Gangrene, revascularization, and limb function improved with E-selectin/adeno-associated virus gene therapy.

OBJECTIVE: Novel therapeutic angiogenic concepts for critical limb ischemia are still needed for limb salvage. E-selectin, a cell-adhesion molecule, is vital for recruitment of the stem/progenitor cells necessary for neovascularization in ischemic tissues. We hypothesized that priming ischemic limb tissue with E-selectin/adeno-associated virus (AAV) gene therapy, in a murine hindlimb ischemia and gangrene model, would increase therapeutic angiogenesis and improve gangrene. METHODS: FVB/NJ mice were given intramuscular hindlimb injections of either E-selectin/AAV or LacZ/AAV and then underwent induction of gangrene via femoral artery ligation and concomitant systemic injections of the nitric oxide synthesis inhibitor L-NAME (L-NG-Nitro arginine methyl ester; 40 mg/kg). Gangrene was evaluated via the Faber hindlimb appearance score. The rate of ischemic limb reperfusion and ischemic tissue angiogenesis were evaluated using laser Doppler perfusion imaging and DiI perfusion with confocal laser scanning microscopy of the ischemic footpads, respectively. The treadmill exhaustion test was performed on postoperative day (POD) 8 to determine hindlimb functionality. RESULTS: The E-selectin/AAV-treated mice (n = 10) had decreased Faber ischemia scores compared with those of the LacZ/AAV-treated mice (n = 7) at both PODs 7 and 14 (P < .05 and P < .01, respectively), improved laser Doppler perfusion imaging reperfusion indexes by POD 14 (P < .01), and greater gangrene footpad capillary density (P < .001). E-selectin/AAV-treated mice also had improved exercise tolerance (P < .05) and lower relative muscular atrophy (P < .01). CONCLUSION: We surmised that E-selectin/AAV gene therapy would significantly promote hindlimb angiogenesis, reperfusion, and limb functionality in mice with hindlimb ischemia and gangrene. Our findings highlight the reported novel gene therapy approach to critical limb ischemia as a potential therapeutic option for future clinical studies.

E-Selectin-Overexpressing Mesenchymal Stem Cell Therapy Confers Improved Reperfusion, Repair, and Regeneration in a Murine Critical Limb Ischemia Model.

AIMS: Novel cell-based therapeutic angiogenic treatments for patients with critical limb ischemia may afford limb salvage. Mesenchymal stem cells (MSCs) do not overexpress E-selectin; however, we have previously demonstrated the cell-adhesion molecule's vital role in angiogenesis and wound healing. Thus, we created a viral vector to overexpress E-selectin on MSCs to increase their therapeutic profile. METHODS AND RESULTS: Femoral artery ligation induced hind limb ischemia in mice and intramuscular injections were administered of vehicle or syngeneic donor MSCs, transduced ex vivo with an adeno-associated viral vector to express either GFP+ (MSCGFP) or E-selectin-GFP+ (MSCE-selectin-GFP). Laser Doppler Imaging demonstrated significantly restored reperfusion in MSCE-selectin-GFP-treated mice vs. controls. After 3 weeks, the ischemic limbs in mice treated with MSCE-selectin-GFP had increased footpad blood vessel density, hematoxylin and eosin stain (H&E) ischemic calf muscle sections revealed mitigated muscular atrophy with restored muscle fiber size, and mice were able to run further before exhaustion. PCR array-based gene profiling analysis identified nine upregulated pro-angiogenic/pro-repair genes and downregulated Tumor necrosis factor (TNF) gene in MSCE-selectin-GFP-treated limb tissues, indicating that the therapeutic effect is likely achieved via upregulation of pro-angiogenic cytokines and downregulation of inflammation. CONCLUSION: This innovative cell therapy confers increased limb reperfusion, neovascularization, improved functional recovery, decreased muscle atrophy, and thus offers a potential therapeutic method for future clinical studies.

Hidden Readmissions after Carotid Endarterectomy and Stenting.

