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BACKGROUND AND AIM: The study 'Periodontitis and Its Relation to Coronary Artery Disease' (PAROKRANK) reported an association between periodontitis (PD) and the first myocardial infarction (MI). This follow-up study aims to test the hypothesis that those with PD-compared to periodontally healthy individuals-are at increased risk for cardiovascular (CV) events and death. METHODS: A total of 1587 participants (age <75 years; females 19%) had a dental examination including panoramic radiographs between 2010 and 2014. PD was categorized as healthy (≥80% alveolar bone height), mild/moderate (79%-66%) or severe (<66%). A composite CV event (first of all-cause death, non-fatal MI or stroke and hospitalization following to heart failure) was investigated during a mean follow-up period of 9.9 years (range 0.2-12.5 years). Participants were divided into two groups: those with and without PD. The primary event rate, stratified by periodontal status at baseline, was calculated using the Kaplan-Meier method and Cox regression. RESULTS: The number of events was 187 in the 985 periodontally healthy participants (19%) and 174 in the 602 participants with PD (29%; p < 0.0001). Those with PD had a higher likelihood for a future event (hazard ratio [HR] = 1.26; 95% CI: 1.01-1.57; p = 0.038), following adjustment for age, smoking and diabetes. CONCLUSION: The PAROKRANK follow-up revealed that CV events were more common among participants with PD, which supports the assumption that there might be a direct relation between PD and CV disease.

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AIM: The present study assessed low-density lipoprotein cholesterol (LDL-C) levels in school-aged children from the Ogasa District of Shizuoka Prefecture and evaluated the utility of non-invasive vascular tests, namely flow-mediated dilation (FMD) and intima-media thickness (IMT), in pediatric patients with familial hypercholesterolemia (FH). METHOD: We analyzed the lipid test results of 8,568 students screened for prevention of lifestyle-related diseases and 78 children under 15 years old with cholesterol levels exceeding 220 mg/dL who visited Chutoen General Medical Center. We examined the LDL-C distribution from school-age screenings and conducted FMD and IMT assessments on those meeting the 2022 Pediatric FH Guidelines criteria. RESULTS: Among the screened students, 186 (2.2%) exhibited LDL-C levels above 140 mg/dL, including 123 fourth-graders (2.8%) and 63 first-year junior high students (1.5%). The mean LDL-C level across all students was 90.0 mg/dL (standard deviation: 21.3 mg/dL), with the 95th percentile at approximately 125.0 mg/dL. Of the 78 children who visited the hospital, 65 met the FH diagnostic criteria. In children ≥ 10 years old, no significant IMT differences were observed between the Definitive and Probable FH groups and the Possible FH group; however, a significant difference in the FMD percentage was noted between these groups (9.9% [8.1%-11.9%] vs. 14.2% [11.6%-16.3%], P=0.003). CONCLUSIONS: Our findings highlight the LDL-C distribution in FH screening and suggest a potential reduction in FMD in pediatric FH patients ≥ 10 years old. These results emphasize the importance of initiating pharmacological interventions in school-aged children to maintain optimal LDL-C levels for lifelong cardiovascular health.

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The complete absence of the nose, arhinia, is a malformation most often associated with severe brain malformations. However, arhinia can be isolated, but only a few cases have been described. The prenatal diagnosis of isolated arhinia is also rarely described, with only three cases describing their follow-up, mostly in the first months of life. In this case report, we describe the prenatal diagnosis of isolated arhinia and the long-term follow-up of 8 years with normal psychological and cognitive development. We also demonstrated the fetal magnetic resonance imaging and pediatric computed tomography three-dimensional reconstructions of the face.

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PURPOSE: Periacetabular bone loss poses a considerable challenge in the longevity and stability of acetabular implants used in total hip arthroplasty (THA). Innovations in implant design, specifically the introduction of three-dimensional (3D) porous titanium constructs, might reduce bone resorption. The purpose of this study was to build upon our previous randomized controlled trial, which found no change in periacetabular bone loss between a 3D porous none-hydroxyapatite coated titanium cup and a standard porous hydroxyapatite coated cup over a two year follow-up period by extending the follow-up duration to ten years post-surgery. METHODS: This was a single-centre, long-term follow-up study conducted over a ten year period in patients who had previously participated in a randomized controlled trial comparing a 3D porous titanium construct shell (PTC group) with a standard porous hydroxyapatite coated titanium shell (PC-group). The primary outcome measured was the change in bone mineral density (BMD) within four specific periacetabular zones, alongside overall bone loss, which was assessed through BMD in the lumbar spine at two, six and ten years postoperatively. Secondary outcomes included clinical outcome measures. RESULTS: In total, 18 in the PTC and 20 in the PC group were analysed for the primary endpoint up to ten years. The mean bone mineral density in zones 1-4 was 3.7% higher in the PTC group than in the PC group at six years postoperatively and 12.0% higher at ten years. Clinical outcomes, and the frequency of adverse events did not differ between the groups. CONCLUSIONS: The PTC group displayed superior long-term bone preservation compared to the PC group while maintaining similar clinical outcomes up to ten years postoperatively. Although with a small sample size, our findings suggest that porous titanium cups have the potential to minimize BMD loss around the cup which could contribute to improving THA outcomes and implant durability.

