Saint Thomas Midtown Hospital

Type 2 diabetes mellitus (T2DM) is a global pandemic, as evident from the global cartographic picture of diabetes by the International Diabetes Federation (http://www.diabetesatlas.org/). Diabetes mellitus is a chronic, progressive, incompletely understood metabolic condition chiefly characterized by hyperglycemia. Impaired insulin secretion, resistance to tissue actions of insulin, or a combination of both are thought to be the commonest reasons contributing to the pathophysiology of T2DM, a spectrum of disease originally arising from tissue insulin resistance and gradually progressing to a state characterized by complete loss of secretory activity of the beta cells of the pancreas. T2DM is a major contributor to the very large rise in the rate of non-communicable diseases affecting developed as well as developing nations. In this mini review, we endeavor to outline the current management principles, including the spectrum of medications that are currently used for pharmacologic management, for lowering the elevated blood glucose in T2DM.

OBJECTIVE: The purpose of this study was to evaluate safety and clinical efficacy of negative pressure wound therapy (NPWT) compared with advanced moist wound therapy (AMWT) to treat foot ulcers in diabetic patients. RESEARCH DESIGN AND METHODS: This multicenter randomized controlled trial enrolled 342 patients with a mean age of 58 years; 79% were male. Complete ulcer closure was defined as skin closure (100% reepithelization) without drainage or dressing requirements. Patients were randomly assigned to either NPWT (vacuum-assisted closure) or AMWT (predominately hydrogels and alginates) and received standard off-loading therapy as needed. The trial evaluated treatment until day 112 or ulcer closure by any means. Patients whose wounds achieved ulcer closure were followed at 3 and 9 months. Each study visit included closure assessment by wound examination and tracings. RESULTS: A greater proportion of foot ulcers achieved complete ulcer closure with NPWT (73 of 169, 43.2%) than with AMWT (48 of 166, 28.9%) within the 112-day active treatment phase (P = 0.007). The Kaplan-Meier median estimate for 100% ulcer closure was 96 days (95% CI 75.0-114.0) for NPWT and not determinable for AMWT (P = 0.001). NPWT patients experienced significantly (P = 0.035) fewer secondary amputations. The proportion of home care therapy days to total therapy days for NPWT was 9,471 of 10,579 (89.5%) and 12,210 of 12,810 (95.3%) for AMWT. In assessing safety, no significant difference between the groups was observed in treatment-related complications such as infection, cellulitis, and osteomyelitis at 6 months. CONCLUSIONS: NPWT appears to be as safe as and more efficacious than AMWT for the treatment of diabetic foot ulcers.

BACKGROUND: In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite primary endpoint of stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke thereafter did not differ between carotid artery stenting and carotid endarterectomy for symptomatic or asymptomatic carotid stenosis. A secondary aim of this randomised trial was to compare the composite endpoint of restenosis or occlusion. METHODS: Patients with stenosis of the carotid artery who were asymptomatic or had had a transient ischaemic attack, amaurosis fugax, or a minor stroke were eligible for CREST and were enrolled at 117 clinical centres in the USA and Canada between Dec 21, 2000, and July 18, 2008. In this secondary analysis, the main endpoint was a composite of restenosis or occlusion at 2 years. Restenosis and occlusion were assessed by duplex ultrasonography at 1, 6, 12, 24, and 48 months and were defined as a reduction in diameter of the target artery of at least 70%, diagnosed by a peak systolic velocity of at least 3·0 m/s. Studies were done in CREST-certified laboratories and interpreted at the Ultrasound Core Laboratory (University of Washington). The frequency of restenosis was calculated by Kaplan-Meier survival estimates and was compared during a 2-year follow-up period. We used proportional hazards models to assess the association between baseline characteristics and risk of restenosis. Analyses were per protocol. CREST is registered with ClinicalTrials.gov, number NCT00004732. FINDINGS: 2191 patients received their assigned treatment within 30 days of randomisation and had eligible ultrasonography (1086 who had carotid artery stenting, 1105 who had carotid endarterectomy). In 2 years, 58 patients who underwent carotid artery stenting (Kaplan-Meier rate 6·0%) and 62 who had carotid endarterectomy (6·3%) had restenosis or occlusion (hazard ratio [HR] 0·90, 95% CI 0·63-1·29; p=0·58). Female sex (1·79, 1·25-2·56), diabetes (2·31, 1·61-3·31), and dyslipidaemia (2·07, 1·01-4·26) were independent predictors of restenosis or occlusion after the two procedures. Smoking predicted an increased rate of restenosis after carotid endarterectomy (2·26, 1·34-3·77) but not after carotid artery stenting (0·77, 0·41-1·42). INTERPRETATION: Restenosis and occlusion were infrequent and rates were similar up to 2 years after carotid endarterectomy and carotid artery stenting. Subsets of patients could benefit from early and frequent monitoring after revascularisation. FUNDING: National Institute of Neurological Disorders and Stroke and Abbott Vascular Solutions.

