Treatment-related Complications Research Articles

Clinical and Immune Effects of Peri-Transplantation JAK Inhibition for Myelofibrosis.

Despite the introduction of JAK inhibitors, allogeneic hematopoietic cell transplant remains the only potentially curative treatment for patients with myelofibrosis but has considerable treatment-related complications. Whether the incorporation of JAK inhibition into the transplant algorithm leads to improved outcomes is still unclear. Here, we analyzed different transplant platforms in myelofibrosis patients undergoing a first transplant, comparing immune profiles and outcomes of (1) 33 patients continuing JAK inhibition at start of conditioning until stable engraftment (PERI-group), (2) 38 patients receiving JAK inhibition prior to transplant until start of conditioning (PRE-group), and (3) 38 patients that had never received JAK inhibition (NON-group). Patients in the PERI-group showed significantly higher early B-cell recovery as well as significantly increased late recovery of gamma-delta T cells and NK cells. We observed excellent neutrophil and platelet engraftment (100% for both) in the PERI-group and no hematotoxic effects or increased rates of infections following peri-transplant JAK inhibition. Cumulative incidence of acute graft-versus-host disease (GvHD) grade II-IV at day 100 after transplant was 15% in the PERI-group versus 29% in the PRE-group versus 34% in the NON-group. Cumulative incidence of relapse at 1 year after transplant was 9% in the PERI-group compared with 16% in the PRE-group and 18% in the NON-group. In conclusion, peri-transplant JAK inhibition was feasible with promising engraftment and acute GvHD rates, though deserves further investigation.

RADT-23. MOLECULAR PROFILING OF GLIOMAS: INSIGHTS INTO RADIONECROSIS AND PSEUDOPROGRESSION THROUGH NEXT-GENERATION SEQUENCING

Abstract BACKGROUND Gliomas, the most common primary tumors of the CNS, presenting diagnostic and therapeutic challenges due to their heterogeneity. Next-generation sequencing (NGS) enhances diagnostic precision by identifying genetic alterations, guiding accurate diagnosis and personalized treatment strategies. Post-treatment complications such as radionecrosis and pseudoprogression present additional diagnostic difficulties, often mimicking tumor recurrence. This study aimed to evaluate the association between genetic alterations detected by NGS and treatment-related complications. METHODS This retrospective study analyzed data from electronic medical records at a Brazilian Radiation Therapy Department (2018-2023). The study included patients with gliomas who underwent surgical resection followed by adjuvant radiochemotherapy and subsequently developed complications such as radionecrosis and pseudoprogression. Genetic alterations detected by the HSL 500 (NGS) test were evaluated for their association with these complications using Fisher’s Exact Test. RESULTS Out of 192 patients treated for glioma, 46 (23.96%) experienced treatment-related complications, with 20 patients having available NGS test results. Among these, eight cases were identified as pseudoprogression, fifteen as radionecrosis, with three patients presenting both conditions. All 20 patients with NGS results were diagnosed with high-grade gliomas, eight of whom underwent reirradiation, resulting in two cases of radionecrosis post-reirradiation. Although no statistically significant association was found between genetic alterations and radionecrosis or pseudoprogression, specific mutations were prevalent in each group. In radionecrosis cases, the most common mutations were TERT promoter (c.1-124C>T) (n=9, p=0.613) and EGFR amplification (n=8, p=1.0). In pseudoprogression, frequent mutations included TERT promoter (c.1-124C>T) (n=6, p=0.642), EGFR (n=5, p=0.67), PTEN (n=4, p=1.0), NF1 (n=2, p=0.537), and P53 (n=2, p=0.197). CONCLUSION Molecular testing for glioma characterization is crucial for diagnosis and prognosis, aiding in understanding treatment-related complications. Strategies to avoid radionecrosis and pseudoprogression are vital to improve patient quality of life, especially in high-grade gliomas. Further studies are needed to confirm these trends and explore clinical relevance of mutations.

