Proton Pump Inhibitor Use After Hiatal Hernia Repair: Inhibitor of Recurrent Symptoms and Potential Revisional Surgery.

BACKGROUND: Hiatal hernia recurrence after hiatal hernia repair (HHR) is often underdiagnosed and underreported but may present with recurrent gastroesophageal reflux disease (GERD) symptoms. Because of their availability, proton pump inhibitor (PPI) use is common and may mask patients who would benefit from revisional surgery, which has been shown to improve symptoms and quality of life. METHODS: A retrospective analysis was performed to evaluate recurrence patterns of patients who underwent HHR, specifically for the indication of GERD, from 2007 to 2015 at a single Veterans Administration Medical Center. Clinicopathologic parameters were reviewed for association with hiatal hernia recurrence, including postoperative PPI use. RESULTS: Sixty-four patients were identified with a median follow-up time of 57.8 mo. Thirty-eight patients developed an anatomic recurrence, which did not demonstrate any associated factors on univariate analysis. Seventy percent of patients remained or were restarted on PPI after their initial surgery. For patients with a documented recurrence, the median time to start a PPI was 224 d, but the time to identify recurrence on imaging or endoscopy was 712.5 d. Eleven (39.3%) patients had a reintervention for anatomic recurrence, of which all had developed recurrent symptoms of GERD. CONCLUSIONS: Most patients who developed recurrent hiatal hernia were restarted on PPI without workup for their symptoms. The time of initiation of PPI was much earlier than the time of identification of a recurrent hiatal hernia. The use of PPIs in patients whom have undergone HHR may delay proper workup to identify recurrent hiatal hernia amenable to surgical repair and should be reserved until patients develop recurrent symptoms and have at least begun a diagnostic workup to rule out an anatomic cause for the recurrent symptoms.

Systemic inflammation as a predictor of clinical outcomes after lower extremity angioplasty/stenting.

OBJECTIVE: The activation state of the systemic inflammatory milieu has been proposed as a critical regulator of vascular repair after injury. We evaluated the early inflammatory response after endovascular intervention for symptomatic peripheral arterial disease to determine its association with clinical success or failure. METHODS: Blood samples were obtained from 14 patients undergoing lower extremity angioplasty/stenting and analyzed using high-throughput gene arrays, multiplex serum protein analyses, and flow cytometry. RESULTS: Time-dependent plasma protein and monocyte phenotype analyses demonstrated endovascular revascularization had a modest influence on the overall activation state of the systemic inflammatory system, with baseline variability exceeding the perturbations induced by the intervention. In contrast, specific time-dependent changes in the monocyte genome are evident in the initial 28 days, predominately in those genes associated with leukocyte extravasation. Investigating the relationship between inflammation and the 1-year success or failure of the intervention showed no single plasma protein was correlated with outcome, but a more comprehensive cluster analysis revealed a clear pattern of protein expression that was closely related to the clinical phenotype. Corresponding examination of the monocyte genome identified a gene subset at 1 day postprocedure that was predictive of clinical outcome, with most of these genes active in cell-cycle signaling. CONCLUSIONS: Although the global influence of angioplasty/stenting on systemic inflammation was modest, circulating cytokine and monocyte genome analyses support a pattern of early inflammation that is associated with ultimate intervention success vs failure. Molecular profiles incorporating genes involved in monocyte cell-cycle progression and homing, or proinflammatory cytokines, or both, offer the most promise for the development of class prediction tools for clinical application.

Hypertension overrides the protective effect of female hormones on the development of aortic aneurysm secondary to Alk5 deficiency via ERK activation.

