Post-treatment mortality after definitive chemoradiotherapy versus resection for esophageal cancer.

In efforts to better characterize incidence and predictors of 30- and 90-day mortality following operative versus nonoperative approaches for locally advanced esophageal cancer (EC), we conducted a novel investigation of a large, contemporary US database. The National Cancer Database was queried for newly-diagnosed T1-3N0-1 squamous cell or adenocarcinoma receiving surgical-based therapy (esophagectomy alone or preceded by chemotherapy and/or radiotherapy) versus definitive chemoradiotherapy (dCRT). Statistics included graphing cumulative incidences of mortality before and following propensity score matching (PSM), based on age-based intervals. Cox regression determined factors independently predictive of 30- and 90-day mortality. Of 15,585 patients, 9,278 (59.5%) received surgical-based therapy and 6,307 (40.5%) underwent dCRT. In the unadjusted population, despite nonsignificant differences at 30 days (3.3% dCRT, 3.6% surgical-based), the dCRT cohort experienced higher 90-day mortality (11.0% vs. 7.5%, P < 0.001). Following PSM, however, dCRT patients experienced significantly lower 30-day mortality (P < 0.001), with nonsignificant differences at 90 days (P = 0.092). Surgical-based management yielded similar (or better) mortality as dCRT in ≤70-year-old patients; however, dCRT was associated with reduced mortality in subjects > 70 years old. In addition to the intervention group, factors predictive for 30- and 90-day mortality included age, gender, insurance status, facility type, comorbidity index, tumor location, histology, and T/N classification. In summary, surgical-based therapy for EC is associated with higher 30-day mortality, which becomes statistically similar to dCRT by 90 days. Differences between surgery and dCRT were most pronounced in patients > 70 years of age. These data may better inform shared decision-making between multidisciplinary providers and patients.

Trimodality therapy for esophageal cancer at high volume facilities is associated with improved postoperative outcomes and overall survival.

Trimodality therapy is the standard of care for locally advanced resectable esophageal cancer (EC) but carries morbidity and mortality risks; thus, therapy at high-volume facilities (HVFs) may offer advantages. This investigation studied postoperative outcomes and overall survival (OS) in EC patients receiving trimodality therapy at HVFs versus lower-volume facilities (LVFs). The National Cancer Data Base was queried for patients with locally advanced EC receiving trimodality therapy. HVFs referred to the 90th percentile of case volume. Multivariate logistic regression determined factors associated with treatment at HVFs, the Kaplan-Meier analysis compared OS between the HVF and LVF groups, and the Cox proportional hazards modeling determined variables associated with OS. Sensitivity analysis evaluated the impact of varying the HVF definition cutoff on OS. A total of 3,229 patients met study criteria, including 330 (10%) treated at HVFs and 2,899 (90%) at LVFs. Treatment at HVFs was associated with decreased 30-day mortality (1.2% vs. 3.3%, P = 0.044) and trends toward lower 90-day mortality (4.8% vs. 7.8%, P = 0.055) and the length of postoperative hospitalization (11.2 vs. 12.3d, P = 0.059). HVF patients experienced higher median OS (55 vs. 36 months, P = 0.004), which also independently correlated on the Cox multivariate analysis (P = 0.001). Sensitivity analysis showed similar results as the HVF/LVF cutoff was decreased until the 80th percentile. This is the first study demonstrating that the trimodality management of EC at HVFs is associated with improved postoperative outcomes and survival. These data have implications for multidisciplinary oncologic providers, in addition to patient counseling by both referring and treating clinicians.

True vasculitis in lupus nephritis.

Vascular lesions are encountered frequently in renal biopsy specimens of patients with systemic lupus erythematosus (SLE) and can present in a variety of morphologic forms. True renal lupus vasculitis (TRLV) is one of the rare vascular lesions associated with lupus nephritis that has been infrequently reported in the medical literature. The primary focus on glomerular pathology and collective classification of the vascular lesions under lupus vasculopathy is one of the reasons why this form of inflammatory vasculitis has been under-recognized as a separate disease entity. Here we have comprehensively reviewed the literature on renal vascular involvement in SLE for a better understanding of the epidemiology, morphologic features, pathogenesis, clinical course and treatment of TRLV. It can be morphologically differentiated from other forms of renal vascular lesions in lupus nephritis, i.e. arteriosclerosis, uncomplicated vascular immune deposits, non-inflammatory necrotizing vasculopathy, and thrombotic microangiopathy. Despite close similarities with antineutrophil cytoplasmic autoantibody associated vasculitis (AASV), there are certain morphological differences that warrant a thorough investigation of the possible pauci-immune mechanism of pathogenesis. The vasculitis follows a severe clinical course in general with rapid progression to renal failure, although favorable outcomes have been reported in certain cases. The standard use of steroids and cytotoxic drugs has yielded variable results in the treatment of TRLV. Current treatment modalities being used in lupus nephritis and AASV have been compared in this article with focus on drugs acting on the inflammatory cells implicated in TRLV pathogenesis.

