Specialized Treatment Centers Research Articles

Arteriovenous Malformations in Osler-Weber-Rendu Syndrome: Pathophysiology, Clinical Manifestations, and Advances in Management

Osler-Weber-Rendu Syndrome, or Hereditary Hemorrhagic Telangiectasia (HHT), is a rare genetic disorder marked by the development of arteriovenous malformations (AVMs) throughout the body. These abnormal vascular connections bypass the capillary network, leading to significant clinical challenges. This article reviews the pathophysiology, clinical manifestations, and advances in the management of AVMs in HHT. The genetic basis of HHT involves mutations in the ENG, ACVRL1, and SMAD4 genes, which play critical roles in the TGF-β signaling pathway. These mutations result in endothelial dysfunction, contributing to the formation of AVMs. The clinical impact of AVMs is significant, particularly when they occur in the brain, lungs, liver, or gastrointestinal tract, where they can lead to life-threatening complications. This review also explores current diagnostic and management strategies, emphasizing the importance of a multidisciplinary approach. Interventional techniques such as embolization, stereotactic radiosurgery, and microsurgical resection are discussed, alongside emerging therapies like anti-angiogenic drugs and gene therapy. These advancements have led to more personalized and effective treatment plans for patients. As a result, the management of AVMs in HHT has seen significant progress, with a growing emphasis on individualized care. Continued research and the development of specialized treatment centers are crucial for further improving patient outcomes in this complex condition.

Multiple Endocrine Neoplasia Type 1: The Current Status of Disease Management.

Multiple endocrine neoplasia type 1 (MEN1) is a rare genetic disease of autosomal dominant inheritance, with an estimated prevalence of 3-20/100 000. Its main feature is neuroendocrine neoplasia in the parathyroid glands, the endocrine pancreas, the duodenum, and the pituitary gland. In this article, we review the diagnostic and therapeutic options for MEN1-associated tumors. We present an analysis and evaluation of retrospective case studies retrieved from PubMed, guidelines from Germany and abroad, and our own experience. The disease is caused by mutations in the MEN1 gene. Mutation carriers should participate in a regular, specialized screening program from their twenties onward. The early diagnosis and individualized treatment of MEN1-associated tumors can prevent the development of life-threatening hormonal syndromes and prolong the expected life span of MEN1 patients from 55 to 70 years, as well as improving their quality of life. Surgical treatment is based on the location, size, growth dynamics, and functional activity of the tumors. The evidence for treatment strategies is derived from retrospective studies only (level III evidence) and the optimal treatment is often a matter of debate. This is a further reason for treatment in specialized centers. MEN1 is a rare disease, and, consequently, the evidence base for its treatment is limited. Carriers of disease-causing mutations in the MEN1 gene should be cared for in specialized interdisciplinary centers, so that any appreciable tumor growth or hormonal activity can be detected early and organ-sparing treatment can be provided.

Drug-resistant epilepsy: Current concepts, pathogenesis, risk factors, outcomes of surgical treatment

Despite the wide choice of antiepileptic drugs (AEDs), a third of patients remain resistant to the effects of modern AEDs. Drug-resistant epilepsy (DRE) is characterized by the inability to control seizures in a patient when using at least two adequate AED regimens at an effective daily dose as monotherapy or in combination. In this case, the mechanisms responsible for drug resistance are mainly either increased excretion of AEDs by transporters from epileptogenic tissue (the multidrug transporter hypothesis) or a decrease in the sensitivity of drug receptors in epileptogenic brain tissue. It is assumed that there are other mechanisms, but they remain understudied. A number of factors are associated with the risk of DRE developing in patients with diagnosed epilepsy, including genetic, iatrogenic, brain malformations, and others. Patients with DRE have a higher probability of developing psychopathological disorders (depression, anxiety, psychosis), the proportion of which is significantly higher than in the general population. They have a 10-fold increased risk of death due to injury, cognitive decline, and sudden unexpected death in epilepsy (SUDEP). The priority treatment method for DRE is surgery. Early identification of DRE is critical for identifying potential treatment alternatives and determining whether a patient is a surgical candidate. Analysis of data from clinical and instrumental research of operated patients with DRE in the early and late postoperative period will allow us to identify factors of unfavorable outcome and to increase the effectiveness of treatment for this category of patients.The aim was to study and to summarize literature data on the pathogenesis and risk factors of drug resistance to antiepileptic drugs in patients with epilepsy, justifying the need for timely identification of drug resistance and referral of patients with drugresistant epilepsy to specialized centers for possible surgical treatment.

