Efficacy and safety of ramucirumab plus carboplatin and paclitaxel in untreated metastatic thymic carcinoma: RELEVENT phase II trial (NCT03921671).

BACKGROUND: Thymic carcinoma (TC) is a rare tumor with aggressive behavior. Chemotherapy with carboplatin plus paclitaxel represents the treatment of choice for advanced disease. Antiangiogenic drugs, including ramucirumab, have shown activity in previously treated patients. The RELEVENT trial was designed to evaluate the activity and safety of ramucirumab plus chemotherapy as first-line treatment in advanced TC. PATIENTS AND METHODS: This phase II trial was conducted within the Italian TYME network. Eligible patients had treatment-naïve advanced TC. They received ramucirumab, carboplatin and paclitaxel for six cycles, followed by ramucirumab maintenance until disease progression or intolerable toxicity. Primary endpoint was objective response rate (ORR) according to RECIST v1.1 as assessed by the investigator. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Centralized radiologic review was carried out. RESULTS: From November 2018 to June 2023, 52 patients were screened and 35 were enrolled. Median age was 60.8 years, 71.4% of patients were male and 85.7% had Masaoka-Koga stage IVB. The Eastern Cooperative Oncology Group performance status was 0 in 68.5% and 1 in 31.4% of patients. At the present analysis carried out some months after the interim analysis (earlier than expected) on 35 patients, ORR was 80.0% [95% confidence interval (CI) 63.1% to 91.6%]. At the centralized radiological review of 33/35 assessable patients, ORR was 57.6% (95% CI 39.2% to 74.5%). After a median follow-up of 31.6 months, median PFS was 18.1 months (95% CI 10.8-52.3 months) and median OS was 43.8 months (95% CI 31.9 months-not reached). Thirty-two out of 35 patients (91.4%) experienced at least one treatment-related adverse event (AE), of which 48.6% were AE ≥ grade 3. CONCLUSIONS: In previously untreated advanced TC, the addition of ramucirumab to carboplatin and paclitaxel showed the highest activity compared to historical controls, with a manageable safety profile. Despite the small number of patients, given the rarity of the disease, the trial results support the consideration of this combination as first-line treatment in TC.

The quality of care in type 1 and type 2 diabetes - A 2023 update of the AMD Annals initiative.

AIMS: An initiative of continuous monitoring of the quality of diabetes care, promoted by the Association of Medical Diabetologists, is in place in Italy since 2006 (AMD Annals). The initiative was effective in improving quality of care indicators, assessed periodically through standardized measures. Here, we show the 2023 AMD Annals data on type 2 (T2D) and type 1 (T1D) diabetes. METHODS: A network of over 1/3 of diabetes centers in Italy periodically extracts anonymous data from electronic medical records, using a standardized software. Process, treatment and outcome indicators, and a validated score of overall care, the Q-score, were evaluated. RESULTS: 296 centers provided data on 573,164 T2D (mean age 69.7 ± 11.2 years) and 42,611 T1D subjects (mean age 48.6 ± 16.9 years). A HbA1c value ≤ 7.0 % was documented in 56.3 % of patients with T2D and 35.9 % of those with T1D. Only 6.6 % of T2D patients and 3.5 % of those with T1D reached the composite outcome of HbA1c ≤ 7.0 % + LDL-C < 70 mg/dl + BP < 130/80 mmHg. Notably, only 2.8 % and 3.2 % of T2D and T1D patients, respectively, showed a Q score < 15, which correlates with an 80 % higher risk of incident CVD events compared to scores > 25. CONCLUSIONS: We documented an overall good quality of care in both T1D and T2D subjects. However, the failure to achieve the targets of the main risk factors, especially if combined, in a still too large proportion of patients testify the difficulty to apply the more and more stringent indications recommended by guidelines in the everyday clinical practice.

Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP).