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Purpose: The natural history in unselected cohorts of patients with pheochromocytoma/ paraganglioma (PPGL) followed for a period >10 years remains limited. We aimed to describe baseline characteristics and outcome of a large cohort and to identify predictors of shorter survival. Methods: This retrospective single-center study included 303 patients with newly diagnosed PPGL from 1968 to December 31, 2023, in 199 prospectively supplemented since July 2020. Mean follow-up was 11.4 (range 0.3-50) years, germline genetic analyses were available in 92.1%. The main outcome measures were overall (OAS), disease-specific (DSS), recurrence-free (RFS) survival and predictors of shorter survival evaluated in patients with metastases at first diagnosis (n=12), metastatic (n=24) and nonmetastatic (n=33) recurrences and without evidence of PPGL after first surgery (n=234). Results: Age at study begin was 49.4 ± 16.3 years. There were 72 (23.8%) deaths, 15 (5.0%), 29 (9.6%) and 28 (9.2%) due to PPGL, cardiovascular disease (CVD) and malignant or other diseases, respectively. Median OAS, DSS1 (tumor-related) and DSS2 (DSS1 and death caused by CVD) were 4.8, 5.9 and 5.2 years (patients with metastases at first diagnosis), 21.2, 21.2 and 19.9 years, and 38.0, undefined and 38.0 years (patients with metastatic and with nonmetastatic recurrences, respectively). Major adverse cardiovascular events (MACE) preceded the first diagnosis in 15% (n=44). Shorter DSS2 correlated with older age (P ≤ 0.001), male sex (P ≤ 0.02), MACE (P ≤ 0.01) and primary metastases (P<0.0001, also for DSS1). Conclusion: The clinical course of unselected patients with PPGL is rather benign. Survival rates remain high for decades, unless there are MACE before diagnosis or metastatic disease.

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Neoplasias de las Glándulas Suprarrenales , Enfermedades Cardiovasculares , Paraganglioma , Feocromocitoma , Humanos , Masculino , Feocromocitoma/mortalidad , Feocromocitoma/patología , Femenino , Persona de Mediana Edad , Neoplasias de las Glándulas Suprarrenales/mortalidad , Neoplasias de las Glándulas Suprarrenales/patología , Estudios de Seguimiento , Paraganglioma/mortalidad , Paraganglioma/patología , Paraganglioma/diagnóstico , Adulto , Estudios Retrospectivos , Enfermedades Cardiovasculares/mortalidad , Anciano , Metástasis de la Neoplasia , Tasa de Supervivencia , Adulto Joven , Pronóstico , Adolescente , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/epidemiología

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OBJECTIVE: To determine survival to discharge and neurological outcomes on long-term follow-up of pediatric patients attended for out of-hospital cardiac arrest (OHCA). METHODS: Retrospective study based on an ongoing OHCA registry. Patients aged 16 years or younger were included. Futile resuscitation attempts were excluded. Neurological outcome on hospital discharge and on follow-up was based on variables in the Pediatric Cerebral Performance Category (PCPC) scale. Cases from January 1, 2008, through December 31, 2019, were extracted, and 2 surveys were carried out in May 2021 and January 2023. Patient follow-up time ranged from 1 to 13 years. RESULTS: Of the 13 778 patients in the registry, we found 277 (2.0%) who were aged 16 years or younger. One hundred thirty-seven patients (49.5%) were transported to a hospital, and spontaneous circulation was restored in 99 (35.7%). Thirty-six patients (13%) were discharged. The median (interquartile range) follow-up time was 2172 (978-3035) days. Thirty-one of these patients (86.1%) were alive at follow-up, 3 had died, and 2 were lost to follow-up. Neurological outcomes had worsened in 2 and improved in 6 patients. The neurological outcome of 27 of the 31 patients with complete follow-up data (87.1%) was good (PCPC scores of 1 or 2). CONCLUSIONS: In spite of the low incidence of shockable rhythm in pediatric OHCA, survival with a good neurological outcome is comparable to survival in adults. Children who are discharged after OHCA maintained or improved their neurological function over the long term.