Immunomodulator tuftsin augments anti-fungal activity of amphotericin B against experimental murine candidiasis.

In the present study, we report the potential of an immunomodulator tuftsin in increasing the efficacy of liposomised Amphotericin B (Amp B) against drug sensitive as well as drug resistant experimental murine candidiasis. The Amp B containing liposomes demonstrated strong potential of eliminating systemic candidiasis (70% survival) in animals infected with Amp B sensitive strain of Candida albicans (C. albicans). The same liposomal formulation was found to be ineffective in treatment of animals infected with drug resistant C. albicans. However, the co-administration of liposomal formulation of Amp B along with an immunomodulator tuftsin, was found to be competent enough in curing even the drug resistant candidiasis. In contrast, none of the animals survived in the control groups, which were treated with free or liposomised Amp B (without tuftsin). Further, the effect of liposomised tuftsin, on T-cell proliferation as well as antibody production reveals that tuftsin elicits strong immunopotentiating effects as well. The pretreatment with liposomised tuftsin prior to challenging the animals with drug resistant C. albicans infection has also been effective and shows an extra edge in prophylactic perspectives.

Post-mortem findings in familial partial lipodystrophy, Dunnigan variety.

AIMS: Familial partial lipodystrophy, Dunnigan variety (FPLD), is an autosomal dominant disorder due to missense mutations in the lamin A/C gene and is characterized by gradual loss of subcutaneous fat from the extremities and trunk, fat accumulation in the head, neck and intra-abdominal areas, insulin resistance and its metabolic complications. We studied autopsy findings in two patients with FPLD to determine fat distribution and organ involvement. RESULTS: Patient 1, a 66-year-old woman with the R482Q mutation, had diabetes mellitus, dyslipidaemia, and coronary artery disease and died suddenly. Autopsy confirmed the typical body fat distribution and further revealed excess fat deposition in the subpectoral regions extending to the axillae, in the axillary lymph nodes and in the retroperitoneum. Atherosclerotic vascular disease including old infarcts of the myocardium, temporal lobe and kidneys were noted. Severe amyloidosis of the pancreatic islets and grouped muscle atrophy of the quadriceps and diaphragmatic muscles were present. Patient 2, a 29-year-old woman belonging to a pedigree with the R62G mutation, died of hyperlipidaemia-induced acute pancreatitis. Autopsy of patient 2 revealed extensive pancreatitis, hepatic steatosis and polycystic ovaries. CONCLUSIONS: Our study confirms typical body fat distribution and describes new sites of excess fat deposition. Our data show predisposition to atherosclerosis and polycystic ovaries and suggest that pancreatic amyloidosis may underlie development of hyperglycaemia in FPLD patients.

Synthesis of (1-->4)-linked 2-deoxy-2-fluoroglucose oligomers. 1.

[reaction: see text] Thioglycosides of natural monosaccharides are readily converted into their corresponding chlorides by diphenylchlorosulfonium chloride. This reagent can likewise effect the conversion of the more stable 4-chlorophenylthio 2-deoxy-2-fluoroglucose derivatives into chloride glycosyl donors. On the basis of this activation strategy, it was possible to assemble unnatural oligosaccharides composed of 2-fluorodeoxy sugars.

Sexual functioning in depressed outpatients taking mirtazapine.

OBJECTIVES: One-third of patients with untreated depression have sexual difficulties manifested by decreased libido, erectile dysfunction or delayed ejaculation. This dysfunction may be exacerbated by stimulation of post-synaptic serotonin 5HT2 receptors, a side-effect of most widely-used antidepressant medications, especially the selective serotonin reuptake inhibitors (SSRIs). Mirtazapine is an atypical antidepressant with alpha 2 adrenergic antagonist and serotonin 5-HT2 and 5-HT3 receptor-blocking activity. In theory, it should not worsen and perhaps may improve sexual function. This pilot study investigated sexual functioning and antidepressant activity in depressed patients taking mirtazapine. EXPERIMENTAL DESIGN: Twenty-five (F = 18, M = 7) sexually active adult outpatients with a DSM-IV-diagnosis of major depressive episode entered a 12-week, flexible-dosing, open-label pilot study. The Arizona Sexual Experiences Scale (ASEX) assessed sexual functioning and the Hamilton Depression Rating Scale (HAM-D) assessed depressive symptoms on a bimonthly basis. PRINCIPAL OBSERVATIONS: Desire, arousal/lubrication, and ease/satisfaction of orgasm improved (by 41%, 52%, and 48%, respectively) in the depressed women. In men, desire, arousal/erection, and ease/satisfaction of orgasm also improved (by 10%, 23% and 14%, respectively) but much more modestly. HAM-D, Clinical Global Impression (CGI) Sheehan Disability Scale (SDS), and Symptom Checklist-90 (SCL-90) scores improved in both groups. There was a 50% dropout rate among women before six weeks of treatment. However, the ASEX and HAM-D scores of the groups terminating before and after six weeks of treatment showed similar rates of improvement. CONCLUSIONS: Mirtazapine has a beneficial effect on sexual functioning in both depressed women and men. Longer-term double-blind research assessing sexual function during the administration of mirtazapine as well as other antidepressants is recommended.