Long-Term Adverse Effects and Complications After Prostate Cancer Treatment

Due to the often indolent nature of prostate cancer (PCA), treatment decisions must weigh the risks and benefits of cancer control with those of treatment-associated morbidities. To characterize long-term treatment-related adverse effects and complications in patients treated for PCA compared to a general population of older males. This cohort study used a novel approach linking data from 2 large PCA prevention clinical trials (the Prostate Cancer Prevention Trial and the Selenium and Vitamin-E Cancer Prevention Trial) with Medicare claims records. This analysis included patients with PCA who had been treated with prostatectomy or radiotherapy compared with an untreated control group. Multivariable Cox regression was used, with a time-varying covariate for the occurrence of PCA treatment, adjusted for age, race, and year of time-at-risk initiation, and stratified by study and intervention arm. Data analyses were performed from September 21, 2022, to March 18, 2024. Prostatectomy and radiotherapy occurring after a PCA diagnosis, identified from trial data or Medicare claims records. Ten potential PCA treatment-related complications identified from Medicare claims data. The study sample comprised 29 196 participants (mean [SD] age at time-at-risk initiation, 68.7 [4.8] years). Of these, 3946 participants had PCA, among whom 655 were treated with prostatectomy and 1056 with radiotherapy. The 12-year hazard risk of urinary or sexual complications was 7.23 times greater for those with prostatectomy (95% CI, 5.96-8.78; P < .001) and 2.76 times greater for radiotherapy (95% CI, 2.26-3.37; P < .001) compared to untreated participants. Moreover, among participants treated with radiotherapy, there was a nearly 3-fold greater hazard risk of bladder cancer than in the untreated (hazard ratio [HR], 2.78; 95% CI, 1.92-4.02; P < .001), as well as an approximately 100-fold increased hazard risk of radiation-specific outcomes including radiation cystitis (HR, 131.47; 95% CI, 52.48-329.35; P < .001) and radiation proctitis (HR, 87.91; 95% CI, 48.12-160.61; P < .001). The incidence per 1000 person-years of any 1 of the 10 treatment-related complications was 124.26 for prostatectomy, 62.15 for radiotherapy, and 23.61 for untreated participants. This cohort study found that, even after accounting for age-related symptoms and disease, PCA treatment was associated with higher rates of complications in the 12 years after treatment. Given the uncertain benefit of PCA treatment for most patients, these findings highlight the importance of patient counseling before PCA screening and treatment and provide a rationale for pursuing opportunities for cancer prevention.

Efficacy and safety of different antibiotic treatment versus surgical treatment for acute appendicitis: A network meta-analysis.

This systematic review and network meta-analysis compared various antibiotic treatments with surgical treatment for acute appendicitis. We searched PubMed, Embase, Cochrane Library, and Wanfang databases for randomized controlled trials (RCTs) that met the prespecified inclusion criteria up to July 2023. The interventions included various antibiotics and surgery. The outcomes measured were initial treatment success, treatment success at 1-year follow-up, and treatment-related complications. Meta-analysis was conducted using R software with the gemtc package. Surfaces under the cumulative ranking curves (SUCRA) were used to rank the interventions. Thirteen RCTs involving nine treatments (cefotaxime [CTX] + tinidazole [TNZ], CTX + metronidazole [MTZ], ampicillin [AMP] + gentamicin [GEN] + MTZ, amoxicillin/clavulanate [AMC] + GEN, meropenem [MEM] + MTZ, AMC, ertapenem [ETP] + MTZ, ETP, and surgery) were included in this network meta-analysis. In head-to-head comparisons, no statistically significant difference was found between any two interventions for initial treatment success (p>0.05). The SUCRA indicated that surgery ranked first (SUCRA, 66.5%) for initial treatment success. Surgery was associated with an increased treatment success rate at 1-year follow-up compared to AMC (OR=0.01, 95% CrI=0.00-0.14, p<0.05), MEM+MTZ (OR=0.06, 95% CrI=0.00-0.42, p<0.05), and AMP+GEN+MTZ (OR=0.02, 95% CrI=0.00-0.23, p<0.05). No statistically significant differences were found between any two interventions regarding complications (p>0.05). Our network meta-analysis suggests that surgery ranks highest for initial treatment success and treatment success at 1-year follow-up. However, surgery may increase the complication rate.

Parkinson disease therapy: current strategies and future research priorities.

Parkinson disease (PD) is the fastestgrowing neurological disorder globally and poses substantial management challenges owing to progressive disability, emergence of levodopa-resistant symptoms, and treatment-related complications. In this Review, we examine the current state of research into PD therapies and outline future priorities for advancing our understanding and treatment of the disease. We identify two main research priorities for the coming years: first, slowing the progression of the disease through the integration of sensitive biomarkers and targeted biological therapies, and second, enhancing existing symptomatic treatments, encompassing surgical and infusion therapies, with the goal of postponing complications and improving long-term patient management. The path towards disease modification is impeded by the multifaceted pathophysiology and diverse mechanisms underlying PD. Ongoing studies are directed at α-synuclein aggregation, complemented by efforts to address specific pathways associated with the less common genetic forms of the disease. The success of these efforts relies on establishing robust end points, incorporating technology, and identifying reliable biomarkers for early diagnosis and continuous monitoring of disease progression. In the context of symptomatic treatment, the focus should shift towards refining existing approaches and fostering the development of novel therapeutic strategies that target levodopa-resistant symptoms and clinical manifestations that substantially impair quality of life.

