In Vivo Porcine Model of Acute Iliocaval Deep Vein Thrombosis.

CLINICAL IMPACT: The study establishes a rapid, technically straightforward, and reproducible porcine large animal model for acute iliocaval deep vein thrombosis (DVT). The procedure can be performed with basic endovascular skillsets. With its procedural efficiency and consistency, the platform is promising for comparative in vivo testing of venous thrombectomy devices in a living host, and for future verification and validation studies to determine efficacy of novel thrombectomy devices relative to predicates.

Variant histology of pediatric nodular lymphocyte-predominant Hodgkin lymphoma with IgD and CD30 expression.

BACKGROUND: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), recently known as nodular lymphocyte-predominant B-cell lymphoma (NLPBL), accounts for 5%-10% of Hodgkin lymphoma (HL). Different morphologic patterns of NLPBL are identified and categorized as typical patterns (type A and B) and variant histologic patterns (types C, D, E, and F). PATIENTS AND METHOD: We investigated different morphologic patterns, CD30 and IgD expression in pediatric patients with NLPBL diagnosed at the Children's Cancer Hospital Egypt. RESULTS: Forty-six (53%) of the patients exhibited a typical histologic pattern, whereas the remaining (47%) exhibited variant histologic pattern. Variant histology is associated with unfavorable clinical characteristics, such as advanced stages, B-symptoms, and extranodal involvements, particularly bone marrow and bone infiltration, with p-values of .06, .05, and 0.01%, respectively. Additionally, 39% of patients with variant histology experienced disease progression or relapse, compared to only 15.2% of patients with typical patterns (p = .009). Types C and D are related to decreased event-free survival (EFS), as shown by a p-value of .05. The 5-year EFS for patients with variant histology was 94.4% for the rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone (RCHOP) versus 33.3% for the adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). IgD expression in lymphocyte-predominant (LP) cells was detected in 44 (50%) patients, while CD30 expression in LP cells was found in 39 (44%) patients. CONCLUSION: Variant histology of NLPBL was associated with advanced disease stages and a poor prognosis, while expression of IgD and CD30 in LP cells was not. The poor outcome of variant histology improved with the RCHOP regimen.

Chronic anti-coagulation therapy reduced mortality in patients with high cardiovascular risk early in COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with provoked thrombo-inflammatory responses. Early in the COVID-19 pandemic this was thought to contribute to hypercoagulability and multi-organ system complications in infected patients. Limited studies have evaluated the impact of therapeutic anti-coagulation therapy (AC) in alleviating these risks in COVID-19 positive patients. Our study aimed to investigate whether long-term therapeutic AC can decrease the risk of multi-organ system complications (MOSC) including stroke, limb ischemia, gastrointestinal (GI) bleeding, in-hospital and intensive care unit death in COVID-19 positive patients hospitalized during the early phase of the pandemic in the United States. METHODS: A retrospective analysis was conducted of all COVID-19 positive United States Veterans between March 2020 and October 2020. Patients receiving continuous outpatient therapeutic AC for a least 90 days prior to their initial COVID-19 positive test were assigned to the AC group. Patients who did not receive AC were included in a control group. We analyzed the primary study outcome of MOSC between the AC and control groups using binary logistic regression analysis (Odd-Ratio; OR). RESULTS: We identified 48,066 COVID-19 patients, of them 879 (1.8%) were receiving continuous therapeutic AC. The AC cohort had significantly worse comorbidities than the control group. On the adjusted binary logistic regression model, therapeutic AC significantly decreased in-hospital mortality rate (OR; 0.67, p = 0.04), despite a higher incidence of GI bleeding (OR; 4.00, p = 0.02). However, therapeutic AC did not significantly reduce other adverse events. CONCLUSION: AC therapy reduced in-hospital death early in the COVID-19 pandemic among patients who were hospitalized with the infection. However, it did not decrease the risk of MOSC. Additional trials are needed to determine the effectiveness of AC in preventing complications associated with ongoing emerging strains of the COVID-19 virus.

