Investigation of Brain Iron in Niemann-Pick Type C: A 7T Quantitative Susceptibility Mapping Study.

BACKGROUND AND PURPOSE: While brain iron dysregulation has been observed in several neurodegenerative disorders, its association with the progressive neurodegeneration in Niemann-Pick type C is unknown. Systemic iron abnormalities have been reported in patients with Niemann-Pick type C and in animal models of Niemann-Pick type C. In this study, we examined brain iron using quantitative susceptibility mapping MR imaging in individuals with Niemann-Pick type C compared with healthy controls. MATERIALS AND METHODS: A cohort of 10 patients with adolescent- and adult-onset Niemann-Pick type C and 14 age- and sex-matched healthy controls underwent 7T brain MR imaging with T1 and quantitative susceptibility mapping acquisitions. A probing whole-brain voxelwise comparison of quantitative susceptibility mapping between groups was conducted. Mean quantitative susceptibility mapping in the ROIs (thalamus, hippocampus, putamen, caudate nucleus, and globus pallidus) was further compared. The correlations between regional volume, quantitative susceptibility mapping values, and clinical features, which included disease severity on the Iturriaga scale, cognitive function, and the Social and Occupational Functioning Assessment Scale, were explored as secondary analyses. RESULTS: We observed lower volume in the thalamus and voxel clusters of higher quantitative susceptibility mapping in the pulvinar nuclei bilaterally in patients with Niemann-Pick type C compared with the control group. In patients with Niemann-Pick type C, higher quantitative susceptibility mapping in the pulvinar nucleus clusters correlated with lower volume of the thalamus on both sides. Moreover, higher quantitative susceptibility mapping in the right pulvinar cluster was associated with greater disease severity. CONCLUSIONS: Our findings suggest iron deposition in the pulvinar nucleus in Niemann-Pick type C disease, which is associated with thalamic atrophy and disease severity. This preliminary evidence supports the link between iron and neurodegeneration in Niemann-Pick type C, in line with existing literature on other neurodegenerative disorders.

Cardiac Sympathetic Denervation for the Management of Ventricular Arrhythmias.

BACKGROUND: The autonomic nervous system contributes to the pathogenesis of ventricular arrhythmias (VA). Though anti-arrhythmic drug therapy and catheter ablation are the mainstay of management of VAs, success may be limited in patients with more refractory arrhythmias. Sympathetic modulation is increasingly recognized as a valuable adjunct tool for managing VAs in patients with structural heart disease and inherited arrhythmias. RESULTS: In this review, we explore the role of the sympathetic nervous system and rationale for cardiac sympathetic denervation (CSD) in VAs and provide a disease-focused review of the utility of CSD for patients both with and without structural heart disease. CONCLUSIONS: We conclude that CSD is a reasonable therapeutic option for patients with VA, both with and without structural heart disease. Though not curative, many studies have demonstrated a significant reduction in the burden of VAs for the majority of patients undergoing the procedure. However, in patients with unilateral CSD and subsequent VA recurrence, complete bilateral CSD may provide long-lasting reprieve from VA.

50 Patients with Malignant Mesothelioma of Both the Pleura and Peritoneum: A Single-Institution Experience.

BACKGROUND: The most common sites of malignant mesothelioma are the pleura and peritoneum, but little is known about the incidence, prognosis, or treatment of patients with disease in both cavities. Previous series suggest that multimodality treatment improves overall survival for pleural or peritoneal disease, but studies typically exclude patients with disease in both cavities. Despite limitations, this investigation is the only study to broadly examine outcomes for patients with malignant mesothelioma in both the pleural and peritoneal cavities. METHODS: This study retrospectively examined 50 patients with both pleural and peritoneal mesothelioma treated with the intent to prolong survival. The primary end point was overall survival from the initial operative intervention. RESULTS: The median overall survival was 33.9 months from the initial intervention. Female gender and intraperitoneal dwell chemotherapy were independent predictors of overall survival. Within 1 year after the initial diagnosis, second-cavity disease was diagnosed in 52% of the patients. The median time to the second-cavity diagnosis for those with a diagnosis 1 year after the initial diagnosis was 30 months. CONCLUSIONS: Well-selected patients with both pleural and peritoneal mesothelioma have a survival benefit over palliative treatment that is comparable with that seen in single-cavity disease. The presence of disease in both cavities is not a contraindication to multimodality treatment aimed at prolonging survival, whether the disease is diagnosed synchronously or metachronously. Patients with an initial diagnosis of single cavity disease are at the highest risk for identification of second-cavity disease within the first year after diagnosis.

