Health-related quality of life and neurocognitive functioning in patients with recurrent glioblastoma treated with intracerebral immune checkpoint inhibition.

PURPOSE: After glioblastoma (GB) recurrence, prognosis is very cumbersome. Therefore, health-related quality of life (HRQoL) and neurocognitive functioning (NCF) have become important endpoints in clinical trials when evaluating novel treatments. We aimed to evaluate the HRQoL and NCF in patients with recurrent glioblastoma (rGB) treated with a combination of surgical intervention (reoperation or biopsy) and intracerebral immune checkpoint inhibition. METHODS: Patients who participated in the trial (N = 23), at a single-center university hospital were included. Data were collected using 3 patient-reported outcome measures (EORTC-QLQ-C30, EORTC-QLQ-BN20, and HADS) and computerized NCF testing. In the responder group, baseline values were compared to results at a 6-month follow-up. Additionally, exploratory analyses compared baseline HRQoL and NCF between responders and non-responders. RESULTS: There were five responders and 18 non-responders. When comparing the mean and individual baseline with follow-up results for the responders, we observed overall a stable to slight clinically relevant improvement of HRQoL in multiple subsets of the questionnaires while maintaining a stable NCF. One patient deteriorated on anxiety and depression symptoms from baseline to follow-up. CONCLUSIONS: In patients that responded to intracerebral immunotherapy in our institutional trial, HRQoL and NCF remained stable over time, suggesting that no detrimental effect on cognitive function or quality of life may be expected with this treatment approach. Furthermore, there seems to be an overall tendency for responders to score better on HRQoL and NCF than non-responders at baseline.

Preoperative Radiotherapy with a Simultaneous Integrated Boost Compared to Chemoradiotherapy for cT3-4 Rectal Cancer: Long-Term Results of a Multicenter Randomized Study.

BACKGROUND: Preoperative chemoradiotherapy (CRT) is the standard treatment for T3-4 rectal cancer. Here, we compared image-guided and intensity-modulated RT (IG-IMRT) with a simultaneous integrated boost (SIB) (instead of concomitant chemotherapy) versus CRT in a multi-centric randomized trial. METHODS: cT3-4 rectal cancer patients were randomly assigned to receive preoperative IG-IMRT 46 Gy/23 fractions plus capecitabine 825 mg/m² twice daily (CRT arm) or IG-IMRT 46 Gy/23 fractions with an SIB to the rectal tumor up to a total dose of 55.2 Gy (RTSIB arm). RESULTS: A total of 174 patients were randomly assigned between April 2010 and May 2014. Grade 3 acute toxicities were 6% and 4% in the CRT and RTSIB arms, respectively. The mean fractional change in SUVmax at 5 weeks after completion of preoperative RT were -55.8% (±24.0%) and -52.9% (±21.6%) for patients in the CRT arm and RTSIB arm, respectively (p = 0.43). The pathologic complete response rate was 24% with CRT compared to 14% with RTSIB. There were no differences in 5-year overall survival (OS), progression-free survival (PFS) or local control (LC). CONCLUSIONS: The preoperative RTSIB approach was not inferior to CRT in terms of metabolic response, toxicity, OS, PFS and LC, and could be considered an available option for patients unfit for fluorouracil-based CRT.

Interception of chronic medication discrepancies by the clinical pharmacist in the emergency department.