BACKGROUND: Historically, carotid procedures incur a readmission rate of approximately 6%; however, these studies are not nationally representative and are limited to tracking only the index hospitals. We sought to evaluate a nationally representative database for readmission rates (including different hospitals) after both carotid endarterectomy (CEA) and carotid artery stenting (CAS) and determine risk factors for poor outcomes including postoperative mortality and myocardial infarction. METHODS: This study was a retrospective analysis utilizing the 2010-2014 Nationwide Readmissions Database to query patients aged >18 years undergoing CEA or CAS. Outcomes included initial admission mortality, and 30-day readmission, including mortality and myocardial infarction (MI). Univariable analysis of 39 demographic, clinical, and hospital variables was conducted with significance set at P < 0.05. Significant variables were included in a multivariable logistic regression to identify independent risk factors for readmission. Results were weighted for national estimates. RESULTS: There were 527,622 patients undergoing carotid procedures and 13% (n = 69,187) underwent CAS. The 30-day readmission rate was 7% (n = 35,782), and of those, 25% (n = 8,862) were readmitted to a different hospital. When controlling for other factors, CAS was a risk factor for mortality at both index admission (odds ratio [OR] 2.29 [2.11-2.49]) and 30-day readmission (OR 1.48 [1.3-1.69]) and 30-day readmissions at both index hospital (OR 1.11 [1.07-1.14]) and different hospital (OR 1.38 [1.29-1.48]). Readmission to a different hospital increased mortality risk (OR 1.45 [1.29-1.63]) but did not have an effect on MI. Postoperative infections comprised 15% of readmissions while 6% of all readmissions were for stroke. CONCLUSIONS: Previously unreported, one in 4 readmissions after carotid procedures occur at a different hospital and this fragmentation of care could increase mortality risk after carotid procedures particularly for CAS which was also an independent risk factor for postoperative mortality and readmissions. Further validation is required to decrease unnecessary hospital after carotid procedures.

Intramuscular E-selectin/adeno-associated virus gene therapy promotes wound healing in an ischemic mouse model.

BACKGROUND: Poor wound healing in critical limb ischemia (CLI) is attributed to impaired neovascularization and reperfusion. Optimizing the ischemic wound with adhesion molecules that enhance stem cell homing may revolutionize treatment. The purpose of this study is to test the efficacy of adhesion molecule E-selectin on wound healing in an ischemic mouse wound. METHODS: Adult FVB/NJ mice underwent unilateral femoral artery and vein ligation to induce CLI. A 4-mm punch biopsy wound was created on the anterior thigh to simulate ischemic wounds. Intramuscular injection of adeno-associated virus (AAV) carrying either E-selectin (E-selectin/AAV, n = 11) or LacZ as control (LacZ/AAV, n = 10) was performed. Gross wound size was measured for 10 d postoperatively. Ischemic hindlimb reperfusion was quantified using laser Doppler imaging. Wound tissue neovascularization was visualized using DiI perfusion and confocal microscopy. E-selectin expression in wounds was verified by immunofluorescence. RESULTS: Immunofluorescence confirmed E-selectin/AAV delivery in treatment versus control limbs. Wounds from E-selectin/AAV mice versus controls revealed surface area healing of 54% versus 20% (P < 0.01) on postoperative day (POD) 1, 78% versus 51% on POD 4 (P < 0.01), and 97% versus 84% on POD 10 (P < 0.01). Laser Doppler imaging revealed greater reperfusion in E-selectin/AAV mice versus controls by POD 10 (0.49 versus 0.27, P < 0.05). DiI perfused ligated hindlimb in E-selectin/AAV versus control mice revealed mean neovascularization intensity score of 30 versus 18 (P < 0.05) on POD 10. CONCLUSIONS: Intramuscularly injected E-selectin/AAV gene therapy in mice with CLI significantly increases wound angiogenesis and limb reperfusion, expediting overall wound healing.

Incidence and outcomes of pediatric extremity melanoma: A propensity score matched SEER study.