Investigation of Prognosis and Related Factors of Premature Neonates

The birth of premature infants remains a challenge in many societies. This cross-sectional study investigates prenatal care and influential factors in preterm infants hospitalized in the Neonatal Intensive Care Unit (NICU) of Fatemieh Educational-Medical Center in Hamadan, Iran, from March 2018 to March 2019. We examined premature infants with a gestational age of less than 37 weeks who were admitted to the NICU. Data on demographic and maternal characteristics, length of hospital stay, maternal underlying diseases, probable causes of preterm birth, neonatal complications, treatment types, treatment-related complications, resuscitation needs, ventilation, and mortality rates were extracted from patient records. Among 388 preterm infants studied, 204 (52.6%) were female. The mean gestational age was 31.8±2.8 weeks, birth weight was 1647.4±625.6 grams, and average hospital stay was 10.2±9.3 days. The most common maternal underlying disease was pregnancy-induced hypertension or preeclampsia (22.2%), respiratory distress syndrome, jaundice, and low birth weight were the leading reasons for hospitalization (84%). Neonatal outcomes included 92 (23.7%) deaths, 25 (6.4%) intraventricular hemorrhages, 39 (10.1%) patent ductus arteriosus cases, 20 (5.2%) bronchopulmonary dysplasia cases, and 41 (10.6%) retinopathy of prematurity cases. Regression analysis revealed significant predictors of neonatal mortality, including male gender, maternal underlying diseases, need for cardiopulmonary resuscitation, low Apgar score at one-minute, lower birth weight, shorter gestational age, and NICU stay duration. This study underscores the high neonatal mortality rate among preterm infants. Implementing preventive measures, particularly addressing maternal underlying diseases and low birth weight, can significantly reduce neonatal mortality.

Phase II Trial of Pathology-based Tripartite Treatment Stratification for Patients with CNS Germ Cell Tumors: A Long-term Follow-up Study.

A previous Phase II clinical trial, conducted from 1995 to 2003, evaluated CNS germ cell tumors (GCTs) using a three-group treatment stratification based on histopathology. The primary objective of the study was to assess the long-term efficacy of standardized treatment regimens, while the secondary objective focused on identifying associated long-term complications. Total 228 patients were classified into three groups for treatment: germinoma (n=161), intermediate prognosis (n=38), and poor prognosis (n=28), excluding one mature teratoma case. Treatment involved stratified chemotherapy regimens and varied radiation doses/coverage. Clinical data was retrospectively analyzed at a median follow-up of 18.5 years. The treatment outcomes for germinoma, with or without syncytiotrophoblastic giant cell, were similar. The 10- and 20-year event-free survival rates for the germinoma, intermediate, and poor prognosis groups were 82/76/49% and 73/66/49%, respectively. Overall survival (OS) rates were 97/87/61% at 10 years and 92/70/53% at 20 years. Germinomas in the basal ganglia, treated without whole-brain radiation therapy (WBRT), frequently relapsed but were effectively managed with subsequent WBRT. Deaths in germinoma cases had varied causes, whereas deaths in the poor prognosis group were predominantly disease-related. Nineteen treatment-related complications were identified in 16 patients, with cumulative event rates of 1.9% at 10 years and 11.3% at 20 years. OS rates at 1 and 2 years post-relapse for tumors initially classified as germinoma, intermediate, and poor prognosis were 94/88/18% and 91/50/9%, respectively. Initial treatment intensity is crucial for managing non-germinomatous GCTs, while long-term follow-up for relapse and complications is imperative in germinomas. Irradiation extending beyond the immediate tumor site is essential for basal ganglia germinomas. Addressing relapse in non-germinomatous GCT remains a significant challenge.

Clinical Burden and Healthcare Resource Utilization Associated With Managing Transfusion-dependent β-Thalassemia in England

PurposePatients with transfusion-dependent β-thalassemia (TDT) have reduced levels of β-globin, leading to ineffective erythropoiesis and iron overload. Patients with TDT depend on regular red blood cell transfusions (RBCTs) and iron chelation therapy for survival and management of disease- and treatment-related clinical complications. This study describes the clinical and economic burden in patients with TDT in England. MethodsThis longitudinal, retrospective study linked the Clinical Practice Research Datalink (CPRD) database with secondary care data from the Hospital Episode Statistics database to identify patients with a diagnosis of β-thalassemia between July 1, 2008, and June 30, 2018. Included patients had a diagnosis of β-thalassemia prior to the index date, ≥8 RBCTs per year for ≥2 consecutive years, and ≥1 year of follow-up data available from the index date. Each eligible patient was exact matched with up to 5 controls in the CPRD. Proportions of deaths and rates of mortality, acute and chronic complications, and healthcare resource utilization (HCRU) were calculated during the follow-up period. FindingsOf 11,359 identified patients with β-thalassemia, 237 patients with TDT met the eligibility criteria and were matched with 1184 controls. The mean age at the index date was approximately 25 years in the patient and control groups. The proportion of deaths (7.17% vs 1.18%; P < 0.05) and mortality rate (1.19 deaths per 100 person-years vs 0.20 deaths per 100 person-years) were higher among patients with TDT compared to controls. Endocrine complications and bone disorders were the most prevalent complications among patients with TDT (58.23%) and included osteoporosis (29.11%), diabetes mellitus (28.27%), and hypopituitarism (28.27%). Patients with TDT had a mean of 13.62 RBCTs per patient per year (PPPY). HCRU was substantially higher among patients with TDT, wherein patients with TDT had higher rates of prescriptions recorded in primary care (24.09 vs 8.61 PPPY), outpatient visits (16.69 vs 1.31 PPPY), and inpatient hospitalizations (17.41 vs 0.24 PPPY) than controls. Inpatient hospitalizations were primarily <1 day, with 16.62 events PPPY lasting <1 day and 0.79 events PPPY lasting ≥1 day. Patients with TDT aged ≥18 years had increased rates of mortality, clinical complications, and HCRU than those aged <18 years. ImplicationsPatients with TDT in England have higher mortality than matched controls, substantial disease-related clinical complications, and substantial HCRU. High mortality and clinical complications highlight the need for additional innovative therapies for TDT.

