Preoperative quality of life and surgical outcomes in gynecologic oncology patients: a new predictor of operative risk?

OBJECTIVE: Quality of life (QoL) for women with gynecologic malignancies is predictive of chemotherapy related toxicity and overall survival but has not been studied in relation to surgical outcomes and hospital readmissions. Our goal was to evaluate the association between baseline, pre-operative QoL measures and 30-day post-operative morbidity and health resource utilization by gynecologic oncology patients. METHODS: We analyzed prospectively collected survey data from an institution-wide cohort study. Patients were enrolled from 8/2012 to 6/2013 and medical record data was abstracted (demographics, comorbid conditions, and operative outcomes). Responses from several validated health-related QoL instruments were collected. Bivariate tests and multivariable linear and logistic regression models were used to evaluate factors associated with QoL scores. RESULTS: Of 182 women with suspected gynecologic malignancies, 152 (84%) were surveyed pre-operatively and 148 (81%) underwent surgery. Uterine (94; 63.5%), ovarian (26; 17.5%), cervical (15; 10%), vulvar/vaginal (8; 5.4%), and other (5; 3.4%) cancers were represented. There were 37 (25%) cases of postoperative morbidity (PM), 18 (12%) unplanned ER visits, 9(6%) unplanned clinic visits, and 17 (11.5%) hospital readmissions (HR) within 30days of surgery. On adjusted analysis, lower functional well-being scores resulted in increased odds of PM (OR 1.07, 95%CI 1.01-.1.21) and HR (OR 1.11, 95%CI 1.03-1.19). A subjective global assessment score was also strongly associated with HR (OR 1.89, 95%CI 1.14, 3.16). CONCLUSION: Lower pre-operative QoL scores are significantly associated with post-operative morbidity and hospital readmission in gynecologic cancer patients. This relationship may be a novel indicator of operative risk.

Respiratory syncytial virus activates epidermal growth factor receptor to suppress interferon regulatory factor 1-dependent interferon-lambda and antiviral defense in airway epithelium.

Respiratory syncytial virus (RSV) persists as a significant human pathogen that continues to contribute to morbidity and mortality. In children, RSV is the leading cause of lower respiratory tract infections, and in adults RSV causes pneumonia and contributes to exacerbations of chronic lung diseases. RSV induces airway epithelial inflammation by activation of the epidermal growth factor receptor (EGFR), a tyrosine kinase receptor. Recently, EGFR inhibition was shown to decrease RSV infection, but the mechanism(s) for this effect are not known. Interferon (IFN) signaling is critical for innate antiviral responses, and recent experiments have implicated IFN-λ (lambda), a type III IFN, as the most significant IFN for mucosal antiviral immune responses to RSV infection. However, a role for RSV-induced EGFR activation to suppress airway epithelial antiviral immunity has not been explored. Here, we show that RSV-induced EGFR activation suppresses IFN regulatory factor (IRF) 1-induced IFN-λ production and increased viral infection, and we implicate RSV F protein to mediate this effect. EGFR inhibition, during viral infection, augmented IRF1, IFN-λ, and decreased RSV titers. These results suggest a mechanism for EGFR inhibition to suppress RSV by activation of endogenous epithelial antiviral defenses, which may be a potential target for novel therapeutics.

Degradation of mechanical behavior in UHMWPE after natural and accelerated aging.

