Staged Repair of Primary Aortoesophageal Fistula.

Primary aortoenteric fistulas are rare with an incidence reported up to .07% at autopsy. Literature review yields few reported cases, and rarer still is a fistula between a normal thoracic aorta and the esophagus. Rather, 83% of cases are associated with an aneurysmal aorta and 54% involve the duodenum. Patients with aortoesophageal fistula (AEF) usually present with a triad of chest pain, dysphasia, and a herald bleed. Without treatment, AEFs will result in exsanguination and are universally fatal; even with traditional open surgical treatment, mortality is reported over 55%. The complex pathology of AEFs makes repair more challenging, given an infected field, friable tissue, and patients who are often hemodynamically unstable. Staged repair using endografts as initial treatment with the primary goal of controlling bleeding and preventing fatal exsanguination has been reported. We present a case where a descending thoracic aorta to esophageal fistula was repaired, and this strategy was utilized.

Characterization of NADH fluorescence properties under one-photon excitation with respect to temperature, pH, and binding to lactate dehydrogenase.

Reduced nicotinamide adenine dinucleotide (NADH) is the principal electron donor in glycolysis and oxidative metabolism and is thus recognized as a key biomarker for probing metabolic state. While the fluorescence characteristics of NADH have been investigated extensively, there are discrepancies in the published data due to diverse experimental conditions, instrumentation and microenvironmental parameters that can affect NADH fluorescence. Using a cuvette-based time-resolved spectrofluorimeter employing one-photon excitation at 375 nm, we characterized the fluorescence intensity, lifetime, spectral response, anisotropy and time-resolved anisotropy of NADH in aqueous solution under varying microenvironmental conditions, namely temperature, pH, and binding to lactate dehydrogenase (LDH). Our results demonstrate how temperature, pH, and binding partners each impact the fluorescence signature of NADH and highlight the complexity of the fluorescence data when different parameters produce competing effects. We hope that the data presented in this study will provide a reference for potential sources of variation in experiments measuring NADH fluorescence.

In vivo label-free optical monitoring of structural and metabolic remodeling of myocardium following infarction.

Cardiac remodeling following myocardial infarction (MI) involves structural and functional alterations in the infarcted and remote viable myocardium that can ultimately lead to heart failure. The underlying mechanisms are not fully understood and, following our previous study of the autofluorescence lifetime and diffuse reflectance signatures of the myocardium in vivo at 16 weeks post MI in rats [Biomed. Opt. Express6(2), 324 (2015)], we here present data obtained at 1, 2 and 4 weeks post myocardial infarction that help follow the temporal progression of these changes. Our results demonstrate that both structural and metabolic changes in the heart can be monitored from the earliest time points following MI using label-free optical readouts, not only in the region of infarction but also in the remote non-infarcted myocardium. Changes in the autofluorescence intensity and lifetime parameters associated with collagen type I autofluorescence were indicative of progressive collagen deposition in tissue that was most pronounced at earlier time points and in the region of infarction. In addition to significant collagen deposition in infarcted and non-infarcted myocardium, we also report changes in the autofluorescence parameters associated with reduced nicotinamide adenine (phosphate) dinucleotide (NAD(P)H) and flavin adenine dinucleotide (FAD), which we associate with metabolic alterations throughout the heart. Parallel measurements of the diffuse reflectance spectra indicated an increased contribution of reduced cytochrome c. Our findings suggest that combining time-resolved spectrofluorometry and diffuse reflectance spectroscopy could provide a useful means to monitor cardiac function in vivo at the time of surgery.

Characterization of NAD(P)H and FAD autofluorescence signatures in a Langendorff isolated-perfused rat heart model.

Autofluorescence spectroscopy is a promising label-free approach to characterize biological samples with demonstrated potential to report structural and biochemical alterations in tissues in a number of clinical applications. We report a characterization of the ex vivo autofluorescence fingerprint of cardiac tissue, exploiting a Langendorff-perfused isolated rat heart model to induce physiological insults to the heart, with a view to understanding how metabolic alterations affect the autofluorescence signals. Changes in the autofluorescence intensity and lifetime signatures associated with reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD) were characterized during oxygen- or glucose-depletion protocols. Results suggest that both NAD(P)H and FAD autofluorescence intensity and lifetime parameters are sensitive to changes in the metabolic state of the heart owing to oxygen deprivation. We also observed changes in NAD(P)H fluorescence intensity and FAD lifetime parameter on reperfusion of oxygen, which might provide information on reperfusion injury, and permanent tissue damage or changes to the tissue during recovery from oxygen deprivation. We found that changes in the autofluorescence signature following glucose-depletion are, in general, less pronounced, and most clearly visible in NAD(P)H related parameters. Overall, the results reported in this investigation can serve as baseline for future investigations of cardiac tissue involving autofluorescence measurements.