Lifespan Trajectories of White Matter Changes in Rhesus Monkeys.

Progress in neurodevelopmental brain research has been achieved through the use of animal models. Such models not only help understanding biological changes that govern brain development, maturation and aging, but are also essential for identifying possible mechanisms of neurodevelopmental and age-related chronic disorders, and to evaluate possible interventions with potential relevance to human disease. Genetic relationship of rhesus monkeys to humans makes those animals a great candidate for such models. With the typical lifespan of 25 years, they undergo cognitive maturation and aging that is similar to this observed in humans. Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking white matter brain maturation and aging. While lifespan trajectories of white matter changes have been mapped in humans, such knowledge is not available for nonhuman primates. Here, we analyze and model lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys. We report quantitative parameters (including slopes and peaks) of lifespan trajectories for 8 individual white matter tracts. We show different trajectories for cellular and extracellular microstructural imaging components that are associated with white matter maturation and aging, and discuss similarities and differences between those in humans and rhesus monkeys, the importance of our findings, and future directions for the field. Significance Statement: Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking brain maturation and aging. While lifespan trajectories of structural white matter changes have been mapped in humans, such knowledge is not available for rhesus monkeys. We present here results of the analysis and modeling of the lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys (age 4-27). We report and anatomically map lifespan changes related to cellular and extracellular microstructural components that are associated with white matter maturation and aging.

Novel Treatment for Anastomotic Leak After Ivor-Lewis Esophagectomy.

Intrathoracic anastomotic leaks after esophagogastrostomy occur frequently, often resulting in prolonged hospitalization and delays in advancing oral nutrition and hydration. Management of anastomotic esophageal leaks vary based on time of occurrence to time of intervention, condition of the patient, and location. Conservative approaches such as endovascular clips and endovascular stents have gained momentum in addressing esophageal leaks and fistulas, replacing the original paradigm of surgical approach as initial management. More recently, the use of intraluminal and intracavitary endoscopic vacuum-assisted therapy has been used to treat esophageal leaks successfully. We present a novel treatment method for anastomotic leaks using a modified percutaneous endoscopic gastrostomy tube.

Greater extracellular free-water in first-episode psychosis predicts better neurocognitive functioning.

Free Water Imaging is a novel diffusion magnetic resonance (MR) imaging method that is able to separate changes affecting the extracellular space from those that reflect changes in neuronal cells and processes. A previous Free Water Imaging study in schizophrenia identified significantly greater extracellular water volume in the early stages of the disorder; however, its clinical and functional sequelae have not yet been investigated. Here, we applied Free Water Imaging to a larger cohort of 63 first-episode patients with psychosis and 70 healthy matched controls to better understand the functional significance of greater extracellular water. We used diffusion MR imaging data and the Tract-Based Spatial Statistics analytic pipeline to first analyze fractional anisotropy (FA), the most commonly employed metric for assessing white matter. This comparison was then followed by Free Water Imaging analysis, where two parameters, the fractional volume of extracellular free-water (FW) and cellular tissue FA (FA-t), were estimated and compared across the entire white matter skeleton between groups, and correlated with cognitive measures at baseline and following 12 weeks of antipsychotic treatment. Our results indicated lower FA across the whole brain in patients compared with healthy controls that overlap with significant increases in FW, with only limited decreases in FA-t. In addition, higher FW correlated with better neurocognitive functioning following 12 weeks of antipsychotic treatment. We believe this is the first study to suggest that an extracellular water increase during the first-episode of psychosis, which may be indicative of an acute neuroinflammatory process, and/or cerebral edema may predict better functional outcome.

Less Common Side Effects of Sympathetic Surgery.

Because of video-assisted thoracic technology and increased patient awareness of treatment options for palmar hyperhidrosis, endoscopic thoracic sympathectomy (ETS) has become a well-accepted treatment for this disorder. Video assistance affords excellent visualization of thoracic anatomy, which allows the procedure to be done quickly with few complications. However, despite the ease of performing ETS, complications can occur unless thoracic anatomy and physiology are well-understood. Awareness of possible intraoperative and postoperative complications is essential if this procedure is gong to be performed safely.

Social anxiety and functional impairment in patients seeking surgical evaluation for hyperhidrosis.