BACKGROUND: There is a paucity of literature on treatment of melanoma in children with surgical management extrapolated from adult experience. The incidence and clinical outcomes of pediatric extremity melanoma were studied. METHODS: SEER registry was analyzed between 1973 and 2010 for patients <20years old with extremity melanoma. Multivariate and propensity-score matched analyses were performed to identify independent predictors of survival. RESULTS: Overall, 917 patients were identified with an age-adjusted incidence of 0.2/100,000 persons, annual percent change 0.96. Most had localized disease (77%), histology revealing melanoma-not otherwise specified (52%). Surgical procedures performed included wide local excision (50%), excisional biopsy (32%), lymphadenectomy (LA) (28%), and sentinel lymph node biopsy (SLNB) (15%). Overall, 30-year disease specific mortality was 7% with lower survival for extremity melanoma (90%), males (89%), nodular histology (69%), and distant disease (36%) (all P<0.05). Post-treatment multivariate analysis revealed localized disease (HR 9.76; P=0.006) as an independent prognosticator of survival; earlier diagnostic years 1988-1999 (HR 2.606; P=0.017) were a negative prognosticator of survival. Propensity-score matched analysis found no difference in survival between SLNB/LA vs no sampling for regional/distant disease. CONCLUSIONS: Pediatric extremity melanoma in SEER demonstrate no survival advantage between children undergoing sampling procedures vs no sampling for regional/distant disease. TYPE OF STUDY: Retrospective, prognostic study. LEVEL OF EVIDENCE: III.

Nationwide overview of survival and management of appendiceal tumors in children.

INTRODUCTION: There remains a paucity of literature on survival related to pediatric appendiceal tumors. The purpose of this study was to determine the incidence, surgical management, and survival outcomes of appendiceal tumors in pediatric patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) Registry was analyzed for pediatric appendiceal tumors from 1973 to 2011. Parameters analyzed were: tumor type, surgical management (appendectomy vs. extensive resection), tumor size, and lymph node sampling. Chi-square analysis for categorical and Student's t test for continuous data were used. RESULTS: Overall, 209 patients had an appendiceal tumor, including carcinoid (72%), appendiceal adenocarcinoma (16%), and lymphoma (12%). Patients undergoing appendectomy vs. extensive resection had similar 15-year survival rates (98% vs. 97%; p=0.875). Appendectomy vs. extensive resection conferred no 15-year survival advantage when patients were stratified by tumor type, including adenocarcinoma (87% vs. 89%; p=0.791), carcinoid (100% vs. 100%; p=0.863), and lymphoma (94% vs. 100%; p=0.639). There was no significant difference in 15-year survival between tumor size groups ≥2 and <2cm (both 100%) and presence or absence of lymph node sampling (96% and 97%; p=0.833) for all patients with a carcinoid tumor. CONCLUSION: Appendectomy may be adequate for pediatric appendiceal tumors. Extensive resection may be of limited utility for optimizing patient survival, placing patient at greater operative risk. TYPE OF STUDY: Retrospective Prognostic Study. LEVEL OF EVIDENCE: III.

Transverse versus Longitudinal Incisions for Femoral Artery Exposure in Treating Patients with Peripheral Vascular Disease.

BACKGROUND: This study evaluates differences in wound complication rate when transverse versus longitudinal incision is utilized to expose femoral vessels in managing patients with peripheral vascular disease. METHODS: A retrospective review from 2013 to 2015 was conducted of 150 patients undergoing 156 lower extremity revascularizations with femoral artery exposure through a groin incision. Patients were stratified into 2 groups, transverse versus longitudinal groin incision. Data were reviewed for 3 surgeons that utilize either transverse or longitudinal groin incision in patients undergoing common or iliofemoral endarterectomies, or where femoral artery was used as inflow and/or outflow vessel for limb revascularization. Each group had a comparative outcomes analysis based on incision type. The primary outcome was wound complication, defined as any wound infection, lymphocele, hematoma, dehiscence, pseudoaneurysm, or necrosis. Other outcomes studied included unplanned return to operating room for wound complication, wound vacuum therapy, and soft-tissue flap closure. Data were analyzed using 2-tailed chi-squared test and Student's t-test. RESULTS: Patients in the transverse (n = 85 cases) versus longitudinal (n = 71 cases) cohorts were similar in relation to demographics and comorbidities. Overall mean follow-up was 220 days. Patients with a transverse as compared to longitudinal incision had a significantly lower overall wound complication rate, 7% vs. 42%, respectively (P < 0.001). Furthermore, transverse incisions were associated with lower incidence of unplanned return to the operating room to manage wound complications than patients with a longitudinal incision (5% vs. 23%, respectively; P < 0.001). Transverse versus longitudinal incisions were also associated with significantly lower need for wound vacuum therapy (6% vs. 15%, respectively; P < 0.05) and muscle flap closure (0% vs. 13%, respectively; P < 0.001) for wound complications. CONCLUSIONS: Transverse groin incisions for femoral artery exposure may offer a lower risk of wound complications for open procedures as compared to a longitudinal incision. While longitudinal incisions may have higher wound complication rates, incisional approach is contingent on anatomical circumstance and treated disease pattern. Patients should undergo appropriate preoperative counseling regarding wound healing in preparation for limb revascularization.