Fifty-one laparoscopic colectomies were attempted at two institutions. The clinical results and methods are presented. Seven cases (14%) were converted to facilitated procedures, and four cases (8%) were converted to "open." Cases of cancer, diverticulitis, endometriosis, regional enteritis, villous adenomas, and sessile polyps were operated. Right, transverse, left, low anterior, and abdominoperineal colectomies were performed. Colotomies and wedge resections were also performed. Laparoscopic suturing was required in five cases of incomplete anastomosis by circular stapler (18%). Suturing was required in all right, transverse colectomies and colotomies. Operative time averaged 2.3 hours. Hospitalization averaged 4.6 days. Four patients had complications (8%), and one 95-year-old died of pneumonia (2%). Laparoscopic colectomies can be performed safely, but require two-handed laparoscopic coordination, as well as suturing and knot-tying skills.

INTRODUCTION: Irreversible electroporation (IRE) has shown promise for ablation of lesions in proximity to vital structures in the preclinical setting. This study aims to evaluate the safety and efficacy of IRE for hepatic tumors in the clinical setting. METHODS: An IRB approved prospective registry of patients undergoing IRE for hepatic tumors over a 2-year period. Factors analyzed included patient and tumor characteristics, treatment related complications, and local recurrence free survival (LRFS) for ablated lesions. LRFS was calculated according to Kaplan-Meier, with secondary analyses stratified by procedural approach (laparotomy, laparoscopy, and percutaneous) and tumor histology. RESULTS: There were 44 patients undergoing 48 total IRE procedures, 20 colorectal mets, 14 hepatocellular, and 10 other metastatsis. Initial success was achieved in 46 (100%) treatments. Five patients had 9 adverse events, with all complications resolving within 30 days. LRFS at 3, 6, and 12 months was 97.4%, 94.6%, and 59.5%. There was a trend toward higher recurrence rates for tumors over 4 cm (HR 3.236, 95% CI: 0.585-17.891; P = 0.178). CONCLUSIONS: IRE appears to be a safe treatment for hepatic tumors in proximity to vital structures. Further prospective evaluation is needed to determine the optimal effectiveness of IRE in relation to size and technique for IRE of the liver.

Fusarium oxysporum is a phylogenetically diverse monophyletic complex of filamentous ascomycetous fungi that are responsible for localized and disseminated life-threatening opportunistic infections in immunocompetent and severely neutropenic patients, respectively. Although members of this complex were isolated from patients during a pseudoepidemic in San Antonio, Tex., and from patients and the water system in a Houston, Tex., hospital during the 1990s, little is known about their genetic relatedness and population structure. This study was conducted to investigate the global genetic diversity and population biology of a comprehensive set of clinically important members of the F. oxysporum complex, focusing on the 33 isolates from patients at the San Antonio hospital and on strains isolated in the United States from the water systems of geographically distant hospitals in Texas, Maryland, and Washington, which were suspected as reservoirs of nosocomial fusariosis. In all, 18 environmental isolates and 88 isolates from patients spanning four continents were genotyped. The major finding of this study, based on concordant results from phylogenetic analyses of multilocus DNA sequence data and amplified fragment length polymorphisms, is that a recently dispersed, geographically widespread clonal lineage is responsible for over 70% of all clinical isolates investigated, including all of those associated with the pseudoepidemic in San Antonio. Moreover, strains of the clonal lineage recovered from patients were conclusively shown to genetically match those isolated from the hospital water systems of three U.S. hospitals, providing support for the hypothesis that hospitals may serve as a reservoir for nosocomial fusarial infections.

