Surgical trends of groin hernia repairs performed for recurrence in medicare patients.

BACKGROUND: The recurrence rate after groin hernia repair (GHR) has been estimated to be between 1-10% in adult patients. Neither national rates nor trends in recurrence over time have been reliably established for Medicare patients in the USA. MATERIALS: We evaluated patients undergoing GHR (inguinal = IHR; femoral = FHR) from 2011 to 2014 from the Medicare Provider Analysis and Review database. Patients were identified using ICD-9 diagnosis and ICD-9 and CPT procedure codes, stratified both by primary vs. recurrent hernia repair and by sex. One-tailed Cochran-Armitage tests evaluated trends over time and a generalized estimating equation model estimated factors associated with recurrent IHR or FHR. RESULTS: We identified 407,717 patients (87.0%, ≥ 65 years) who underwent an IHR and 11,578 (91.0%, ≥ 65 years) who underwent a FHR. The proportion of IHRs for recurrence decreased statistically from 14.3% in 2011 to 13.9% in 2014 (p < 0.01) in males and was increased, but not statistically so (7.0-7.4%) in females (p = 0.08). The proportion of FHRs for recurrence was decreased, but not statistically so (16.3-14.8%, p = 0.29) in males and increased in females (5.3-6.3%, p = 0.02). On multivariable analysis, males were more than twice as likely as females to undergo recurrent repair (IHR or FHR, both p < 0.01). CONCLUSIONS: Within the Medicare population, recurrence rates after groin hernia repairs were found to be higher than previously reported but have remained clinically stable over time. Establishing and reducing this rate is important for patient outcomes and expectations.

Proportion of femoral hernia repairs performed for recurrence in the United States.

PURPOSE: Recurrence rates after femoral hernia repair (FHR) have not been reliably established in the USA. We sought to determine this trend over time. METHODS: The proportion of primary and recurrent FHRs was determined for patients age ≥ 18 from: ACS-NSQIP (1/2005-12/2014), Premier (1/2010-09/2015), and institutional (1/2005-12/2014) data. Trends were analyzed using a one-tailed Cochran-Armitage test. RESULTS: In the NSQIP database, 6649 patients underwent a FHR. In females, the proportion of FHRs performed for recurrence decreased from 14.0% in 2005 to 6.2% in 2014, p = 0.02. In males, there was no change: 16.7-16.1% 2005-2014 (p = 0.18). The Premier database included 4495 FHRs and our institution 315 FHRs. There was no difference for either gender over time in either data source, all p > 0.05. CONCLUSIONS: The proportion of femoral hernia repairs performed for recurrence in the USA remained relatively constant in males in two large national databases between 2005 and 2015. In females, a decrease was seen in one of the large national databases.

Novel MYC-driven medulloblastoma models from multiple embryonic cerebellar cells.

Group3 medulloblastoma (MBG3) that predominantly occur in young children are usually associated with MYC amplification and/or overexpression, frequent metastasis and a dismal prognosis. Physiologically relevant MBG3 models are currently lacking, making inferences related to their cellular origin thus far limited. Using in utero electroporation, we here report that MBG3 mouse models can be developed in situ from different multipotent embryonic cerebellar progenitor cells via conditional expression of Myc and loss of Trp53 function in several Cre driver mouse lines. The Blbp-Cre driver that targets embryonic neural progenitors induced tumors exhibiting a large-cell/anaplastic histopathology adjacent to the fourth ventricle, recapitulating human MBG3. Enforced co-expression of luciferase together with Myc and a dominant-negative form of Trp53 revealed that GABAergic neuronal progenitors as well as cerebellar granule cells give rise to MBG3 with their distinct growth kinetics. Cross-species gene expression analysis revealed that these novel MBG3 models shared molecular characteristics with human MBG3, irrespective of their cellular origin. We here developed MBG3 mouse models in their physiological environment and we show that oncogenic insults drive this MB subgroup in different cerebellar lineages rather than in a specific cell of origin.

Contributions of mature granule cells to structural plasticity in temporal lobe epilepsy.

