Venous thromboembolism in Cushing syndrome: results from an EuRRECa and Endo-ERN survey.

Background: Patients with Cushing syndrome (CS) are at increased risk of venous thromboembolism (VTE). Objective: The aim was to evaluate the current management of new cases of CS with a focus on VTE and thromboprophylaxis. Design and methods: A survey was conducted within those that report in the electronic reporting tool (e-REC) of the European Registries for Rare Endocrine Conditions (EuRRECa) and the involved main thematic groups (MTG's) of the European Reference Networks for Rare Endocrine Disorders (Endo-ERN) on new patients with CS from January 2021 to July 2022. Results: Of 222 patients (mean age 44 years, 165 females), 141 patients had Cushing disease (64%), 69 adrenal CS (31%), and 12 patients with ectopic CS (5.4%). The mean follow-up period post-CS diagnosis was 15 months (range 3-30). Cortisol-lowering medications were initiated in 38% of patients. One hundred fifty-four patients (69%) received thromboprophylaxis (including patients on chronic anticoagulant treatment), of which low-molecular-weight heparins were used in 96% of cases. VTE was reported in six patients (2.7%), of which one was fatal: two long before CS diagnosis, two between diagnosis and surgery, and two postoperatively. Three patients were using thromboprophylaxis at time of the VTE diagnosis. The incidence rate of VTE in patients after Cushing syndrome diagnosis in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Conclusion: Thirty percent of patients with CS did not receive preoperative thromboprophylaxis during their active disease stage, and half of the VTE cases even occurred during this stage despite thromboprophylaxis. Prospective trials to establish the optimal thromboprophylaxis strategy in CS patients are highly needed. Significance statement: The incidence rate of venous thromboembolism in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Notably, this survey showed that there is great heterogeneity regarding time of initiation and duration of thromboprophylaxis in expert centers throughout Europe.

Neural Stem Cells from Shank3-ko Mouse Model Autism Spectrum Disorders.

Autism spectrum disorders (ASD) comprise a complex of neurodevelopmental disorders caused by a variety of genetic defects and characterized by alterations in social communication and repetitive behavior. Since the mechanisms leading to early neuronal degeneration remain elusive, we chose to examine the properties of NSCs isolated from an animal model of ASD in order to evaluate whether their neurogenic potential may recapitulate the early phases of neurogenesis in the brain of ASD patients. Mutations of the gene coding for the Shank3 protein play a key role in the impairment of brain development and synaptogenesis in ASD patients. Experiments here reported show that NSCs derived from the subventricular zone (SVZ) of adult Shank3Δ11-/- (Shank3-ko) mice retain self-renewal capacity in vitro, but differentiate earlier than wild-type (wt) cells, displaying an evident endosomal/lysosomal and ubiquitin aggregation in astroglial cells together with mitochondrial impairment and inflammasome activation, suggesting that glial degeneration likely contributes to neuronal damage in ASD. These in vitro observations obtained in our disease model are consistent with data in vivo obtained in ASD patients and suggest that Shank3 deficit could affect the late phases of neurogenesis and/or the survival of mature cells rather than NSC self-renewal. This evidence supports Shank3-ko NSCs as a reliable in vitro disease model and suggests the rescue of glial cells as a therapeutic strategy to prevent neuronal degeneration in ASD.

Quality of life before intensive care admission: agreement between patient and relative assessment.

OBJECTIVE: To assess the agreement between patients and relatives concerning the formers' quality of life (QOL) before intensive care unit (ICU) admission. DESIGN: Prospective study involving direct interviews of patients and relatives during ICU stay. SETTING: Two four-bed surgical-medical ICUs in a 960-bed teaching hospital. PATIENTS AND METHODS: A hundred seventy-two adult, co-operative patients consecutively admitted to ICU for more than 24 h, and their relatives were interviewed. The instruments used were two questionnaires suitable for ICU patients: QOL-IT and QOL-SP. Interobserver reproducibility was investigated in 36 patients. RESULTS: Interobserver reproducibility was nearly perfect (weighted Kappa 0.99 for QOL-IT and QOL-SP). Considering global scores, weighted Kappa was 0.78 for QOL-IT and 0.82 for QOL-SP, with the mean difference between patients and relatives lower than 0.3 for both scores but with limits of agreement wider than 4. Among the items, concordance was excellent in the areas of physical activity and social life for both questionnaires. Gender, living together with the patient and the degree of relationship of relatives did not influence the agreement. CONCLUSIONS: The relatives give global scores for both instruments which can be regarded as acceptable substitutes for those given by patients. However, the wide limits of agreement should make investigators cautious in analysing together scores generated by patients and by relatives. The emotional dimension seems to be assessed less accurately by relatives than the physical one.