Acquired aplastic anemia (AA) is a rare heterogeneous disorder characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2-3 per million population per year in the Western world, but 3 times higher in East Asia. Survival in severe aplastic anemia (SAA) has improved significantly due to advances in hematopoietic stem cell transplantation (HSCT), immunosuppressive therapy, biologic agents, and supportive care. In SAA, HSCT from a matched sibling donor (MSD) is the first-line treatment. If a MSD is not available, options include immunosuppressive therapy (IST), matched unrelated donor, or haploidentical HSCT. The purpose of this guideline is to provide health care professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary evidence-based document prepared by a group of pediatric hematologists of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Hemato-Oncology (AIEOP) was discussed, modified and approved during a series of consensus conferences that started online during COVID 19 and continued in the following years, according to procedures previously validated by the AIEOP Board of Directors.

Role of nutritional therapy on dietary habits and glycemic control in insulin-treated kidney transplant patients with diabetes.

AIMS: To evaluate the effect of nutritional therapy on glycemic compensation and key cardio-renal risk markers in patients with diabetes and kidney transplant, on insulin treatment by Multiple Daily Injection (MDI) or Continuous Subcutaneous Insulin Infusion (CSII). METHODS: 34 patients with diabetes on insulin treatment and kidney transplant recipients were enrolled;12 participated in the structured nutritional program (intervention group), 22 patients (control group) did not receive nutritional protocol. Both groups were then divided into subgroups according to the method of insulin administration (MDI and CSII). RESULTS: Statistically significant reduction in fasting blood glucose values, glycosylated hemoglobin (HbA1c) and glycosuria were observed in both groups at the end of the study. The intervention group, significantly reduced total cholesterolemia and the glycemic index, together with reduced dietary intake of lipids, cholesterol, soluble carbohydrates and increased consumption of carbohydrates and fiber. These improvements were even more pronounced in patients treated with CSII. CONCLUSIONS: A proper nutritional approach optimize glycometabolic outcomes and contribute significantly to the reduction of the major cardiovascular risk factors in renal transplant patients.

Quality of care and clinical inertia in the management of cardiovascular risk factors in patients with type 1 and type 2 diabetes: data from AMD annals.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality among patients with diabetes, and for this reason, all guidelines for CV risk management provide the same targets in controlling traditional CV risk factors in patients with type 1 or type 2 diabetes at equal CV risk class. Aim of our study was to evaluate and compare CV risk management in patients with type 1 and type 2 diabetes included in AMD Annals Database paying particular attention to indicators of clinical inertia. METHODS: This was a multicenter, observational, retrospective study of AMD Annals Database during year 2022. Patients with diabetes were stratified on the basis of their cardiovascular risk, according to ESC-EASD guidelines. The proportion of patients not treated with lipid-lowering despite LDL cholesterol > to 100 mg/dl or the proportion of patients not treated with antihypertensive drug despite BP > 140/90 mmhg and proportion of patients with proteinuria not treated with angiotensin converting enzyme inhibitors or angiotensinogen receptor blockers (ACE/ARBs) were considered indicators of clinical inertia. The proportion of patients reaching at the same time HbA1c < 7% LDL < 70 mg/dl and BP < 130/80 mmhg were considered to have good multifactorial control. Overall quality of health care was evaluated by the Q-score. RESULTS: Using the inclusion criteria and stratifying patients by ESC/EASD Cardiovascular Risk categories, we included in the analysis 118.442 patients at High Cardiovascular risk and 416.246 patients at Very High Cardiovascular risk. The proportion of patients with good multifactorial risk factor control was extremely low in both T1D and T2D patients in each risk class. At equal risk class, the patients with T1D had lower proportion of subjects reaching HbA1c, LDL, or Blood Pressure targets. Indicators of clinical inertia were significantly higher compared with patients with T2D at equal risk class. Data regarding patients with albuminuria not treated with RAAS inhibitors were available only for those at Very High risk and showed that the proportion of patients not treated was again significantly higher in patients with T1DM. CONCLUSIONS: In conclusion, this study provides evidence of wide undertreatment of traditional cardiovascular risk factors among patients with diabetes included in AMD Annals Database. Undertreatment seems to be more pronounced in individuals with T1D compared to those with T2D and is frequently due to clinical inertia.

Temporal trends in the starting of insulin therapy in type 2 diabetes in Italy: data from the AMD Annals initiative.