Voluntary deep inspiration breath-hold with volumetric modulated arc therapy in pediatric patients with mediastinal Hodgkin lymphoma.

Background: Deep inspiration breath-hold (DIBH) has been established to decrease normal tissue radiation dose in breast cancer. Methods: Forty-nine patients had two CT scans during DIBH or free breathing. Chest-wall position, setup verification and breath-hold monitoring were performed. Cone-beam CT and a surface image system were used for verification. Results: A total of 1617 breath-holds were analyzed in 401 fractions. The mean time bit was 6.01 min. The mean breaths-holds per fraction was 4.96. The median for intra-breath hold variability was 3 mm. No patient stopped treatment for intolerance. Clinical target volume margins were calculated as 0.36, 0.36 and 0.32 for the three translational positions. The mean saved volume was 26.3%. Conclusion: Voluntary DIBH is feasible, tolerable and easy to apply for children with Hodgkin lymphoma involving the mediastinum.

Deep inspiration breath-hold (DIBH) is a radiotherapy maneuver to decrease the exposure of normal tissues during the radiation of the target organ. It was developed for the treatment of breast cancer, both intact breast and chest wall, after mastectomy. For mediastinal Hodgkin lymphoma, especially in children and adolescents, DIBH will benefit in decreasing the radiation dose to the lungs and heart in this category of patients who still have normal growing tissues. We treated 49 pediatric and adolescent patients with DIBH and precise radiotherapy (volumetric modulated arc therapy) to augment the benefit of lowering the dose to normal tissues. All patients were trained and coached to breath-hold for more than 20 s. No patient stopped treatment due to poor tolerance or discomfort. Only one breath-hold was required for CT simulation in all populations (100%). The mean number of breath-holds per treatment fraction was 5.1 ± 1.8. The mean treatment time was 6 ± 1.8 min. DIBH is feasible, tolerable and easy to apply for children and adolescents with Hodgkin lymphoma involving the mediastinum. A considerable dose volume could be saved, hence decreasing the rate of side effects.

Prognostic factors affecting infantile medulloblastoma outcomes in the molecular era: a 12-year single-center experience from Egypt.

Aims: To assess the clinical, pathological and molecular characteristics (Sonic hedgehog and group 3/4 molecular subtypes expression) and treatment modalities for infantile medulloblastoma in correlation with outcomes. Materials & methods: A retrospective study of 86 medulloblastoma patients (≤3 years) was conducted. M0 patients <2.5 years received four cycles of chemotherapy followed by focal radiotherapy (FRT) and chemotherapy. Between 2007 and 2015, Metastatic patients <2.5 years received craniospinal irradiation (CSI) after the end of chemotherapy. After 2015, metastatic patients <2.5 years received CSI postinduction. Results: The hazard ratio for death was significantly higher in the FRT (HR = 2.8) group compared with the CSI group (hazard ratio = 1). Metastatic disease significantly affected the overall survival of the Sonic hedgehog group and the overall survival and event-free survival of group 3/4. Conclusion: Metastatic disease had a significant impact on outcomes. FRT is not effective in treating infantile medulloblastoma.

This study aimed to analyze the management of and prognostic factors affecting the outcomes of 86 young children (<3 years of age at presentation) diagnosed with medulloblastoma, an aggressive brain tumor that is commonly seen in this age group. All children had surgical operations aiming at resecting their tumors, followed by chemotherapy and irradiation. Study results showed that disease disseminated into the nervous system was associated with poorer outcomes compared with localized disease. Administration of local irradiation to the primary tumor site in the brain only, without exposing the spinal cord to radiotherapy, was associated with a higher risk of death.

Female Gender is a Predictor of Lower Iliac Vein Stenting Patency Rates.