A clinical practice guideline for primary care physiotherapy in patients with haemophilia.

As a result of centralisation of haemophilia care to a limited number of intramural settings, many persons with haemophilia have to travel long distances to attend their haemophilia specialised treatment centre. However, regular physiotherapy treatment can be provided by primary care physiotherapists in the person's own region. Due to the rarity of the disease most primary care physiotherapists have limited experience with this population. This study aims to provide a clinical practice guideline for primary care physiotherapists working with persons with bleeding disorders. A list of the most urgent key-questions was derived from a previous study. Literature was summarised using the grading of recommendations assessment, development, and evaluation (GRADE) evidence-to-decision framework. Recommendations were drafted based on four 90min consensus meetings with expert physiotherapists. Recommendations were finalised after feedback and >80% consensus of all stakeholders (including PWH, physiotherapists, haematologists and the corresponding societies). A list of 82 recommendations was formulated to support primary care physiotherapists when treating a person with a bleeding disorder. These recommendations could be divided into 13 categories: two including recommendations on organisation of care, six on therapy for adult patients with bleeding disorders and five on therapy adaptations for paediatric care. Therapy recommendations included treatment after a joint- or muscle bleed, haemophilic arthropathy, chronic synovitis, non-haemophilia related conditions and orthopaedic surgery. An evidence-based practice guideline, based on current evidence from literature and clinical expertise, has been developed for primary care physiotherapists treating a person with haemophilia. To improve care, the recommendations should be implemented in daily practice.

Wearable device for personalized EMG feedback-based treatments

Curative effects of electromyography (EMG) feedback in treatment of various conditions and/or recovery after injuries have been earlier reported. However, wider application on EMG feedback is somehow limited due to the overall price of such systems and limited availability outside of the specialized treatment centers. Development of a personalized device for EMG feedback would be of great importance for home recovery after stroke or injuries, achieving better success in fitness and improving biofeedback-based treatments of conditions such as urinary incontinence. Despite extensive research on EMG signal collection, there is a lack of focus on in-situ EMG analysis that considers the intensity and duration of muscle activities. This gap presents the motivation for our research. In this paper, we present a methodology for the realization of wearable, rechargeable battery-powered, small-sized (90 mm × 60 mm) electronic device for recording two EMG channels (12-bits resolution, sampling frequency up to 1.6 kHz) with Bluetooth Low Energy connectivity to a smartphone. An average current consumption of 20.5 mA was experimentally determined, suggesting that multiday continuous functionality is possible. Advancing the state of the art, we propose a cross-correlation-based algorithm for in-situ dynamical computing and evaluation of muscle activation levels. This algorithm can determine if the muscle follows a predefined profile of contractions/relaxations (as needed for the treatment) and indicate if two muscles in a specific exercise were or were not engaged in proper time and with the proper intensity. The performed simulation analysis showed that the proposed approach exhibited shorter processing time compared to Morlet Wavelet Transform and Dynamic Time Warping. Finally, experimental work with five human volunteers demonstrated the reliability in EMG acquisition and signal processing. Therefore, the main contribution of this work is a cost-effective, small-sized, customizable EMG recording system with an efficient cross-correlation-based algorithm for in-situ EMG collection and processing.

The predictors of short and long term urinary continence recovery after laparoscopic radical prostatectomy: a single cancer center report in China

PurposeTo evaluate the predictors for short and long term urinary continence (UC) recovery after laparoscopic radical prostatectomy (LRP) from clinical and oncological variables.MethodsWe retrospectively collected data from 142 prostate cancer patients who underwent LRP between September 2014 and June 2021 at a tumor specialist diagnosis and treatment center in China. The rate of post-prostatectomy incontinence (PPI) was evaluated from immediate and at 3, 6 and 12 mo after LRP, and UC was defined as the use of no or one safety pad. Sixteen clinical and oncological variables were analyzed by univariate and multivariate regression analysis to determine whether they were associated with short (3 mo) or long term (12 mo) UC recovery after LRP.ResultsAfter eliminating patients who were lost to follow-up, 129 patients were eventually included. The mean ± SD age was 68 ± 6.3 years. The UC rates of immediate, 3, 6 and 12 mo after the operation were 27.9%, 54.3%, 75.2% and 88.4%, respectively. Multivariate analyses revealed that membranous urethral length (MUL) was a protective predictor of UC after catheter extraction(P < 0.001), and at 3 mo (P < 0.001), 6 mo (P < 0.001) and 12 mo (P = 0.009) after surgery.ConclusionMUL is a significant independent factor that can contribute to short and long term UC recovery post-LRP, which may assist clinicians and their patients in counseling of treatment.