OBJECTIVE: The recurrence rate of anti-SSA/Ro-associated congenital heart block (CHB) is 17%. Sustained reversal of third-degree block has never been achieved. Based on potential reduction of maternal autoantibody titers as well as fetal inflammatory responses, intravenous immunoglobulin (IVIG) was evaluated as preventive therapy for CHB. METHODS: A multicenter, prospective, open-label study based on Simon's 2-stage optimal design was initiated. Enrollment criteria included the presence of anti-SSA/Ro antibodies in the mother, birth of a previous child with CHB/neonatal lupus rash, current treatment with < or = 20 mg/day of prednisone, and <12 weeks pregnant. IVIG (400 mg/kg) was given every 3 weeks from week 12 to week 24 of gestation. The primary outcome was the development of second-degree or third-degree CHB. RESULTS: Twenty mothers completed the IVIG protocol before the predetermined stopping rule of 3 cases of advanced CHB in the study was reached. CHB was detected at 19, 20, and 25 weeks; none of the cases occurred following the finding of an abnormal PR interval on fetal Doppler monitoring. One of these mothers had 2 previous children with CHB. One child without CHB developed a transient rash consistent with neonatal lupus. Sixteen children had no manifestations of neonatal lupus at birth. No significant changes in maternal titers of antibody to SSA/Ro, SSB/La, or Ro 52 kd were detected over the course of therapy or at delivery. There were no safety issues. CONCLUSION: This study establishes the safety of IVIG and the feasibility of recruiting pregnant women who have previously had a child with CHB. However, IVIG at low doses consistent with replacement does not prevent the recurrence of CHB or reduce maternal antibody titers.

Background: The optimal approach to conducting antibiotic stewardship interventions has not been defined. We compared days of antibiotic therapy (DOT) using preprescription authorization (PPA) vs postprescription review with feedback (PPRF) strategies. Methods: A quasi-experimental, crossover trial comparing PPA and PPRF for adult inpatients prescribed any antibiotic was conducted. For the first 4 months, 2 medicine teams were assigned to the PPA arm and the other 2 teams to the PPRF arm. The teams were then assigned to the alternate arm for an additional 4 months. Appropriateness of antibiotic use was adjudicated by at least 2 infectious diseases-trained clinicians and according to institutional guidelines. Results: There were 2686 and 2693 patients admitted to the PPA and PPRF groups, with 29% and 27% of patients prescribed antibiotics, respectively. Initially, antibiotic DOTs remained relatively unchanged in the PPA arm. When changed to the PPRF arm, antibiotic use decreased (-2.45 DOT per 1000 patient-days [PD]). In the initial PPRF arm, antibiotic use decreased (slope of -5.73 DOT per 1000 PD) but remained constant when changed to the PPA arm. Median patient DOTs in the PPA and PPRF arms were 8 and 6 DOT per 1000 PD, respectively (P = .03). Antibiotic therapy was guideline-noncompliant in 34% and 41% of patients on days 1 and 3 in the PPA group (P < .01) and in 57% and 36% of patients on days 1 and 3 in the PPRF group (P = .03). Conclusions: PPRF may have more of an impact on decreasing antibiotic DOTs compared with PPA. This information may be useful for institutions without sufficient resources to incorporate both stewardship approaches.

CONTEXT: The inability to accurately localize the parathyroid glands during parathyroidectomy and thyroidectomy procedures can prevent patients from achieving postoperative normocalcemia. There is a critical need for an improved intraoperative method for real-time parathyroid identification. OBJECTIVE: The objective of the study was to test the accuracy of a real-time, label-free technique that uses near-infrared (NIR) autofluorescence imaging to localize the parathyroid. SETTING: The study was conducted at the Vanderbilt University endocrine surgery center. SUBJECTS AND METHODS: Patients undergoing parathyroidectomy and/or thyroidectomy were included in this study. To validate the intrinsic fluorescence signal in parathyroid, point measurements from 110 patients were collected using NIR fluorescence spectroscopy. Fluorescence imaging was performed on 6 patients. Imaging contrast is based on a previously unreported intrinsic NIR fluorophore in the parathyroid gland. The accuracy of fluorescence imaging was analyzed in comparison with visual assessment and histological findings. MAIN OUTCOME MEASURE: The detection rate of parathyroid glands was measured. RESULTS: The parathyroid glands in 100% of patients measured with fluorescence imaging were successfully detected in real time. Fluorescence images consistently showed 2.4 to 8.5 times higher emission intensity from the parathyroid than surrounding tissue. Histological validation confirmed that the high intrinsic fluorescence signal in the parathyroid gland can be used to localize the parathyroid gland regardless of disease state. CONCLUSION: NIR fluorescence imaging represents a highly sensitive, real-time, label-free tool for parathyroid localization during surgery. The elegance and effectiveness of NIR autofluorescence imaging of the parathyroid gland makes it highly attractive for clinical application in endocrine surgery.