BACKGROUND: Iliac venous stenting (IVS) for thrombotic and nonthrombotic venous disease is increasingly used as evidence of the safety, efficacy and durability of these interventions increases. Female gender has been implicated as a predictor of failure in arterial endovascular interventions. We hypothesize that female gender could be predictive of patency rates of iliac vein stenting. METHODS: Consecutive patients who underwent IVS for thrombotic or nonthrombotic venous disease at our institution from 2007 until 2019 were identified and divided into groups based on gender. Operative notes, venograms, and the electronic health record were then queried to obtain operative details, co-morbid conditions, postoperative outcomes and stent patency. Study outcome was long term patency rate. The data was analyzed using chi-square, logistic regression, and Kaplan-Meier analysis as appropriate. RESULTS: A total of 200 consecutive patients (231 limbs) were identified in our retrospective analysis, with a mean age of 48.8 ± 17.3, and BMI of 31.6 ± 8.6. Of those, 119 (59.5%) patients, (131 [56.8%] limbs) were female. Comparisons between the gender groups revealed no difference in age, BMI, or preoperative comorbidities. There was no difference in type of venous disease between male (85% thrombotic, 15% nonthrombotic) and female (84% thrombotic, 16% nonthrombotic), P= 0.830. The male cohort was more likely to present with leg ulceration (17% vs. 4.6%, P = 0.002), and the female cohort was more likely to present with leg edema (98.5% vs. 93.0%, P= 0.03). The male cohort had a higher rate of caval (48% vs. 33.6%, P= 0.027) and infrainguinal stent extension. (11% vs. 6.9%, P= 0.02). Females had a higher rate of left sided stenting (80.9% vs. 66/0%, P= 0.010). There was no difference in the median stent diameter used between the cohorts. Primary patency at 5 years was significantly higher for the male cohort (94.1% vs. 74.4%, P= 0.01) On adjusted multivariable cox regression female gender was a predictor of loss of primary patency within 5 years (HR, 4.04; P= 0.007). CONCLUSIONS: In this single center retrospective analysis of IVS, male patients were found to have better primary stent patency compared to female.

Poor runoff and distal coverage below the knee are associated with poor long-term outcomes following endovascular popliteal aneurysm repair.

OBJECTIVE: Reports of good short-term outcomes for endovascular repair of popliteal artery aneurysms have led to an increased use of the technique. However, data are lacking on long-term limb-related outcomes and factors associated with the failure of endovascular repair. METHODS: All patients who underwent endovascular popliteal aneurysm repair (EPAR) at a single institution from January 2006 to December 2018 were included in the study. Demographics, indications, anatomic and operative details, and outcomes were reviewed. Long-term patency, major adverse limb event-free survival (MALE-FS) and graft loss/occlusion were analyzed with multivariable cox regression analysis and Kaplan-Meier curves. RESULTS: We included 117 limbs from 101 patients with a mean follow-up of 55.6 months (range, 0.43-158 months). The average age was 73 ± 9.3 years. Thirty-two patients (29.1%) were symptomatic (claudication, rest pain, tissue loss, or rupture). The stent grafts crossed the knee joint in 91.4% of cases. In all, 36.8% of procedures used one stent graft, 41.0% used two stent grafts, and 22.2% of procedures used more than two stent grafts. The median arterial length covered was 100 mm, with an average length of stent overlap of 25 mm. Tapered configurations were used in 43.8% of cases. The majority of limbs (62.8%) had a three-vessel runoff, 20.2% had a two-vessel runoff, and 17% has a one-vessel runoff. The Kaplan-Meier estimates of graft occlusion at 1 and 3 years were 6.3% and 16.2%, respectively. The 1- and 3-year primary patency rates were 88.2% and 72.6%, and the 1- and 3-year major adverse limb event-free survival (MALE-FS) rates were 82% and 57.4%. The 1- and 3-year survival rates were 92.9% and 76.2%, respectively. On multivariable Cox regression, aneurysm size, one-vessel runoff, and coverage below the knee were associated with a lower 3-year MALE-FS. Coverage below the knee was also associated with a lower 3-year MALE-FS. Other anatomic or technical details were not associated with limb-related events or patency. CONCLUSIONS: This study is the largest single center analysis to describe the predictors of poor outcomes after EPAR. EPAR is a safe and effective way to treat popliteal artery aneurysms. Factors associated with poor MALE-FS after EPAR include single-vessel tibial runoff and coverage below the knee.