Viral Load Suppression in People Living with HIV Before and During the COVID-19 Pandemic in Brooklyn, New York.

Consistent care is crucial for the health maintenance of people living with human immunodeficiency virus (HIV) (PWH). The coronavirus 2019 (COVID-19) epidemic disrupted patient care in New York City (NYC), yet few studies investigated the association between COVID-19 and viral load suppression in PWH in NYC. This study aims to assess how the COVID-19 pandemic impacted HIV viral load and CD4 + T-cell counts in PWH. Medical records of 1130 adult HIV patients who visited the Special Treatment and Research Health Center in Brooklyn, NY, between January 2019 and May 2023 were compared across three timeframes (pre-pandemic, January 1, 2019 to December 31, 2019; first pandemic phase, March 19, 2020 to December 31, 2020; and second pandemic phase, January 1, 2021 to May 11, 2023). Demographic and clinical variables (e.g. viral load and CD4 + T cell count) were assessed. About 40% of patients did not have routine laboratory monitoring during the first pandemic phase compared with pre-pandemic. The mean HIV viral load was higher during the second pandemic phase compared with pre-pandemic (p = 0.009). The percentages of patients with undetectable HIV viral load and numbers (mm3) of CD4 + T-cells were similar for all time periods. These findings indicate that the COVID-19 pandemic may have exacerbated challenges for individuals who already had barriers to medication adherence or access. However, most individuals remained consistently on their antiretrovirals throughout the pandemic. Further studies are warranted to determine how to mitigate the impact of future pandemics for the health of PWH.

Factors Associated with Primary Liver Cancer Survival in a Southern Italian Setting in a Changing Epidemiological Scenario.

A retrospective observational study utilising cancer incidence data from a population-based registry investigated determinants affecting primary liver cancer survival in a southern Italian region with high hepatitis viral infection rates and obesity prevalence. Among 2687 patients diagnosed between 2006 and 2019 (65.3% male), a flexible hazard-based regression model revealed factors influencing 5-year survival rates. High deprivation levels [HR = 1.41 (95%CI = 1.15-1.76); p < 0.001], poor access to care [HR = 1.99 (95%IC = 1.70-2.35); p < 0.0001], age between 65 and 75 [HR = 1.48 (95%IC = 1.09-2.01); p < 0.05] or >75 [HR = 2.21 (95%CI = 1.62-3.01); p < 0.0001] and residing in non-urban areas [HR = 1.35 (95%CI = 1.08-1.69); p < 0.01] were associated with poorer survival estimates. While deprivation appeared to be a risk factor for primary liver cancer patients residing within the urban area, the geographic distance from specialised treatment centres emerged as a potential determinant of lower survival estimates for residents in the non-urban areas. After balancing the groups of easy and poor access to care using a propensity score approach, poor access to care and a lower socioeconomic status resulted in potentially having a negative impact on primary liver cancer survival, particularly among urban residents. We emphasise the need to interoperate cancer registries with other data sources and to deploy innovative digital solutions to improve cancer prevention.

Total Knee Arthroplasty in People with Hemophilia: Higher Incidence of Periprosthetic Joint Infection and 1-Year Revision/Re-Operation than the General Population and Lower Prosthetic Survival When Early Postoperative Bleeding Complications Occurred: Current Literature Review.