BACKGROUND: Mechanical thrombectomy with stent-retrievers results in higher recanalization rates compared with previous devices. Despite successful recanalization rates (Thrombolysis in Cerebral Infarction (TICI) score ≥2b) of 70-83%, good outcomes by 90-day modified Rankin Scale (mRS) score ≤2 are achieved in only 40-55% of patients. We evaluated predictors of poor outcomes (mRS >2) despite successful recanalization (TICI ≥2b) in the North American Solitaire Stent Retriever Acute Stroke (NASA) registry. METHODS: Logistic regression was used to evaluate baseline characteristics and recanalization outcomes for association with 90-day mRS score of 0-2 (good outcome) vs 3-6 (poor outcome). Univariate tests were carried out for all factors. A multivariable model was developed based on backwards selection from the factors with at least marginal significance (p≤0.10) on univariate analysis with the retention criterion set at p≤0.05. The model was refit to minimize the number of cases excluded because of missing covariate values; the c-statistic was a measure of predictive power. RESULTS: Of 354 patients, 256 (72.3%) were recanalized successfully. Based on 234 recanalized patients evaluated for 90-day mRS score, 116 (49.6%) had poor outcomes. Univariate analysis identified an increased risk of poor outcome for age ≥80 years, occlusion site of internal carotid artery (ICA)/basilar artery, National Institute of Health Stroke Scale (NIHSS) score ≥18, history of diabetes mellitus, TICI 2b, use of rescue therapy, not using a balloon-guided catheter or intravenous tissue plasminogen activator (IV t-PA), and >30 min to recanalization (p≤0.05). In multivariable analysis, age ≥80 years, occlusion site ICA/basilar, initial NIHSS score ≥18, diabetes, absence of IV t-PA, ≥3 passes, and use of rescue therapy were significant independent predictors of poor 90-day outcome in a model with good predictive power (c-index=0.80). CONCLUSIONS: Age, occlusion site, high NIHSS, diabetes, no IV t-PA, ≥3 passes, and use of rescue therapy are associated with poor 90-day outcome despite successful recanalization.

OBJECTIVE: To analyze various quantitative measures of inflammatory activity and joint damage, including articular, radiographic, laboratory, questionnaire, and physical function measures, in regard to changes in status in surviving patients and prediction of mortality in non-survivors over 5 years in a cohort of patients with rheumatoid arthritis (RA) monitored in the mid-1980s and early 1990s. METHODS: A comprehensive evaluation, which included a complete joint count, radiograph, laboratory tests, physical measures of function, and self-report questionnaire scales, was performed at baseline and 5 years later in 210 consecutive patients with RA. RESULTS: Five years after baseline, 206 of the 210 patients were accounted for: 37 had died, 130 had a comprehensive repeat assessment, and 39 had a more limited repeat assessment. In surviving patients, most measures of activity were generally unchanged or somewhat better, including joint tenderness, pain on motion, and swelling; erythrocyte sedimentation rate and rheumatoid factor; as well as questionnaire scores for pain, global status, helplessness, and difficulty in performing 8 activities of daily living (ADL) according to a modified Health Assessment Questionnaire (MHAQ). By contrast, measures of damage, including joint deformity, grip strength, walk time, and radiographic scores, indicated worse status. Mortality over 5 years was predicted significantly in univariable analyses by American College of Rheumatology (formerly the American Rheumatism Association) Functional Class, limited joint motion, scores for MHAQ, global status, helplessness, grip strength, walk time, button time, and number of comorbidities and duration of diseases, as well as the sociodemographic measures of age and formal education. In multivariable Cox regressions, age, comorbidities, MHAQ, and other measures of functional status were the most effective predictors of 5-year mortality. CONCLUSION: In patients with RA, most measures of inflammatory activity were unchanged and sometimes better, while measures of damage indicated worse status in the same patients over 5 years. Measures indicating functional disability, as well as age and comorbidities, predict 5-year mortality more effectively than radiographic and laboratory data. Measures of inflammatory activity may underestimate long-term outcomes in RA, and long-term studies should include measures of damage.