Nationwide analysis of adrenocortical carcinoma reveals higher perioperative morbidity in functional tumors.

BACKGROUND: Current adrenalectomy outcomes for functional adrenocortical carcinoma (ACC) remain unclear. This study examines nationwide in-hospital post-adrenalectomy outcomes for ACC. METHODS: A retrospective analysis of the Nationwide Inpatient Sample database (2006-2011) to identify unilateral adrenalectomy patients for functional or nonfunctional ACC was performed. Patient demographics, comorbidities and postoperative outcomes were evaluated by t-test, Chi-square and multivariate regression. RESULTS: Of 2199 patients who underwent adrenalectomy, 87% had nonfunctional and 13% had functional ACC (86% hypercortisolism, 16% hyperaldosteronism, 4% hyperandrogenism). Functional ACC patients had significantly more comorbidities, and experienced certain postoperative complications more frequently including wound issues, adrenocortical insufficiency and acute kidney injury with longer hospital stay compared to nonfunctional ACC (P < 0.01). On multivariate analysis, functional ACC was an independent prognosticator for wound complications (28.1, 95%CI 4.59-176.6). CONCLUSION: Patients with functional ACC manifest significant comorbidities with certain in-hospital complications. Such high-risk patients require appropriate preoperative medical optimization prior to adrenalectomy.

A Reliable Mouse Model of Hind limb Gangrene.

BACKGROUND: Lack of a reliable hind limb gangrene animal model limits preclinical studies of gangrene, a severe form of critical limb ischemia. We develop a novel mouse hind limb gangrene model to facilitate translational studies. METHODS: BALB/c, FVB, and C57BL/6 mice underwent femoral artery ligation (FAL) with or without administration of NG-nitro-L-arginine methyl ester (L-NAME), an endothelial nitric oxide synthase inhibitor. Gangrene was assessed using standardized ischemia scores ranging from 0 (no gangrene) to 12 (forefoot gangrene). Laser Doppler imaging (LDI) and DiI perfusion quantified hind limb reperfusion postoperatively. RESULTS: BALB/c develops gangrene with FAL-only (n = 11/11, 100% gangrene incidence), showing mean limb ischemia score of 12 on postoperative days (PODs) 7 and 14 with LDI ranging from 0.08 to 0.12 on respective PODs. Most FVB did not develop gangrene with FAL-only (n = 3/9, 33% gangrene incidence) but with FAL and L-NAME (n = 9/9, 100% gangrene incidence). Mean limb ischemia scores for FVB undergoing FAL with L-NAME were significantly higher than for FVB receiving FAL-only. LDI score and capillary density by POD 28 were significantly lower in FVB undergoing FAL with L-NAME. C57BL/6 did not develop gangrene with FAL-only or FAL and L-NAME. CONCLUSIONS: Reproducible murine gangrene models may elucidate molecular mechanisms for gangrene development, facilitating therapeutic intervention.

Looped suture versus stapler device in pediatric laparoscopic appendectomy: a comparative outcomes and intraoperative cost analysis.

BACKGROUND: Appendiceal ligation during pediatric laparoscopic appendectomy (LA) may be performed using looped suture versus stapler. Controversy regarding the utility of either method exists. Clinical outcomes and cost analysis of LA with both methods were compared. METHODS: All pediatric LA were performed from fiscal years 2013 and 2014 by two pediatric surgeons. While one surgeon used looped suture, the other used stapler exclusively. chi-Square tests were performed to analyze associations. RESULTS: Two hundred thirty-eight cases were analyzed where looped suture versus stapler LA was performed in 46% and 54% of patients, respectively. Operating room costs were $317.10 and $707.12/person for looped suture and stapler LA, respectively (P<0.0001). Difference in cost of $390.02/person was attributed solely to ligation type. On bivariate analysis, rate of in-hospital complications, length of stay, return-to-ER and readmission within 30 days did not significantly differ between groups. CONCLUSION: A comparative analysis of looped suture versus stapler device during LA for pediatric appendicitis revealed that postoperative complications, length of stay, ER visits and readmissions were not significantly different. Looped suture LA was significantly more cost efficient than stapler LA. In pediatric appendicitis, appendiceal ligation during LA may be performed safely and cost effectively with looped suture versus stapler. TYPE OF STUDY: Cost effectiveness LEVEL OF EVIDENCE: III.

