Effect of insulin resistance on CAC scores in cancer survivors.

BACKGROUND: Many ca. survivors exhibit signs of IR, an important risk factor for the development of CAD. CAC scans offer a risk assessment of CV disease before cardiac damage has occurred. We investigated how IR affects CAC scores in cancer survivors. OBJECTIVES: The aim of this study was to show that CAC scores differ significantly between insulin-sensitive- and -resistant cancer survivors. METHODS: We enrolled 90 cancer survivors of a large community hospital from March 2021 to January 2022 into this pilot study. Patients were subdivided into three groups: insulin-sensitive (IS), insulin-resistant/prediabetic and insulin-resistant/diabetic. All patients received a CAC scan. RESULTS: 70% of asymptomatic survivors overall and 81% of asymptomatic IR patients show CAD on CAC scans. 17 CAC scans in the IS group, 6 CAC scans in the IR/prediabetic group and 5 CAC scans in the IR/diabetic group showed an Agatston score of 0. The p-value between the three groups was statistically significant (p = 0.005) whereas the IR/prediabetic- and the IR/diabetic group did not differ statistically from each other. The mean MESA 10-year CHD risk with CAC was 7.8. There was a highly significant difference between the 3 groups (p < 0.001). The two IR groups did not differ statistically (p = 0.076). CONCLUSIONS: Survivors with IR including prediabetes have less frequent zero CAC scores than insulin-sensitive survivors. Our study also showed that IR including prediabetes significantly increases the MESA 10-yr. CHD Risk with CAC in cancer survivors. This trial highlights the importance of screening survivors for IR and draws attention to the association of IR to CAC not only in diabetes but also in prediabetes. The high fraction of asymptomatic survivors with CAD is concerning and calls for further investigation. CAC scans are an inexpensive and efficient way of screening asymptomatic cancer survivors for CAD.

Prognostic factors in follicular lymphoma: a single institution study.

Recently developed prognostic models for follicular lymphoma have proven useful in predicting overall survival (OS), but most have used data from multiple centers. Our goal was to look at prognostic factors within a single institution. We conducted a retrospective study on 77 newly diagnosed patients with follicular lymphoma, focussing on clinical characteristics, symptom duration before diagnosis, pathologic findings, including grade, laboratory data, imaging studies at initial presentation and management. The study population was 53% male. Ages ranged from 25 to 87 years (median 51). By Ann Arbor classification 4% were stage I, 8% stage II, 18% stage III and 69% stage IV. Initial therapy was deferred in 39%. The remaining patients received stage-appropriate therapy. Survival was measured from time of diagnosis to death. Prognostic factors at initial diagnosis that were statistically significant in univariate log-rank comparisons of Kaplan-Meier survival curves were used to build a multi-variate proportional hazard regression model of OS. Median OS for these patients was 10.3 years. OS differed only with high (>12 g/dl) versus low (<12 g/dl) hemoglobin (p=0.001) and in younger (<60 years) versus older (>60 years) patients (p=0.05), as indicated by univariate log-rank tests. Both hemoglobin and age were also significant in a multivariate proportional hazards analysis. Low hemoglobin and increased age were independent predictors of lower OS with hazard ratios of 6.6 (95% CI, 2.2-20.1) and 3.7 (95% CI, 1.2-11.7), respectively. Median survival for older patients who also had anemia was only 3.1 years. A test for interaction between age and hemoglobin was negative (p=0.35). The estimated hazard ratio for an older individual with low hemoglobin was 24.7 (95% CI, 4.0-153.3). To assess the proportional hazards assumption we tested for an interaction between time and both age (p=0.92) and hemoglobin (p=0.66) and found no evidence against proportionality. A hemoglobin <12 g/dl and age >60 years at diagnosis are significant predictors of worse OS.

Low-dose gamma-interferon therapy is ineffective in renal cell carcinoma patients with large tumour burden.