Safety and tolerability of losartan to treat recessive dystrophic epidermolysis bullosa in children (REFLECT): an open-label, single-arm, phase 1/2 trial

Recessive dystrophic epidermolysis bullosa (RDEB) is a skin fragility disorder characterised by life-long mechanically induced skin blistering, fibrosis-driven pseudosyndactyly, and multi-organ involvement. Preclinical studies have suggested mitigated progression by angiotensin II type I receptor blockade through losartan. We aimed to determine the safety and tolerability of systemic losartan treatment among children with RDEB, and to obtain initial data on its clinical benefit. We conducted an open-label, single-arm, phase 1/2 trial at the Medical Center-University of Freiburg, Germany. Children with molecularly-confirmed RDEB, aged 2-16 years (starting from the 25th month of life) were eligible. Key exclusion criteria comprised anaemia with haemoglobin <8g/dl; hypotension (defined as age-related systolic blood pressure under the 5th percentile); cardiologic contraindications, requirement for any medications that are likely to cause interactions with losartan; renal artery stenosis or renal insufficiency with creatinine clearance <30ml/min; severe liver failure; severe, untreated electrolyte disturbances; history of cancer or chronic viral infections; hypersensitivity to losartan or any of the excipients and known or persistent abuse of medication, drugs, or alcohol. Treatment duration with losartan comprised 10 months, encompassing 16 weeks up-dosing of losartan, 24 weeks full dose losartan (final target dose of 1.4mg/kg), and 4 weeks losartan tapering, followed by 12 weeks follow-up without losartan. The primary endpoint was occurrence of a serious safety concern, defined as one of the following side effects of losartan: clinically relevant severe hypotension, immediate hypersensitivity reactions to the drug or clinical relevant severe hypo- and hyperkalaemia. EB-specific scores (the EBDASI activity and damage score, Birmingham Epidermolysis Bullosa Severity Score (BEBS)) and other clinical outcome parameters were evaluated at five clinical visits as secondary outcomes: pain (Wong-Baker FACES Scale for pain), quality of life (Quality Of Life in EB [QOLEB] questionnaire and Children's Dermatology Life Quality Index [CDLQI]), itch (Itch Assessment Scale for the Paediatric Burn Patients), dysphagia (Mayo Dysphagia Questionnaire-day 30 [MDQ-30]), pseudosyndactyly progression (our own morphometric scoring instrument), and hand function (Score of Colville and Terrill). All analyses (safety and efficacy) were performed in the safety population, defined as participants who received at least one dose of trial medication with losartan. This trial is registered with EudraCT, 2015-003670-32. Between Jul 28, 2017, and Feb 12, 2021, 29 children were enrolled. Of those 27 received the full treatment. Losartan was well tolerated, no treatment-related severe complications leading to a serious safety concern occurred. The patients revealed improvement in the RDEB clinical scores, namely a mean reduction at week 40 of-7.36 points (95%-CI:-16.13 to 1.41) in the EBDASI activity score and-10.50 points (95%-CI:-20.81 to-0.19) in the EBDASI damage score, while the Children's Dermatology Life Quality Index rose by 2.64 points (95%-CI:-4.55 to-0.90). Similar to the EBDASI score, the BEBS showed a mean reduction of-3 points, 95%-CI:-0.21 to-5,79, P=0.036). In the Wong-Baker FACES Scale for Pain an improvement of at least one level was identified for 9 of 28 patients between baseline and at month 9 (95%-CI: 15.9%-52.4%; P=0.57). Regarding the Quality of Life in EB Score, five of 28 patients showed an improvement in the total scale of at least one level at month 9 (95%-CI: 6.1%-36.9%; P=0.71). With the Itch assessment scale for the paediatric burn patients an improvement of at least one level could be observed in 12 of 28 patients (95%-CI: 24.5%-62.8%; P=0.24). The MDQ-30 showed no relevant difference at 9 months after treatment start, as compared to baseline. We observed improvement of finger span with our own morphometric scoring instrument of pseudosyndactyly progression, revealing an increase of the maximal distance between thumb and index finger at month 9 by 6.92mm, 95%-CI [3.48, 10.37] P=0.0009. With the Hand function assessment score of Colville and Terrill, an improvement of at least one level was documented for 3 of 28 patients, i.e., 10.7% (95%-CI: 2.3%-28.2%; P=0.63). Our results suggest that losartan was well tolerated by children with RDEB, and provide preliminary evidence that it may reduce disease burden. Further research with larger sample sizes and longer durations is needed to establish the treatment's long-term efficacy and safety. Debra International, the Department of Dermatology, Medical Center-University of Freiburg (Berta-Ottenstein Advanced Clinician Scientist Program of the Medical Faculty), and the German Research Foundation.