Ultra-high molecular weight polyethylene (UHMWPE) is known to degrade during natural (shelf) aging following gamma irradiation in air, but the mechanical signature of degradation remains poorly understood. Accelerated aging methods have been developed to reproduce the natural aging process as well as to precondition total joint replacement components prior to joint simulator wear testing. In this study, we compared the mechanical behavior of naturally (shelf) aged and accelerated aged tibial inserts using a previously validated miniature specimen testing technique known as the small punch test. Tibial inserts made-of GUR 1120 and sterilized with 25 to 40 kGy of gamma radiation (in air) in 1988, 1993, and 1997 were obtained; a subset of the 1997 implants were subjected to 4 weeks of accelerated aging in air at 80 degrees C. To determine the spatial variation of mechanical properties within each insert, miniature disk shaped specimens were machined from the surface and subsurface regions of the inserts. Analysis of variance of the test data showed that aging significantly affected the small punch test measures of elastic modulus, initial load, ultimate load, ultimate displacement, and work to failure. The accelerated aging protocol was unable to reproduce the spatial mechanical profile seen in shelf aged components, but it did mechanically degrade the surface of GUR 1120 tibial components to an extent comparable to that seen after 10 years of natural aging. Test specimens showed a fracture morphology consistent with the decreased ductility and toughness which was corroborated by the small punch test metrics of this study. Our data support the hypothesis that UHMWPE undergoes a spatially nonuniform change towards a less ductile (more brittle) mechanical behavior after gamma irradiation in air and shelf aging.

Neuropsychological probes of fronto-limbic system dysfunction in schizophrenia. Olfactory identification and Wisconsin Card Sorting performance.

Schizophrenic patients and normal control subjects took the University of Pennsylvania Smell Identification Test (UPSIT) and Wisconsin Card Sorting Test (WCST) as dual neuropsychological 'probes' of orbitofrontal (OF) and dorsolateral (DL) prefrontal function respectively. Patients were significantly impaired on both tasks compared to controls. UPSIT and WCST performance were uncorrelated in patients but were positively correlated in controls. The lack of correlation found in the patients suggests that the tasks may be tapping independent dysfunctions in schizophrenia reflecting differential impairment in fronto-limbic brain systems. Individual profiles of preserved and impaired performance on the UPSIT and WCST suggested that three schizophrenic patients had OF dysfunction, five had DL dysfunction and seven had a generalized (OF and DL) frontal system dysfunction. The reduced ability of schizophrenic patients to identify odors was largely independent of many deficits or confounds typically associated with schizophrenia and did not appear to be simply a function of generalized deficit. These data are preliminary and require replication with larger samples and validation with other measures of fronto-limbic system dysfunction.

The clinical utility of Tc-99m sestamibi scintimammography in detecting multicentric breast cancer.

The ability to recognize multicentric breast cancer preoperatively would assist in identifying appropriate candidates for breast conservation surgery. Tc-99m scintimammography (SMM) is an adjunct to conventional mammography in identifying selected patients with breast cancer. The purpose of this study is to report the utility of SMM in identifying patients with multicentric breast cancer. Breast cancer patients treated by mastectomy who underwent a preoperative SMM between 1992 and 1999 were identified using the institution's Tumor Registry. The pathology report of each patient was reviewed for multicentric disease defined as an additional focus of cancer within a different quadrant of the breast or greater than 2.5 cm from the dominant tumor mass. Each patient's preoperative SMM was reviewed and compared with the pathologic findings to obtain correlative data. Fifty-eight women treated by mastectomy had preoperative SMM (age range 35-78 years; median 52 years). Pathology revealed infiltrating ductal carcinoma in 49 patients (84.5%), infiltrating lobular carcinoma in five patients (8.6%), ductal carcinoma in situ in three patients (5.1%), and colloid carcinoma in one patient (1.7%). Multicentric disease was present in the specimens of eight patients for a prevalence of 10.3 per cent. SMM was positive for uptake in 36 of 58 patients (sensitivity 62.1%). The sensitivity, specificity, positive predictive value, and negative predictive value of SMM in the detection of multicentric disease were 62.5, 96, 71, and 94 per cent, respectively. Although the overall sensitivity of SMM in the detection of breast cancer is superior to that of conventional mammography and physical examination in identifying multicentric breast cancer it is not an accurate modality for detecting multicentric disease in this study group. However, it may have limited applications in specific cases.

Methionine and cystine requirements of slow- and fast-feathering male broilers from zero to three weeks of age.

