A Novel HR-pQCT Image Registration Approach Reveals Sex-Specific Changes in Cortical Bone Retraction With Aging

During aging, changes in endosteal and periosteal boundaries of cortical bone occur that differ between men and women. We here develop a new procedure that uses high-resolution peripheral quantitative CT (HR-pQCT) imaging and 3D registration to identify such changes within the timescale of longitudinal studies. A first goal was to test the sensitivity of the approach. A second goal was to assess differences in periosteal/endosteal expansion over time between men and women. Rigid 3D registration was used to transform baseline and all follow-up (FU) images to a common reference configuration for which the region consisting of complete slices (largest common height) was determined. Periosteal and endosteal contours were transformed to the reference position to determine the net periosteal and endosteal expansion distances. To test the sensitivity, images from a short-term reproducibility study were used (15 female, aged 21 to 47 years, scanned three times). To test differences between men and women, images from a subset of the Geneva Retirees Cohort were used (248 female, 61 male, average age 65 years, 3.5 and 7 years FU). The sensitivity study indicated a least significant change for detecting periosteal/endosteal expansion of 41/31 microns for the radius and 17/26 microns for the tibia. Results of the cohort study showed significant net endosteal retraction only in females at the radius and tibia after 3.5 years (38.0 and 38.4 microns, respectively) that further increased at 7 years FU (70.4 and 70.8 microns, respectively). No significant net periosteal changes were found for males or females at 7 years. The results demonstrate that it is possible to measure changes in endosteal contours in longitudinal studies within several years. For the investigated cohort, significant endosteal retraction was found in females but not in males. Whether these changes in cortical geometry are related to fracture risk remains to be investigated in larger cohorts © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Influence of HRT on prognostic factors for breast cancer: a systematic review after the Women's Health Initiative trial

INTRODUCTION: Mortality due to breast cancer has been reported to be the same or even lower in HRT users than in non-users. This has been attributed to earlier diagnosis and to better prognosis. Nevertheless, more advanced disease in HRT users was reported recently by the Women's Health Initiative (WHI) study. The objective of this study was to assess, using a systematic review of current literature, whether the data of the WHI study are in contradiction to observational data. METHODS: We selected 25 studies, for which we evaluated the methodology, the characteristics of the studied populations, confounding breast cancer risk factors and prognostic indicators. RESULTS: The WHI study, showing a worsening of some prognostic parameters, is in contradiction to most published observational studies. Most observational studies are retrospective, not well matched and did not consider most confounding factors. Their methodology and selection criteria varied considerably and the number of patients was often small. No differences in the distributions of histology, grade or steroid receptors were observed in the WHI trial, while this was the case in some of the observational studies. Other parameters (S phase, protein Neu, Bcl-2 gene, protein p53 and E-cadherin, cathepsin D) were not reported in the WHI trial. CONCLUSIONS: In view of these data, the current clinical message to patients should be changed: one can no longer declare that breast cancers developed while using HRT are of better prognosis.     

Protein tyrosine kinase activity in 350 T1/T2, N0/N1 breast cancer. Preliminary results

Protein tyrosine kinases (PTKs) are a family of enzymes sharing a highly conserved catalytic domain which phosphorylates substrate proteins on tyrosine residues. PTKs play a major role in the transduction of the mitogenic signal and are involved in the control of cell proliferation, differentiation, and transformation processes. PTKs can be subdivided into two major types: membrane associated PTKs consisting essentially of growth factor receptors (receptor tyrosine kinases or RTKs) and cytosolic PTKs involved in the intracellular transduction of mitogenic and differentiation signals. From January 1988 to January 1992, PTK activity was assayed in cytosolic fractions prepared from 350 T1-T2, N0-N1 M0, breast carcinomas. Enzymatic activity was measured using phosphate transfer from [³²P]-ATP to poly-Glu-Tyr as an artificial substrate. According to our previously reported pilot study, we chose a cut-off value of 12 pmol³²P incorporated min^–1 mg^–1 protein, corresponding to the median value. We found positive PTK levels ( 12 pmol/min/mg) to be correlated with a loss of differentiation according to Scarff-Bloom grade (p < 0.001), negative PR (p = 0.03) and ER status (p = 0.04). With a median follow-up of 30 months (0–82), patients with a positive PTK level presented a smaller 3-year disease free survival than in the PTK negative group of patients (p = 0.07). In Cox multivariate analysis including pT, pN, Scarff-Bloom grade, PR and ER, PTK activity does not emerge as a significant prognostic factor.     