Primary hyperhidrosis is characterized by excessive sweating and often accompanied by social avoidance. Social anxiety disorder (SAD) is characterized by fear and avoidance of social situations, often partly related to fears of showing signs of excessive autonomic nervous system activation, such as sweating. To clarify the relationship of hyperhidrosis and SAD, this study assessed severity of sweating, overall social anxiety and social anxiety due to sweating, and disability in 2 groups: patients seeking surgical treatment for hyperhidrosis (n = 40) and patients seeking treatment for SAD (n = 64). Hyperhidrosis and SAD patients overlapped in severity of overall social anxiety and social anxiety related to sweating. Hyperhidrosis patients reported elevated levels of social anxiety, with mean severity near the threshold for the generalized subtype of SAD, but significantly lower social anxiety than in the SAD patients. Significantly more hyperhidrosis patients than SAD patients attributed most of their social anxiety to sweating (76% vs 20%). Among hyperhidrosis patients, the pattern of correlations of sweating, social anxiety, and disability was consistent with a model of social anxiety as a mediator of sweating-related disability. The overlap of symptoms in patients presenting for treatment of SAD or hyperhidrosis suggests that both social anxiety and sweating should be assessed in these patients and considered as potential targets of treatment.

The use of a tailored surgical technique for minimally invasive esophagectomy.

OBJECTIVE: Uncertainty exists among surgeons as to whether minimally invasive esophagectomy (MIE) is a comparable operation to open esophagectomy (OE). The surgical technique and oncologic dissection should not be degraded when using a minimally invasive approach. METHODS: We reviewed a single hospital's experience with both OE and MIE. From 2000 to 2010, 257 patients underwent esophagectomy by 1 of 3 surgical techniques: transhiatal, Ivor Lewis, or 3-hole. RESULTS: Of the 257 patients (median age, 67 years; range, 58-74), 92 underwent MIE. Both groups were comparable in terms of gender, age, comorbidities, surgical technique, and induction chemotherapy and radiotherapy. The overall median follow-up was 29.5 months (range, 9.9-61.5). The MIE group had a significantly shorter operative time (MIE vs OE, 330 vs 365 minutes, P = .04), length of stay (MIE vs OE, 9 vs 12 days, P < .01), intensive care unit admission rate (MIE vs OE, 55% vs 81%, P < .01), intensive care unit length of stay (MIE vs OE, 1 vs 2 days, P < .01), and estimated blood loss (MIE vs OE, 100 vs 400 mL, P < .01). More lymph nodes were harvested in the MIE group than in the OE group (17 vs 11 nodes, P < .01). There were insignificant differences in 30-day mortality (MIE vs OE, 2.2% vs 3.0%; P = .93) and overall survival (P = .19), as well as in the rates of all complications, except pneumonia (MIE vs OE, 2% vs 13%; P = .01). CONCLUSIONS: A thoracic surgeon can safely tailor the MIE to a patient's anatomy and oncologic demands while maintaining equivalent survival.

Motivational counselling for physical activity in patients with coronary artery disease not participating in cardiac rehabilitation.

BACKGROUND: Many patients with coronary artery disease (CAD) fail to attend cardiac rehabilitation following acute coronary events because they lack motivation to exercise. Theory-based approaches to promote physical activity among non-participants in cardiac rehabilitation are required. DESIGN: A randomized trial comparing physical activity levels at baseline, 6, and 12 months between a motivational counselling (MC) intervention group and a usual care (UC) control group. METHOD: One hundred and forty-one participants hospitalized with acute coronary syndromes not planning to attend cardiac rehabilitation were recruited at a single centre and randomized to either MC (n = 69) or UC (n = 72). The MC intervention, designed from an ecological perspective, included one face-to-face contact and eight telephone contacts with a trained physiotherapist over a 52-week period. The UC group received written information about starting a walking programme and brief physical activity advice from their attending cardiologist. Physical activity was measured by: 7-day physical activity recall interview; self-report questionnaire; and pedometer at baseline, 6, and 12 months after randomization. RESULTS: Latent growth curve analyses, which combined all three outcome measures into a single latent construct, showed that physical activity increased more over time in the MC versus the UC group (µ(add) = 0.69, p < 0.05). CONCLUSION: Patients with CAD not participating in cardiac rehabilitation receiving a theory-based motivational counselling intervention were more physically active at follow-up than those receiving usual care. This intervention may extend the reach of cardiac rehabilitation by increasing physical activity in those disinclined to participate in structured programmes.