During the development of epilepsy in adult animals, newly generated granule cells integrate abnormally into the hippocampus. These new cells migrate to ectopic locations in the hilus, develop aberrant basal dendrites, contribute to mossy fiber sprouting, and exhibit changes in apical dendrite structure and dendritic spine number. Mature granule cells do not appear to exhibit migration defects, basal dendrites, and mossy fiber sprouting, but whether they exhibit apical dendrite abnormalities or spine changes is not known. To address these questions, we examined the apical dendritic structure of bromodeoxyuridine (Brdu)-birthdated, green fluorescent protein (GFP)-expressing granule cells born 2 months before pilocarpine-induced status epilepticus. In contrast to immature granule cells, exposing mature granule cells to status epilepticus did not significantly disrupt the branching structure of their apical dendrites. Mature granule cells did, however, exhibit significant reductions in spine density and spine number relative to age-matched cells from control animals. These data demonstrate that while mature granule cells are resistant to developing the gross structural abnormalities exhibited by younger granule cells, they show similar plastic rearrangement of their dendritic spines.

Sensitivity and specificity of eight CT signs in the preoperative diagnosis of internal mesenteric hernia following Roux-en-Y gastric bypass surgery.

AIM: To evaluate the sensitivity and specificity of eight previously reported computed tomography (CT) signs in diagnosing internal mesenteric hernia following Roux-en-Y gastric bypass surgery. MATERIALS AND METHODS: Preoperative CT images of nine patients with surgically proven internal mesenteric hernia as a complication of gastric bypass surgery and 10 matched control patients were reviewed in a blinded fashion by three radiologists. The presence of eight previously reported signs of internal mesenteric hernia was assessed: mesenteric swirl sign, hurricane eye sign, mushroom sign, small bowel obstruction, clustered small bowel loops, small bowel other than duodenum located behind the superior mesenteric artery (SMA), presence of the jejunal anastomosis to the right of the midline, and engorged mesenteric lymph nodes. The sensitivity and specificity were calculated for each sign, as well as inter-observer reliability in recognizing these signs. RESULTS: Mesenteric swirl was the most predictive sign of internal hernia (sensitivity 78-100%, specificity 80-90%). Other CT signs showed good specificity (70-100%), but sensitivities were low (0-44%). The presence of a small-bowel obstruction and engorged mesenteric nodes was found to be 100% specific in predicting the presence of an underlying hernia. There was substantial inter-observer agreement in detecting mesenteric swirl sign (kappa=0.48-0.79), but agreement was relatively poor for all other signs. CONCLUSION: Mesenteric swirl is an easily recognized CT sign, and is the best indicator of internal hernia following Roux-en-Y gastric bypass surgery. Other reported CT signs are diagnostically insensitive. The presence of small-bowel obstruction with engorged mesenteric nodes is highly specific in diagnosing internal mesenteric hernia.

CT of blunt trauma bowel and mesenteric injury: typical findings and pitfalls in diagnosis.

Detection of bowel and mesenteric injury can be challenging in patients after blunt abdominal trauma. Early diagnosis and treatment are critical to decrease patient morbidity and mortality. Computed tomography (CT) has become the primary modality for the imaging of these patients. Signs of bowel perforation such as free air and contrast material are virtually pathognomonic. Bowel-wall thickening, free fluid, and mesenteric infiltration may be seen with this type of injury and partial thickness injuries. The authors present and discuss the range of CT findings seen with bowel and mesenteric injuries. Examples of observation and interpretation errors are also provided to highlight pitfalls encountered in the evaluation of abdominopelvic CT scans in patients after blunt trauma.

Clozapine reverses the spatial working memory deficits induced by FG7142 in monkeys.