How to optimize physicians' communication skills in cancer care: results of a randomized study assessing the usefulness of posttraining consolidation workshops.

PURPOSE: Although there is wide recognition of the usefulness of improving physicians' communication skills, no studies have yet assessed the efficacy of post-training consolidation workshops. This study aims to assess the efficacy of six 3-hour consolidation workshops conducted after a 2.5-day basic training program. METHODS: Physicians, after attending the basic training program, were randomly assigned to consolidation workshops or to a waiting list. Training efficacy was assessed through simulated and actual patient interviews that were audiotaped at baseline and after consolidation workshops for the consolidation-workshop group, and approximately 5 months after the end of basic training for the waiting-list group. Communication skills were assessed according to the Cancer Research Campaign Workshop Evaluation Manual. Patients' perceptions of communication skills improvement were assessed using a 14-item questionnaire. RESULTS: Sixty-three physicians completed the training program. Communication skills improved significantly more in the consolidation-workshop group compared with the waiting-list group. In simulated interviews, group-by-time repeated measures analysis of variance showed a significant increase in open and open directive questions (P =.014) and utterances alerting patients to reality (P =.049), as well as a significant decrease in premature reassurance (P =.042). In actual patient interviews, results revealed a significant increase in acknowledgements (P =.022) and empathic statements (P =.009), in educated guesses (P =.041), and in negotiations (P =.008). Patients interacting with physicians who benefited from consolidation workshops reported higher scores concerning their physicians' understanding of their disease (P =.004). CONCLUSION: Consolidation workshops further improve a communication skills training program's efficacy and facilitate the transfer of acquired skills to clinical practice.     

Treatment of External Auditory Canal Exostoses

Exostoses of the external auditory canal can occur in patients living in coastal, southern California communities with a history of cold-water aquatic activities such as ocean surfing and swimming. Although most canal exostoses are asymptomatic, patients with canal obstruction greater than 80% can have recurrent episodes of external otitis and a related conductive hearing loss. In most cases, medical treatment resolves the symptomatic external otitis and related hearing loss. Patients recalcitrant to medical treatment are candidates for surgical removal of the exostoses. This report reviews the authors' surgical experience with 18 patients (27 ears) who have undergone surgical removal of exostoses. Their preferred surgical technique of transmeatal removal of exostoses with a specialized mallet and thin chisel under local anesthesia is described.     

Wait Times and Survival in Lung Cancer Patients across the Province of Quebec,Canada

Lung cancer is the leading cause of cancer death worldwide, with a five-year survival of 22% in Canada. Guidelines recommend rapid evaluation of patients with suspected lung cancer, but the impact on survival remains unclear. We reviewed medical records of all patients with newly diagnosed lung cancer in four hospital networks across the province of Quebec, Canada, between 1 February and 30 April 2017. Patients were followed for 3 years. Wait times for diagnosis and treatment were collected, and survival analysis using a Cox regression model was conducted. We included 1309 patients, of whom 39% had stage IV non-small cell lung cancer (NSCLC). Median wait times were, in general, significantly shorter in patients with stage III–IV NSCLC or SCLC. Surgery was associated with delays compared to other types of treatments. Median survival was 12.9 (11.1–15.7) months. The multivariate survival model included age, female sex, performance status, histology and stage, treatment, and the time interval between diagnosis and treatment. Longer wait times had a slightly protective to neutral effect on survival, but this was not significant in the stage I–II NSCLC subgroup. Wait times for the diagnosis and treatment of lung cancer were generally within targets. The shorter wait times observed for advanced NSCLC and SCLC might indicate a tendency for clinicians to act quicker on sicker patients. This study did not demonstrate the detrimental effect of longer wait times on survival.     