Two experiments were conducted with fast- (Ross x 3F8) and slow- (Ross x 308) feathering broiler males from 0 to 3 wk of age to determine Met and Cys requirements. A corn-soybean meal basal diet was formulated to be deficient in Met and Cys but was adequate in all other nutrients (22.0% CP; 3,050 kcal ME/kg). In experiment 1, diets contained 0.50% dietary Cys with 0.35, 0.40, 0.45, and 0.50% total Met. Feed conversion (FC) of slow- and fast-feathering males improved in a similar manner to 0.50% Met (linear, P < 0.05). Nitrogen retention measured from 20 to 21 d of age optimized at 0.46% Met (quadratic, P < 0.01), regardless of feathering rate. Experiment 2 examined the response to feeding 0.35, 0.40, 0.45, and 0.50% total Cys in diets having total Met at 0.45%. Increasing Cys improved FC that optimized at 0.40% with fast-feathering birds (quadratic, P < 0.01), whereas slow-feathering broilers were not responsive. Nitrogen retention measured from d 20 to 21 did not indicate a difference attributable to feathering but a Cys optimization at 0.43% with both broiler sources. Present experimentation indicates a Met requirement approximating 0.50% is appropriate for broilers 0 to 3 wk of age, regardless of feather rate; however, the estimated Cys requirement for slow-feathering males (0.39%) was less than for fast-feathering (0.44%) males.

Methionine and cystine requirements of slow- and fast-feathering broiler males from three to six weeks of age.

Two experiments were conducted to first determine Met then Cys needs of broilers from 3 to 6 wk of age and whether differences existed between slow-feathering (Ross x 308) and fast-feathering (Ross x 3F8) males. A corn-soybean meal diet (20.0% CP; 3,150 kcal ME/kg) with graded levels of Met or Cys was offered. The first experiment had dietary Met levels of 0.32, 0.38, 0.44, and 0.50% with surfeit Cys (0.40%). Broilers from both feathering strains responded similarly to supplemental Met. Although body weight was not responsive, F/G improved through to the highest level of dietary Met (linear, P < 0.05). Chilled carcass weight increased with Met (linear, P < 0.05) paralleling F/G; however, no differences were detected in the amount of associated abdominal fat. Breast fillet yield increased with Met to maximize at 0.48% (quadratic, P < or = 0.009). In a satellite study using the same birds in cages and feeds, N retention at d 29 maximized at 0.46% Met (quadratic, P < 0.05). The second experiment had Cys at 0.32, 0.34, 0.38, and 0.46% with Met fixed at a submarginal level of 0.38%. Increasing dietary Cys had no effect on live performance of slow-feathering birds, whereas weight gain of fast-feathering birds achieved maximum at 0.36% Cys (cubic; P < 0.05) with F/G responding similarly. Chilled carcass (cubic, P < 0.002) and breast fillet weights (cubic, P < 0.001) of fast-feathering birds also increased with Cys to maximize at 0.36%, and the amount of abdominal fat was not influenced by feathering or Cys supplementation. Separate measurement of N retention at d 31 failed to detect a difference in protein utilization attributable to feathering, but an optimum was achieved at 0.40% Cys with both broiler sources. Overall results suggest that the Met requirement for broiler males between 3 and 6 wk of age was independent of feathering and approximated 0.46% (95% of the level of maximal response). Cystine requirements once corrected for submarginal Met status indicated a greater demand by fast- than slow-feathering male broilers corresponding to 0.42 and 0.37%, respectively.

A latent trait approach to the development of persistent stuttering.

The premise that stuttering disorders develop according to the orthogenetic principle, preceding in a continuous, unilinear fashion from a state of relative lack of differentiation to a state of increasing differentiation and hierarchic integration, was examined. Responses to Woolf's Perceptions of Stuttering Inventory of 87 individuals who stutter were analyzed using a Rasch 1980 latent trait model for dichotomously scored data. Analyses of responses indicated struggle, avoidance, and expectation through the development of stuttering that became increasingly articulated, integrated, stable, and yet responsive to environmental changes. Four stages of development were noted: Stage I was characterized by the expectation of interruptions in the flow of speech, the addition of unnecessary sounds, and general body tension. Stage II was typified by distinctions between troublesome and not so troublesome words and sounds and between the speaker and various audiences and contexts for speaking. In Stage III, speech control decreased despite more focused and complex efforts to control the environment and the speech apparatus. Stage IV was characterized by automatic scanning of all speech, increasingly uncontrolled body movements, and attempts to produce fluent speech by way of comprehensive changes to sound, rhythm, and pitch. Follow-up of 29 respondents suggested the latent struggle was generally stable over time.

