High Cardiovascular Risk in Older Men with Poor Bone Microarchitecture—The Prospective STRAMBO Study

Data on the association between bone microarchitecture and cardiovascular disease (CVD) in men are scarce. We studied the link of bone microarchitecture and areal bone mineral density (aBMD) with the risk of major adverse coronary event (MACE) in a cohort of men aged 60 to 87 years followed prospectively for 8 years. At baseline, aBMD was measured using a Hologic Discovery-A device. Bone microarchitecture was assessed at distal radius and tibia by high-resolution peripheral quantitative computed tomography (XtremeCT Scanco device). During the study, 53 men had incident MACE. The analyses were adjusted for confounders related to bone and CVD. In 813 men (53 MACEs), higher aBMD at the lumbar spine, hip, whole body, and radius was associated with lower risk of MACE (hazard ratio [HR] = 0.44–0.71/SD, p < .025 to < .001). In 745 men having valid distal radius scan (47 MACEs), higher cortical density (Ct.BMD) and higher cortical thickness (Ct.Th^d) were associated with lower risk of MACE. This risk was higher in men in the lowest quintile of cortical measures versus the four upper quintiles combined (Ct.BMD: HR = 2.12, 95% confidence interval [CI] 1.08–4.17, p < .025). Findings were similar in 779 men having valid distal tibia scan (48 MACEs). At both sites, higher estimated stiffness and higher failure load were associated with a lower risk of MACE. The risk of MACE was higher in men in the lowest quintile of the measures of bone strength versus four upper quintiles jointly (distal radius stiffness: HR = 2.46, 95% CI 1.27–4.74, p < .01). Similar results were obtained in 638 men without prior fragility fracture and in 689 men without ischemic heart disease at baseline. Thus, in older men followed prospectively for 8 years, higher aBMD, preserved cortical bone status, and higher estimated bone strength were associated with lower risk of MACE after adjustment for relevant confounders. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Reliability of the assessment of disc degeneration on the lateral DXA scans

IntroductionGiven the prevalence and costs induced by osteoarthritis (OA), it is necessary to find a cheap and safe technique to evaluate it reliably.ObjectiveTo assess the value of the lateral dual energy X-ray absorptiometry (DXA) spine scans for the diagnosis of disc degeneration.MethodSeventy-seven individuals aged 18 and over, with or without disc degeneration, had both lateral thoracolumbar spine radiographs and DXA spine scans (≤ 6 months between both exams). Disc degeneration was assessed using the Lane score. The images of 20 randomly selected individuals were assessed by two readers.ResultsAlmost 13% of the thoracic levels were not assessable on the DXA scans. For the identification of the intervertebral levels on the DXA scans as interpretable or not, the intra-reader agreement was good (κ = 0.81) and the inter-reader agreement was fair (κ = 0.27–0.36). For the diagnostic criteria (osteophytes, disc space narrowing, osteosclerosis, overall grade), the intra-reader agreement was excellent for the radiographs (κ = 0.89–0.92), good for the DXA scans (κ = 0.64–0.83) and fair to moderate for the between-method comparison (κ = 0.25–0.44). The inter-reader agreement was moderate to good for the radiographs (κ = 0.49–0.66) and fair to good for the DXA scans (κ = 0.32–0.74). In the per patient analysis (the most severe grade), the intra-reader agreement was excellent for the radiographs (κ = 0.85–0.94), moderate to excellent for the DXA scans (κ = 0.53–0.85) and poor to good for the between-methods comparison (κ = 0.17–0.63).ConclusionOur results do not support the use of DXA scans for the assessment of thoracolumbar disc degeneration.     

Amperozide and clozapine but not haloperidol or raclopride increase the secretion of oxytocin in rats

The aim of the present study was to investigate whether amperozide, an antipsychotic drug which possesses anti-aggressive and anxiolytic-like properties, stimulates the secretion of oxytocin and if so, by which receptor mechanism. For this purpose, female or male Sprague Dawley rats were given amperozide (0.5, 2.5 and 5.0 mg/kg IP), ritanserin (5.0 mg/kg), raclopride (2.0 mg/kg) and prazosin (1.0 mg/kg) and were subsequently decapitated for collection of blood (30 and 120 min) after injection. Oxytocin levels were measured with radioimmunoassay. Amperozide 2.5 and 5 mg/kg increased plasma levels of oxytocin significantly (P<0.05 and <0.001). The effect appeared maximal about 30 min after injection of the drug and oxytocin levels were almost back to basal within 120 min. Similar effects were obtained in female and male rats as well as in animals that were freely fed or food deprived for 24 h. CSF levels of oxytocin were also increased. Ritanserin, a 5-HT₂-receptor antagonist but not the D₂ receptor antagonist raclopride or the ₁-adrenoceptor antagonist prazosin stimulated oxytocin release. In addition, clozapine, a neuroleptic with potent HT₂-antagonistic properties, was a potent releaser of oxytocin, whereas haloperidol was without effect. A possible role for oxytocin in the behavioural effects of amperozide and clozapine remains to be explored.     