No Association between Vitamin D and Weight Gain: A Prospective,Population-Based Study

Background: The association between vitamin D and weight gain remains controversial due to important limitations in the studies. We investigated the relationship between vitamin D levels and 5 and 10 years of weight and waist circumference change in a population-based prospective cohort study. Methods: Prospective study including participants aged between 35 and 75 years living in the city of Lausanne, Switzerland. Weight and waist change at 5- and 10-year follow-up were assessed according to baseline vitamin D status (normal, insufficiency and deficiency). Results: A total of 3638 participants (47.9 % women, mean age 51.6 ± 10.4 years) were included for the 5-year follow-up. No association was found between vitamin D categories and weight change, multivariate-adjusted average ± standard error: 1.6 ± 0.3, 1.5 ± 0.2 and 1.2 ± 0.1 kg for normal, insufficiency and deficiency, respectively, p = 0.159. For waist change, the corresponding values were 3.3 ± 0.4, 3.3 ± 0.2 and 3.4 ± 0.2 cm, p = 0.792. For the 10-year follow-up, data from 2999 participants (45.8% women, mean age 50.8 ± 10.3 years) were used. No association was found for weight 2.3 ± 0.4, 2.3 ± 0.2 and 2.0 ± 0.2 kg, p = 0.588, or for waist 3.7 ± 0.4, 3.6 ± 0.3 and 4.2 ± 0.2 cm for normal, insufficiency and deficiency, respectively, p = 0.259. Conclusion: No association between vitamin D status and weight or waist gain at 5- and 10-year follow-up was found.     

Acute hepatitis associated with treatment of Peyronie's disease with potassium para-aminobenzoate (Potaba)

IntroductionPotassium para‐aminobenzoate is an agent used in the treatment of sclerotic diseases including Peyronie's disease of the penis. It has been reported that this medication may have been responsible for cases of acute liver injury.AimTo inform clinicians of the possibility of an adverse drug event associated with the oral intake of potassium para‐aminobenzoate by reporting an additional case and compiling information from previous reports.MethodsThe affected patient's medical records were diligently reviewed; all available and relevant information pertaining to this adverse event is reported. Similar case reports were analyzed and compared, and relevant information was compiled in this report.ResultsThe patient enjoyed a full biochemical recovery from his hepatitis 4 months after discontinuation of potassium para‐aminobenzoate.ConclusionTo date, the oral use of potassium para‐aminobenzoate has been reported to be linked to acute liver injury in six individuals. Appropriate management of this adverse drug event is the immediate discontinuation of the offending drug and general patient support measures. Roy J, and Carrier S. Acute hepatitis associated with treatment of Peyronie's disease with potassium para‐aminobenzoate (Potaba). J Sex Med **;**:**–**.     

Furan oligomers and beta-carbolines from terrestrial streptomycetes

2,5-Bis(hydroxymethyl)furan monoacetate (3) and 2,5-bis(hydroxymethyl)furan diacetate (4) were obtained as new natural products from an ethyl acetate extract of the terrestrial Streptomyces sp. isolate GW11/1695. Another Streptomyces isolate, GW21/1313, delivered a dimer (6) and a trimer (7) of (hydroxymethyl)furfural. The latter strain also produced 4-hydroxy-2-(5-(hydroxymethyl)furan-2-ylmethylene)-5-methylfuran-3-one (5), perlolyrin (8), and two new beta-carboline derivatives, 9 and 10. 2,5-Bis(hydroxymethyl)furan diacetate (4) exhibited weak cytotoxic activity against brine shrimp larvae.     

Hualyzin, a symmetrical urea derivative isolated from Penicillium herquei isolate GA4

Penicillium herquei isolate GA4 was isolated from the infected Conchocelis of Porphyra yezoensis. A large-scale fermentation using yeast extract sucrose medium and repeated chromatography afforded a new symmetrical urea derivative, hualyzin (1). The structure was determined by detailed NMR spectroscopic investigations and MS fragmentation analysis.