Nationwide review of hormonally active adrenal tumors highlights high morbidity in pheochromocytoma.

BACKGROUND: Adrenal adenomas are benign tumors often discovered incidentally, and >70% are hormonally inactive. The remaining subset may produce excess aldosterone, cortisol, or catecholamine. Perioperative outcomes after adrenalectomy for such "hormonally active" tumors remain unclear. This study examines in-hospital outcomes after unilateral adrenalectomy for hormonally active tumors. METHODS: A retrospective review was performed using the Nationwide Inpatient Sample (2006-2011) to identify patients undergoing unilateral adrenalectomy for hormonally active or inactive tumors. Malignant adrenal tumors were excluded. Demographics, comorbidities, and postoperative complications were evaluated by univariate analysis, using two-tailed Chi-square and t-tests and multivariate logistic regression. RESULTS: Of 27,312 patients who underwent adrenalectomy, 78% (n = 21,279) had hormonally inactive and 22% (n = 6033) had hormonally active adrenal tumors. Among the latter, 65% (n = 4000) had primary hyperaldosteronism (Conn's syndrome), 33% (n = 1996) had hypercortisolism (Cushing's syndrome), and 1.4% (n = 85) had pheochromocytoma. Patients with pheochromocytoma had higher rate of comorbidities including congestive heart failure, chronic lung disease, and malignant hypertension compared with remaining hormonally active tumors (12% versus 4%, 18% versus 11%, 6% versus 2%; P < 0.01). For patients with pheochromocytoma versus other hormonally active tumors, mean length of stay was 5 versus 3 d and total in-hospital cost was $50,000 versus $41,000 (P < 0.01). On multivariate analysis, pheochromocytoma had an independently higher risk for intraoperative blood transfusion (4.2, 95% confidence interval [CI] 2.4-7.2), postoperative cardiac (7.6, 95% CI 2.8-20.2), and respiratory (1.9, 95% CI 1.0-3.3) complications. CONCLUSIONS: Patients with pheochromocytoma have high rates of preoperative comorbidities, postoperative cardiopulmonary complications, and longer and more costly hospitalizations. Such high-risk patients should undergo appropriate preoperative medical optimization in preparation for adrenalectomy.

Postoperative Outcomes in Graves' Disease Patients: Results from the Nationwide Inpatient Sample Database.

BACKGROUND: Current surgical indications for Graves' disease include intractability to medical and/or radioablative therapy, compressive symptoms, and worsening ophthalmopathy. Total thyroidectomy for Graves' disease may be technically challenging and lead to untoward perioperative outcomes. This study examines outcomes in patients with Graves' disease who underwent total thyroidectomy and assesses its safety for this patient population. METHODS: A retrospective cross-sectional analysis was performed using the Nationwide Inpatient Sample database from 2006 to 2011. Total thyroidectomy performed in patients with Graves' disease, benign multinodular goiter (MNG), and thyroid cancer was identified. Demographic factors, comorbidities, and postoperative complications were evaluated. Chi-square, one-way analysis of variance, and risk-adjusted multivariable logistic regression were performed. RESULTS: Of 215,068 patients who underwent total thyroidectomy during the study period, 11,205 (5.2%) had Graves' disease, 110,124 (51.2%) MNG, and 93,739 (43.6%) thyroid malignancy. Patients with Graves' disease were younger than MNG and thyroid cancer patients (Mage = 42.8 years vs. 55.5 and 51.0 years; p < 0.01). The Graves' disease group included a higher proportion of women (p < 0.01) and nonwhites (p < 0.01). Postoperatively, Graves' patients had significantly higher rates of hypocalcemia (12.4% vs. 7.3% and 10.3%; p < 0.01), hematomas requiring reoperation (0.7% vs. 0.4% and 0.4%; p < 0.01), and longer mean hospital stay (2.7 days vs. 2.4 and 2.2 days; p < 0.01) compared to MNG and thyroid cancer patients, respectively. On risk-adjusted multivariate logistic regression, Graves' disease was independently associated with a higher risk of vocal-cord paralysis (odds ratio [OR] = 1.36 [confidence interval (CI) 1.08-1.69]), tracheostomy (OR = 1.35 [CI 1.1-1.67]), postoperative hypocalcemia (OR = 1.65 [CI 1.54-1.77]), and hematoma requiring reoperation (OR = 2.79 [CI 2.16-3.62]) compared to MNG patients. High-volume centers for total thyroidectomy were independently associated with lower risk of postoperative complications, including in patients with Graves' disease. CONCLUSIONS: Despite low overall morbidity following total thyroidectomy, Graves' disease patients are at increased risk of postoperative complications, including bleeding, vocal-cord paralysis, tracheostomy, and hypocalcemia. These risks appear to be lower when performed at high-volume centers, and thus referral to these centers should be considered. Total thyroidectomy may therefore be a safe treatment option for appropriately selected patients with Graves' disease when performed by experienced surgeons.

