Brandon M. Wojcik

Statins, inflammation and deep vein thrombosis: a systematic review

Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism. The 2009 JUPITER trial showed a significant decrease in DVT in non-hyperlipidemic patients, with elevated C-reactive protein (CRP) levels, treated with rosuvastatin. The effects of statins on thrombosis are unclear, prompting this literature review. A literature search was performed (1950 to February 2011) with MEDLINE, EMBASE, and PUBMED databases including the following keywords: “statins”, “hydroxymethylglutaryl-CoA reductase inhibitors”, “VTE”, “PE”, “DVT”, and either “anti-coagulation” or “inflammation”. Editorials, reviews, case reports, meta-analysis and duplicates were excluded. Inflammatory biomarkers of DVT, include interleukin (IL)-6, CRP, IL-8, and monocyte chemotactic protein 1 (MCP-1). Statin therapy reduces IL-6 expression of CRP and MCP-1, usually elevated in VTE. Reduction of IL-6 induced MCP-1 has been linked to vein wall fibrosis, promoting post thrombotic syndrome (PTS) and recurrent DVT in patients. Also, our review suggests that the anti-thrombotic effects are likely exhibited through the anti-inflammatory properties of statins. This work supports that statin therapy has the ability to decrease the incidence and recurrence of VTE and the potential to decrease PTS. This is mainly due to the anti-inflammatory effects of statins and may explain why normolipidemic patients, with elevated CRP, appear to have the greatest reduction in VTE. Given their low risk of bleeding, statins have the potential to serve as a safe adjunctive pharmacological therapy to current treatments in select patients with VTE, however further investigations into this concept are needed and essential.

Interleukin-6: A potential target for post-thrombotic syndrome

BACKGROUND Deep vein thrombosis (DVT) and its associated sequelae, post-thrombotic syndrome (PTS), are significant health care problems in the United States. It is estimated that a maximum of 60% of patients diagnosed with DVT develop PTS, which is characterized by extensive perivenous and mural fibrosis. Interleukin-6 (IL-6) has been linked to fibrosis, and high circulating plasma levels have been found to increase the risk of developing DVT. The aim of this study was to elucidate the role of IL-6 in the progression of vein wall fibrosis by using a mouse model of DVT. METHODS AND RESULTS C57BL/6 mice (n = 136) were treated with either anti-IL-6 monoclonal antibody or control rat-immunoglobulin G. Thrombus was induced by using an inferior vena cava ligation model. The inferior vena cava and thrombus were harvested at days 2, 6, or 14 for thrombus weight, gene expression of IL-6 and/or C-C motif chemokine ligand 2 (CCL2), inflammatory cell recruitment, and morphometric analysis of vein wall fibrosis. Mice treated with anti-IL-6 had smaller thrombus weights at day 2, decreased vein wall gene expression and protein concentration of CCL2 at day 2, and impaired vein wall influx of monocytes from days 2 to 6, as compared with controls. Intimal thickness was reduced by 44% (p < 0.05) and vein wall collagen deposition was decreased by 30% at day 14 in the anti-IL-6 group (p < 0.05). CONCLUSIONS Neutralizing IL-6 throughout venous thrombogenesis decreased the production of CCL2, reduced monocyte recruitment, and decreased vein wall intimal thickness and fibrosis. These results suggest that IL-6 may serve as a therapeutic target to prevent the fibrotic complications seen in PTS.