Global pediatric radiation therapy in resource-limited settings.

This report provides a summary of the global burden of childhood cancer morbidity and mortality, which disproportionately affects low- and middle-income countries as well as low- and middle-income communities within high-income countries. We review past successes and current challenges to improving clinical pediatric radiotherapy, education, and research in these regions. The Pediatric Radiation Oncology Society Taskforce in Low- and Middle-Income Countries recently outlined specific aims: (a) to increase access and quality of radiotherapy for children and adolescents afflicted with cancer; (b) to enumerate, engage, and educate a global community of providers of childhood and adolescent radiotherapy; and (c) to create evidence establishing the outcomes of setting-specific treatment standards of care when first-world standards are not achievable. This report will improve awareness of these disparities and promote attempts to correct them.

Whole lung irradiation for completely responding pulmonary metastases in pediatric Ewing sarcoma.

Aim: Scarce data assessing the real value of whole lung irradiation (WLI) in Ewing's sarcoma (ES) with lung-only metastasis, with published conflicting results. We studied the impact of WLI in a homogenous pediatric population. Materials & methods: Retrospective study evaluating the survival outcomes of WLI in these patients. Results: Out of 163 metastatic ES; 41 patients were eligible for WLI. 30 patients (73.1%) received WLI (+ve) while 11 patients (26.8%) did not receive WLI (-ve). Five-year event-free survival was statistically significant in WLI (+ve). Five-year pulmonary relapse-free survival showed trend for improvement with WLI (+ve), while 5-year overall survival was not statistically significant between the two arms. Conclusion: WLI added significantly to the long term clinical outcome of metastatic ES patients, with no irreversible toxicity.

Pediatric low grade focal brainstem glioma: outcomes of different treatment strategies and prognostic factors.

Background: This study explores the prognostic factors and outcomes of different treatment modalities in focal brain stem glioma (FBSG). Materials & methods: Pediatric FBSG patients diagnosed during 2010-2017 were retrospectively reviewed for clinical and therapeutic data. Results: A total of 71 cases were identified and the median age was 6.4 years. The 5-year overall- and progression-free survival were 74.5 and 70.6%, respectively. Radiotherapy was the main line of treatment (66.2%) and there were no survival differences between radiotherapy, chemotherapy and surveillance groups. Two independent poor prognostic factors were identified on multivariate analysis: age <8 years and cervicomedullary tumor site (p = 0.02 for both). Conclusion: Surveillance, radiotherapy and chemotherapy have comparable clinical outcomes in pediatric FBSG.

Implementation of breast cancer continuum of care in low- and middle-income countries during the COVID-19 pandemic.

Breast cancer is the most common malignancy among women worldwide. The current COVID-19 pandemic represents an unprecedented challenge leading to care disruption, which is more severe in low- and middle-income countries (LMIC) due to existing economic obstacles. This review presents the global perspective and preparedness plans for breast cancer continuum of care amid the COVID-19 outbreak and discusses challenges faced by LMIC in implementing these strategies. Prioritization and triage of breast cancer patients in a multidisciplinary team setting are of paramount importance. Deescalation of systemic and radiation therapy can be utilized safely in selected clinical scenarios. The presence of a framework and resource-adapted recommendations exploiting available evidence-based data with judicious personalized use of current resources is essential for breast cancer care in LMIC during the COVID-19 pandemic.

Correction to: Risk stratification of pediatric high-grade glioma: a newly proposed prognostic score.

The original version of this article unfortunately contained an error. The author apologizes for having provided an incorrect name: "Mohamed S. Zaghluol" should be "Mohamed S. Zaghloul". Given in this article is the correct author name.

Reconstruction of the Scapula in Pediatric and Adolescent Patients After Total Scapulectomy. A Report of 10 Patients Treated by Extracorporeal Irradiation and Reimplantation of the Scapula.