A Molecular and Clinical Review of Stem Cell Therapy in Critical Limb Ischemia.

Peripheral artery disease (PAD) is one of the major vascular complications in individuals suffering from diabetes and in the elderly that can progress to critical limb ischemia (CLI), portending significant burden in terms of patient morbidity and mortality. Over the last two decades, stem cell therapy (SCT) has risen as an attractive alternative to traditional surgical and/or endovascular revascularization to treat this disorder. The primary benefit of SCT is to induce therapeutic neovascularization and promote collateral vessel formation to increase blood flow in the ischemic limb and soft tissue. Existing evidence provides a solid rationale for ongoing in-depth studies aimed at advancing current SCT that may change the way PAD/CLI patients are treated.

Intraoperative Parathormone Monitoring Mitigates Age-Related Variability in Targeted Parathyroidectomy for Patients with Primary Hyperparathyroidism.

BACKGROUND: Preoperative parathyroid localization studies, namely, sestamibi (MIBI) and surgeon-performed ultrasound (SUS), are commonly used for targeted parathyroidectomy (PTX) with intraoperative parathormone monitoring (IPM) in patients with primary hyperparathyroidism (pHPT). This study examined age-related variability in abnormal parathyroid gland localization for targeted PTX and the value of IPM across age groups. METHODS: A retrospective review examined prospectively collected data of 833 patients who underwent targeted PTX guided by IPM. The patients were stratified into three age groups as follows: younger [<47 years; mean -1 standard deviation (SD)], typical (47-73 years), and older (>73 years; mean +1 SD) based on an age distribution curve for pHPT. The accuracy, sensitivity, and positive predictive value (PPV) for MIBI, SUS, and IPM were analyzed and compared among age groups. Operative success was defined as eucalcemia for 6 months or longer after PTX, and operative failure was defined as elevated calcium and PTH levels within 6 months after PTX. RESULTS: Of the 833 patients, the youngest group had the highest accuracy and sensitivity for MIBI, SUS, and IPM compared with the older groups (p < 0.05). The accuracy and sensitivity of MIBI and SUS also decreased significantly with increased age (p < 0.05). Within all three age groups, IPM was consistently more accurate and sensitive than SUS or MIBI (p < 0.05). CONCLUSIONS: Age can significantly affect the accuracy and sensitivity of MIBI and SUS in targeted PTX for patients with pHPT. Across all age groups, IPM remains more accurate than preoperative localization studies. For the elderly, in whom multiglandular disease appears increased, surgeons should have a lower threshold for conversion to bilateral neck exploration.

Long-term effectiveness of localization studies and intraoperative parathormone monitoring in patients undergoing reoperative parathyroidectomy for persistent or recurrent hyperparathyroidism.