BACKGROUND: The practices of euthanasia and physician-assisted suicide remain controversial. OBJECTIVE: To achieve better understanding of attitudes and practices regarding euthanasia and physician-assisted suicide in the context of end-of-life care. DESIGN: Cohort study. SETTING: United States. PARTICIPANTS: 3299 oncologists who are members of the American Society of Clinical Oncology. MEASUREMENTS: Responses to survey questions on attitudes toward euthanasia and physician-assisted suicide for a terminally ill patient with prostate cancer who has unremitting pain, requests for and performance of euthanasia and physician-assisted suicide, and sociodemographic characteristics. RESULTS: Of U.S. oncologists surveyed, 22.5% supported the use of physician-assisted suicide for a terminally ill patient with unremitting pain and 6.5% supported euthanasia. Oncologists who were reluctant to increase the dose of intravenous morphine for terminally ill patients in excruciating pain (odds ratio [OR], 0.61 [95% CI, 0.48 to 0.77]) and had sufficient time to talk to dying patients about end-of-life care issues (OR, 0.79 [CI, 0.71 to 0.87]) were less likely to support euthanasia or physician-assisted suicide. During their career, 3.7% of surveyed oncologists had performed euthanasia and 10.8% had performed physician-assisted suicide. Oncologists who were reluctant to increase the morphine dose for patients in excruciating pain (OR, 0.58 [CI, 0.43 to 0.79]) and those who believed that they had received adequate training in end-of-life care (OR, 0.86 [CI, 0.79 to 0.95]) were less likely to have performed euthanasia or physician-assisted suicide. Oncologists who reported not being able to obtain all the care that a dying patient needed were more likely to have performed euthanasia (P = 0.001). CONCLUSIONS: Requests for euthanasia and physician-assisted suicide are likely to decrease as training in end-of-life care improves and the ability of physicians to provide this care to their patients is enhanced.

BACKGROUND: Coronary computed tomography angiography (CTA) enables accurate anatomic evaluation of coronary artery stenosis but lacks information about hemodynamic significance. The aim of this study was to evaluate 128-slice myocardial CT perfusion (CTP) imaging with adenosine stress using a high-pitch mode, in comparison with cardiac MRI (CMR). METHODS AND RESULTS: Thirty-nine patients with intermediate to high coronary risk profile underwent adenosine stress 128-slice dual source CTP (128×0.6 mm, 0.28 seconds). Among those, 30 patients (64 ± 10 years, 6% women) also underwent adenosine stress CMR (1.5T). The 2-step CTP protocol consisted of (1) adenosine stress-CTP using a high-pitch factor (3.4) ECG-synchronized spiral mode and (2) rest-CTP/coronary-CTA using either high-pitch (heart rate <63 bpm) or prospective ECG-triggering (heart rate >63 bpm). Results were compared with CMR and with invasive angiography in 25 patients. The performance of stress-CTP for detection of myocardial perfusion defects compared with CMR was sensitivity, 96%; specificity, 88%; positive predictive value (PPV), 93%; negative predictive value (NPV), 94% (per vessel); and sensitivity, 78%; specificity, 87%; PPV, 83%; NPV, 84% (per segment). The accuracy of stress-CTP for imaging of reversible ischemia compared with CMR was sensitivity, 95%; specificity, 96%; PPV, 95%; and NPV, 96% (per vessel). In 25 patients who underwent invasive angiography, the accuracy of CTA for detection of stenosis >70% was (per segment): sensitivity, 96%; specificity, 88%; PPV, 67%; and NPV, 98.9%. The accuracy improved from 84% to 95% after adding stress CTP to CTA. Radiation exposure of the entire stress/rest CT protocol was only 2.5 mSv. CONCLUSIONS: Adenosine-induced stress 128-slice dual-source high-pitch myocardial CTP allows for simultaneously assessment of reversible myocardial ischemia and coronary stenosis, with good diagnostic accuracy as compared with CMR and invasive angiography, at a very low radiation exposure.