BACKGROUND: Ewing sarcoma of the scapula is uncommon. Restoration of shoulder function after total scapulectomy is challenging. Extracorporeal irradiation and reimplantation is a well-known method of biological reconstruction in orthopaedic oncology; yet very few reports in the literature describe its specific use in tumors of the scapula. PATIENTS AND METHODS: Ten patients with the diagnosis of Ewing sarcoma of the scapula were surgically treated by total scapulectomy and extracorporeal irradiation and reimplantation of the scapula. The mean age at presentation was 10 years (3 to 15 y). Six patients were male individuals and 4 were female individuals. An extracorporeal single dose of 5000 cGy was applied to each graft. At reimplantation, internal fixation was used in the first 2 cases, whereas, in the following 8 patients, stabilization was carried out by resuturing of the glenohumeral and acromioclavicular joint capsules without internal fixation. An ipsilateral Latissimus Dorsi muscle flap was used in all patients to cover the irradiated scapula. RESULTS: The mean follow-up duration was 29.2 months (13 to 50 m). At the latest follow-up, 8 patients were continuously disease free and 2 patients had systemic relapse. No patient had local recurrence. The mean musculoskeletal tumor society functional score was 87% (66.6% to 100%). Eight of the 10 patients (80%) could actively elevate the upper limb up to and beyond 90 degrees in both the forward and scapular planes. Complications included wound gaping in 2 patients (20%), dislocation of the acromioclavicular joint in 3 patients (30%), and partial resorption of the scapular graft in 5 patients (50%). No patient showed any progressive deterioration of his or her shoulder function throughout the follow-up period. CONCLUSIONS: The irradiated scapular graft provides a stable biological fulcrum for the reattached muscles of the shoulder joint after total scapulectomy, thereby providing an adequate postoperative range of shoulder elevation. A longer follow-up study is needed to evaluate the progression and effect of graft resorption on the functional outcome. LEVEL OF EVIDENCE: Level IV.

A Qualitative assessment of the impact of handedness among left-handed surgeons in Saudi Arabia.

Among Muslims, the use of the left hand in daily activities is discouraged; many people believe that left-handed physicians lack the competency for surgery. The study aim was to document the experience of left-handed surgeons in Saudi Arabia and the impact of handedness on their training, job performance, collegial relationships, and career progression. This qualitative study included 9 left-handed physicians in various surgical specialties from 4 major hospitals in Al-Qassim, Saudi Arabia. Face-to-face interviews using a semi-structured questionnaire were conducted. Interview transcripts were analysed with Qualitative Content Analysis Method. Of the participants, 78% were male and the mean age was 40 years. Twenty-two per cent were consultants, 67% were specialists, and 11% were resident physicians. Participants reported the following: (a) a lack of training programmes specific to handedness in undergraduate and postgraduate medical training, (b) inconvenience while being assisted by a right-handed colleague, (c) stress, fatigue, and physical pain due to the use of right-handed instruments, and (d) training of the right hand being the most common adaptation technique for a left-handed surgeon. It was concluded that left-handed surgeons experience difficulty with right-handed instruments and right-handed colleagues during surgery. It is recommended that clinical curriculum incorporate hand-specific training in surgery.

Atypical teratoid rhabdoid tumor in a lower middle­income country: Challenges to cure.