Feeding Complications in Hypoplastic Left Heart Syndrome After the Norwood Procedure: A Systematic Review of the Literature

Gastrointestinal and feeding complications after the Norwood procedure in infants with hypoplastic left heart syndrome increases morbidity and mortality. These problems are the result of intraoperative challenges, shunt-dependent physiology, and the absence of best-practice guidelines. In response, a systematic review of feeding-related complications and management strategies was performed. A literature search from 1950 to March 2010 identified 21 primary research articles and 4 reviews. Dysphagia, necrotizing enterocolitis (NEC), and poor nutritional status are significant feeding-related complications. Three studies directly compared the modified Blalock-Taussig shunt with the right ventricle-to-pulmonary artery conduit (RV-PA). Patients palliated with either shunt had impaired mesenteric blood flow. Mortality did not differ between shunt types. Three studies demonstrated improved outcomes, e.g., increased survival, decreased incidence of NEC, and decreased median time to recommended daily allowance of calories, with a postoperative feeding algorithm. Two studies showed increased survival between stage I and II surgical palliation after implementation of a home-monitoring system consisting of daily weight and systemic oxygen saturation measurements. The RV-PA shunt does not significantly alter mortality or increase mesenteric blood flow. A postoperative feeding algorithm and a home-monitoring system may improve outcomes and decrease average hospital length of stay (LOS). Additional studies are needed to determine which interventions, as part of a standardized protocol, improve survival and decrease complications.

ABI domain‐containing proteins contribute to surface protein display and cell division in Staphylococcus aureus

The human pathogen Staphyloccocus aureus requires cell wall anchored surface proteins to cause disease. During cell division, surface proteins with YSIRK signal peptides are secreted into the cross‐wall, a layer of newly synthesized peptidoglycan between separating daughter cells. The molecular determinants for the trafficking of surface proteins are, however, still unknown. We screened mutants with non‐redundant transposon insertions by fluorescence‐activated cell sorting for reduced deposition of protein A (SpA) into the staphylococcal envelope. Three mutants, each of which harboured transposon insertions in genes for transmembrane proteins, displayed greatly reduced envelope abundance of SpA and surface proteins with YSIRK signal peptides. Characterization of the corresponding mutations identified three transmembrane proteins with abortive infectivity (ABI) domains, elements first described in lactococci for their role in phage exclusion. Mutations in genes for ABI domain proteins, designated spdA, spdB and spdC (surface protein display), diminish the expression of surface proteins with YSIRK signal peptides, but not of precursor proteins with conventional signal peptides. spdA, spdB and spdC mutants display an increase in the thickness of cross‐walls and in the relative abundance of staphylococci with cross‐walls, suggesting that spd mutations may represent a possible link between staphylococcal cell division and protein secretion.

The Use of CO2 Fractional Photothermolysis for the Treatment of Burn Scars.

A recent advancement in the treatment of burn scars has been the use of the carbon dioxide (CO2) laser to perform fractional photothermolysis. In this analysis, we describe our results and patient-reported outcomes with the use of fractional CO2 laser for the treatment of burn-related scarring. We performed a retrospective study of all patients who underwent CO2 laser procedures for treatment of symptomatic burn scars and skin grafts at one accredited regional burn center. Burn injury and laser treatment demographics, as well as complications, are reported. A questionnaire was administered to all patients and included patient-reported outcome measures aimed at understanding the patient experience and their subjective response to treatment. A total of 387 CO2 laser procedures were performed on 131 patients for the treatment of symptomatic burn scars and skin grafts between October 1, 2011, and May 1, 2014 (average, 2.95 procedures/patient; range, 1–11). Average time between injury and first laser was 597.35 days (range, 60–13,475). Average time between laser treatments (when multiple) was 117.73 days (range, 22–514). There were no infections requiring treatment with oral antibiotics. Overall patient satisfaction with laser therapy was 96.7%. Patients reported reductions in neuropathic pain, tightness (contracture), and pruritus (54.0, 50.6, and 49.0%, respectively). Fractional photothermolysis utilizing the CO2 laser is a safe and effective modality for the treatment of symptomatic burn scars, donor sites, and skin grafts. Patient satisfaction with this procedure is high, and complications are low. Significant improvements in scar appearance, pliability, tightness, neuropathic pain, and pruritus were commonly reported.