Long-Term Survey of Japanese Children with Recurrent Nephroblastoma: A Report from Japan Children’s Cancer Group

In prospective Japanese studies of pediatric renal tumors, 5-year event-free survival and overall survival (OS) for patients with nephroblastoma ranges from 75–90% and 89–97%, respectively. However, treatments strategies for recurrent nephroblastoma in Japanese patients remain unclear. This retrospective study aimed to inform the development of treatment strategies by analyzing the long-term results and side effects of salvage therapies for recurrent nephroblastoma in Japan. A questionnaire survey involving 41 institutions (74 patients) collected clinical data on recurrent cases reported to the Renal Tumor Committee of the Japan Children’s Cancer Group. Survey forms from 54 cases were evaluated. Median time to recurrence was 9.5 months among 51 patients without underlying disorders. Recurrence occurred at lung-only in 18 patients and at other sites in 33. The 5-year OS for all 51 patients was 70.6%, with recurrent disease causing death in 15 patients and one patient dying from treatment-related complications. Patients with lung-only recurrence had higher 5-year OS rates than those with other-site recurrence. Initial chemotherapy intensity also affected prognosis, with lower intensity associated with higher 5-year OS. In 17 survivors with lung-only recurrence, the most frequent treatment approach combined chemotherapy, surgery and radiotherapy. Conventional chemotherapy included platinum-containing regimens and/or Regimen I-based treatment containing cyclophosphamide and etoposide. Salvage therapies showed remarkable effectiveness for patients with lung-only recurrence or low intensity of the initial chemotherapy, highlighting the need to standardize prospective studies for post-recurrence treatment and identify risks of late complications for long-term survivors.

Comparison of Prognostic Outcomes Between Repeat Liver Resection and Particle Therapy for Patients with Recurrent Hepatocellular Carcinoma.

Particle therapy (PT) as an initial hepatocellular carcinoma (HCC) treatment has been reported to be effective; however, its efficacy for the treatment of recurrent HCC remains unclear. This study aimed to evaluate the efficacy of PT compared with repeat liver resection for treating recurrent HCC after initial LR, with a focus on prognostic outcomes. Between 2005 and 2019, 89 and 49 patients underwent repeat LR and PT for recurrent HCC after initial LR, respectively. The 5-year overall survival (OS) and recurrence-free survival (RFS) were evaluated using propensity score matching. Treatment-related complications were scored using the National Institute Common Terminology Criteria for Adverse Events (CTCAE) and were compared between the repeat LR and PT groups. In the entire cohort, the 5-year OS was significantly better in the repeat LR group than in the PT group (75% vs. 48%; p=0.0003), and the 5-year RFS was comparable in both groups (22% vs. 13%; p=0.088). Propensity score matching created 34 pairs of patients; no significant differences in the 5-year OS (65% vs. 48%; p=0.310) and RFS (21% vs. 8%; p=0.271) were observed between the repeat LR and PT groups. The proportion of CTCAE grade ≥3 complications was 8.8% and 5.9% in the repeat LR and PT groups, respectively (p=0.641). After initial LR, the prognosis and treatment-related complications in patients with recurrent HCC were comparable between the repeat LR and PT groups in the matched cohort; therefore, PT may remain one of the multidisciplinary treatment options for recurrent HCC.

Impact of select actionable genomic alterations on efficacy of neoadjuvant immunotherapy in resectable non-small cell lung cancer

BackgroundNeoadjuvant immune checkpoint inhibitors (ICIs) have improved survival outcomes compared with chemotherapy in resectable non-small cell lung cancer (NSCLC). However, the impact of actionable genomic alterations (AGAs) on the efficacy...