BACKGROUND: In recent years, laboratory and clinical research has suggested the need for peritoneal dialysis fluids (PDFs) that are more biocompatible than the conventional PDFs commonly used today. Bioincompatibility of PDF has been attributed to low pH, lactate, glucose, glucose degradation products (GDPs), and osmolality. PDFs with neutral pH and low GDPs are now available commercially. In vitro and early clinical studies suggest that these solutions are indeed more biocompatible but, as of now, there is no evidence that their use improves patient outcome. METHODS: Using a dedicated database of over 2000 patients treated with PD in Korea, we were able to conduct a retrospective observational study comparing outcomes for incident continuous ambulatory PD patients treated with a standard, conventional, heat-sterilized PDF to the outcomes for patients treated with a novel, low GDP, neutral-pH PDF prepared in a dual-compartment, double-bag PD system (Balance; Fresenius Medical Care, St. Wendel, Germany). In an intention-to-treat analysis, patient and technique survival, peritonitis-free survival, and peritonitis rates were compared in 611 patients treated with Balance for up to 30 months and 551 patients with a standard PDF (stay . safe; Fresenius Medical Care) treated in the same era and with equivalent follow-up. RESULTS: The patients were well matched for most relevant characteristics except older age distribution for the patients treated with the standard PDF. Patients treated with Balance had significantly superior survival compared to those treated with the standard PDF (74% vs 62% at 28 months, p = 0.0032). In a multivariate Cox regression model including age, diabetes, and gender, the survival advantage persisted (relative risk of death for Balance 0.75, 95% confidence interval 0.56 - 0.99, p = 0.0465). Modality technique survival was similarin Kaplan-Meieranalysis for both PDFs. No differences were detected in peritonitis-free survival or in peritonitis rates between the two solutions. CONCLUSION: This study, for the first time, suggests that treatment with a novel biocompatible PDF with low GDP concentration and neutral pH confers a significant survival advantage. The exact mechanisms for such a survival advantage cannot be determined from this study. The usual criticisms of observational studies apply and the results reported here strongly warrant the undertaking of appropriately designed, randomized, controlled clinical trials.

BACKGROUND: Recent studies have suggested that antiemetic therapy with a triple combination of the neurokinin-1 receptor antagonist MK-869, a serotonin (5-HT(3)) antagonist, and dexamethasone provides enhanced control of cisplatin-induced emesis compared with standard therapy regimens. The authors compared the antiemetic activity of a dual combination of MK-869 and dexamethasone with that of a standard dual combination of ondansetron and dexamethasone to characterize further the efficacy and tolerability profile of MK-869. METHODS: This was a multicenter, double-blind, randomized, active agent-controlled study of 177 cisplatin-naïve patients with malignant disease. On Day 1, MK-869 was given intravenously as its water-soluble prodrug, L-758,298. Patients were randomized to one of three groups as follows. Group I received L-758,298 100 mg intravenously (i.v.), then dexamethasone 20 mg i.v., and cisplatin >or= 70 mg/m(2) on Day 1 followed by 300 mg MK-869 (tablet) orally on Days 2-5; Group II received L-758,298 100 mg i.v., then dexamethasone 20 mg i.v., and cisplatin >or= 70 mg/m(2) on Day 1 followed by placebo on Days 2-5; and Group III received ondansetron 32 mg i.v., then dexamethasone 20 mg i.v., and cisplatin >or= 70 mg/m(2) on Day 1 followed by placebo on Days 2-5. Emesis was recorded over Days 1-5 in a diary. Nausea was assessed every 24 hours by visual analog scale. Additional medication was available for emesis or nausea at any time. The primary efficacy parameters of interest were the proportion of patients without emesis and the proportion without emesis or rescue therapy on Day 1 (acute phase) and on Days 2-5 (delayed phase). RESULTS: No serious adverse events were attributed to L-758,298 or MK-869. On Day 1, the proportions of patients with no emesis and no use of rescue medication were 44% of patients in Group I, 36% of patients in Group II, 40% of patients in Groups I and II combined, and 83% of patients in Group III (P < 0.001 for Group III vs. the combined Groups I and II). The proportions of patients with no emesis and no use of rescue medication on Days 2-5 were 59% of patients in Group I, 46% of patients in Group II, and 38% of patients in Group III (P < 0.05 for Group I vs. Group III). The proportions of patients who were without emesis on Day 1 were 49% of patients in Group I, 47% of patients in Group II, and 84% of patients in Group III (P < 0.01 for Group I or II vs. Group III). On Days 2-5, however, the proportions of patients who were without emesis on Days 2-5 were 65% of patients in Group I, 61% of patients in Group II, and 41% of patients in Group III (P < 0.05 for Group I or II vs. Group III). Nausea scores in the acute phase were lower for Group III than for Group I, Group II, or Groups I and II combined (P < 0.05), although there was no significant difference among groups either for the delayed phase or overall for Days 1-5. CONCLUSIONS: Although the L-758,298 and dexamethasone combination reduced acute (Day 1) emesis compared with historic rates, dual therapy with ondansetron and dexamethasone was superior in controlling acute emesis. Continued dosing with MK-869 may enhance control of other measures of delayed emesis, such as the use of rescue medication, although confirmation is required before a definitive conclusion may be drawn. MK-869 given as dual therapy with dexamethasone was superior to ondansetron with dexamethasone for the control of delayed emesis (Days 2-5) and control of the need for rescue medication on Days 2-5.