The atypical neuroleptic, clozapine, has been shown to have encouraging, but mixed, effects on prefrontal cortical (PFC) cognitive deficits in schizophrenia, a stress-exacerbated disorder involving dopamine (DA) dysregulation. The current study examined the effects of acute clozapine pretreatment on the spatial working memory deficits induced by the pharmacological stressor, FG7142, in monkeys. Previous research has shown that FG7142 impairs spatial working memory in rats and monkeys through excessive DA receptor stimulation in the PFC (Murphy et al. 1996). Lower clozapine doses (1-3 mg/kg p.o.) reversed the FG7142-induced spatial working memory deficits, whereas doses in the clinical range (e.g., 6 mg/kg, p.o.) did not improve cognitive function in most animals. Clozapine alone produced a dose-related impairment in delayed response performance. These results from nonhuman primates suggest that the clozapine doses commonly used to treat schizophrenia may not be optimal for treating the PFC cognitive deficits associated with this illness.

Mucinous ductal ectasia of the pancreas.

PURPOSE: Pancreatic mucinous ductal ectasia (MDE) is a recently described and poorly understood disorder, with few cases reported in the imaging literature. We undertook this study to describe the spectrum of CT and pancreatographic findings of MDE and to investigate the incidence of associated pancreatic malignancy. METHOD: The medical records, CT scans, and pancreatograms of 12 consecutive patients with pathologically proven MDE were retrospectively reviewed. There were nine men and three women, ranging in age from 37 to 72 years (mean 59 years). RESULTS: Focal lesions involved primarily the uncinate (two patients) and head (eight patients) by CT imaging. The entire gland was involved in two patients. CT findings were variable and included focal pancreatic enlargement, a low attenuation or cystic mass, low attenuation of the entire gland, or marked ductal dilatation. Pancreatographic findings were more consistent, showing ductal dilatation with or without intraluminal filling defects, obstruction, or displacement. In all cases, findings at endoscopy were felt to be characteristic, with ductal dilatation, filling defects, or abundant mucus seen upon cannulation of the pancreatic duct. Carcinoma-in-situ was present in six cases, cellular atypia without malignancy in two, and in three cases the lesions were histologically benign. One case demonstrated invasive adenocarcinoma. No finding or group of findings on CT or pancreatography permitted differentiation between benign and malignant lesions. CONCLUSION: MDE can present with a variety of appearances on CT, none of which is diagnostic. Pancreatography can be diagnostic if dilatation and intraluminal filling defects are seen. Carcinoma-in-situ, invasive adenocarcinoma, or cellular atypia is present in approximately 75%, but cannot be accurately diagnosed prospectively.

Evaluation of quantitative CT vertebral bone mineral density measurement and the Singh index in elderly females with hip fractures--a case control study.

This study aims to evaluate the ability of quantitative computed tomography (QCT) bone mineral density (BMD) measurement of vertebral bodies to predict risk of hip fracture. We also examine the predictive value of the radiographic Singh index and its relationship to the vertebral BMD. The vertebral BMD (using a QCT protocol) and radiographic Singh index were evaluated in 86 white females who had sustained a hip fracture after minor trauma. 86 age-matched female controls were also studied. All patients were post-menopausal, the age range was 52-95 years. BMD values were found to be low in both the study group and controls; there was no statistically significant difference between the groups. A low Singh index did not correlate with hip fracture, nor did it correlate with low vertebral BMD measurement. We conclude that vertebral BMD and radiographic Singh index are not reliable predictors of hip fracture in the elderly female.

Dopamine and spatial working memory in rats and monkeys: pharmacological reversal of stress-induced impairment.