The prevalence of aortic aneurysm is five times higher in men than women among the general population. Similar sexual dimorphism also exists in syndromic aortic aneurysms triggered by TGF-ß signaling disorders. To understand the responsible mechanisms, we developed an animal model where inducible deletion of the type I TGF-ß receptor, Alk5, specifically in smooth muscle cells (Alk5iko) causes spontaneous aortic aneurysm formation. This model recapitulated an extreme scenario of the dimorphism in aortic aneurysm development between genders. In a comparative experiment, all Alk5iko males (n=42) developed aortic aneurysms and 26% of them died prematurely from aortic rupture. In contrast, the Alk5iko females (n=14) presented only a subclinical phenotype characteristic of scarcely scattered elastin breaks. Removal of male hormones via orchiectomy (n=7) resulted in only minimal influence on aortic pathology. However, reduction of female hormones via ovariectomy (n=15) increased the phenotypic penetrance from zero to 53%. Finally, an elevation of systolic blood pressure by 30 points unmasked the subclinical phenotype of Alk5iko females (n=17) to 59%. This exaggerated phenotypic penetrance was coupled with an early intensification of ERK signaling, a molecular signature that correlated to 100% phenotypic penetrance in normotensive Alk5iko males. In conclusion, aortic aneurysm induced by Alk5iko exhibits dimorphic incidence between genders with females less susceptible to aortic disease. This sexual dimorphism is partially the result from the protective effects of female hormones. Hypertension, a known risk factor for aortic aneurysm, is able to break the female sex protective effects through mechanisms associated with enhanced ERK activity.

The correlation between computed tomography and duplex evaluation of autogenous vein bypass grafts and their relationship to failure.

OBJECTIVE: Duplex ultrasound (DUS) imaging for vein bypass graft (VBG) surveillance is confounded by technical and physiologic factors that reduce the sensitivity for detecting impending graft failure. In contrast, three-dimensional computed tomography angiography (CTA) offers high-fidelity anatomic characterization of VBGs, but its utility in detecting at risk grafts is unknown. The current study analyzed the correlation between DUS and CTA for detection of vein graft stenosis and evaluated the relationship of the observed abnormalities to VBG failure. METHODS: Consecutive lower extremity VBG patients underwent surveillance with concurrent DUS imaging and CTA at 1 week and at 1, 6, and 12 months postoperatively. A standardized algorithm was used for CT reconstruction and extraction of the lumen geometries at 1-mm intervals. At each interval, CT-derived cross-sectional areas were coregistered and correlated to DUS peak systolic velocities (PSVs) within six predesignated anatomic zones and then analyzed for outcome association. Vein graft failure was defined as pathologic change within a given anatomic zone resulting in thrombosis, amputation, or reintervention within the 6-month period after the observed time point. RESULTS: The study recruited 54 patients, and 10 (18%) experienced failure ≤18 months of implantation. The expected inverse relationship between cross-sectional area and PSV was only weakly correlated (Spearman rank coefficient = -0.19). Moderate elevations in the PSV ratio (PSVr; 2-3.5) were frequently transient, with 14 of 18 grafts (78%) demonstrating ratio reduction on subsequent imaging. A PSVr ≥3.5 was associated with a 67% failure rate. CT stenosis <50% was highly correlated with success (0 failures); however, high-grade (>80%) CT stenosis was more likely to succeed than to fail (25%). Significant discordance between CT and DUS was found in 18 patients. Although 14 of these patients had CT stenosis >70% with a PSVr <3.5, subsequent failure occurred in only two. Conversely, graft failure occurred in three of four patients with CT stenosis <70% but PSVr >3.5. Focused analysis of these patients using computational fluid dynamic modeling demonstrated that vein side branches, local tortuosity, regional diameter variations, and venovenostomies were the drivers of these discrepancies. CONCLUSIONS: This analysis demonstrated that a PSVr ≥3.5 is strongly correlated with VBG failure, whereas the natural history of moderately elevated PSVr (2-3.5) is largely clinically benign. Although minimum stenosis on the CT scan was highly predictive of success, high-grade CT stenosis was infrequently associated with failure. The interaction of anatomic features with the local flow dynamics was identified as the primary confounder for a direct correlation between CT and DUS imaging.

Outcomes after redo aortobifemoral bypass for aortoiliac occlusive disease.