Validation of two quality of life questionnaires suitable for intensive care patients.

OBJECTIVE: To validate two instruments measuring quality of life (QOL) suitable for patients admitted to the intensive care unit (ICU): QOL-IT and QOL-SP. DESIGN: Prospective study using patient interviews. SETTING: Two four-bed surgical-medical ICUs in a 960-bed teaching hospital. PATIENTS AND METHODS: One hundred seventy-two adult, co-operative patients consecutively admitted to ICU for more than 24 h were interviewed. One year after hospital discharge, 84 survivors were interviewed again. Inter-observer reproducibility was investigated in 36 patients. To validate the instruments, the QOL-IT and QOL-SP scores reported by patients were considered according to the functional limitation evaluated by the interviewer. Moreover, the theoretical prediction that patients with chronic diseases should have a worse QOL before ICU admission than patients with only acute illness was tested. QOL-IT and QOL-SP scores given 1 year after hospital discharge were compared with those recorded at the first interview. RESULTS: Inter-observer reproducibility was excellent. The possible range of QOL-IT is 0-20 and that of QOL-SP 0-29. According to the functional limitation (absent, mild or severe), the median QOL-IT score increased from 3 to 6 to 13 and QOL-SP from 2 to 6 to 12 (p< 0.0001). The patients with chronic diseases gave scores significantly higher than the patients with only acute illness (median QOL-IT 8 versus 3, p< 0.013; QOL-SP 8 versus 4, p< 0.004). The median QOL-IT score changed from 3 to 4 one year after hospital discharge, a difference which is statistically (p< 0.001), but not clinically, significant. The median QOL-SP score was 3 and did not change. CONCLUSIONS: QOL-IT and QOL-SP are instruments able to discriminate between different health states.

[Reproduction of the anatomy (offset, CCD, leg length) with a modern short stem hip design--a radiological study]. / Postoperative Veränderungen von Offset, CCD-Winkel und Beinlänge nach Implantation einer metadiaphysär fixierten Kurzschaftprothese--eine radiologische Untersuchung.

AIM: The purpose of the study was to analyse different parameters before and after implantation of a modern short-stem hip design. MATERIAL AND METHODS: In this prospective radiological study 250 consecutive hips with degenerative hip osteoarthritis were included (246 patients). The patients were operated by five different surgeons at 4 different hospitals and a metadiaphysial fixed short-stem prothesis (Mini Hip, Corin) was used. Standardised X-rays were performed with the same technique pre- and postoperatively in all patients. Different anatomic parameters of the hip were documented by using the pre- and postoperative Xrays (ofset, CCD angle, length of leg). All measurements were performed by an independent examiner. The 246 patients included 129 females and 117 males. The average age of the patients was 59.7 years (range: 27-82 years). RESULTS: The offset only changed by + 0.28 cm (SD: 0.45 cm) after surgery. We could document only a small decrease of -0.51° (SD: 4.10°) of the CCD angle. The length of the leg increased on average by + 0.09 cm (SD: 0.34 cm). We found no difference between the measurements of female and male patients. Conspicuous was also the increasing use of small protheses (size 2) for hips with a small CCD angle and the increasing implantation of large protheses (size 9) in hips with a high CCD angle. CONCLUSION: Our results showed that we could reconstruct the individual geometry of the hip quite well by using the metadiaphysial short-stem prothesis. The tendency of an increasing CCD angle and a decrease of the offset seems not to be existent with the design of this kind of short-stem prothesis.