The purpose of this narrative review of the recent literature is to analyze the outcomes, complications, and implant survival of total knee arthroplasty (TKA) carried out on people with hemophilia (PWH). It has been shown that TKA substantially alleviates preoperative pain and improves knee function and the patient's quality of life. However, the complication rates of TKA range between 8.5% and 28.7, with postoperative hemarthrosis being the most frequent (7.6%). Besides, when comparing if the TKA was implanted before or after the year 2000, a reduction was found in the rates of periprosthetic joint infection-PJI (6.2% to 3.9%) and aseptic loosening (3.8% to 2.1%). Comparing prosthesis survival between PWH who had suffered early postoperative bleeding complications (EPBC) and patients who did not suffer EBPC, the mean survival duration was 17 years for the EPBC group and 22.1 years for the non-EPBC group. Survival rates were 80% for the EPBC group and 96.4% for the non-EPBC group. Compared to patients without hemophilia, PWH had a substantially higher incidence of PJI (Odds Ratio-OR 1.6) and 1-year revision/re-operation (OR 1.4). In short, although TKA substantially improves the quality of life of PWH, it is an intervention that has a non-negligible percentage of complications. TKA in PWH should preferably be performed only in highly specialized centers for the orthopedic treatment of hemophilia.

Identification and Clinical Characteristics of Community-Acquired Acinetobacter baumannii in Patients Hospitalized for Moderate or Severe COVID-19 in Peru.

Acinetobacter baumannii has been described as a cause of serious community-acquired infections in tropical countries. Currently, its implications when simultaneously identified with other pathogens are not yet adequately understood. A descriptive study was conducted on hospitalized patients with a diagnosis of moderate/severe SARS-CoV-2-induced pneumonia confirmed via real-time RT-PCR. Patients aged > 18 years who were admitted to a specialized COVID-19 treatment center in Peru were selected for enrollment. A. baumannii was detected via the PCR amplification of the blaOXA-51 gene obtained from nasopharyngeal swabs within 48 h of hospitalization. A total of 295 patients with COVID-19 who met the study inclusion criteria were enrolled. A. baumannii was simultaneously identified in 40/295 (13.5%) of COVID-19-hospitalized patients. Demographic data and comorbidities were comparable in both Acinetobacter-positive and -negative subgroups. However, patients identified as being infected with Acinetobacter were more likely to have received outpatient antibiotics prior to hospitalization, had a higher requirement for high-flow nasal cannula and a higher subjective incidence of fatigue, and were more likely to develop Acinetobacter-induced pneumonia during hospitalization. Conclusions: The group in which SARS-CoV-2 and A. baumannii were simultaneously identified had a higher proportion of fatigue, a higher frequency of requiring a high-flow cannula, and a higher proportion of superinfection with the same microorganism during hospitalization.

Health Disparities in Young Adults: A Direct Comparison of Distress and Unmet Needs Across Cancer Centers.

Information on concerns that young adults (YAs) with cancer face when receiving care outside of specialized treatment centers is needed to increase equitable care to YAs at greater risk of marginalization by the health care system. The current study compared distress and unmet needs at the time of clinic visit between YAs receiving care from three different cancer clinics: (1) a National Cancer Institute-designated center, (2) a community-based clinic, and (3) a county hospital outpatient clinic. The Adolescent and Young Adult Psycho-Oncology Screening Tool (AYA-POST) was administered to measure distress and cancer-related concerns of YAs in active treatment. A one-way analysis of variance (ANOVA) compared distress scores by treatment site. A Fisher's exact test compared the number of participants endorsing each item on the Needs Assessment Checklist from each site. A simple linear regression determined the association between distress and number of items endorsed on the Needs Assessment Checklist. Ninety-seven participants completed the AYA-POST, endorsing, on average, 11 concerns. Fisher's exact test showed significant differences between sites in the proportion of participants endorsing eight items: boredom (P < .001), eating/appetite (P < .001), nausea/vomiting (P < .001), financial concern (P = .002), hopelessness/helplessness (P = .03), confidentiality (P = .04), sibling concern (P = .04), and insurance (P = .05). The simple linear regression model was significant (F(1, 94) = 39.772, P < .001, R2 = 0.297), indicating the number of unmet needs accounted for almost 30% of the variance in distress. The one-way ANOVA was not significant (F(2, 93) = 1.34, P = .267). Social determinants of health can influence the number and type of unmet needs experienced, affecting distress and other outcomes and underscoring the importance of timely, effective, age-appropriate screening and intervention for distress and unmet needs in YAs with cancer.