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OBJETIVO: Conocer la supervivencia al alta y la evolución neurológica tras seguimiento a largo plazo de pacientes pediátricos atendidos por parada cardíaca extrahospitalaria. METODO: Estudio retrospectivo basado en un registro continuo de parada cardiaca extrahospitalaria. Se incluyeron los pacientes pediátricos (edad menor o igual a 16 años). Se excluyeron reanimaciones consideradas fútiles. Se tomaron como variables resultado el estado neurológico al alta hospitalaria y al seguimiento de los pacientes, siguiendo el modelo de la Pediatric Cerebral Performance Category. El periodo fue del 1 de enero de 2008 al 31 de diciembre de 2019. Se realizaron dos encuestas, en mayo del 2021 y enero del 2023 con un periodo de seguimiento entre 1 y 13 años. RESULTADOS: De los 13.778 pacientes, 277 (2,0%) eran menores de 16 años; 137 (49,5%) trasladados al hospital, 99 de ellos (35,7%) con recuperación de circulación espontánea. Recibieron el alta hospitalaria 36 pacientes (13%). En el seguimiento, mediana (RIC) de 2.172 [978-3.035] días, 31 pacientes (86,1%) seguían con vida, 3 pacientes fallecieron y en dos casos no obtuvimos información. Dos pacientes sufrieron un empeoramiento del estado neurológico y 6 mejoraron. Finalmente, 27 de los 31 pacientes (87,1%) que completaron el seguimiento tenían una buena situación neurológica (PCPC1-2). CONCLUSIONES: A pesar de presentar una incidencia baja, la supervivencia con buen estado neurológico al alta hospitalaria de la parada cardiorrespiratoria extrahospitalaria pediátrica es comparable a la del adulto. Los pacientes pediátricos que recibieron el alta hospitalaria tras una parada cardiorrespiratoria extrahospitalaria mantuvieron o mejoraron su estado neurológico en el seguimiento a largo plazo.

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Paro Cardíaco Extrahospitalario , Sistema de Registros , Humanos , Paro Cardíaco Extrahospitalario/mortalidad , Paro Cardíaco Extrahospitalario/terapia , Niño , Estudios Retrospectivos , Masculino , Femenino , Preescolar , Adolescente , Lactante , España/epidemiología , Reanimación Cardiopulmonar/estadística & datos numéricos , Alta del Paciente/estadística & datos numéricos , Estudios de Seguimiento , Tasa de Supervivencia , Factores de Tiempo

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OBJECTIVE: Schizophrenia disorders severely impact social and occupational function and reduce quality of life, furthermore patients often suffer from social withdrawal and isolation. The aim of this study was to investigate long-term quality of life and social disconnection and determine 10-year changes in quality of life and social disconnection later in life in association with changes in symptom severity, cognition, and global function. METHODS: We used assessments of quality of life and assessor rated social disconnection from the 10- and 20-year follow-up of the OPUS trial to examined 10-year changes in self-rated quality of life and social disconnection in the later stage of illness following a first episode psychosis. Self-rated social disconnection was only assessed in the 174 participants of the 20-year follow-up. RESULTS: Twenty years after a first episode psychosis only half of the participants reported having face-to-face contact with someone in their network more than once a week, while 90 % reported often or always being able to get emotional support when needed. Quality of life ratings were lower in our study population compared to the general population. On average physical and environmental quality of life worsened from the 10- to the 20-year follow-up while psychological and social quality of life remained stable. All quality-of-life domains were associated with negative symptoms (physical QoL: b = -6.6, p < 0.001, psychological QoL: b = -8, p < 0.001, social QoL: b = -5.7, p < 0.001 and environmental QoL: b = -6.5, p < 0.001) and global function (physical QoL: b = -0. 47, p < 0.001, psychological QoL: b = 0.52, p < 0.001, social QoL: b = 0.31, p < 0.001 and environmental QoL: b = 0.49, p < 0.001). CONCLUSION: Social disconnection seems to persist over time. Social disconnection and quality of life were associated with negative symptoms and poor functioning, therefore interventions aimed at improving global and social function might likely also improve quality of life.