OBJECTIVES: To investigate the hypothesis that strokes occurring in patients with coronavirus disease 2019 (COVID-19) have distinctive features, we investigated stroke risk, clinical phenotypes, and outcomes in this population. METHODS: We performed a systematic search resulting in 10 studies reporting stroke frequency among patients with COVID-19, which were pooled with 1 unpublished series from Canada. We applied random-effects meta-analyses to estimate the proportion of stroke among COVID-19. We performed an additional systematic search for cases series of stroke in patients with COVID-19 (n = 125), and we pooled these data with 35 unpublished cases from Canada, the United States, and Iran. We analyzed clinical characteristics and in-hospital mortality stratified into age groups (<50, 50-70, >70 years). We applied cluster analyses to identify specific clinical phenotypes and their relationship with death. RESULTS: = 0.003). CONCLUSIONS: Stroke is relatively frequent among patients with COVID-19 and has devastating consequences across all ages. The interplay of older age, comorbid conditions, and severity of COVID-19 respiratory symptoms is associated with an extremely elevated mortality.

BACKGROUND: Irreversible electroporation (IRE) is a novel technology that uses peri-target discrete probes to deliver high-voltage localized electric current to induce cell death without thermal-induced coagulative necrosis. "Learnability" and consistently effective results by novice practitioners is essential for determining acceptance of novel techniques. This multi-center prospectively-collected database study evaluates the learning curve of IRE. METHODS: Analysis of 150 consecutive patients over 7 institutions from 9/2010-7/2012 was performed with patients treated divided into 3 groups A (1(st) 50 patients treated), B (2(nd) 50) and C (3(rd) 50 patients treated) chronologically and analyzed for outcomes. RESULTS: A total of 167 IRE procedures were performed, with a majority being liver(39.5%) and pancreatic(35.5%) lesions. The three groups were similar with respect to co-morbidities and demographics. Group C had larger lesions (3.9 vs 3 cm,p=0.001), more numerous lesions (3.2 vs 2.2,p=0.07), more vascular invasion(p=0.001), underwent more associated procedures(p=0.001) and had longer operative times(p<0.001). Despite this, they had similar complication and high-grade complication rates(p=0.24). Attributable morbidity rate was 13.3%(total 29.3%) and high-grade complications were seen in 4.19%(total 12.6%). Pancreatic lesions(p=0.001) and laparotomy(p=0.001) were associated with complications. CONCLUSION: The review represents that single largest review of IRE soft tissue ablation demonstrating initial patient selection and safety. Over time, complex treatments of larger lesions and lesions with greater vascular involvement were performed without a significant increase in adverse effects or impact on local relapse free survival. This evolution demonstrates the safety profile of IRE and speed of graduation to more complex lesions, which was greater than 5 cases by institution. IRE is a safe and effective alternative to conventional ablation with a demonstrable learning curve of at least 5 cases to become proficient.