BACKGROUND: Reoperative parathyroidectomy (RPTX) for persistent or recurrent hyperparathyroidism is associated with a high rate of operative failure. The long-term effectiveness of RPTX using localization studies and intraoperative parathormone monitoring (IPM) was examined. METHODS: Retrospective analysis of prospectively collected data from patients undergoing targeted RPTX with IPM for persistent or recurrent hyperparathyroidism was performed. Persistent hyperparathyroidism was defined as elevated calcium and parathormone (PTH) levels above normal range less than 6 months after parathyroidectomy. Recurrent hyperparathyroidism was defined as elevated calcium and PTH levels greater than 6 months after successful parathyroidectomy. Sensitivity and positive predictive value (PPV) for sestamibi, surgeon-performed ultrasound, intraoperative PTH dynamics, and surgical outcomes were evaluated. RESULTS: Of the 1,064 patients, 69 patients underwent 72 RPTXs with localizing studies and IPM. Sestamibi (n = 69) had a sensitivity of 74% and a PPV of 83%, whereas surgeon-performed ultrasound (n = 38) had a sensitivity of 55% and a PPV of 76%. IPM had a sensitivity of 100% and a PPV of 98%. An intraoperative PTH drop greater than or equal to 50% was predictive of operative success (P < .01). Overall, operative success and recurrence were 94% and 1.4%, with a mean patient follow-up of 59 ± 12.8 months. CONCLUSION: RPTX can be performed in a targeted approach using preoperative localization studies and IPM, leading to a low rate of complications and a high rate of long-term operative success.

Are burn patients really at risk for thrombotic events?

There continues to be debate about the routine use of deep vein thrombosis (DVT) prophylaxis in burn patients. The concern is that routine prophylaxis may lead to adverse events. The debate hinges on the incidence of DVT and its relation to the risk-benefit ratio. This study seeks to estimate the true rate of DVT in burn patients, and to evaluate possible risk factors to its development. The Nationwide Inpatient Sample was queried for all patients with age ≥18 years with ICD-9 codes for burn injuries. Demographic data, comorbidities, burn data, length of stay, total charges, procedures, presence of central venous catheter, and mortality were recorded. Patients were classified based on the presence of DVT. Student's t-test, χ test, and logistic regression were performed. 36,638 burn patients were identified. DVT rate was 0.8%. Patients with DVT were older, had longer hospitalizations, more procedures, and higher charges. On logistic regression, black race, TBSA ≥20%, history of previous venous thrombotic events, blood transfusion, and mechanical ventilation were the significant factors associated with DVT. Patients with DVT were almost twice as likely to die during the admission (P = .011). This is the largest series to date examining the risk factors for DVT in burn patients. DVT developed in approximately 0.8% of burn patients. Black race, TBSA ≥20%, blood transfusions, and mechanical ventilation were associated with approximately 2-fold odds of developing DVT. Identification of these additional risk factors may allow targeted patient prophylaxis. Additionally, patients with DVT incurred higher total charges and longer hospitalization.

Infant with bilateral pulmonary sequestrations with portal venous drainage excised by video-assisted thoracic surgery.

INTRODUCTION: Bilateral pulmonary sequestrations are rare congenital anomalies. Despite its benign nature, the potential complications of pulmonary sequestration (PS) are significant, including recurrent pulmonary infections, hemoptysis, congestive heart failure, and malignant potential. Therefore, the main treatment is surgical excision, even for patients with asymptomatic PS. CASE: We present an infant in whom an intralobar PS of the right lung and an extralobar PS of the left lung were diagnosed on prenatal screening ultrasonography. Both were found to have venous drainage into the portal vein. Surgical excision was performed via video-assisted thoracic surgery (VATS) at 14 months of age. CONCLUSION: PS may present with unique vascular connections, including venous drainage into the portal vein. VATS resection for pulmonary sequestration is feasible and effective as an alternative to bilateral thoracotomies, in the setting of extensive preoperative planning and performance by an experienced thoracoscopic surgeon.

A nationwide analysis of clinical outcomes among newborns with esophageal atresia and tracheoesophageal fistulas in the United States.