The anxiogenic benzodiazepine inverse agonist FG7142 increases dopamine turnover in rodent prefrontal cortex but not in other dopamine terminal field areas. FG7142-induced increases in prefrontal cortical dopamine receptor stimulation impair prefrontal-dependent, but not nonprefrontal-dependent, cognitive tasks in rats and monkeys. The degree of impairment correlates with levels of prefrontal cortical dopamine turnover in rats and can be blocked in rats and monkeys with dopamine receptor antagonists, suggesting that increased dopamine turnover is directly related to the cognitive deficits. The current study examined nondopaminergic drug effects on FG7142-perturbed biochemistry and cognition. Both the noradrenergic alpha-2 agonist clonidine and the glycine/NMDA antagonist (+)HA966 prevented the FG7142-induced increase in dopamine turnover in rodent prefrontal cortex. Infusion of (+)HA966 into the ventral tegmental area (VTA) also blocked this increase in dopamine turnover, indicating that critical modulatory effects of (+)HA966 on FG7142-induced changes in dopamine turnover are occurring at the level of mesoprefrontal dopamine neuron cell bodies. Systemic (+)HA966 and clonidine, but not propranolol or D-cycloserine, prevented FG7142-associated spatial working memory deficits in rats and monkeys. These results support the idea of a critical range of dopamine turnover for optimal prefrontal cortical cognitive functioning, with excessive dopamine turnover leading to cognitive impairment. These studies also provide evidence for the regulation of prefrontal cortical dopamine turnover and cognition by multiple neurotransmitter systems and suggest that the VTA is an important regulatory site for these effects.

Gonadal vein recruitment in renal cell carcinoma: incidence, pathogenesis and clinical significance.

OBJECTIVE: Gonadal vein recruitment by collateral veins in patients with renal cell carcinoma is not routinely searched for during abdominal computed tomography. We performed a retrospective view to determine the incidence of gonadal vein recruitment for collateral venous drainage in patients with renal cell carcinoma and we discuss its potential importance. PATIENTS AND METHODS: Abdominal CT examinations were available for 58 of 95 patients with renal cell carcinoma identified during a 3-year-period. The presence of collateral veins and recruitment of the ipsilateral gonadal vein was recorded and correlated with the estimated blood loss at surgery. RESULTS: Eighteen of 58 tumours were small (less than 5 cm). Multiple (greater than three) collateral renal capsular veins were noted in 26 of 58 patients and few (less than three) were noted in 11. Recruitment of the gonadal vein (range 4-18 mm, mean 8 mm) was seen in 18 of 58 patients (31%) who all had multiple collaterals. Gonadal vein recruitment was only seen in patients with tumours greater than 5 cm. Mean estimated blood loss at surgery was significantly different (P < 0.01) in 18 of 58 patients (mean, 1078 ml) with gonadal vein recruitment compared to 40 of 58 patients (mean 304 ml) without distinct visualization of the gonadal vein and compared to 22 of 40 patients with large tumours (mean 368 ml). CONCLUSION: Gonadal vein recruitment signifies well-developed arteriovenous shunting and high flow collateral venous drainage pathways and may be used as an index of tumour vascularity. This finding may have clinical potential in triaging patients toward pre-operative renal embolization.

Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys.

The selective activation of the prefrontal cortical dopamine system by mild stress can be mimicked by anxiogenic beta-carbolines such as FG7142. To investigate the functional relevance of elevated levels of dopamine turnover in the prefrontal cortex, the current study examined the effects of FG7142 on the performance of spatial working memory tasks in the rat and monkey. FG7142 selectively increased prefrontal cortical dopamine turnover in rats and significantly impaired performance on spatial working memory tasks in both rats and monkeys. Spatial discrimination, a task with similar motor and motivational demands (rats), or delayed response performance following zero-second delays (monkeys) was unaffected by FG7142. Further, biochemical analysis in rats revealed a significant positive correlation between dopamine turnover in the prefrontal cortex and cognitive impairment on the delayed alternation task. The cognitive deficits in both rats and monkeys were prevented by pretreatment with the benzodiazepine receptor antagonist, RO15-1788, which blocked the increase in dopamine turnover and by the dopamine receptor antagonists, haloperidol, clozapine, and SCH23390. These findings indicate that excessive dopamine activity in the prefrontal cortex is detrimental to cognitive functions mediated by the prefrontal cortex.

Dopamine D1 receptor mechanisms in the cognitive performance of young adult and aged monkeys.

