipulation in the laboratory.

Prevalence of positive QuantiFERON gold in-tube testing in hidradenitis suppurativa

To study the complex cellular interactions involved in wound healing, it is essential to have an animal model that adequately mimics the human wound microenvironment. Currently available murine models are limited because wound contraction introduces bias into wound surface area measurements. The purpose of this study was to demonstrate utility of a human–mouse xenograft model for studying human wound healing. Normal human skin was harvested from elective abdominoplasty surgery, xenografted onto athymic nude (nu/nu) mice, and allowed to engraft for 3 months. The graft was then wounded using a 2‐mm punch biopsy. Wounds were harvested on sequential days to allow tissue‐based markers of wound healing to be followed sequentially. On the day of wound harvest, mice were injected with XenoLight RediJect cyclooxygenase‐2 (COX‐2) probe and imaged according to package instructions. Immunohistochemistry confirms that this human–mouse xenograft model is effective for studying human wound healing in vivo. Additionally, in vivo fluorescent imaging for inducible COX‐2 demonstrated upregulation from baseline to day 4 (P = 0·03) with return to baseline levels by day 10, paralleling the reepithelialisation of the wound. This human–mouse xenograft model, combined with in vivo fluorescent imaging provides a useful mechanism for studying molecular pathways of human wound healing.