The emergency department (ED) is a high-risk setting for the occurrence of medication discrepancies (MDs) due to inconsistencies between real and documented chronic medication therapies. A clinical pharmacist (CP) improves medication safety by performing a structured medication reconciliation on ED admission. The main objective was to identify the frequency and type of MDs in the chronic medication therapy by comparing the medication displayed in the home medication module of the electronic medical record and in the genereal practitioner's (GP) referral letter with the best possible medication history by performing a structured medication reconciliation on ED admission. This prospective, monocentric, interventional study was carried out in the ED of a tertiary care university hospital in Brussels, Belgium. Inclusion criteria were patients of at least 65 years, polypharmacy, ED admission between 8 a.m. and 4 p.m. on weekdays, hospitalization and signed informed consent. During 24 days, a CP performed a structured medication reconciliation in order to obtain the best possible medication history and registered all MDs. The CP compared the best possible medication history with the home medication module and the GP's referral letter and registered the different types of MDs. Eighty-three patients were included. The median number of medications in the home medication module and the best possible medication history was significantly different {7.0 [interquartile range (IQR), 5.0-11.0] vs. 8.0 (IQR, 6.0-11.0)/patient; P < 0.0001} with a median of 5.0 (IQR, 3.0-8.0) MDs per patient. Main MDs were omission (38.8%), addition (18.4%) and a deviant administration time (15.2%). Only 22.9% of patients ( N = 19) had a GP's referral letter containing their chronic medication therapy. The median number of medications in the GP's referral letter and the best possible medication history were significantly different [6.0 (IQR, 4.0-9.0) vs. 8.0 (IQR, 7.0-11.0)/patient; P < 0.0001] with a median of 6.0 (IQR, 5.0-11.0) MDs per patient. Main MDs were omissions (39.9%), deviant frequencies (35.3%) and doses (16.7%). A CP, integrated in a multidisciplinary ED team, enhances medication safety by intercepting MDs on ED admission. Few patients possess a GP's referral letter containing their chronic medication therapy and when they do, the accuracy and completeness are poor.

Occurrence of Macular Neovascularization after Retinal Pigment Epithelium-Choroid Translocation Surgery to Treat Complicated Age-Related Macular Degeneration: Incidence, Management, and Outcome.

INTRODUCTION: This study investigates the incidence, clinical characteristics, and treatment response of macular neovascularization (MNV) occurring after retinal pigment epithelium (RPE) and choroid graft translocation surgery (RPE-choroid TS). METHODS: Retrospective analysis of 36 eyes of 36 consecutive patients who underwent RPE-choroid TS. Longer term follow-up of graft survival focusing on the occurrence of MNV was performed using multimodal imaging. RESULTS: Indications for RPE-choroid TS included complications of neovascular age-related macular degeneration in 34 patients and drusenoid pigment epithelial detachment in 2 patients. With a mean follow-up of 30 months, 8 patients out of 36 developed signs of MNV. Of these 8 patients, 4 presented with a drop in visual acuity (VA) due to centrally located type 3 MNV. Early diagnosis and treatment prevented significant functional consequences. Four patients developed type 2 MNV at the border of the graft, which did not tend to affect the VA. CONCLUSION: We report a high incidence of MNV after RPE-choroid TS. Early diagnosis and treatment may preserve function in these patients. The type of MNV and location can be used to guide the management.

Self-Reported Alcohol, Tobacco, and Cannabis Use during COVID-19 Lockdown Measures: Results from a Web-Based Survey.

BACKGROUND: The outbreak of coronavirus disease 19 (COVID-19) has led to measures of social distancing and quarantine worldwide. This stressful period may lead to psychological problems, including increases in substance use. OBJECTIVE: To investigate changes in alcohol, tobacco, and cannabis consumption before and during COVID-19 lockdown and motives for these changes in substance use. METHOD: A web-based survey was filled out by an unselected population during the social distancing measures of the COVID-19 pandemic in Belgium that assessed changes in alcohol, tobacco, and cannabis consumption in the period before and during the COVID-19 lockdown and also asked about reasons for change. RESULTS: A total of 3,632 respondents (mean age 42.1 ± 14.6 years; 70% female) filled out the survey. Overall, respondents reported consuming more alcohol (d = 0.21) and smoking more cigarettes (d = 0.13) than before the COVID-19 pandemic (both p < 0.001), while no significant changes in the consumption of cannabis were noted. The odds of consuming more alcohol during the lockdown were associated with younger age (OR = 0.981, p < 0.001), more children at home (OR = 1.220, p < 0.001), non-healthcare workers (p < 0.001), and being technically unemployed related to COVID-19 (p = 0.037). The odds of smoking more cigarettes during the lockdown were associated with younger age (OR = 0.988, p = 0.027), current living situation (p < 0.001), lower education (p = 0.015), and working situation related to COVID-19 (p = 0.018). Boredom, lack of social contacts, loss of daily structure, reward after a hard-working day, loneliness, and conviviality were the main reasons for consuming more of the various substances. CONCLUSIONS: During the lockdown, individuals consumed slightly more alcohol and smoked marginally more cigarettes compared to the period before the lockdown. Further research focussing on follow-up of individuals at risk may be useful to provide appropriate care in post-COVID times.