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Multisystem inflammatory syndrome is a severe complication of SARS-CoV-2 infection in children (MIS-C). To date, data on long-term sequelae mainly concern cardiac outcomes. All ≤ 18 year olds consecutively admitted to the Buzzi Children's Hospital with a diagnosis of MIS-C between October 1, 2020, and May 31, 2022, were followed up for up to 12 months by a dedicated multidisciplinary team. They underwent laboratory tests, multi-organ clinical and instrumental assessments, and psychosocial evaluation. 56/62 patients, 40 M, mean age 8.7 years (95% CI 7.7, 9.7), completed the follow-up. Cardiological, gastroenterological, pneumological, and neurological evaluations, including IQ and EEG, were normal. Alterations of HOMA-IR index and/or TyG index, observed in almost all patients during hospitalisation, persisted in about a third of the population at 12 months. At 6 and 12 months respectively, impairment of adaptive functions was observed in 38/56 patients (67.9%) and 25/56 (44.6%), emotional and behavioural problems in 10/56 (17.9%) and 9/56 (16.1%), and decline in QoL in 14/56 (25.0%) and 9/56 (16.1%). Psychosocial well-being impairment was significantly more frequent in the subgroup with persistent glycometabolic dysfunction at 12 months (75% vs. 40.9% p < 0.001). CONLUSION: The mechanisms that might explain the long-term persistence of both metabolic alterations and neuro-behavioural outcomes and their possible relationship are far from being clarified. Our study points out to the potential long-term effects of pandemics and to the importance of a multidisciplinary follow-up to detect potential negative sequelae in different areas of health, both physical and psychosocial. WHAT IS KNOWN: • Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. • Few data exist on the medium- and long-term outcomes of MIS-C, mostly focused on cardiac involvement. Emerging evidence shows neurological and psychological sequelae at mid- and long-term follow-up. WHAT IS NEW: • This study reveals that MIS-C may lead to long-term glycometabolic dysfunctions joined to impairment in the realm of general well-being and decline in quality of life, in a subgroup of children. • This study highlights the importance of a long-term multidisciplinary follow-up of children hospitalised with MIS-C, in order to detect the potential long-term sequelae in different areas of health, both physical and psychosocial well-being.

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The systematic review and meta-analysis titled "The Effects of Dabrafenib and/or Trametinib Treatment in BRAF V600-Mutant Glioma" provides a critical evaluation of these targeted therapies for a challenging subset of gliomas. This review is notable for its comprehensive data integration, offering a robust assessment of the efficacy and safety of dabrafenib and trametinib. By focusing on BRAF V600 mutations, it contributes valuable insights into personalized treatment strategies. However, limitations include study heterogeneity and a lack of long-term follow-up data, which hinder the generalizability and complete understanding of treatment effects. Additionally, while the review emphasizes therapeutic potential, it requires a thorough evaluation of adverse effects. Future research should address these limitations by providing more consistent data, longer follow-up, and a balanced view of treatment risks and benefits.

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Neoplasias Encefálicas , Glioma , Imidazoles , Mutación , Oximas , Proteínas Proto-Oncogénicas B-raf , Piridonas , Pirimidinonas , Humanos , Oximas/uso terapéutico , Pirimidinonas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/genética , Piridonas/uso terapéutico , Glioma/tratamiento farmacológico , Glioma/genética , Imidazoles/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética

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In patients with apical hypertrophic cardiomyopathy (HCM), progressive electrocardiographic changes are observed during long-term follow-up. However, it is difficult to correspond these changes to the specific myocardial changes. Cardiac magnetic resonance (CMR) imaging can elucidate myocardial changes by late gadolinium enhancement. Here, we present the long-term follow-up (>18 years) on a patient with apical HCM, whereupon, precise and continuous changes in the myocardium, causing ST segment and T wave changes on electrocardiography, were observed on CMR images. The combination of electrocardiography and CMR facilitates management of patients with apical HCM because it helps explain and understand the nature of electrocardiography changes over time.