BACKGROUND: The aim of this study was to examine national outcomes in newborn patients with esophageal atresia and tracheoesophageal fistula (EA/TEF) in the United Sates. METHODS: Kids' Inpatient Database (KID) is designed to identify, track, and analyze national outcomes for hospitalized children in the United States. Inpatient admissions for pediatric patients with EA/TEF for kids' Inpatient Database years 2000, 2003, 2006, and 2009 were analyzed. Patient demographics, socioeconomic measures, disposition, survival and surgical procedures performed were analyzed using standard statistical methods. RESULTS: A total of 4168 cases were identified with diagnosis of EA/TEF. The overall in-hospital mortality was 9%. Univariate analysis revealed lower survival in patients with associated acute respiratory distress syndrome, ventricular septal defect (VSD), birth weight (BW) < 1500 g, gestational age (GA), time of operation within 24 h of admission, coexisting renal anomaly, imperforate anus, African American race, and lowest economic status. Multivariate logistic regression identified BW < 1500 g (odds ratio [OR] = 4.5, P < 0.001), operation within 24 h (OR = 6.9, P < 0.001), GA <28 wk (OR = 2.2, P < 0.030), and presence of VSD (OR = 3.8, P < 0.001) as independent predictors of in-hospital mortality. Children's general hospital and children's unit in a general hospital were found to have a lower mortality rate compared with not identified as a children's hospital after excluding immediate transfers (P = 0.008). CONCLUSIONS: BW < 1500 g, operation within 24 h, GA < 28 wk, and presence of VSD are the factors that predict higher mortality in EA/TEF population. Despite dealing with more complicated cases, children's general hospital and children's unit in a general hospital were able to achieve a lower mortality rate than not identified as a children's hospital.

Surgical treatment of patients with mildly elevated parathormone and calcium levels.

BACKGROUND: Patients with mildly elevated parathormone (PTH) and calcium levels consistent for primary hyperparathyroidism (pHPT) may present with more underlying multiglandular disease (MGD) and higher operative failure and recurrence rates than those with conventional, or "classic" pHPT. This study compared the clinical characteristics and surgical outcomes of patients with biochemically mild versus conventional pHPT. METHODS: A series of 707 consecutive patients underwent initial targeted parathyroidectomy with intraoperative parathormone monitoring (IPM) at a single institution. Biochemically mild (BM) pHPT was defined as PTH > 65 and <100 pg/ml with serum calcium >10.4 and <11 mg/dl. Conventional pHPT was defined as calcium ≥11 mg/dl and PTH ≥ 100 pg/ml. Prospectively collected data for all patients, including operative indication, preoperative laboratory values, imaging, IPM dynamics, and postoperative laboratory values were retrospectively reviewed. Additional assessments included presence of MGD, bilateral neck exploration (BNE), single-gland volume, and operative failure or success, and recurrence. RESULTS: Of 60 patients with BM-pHPT, 46 reported preoperative bone pain, kidney stones, fatigue, and/or mental disturbances. The remaining 14 BM-pHPT patients underwent parathyroidectomy based on published asymptomatic guidelines. Patients with BM-pHPT had significantly more kidney stones, MGD, and BNE. Average single-gland volume and postoperative PTH levels were significantly lower in BM-pHPT patients. There were no significant differences between groups regarding preoperative localization accuracy, IPM dynamics, or operative success/failure, recurrence rates. CONCLUSIONS: BM-pHPT patients had more MGD requiring BNE but achieved operative success rates similar to those of patients with conventional disease. IPM successfully identifies MGD in BM-pHPT patients, who should be counseled regarding more extensive operations than limited parathyroidectomy.

A review of 218 pediatric cases of hepatocellular carcinoma.

PURPOSE: This study evaluates the incidence trends and clinical outcomes of children with hepatocellular carcinoma (HCC) and assesses factors predictive of patient survival. METHODS: The Surveillance, Epidemiology, and End Results registry was queried from 1973 to 2009 for all patients between ages 0 and 19 with primary HCC. Demographics, tumor histology, surgical intervention, and patient survival were collected. RESULTS: Overall, 218 patients were identified. The annual age-adjusted incidence was 0.05 cases per 100,000 in 2009. Fibrolamellar subtype tumors were exclusive to children >5years old and exhibited greater survival compared to non-fibrolamellar subtype (57% vs. 28%, respectively, p=0.002). Tumor extirpation for patients with resectable disease significantly improved overall survival at 5years compared to no surgery (60% vs. 0%, respectively, p<0.0001). Overall 5-, 10- and 20-year survival for the entire cohort was 24%, 23%, and 8%, respectively. Independent prognostic factors of lower mortality according to multivariate analysis were surgical resection (hazard ratio (HR)=0.18), non-Hispanic ethnicity (HR=0.52), and local disease at presentation (HR=0.46). CONCLUSION: Over the past four decades, the incidence of HCC has remained relatively stable. Children of Hispanic ethnicity have high mortality rates. However, HCC resection for curative intent significantly improves outcomes.