Introduction of the orthogeriatric co-management model increases the quality of care : a pilot study.

Traditionally, geriatric patients with musculoskeletal or osteoarticular problems will be admitted to an orthopedic ward and will be treated by sur- geons. However, these patients often suffer from comorbidities requiring geriatric management. In this study, the orthogeriatric co-management (OG- CM) model is compared to traditional orthopedic care model in a retrospective pilot study. In this study, two patients groups were compared during two similar time periods : (1) Group 1 consisted of 119 geriatric patients admitted to an orthopedic (trauma) ward who were treated, with conventional geriatric care on demand (before OG- CM ; October 1-December 31, 2013) and (2) Group 2 consisted of 132 geriatric patients who were admitted after the implementation of the OG-CM model (after OG-CM ; October 1-December 31, 2014). Outcomes measured were : quality of care outcome, mortality and costs. After the introduction of OG-CM, the number of diagnoses increased (P = 0.011) adjusting for sex, age, length of stay (LOS), urgency and getting surgery (yes/ no). However, this did not lead to a significant higher severity of illness (SOI). The number of readmissions within a year were significantly lower after OG-CM (0.31 per patient) compared to before OG-CM (0.89 per patient) (P < 0.001). No significant difference in in-house and reported mortality after 3 months was observed. Costs increased, but no significant differences were found. The OG-CM model demonstrated an increase in quality of care. This was indicated by an increased number of medical diagnoses resulting in having less readmissions, without affecting the mortality rates and the LOS. Future randomized multi-centered studies are required to enable causal relationships.

Effect of recombinant human vascular endothelial growth factor on testis tissue xenotransplants from prepubertal boys: a three-case study.

RESEARCH QUESTION: Does recombinant human vascular endothelial growth factor (VEGF-165) improve the efficiency of human immature testis tissue (ITT) xenotransplantation? DESIGN: ITT fragments from three prepubertal boys were cultured for 5 days with VEGF-165 or without (control) before xenotransplantation into the testes of immunodeficient mice. Xenotransplants were recovered at 4 and 9 months post-transplantation and vascularization, seminiferous tubule integrity, number of spermatogonia and germ cell differentiation were evaluated by histology and immunohistochemistry. RESULTS: Transplants from donor 1 and donor 2 treated with VEGF demonstrated higher vascular surface (P = 0.004) and vessel density (P = 0.011) overall and contained more intact seminiferous tubules (P = 0.039) with time, compared with controls. The number of spermatogonia was increased over time (P < 0.001) irrespective of treatment and donor, whereas, for the VEGF-treated transplants, the increase was even higher over time (P = 0.020). At 9 months, spermatocytes were present in the xenotransplants, irrespective of treatment. No transplants could be recovered from donor 3, who had already received treatment with cyclosporine for aplastic anaemia before biopsy. CONCLUSIONS: In-vitro pre-treatment of human prepubertal testis tissue with VEGF improved transplant vascularization in two out of three cases, resulting in improved seminiferous tubule integrity and spermatogonial survival during xenotransplantation. Although further studies are warranted, we suggest VEGF to be considered as a factor for improving the efficiency of immature testis tissue transplantation in the future.