The pros and cons of probiotic use in pediatric oncology patients following treatment for acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) treatment, involving chemotherapy, radiotherapy, and pharmacotherapy (antibiotics, antineoplastics) perturbs the gut microbiota in pediatric patients, with enduring effects post-treatment. ALL treatments diminish microbial richness and diversity, favoring pathogenic bacteria. Probiotics may offer promise in mitigating these disruptions and associated side effects. This mini-review explores the impact of ALL treatment on the gut microbiota and the potential benefits of probiotics in pediatric oncology. Probiotics have shown promise in restoring gut microbial balance, reducing treatment-associated side effects, and potentially improving quality of life. However, potential adverse effects, particularly in immunocompromised patients, warrant caution. Notably, there's emerging interest in probiotics' role in bone health and mineral bioaccessibility. Further research is needed to elucidate probiotics' mechanisms and their broader impact on pediatric health. Integration of probiotics into ALL treatment and post-treatment regimens offers significant potential for improving patient outcomes and reducing treatment-related complications and long-lasting disruptions, although careful monitoring is essential.

Bereaved parents' perceptions of their cancer-ill child's last month with or without palliative care -a nationwide study.

Cancer is still the leading cause of non-accidental death in childhood, although the majority of children diagnosed in high-income countries survive their illness. In accordance with international standards, equal and early access to palliative care should be available to children and adults. Yet communication and prognostic disclosure may influence the timing of involvement in palliative care. Purpose: To investigate whether parents perceived that their child received palliative care and to what extent that contrasted parents' perceptions of their child's care and symptoms in the last month of life. A nationwide population-based parental questionnaire study in Sweden, one to five years after their child's death (n=226). Descriptive statistics were used. A majority of parents (70%) reported that they were aware that their child received palliative care and they were informed about the incurable disease (57%) within 3 months before the child died. The most common diagnosis among children receiving palliative care was a brain tumor (45%) with a disease related death (90%) and the care was often received at home (44%). Based on the reports of parents who felt that their child did not receive palliative care, 45% were informed within days or hours about the child's incurable disease, 45% of these children were diagnosed with leukemia, 60% died at the intensive care unit, and 49% died of treatment-related complications. It was most common for families who lived in urban areas (28%) to report their child received palliative care, in comparison to families living in sparsely populated areas (11%). A significant proportion of parents whose child received palliative care (96%) stated that the healthcare professionals were competent in caring for their child, for those who reported no palliative care it was slightly lower (74%). In both groups many children were affected by multiple symptoms the last month of life. The study findings highlight the role of understanding parental perceptions of pediatric palliative oncology care, the role of initiating palliative care early, the need of access to national equitable PC and professional competence across the lifespan, regardless of diagnosis and place of residence.

Immune Checkpoint Inhibitors in the Emergency Department

Immune-checkpoint inhibitors (ICIs) have transformed the landscape for cancer treatment by enhancing the endogenous immune system’s ability to eliminate cancer cells. Tumor cells evade the body’s immune response by blocking T cell activation; ICIs function by blocking this inhibition, thereby boosting the immune system’s ability to kill tumor cells. Despite producing astonishing improvements in prognosis and remission-free time frames for cancer patients, ICIs carry risks for well documented treatment-related complications and immune-related adverse events (irAEs) that can be life-threatening. IrAEs can occur in almost any organ system, and they usually occur early in treatment, typically within the first three months. Some common complications involve the cutaneous, gastrointestinal tract, pulmonary, and endocrine organ systems. Guidelines outlining the general treatment algorithms for irAEs have been published by the Society for Immunotherapy of Cancer (SITC) and the National Comprehensive Cancer Network (NCCN). When patients present to the Emergency Department with symptoms consistent with irAEs, a rigorous and thorough infectious work-up is required, and treatment usually begins. This includes immunosuppression with corticosteroids, symptomatic treatment, and/or discontinuation of the ICI depending on the grade and severity of presentation. Early recognition and management of irAEs among ED providers, in conjunction with treating oncologists, are imperative to improve patient outcomes in the Emergency Department.

Bado type III Monteggia fractures have a high injury- and treatment-related complication rate: a single center study of 73 fractures.

Monteggia fractures can be problematic injuries. The aim of this population-based study is to evaluate the risk of complications according to the Bado types, clinical outcome, and incidence. 72 children (median age 6, range 2-11 years) with 73 Monteggia fractures treated during 2014-2022 were identified from the institutional fracture register. Timing of diagnosis, complications, and method of treatment were registered. Outcomes were assessed at mean 4 years (1-9) follow-up in 68 (94%) children. The census population (< 16 years old) in Helsinki metropolitan area during the study period was assessed. Bado types I (n = 43) and III (n = 27) comprised all but 3 of the fractures. Diagnosis was made on admission in 57, and with a 1-8-day delay in 16 children. 8 children had sustained an associated nerve injury. 35 children were treated operatively, 7 after failed closed treatment. 4 reoperations were performed, including 3 ulnar osteotomies. The risk of complications (odds ratio [OR] 4.9, 95% confidence interval [CI] 1.7-14) and closed treatment failures (OR 12.3, CI 1.3-118) was higher in Bado type III than in type I injuries. 60 children attended for clinical follow-up, all had congruent radio-humeral joints and full range of elbow and forearm motion. Mean PedsQL was 94 (72-100) and QuickDash 3 (0-13). 8 additional children reported normal elbow functions by phone. The calculated mean annual incidence of Monteggia injuries was 2.9/100,000 children. Monteggia fractures are rare (2.9/100,000 yearly). Bado type III injuries are associated with a high risk of complications.