Incidence and centralization of chordoma in the Netherlands: A nationwide study between 1991 and 2020

IntroductionChordomas are rare malignant bone tumors arising in the axial skeleton, with an incidence of 0.3–0.88 per million inhabitants. We studied the annual incidence rate and centralization of treatment for chordoma in the Netherlands. MethodsWe retrieved pathology excerpts from the PALGA nationwide Dutch Pathology Registry between 1991 and 2019 for patients with a chordoma to calculate incidence rates. From pathology reports we extracted patient age at diagnosis, sex, year of diagnosis, localization of primary tumor, histologic chordoma subtype (conventional including chondroid, poorly differentiated or dedifferentiated), center of diagnosis (bone tumor referral center (BTC) or other hospital), and partial identification of the BTCs. ResultsA total of 420 individual chordoma patients were identified in the given time period. The incidence of chordoma increased from 0.593 per million inhabitants between 1991–1995 to 1.111 from 2015–2019 (P = 0.001). Median age at diagnosis was 63 years (range 1–95), 252 patients (60%) were male. The proportion of samples analyzed in a BTC either primarily or secondary, as a consultation, revision or referral, increased significantly from 29.3% to 84.4% (P < 0.001). Most primary and secondary samples were analyzed at the Leiden University Medical Center (LUMC, 54.4% and 57% respectively). ConclusionsThis study shows an increase in the standardized incidence of pathology proven chordoma in the Netherlands. We observed an increase in samples being analysed in the specialized BTCs as well, which is in line with current guidelines and will hopefully lead to more accurate diagnoses and optimal treatment plans for chordoma patients in specialized treatment centers.

PERIOPERATIVE CHEMOTHERAPY, ADJUVANT CHEMOTHERAPY AND ADJUVANT CHEMORADIOTHERAPY IN THE SURGICAL TREATMENT OF GASTRIC CANCER IN A HOSPITAL OF THE BRAZILIAN UNIFIED HEALTH SYSTEM.

Despite the preference for multimodal treatment for gastric cancer, abandonment of chemotherapy treatment as well as the need for upfront surgery in obstructed patients brings negative impacts on the treatment. The difficulty of accessing treatment in specialized centers in the Brazilian Unified National Health System (SUS) scenario is an aggravating factor. To identify advantages, prognostic factors, complications, and neoadjuvant and adjuvant therapies survival in gastric cancer treatment in SUS setting. The retrospective study included 81 patients with gastric adenocarcinoma who underwent treatment according to INT0116 trial (adjuvant chemoradiotherapy), CLASSIC trial (adjuvant chemotherapy), FLOT4-AIO trial (perioperative chemotherapy), and surgery with curative intention (R0 resection and D2 lymphadenectomy) in a single cancer center between 2015 and 2020. Individuals with other histological types, gastric stump, esophageal cancer, other treatment protocols, and stage Ia or IV were excluded. Patients were grouped into FLOT4-AIO (26 patients), CLASSIC (25 patients), and INT0116 (30 patients). The average age was 61 years old. More than 60% of patients had pathological stage III. The treatment completion rate was 56%. The pathological complete response rate of the FLOT4-AIO group was 7.7%. Among the prognostic factors that impacted overall survival and disease-free survival were alcoholism, early postoperative complications, and anatomopathological status pN2 and pN3. The 3-year overall survival rate was 64.9%, with the CLASSIC subgroup having the best survival (79.8%). The treatment strategy for gastric cancer varies according to the need for initial surgery. The CLASSIC subgroup had better overall survival and disease-free survival. The INT0116 regimen also protected against mortality, but not with statistical significance. Although FLOT4-AIO is the preferred treatment, the difficulty in carrying out neoadjuvant treatment in SUS scenario had a negative impact on the results due to the criticality of food intake and worse treatment tolerance.

Case report: role of multidisciplinary approach in a case of spine osteosarcoma with oligometastatic heart disease

Introduction. Primary spinal osteosarcoma and rare metastatic heart lesion are considered significant factors for poor prognosis. The available work indicates that combined treatment, including the radical surgery of heart solitary metastatic lesion, probably provides the best outcome.Case report. Man, 27-year-old, with Th8 spinal osteosarcoma and solitary left atrial metastasis. From October 2019 to February 2020 5 cycles of chemotherapy (high doses of platinum and doxorubicin) were carried out with positive effect. Next steps were surgery: March 2020 – spondylectomy of the Th8 vertebra with combined stabilization; September 2020 – subtotal resection with plasty of the right atrium, tricuspid valve and prosthesis of the right coronary artery. Between the first and second surgery, 4 more same chemotherapy cycles were carried out. Currently, 24 months after completion of treatment, there are no signs of the disease.Conclusion. The article presents a unique case of treatment of primary osteosarcoma and metastatic lesion of rare location. Multidisciplinary approach and combination treatment in specialized centers increase the probability of favorable outcome in such cases.