[Personality as a predictor of therapy effectiveness in endogenous depression]. / Znaczenie osobowosci osób z depresja endogenna w procesie oddzialywan terapeutycznych.

On the basis of personality assessment (MMPI, MPI) patients with endogenous depression were shown to react differently to treatment. Women who obtained low scores on the Lie (L), Depression (D) and Repression (R) scales as well as high scores on the Psychopathic deviate (Pd) and Alcoholism (Mac) scales had better therapy outcomes. On the other hand from among men with endogenous depression those reacting better to treatment were those who obtained low scores on the Depression (D) and high scores on the Mania (Ma) scales.

[Treatment of depression with intravenous infusions of clomipramine and maprotiline]. / Leczenie depresji wlewami dozylnymi klomipraminy i maprotyliny.

28 patients aged from 31 to 69 years with endogenous depression were studied. All cases were drug-resistant i.e. they did not improve after a treatment with tricyclic antidepressants and in four cases also after electroconvulsive therapy. The group were managed with intravenous infusions of clomipramine or maprotiline followed by oral administration of the drug. Clomipramine was given i.v. at doses 75-300 mg daily for 7 to 16 days and maprotiline at 75-200 mg daily for 6 to 20 days. Remission of depressive symptoms was observed in 43% of cases and the first signs of improvement were observed on tenth day of the treatment. Tolerance to both drugs given parenterally in majority of cases was satisfactory. Half of the group did not show any untoward events. The rest of the group displayed local tissue reactions, both increased and decreased blood pressure, weakness, drowsiness, anxiety, vertigo, hyperpyretic reactions. Four patients had the treatment discontinued because of local tissue reactions or increased blood pressure or hyperpyretic reactions.

[Psychotropic profile of essential antidepressants (amitriptyline, imipramine, desipramine, chlorimipramine): comparative study]. / Badania porównawcze profilu psychotropowego podstawowych trójpierscieniowych leków przeciwdepresyjnych (amitryptyliny, imipraminy, dezypraminy, chlorimipraminy).

Comparative studies of the therapeutic activity of amitriptyline, imipramine, desipramine and chlorimipramine were studied in a group of 185 patients with endogenous depression. After standard 28-day treatment, the best results were obtained while using amitriptyline (improvement rate 67%, the greatest reduction in the Hamilton Depression Scale scored on 28-day of the treatment). The profile and characteristics of antidepressive action of all the drugs taken into consideration are comparable (including slightly more expressed sedative and deliberative effects of amitriptyline). Desinhibitive influence of desipramine and imipramine was not proved. Neither was tachythymoleptic activity of desipramine found. The study does not support the relation between the antidepressive action profile of tricyclic antidepressants and their influence on reuptake of monoamines (norepinephrine and serotonine).

[Drug resistance and various selected demographic and clinical characteristics of patients with endogenous depression]. / Zjawisko lekoopornosci a wybrane cechy demograficzne i kliniczne chorych z depresja endogenna.

The influence of some selected demographic and clinical characteristics on the formation of resistance to antidepressant drugs were studied in the group of 115 patients with affective disorders. Drug resistance occurs as frequently in women as in men. It appears much frequently in patients after 40 (about 30%). Persons under 30 are not or very rarely affected. Type I of bipolar affective disorder and the occurrence of affective disorder in relatives are positive prognostic factors. The long relapses (greater than 20 weeks) are of the worse prognostic value than shorter ones (less than 3 months). Previous poor efficiency of antidepressant drugs predicts very often an identical response during current episode. Alcohol abuse is an unfavourable prognostic factor in men with endogenous depression.