Eculizumab as first-line treatment for patients with severe presentation of complement factor H antibody-mediated hemolytic uremic syndrome.

Complement factor H (FH) antibody-mediated hemolytic uremic syndrome (HUS) has varying prevalence globally. Plasmapheresis and immunosuppressive drugs are the standard treatment. Recently, eculizumab has been reported as an effective alternative. This study aims to report four children with FH antibody-mediated HUS managed with eculizumab plus immunosuppression as first-line therapy. A retrospective chart review was conducted for children aged ≤ 18years old with complement-mediated HUS in two referral centers. Patients with FH antibody-mediated HUS treated with eculizumab as first-line therapy were included. Four children (aged 6-11years old) were included. Dialysis was necessary in three patients. Eculizumab was administered 5-23days after onset. None of them received plasmapheresis. Prednisone and mycophenolate mofetil were added after receiving positive FH antibody results. Hematological signs and kidney function improved after the second eculizumab dose. Eculizumab was discontinued in three patients after 6months. One patient required rituximab due to persistent high FH antibody titers; discontinuation of eculizumab occurred after 15months without recurrence. No treatment-related complications were observed. During a mean 12-month follow-up (range 6-24months), no relapses were recorded and all patients ended with normal GFR. Our data suggest that a short course of 6months of C5 inhibitor might be sufficient to reverse thrombotic microangiopathy symptoms and improve kidney function in patients with severe FH antibody-mediated HUS. Simultaneously, adding immunosuppressive agents might reduce the risk of relapse and allow cessation of C5 inhibition in a shorter period of time.

Robotic Repair of Ureteral Strictures After Kidney Transplantation

Background. Approximately 5% to 10% of patients who undergo kidney transplantation develop ureteral stricture, which can be treated endoscopically or by open surgery, which is more effective but complications are common and potentially severe. Robotic surgery has begun to emerge as an alternative in reconstructive procedures. However, few studies have evaluated the role of robotic surgery in this clinical setting. The aim of this study was to assess the efficacy and safety of robotic surgery in treating ureteral stricture after kidney transplantation. Methods. Single-center study of patients (n = 27), who developed ureteral stricture following kidney transplantation. All patients were treated from 2018 to 2023. We describe the patients’ baseline characteristics and clinical and surgical features. We determined the success rate as a measure of efficacy and complications to measure safety. Results. We perform 15 pyeloureterostomies to the native ureter and 12 ureteroneocystostomies. At a median follow-up of 15 mo, the success rate was 92.6%. Fourteen patients (52%) developed treatment-related complications, mainly grade II (Clavien-Dindo classification), except for one grade IVb complication. The median length of hospital stay was 3 d [interquartile range (2–6)]. Conclusions. These data show that robotic surgery is a safe and effective procedure for the treatment of ureteral strictures after kidney transplantation. The success rate was high with a low complication rate. To our knowledge, this is the largest series to date to evaluate robotic surgery in this clinical setting.

Application of mitoxantrone hydrochloride in lymph node imaging during radical thyroidectomy

Objective: To investigate the clinical application value of the new tracer mitoxantrone hydrochloride in imaging of cervical lymph nodes and identifying of parathyroid, recurrent laryngeal nerve during thyroid cancer radical surgery. Methods: A prospective controlled study was conducted between January 2022 and April 2024 at Tianjin First Central Hospital, recruiting 180 patients with thyroid cancer, including 54 males and 126 females, aged from 26 to 69 years. The patients were randomly divided into three groups: the mitoxantrone hydrochloride lymph node tracing group (MHI group), the nanocarbon lymph node tracing group (nanocarbon group), and the control group without lymph node tracers, with 60 cases in each group. All patients underwent total thyroid resection and regional lymph node dissection. The number of detected lymph nodes and positive metastatic lymph nodes and surgical field clarity scores and the identification rate of parathyroid glands and the instances of inadvertent excision were compared between the groups. Serum calcium and parathyroid hormone (PTH) levels at different perioperative time points and treatment-related complications were analyzed. One-way ANOVA, chi-square test and two independent sample non-parametric tests, were employed for statistical analyses. Results: The mean operation time, neck drainage volume and hospital stay in the MHI group and the nanocarbon group were respectively significantly lower than those in the control group (P<0.05). The mean staining intensity score, tracer success rate and surgical field clarity score in MHI group were respectively significantly higher than those in nanocarbon group (P<0.05). The mean numbers of dissected lymph nodes positive metastatic nodes and identification rates of parathyroid glands in MHI group were respectively significantly higher than those in both the nanocarbon and control groups (P<0.05). The rates of inadvertent parathyroid excision in both MHI group and nanocarbon group were significantly lower than those in control group (P<0.05). On postoperative day 1 and day 5, mean serum calcium and PTH levels in MHI group were respectively significantly higher than those in nanocarbon group and control groups. However, on postoperative day 1, there was no difference in mean serum calcium levels between the nanocarbon group and the control group (P>0.05), though PTH level in the nanocarbon group was higher than that in the control group. By postoperative day 5, both serum calcium and PTH levels were higher in the nanocarbon group compared to the control group (P<0.05). On postoperative days 30, there were no differences in serum calcium and PTH levels between the MHI group and the nanocarbon group (P>0.05). The risks of facial numbness, hand and foot tetany and choking during drinking were lower in both the MHI and nanocarbon groups compared to the control group (P<0.05). Conclusion: MHI demonstrates advantages in rapid targeted delivery and clear staining of the surgical field during regional lymph node dissection in radical thyroidectomy for thyroid cancer, effectively reducing the risk of collateral damage to the recurrent laryngeal nerve and parathyroid glands.