Maspin expression is characteristic for cisplatin-sensitive ovarian cancer cells and for ovarian cancer cases of longer survival rates.

High cytoplasmic expression of maspin was described in ovarian cancers of shorter survival rates. Until now, no relationship has been described between expression of maspin and sensitivity to cisplatin in ovarian cancers. This study aimed at examining the relationship between expression of maspin, detected by immunohistochemistry and clinical response to cisplatin in ovarian cancer cases as well as the in vitro sensitivity to cisplatin of 11 ovarian cancer cell lines. The analyzes were performed on 73 samples of ovarian cancer and on A2780P, A2780RCIS, CAOV-3, EFO 21, EFO 27, ES-2, Mdah 2774, OAW 42, OVCAR-3, PA-1, and SKOV-3 ovarian cancer cells. Cytoplasmic maspin expression in studied cells significantly correlated with cisplatin sensitivity. A significantly shorter overall survival and progression-free survival was associated with lower cytoplasmic maspin expression at first-look laparotomies and nuclear maspin expression and secondary cytoreductions. Higher nuclear maspin at first-look laparotomies expression was specific for cases of complete response. In the study, the elevated expression of maspin was shown to be typical for cisplatin-sensitive ovarian cancers.     

The effective dose (Deff) for electron beams.

BACKGROUND AND PURPOSE: Calculation of the effective dose and proposal of a dose specification method for the electron beams. PATIENTS AND METHODS: In a homogenous water phantom the 3D dose distributions for electron beams of energy 6, 9, 12, 15, 18 and 21 MeV and beam size 10x10 cm were calculated. For a volume encompassed with 80, 85 and 90% isodose, the mean dose and the SD were calculated for each energy. Using the Brahme's formulae, the effective dose was calculated. RESULTS: The larger the minimum dose (value of the encompassing isodose), the larger the mean dose and the smaller the SD. The mean doses and SD to the volume encompassed with 80, 85 and 90% are in the range of 91-94%, and 5.1-6.2%, 93-96% and 4.2-4.6%, 94-96% and 3.0-3.2%, respectively. Thus the effective dose for the volume encompassed with 80, 85 and 90% are about 90, 93 and 95%, respectively. CONCLUSION: Taking into account the requirements regarding dose uniformity within the PTV and the sparing effect for normal tissue situated under the PTV, we propose to keep the 85% isodose as a minimum one and to prescribe the dose to the 90% isodose. The present method may be applied for single electron beams and typical cases.     

Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma.

BACKGROUND: A phase III trial in patients with malignant pleural mesothelioma demonstrated a survival advantage for pemetrexed plus cisplatin compared with single-agent cisplatin. Because post-study chemotherapy (PSC) may have influenced the outcome of the trial, we examined its use and association with survival. PATIENTS AND METHODS: Eighty-four patients from the pemetrexed plus cisplatin arm and 105 patients from the single-agent cisplatin arm received PSC. Kaplan-Meier survival estimates were compared by treatment groups, and by PSC and non-PSC subgroups. RESULTS: The percentage of patients receiving PSC was imbalanced between the treatment arms. Fewer pemetrexed plus cisplatin treated patients received PSC (37.2% versus 47.3%). A multiple regression analysis performed in this trial showed that PSC had a statistically significant correlation with prolonged survival (P <0.01), adjusting for baseline prognostic factors and treatment intervention. The adjusted hazard ratio for PSC over non-PSC subgroups was 0.56 (confidence interval 0.44-0.72). CONCLUSIONS: PSC in malignant pleural mesothelioma was significantly associated with prolonged survival. It is not known whether the reduced risk of death was associated with PSC or whether patients who had prolonged survival tended to receive more PSC. The pemetrexed plus cisplatin treatment group had a statistically significant survival advantage even though fewer patients from that arm of the trial received PSC. The potentially beneficial role of PSC should be assessed in prospective trials.     

Inflammatory Markers: Exhaled Nitric Oxide and Carbon Monoxide During the Ovarian Cycle

Nitric oxide (NO) production and carbon monoxide (CO) production are increased in inflammatory lung diseases. Although there are some pieces of evidence for hormonal modulation by estrogen, little is known about exhaled NO and CO during the ovarian cycle. In 23 subjects, we measured exhaled NO and CO by an online analyzer. Significantly higher levels of exhaled NO were found at the midcycle compared with those in the premenstrual period or during menstruation. Higher levels of CO were after ovulation and reached a peak in the premenstrual phase. The lowest levels of CO were observed in the first days of the estrogen phase. In males, there was no significant variation in exhaled NO and CO. Exhaled NO and CO levels vary during the ovarian cycle in women, and this fact should be taken into account during serial measurements of these markers in the female population.