Co-transplantation of mesenchymal stem cells improves spermatogonial stem cell transplantation efficiency in mice.

BACKGROUND: Spermatogonial stem cell transplantation (SSCT) could become a fertility restoration tool for childhood cancer survivors. However, since in mice, the colonization efficiency of transplanted spermatogonial stem cells (SSCs) is only 12%, the efficiency of the procedure needs to be improved before clinical implementation is possible. Co-transplantation of mesenchymal stem cells (MSCs) might increase colonization efficiency of SSCs by restoring the SSC niche after gonadotoxic treatment. METHODS: A mouse model for long-term infertility was developed and used to transplant SSCs (SSCT, n = 10), MSCs (MSCT, n = 10), a combination of SSCs and MSCs (MS-SSCT, n = 10), or a combination of SSCs and TGFß1-treated MSCs (MSi-SSCT, n = 10). RESULTS: The best model for transplantation was obtained after intraperitoneal injection of busulfan (40 mg/kg body weight) at 4 weeks followed by CdCl2 (2 mg/kg body weight) at 8 weeks of age and transplantation at 11 weeks of age. Three months after transplantation, spermatogenesis resumed with a significantly better tubular fertility index (TFI) in all transplanted groups compared to non-transplanted controls (P < 0.001). TFI after MSi-SSCT (83.3 ± 19.5%) was significantly higher compared to MS-SSCT (71.5 ± 21.7%, P = 0.036) but did not differ statistically compared to SSCT (78.2 ± 12.5%). In contrast, TFI after MSCT (50.2 ± 22.5%) was significantly lower compared to SSCT (P < 0.001). Interestingly, donor-derived TFI was found to be significantly improved after MSi-SSCT (18.8 ± 8.0%) compared to SSCT (1.9 ± 1.1%; P < 0.001), MSCT (0.0 ± 0.0%; P < 0.001), and MS-SSCT (3.4 ± 1.9%; P < 0.001). While analyses showed that both native and TGFß1-treated MSCs maintained characteristics of MSCs, the latter showed less migratory characteristics and was not detected in other organs. CONCLUSION: Co-transplanting SSCs and TGFß1-treated MSCs significantly improves the recovery of endogenous SSCs and increases the homing efficiency of transplanted SSCs. This procedure could become an efficient method to treat infertility in a clinical setup, once the safety of the technique has been proven.

Short-Term Results after Total Trapeziectomy with a Poly-L/D-Lactide Spacer.

Background Proximal migration of the first metacarpal can be seen after total trapeziectomy and various techniques have been described to prevent this subsidence. Purpose We hypothesized the insertion of a poly-L/D-lactide spacer to prevent proximal migration of the first metacarpal without the need of an additional ligament reconstruction, allowing early mobilization and less demanding rehabilitation. Patients and Methods Ten thumbs were treated with a total trapeziectomy and insertion of a poly-L/D-lactide scaffold. Clinical and radiological evaluation was performed after 6 months and 1 year. Patient satisfaction, pain, Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, mobility of the thumb, and strength were assessed. Results Pain according to the visual analog scale decreased ( p = 0.01) and QuickDASH score decreased ( p = 0.02) significantly after 1 year. Radiological evaluation after 12 months showed a collapse of the scaphometacarpal distance of 45% ( p = 0.01). Osteolysis of the distal scaphoid pole and/or proximal metacarpal was seen in 6 out of 10 cases. Because of the osteolysis, the use of the poly-L/D-lactide scaffold was discontinued in our practice. Conclusion In this limited series, total trapeziectomy with the use of the poly-L/D-lactide scaffold provides significant pain reduction and improvement of overall function. Radiographic evaluation shows significant collapse of the scaphometacarpal distance after 1 year and frequent signs of osteolysis. We do not encourage the use of the poly-L/D-lactide scaffold with total trapeziectomy before long-term clinical and radiological follow-ups of the osteolysis are available.