7255 Tirzepatide Helps Achieve Glycemic Control and Lower Triglycerides in Seven Patients with Lipodystrophy

Abstract Disclosure: R. Meral: None. E.D. Frontera: None. M. Celik Guler: None. M.C. Foss de Freitas: None. N. Nachawi: None. D.T. Broome: Consulting Fee; Self; Tayco, Inc.. Research Investigator; Self; Novo Nordisk, Fractyl Laboratories, Rhythm Pharmaceuticals. S.I. Taylor: None. E.A. Oral: Advisory Board Member; Self; Amryt, Regeneron Pharmaceuticals. Consulting Fee; Self; Regeneron Pharmaceuticals, Amryt, Third Rock Ventures. Grant Recipient; Self; Regeneron Pharmaceuticals, Amryt. Research Investigator; Self; Novo Nordisk, Fractyl, Ionis Pharmaceuticals Inc., GI Dynamics, Rhythm Pharmaceuticals. Other; Self; Amryt. Lipodystrophy encompasses a group of rare disorders associated with severe metabolic disease. These disorders are defined by abnormal distribution of fat, with near-total (generalized lipodystrophy, GL) or partial (partial lipodystrophy, PL; i.e. familial partial lipodystrophy, FPLD) absence of adipocyte mass leading to a decreased ability to store triglycerides safely. Excess triglycerides are more likely to be stored in ectopic tissues such as hepatocytes, which leads to the metabolic manifestations of the disease state. Patients with GL have near absent levels of leptin hormone and leptin replacement therapy leads to dramatic improvement, which has mainly been attributed to a reduction in caloric intake. Patients with PL are not as leptin deficient and their response to leptin replacement therapy has been variable. We hypothesized that the clinical use of tirzepatide in patients with lipodystrophy may lead to favorable outcomes through the reduction of caloric intake. We closely observed 7 patients who were prescribed tirzepatide for their diabetes with information presented respectively [Age: 44; 54; 34; 53; 44; 46; 38 years | Sex: F; F; F; F; F; M; F | Subtype: FPLD type 1; FPLD type 2; FPLD type 1; Acquired GL; FPLD type 2; FPLD type 1; FPLD type 3]. At baseline, all patients had poor control of their disease despite aggressive medical therapy (except patient #5). Follow-up durations varied due to the observational nature of the study [follow-up duration (months): 6; 12; 7; 3; 8; 9; 5]. Reductions in A1c, triglycerides, and body mass index (BMI) were observed [A1c (%): 13.4-&amp;gt;7.1; 7.1-&amp;gt;6.6; 7.6-&amp;gt;5.2; 8.7-&amp;gt;6.9; 5.4-&amp;gt;5.1; 8.9-&amp;gt;7.8; 9.7-&amp;gt;7.1 | triglycerides (mg/dL): 539-&amp;gt;339; 164-&amp;gt;109; 367-&amp;gt;NA; 151-&amp;gt;113; 388-&amp;gt;101; 459-&amp;gt;319; 4081-&amp;gt;259 | BMI (Kg/m2): 25.0-&amp;gt;24.5; 30.6-&amp;gt;28.3; 37.7-&amp;gt;33.9; 22.8-&amp;gt;20.9; 27.6-&amp;gt;23.4; 40.1-&amp;gt;37.9; 24.0-&amp;gt;24.9]. Those who were on insulin had decreased daily requirements [total daily insulin requirement (units): 160-&amp;gt;25; 82-&amp;gt;18; not on insulin; 85-&amp;gt;0; not on insulin; 280-&amp;gt;200; 124-&amp;gt;111]. All patients reported a reduction in their daily food intake. Treatment related complications were limited to known gastrointestinal issues which the patients rated as tolerable. Based on our results, a randomized controlled trial to test the efficacy of tirzepatide in patients with lipodystrophy may be warranted. Presentation: 6/3/2024