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BACKGROUND: Severely underweight (SUW) children contribute significantly to under-five mortality and morbidity. There are WHO guidelines for the management of severe acute malnutrition but no specific guidelines for SUW management. OBJECTIVE: The objectives were to achieve a recovery rate of 30% at 90 days of treatment for severe underweight (SUW) children aged 6-60 months, compare changes in weight-for-age Z (WAZ) scores, growth patterns, and case fatality rates between intervention and reference arms (RA), and reduce the prevalence of SUW in the intervention arm (IA). The target of a 30% recovery rate was achievable and significant based on our past research conducted in similar settings. METHODS: Design: A prospective controlled community-based, longitudinal, two arms (IA, RA), intervention study with long follow-up was conducted between January 2011 and October 2023. SETTING: Primary care for participants from 14 villages in rural Melghat, India. PARTICIPANTS: The study participants included SUW children aged 6-60 months and age-matched (±2 weeks) normal controls. The SAMMAN (Acronym for SAM-Management) intervention was comprised of local therapeutic food-micronutrient (LTF-MN) therapy for 90 days, intensive behavior change communication, infection treatment, and quarterly anthropometric records. SUW recovery, growth patterns, case fatality rate, prevalence at 90 days of therapy and at 60 months of age, and survival until early adolescence were assessed. ANCOVA analysis was used to obtain changes in Z-scores. RESULTS: In the IA, the recovery rate was 36.8% at 90 days and 78.2% at 60 months of age. The mean difference in change in WAZ scores between the intervention arm and the reference arm was statistically significant (p < 0.0001). Growth patterns were similar between the two arms up to early adolescence. The SUW case fatality rate was significantly lower in the IA (0.9%) as compared to 4.62% in the RA at 60 months (p = 0.022). The reduction in SUW prevalence in intervention villages was higher than in the control villages (p < 0.001). The cost of management per SUW child was 3888 INR (47 USD) less than RUTF. CONCLUSION: The SAMMAN intervention is safe and cost-effective for significantly improving WAZ scores, sustainable, and hence replicable in resource-limited areas.

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Población Rural , Delgadez , Humanos , India/epidemiología , Lactante , Preescolar , Estudios Prospectivos , Femenino , Masculino , Población Rural/estadística & datos numéricos , Delgadez/epidemiología , Estudios de Seguimiento , Micronutrientes/administración & dosificación , Estudios Longitudinales , Prevalencia , Desnutrición Aguda Severa/terapia , Desnutrición Aguda Severa/epidemiología , Desnutrición Aguda Severa/mortalidad

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OBJECTIVE: To assess the cumulative rates of re-operations after hypospadias repair and evaluate long-term surgical outcomes at a tertiary paediatric urology centre. PATIENTS AND METHODS: Retrospective analysis of 293 boys born between 1991 and 2003 undergoing hypospadias surgery was conducted. The study included 274 patients: 165 with distal, 34 with midshaft, and 75 with proximal hypospadias. Kaplan-Meier methods were used to evaluate the re-operation data. RESULTS: The median age at primary surgery was 1.3 years, with a median follow-up of 14.4 years. The overall re-operation rate was 48.2%, with approximately half of the problems detected within the first 3 months after surgery. The risk of re-operation was correlated with hypospadias severity, with 5- and 15-year re-operation risks at 39.3% and 51.8%, respectively. Limitations of the study include its retrospective nature and variations in surgical techniques from current standards. CONCLUSION: There is a significant risk of unplanned re-operations following hypospadias repair, increasing with the severity of the original condition. This underscores the need for extended follow-up and effective communication with patients and their families about the likelihood of requiring multiple surgeries for optimal outcomes.

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BACKGROUND: Evidence for the effect of favipiravir treatment of acute COVID-19 on recovery, hospital admissions and longer-term outcomes in community settings is limited. METHODS: In this multicentre. open-label, multi-arm, adaptive platform randomised controlled trial participants aged ≥18 years in the community with a positive test for SARS-CoV-2 and symptoms lasting ≤14 days were randomised to: usual care; usual care plus favipiravir tablets (loading dose of 3600 mg in divided doses on day one, then 800 mg twice a day for four days); or, usual care plus other interventions. Co-primary endpoints were time to first self-reported recovery and hospitalisation/death related to COVID-19, within 28 days, analysed using Bayesian models. Recovery at six months was the primary longer-term outcome. TRIAL REGISTRATION: ISRCTN86534580. FINDINGS: The primary analysis model included 8811 SARS-CoV-2 positive mostly COVID vaccinated participants, randomised to favipiravir (n = 1829), usual care (n = 3256), and other treatments (n = 3726). Time to self-reported recovery was shorter in the favipiravir group than usual care (estimated hazard ratio 1·23 [95% credible interval 1·14 to 1·33]), a reduction of 2·98 days [1·99 to 3·94] from 16 days in median time to self-reported recovery for favipiravir versus usual care alone. COVID-19 related hospitalisations/deaths were similar (estimated odds ratio 0·99 [0·61 to 1·61]; estimated difference 0% [-0·9% to 0·6%]). 14 serious adverse events occurred in the favipiravir group and 4 in usual care. By six months, the proportion feeling fully recovered was 74·9% for favipiravir versus 71·3% for usual care (RR = 1·05, [1·02 to 1·08]). INTERPRETATION: In this open-label trial in a largely vaccinated population with COVID-19 in the community, favipiravir did not reduce hospital admissions, but shortened time to recovery and had a marginal positive impact on long term outcomes.