The surgical management of stage I and stage II lung cancer.

There have been recent advances in the treatment of non-small cell lung cancer (NSCLC). Surgical resection remains the cornerstone in the treatment of patients with stages I and II NSCLC. Anatomic lobectomy combined with hilar and mediastinal lymphadenectomy constitutes the oncologic basis of surgical resection. The surgical data favor video-assisted thoracic surgery (VATS) lobectomy over open lobectomy and have established VATS lobectomy as a gold standard in the surgical resection of early-stage NSCLC. However, the role of sublobar pulmonary resection, either anatomic segmentectomy or nonanatomic wedge resection, in patients with subcentimeter nodules may become important.

Lung volume reduction surgery using the NETT selection criteria.

BACKGROUND: The National Emphysema Treatment Trial (NETT) proved that lung volume reduction surgery (LVRS) was safe and effective in patients with certain clinical characteristics and using defined inclusion-exclusion criteria. Based on the selection criteria developed in that trial, we performed bilateral LVRS on 49 patients during the period of February 2004 until May 2009. METHODS: Forty-nine patients underwent lung volume reduction by either median sternotomy (10) or video-assisted thoracoscopic surgery (39) selected according to NETT described parameters. Preoperative characteristics were the following: mean (±SD) age 62.5±6.6 years, preoperative FEV1 (forced expiratory volume in the first second of expiration) 691 cc (±159), % of predicted FEV1 25.3 (±6.2), preoperative Dlco (diffusing capacity of lung for carbon monoxide) 7.6 (±2.7), and % of predicted DLCO 27% (±7.3). All patients had upper lobe predominant disease and either low exercise capacity (n=23) or high exercise capacity (n=26) as defined by the NETT. RESULTS: There was no operative or 90-day mortality. Median length of stay was 8 days (interquartile range=6 to 10). Two patients required reintubation and tracheostomy but were decannulated prior to discharge. The BODE index (body mass index, airflow obstruction, dyspnea, and exercise capacity), a multidimensional predictor of survival in chronic obstructive pulmonary disease, improved -2.3 (±1.5, p<0.0001) (missing data: 5 of 42, 11.9%) and the FEV1 improved 286 cc (±221, p<0.0001), both 1 year after surgery. Probability of survival was 0.98 (95% CI [confidence interval]=0.94 to 1) at 1 year, and 0.95 (95% CI=0.88 to 1) at 3 years. CONCLUSIONS: Surgical lung volume reduction for emphysema can be performed in patients using selection criteria developed by the NETT with very low surgical risk and excellent midterm results. Surgical LVRS is the standard against which other nonsurgical treatments for advanced emphysema should be judged.

Intrathoracic linear stapled esophagogastric anastomosis: an alternative to the end to end anastomosis.

Minimally invasive esophagectomy (MIE) is gradually gaining acceptance as an oncological sound procedure. The advantages of MIE arise from avoidance of a thoracotomy or laparotomy, resulting in decreased pulmonary morbidity and generally a faster recovery, yet not compromising the surgical benefit of esophagectomy in patients with cancer of the esophagus. No single technique of esophagectomy has proven itself superior to another from either an oncologic or survival perspective. The MIE is a technically demanding procedure that requires advanced endoscopic skills, especially when performing an intrathoracic anastomosis. We present an alternative intrathoracic anastomotic technique to the commonly performed EEA anastomosis.

Analysis of clamping versus cutting of T3 sympathetic nerve for severe palmar hyperhidrosis.

OBJECTIVES: Endoscopic thoracic sympathectomy can predictably eliminate the disabling symptoms of palmar hyperhidrosis. Debate has ensued over competing techniques, in particular, cutting versus clamping of the sympathetic chain. We subjectively assessed the sweat severity in different areas of the body and evaluated changes in the quality of life in patients undergoing either the cutting or clamping technique. METHODS: Patients examined between June 2003 and March 2007 were asked to quantify the severity of their symptoms before and after endoscopic thoracic sympathectomy. The interviews were conducted approximately 1 year after the procedure. Only the patients undergoing sympathectomy at the T3 level for a chief complaint of palmar hyperhidrosis were included in the analysis (n = 152). In 45% of these patients, clamping of the sympathetic chain was performed, and the remaining 55% had the chain cut. RESULTS: After surgery, no patients had continued excessive sweating of the hands. Of all the patients, 95% were satisfied with the results after the cutting procedure and 97% were satisfied after clamping. No difference was seen in any outcome between the patients undergoing clamping versus cutting of the sympathetic chain, including sweating on the hands, face, armpits, feet, trunk, and thighs or in the quality of life. CONCLUSIONS: We found high rates of success and patient satisfaction when T3 sympathectomy was performed for palmar hyperhidrosis, with no differences found between the cutting and clamping techniques.