Dopamine (DA) D1 receptor compounds were examined in monkeys for effects on the working memory functions of the prefrontal cortex and on the fine motor abilities of the primary motor cortex. The D1 antagonist, SCH23390, the partial D1 agonist, SKF38393, and the full D1 agonist, dihydrexidine, were characterized in young control monkeys, and in aged monkeys with naturally occurring catecholamine depletion. In addition, SKF38393 was tested in young monkeys experimentally depleted of catecholamines with chronic reserpine treatment. Injections of SCH23390 significantly impaired the memory performance of young control monkeys, but did not impair aged monkeys with presumed catecholamine depletion. Conversely, the partial agonist, SKF38393, improved the depleted monkeys (aged or reserpine-treated) but did not improve young control animals. The full agonist, dihydrexidine, did improve memory performance in young control monkeys as well as in a subset of aged monkeys. Consistent with D1 receptor mechanisms, agonist-induced improvements were blocked by SCH23390. Drug effects on memory performance occurred independently of effects on fine motor performance. These results underscore the importance of DA D1 mechanisms in cognitive function, and provide functional evidence of DA system degeneration in aged monkeys. Finally, high doses of D1 agonists impaired memory performance in aged monkeys, suggesting that excessive D1 stimulation may be deleterious to cognitive function.

Optic nerve coloboma (morning glory syndrome): CT findings.

This study demonstrates computed tomographic (CT) findings of morning glory syndrome. CT examination of the orbits was performed in three patients. Images of 2-mm-thick sections were acquired at 2-mm intervals without use of contrast material. Excellent demonstration of coloboma was achieved in each case. Because both magnetic resonance imaging and ultrasonography have limitations in imaging of coloboma, CT is the imaging method of choice in diagnosis of this disorder.

Assessing the contribution from lead in mining wastes to blood lead.

Lead has been recognized for years as an environmental pollutant of concern for young children. Nonetheless, many children in the United States still experience high body burdens of lead. Reducing exposure to lead must include an assessment of all potential sources of lead and a definition of routes of exposure. In this paper, the relationships between soil lead and blood lead concentrations in residents in communities with high soil lead concentrations resulting from past mining and ore processing (milling) activities are compared to those derived from studies in urban communities or communities with operating smelters. The impact of mine waste-derived lead in soil (usually in the form of lead sulfide) on blood lead is less than that for lead in soil derived from smelter, vehicle, or paint sources. Possible reasons for a reduced impact of lead sulfide on blood lead in children in mining communities include the following: lead from mining sources contributes less to lead in the immediate environment of children than lead from other sources; mine wastes typically are of larger particle size, which decreases the bioavailability of lead in the gastrointestinal tract; and lead sulfide is absorbed less in the gastrointestinal tract compared to other lead species. A reduced impact of mine waste-derived lead on blood lead may be important from a regulatory point of view. Expensive cleanup actions for lead-contaminated soils in mining communities based on acceptable soil lead concentrations derived from smelter or urban communities may be questionable in terms of reducing blood lead in children.

Health risk assessment for arsenic contaminated soil.

This paper describes risk assessment methods for two chronic exposure pathways involving arsenic contaminated soil, namely inhalation of fugitive dust emissions over a lifetime, and inadvertent soil/house dust ingestion. The endpoint in the first case is assumed to be lung cancer and in the second case skin cancer. In order to estimate exposures, inhalation rates and soil/dust ingestion rates are estimated for different age groups; indoor/outdoor time budgets for different age groups are developed; and indoor surface dust and air arsenic concentrations are estimated based on outdoor concentration measurements. Differences observed in indoor/outdoor ratios and arsenic containing dust particle size among different types of communities are noted, as well as possible relationship of particle size to bioavailability. Calculations of risk are presented using cancer potency factors developed by the U.S. Environmental Protection Agency, and uncertainties in these toxicity estimates are described based on: (1) evidence that arsenic may be neither a cancer initiator nor promotor, but may act instead as a late stage carcinogen and (2) evidence that the arsenic dose-response relationship for ingestion may be nonlinear at low doses due to increasing methylation of inorganic arsenic. The first of these considerations influences the relative importance ascribed to arsenic doses in different age groups. The latter consideration indicates that the risk estimates described here are probably very conservative.