Survival Outcomes of Rural Patients with Mantle Cell Lymphoma

Background Mantle cell lymphoma (MCL) is a rare and aggressive malignancy, representing approximately 6-8% of all non-Hodgkin lymphomas, and is generally associated with poor outcomes. Patients (pts) with MCL often require intensive up-front treatment with consideration for stem cell transplant consolidation. Due to geographic limitations, pts living in rural areas with MCL may not have access to specialized treatment centers experienced in managing this rare disease. There is a paucity of data available evaluating the impact of rurality in MCL, and it is unknown how population density and access to major metropolitan centers and their healthcare systems may impact survival outcomes. Methods The National Cancer Database was used to identify MCL pts diagnosed from 2004-2020. Demographic and treatment characteristics were compared by county level measures of rurality and urban influence, categorized into metropolitan (metro), non-metropolitan urban (urban), and non-metropolitan rural (rural) counties. These data are provided from the 2013 Department of Agriculture Economic Research service data Rural-Urban Continuum Codes which uses population, population density, and commuting distance to determine these codes. Pts without rurality data or who were not treated at the reporting facility were excluded. Kaplan Meier and adjusted Cox regression survival analysis were used to compare overall survival by rural-urban codes. Results Of the 29,464 pts with MCL identified, 83.4% (N= 24,849) resided in metro counties, 14.6% (N=4,356) resided in urban counties, 1.9% (N=573) resided in rural counties. Non-metro pts were more likely to be male (70.7% male metro vs 73.0% and 72.1% for urban and rural counties, respectively), with similar age at diagnosis across county types (median age of 68 for metro pts and 69 for rural pts). Rural pts had a higher burden of comorbidities, as determined by the Charlson-Deyo comorbidity index (11.3% of rural pts with a score of 2 or greater, compared to 8.7% urban, and 7.9% of metro pts). Pts from metro counties were more likely to have private insurance (38.5% metro vs. 32.4% for urban and 28.6% for rural pts), where non-metro pts were more often uninsured (3.3% of rural, vs 2.4% of metro) or Medicare insured (61.6% rural vs 53.4% of metro pts). Notably, pts were less likely to be managed with active surveillance if they were from a rural county (4.8% vs 6.9% of metro pts), and were more likely to receive systemic disease related therapy at diagnosis (90.6% rural vs 85.2% metro). With a median follow up of 42 months, pts from metro counties had a median overall survival (OS) of 70.6 months (95% confidence interval (CI) 68.6-72.7), which was significantly longer than those from urban (61.1 months [95% CI 56.4-65.9], p&amp;lt;0.001) and rural counties (59.8 months [95% CI 54.0-65.6], p&amp;lt;0.001). The survival disparity was persistent for metro, urban, rural pts at 1-year (81%, 80%, and 78% respectively, p&amp;lt;0.001), 5-years (54%, 50%, 50% respectively, p&amp;lt;0.001) and 10-years (36%, 30%, 29% respectively, p=0.066). When referenced to pts from metro counties on Cox regression, non-metro counties had a greater risk of all-cause mortality, with hazard ratio (HR) of 1.13 (95% CI 1.08-1.18; p&amp;lt;0.001) for urban and 1.14 (95% CI 1.02-1.28; p=0.024) for rural pts. When adjusted for age and Charlson-Deyo comorbidity score this survival disparity persisted, with a HR of 1.12 (95% CI 1.07-1.17), p&amp;lt;0.001 for urban pts and HR 1.05 (95% CI 0.94-1.18), p=0.408, for rural pts, when referenced to pts from metro counties. Discussion We demonstrate a population density-based survival disparity in MCL pts, finding that pts living in more rural counties have worse survival outcomes. Rural pts had a higher comorbidity burden and were more likely to be underinsured. Additionally, they received less active surveillance, which may indicate delays in diagnosis and/or consultation with an oncologist. Given the rapidly evolving treatment landscape of MCL, these data support the need for efforts to improve healthcare access for MCL pts, such as earlier referrals to academic centers with expertise in MCL management, expanded access to telehealth, rural partnerships with academic medical centers, and programs that support patient and family travel.

PDGF, NGF, and EGF as main contributors to tumorigenesis in high-risk retinoblastoma.