The efficacy and immunomodulatory effects of low-dose gamma-interferon (gamma IFN) were investigated in an unselected population of patients with metastasising renal cell carcinoma. 36 patients suffering from metastasising renal cell carcinoma with a performance status exceeding Karnofsky index of 50 were entered into the open phase I/II trial. The majority of the patients recruited displayed a large tumour burden, and 28 patients (78%) had metastases involving two to six organ sites. Treatment was started with a 2-week cycle of either daily or weekly subcutaneous administration of either 100, 200 or 400 micrograms gamma IFN. After a therapy-free interval of 2 weeks treatment was switched to the alternate mode of administration. Subsequently, treatment was continued with the same dose applied once a week for a minimum of 3 months. Serum levels of neopterin and beta-2-microglobulin, as well as flow cytometric analyses of peripheral blood mononuclear cells, were used for the assessment of biological response. Minimal antitumour activity was observed in this high-risk patient group and only 1 patient experienced a partial response (PR) lasting 36 + months. Comparison of the patients' characteristics to those of other low-dose gamma IFN trials revealed a highly significant difference in the tumour burden and clinical response. We conclude that patient selection is a decisive parameter for the outcome of treatment with low-dose gamma IFN, and that patients with poor prognostic features and a large tumour burden are not likely to respond to this almost atoxic treatment.

Dihydrospirorenone (ZK30595): a novel synthetic progestagen--characterization of binding to different receptor proteins.

Dihydrospirorenone (6 beta, 7 beta, 15 beta, 16 beta-dimethylen-3-oxo-17a-pregn-4-en-21, 17-carbolacton) is a new type of progestin with no other agonistic activities, in particular no estrogenic, androgenic or glucocorticoid activity. Dihydrospirorenone is a potent aldosterone antagonist 8 times as potent as spironolactone and antiandrogenic (0.3 times cyproterone acetate). The aim of the present study is to make a broad characterization of dihydrospirorenone at the receptor level and to discuss the results in comparison to those of established progestins. Kinetic studies of 3H-dihydrospirorenone uptake show a rapid increase in the amount of specific binding during the first three hours. The dissociation of 3H-dihydrospirorenone from the cytoplasmic human uterine progesterone receptor, measured by displacement of labeled steroid with dextran-coated charcoal treatment at 4 degrees C at various times, showed a monophasic or one-component, first order dissociation curve like progesterone. Sucrose density gradient centrifugation of the 3H-dihydrospirorenone-labeled myometrial cytosol showed that the dihydrospirorenone binding components sedimented in the 4S and 8S region which is typical for the progesterone receptor under low salt conditions. The high binding affinity of dihydrospirorenone to the binding sites of the mineralocorticoid receptor of rat kidney with an RBA value of 230% compared to aldosterone is remarkable. This reflects the strong antimineralocorticoid activity of this compound which was evaluated in adrenalectomized rats. Furthermore, competitive studies indicated that dihydrospirorenone also displays high affinity for the androgen and some affinity for the glucocorticoid receptors but no measurable affinity for the estrogen receptor.

Assessment of alcoholism among dually diagnosed psychiatric inpatients.

Alcohol is an increasingly abused substance among psychiatric inpatients, and the extent to which alcohol dependence history is documented and the alcoholism subsequently treated is a compelling issue. This study is a retrospective review of the extent to which alcohol dependence history was obtained, and if applicable, whether a diagnosis and/or treatment plan were made, for acute psychiatric inpatients. For these purposes, an original instrument was constructed. Our results indicate that the predominant focus for acute inpatients is on diagnostic assessment of the severity of the alcohol problem, reflecting the need to deal with those issues requiring the most immediate attention. For patients with schizophrenia, attention to alcoholism diagnosis and treatment was less than that for nonschizophrenic patients. The implications of these findings are discussed with reference to the evaluation and treatment of dually diagnosed patients, along with further directions for research.

Fetal bradycardia following vibratory acoustic stimulation: a sign of distress?

In two cases the application of vibratory acoustic stimulation, at term, resulted in severe fetal bradycardia of 4 and 5 min duration. The spontaneous return to a normal fetal heart rate pattern allowed normal vaginal deliveries of healthy neonates. Transient fetal bradycardias that follow vibratory acoustic stimulation should not be regarded as an unequivocal sign of fetal distress.