Portal vein thrombosis and outcomes for pediatric liver transplant candidates and recipients in the United States

The effect of occlusive portal vein thrombosis (PVT) on the mortality of pediatric liver transplant candidates and recipients is poorly defined. Using standard multivariate techniques, we studied the relationship between PVT and waiting‐list and posttransplant survival rates with data from the Scientific Registry of Transplant Recipients (September 2001 to December 2007). In all, 5087 liver transplant candidates and 3630 liver transplant recipients were evaluated during the period. PVT was found in 1.4% of the liver transplant candidates (n = 70) and in 3.7% of the liver transplant recipients (n = 136). PVT was not associated with increased wait‐list mortality [hazard ratio (HR) = 1.1, 95% confidence interval (CI) = 0.5‐2.4, P = 0.77]. Conversely, PVT patients had a significantly lower unadjusted survival rate in the posttransplant period (P = 0.01). PVT was independently associated with increased posttransplant mortality in multivariate models (30‐day survival: HR = 2.9, 95% CI = 1.6‐5.3, P = 0.001; overall survival: HR = 1.7, 95% CI = 1.1‐2.4, P = 0.01). The presence of PVT in pediatric liver candidates was not associated with increased wait‐list mortality but was clearly associated with posttransplant mortality, especially in the immediate postoperative period. Liver Transpl 17:1066–1072, 2011.

The Resident-Run Minor Surgery Clinic: A Pilot Study to Safely Increase Operative Autonomy

OBJECTIVE General surgery training has evolved to align with changes in work hour restrictions, supervision regulations, and reimbursement practices. This has culminated in a lack of operative autonomy, leaving residents feeling inadequately prepared to perform surgery independently when beginning fellowship or practice. A resident-run minor surgery clinic increases junior resident autonomy, but its effects on patient outcomes have not been formally established. This pilot study evaluated the safety of implementing a resident-run minor surgery clinic within a university-based general surgery training program. DESIGN Single institution case-control pilot study of a resident-run minor surgery clinic from 9/2014 to 6/2015. Rotating third-year residents staffed the clinic once weekly. Residents performed operations independently in their own procedure room. A supervising attending surgeon staffed each case prior to residents performing the procedure and viewed the surgical site before wound closure. Postprocedure patient complications and admissions to the hospital because of a complication were analyzed and compared with an attending control cohort. SETTING Massachusetts General Hospital General in Boston, MA; an academic tertiary care general surgery residency program. PARTICIPANTS Ten third-year general surgery residents. RESULTS Overall, 341 patients underwent a total of 399 procedures (110 in the resident clinic vs. 289 in the attending clinic). Minor surgeries included soft tissue mass excision (n = 275), abscess incision and drainage (n = 66), skin lesion excision (n = 37), skin tag removal (n = 15), and lymph node excision (n = 6). There was no significant difference in the overall rate of patients developing a postprocedure complication within 30 days (3.6% resident vs. 2.8% attending; p = 0.65); which persisted on multivariate analysis. Similar findings were observed for the rate of hospital admission resulting from a complication. Resident evaluations overwhelmingly supported the rotation, citing increased operative autonomy as the greatest strength. CONCLUSIONS Implementation of a resident-run minor surgery clinic is a safe and effective method to increase trainee operative autonomy. The rotation is well suited for mid-level residents, as it provides an opportunity for realistic self-evaluation and focused learning that may enhance their operative experience during senior level rotations.

A20 Haploinsufficiency Aggravates Transplant Arteriosclerosis in Mouse Vascular Allografts: Implications for Clinical Transplantation.