The Integration of Adult Acute Care Surgeons into Pediatric Surgical Care Models Supplements the Workforce without Compromising Quality of Care.

Acute care of children remains a challenge due to a shortage of pediatric surgeons, particularly in rural areas. In our institutional norm, all cases in patients age six and older are managed by dedicated general surgeons. The provision of care to these children by these surgeons alleviates the impact of such shortages. We conducted a five-year retrospective analysis of all acute care pediatric surgical cases performed in patients aged 6 to 17 years by a dedicated group of adult general surgeons in a rural tertiary care hospital. Demographics, procedure, complications, outcomes, length of stay, and time of consultation/operation were obtained via chart review. Elective, trauma related, or procedures performed by a pediatric surgeon were excluded. Descriptive statistics are reported. A total of 397 cases were performed by six dedicated general surgeons during the study period. Mean age was 11.5 ± 3.1 years. In all, 100 (25.2%) were transferred from outlying facilities and 52.6 per cent of consultations/operations occurred at night (7P-7A), of which 33.2 per cent occurred during late night hours (11P-7A). On weekends, 34.0 per cent occurred. Appendectomy was the most commonly performed operation (n = 357,89.9%), of which 311 were laparoscopic (87.1%). Others included incision/drainage (4.5%), laparoscopic cholecystectomy (2.0%), bowel resection (1.5%), incarcerated hernia (0.5%), small bowel obstruction (0.5%), intra-abdominal abscess drainage (0.3%), resection of intussusception (0.3%), Graham patch (0.3%), and resection omental torsion (0.3%). Median length of stay was two days. Complications occurred in 23 patients (5.8%), of which 22(5.5%) were the result of the disease process. These results parallel those published by pediatric surgeons in this age group and for the diagnoses treated. Models integrating dedicated general surgeons into pediatric call rotations can be designed such that quality of pediatric care is maintained while providing relief to an overburdened pediatric surgical workforce.

Gastric electrical stimulation for refractory gastroparesis: predictors of response and redefining a successful outcome.

Predictors of a favorable response and measures of success with gastric electrical stimulation (GES) for gastroparesis remain elusive. Published results remain inconsistent with respect to patient perceived benefit, despite statistical improvements in objective measures of symptom severity. We performed a retrospective analysis of 56 patients with gastroparesis who underwent insertion of a gastric electrical stimulator during the study period. Data included demographics, symptoms, total symptom severity score (TSS, range 0-24, initial and most recent), and gastric emptying times. TSS were grouped into four severity categories (0-10, 11-14, 15-18, 19-24). TSS improvement was defined as movement to a lower severity category. Perception of improvement was compared with that of TSS score improvement using χ(2) test. Etiology as a predictor of improvement was measured using logistic regression. Initial mean TSS was 21, and post-treatment TSS was 13.5. Improvement was significant for individual symptoms and in reduction of TSS for both diabetic/idiopathic etiologies (P ≤ 0.001). No correlation was noted between likelihood of success/failure and gastric emptying times (P = 0.32). Thirty-eight improved (moved to lower TSS category), whereas 18 failed (remained in same category) (P ≤ 0.001), which correlated with perception of improvement. Of 18 failures, 14 (77.7%) were idiopathic. On logistic regression, diabetics were more likely than idiopathic patients to move to a lower TSS category (odds ratio 14, P = 0.003) and even more likely to improve based on patient perception (odds ratio 45, P = 0.005). GES produces far more consistent improvement in diabetics. Further study of GES in idiopathic gastroparesis is needed. Application of the proposed TSS severity categories allowed differentiation of small, statistically significant (but clinically insignificant) reductions in TSS from larger, clinically significant reductions, thereby permitting more reliable application of TSS to the evaluation of GES efficacy.

Application of time-resolved autofluorescence to label-free in vivo optical mapping of changes in tissue matrix and metabolism associated with myocardial infarction and heart failure.