Retinoblastoma (RB) is the most common form of eye cancer experienced in childhood. Its aggressive malignancy is associated with excellent survival rates in high-income countries; however, the prognosis in third-world countries is less favorable. Early diagnosis can maximize the patient's visual outcomes and their survival rate. Therapy should be conducted in highly specialized treatment centers. Intravenous chemotherapy (IVC) in bilaterally affected children currently forms the majority of therapy. Local destructive procedures and local chemotherapies such as intra-arterial chemotherapy (IAC) or intravitreal chemotherapy can be taken into consideration depending on the extent and size of the tumor. Nonetheless, children and parents remain under constant stress, revisiting doctors for medical treatment and fearing vision loss and even enucleation of the eye. Adequate molecular patient stratification to improve targeted therapy is still lacking. This retrospective study analyzed formalin-fixed paraffin-embedded specimens from a cohort of 21 RB samples. A total of 11 of those samples showed undifferentiated retinoblastoma (URB) histopathological risk features, and the other 10 showed differentiated retinoblastoma (DRB) histopathological grading. RNA from all samples was isolated and analyzed via digital gene expression patterns. Conductors of cell survival and DNA repair were dominant in the DRB samples. In contrast, the agents responsible for cell-cycle progression and apoptosis were overexpressed in URB samples. Our work reveals the importance of molecular mechanisms within the immune system subjected to histologic subtypes of RB, providing more detailed background on their genetic behavior. This is of great interest for therapeutic strategies, such as targeted immune- and gene-based therapies, for retinoblastoma.

Community-based treatment of cutaneous leishmaniasis using cryotherapy and miltefosine in Southwest Ethiopia: the way forward?

Cutaneous leishmaniasis (CL) is a common, yet massively underreported skin morbidity in Ethiopia. Most patients never seek treatment, as this is offered only in specialized treatment centers. Early diagnosis and treatment through decentralization is crucial to decrease transmission and to reach the NTD roadmap goals. However, little information is available on outcomes and challenges of community-based treatment initiatives. A community-based prospective cohort study was conducted in Ochollo. Patients with clinically or microscopy confirmed CL were included. Cryotherapy was (to be) given weekly with at least four sessions for uncomplicated lesions, and miltefosine was given for 4 weeks for complicated lesions. Miltefosine adherence was assessed by counting pill strips. Clinical and patient-reported outcomes (dermatological life quality index and patient-global assessment) were assessed at month 6 (M6). A total of 107 patients were included, with a median age of 6 years. Two patients refused, and 15 could not be treated as they were too young (<4 years) for miltefosine. Giving cryotherapy to patients weekly was not feasible due to long wound healing times and required use of topical antibiotics. Only 52.4% of miltefosine patients finished >90% of their tablets by M1. Among 46 patients treated with cryotherapy, 24 (52.2%) were cured at M6, and 9 (19.6%) had substantial improvement. The cure rate was 16/39 (41.0%) for miltefosine with 28.2% (11/39) substantial improvement. Before treatment, more than half (57.8%) of patients reported that CL did not negatively impact their life, which significantly increased to 95.2% at M6. At this time, 61.7% of patients said their lesion was clear, which was 1% before treatment. Our study is the first to identify the challenges and opportunities of miltefosine and cryotherapy for community treatment of CL. Although overall cure rates were lower than expected, patient-reported outcomes were generally positive and quite some patients had good improvement.

Comorbidity, Criminality, and Costs of Patients Treated for Gambling Disorder in Denmark

Gambling disorder is associated with increased mental comorbidity, unhealthy lifestyle, criminality, and costs-of-illness, but the available evidence is mainly based on self-reported survey data. We examined the registry-recorded mental and somatic comorbidities, medication use, criminality, and costs-of-illness associated with gambling disorder. We identified individuals diagnosed with or treated for gambling disorder in hospitals or specialized treatment centers during 2013–2017 and matched them by age and sex to general population comparisons. Using individual-level healthcare and socioeconomic registries, we characterized their history of mental and somatic comorbidities, medication use, and criminality. We estimated their cost-of-illness of welfare services (direct) and lowered productivity (indirect) using the human capital approach. We identified 1381 individuals with gambling disorder, primarily young (median age: 34 years) men (87%). Individuals with gambling disorder more frequently than their comparisons had previous hospital-recorded comorbidity [e.g., myocardial infarction (0.8% vs. 0.5%)], medication use [e.g., respiratory system drugs (35.6% vs. 28.6%)], and hospital-recorded or pharmacologically treated mental comorbidity [e.g., depression (39.8% vs. 14.9%)]. Also, sentenced criminality was much more common in individuals with gambling disorder (7.0%) than in comparisons (1.1%). The estimated attributable direct costs were €4.0 M corresponding to €2.9 K per person with gambling disorder, and attributable indirect costs were €17.6 M, corresponding to €13.2 K per person with gambling disorder in 2018. In conclusion, individuals diagnosed with or treated for gambling disorder have a high burden of mental and somatic comorbidities as well as criminality compared with the general population. This needs attention to minimize the societal and personal costs of gambling disorder.