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Amidas , Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Pirazinas , SARS-CoV-2 , Humanos , Pirazinas/uso terapéutico , Pirazinas/administración & dosificación , Amidas/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Antivirales/uso terapéutico , Antivirales/administración & dosificación , COVID-19/mortalidad , Resultado del Tratamiento , Anciano , Hospitalización/estadística & datos numéricos

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We have previously reported two single-agent phase I trials, evaluating the dose or schedule, of a DNA vaccine (pTVG-HP) encoding prostatic acid phosphatase (PAP) administered with GM-CSF as the adjuvant. These were in patients with PSA-recurrent, radiographically non-metastatic, prostate cancer (PCa). We report here the long-term safety and overall survival of these patients. Specifically, 22 patients with non-metastatic, castration-sensitive PCa (nmCSPC) were treated with pTVG-HP, 100-1500 µg, administered over 12 weeks and followed for 15 y. 17 patients with non-metastatic castration-resistant PCa (nmCRPC) were treated with 100 µg pTVG-HP with different schedules of administration over 1 y and followed for 5 y. No adverse events were detected in long-term follow-up from either trial that were deemed possibly related to vaccination. Patients with nmCSPC had a median overall survival of 12.3 y, with 5/22 (23%) alive at 15 y. 8/22 (36%) died due to prostate cancer with a median survival of 11.0 y, and 9/22 (41%) died of other causes. Patients with nmCRPC had a median overall survival of 4.5 y, with 8/17 (47%) alive at 5 y. The presence of T-cells specific for the PAP target antigen was detectable in 6/10 (60%) individuals with nmCSPC, and 3/5 (60%) individuals with nmCRPC, many years after immunization. The detection of immune responses to the vaccine target years after immunization suggests durable immunity can be elicited in patients using a DNA vaccine encoding a tumor-associated antigen.Trial Registration: NCT00582140 and NCT00849121.

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Vacunas contra el Cáncer , Antígeno Prostático Específico , Neoplasias de la Próstata , Vacunas de ADN , Humanos , Masculino , Vacunas de ADN/inmunología , Vacunas de ADN/administración & dosificación , Vacunas de ADN/efectos adversos , Antígeno Prostático Específico/inmunología , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/efectos adversos , Vacunas contra el Cáncer/administración & dosificación , Anciano , Estudios de Seguimiento , Neoplasias de la Próstata/inmunología , Persona de Mediana Edad , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/efectos adversos , Resultado del Tratamiento , Anciano de 80 o más Años , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Recurrencia Local de Neoplasia , Análisis de Supervivencia , Fosfatasa Ácida , Proteínas Tirosina Fosfatasas/inmunología

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Introduction: Mesenchymal stromal cells (MSCs) have been extensively studied as a potential treatment for steroid refractory acute graft-versus-host disease (aGVHD). However, the majority of clinical trials have focused on bone marrow-derived MSCs. Methods: In this study, we report the outcomes of 86 patients with grade III-IV (82.6% grade IV) steroid refractory aGVHD who were treated with human umbilical cord-derived mesenchymal stromal cells (UC-MSCs). The patient cohort included 17 children and 69 adults. All patients received intravenous infusions of UC-MSCs at a dose of 1 × 106 cells per kg body weight, with a median of 4 infusions (ranging from 1 to 16). Results: The median time between the onset of aGVHD and the first infusion of UC-MSCs was 7 days (ranging from 3 to 88 days). At day 28, the overall response (OR) rate was 52.3%. Specifically, 24 patients (27.9%) achieved complete remission, while 21 (24.4%) exhibited partial remission. The estimated survival probability at 100 days was 43.7%. Following a median follow-up of 108 months (ranging from 61 to 159 months), the survival rate was approximately 11.6% (10/86). Patients who developed acute lower GI tract and liver GVHD exhibited poorer OR rates at day 28 compared to those with only acute lower GI tract GVHD (22.2% vs. 58.8%; p= 0.049). No patient experienced serious adverse events. Discussion: These finding suggest that UC-MSCs are safe and effective in both children and adults with steroid refractory aGVHD. UC-MSCs could be considered as a feasible treatment option for this challenging conditon. (NCT01754454).