We investigate the potential of an instrument combining time-resolved spectrofluorometry and diffuse reflectance spectroscopy to measure structural and metabolic changes in cardiac tissue in vivo in a 16 week post-myocardial infarction heart failure model in rats. In the scar region, we observed changes in the fluorescence signal that can be explained by increased collagen content, which is in good agreement with histology. In areas remote from the scar tissue, we measured changes in the fluorescence signal (p < 0.001) that cannot be explained by differences in collagen content and we attribute this to altered metabolism within the myocardium. A linear discriminant analysis algorithm was applied to the measurements to predict the tissue disease state. When we combine all measurements, our results reveal high diagnostic accuracy in the infarcted area (100%) and border zone (94.44%) as well as in remote regions from the scar (> 77%). Overall, our results demonstrate the potential of our instrument to characterize structural and metabolic changes in a failing heart in vivo without using exogenous labels.

Component separation with porcine acellular dermal reinforcement is superior to traditional bridged mesh repairs in the open repair of significant midline ventral hernia defects.

The optimal technique for complex ventral hernia repair (VHR) remains controversial. Component separation (CS) reinforced with porcine acellular dermal matrix (PADM) has shown favorable results compared with series of conventional bridged VHR, but few comparative studies exist. We conducted a retrospective cohort study comparing 40 randomly selected patients who underwent CS/PADM reinforcement against an identical number of patients who underwent conventional open VHR with mesh at our institution. Patient characteristics, operative findings, outcomes, complications, reoperations, and recurrences were obtained by chart review. Fisher's exact/t test compared outcomes between the two cohorts. Statistical significance was set as P < 0.05. Mean follow-up was 33.1 months. Patient groups did not differ significantly in race (P = 1.00), age (P = 0.82), body mass index (P = 0.14), or comorbid conditions (smoking, chronic obstructive pulmonary disease, obesity, steroid use; P values 0.60, 0.29, 0.08, and 0.56, respectively). Defect size was greater in the CS/PADM group (mean, 372.5 vs 283.7 cm(2), P = 0.01) as was the percentage Ventral Hernia Working Group Grade III/IV hernias (65.0 vs 30.0%, P = 0.03). Recurrences were lower in the CS/PADM group (13.2 vs 37.5%, P = 0.02). Mesh infection was lower in the CS/PADM group (0 vs 23% in the bridged group, P = 0.002), all of which occurred with synthetic mesh. Indications for reoperation (recurrence or complications requiring reoperation) were also lower in the CS/PADM group (17.5 vs 52.5%, P = 0.002). Superior results are achieved with CS/PADM reinforcement over traditional bridged VHR. This is evidenced by lower recurrence rates and overall complications requiring reoperation, particularly mesh infection. This is despite the greater use of CS in larger defects and contaminated hernias (VHWG Grade III and IV). CS/PADM reinforcement should be strongly considered for the repair of significant midline ventral hernia defects.

Allosteric inhibition of human immunodeficiency virus integrase: late block during viral replication and abnormal multimerization involving specific protein domains.

HIV-1 replication in the presence of antiviral agents results in evolution of drug-resistant variants, motivating the search for additional drug classes. Here we report studies of GSK1264, which was identified as a compound that disrupts the interaction between HIV-1 integrase (IN) and the cellular factor lens epithelium-derived growth factor (LEDGF)/p75. GSK1264 displayed potent antiviral activity and was found to bind at the site occupied by LEDGF/p75 on IN by x-ray crystallography. Assays of HIV replication in the presence of GSK1264 showed only modest inhibition of the early infection steps and little effect on integration targeting, which is guided by the LEDGF/p75-IN interaction. In contrast, inhibition of late replication steps was more potent. Particle production was normal, but particles showed reduced infectivity. GSK1264 promoted aggregation of IN and preformed LEDGF/p75-IN complexes, suggesting a mechanism of inhibition. LEDGF/p75 was not displaced from IN during aggregation, indicating trapping of LEDGF/p75 in aggregates. Aggregation assays with truncated IN variants revealed that a construct with catalytic and C-terminal domains of IN only formed an open polymer associated with efficient drug-induced aggregation. These data suggest that the allosteric inhibitors of IN are promising antiviral agents and provide new information on their mechanism of action.

Streptococcus bovis bacteremia as the initial presentation of carcinoma of the gallbladder.

There is a well known association between Streptococcus bovis infection and the presence of a coexisting colonic adenocarcinoma. Association of S. bovis with other malignancies has only been rarely reported. We report a 77-year-old male who presented with with Streptococcus bovis bacteremia in the setting of acute cholecystitis. Given the association of colon adenocarcinoma and Streptococcus bovis bacteremia, colonoscopy was performed prior to cholecystectomy to evaluate a possible coexisting colon neoplasm, which was negative. At cholecystectomy, the patient was found to have a carcinoma of the gallbladder, which was treated with radical cholecystectomy and periportal lymphadenectomy. This is the first case of Streptococcus bovis infection and coexisting gallbladder cancer to be reported, and highlights the need for maintenance of a high index of suspicion for malignancies other than colon cancer when patients present with Streptococcus bovis bacteremia.