OBJECTIVE: Patients presenting with occluded aortobifemoral (ABF) bypass grafts are managed with a variety of techniques. Redo ABF (rABF) bypass procedures are infrequently performed because of concerns about procedural complexity and morbidity. The purpose of this analysis was to compare midterm results of rABF bypass with those of primary ABF (pABF) bypass for aortoiliac occlusive disease to determine if there are significant differences in outcomes. METHODS: A retrospective review was performed of all patients undergoing ABF bypass for occlusive disease between January 2002 and March 2012. A total of 19 patients underwent rABF bypass and 194 received pABF bypass during that period. Data for an indication- and comorbidity-matched case-control cohort of 19 elective pABF bypass patients were collected for comparison to the rABF bypass group. Primary end points included rate of major complications as well as 30-day and all-cause mortality. Secondary end points were amputation-free survival and freedom from major adverse limb events. RESULTS: The rABF bypass patients more frequently underwent prior extra-anatomic or lower extremity bypass operations compared with pABF bypass patients (P = .02); however, no difference was found in the incidence of prior failed endovascular iliac intervention (P = .4). By design, indications for the rABF and pABF bypass groups were the same (claudication, n = 6/6 [31.6%]; P = 1; critical limb ischemia, n = 13/13 [78.4%]; P = 1). Aortic access was more frequently by retroperitoneal exposure in the rABF bypass group (n = 13 vs n = 1; P < .0001), and a significantly higher proportion of the rABF bypass patients required concomitant infrainguinal bypass or intraprocedural adjuncts such as profundaplasty (n = 14 vs n = 5; P = .01). The rABF bypass patients experienced greater blood loss (1097 ± 983 mL vs 580 ± 457 mL; P = .02), received more intraoperative fluids (3400 ± 1422 mL vs 2279 ± 993 mL; P = .01), and had longer overall procedure times (408 ± 102 minutes vs 270 ± 48 minutes; P < .0001). Length of stay (days ± standard deviation) was similar (pABF bypass, 11.2 ± 10.4; rABF bypass, 9.1 ± 4.5; P = .7), and no 30-day or in-hospital deaths occurred in either group. Similar rates of major complications occurred in the two groups (pABF bypass, n = 6 [31.6%]; rABF bypass, n = 4 [21.1%]; observed difference, 9.5%; 95% confidence interval, -17.6% to 36.7%; P = .7). Two-year freedom from major adverse limb events (±standard error mean) was 82% ± 9% vs 78% ± 10% for pABF and rABF bypass patients (log-rank, P = .6). Two-year amputation-free survival was 90 ± 9% vs 89 ± 8% between pABF and rABF bypass patients (P = .5). Two-year survival was 91% ± 9% and 90% ± 9% for pABF and rABF bypass patients (P = .8). CONCLUSIONS: Patients undergoing rABF bypass have higher procedural complexity compared with pABF bypass as evidenced by greater operative time, blood loss, and need for adjunctive procedures. However, similar perioperative morbidity, mortality, and midterm survival occurred in comparison to pABF bypass patients. These results support a role for rABF bypass in selected patients.

Failure to follow evidence-based best practice guidelines in the treatment of severe acute pancreatitis.

OBJECTIVES: Evidence-based guidelines for the treatment of severe acute pancreatitis have been established. This study was conducted to investigate the hypothesis that deviation from guidelines occurs frequently. METHODS: With institutional review board approval, the outside medical records of patients with severe pancreatitis who were transferred to the study institution during the period from July 2005 to May 2012 were reviewed. Severe pancreatitis was defined using the Atlanta Classification criteria. Records were reviewed with respect to published guidelines defining the appropriate use of imaging, antibiotics and nutritional support. RESULTS: A total of 538 patients with acute pancreatitis were identified. Of 67 patients with severe acute pancreatitis, 44 (66%) were male. The mean age of the patients was 55 years. Forty-five of 61 (74%) patients for whom relevant data were available were imaged upon admission, but only 15 (31%) patients were imaged appropriately by computerized tomography with i.v. contrast to assess the presence of necrosis or other complications. In patients for whom relevant data were available, prophylactic antibiotics were initiated in the absence of culture data or a specific infectious target in 26 (53%) patients. Total parenteral nutrition (TPN) was administered to 38 (60%) of 63 patients for whom relevant data were available; only 10 (17%) patients received enteric feeding. No nutritional support was provided to 15 (23%) patients. CONCLUSIONS: Adherence to best practice guidelines in the treatment of severe pancreatitis is poor. The consistent application of current knowledge might improve outcomes in these patients.

