The Most Common Comorbidities in Dandy-Walker Syndrome Patients: A Systematic Review of Case Reports.

OBJECTIVE: Dandy-Walker syndrome (DWS) is a rare neurologic multi-entity malformation. This review aimed at reporting its main nonneurologic comorbidities. METHODS: Following PRISMA guidelines, search in Medline was conducted (2000-2014, keyword: dandy-walker). Age, sex, country, DWS type, consanguinity or siblings with DWS, and recorded coexistent conditions (by ICD10 category) were extracted for 187 patients (46.5% male, 43% from Asia) from 168 case reports. RESULTS: Diagnosis was most often set in 12 years old (27.8%). One-third of cases had a chromosomal abnormality or syndrome (n = 8 PHACE), 27% had a cardiovascular condition (n = 7 Patent Ductus Arteriosus), 24% had a disease of eye and ear (n = 9 cataract); most common malignancy was nephroblastoma (n = 8, all Asian). Almost one-fifth had a mental illness diagnosis; only 6.4% had mild or severe intellectual disability. CONCLUSION: The spread of comorbidities calls for early diagnosis and multidisciplinary research and practice, especially as many cases remain clinically asymptomatic for years

Access to health for refugees in Greece: lessons in inequalities

Eastern Greek islands have been direct passageways of (mainly Syrian) refugees to the European continent over the past year. However, basic medical care has been insufficient. Despite calls for reform, the Greek healthcare system has for many years been costly and dysfunctional, lacking universal equity of access. Thus, mainly volunteers look after the refugee camps in the Greek islands under adverse conditions. Communicable diseases, trauma related injuries and mental health problems are the most common issues facing the refugees. The rapid changes in the epidemiology of multiple conditions that are seen in countries with high immigration rates, like Greece, demand pragmatic solutions. Best available knowledge should be used in delivering health interventions. So far, Greece is failed by international aid, and cross-border policies have not effectively tackled underlying reasons for ill-health in this context, like poverty, conflict and equity of access

Genetic architecture of the acute and persistent immune cell response after radiation exposure.

Hematologic toxicity is a common side effect of multimodal cancer therapy. Nearly all animal studies investigating the causes of radiotherapy-induced hematologic toxicity use inbred strains with limited genetic diversity and do not reflect the diverse responses observed in humans. We used the population-based Collaborative Cross (CC) mouse resource to investigate the genetic architecture of the acute and persistent immune response after radiation exposure by measuring 22 immune parameters in 1,720 CC mice representing 35 strains. We determined relative acute and persistent radiation resistance scores at the individual strain level considering contributions from all immune parameters. Genome-wide association analysis identified quantitative trait loci associated with baseline and radiation responses. A cross-species radiation resistance score predicted recurrence-free survival in medulloblastoma patients. We present a community resource of immune parameters and genome-wide association analyses before and after radiation exposure for future investigations of the contributions of host genetics on radiosensitivity

Definitive high-dose, proton-based radiation for unresected mobile spine and sacral chordomas

•High-dose radiation therapy should be considered for unresected chordoma patients.•High-dose radiotherapy achieved by proton-based treatment has acceptable toxicity.•Large tumor volume is associated with worse disease-free survival post-radiotherapy. Treatment of spine and sacral chordoma generally involves surgical resection, usually in conjunction with radiation therapy.In certain locations, resection may result in significant neurological dysfunction, so definitive radiation has been used as an alternative to surgery. The purpose of this study is to report the results of high-dose, proton-based definitive radiotherapy for unresected spinal and sacral chordomas. Retrospective review of 67 patients with newly diagnosed, unresected spinal chordomas treated with high-dose definitive, proton-based radiotherapy at our center from 1975 to 2019. Reasons for radiotherapy alone included medical inoperability and/or concern for neurological dysfunction based on spine level or patient choice. Tumor locations included cervical (n = 10), thoracic (n = 1), lumbar (n = 4) spine, and sacrum (n = 52). Median maximal tumor diameter was 7.4 cm (range 1.8–25 cm). Median total dose was 77.4 Gy (RBE) (range 73.8–85.9 Gy RBE). Analysis with median follow-up of 56.2 months (range, 4–171.7 months) showed overall survival of 83.5 % (95%CI: 69.4–91.5%) and 65.9% (95%CI: 47.3–79.3%), disease-free survival of 64% (95%CI: 49.3–75.4) and 44.1% (95%CI: 27.8–59.2%), local control of 81.8% (95%CI: 67.6–90.2%) and 63.6% (95%CI: 44.7–77.5%), and distant control of 77.4% (95%CI: 63.6–86.5%) and 72.5% (95%CI: 55.7–83.8%) at 5 and 8 years respectively. The most common late side effect was insufficiency fracture. These results continue to support the use of high-dose definitive radiotherapy for patients with medically inoperable or otherwise unresected mobile spine or sacrococcygeal chordomas. There is a trend towards better disease-free survival with doses > 78 Gy (RBE)

Circulating Lymphocyte Counts Early During Radiotherapy are Associated with Recurrence in Pediatric Medulloblastoma

Background Decreased peripheral lymphocyte counts are associated with outcome after RT in several solid tumors, though appear late during or after the radiation course and often correlate with other clinical factors. Here we investigate if absolute lymphocyte counts (ALC) are independently associated with recurrence in pediatric medulloblastoma early during RT. Methods We assessed 202 medulloblastoma patients treated between 2000 and 2016 and analyzed ALC throughout therapy, focusing on both early markers (ALC during week 1 – ALC wk1; grade 3+ Lymphopenia during week 2 – Lymphopenia wk2) and late markers (ALC nadir). Uni- and multivariable regressions were used to assess association of clinical and treatment variables with ALC and of ALC with recurrence. Results Thirty-six recurrences were observed, with a median time to recurrence of 1.6 years (Range 0.2-10.3) and 7.1 years median follow-up. ALC during RT was associated with induction chemotherapy (p<0.001), concurrent carboplatin (p=0.009), age (p=0.01) and high-risk status (p=0.05). On univariable analysis, high-risk disease (HR 2.0[1.06–3.9],p=0.03) and M stage≥1 (HR 2.2[1.1–4.4]) were associated with recurrence risk, as was lower ALC early during RT (ALC wk1 HR 0.28[0.12–0.65],p=0.003; Lymphopenia wk2 HR 2.27[1.1-4.6],p=0.02). Neither baseline ALC nor nadir correlated with outcome. These associations persisted when excluding carboplatin and pre-RT chemotherapy patients, and in the multivariable analysis accounting for confounders lymphocyte counts remain significant (ALC wk1 HR 0.23[0.09–0.57],p=0.002; Lymphopenia wk2 HR 2.3[1.1–4.8],p=0.03). Conclusion ALC during weeks 1 and 2 of RT was associated with recurrence and low ALC is an independent prognostic factor in medulloblastoma. Strategies to mitigate the risk of radiation-induced lymphopenia should be considered