Angioplasty and stenting versus carotid-subclavian bypass for the treatment of isolated subclavian artery disease.

PURPOSE: To compare the results of a large series of percutaneous transluminal angioplasty (PTA)/stenting procedures in the subclavian artery with the results of a series of carotid-subclavian bypass grafts (CSBG) performed at the same institution for subclavian artery disease. METHODS: Between 1993 and 2006, 121 patients (43 men; mean age 63 years, range 38-85) underwent subclavian artery PTA/stenting and were compared to a group of 51 patients (29 men; mean age 62 years, range 46-75) with isolated subclavian artery occlusive disease treated with CSBG using polytetrafluoroethylene grafts. Graft or PTA/stenting patency was determined clinically and confirmed by Doppler pressures and/or duplex ultrasound/angiography. The cumulative patency and overall survival rates were calculated using the life-table method. RESULTS: The mean follow-up for the PTA/stent group was 3.4 years versus 7.7 years for the CSBG group. The technical success rate for the CSBG group was 100% versus 98% (119/121) for the PTA/stent group. The overall perioperative complication rate in the stent group was 15.1% (18/119: 11 minor and 7 major complications) versus 5.9% (3/51: 2 phrenic nerve palsy and 1 myocardial infarction) in the bypass group (p=0.093). There was no perioperative stroke or mortality in the CSBG group. The major perioperative complications in the stent group included 4 thromboembolic events, 1 congestive heart failure, 1 reperfusion arm edema, and 1 pseudoaneurysm. There was 1 perioperative death in the stent group. The 30-day patency rate was 100% for the bypass group and 97% (118/121) for the PTA/stent group. The primary patency rates at 1, 3, and 5 years were 100%, 98%, and 96% for the CSBG group versus 93%, 78%, and 70% for the stent group, respectively (p<0.0001). Freedom from symptom recurrence was also statistically superior in the bypass group versus the stent group (p<0.0001). There were no significant differences in the survival rates between both groups at any time point (p=0.322). CONCLUSION: Both CSBGs using PTFE grafts and subclavian PTA/stenting are safe, effective, and durable; however, CSBG is more durable in the long term. PTA/stenting of the subclavian artery should be the procedure of choice for high-risk patients; however, CSBG should be offered to good-risk surgical candidates who may be seeking a more durable procedure.

Tension pneumoperitoneum resulting from endoscopic duodenal perforation: a case report.

Tension pneumoperitoneum is defined as an accumulation of free air within the peritoneal cavity sufficient to cause respiratory or hemodynamic compromise. We report a case of a 75-year-old woman who underwent upper endoscopy for evaluation of severe upper gastrointestinal hemorrhage. During the procedure, she developed massive abdominal distension, raising concern about possible perforation. Endoscopy was terminated and prompt surgical consultation obtained. This revealed massive abdominal distension, hypotension, and elevated airway pressures. Tension pneumoperitoneum was suspected. There was immediate decompression via a small umbilical incision, after which the patient's condition stabilized. A full exploration was then carried out, allowing definitive surgical treatment of both the source of bleeding and the perforation. We review the literature regarding this unusual event.

Computed tomography versus color duplex ultrasound for surveillance of abdominal aortic stent-grafts.

PURPOSE: To compare the ability of computed tomography (CT) and color duplex ultrasound (CDUS) to detect endoleak and accurately measure aortic aneurysm diameters after endovascular repair. METHODS: Between February 2000 and October 2004, 178 consecutive patients (156 men; mean age 74 years, range 49-89) were treated with aortic stent-grafts (86 Ancure, 55 AneuRx, and 37 Excluder). The follow-up protocol included serial CT and CDUS at 1 month and every 6 months thereafter. Sensitivity, specificity, positive predictive value, negative predictive value, and Kappa statistics (kappa) were calculated using CT as the gold standard; Bland-Altman analysis was used to determine the 95% limits of agreement. Paired and unpaired t tests and correlation coefficients were used to compare the methods. RESULTS: Follow-up ranged from 1 to 53 months (mean 16), during which 367 paired CT and CDUS studies were acquired. The mean diameter of the AAA sac after repair was 5.15 cm by CT versus 4.99 cm by CDUS (p=0.07); 93% of paired studies were somewhat similar (