Behavior therapy and the transdermal nicotine patch: effects on cessation outcome, affect, and coping.

The process and outcome of a smoking cessation program using behavior therapy alone (BT) or behavior therapy plus the nicotine patch (BTP) was studied in 64 participants. Participants quit smoking on a target date after a period of ad libitum smoking, cognitive-behavior therapy preparing them for cessation, and behavioral rehearsal for high-risk situations, including stress management, and coping with negative affect. Abstinence was significantly higher for the BTP group versus the BT group from the end of behavioral treatment (79% vs. 63%) through the 3-month follow-up (p < .01), with the effects weakening at the 6- (p = .06) and 12-month marks (p = 38% vs. 22%). More general distress was observed among BT versus BTP participants (i.e., increased withdrawal, tension, fatigue, and coping frequency with decreased coping effort; coping-to-urge ratio). The coping behavior of the BTP group may have been more effective than that of the BT group, as indicated by their significantly higher level of self-efficacy.

Hemodynamic effects of supplemental oxygen administration in congestive heart failure.

OBJECTIVES: This study sought to determine the hemodynamic effects of oxygen therapy in heart failure. BACKGROUND: High dose oxygen has detrimental hemodynamic effects in normal subjects, yet oxygen is a common therapy for heart failure. Whether oxygen alters hemodynamic variables in heart failure is unknown. METHODS: We studied 10 patients with New York Heart Association functional class III and IV congestive heart failure who inhaled room air and 100% oxygen for 20 min. Variables measured included cardiac output, stroke volume, pulmonary capillary wedge pressure, systemic and pulmonary vascular resistance, mean arterial pressure and heart rate. Graded oxygen concentrations were also studied (room air, 24%, 40% and 100% oxygen, respectively; n = 7). In five separate patients, muscle sympathetic nerve activity and ventilation were measured during 100% oxygen. RESULTS: The 100% oxygen reduced cardiac output (from 3.7 +/- 0.3 to 3.1 +/- 0.4 liters/min [mean +/- SE], p < 0.01) and stroke volume (from 46 +/- 4 to 38 +/- 5 ml/beat per min, p < 0.01) and increased pulmonary capillary wedge pressure (from 25 +/- 2 to 29 +/- 3 mm Hg, p < 0.05) and systemic vascular resistance (from 1,628 +/- 154 to 2,203 +/- 199 dynes.s/cm5, p < 0.01). Graded oxygen led to a progressive decline in cardiac output (one-way analysis of variance, p < 0.0001) and stroke volume (p < 0.017) and an increase in systemic vascular resistance (p < 0.005). The 100% oxygen did not alter sympathetic activity or ventilation. CONCLUSIONS: In heart failure, oxygen has a detrimental effect on cardiac output, stroke volume, pulmonary capillary wedge pressure and systemic vascular resistance. These changes are independent of sympathetic activity and ventilation.

Death following suspected alprazolam withdrawal seizures: a case report.

This is a case report of severe psychosis and seizures following abrupt discontinuation of alprazolam and then the recurrence of seizures at the end of a gradual tapering schedule. The last of these seizures appeared to be a contributing factor in the patient's death. To the authors' knowledge, this is the first published report of a fatality associated with alprazolam withdrawal.

Very low-density lipoprotein metabolism in an unusual case of lipoatrophic diabetes.

Complete acquired lipoatrophic diabetes (LD) is characterized by nonketotic insulin-resistant diabetes, elevated very low-density lipoprotein (VLDL) triglyceride (TG) levels, and absent subcutaneous fat. We studied a young child in whom LD atypically developed after the onset of type 1 diabetes mellitus. On uncontrolled home diet the patient had triglyceride levels over 1,000 mg/dL on multiple occasions. In order to demonstrate the effects of caloric and dietary-fat restriction on VLDL metabolism, 3H-glycerol and autologous 125I-VLDL were used to quantitate the turnover of VLDL-TG and VLDL-apolipoprotein B (apo B) during two periods of caloric restriction. Consumption of a 900-kcal 40-g fat diet resulted in a plasma triglyceride level of 1383 mg/dL (ten-fold elevation). This hypertriglyceridemia was associated with markedly increased production rates of both VLDL-TG (73.7 mg/kg/h) and VLDL-apo B (126.9 mg/kg/d). Consumption of a 900-kcal 25-g fat diet resulted in a plasma TG level of 663 mg/dL. This reduction in plasma TG was associated with a 40% decrease in VLDL-TG production rate (PR) (45.1 mg/kg/h). There was no change in the production rate (PR) of VLDL-apo B. The hypertriglyceridemia in this patient was due to marked over production of VLDL. Furthermore, the studies demonstrate: (1) the independent benefits of caloric and dietary-fat restriction in the treatment of LD, and (2) that fat restriction lowered plasma triglyceride by its effect on the VLDL-TG production rate.