Pediatric infiltration injury and compartment syndrome.

Pediatric intravenous infiltration injuries are relatively common, and pediatric compartment syndrome is relatively rare. We have reviewed the causes, means of diagnosis, and treatment of compartment syndrome. Neonatal compartment syndrome is distinguished from intravenous infiltration injuries in the neonate by its associated skin lesions and requires prompt decompression.

Preexisting smooth muscle cells contribute to neointimal cell repopulation at an incidence varying widely among individual lesions.

BACKGROUND: With the diverse origin of neointimal cells, previous studies have documented differences of neointimal cell lineage composition across models, but the animal-to-animal difference has not attracted much attention, although the cellular heterogeneity may impact neointimal growth and its response to therapeutic interventions. METHODS: R26R(+);Myh11-CreER(+), and R26R(+);Scl-CreER(+) mice were used to attach LacZ tags to the preexisting smooth muscle cells (SMCs) and endothelial cells (ECs), respectively. Neointimal lesions were created via complete ligation of the common carotid artery (CCA) and transluminal injury to the femoral artery (FA). RESULTS: LacZ-tagged SMCs were physically relocated from media to neointima and changed to a dedifferentiated phenotype in both CCA and FA lesions. The content of SMCs in the neointimal tissue, however, varied widely among specimens, ranging from 5 to 70% and 0 to 85%, with an average at low levels of 27% and 29% in CCA (n = 15) and FA (n = 15) lesions, respectively. Bone marrow cells, although able to home to the injured arteries, did not differentiate fully into SMCs after either type of injury. Preexisting ECs were located in the subendothelial region and produced mesenchymal marker α-actin, indicating endothelial-mesenchymal transition (EndoMT); however, EC-derived cells represented only 7% and 3% of the total neointimal cell pool of CCA (n = 7) and FA (n = 7) lesions, respectively. ECs located on the luminal surface exhibited little evidence of EndoMT. CONCLUSION: Neointimal hyperplasia proceeds with a wide range of variation in its cellular composition between individual lesions. Relative to ECs, SMCs are major contributors to the lesion-to-lesion heterogeneity in neointimal cell lineage composition.

Smooth muscle cell-specific Tgfbr1 deficiency promotes aortic aneurysm formation by stimulating multiple signaling events.

Transforming growth factor (TGF)-ß signaling disorder has emerged as a common molecular signature for aortic aneurysm development. The timing of postnatal maturation plays a key role in dictating the biological outcome of TGF-ß signaling disorders in the aortic wall. In this study, we investigated the impact of deficiency of TGFß receptors on the structural homeostasis of mature aortas. We used an inducible Cre-loxP system driven by a Myh11 promoter to delete Tgfbr1, Tgfbr2, or both in smooth muscle cells (SMCs) of adult mice. TGFBR1 deficiency resulted in rapid and severe aneurysmal degeneration, with 100% penetrance of ascending thoracic aortas, whereas TGFBR2 deletion only caused mild aortic pathology with low (26%) lesion prevalence. Removal of TGFBR2 attenuated the aortic pathology caused by TGFBR1 deletion and correlated with a reduction of early ERK phosphorylation. In addition, the production of angiotensin (Ang)-converting enzyme was upregulated in TGFBR1 deficient aortas at the early stage of aneurysmal degeneration. Inhibition of ERK phosphorylation or blockade of AngII type I receptor AT1R prevented aneurysmal degeneration of TGFBR1 deficient aortas. In conclusion, loss of SMC-Tgfbr1 triggers multiple deleterious pathways, including abnormal TGFBR2, ERK, and AngII/AT1R signals that disrupt aortic wall homeostasis to cause aortic aneurysm formation.