Man's best friend? Infective endocarditis due to Capnocytophaga canimorsus.

Infective endocarditis caused by zoonotic microorganisms is an uncommon clinical entity. A 55-year-old man was diagnosed with endocarditis due to Capnocytophaga canimorsus, a commensal bacterium contained in the saliva of dogs, that involved the aortic and tricuspid valves and was complicated by a para-aortic valve abscess and aorta-to-right atrial fistula. The patient was successfully treated with antibiotic therapy and surgical intervention. C canimorsus endocarditis should be considered in patients with culture-negative endocarditis, particularly in immunosuppressed, asplenic or alcoholic individuals who have recently suffered a dog bite or have had close contact with dogs.

Factors affecting anastomotic complications following anterior resection in rectal cancer.

OBJECTIVE: Anastomotic complications following sphincter saving rectal surgery remains a significant clinical problem in rectal cancer surgery. Preoperative combined modality therapy followed by anterior resection with total mesorectal excision (TME) has become the preferred treatment paradigm for locally advanced rectal cancer. However, its impact on anastomotic complications has not been adequately evaluated. This study aimed to assess the relationship between the response of the primary tumour to neo-adjuvant therapy with anastomotic complications and to evaluate the effect of other clinico-pathological factors previously implicated, in this patient cohort. METHOD: A total of 119 consecutive patients with primary rectal cancer were assessed of which there were 87 anterior resections. A prospectively collected database was queried to determine the incidence of anastomotic complications, association with response to neo-adjuvant therapy and other clinico-pathological factors. Data were analysed with SPSS 14.0. RESULTS: Anterior resection was performed in 87/111 (78.4%) patients of which 46/84 (56%) were low resections, with an abdominoperineal excision of rectum rate of 11/111 (9.9%). Anastomotic complications were seen as clinical leaks in 10/87 (11.5%) and late colo-visceral fistulae in 2/87 (2.2%) patients. Subclinical/ radiological 'leaks' were quantified as 4/87 (4.5%). A good pathological response to neo-adjuvant therapy was found to be strongly associated with anastomotic complications (P = 0.006). Presence of a perioperative cardiac event was the only other clinical factor associated with anastomotic complications (P = 0.004) in our study. CONCLUSION: Rectal cancer treated with neo-adjuvant therapy and radical resection with TME for better local control may be associated with greater anastomotic complications particularly when a good pathological response is seen.

Lung-volume reduction surgery for pulmonary emphysema: Improvement in body mass index, airflow obstruction, dyspnea, and exercise capacity index after 1 year.

OBJECTIVES: We hypothesized that lung-volume reduction surgery for pulmonary emphysema would improve body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index, a multidimensional predictor of survival in chronic obstructive pulmonary disease. We also aimed to identify preoperative predictors of improvement in the BODE index. METHODS: In a prospective cohort study of patients undergoing lung-volume reduction surgery at our center, with the methodology of the National Emphysema Treatment Trial, we compared clinical characteristics before and 1 year after surgery with the Wilcoxon signed rank test. Changes in the BODE index were correlated with preoperative variables with the Spearman correlation coefficient. RESULTS: Twenty-three patients with predominantly upper-lobe pulmonary emphysema underwent lung-volume reduction surgery (14 by video-assisted thoracoscopic surgery, 9 by median sternotomy). There were no postoperative or follow-up deaths. The BODE index improved from a median of 5 (interquartile range 4-5) before surgery to 3 (interquartile range 2-4) 1 year after surgery (P < .0001). Improvements were seen in the lung function and dyspnea components of the BODE index. Lower preoperative 6-minute walk distance and lower postwalk Borg fatigue scores were each associated with greater improvement in the BODE index after 1 year. CONCLUSION: Lung-volume reduction surgery for pulmonary emphysema improved the BODE index in patients with predominantly upper-lobe disease. Lower preoperative 6-minute walk distance correlated with greater improvement in the BODE index.