Background Inflammation is central to the pathogenesis of transplant arteriosclerosis (TA). We questioned whether physiologic levels of anti-inflammatory A20 influence TA severity. Methods We performed major histocompatibility complex mismatched aorta to carotid artery interposition grafts, using wild type (WT) or A20 heterozygote (HET) C57BL/6 (H-2b) donors and BALB/c (H-2d) recipients, and conversely BALB/c donors and WT/HET recipients. We analyzed aortic allografts by histology, immunohistochemistry, immunofluorescence, and gene profiling (quantitative real-time reverse-transcriptase polymerase chain reaction). We validated select in vivo A20 targets in human and mouse smooth muscle cell (SMC) cultures. Results We noted significantly greater intimal hyperplasia in HET versus WT allografts, indicating aggravated TA. Inadequate upregulation of A20 in HET allografts after transplantation was associated with excessive NF-кB activation, gauged by higher levels of IkB&agr;, p65, VCAM-1, ICAM-1, CXCL10, CCL2, TNF, and IL-6 (mostly localized to SMC). Correspondingly, cytokine-induced upregulation of TNF and IL-6 in human and mouse SMC cultures inversely correlated with A20 expression. Aggravated TA in HET versus WT allografts correlated with increased intimal SMC proliferation, and a higher number of infiltrating IFN&ggr;+ and Granzyme B+ CD4+ T cells and natural killer cells, and lower number of FoxP3+ regulatory T cells. A20 haploinsufficiency in allograft recipients did not influence TA. Conclusions A20 haploinsufficiency in vascular allografts aggravates lesions of TA by exacerbating inflammation, SMC proliferation, and infiltration of pathogenic T cells. A20 single nucleotide polymorphisms associating with lower A20 expression or function in donors of vascularized allografts may inform risk and severity of TA, highlighting the clinical implications of our findings.

Progression of Noncirrhotic Portal Hypertension in a Pediatric Population

BACKGROUND/OBJECTIVES The optimal management of children with noncirrhotic portal hypertension is controversial. Some groups suggest early and aggressive surgical intervention, while others report long-term success with conservative management. METHODS We conducted a retrospective study of 26 patients with noncirrhotic portal hypertension treated at our institution. We compared platelet counts, white blood cell (WBC) counts, spleen size, hospital admissions, gastrointestinal bleeds, and longitudinal trends of specific clinical parameters using standard univariate and time-trend analytic techniques. RESULTS Mean age at the time of diagnosis was 5.2 years. Portal vein thrombosis was found in 84.6% of patients (n=22). There was one mortality related to malignancy. There was not a progression of hypersplenism in patients that did not receive a shunt and conversely, we did not notice a significant decrease in spleen size following shunt surgery (P=0.2). Platelet and WBC counts trended downward among patients managed medically, while platelets increased and WBC counts remained stable in surgical patients. There was a significant decrease in hospital admissions for gastrointestinal bleeding following surgical intervention in the shunt group compared with nonshunt (P=0.0009). CONCLUSION While our analysis was limited given small sample sizes and selection bias, it suggests that the majority of pediatric patients with noncirrhotic portal hypertension will do well long-term without surgical intervention.

An Assessment of the Academic Impact of Shock Society Members

ABSTRACT Professional society membership enhances career development and productivity by offering opportunities for networking and learning about recent advances in the field. The quality and contribution of such societies can be measured in part through the academic productivity, career status, and funding success rates of their members. Here, using Scopus, NIH RePORTER, and departmental websites, we compare characteristics of the Shock Society membership to those of the top 55 NIH-funded American university and hospital-based departments of surgery. Shock Society members’ mean number of publications, citations and H-indices were all significantly higher than those of non-members in surgery departments (P < 0.001). A higher percentage of members also have received funding from the NIH (42.5% vs. 18.5%, P < 0.001). Regression analysis indicated that members were more likely to have NIH funding compared with non-members (OR 1.46, 95% CI 1.12–1.916). Trauma surgeons belonging to the Shock Society had a higher number of publications and greater NIH funding than those who did not (130.4 vs. 42.7, P < 0.001; 40.4% vs. 8.5%, P < 0.001). Aggregate academic metrics from the Shock Society were superior to those of the Association for Academic Surgery and generally for the Society of University Surgeons as well. These data indicate that the Shock Society represents a highly academic and productive group of investigators. For surgery faculty, membership is associated with greater academic productivity and career advancement. While it is difficult to ascribe causation, certainly the Shock Society might positively influence careers for its members.