Atypical teratoid rhabdoid tumor (ATRT) is a rare type of potentially fatal childhood brain tumor. The present study aimed to examine the overall survival (OS) and event-free survival (EFS) outcomes of pediatric patients with ATRT and to analyze the impact of different prognostic factors, including age, sex, tumor site and size, metastatic disease, the extent of resection, radiotherapy, and chemotherapy, on survival. The present study included 47 patients with ATRT treated at the Children's Cancer Hospital of Egypt (Cairo, Egypt) between July 2007 and December 2017. These patients were treated according to the Dana-Farber Cancer Institute protocol 02-294 for 51 weeks. Various prognostic factors, including age, sex, tumor size and initial metastatic status, exhibited no impact on the radiological response measured at 6 weeks and at the end of treatment. The primary tumor site significantly affected the response to treatment at 6 weeks (P=0.008). Toxicity-related mortality occurred in 29.8% of patients. The median duration of the treatment protocol was 66.9 weeks. The duration of treatment was in the present cohort was longer than the actual 51 weeks of the protocol due to prolonged supportive care of the included patients. Patients who encountered toxicity received reduced dose of chemotherapy in the subsequent cycles in the protocol. Age, initial metastatic status, tumor site and resection extent did not significantly affect the patient outcomes. Preoperative tumor size significantly affected the EFS (P=0.03) and OS (P=0.04). Radiotherapy administration significantly affected the OS (P<0.001) and EFS (P<0.001). The median EFS and OS of patients were 9.3 and 10.3 months, respectively. A total of 24 (51.1%) patients exhibited disease progression or recurrence. The progression sites were local (n=6), metastatic (n=9) or both local and metastatic (n=9). The results of the present study demonstrated that the therapeutic regimen should be patient-adjusted to maintain the treatment intensity and avoid toxicity-related mortality. In lower middle-income countries, short and intensified induction followed by consolidation of treatment, either by single or tandem autologous stem cell transplant, is needed to avoid prolonged exposure to myelosuppression and toxicity-related mortality.

The value and safety of adjuvant radiotherapy (ART) after radical cystectomy in locally advanced urothelial bladder cancer: A controlled randomized study.

BACKGROUND: Adjuvant radiotherapy after radical cystectomy in locally advanced bladder cancer was revived after the advancement in precise radiotherapy that decreased the normal pelvic tissue radiation hazards. However, there are still scarce controlled randomized studies addressing this issue. PATIENTS AND METHODS: One hundred thirty-one cystectomized urothelial bladder cancer patients were enrolled; a hundred and twenty-two were randomized to receive adjuvant radiotherapy (ART) 50 Gy/25 fractions, 4 weeks' post-cystectomy or cystectomy alone (CY). Sixty-two were included in the ART arm and sixty in the CY arm. Twenty-four ART and 30 CY patients received Neoadjuvant chemotherapy. Eleven patients (9%) had cotenant neo-bladder diversion, 6 in ART, and 5 in CY arms. All ART patients were treated with intensity-modulated radiotherapy (IMRT) with daily verification cone-beam CT (CBCT). The median follow-up was 42.7 months. RESULTS: The 3-year adjusted Locoregional relapse-free survival (LRFS) rate was higher in the ART arm, measuring 81% (95%CI: 69-94) compared to 71% (95% CI: 60-80) (p=0.0457). ART significantly improved the locoregional relapse-free rate in the cystectomy bed and the pelvic side wall (p= 0.016 and 0.001, respectively). The overall survival, event-free, and distant metastasis-free survival did not rank to the level of statistical significance in the 2 arms. Even though the acute side effects were slightly higher in ART, the late toxicities were almost equal in the two groups. CONCLUSIONS: Adjuvant radiotherapy is safe and quite tolerable after radical cystectomy when using precise radiation techniques. These techniques significantly improved the LRFS but had insignificant improvement on the overall survival. ART did not affect the distant metastasis-free survival. Similar studies are performed in different centers around the world to confirm the value of ART in urothelial bladder cancer.

Scoliosis After Resection of Primary Pediatric Chest Wall Tumors.