Transoral excision of supraglottic and hypopharynx cancer as a single modality is effective when lesions are selected for small size and endoscopic accessibility. Excisional biopsy with clear margins of larger supraglottic tumors in combination with postoperative radiotherapy provides an excellent treatment alternative for selected lesions in patients who are not candidates for open surgery. In this preliminary report, 45 cases using this minimally invasive approach are reviewed outlining oncologic rationale and functional advantages. A large bore tubed laryngoscope or the adjustable bivalve supraglottiscope was used along with a carbon dioxide laser in all cases. In 22 of the 45 patients (mostly T1), local en bloc excision of the primary cancer was performed as sole treatment on selected lesions of the supraglottis and hypopharynx. There were no local recurrences, however, 1 patient developed a neck recurrence and was salvaged by neck dissection. Twenty-three of the 45 patients had more extensive primaries (mostly T2, T3) and N0 necks. Transoral excisional biopsy was followed by full-course radiation therapy to the primary site and both necks. All 23 were followed a minimum of 2 years, and the median follow-up period was 58 months. Clear margins were obtained in 16 of 23, and there were no recurrences in the larynx. Two of 16 did fail in the neck and died despite neck dissection. Seven of 23 patients had positive margins and, despite full-course radiotherapy to the primary site and both necks, 5 of 7 failed locally or regionally. Two of the 7 died of their disease despite open salvage surgery. Therefore, 4 of 23 patients who underwent transoral excision of larger lesions followed by full-course radiotherapy died of recurrent cancer.

OBJECTIVE Aneurysmal subarachnoid hemorrhage (aSAH) may be complicated by hydrocephalus in 6.5%-67% of cases. Some patients with aSAH develop shunt dependency, which is often managed by ventriculoperitoneal shunt placement. The objectives of this study were to review published risk factors for shunt dependency in patients with aSAH, determine the level of evidence for each factor, and calculate the magnitude of each risk factor to better guide patient management. METHODS The authors searched PubMed and MEDLINE databases for Level A and Level B articles published through December 31, 2014, that describe factors affecting shunt dependency after aSAH and performed a systematic review and meta-analysis, stratifying the existing data according to level of evidence. RESULTS On the basis of the results of the meta-analysis, risk factors for shunt dependency included high Fisher grade (OR 7.74, 95% CI 4.47-13.41), acute hydrocephalus (OR 5.67, 95% CI 3.96-8.12), in-hospital complications (OR 4.91, 95% CI 2.79-8.64), presence of intraventricular blood (OR 3.93, 95% CI 2.80-5.52), high Hunt and Hess Scale score (OR 3.25, 95% CI 2.51-4.21), rehemorrhage (OR 2.21, 95% CI 1.24-3.95), posterior circulation location of the aneurysm (OR 1.85, 95% CI 1.35-2.53), and age ≥ 60 years (OR 1.81, 95% CI 1.50-2.19). The only risk factor included in the meta-analysis that did not reach statistical significance was female sex (OR 1.13, 95% CI 0.77-1.65). CONCLUSIONS The authors identified several risk factors for shunt dependency in aSAH patients that help predict which patients are likely to require a permanent shunt. Although some of these risk factors are not independent of each other, this information assists clinicians in identifying at-risk patients and managing their treatment.

INTRODUCTION: Mexican Americans remain severely underrepresented in Alzheimer's disease (AD) research. The Health & Aging Brain among Latino Elders (HABLE) study was created to fill important gaps in the existing literature. METHODS: Community-dwelling Mexican Americans and non-Hispanic White adults and elders (age 50 and above) were recruited. All participants underwent comprehensive assessments including an interview, functional exam, clinical labs, informant interview, neuropsychological testing, and 3T magnetic resonance imaging (MRI) of the brain. Amyloid and tau positron emission tomography (PET) scans were added at visit 2. Blood samples were stored in the Biorepository. RESULTS: Data was examined from n = 1705 participants. Significant group differences were found in medical, demographic, and sociocultural factors. Cerebral amyloid and neurodegeneration imaging markers were significantly different between Mexican Americans and non-Hispanic Whites. DISCUSSION: The current data provide strong support for continued investigations that examine the risk factors for and biomarkers of AD among diverse populations.