[Drug resistance in endogenous depression. Part I. Refractoriness to antidepressants in patients with depression admitted to a psychiatric clinic for the first time]. / Lekoopornosc w depresjach endogennych. Czesc I. Wystepowanie lekoopornosci u osób hospitalizowanych po raz pierwszy z powodu endogennego zespolu depresyjnego.

The efficacy of antidepressive treatment (mainly pharmacotherapy) was evaluated among 284 patients, admitted for the first time to the hospital with the diagnosis of endogenous depression. The first antidepressant therapy was found effective in 58% of the patients. Furthermore treatment with other antidepressants in the patients not responding to the initial therapy was successful in 57% of the cases. Drug resistance (defined as no therapeutical effect after 2 adequate courses of antidepressant treatment) was established in 7% of this sample. It was established that the drug resistance is more frequent after the 45th year of life. No relation between the drug resistance and sex, type of affective disorder, life events or somatic disorders were found.

[Drug resistance in endogenous depression Part II. Refractoriness to antidepressants in affective disorders]. / Lekoopornosc w depresjach endogennych Czesc II. Wystepowanie lekoopornosci w kolejnych nawrotach depresji.

Among 67 patients admitted for the first time to the hospital drug resistance was evaluated in the further course of disease for at least 3 consecutive depressive phases. It was established that drug resistance occurs (usually as a single episode) in 28% of patients with endogenous depression and it concerns 10% of all depressive phases. The drug resistance is more frequent after the 45th year of life. The incidence of therapeutic failures is 3% during the first depressive phase and goes up in the consecutive phases. The occurrence of drug resistance in the past has no prognostic value for the next phase. There is a certain subgroup of patients, characterized by repetitive drug resistance during several phases. This phenomenon needs further evaluation.

[Reaction to sleep deprivation as a prognostic factor in the treatment of endogenous depression]. / Reakcja na bezsenna noc jako czynnik prognostyczny w leczeniu depresji endogennej.

Studies conducted on a group of 38 patients with endogenous depression demonstrated that a reaction to sleep-deprivation presenting as improved well-being has a significant predictive potential for treatment with imipramine. Patients who displayed the reaction also significantly more frequently displayed improvement of clinical course (remission; good response). Risk of switching from depression to mania also increased among these patients. Patients responding to sleep-deprivation with improved well-being belonged mainly to the bipolar affective disorder. Neither clinical manifestations of depression, nor the number of relapses, nor the duration period of the disorder, nor basic demographic patterns did show distinct features; nor did they differ significantly from patients who did not respond to sleep-deprivation with improved well-being.

[Blood MAO/DBH index and the results of the treatment of endogenous depression]. / Wskaznik MAO/DBH we krwi, a wyniki leczenia depresji typu endogennego.

In the group of 115 endogenous depression patients 84 responded to tricyclic antidepressant medication and 31 remained drug-resistance. The changes of platelet MAO activity and serum DBH activity in the latter group were found. Among drug-resistant patients, 40% showed low MAO/DBH index (.6) and in 36% the index was within the medium range (.6-1.9). The low value of the index is predominantly connected with the increase of DBH and decrease of MAO activity, and it may become the potential predictive factor for the pharmacotherapy in endogenous depression. The results show the influence of the disturbances of catecholamines synthesis and degradation on the phenomenon of drug-resistance to tricyclic antidepressants.

[Clinical evaluation of fluoxetine]. / Ocena kliniczna fluoksetyny (wyniki badan wieloosrodkowych).

The multicenter trials were performed in a group of 86 depressive inpatients (among them 64 with endogenous depression) managed with fluoxetine (Prozac). It was established that the drug is most effective in managing psychogenic depressions and may also be of use in endogenous depressions, among them in drug resistant ones. Tolerance to the drug was satisfactory, 62% did not show any unwanted side-effects. The rest of the group displayed sleep disorders, increased anxiety, lost of appetite and nausea. Changes in the laboratory parameters and non-specific changes in the electrocardiogram were observed sporadically. Fluoxetine seemed not to have any direct cholinolytic effect.