BACKGROUND: Scoliosis is one of the long-term consequences of surgical resection of pediatric chest wall tumors. This study aimed to identify the risk factors associated with scoliosis development following the resection of chest wall tumors. METHODS: Retrospective cohort study of 64 children who underwent resection of malignant chest wall tumors from 2009 to 2022. Univariate and multivariate analyses were used to investigate factors associated with scoliosis development. RESULTS: The median age at the time of surgery was 7 years (range, 3-21), with 33 (51.6%) patients undergoing surgery before the age of 10 years. The most common histology was Ewing sarcoma (n = 57). A median of 3 (range, 1-5) contiguous ribs were resected. A total of 34 (53.1%) patients had anterior CWTs and 30 (46.9%) had posterior CWTs. Concomitant partial lung and diaphragmatic resection were performed in 12 patients (lung, n = 7; diaphragm, n = 5). Scoliosis convex towards the resection side developed in 21 (32.8%). The primary risk factors for scoliosis were resecting 3 or more ribs (OR 6.44) and resection of the posterior rib segment (OR 5.49). Patients with a tumor resection below 10 years old were not associated with a higher risk of scoliosis. CONCLUSIONS: Scoliosis following resection of a primary malignant pediatric chest wall tumor is associated with resection involving three or more ribs and resection of the posterior rib sector. TYPE OF STUDY: Retrospective observational. LEVEL OF EVIDENCE: IV.

Estimation of the optimal radiotherapy utilization rate for childhood neuroblastoma.

BACKGROUND AND PURPOSE: The optimal utilization rate of radiotherapy (oRUR) serves as a benchmark for assessing service demand and improving access to cancer care. While it is estimated that approximately 50 % of adult cancer patients require external beam radiotherapy during their treatment, there is a scarcity of data regarding the optimal use of radiotherapy in pediatric cancer. In this study, we adopted an established method and developed a model to estimate the oRUR in childhood neuroblastoma. MATERIALS AND METHODS: We developed a decision tree model to calculate the oRUR using indications for radiotherapy and corresponding epidemiological data collected through systematic review and meta-analysis. Sensitivity analyses were performed to evaluate the impact of variations in radiotherapy indications between treatment protocols and variables in the model. We calculated and compared the oRUR for global, high-income, and low- and middle-income settings. RESULTS: The oRUR for pediatric neuroblastoma was 64 % (95 % CI: 58 %-71 %) in the global setting, 50 % in high-income countries, and 68 % in low- and middle-income countries. The impact of variation in radiotherapy indications between major international treatment protocols was negligible. CONCLUSION: The knowledge of oRUR is crucial for evaluating current practices, identifying gaps in access, and planning future radiotherapy services for treating childhood cancer. Based on our results, 64 % of children with neuroblastoma have an indication for radiotherapy. Patients in low- and middle-income countries have more indications for radiotherapy than those in high-income countries, due to a more adverse tumour stage distribution caused by limited access to healthcare resources.

Ketosis prevents abdominal aortic aneurysm rupture through C-C chemokine receptor type 2 downregulation and enhanced extracellular matrix balance.

Abdominal aortic aneurysms (AAAs) are prevalent with aging, and AAA rupture is associated with increased mortality. There is currently no effective medical therapy to prevent AAA rupture. The monocyte chemoattractant protein (MCP-1)/C-C chemokine receptor type 2 (CCR2) axis critically regulates AAA inflammation, matrix-metalloproteinase (MMP) production, and extracellular matrix (ECM) stability. We therefore hypothesized that a diet intervention that can modulate CCR2 axis may therapeutically impact AAA risk of rupture. Since ketone bodies (KBs) can trigger repair mechanisms in response to inflammation, we evaluated whether systemic ketosis in vivo could reduce CCR2 and AAA progression. Male Sprague-Dawley rats underwent surgical AAA formation using porcine pancreatic elastase and received daily ß-aminopropionitrile to promote AAA rupture. Rats with AAAs received either a standard diet, ketogenic diet (KD), or exogenous KBs (EKB). Rats receiving KD and EKB reached a state of ketosis and had significant reduction in AAA expansion and incidence of rupture. Ketosis also led to significantly reduced aortic CCR2 content, improved MMP balance, and reduced ECM degradation. Consistent with these findings, we also observed that Ccr2-/- mice have significantly reduced AAA expansion and rupture. In summary, this study demonstrates that CCR2 is essential for AAA expansion, and that its modulation with ketosis can reduce AAA pathology. This provides an impetus for future clinical studies that will evaluate the impact of ketosis on human AAA disease.