THU218 Congenital Craniopharyngioma - Cases Recruited In The German Kraniopharyngeom Trials And Review Of The Literature

Abstract Disclosure: S. Boekhoff: None. J. Beckhaus: None. B. Bison: None. C. Friedrich: None. H.L. Muller: None. Background: Craniopharyngiomas (CP) are rare malformational tumors. Clinical presentation and outcome of patients with congenital CP (cCP) are not clear and refer mainly to few case reports in the literature. The aim of this study was to analyze clinical presentation and outcome in patients with cCP. Clinical cases: Seven hundred and nine patients diagnosed with adamantinomatous CP were recruited 1999-2021 in HIT-ENDO, KRANIOPHARYNGEOM 2000 / 2007 / Registry 2019 and prospectively observed. In 3 cases, cCP was diagnosed prenatally and in one case at the 2nd day of life. Pre- and perinatal diagnostic findings, postnatal evaluation, therapeutic interventions and outcome in these 4 cases of cCP were analyzed. When compared to cases of cCP reported in the literature, more recent cases like our reported cCP have an overall better prognosis with regard to survival and sequelae. Two of our 4 cCP suffered from hemiparesis and one patient presented with mild motor retardation. In contrast to historical reports (lethal rate of &amp;gt;50%), all patients in our report recruited after 2000 survived. Prenatal routine ultrasound examination was the usual diagnostic procedure leading to diagnosis of cCP. Tumor resection was performed during early postnatal period (range: 11 - 51 days of age). Complete resection of the mostly large sized tumors could be achieved in two of four patients with cCP. Conclusion: Based on improvements of diagnostic and therapeutical methods and techniques, earlier prenatal diagnosis of cCP should lead to intrauterine transfer of cCP patients to a specialized center for postnatal treatment of newborns with sellar masses by a multidisciplinary team to secure an improved prognosis of these patients. Presentation: Thursday, June 15, 2023

Changes in adipose tissue distribution and relation to cardiometabolic risk factors after Roux-en-Y gastric bypass in adolescents.

Roux-en-Y gastric bypass (RYGB) among adolescents with obesity results in significant weight loss; however, depot-specific changes have been understudied. We hypothesized that visceral adipose tissue (VAT) reduction in adolescents undergoing RYGB would be greater than other depots and associated with improvement in cardiometabolic risk factors. Three specialized treatment centers in Sweden. Fifty-nine adolescents underwent dual x-ray absorptiometry before surgery and at 1, 2, and 5 years after RYGB. Changes in body composition in multiple depots (total fat, lean body, gynoid fat, android fat, subcutaneous adipose tissue, and VAT) and cardiometabolic risk factors were assessed using multiple linear regression analysis and generalized estimating equations adjusting for age, sex, and baseline risk factor levels. Data are presented as percent change (95% CI) with regression models showing slopes and estimated P values. At 1 year post-RYGB, a significant reduction was observed across all body composition measures (P < .001) with the greatest reduction observed in VAT (-65.1% [-68.7, -61.8]). From year 1 to 5 years post-RYGB, a regain was observed in all depots except lean body mass (1.2% [.3, 2.7], P = .105). A sex-specific difference in overall trajectories was only observed in lean body mass with males consistently having higher mean levels. Change in VAT at 1 year correlated with change in triglycerides (slope: .21 mg/dL/kg, P = .034) and fasting plasma insulin (slope: 44 pmol/L/kg, P = .027). Adiposity measures all decreased after RYGB but poorly predicted change in cardiometabolic risk. Despite significant reductions at 1 year, a steady regain was observed out to 5 years, with values still well below baseline. Further research should consider control group comparison and extended follow-up.