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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Cordón Umbilical , Adulto , Niño , Humanos , Enfermedad Aguda , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/terapia , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Trasplante de Células Madre Mesenquimatosas/métodos , Esteroides/farmacología , Esteroides/uso terapéutico , Resultado del Tratamiento , Cordón Umbilical/citología , Estudios de Factibilidad

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Purpose: The main objective of this study was to identify the facilitators of and barriers to the transition from pediatric to adult care for adolescents and young adults (AYAs) with cancer according to physicians and nurses working in oncology. The secondary objectives were (1) to explore the viewpoints of health care professionals (HCPs) on this transition and (2) to discover HCP's needs and the needs they perceive among AYAs and their parents. Methods: Semistructured interviews were conducted with 19 HCPs to discover their experiences with pediatric to adult care transitions. Thematic analysis was then conducted. Results: Participants reported that transitioning is a complex process influenced by numerous barriers and facilitators, which can be classified into four themes: (1) balancing the needs and relationships of the three actors involved in the transition process, (2) factors that enable HCPs to determine the ideal time for transitions, (3) institutional and organizational barriers and facilitators that challenge HCPs, and (4) HCPs' reflections on defining and improving the transition process. Conclusion: Beyond the lack of human and financial resources, which hinders the structuring of transitions, our results suggest the need for a paradigm shift. That is, the position given to AYAs in pediatrics before the transition needs to evolve so that they are gradually positioned at the center of the relationship with HCPs and, therefore, are the focus of care and the transition process. This will enable them to acquire the skills, knowledge, and autonomy needed for a successful transition to adult care.

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To the best of our knowledge, this case presents the first prenatal magnetic resonance imaging diagnosis of focal dermal hypoplasia with long-term follow-up, with important discordance between the prenatal and postnatal imaging characteristics of the skin malformation.

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BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood, but the prognosis has remarkably improved over the last 50 years in high-income countries, and thus, there is a focus on long-term health outcomes following survival and how to best provide health care support to adult long-term survivors of childhood ALL to prevent and handle potential health problems. Digital health interventions are promising to deliver feasible health promotion and prevention programs. This is particularly relevant for ensuring long-term follow-up in cases where continuous contact with oncology care may be disrupted. Moreover, these interventions are beneficial in reaching geographically dispersed target groups and overcoming the time constraints of everyday life that often hinder participation in such programs. OBJECTIVE: This study aimed to fill the gaps in existing research on adult long-term survivors of childhood ALL and provide formative data that can inform the development of formalized follow-up services designed to meet the needs of these survivors in ways that align with their preferences for digital health interventions. METHODS: In this cross-sectional national study, adult survivors (aged ≥18 years) of childhood ALL for over 10 years after diagnosis were compared to their siblings in terms of mental and physical health-related factors, including sleep, stress, anxiety, and depression (Depression Anxiety and Stress Scale 21 [DASS-21]); several dimensions of fatigue (Multidimensional Fatigue Inventory 20 [MFI-20]); work ability (Work Ability Index); chronic pain; and prevalences of diabetes, cardiovascular disease, headache or migraine, and rheumatic disease. RESULTS: Overall, 426 of 855 eligible ALL survivors responded (mean age 30.9, SD 7.7 years), and they participated at an average of 24 (SD 6.9) years after ALL diagnosis. Siblings (n=135; mean age 31.5, SD 7.7 years) acted as controls. Sleep quality, sleep quantity, and mean work ability scores were significantly lower, and physical fatigue, reduced motivation, and reduced activity scores were higher in ALL survivors than in siblings. There were no significant differences between the groups in terms of BMI and prevalence of chronic pain, depression, anxiety, or stress. Physical and psychological complications were more frequent among adult ALL survivors who had received hematopoietic stem cell transplantation (HSCT) than among those who had not received HSCT. CONCLUSIONS: Our nationwide cross-sectional study addressed the scarcity of knowledge regarding the self-reported health outcomes of adult long-term survivors of childhood ALL. We highlighted significant disparities within this population and emphasized the potential of comprehensive digital interventions that target vitality, sleep quality, fatigue, and psychosocial well-being to enhance well-being and bolster the capacity for managing chronic health conditions in this target group. Such an intervention would align with the needs of this target group, which is a prerequisite for successfully incorporating technology into the daily lives of survivors of childhood ALL.

RESUMEN

BACKGROUND: Nivolumab plus ipilimumab (NIVO+IPI) has demonstrated superior overall survival (OS) and durable response benefits versus sunitinib (SUN) with long-term follow-up in patients with advanced renal cell carcinoma (aRCC). We report updated analyses with 8 years of median follow-up from CheckMate 214. PATIENTS AND METHODS: Patients with aRCC (N = 1096) were randomized to NIVO 3 mg/kg plus IPI 1 mg/kg Q3W × four doses, followed by NIVO (3 mg/kg or 240 mg Q2W or 480 mg Q4W); or SUN (50 mg) once daily for 4 weeks on, 2 weeks off. The endpoints included OS, independent radiology review committee (IRRC)-assessed progression-free survival (PFS), and IRRC-assessed objective response rate (ORR) in intermediate/poor-risk (I/P; primary), intent-to-treat (ITT; secondary), and favorable-risk (FAV; exploratory) patients. RESULTS: With 8 years (99.1 months) of median follow-up, the hazard ratio [HR; 95% confidence interval (CI)] for OS with NIVO+IPI versus SUN was 0.72 (0.62-0.83) in ITT patients, 0.69 (0.59-0.81) in I/P patients, and 0.82 (0.60-1.13) in FAV patients. PFS probabilities at 90 months were 22.8% versus 10.8% (ITT), 25.4% versus 8.5% (I/P), and 12.7% versus 17.0% (FAV), respectively. ORR with NIVO+IPI versus SUN was 39.5% versus 33.0% (ITT), 42.4% versus 27.5% (I/P), and 29.6% versus 51.6% (FAV). Rates of complete response were higher with NIVO+IPI versus SUN in all International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups (ITT, 12.0% versus 3.5%; I/P, 11.8% versus 2.6%; FAV, 12.8% versus 6.5%). The median duration of response (95% CI) with NIVO+IPI versus SUN was 76.2 versus 25.1 months [59.1 months-not estimable (NE) versus 19.8-33.2 months] in ITT patients, 82.8 versus 19.8 months (54.1 months-NE versus 16.4-26.4 months) in I/P patients, and 61.5 versus 33.2 months (27.8 months-NE versus 24.8-51.4 months) in FAV patients. The incidence of treatment-related adverse events was consistent with previous reports. Exploratory post hoc analyses are reported for FAV patients, those receiving subsequent therapy based on their response status, clinical subpopulations, and adverse events over time. CONCLUSIONS: Superior survival, durable response benefits, and a manageable safety profile were maintained with NIVO+IPI versus SUN at 8 years, the longest phase III follow-up for a first-line checkpoint inhibitor combination therapy in aRCC.

RESUMEN

BACKGROUND: Botulinum toxin A (BTA) injections are effective for facial neuropathy. However, there is insufficient number of studies devoted to long-term management of these patients. OBJECTIVE: To evaluate the effectiveness and safety of BTA therapy in patients with facial neuropathy after neurosurgical interventions. MATERIAL AND METHODS: The study included 86 patients with facial neuropathy after surgical treatment of posterior cranial fossa and cerebellopontine angle tumors. All ones were divided into 2 groups: group I (main) - 57 patients with BTA prescribed early after facial nerve injury, group II (control) - 29 people undergoing exercise therapy, as well as special exercises and acupressure of painful muscle cords. The Sunnybrook Facial Grading Scale (SFGS) was used to assess facial symmetry and synkinesis, the Facial Disability Index (FDI scale) - to assess the quality of life. Overall duration of the study was 5 years (control points: 6 months, 1, 2, 3 and 5 years). RESULTS: The SFGS scores after 1, 2, 3 and 5 years were significantly better in the main group (resting symmetry p<0.01, voluntary movement symmetry p<0.01, synkinesis p<0.01, general condition of facial muscles p<0.01). Scores of physical and social functioning were significantly higher in the main group after 1 (p<0.01), 2 (p<0.01), 3 (p<0.01) and 5 years (p<0.01) after surgery. There was no need to change BTA dosage over 5 years. Thus, this form of BTA may be the most effective for synkinesis of facial muscles. CONCLUSION: Correction of synkinesis caused by facial neuropathy requires long-term follow-up and long-term treatment. BTA is effective and may be recommended for long-term treatment of these patients.

Asunto(s)

Procedimientos Neuroquirúrgicos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios de Seguimiento , Procedimientos Neuroquirúrgicos/métodos , Toxinas Botulínicas Tipo A/administración & dosificación , Enfermedades del Nervio Facial/cirugía , Enfermedades del Nervio Facial/etiología , Calidad de Vida , Anciano