AIMS: Opportunities and needs for starting insulin therapy in Type 2 diabetes (T2D) have changed overtime. We evaluated clinical characteristics of T2D subjects undergoing the first insulin prescription during a 15-year-observation period in the large cohort of the AMD Annals Initiative in Italy. METHODS: Data on clinical and laboratory variables, complications and concomitant therapies and the effects on glucose control after 12 months were evaluated in T2D patients starting basal insulin as add-on to oral/non-insulin injectable agents, and in those starting fast-acting in add-on to basal insulin therapy in three 5-year periods (2005-2019). RESULTS: We evaluated data from 171.688 T2D subjects who intensified therapy with basal insulin and 137.225 T2D patients who started fast-acting insulin. Overall, intensification with insulin occurred progressively earlier over time in subjects with shorter disease duration. Moreover, the percentage of subjects with HbA1c levels > 8% at the time of basal insulin initiation progressively decreased. The same trend was observed for fast-acting formulations. Clinical characteristics of subjects starting insulin did not change in the three study-periods, although all major risk factors improved overtime. After 12 months from the starting of basal or fast-acting insulin therapy, mean HbA1c levels decreased in all the three investigated time-periods, although mean HbA1c levels remained above the recommended target. CONCLUSIONS: In this large cohort of T2D subjects, a progressively earlier start of insulin treatment was observed during a long observation period, suggesting a more proactive prescriptive approach. However, after 12 months from insulin prescription, in many patients, HbA1c levels were still out-of-target.

Effectiveness of oral semaglutide on glucose control and body weight up to 18 months: a multicenter retrospective real-world study.

AIM: Oral semaglutide, an innovative orally administered GLP-1 receptor agonist for type 2 diabetes (T2D) management was herein evaluated for its effectiveness in a multi-center retrospective real-world study. METHODS: We included new-users of oral semaglutide from 18 specialist care centres and collected retrospective data on baseline clinical characteristics. Updated values of HbA1c and body weight were analyzed using the mixed model for repeated measures. RESULTS: The study included 166 individuals with T2D, predominantly men (64.5%), with a mean age of 64.4 years and a mean diabetes duration of 10.1 years. In the majority of patients (68.3%) oral semaglutide was used as a second-line drug, mostly with metformin. At baseline, mean BMI was 28.9 kg/m2 and HbA1c was 7.5%. During the 18-month observation period, oral semaglutide demonstrated significant reductions in HbA1c, with a maximum change of - 0.9%, and 42.1% of patients achieved HbA1c values below 7.0%. Additionally, there was a substantial reduction in body weight, with an estimated change of - 3.4 kg at 18 months, and 30.3% of patients experienced a 5% or greater reduction in baseline body weight. Only 24.2% of patients reached the 14 mg dose. Subgroup analysis revealed that baseline HbA1c > 7%, persistence on drug, not being on a prior therapy with DPP-4 inhibitors, and loosing 5% or more the initial body weight were associated with greater HbA1c reductions. CONCLUSION: This study supports oral semaglutide as an effective option for T2D treatment, offering improved glucose control and weight management in a real-world setting.

Yogurt is tolerated by the majority of children with IgE-mediated cow's milk allergy

Background: Children with IgE-mediated cow's milk allergy (IgE-CMA) with gastrointestinal symptoms tolerate yogurt at 100%. Yogurt tolerance in children with IgE-CMA with urticaria and anaphylaxis was 7%. Methods: We enrolled children with IgE-CMA with cutaneous, respiratory, gastrointestinal and anaphylactic symptoms. All performed prick by prick (PbP) and oral food challenge (OFC) with yogurt. Some children performed also an OFC with CM mixed with wheat flour and baked, baked liquid CM, parmesan. Results: 34 children were enrolled, 31/34 (91%) with systemic adverse reaction after ingestion of CM (systemic CMA), 3/34 (9%) with isolated contact urticaria (ICU CMA). PbP with yogurt was negative only in one patient. OFC with yogurt was passed (that is, the OFC was negative) by 20/31 (64%) of the children with systemic CMA. 10/11 (91%) of the patients who failed OFC (that is, the OFC was positive) with yogurt were positive to SPT with casein vs. 8/20 (40%) of the patients who passed it (p = 0.018). None of the 19 children who passed OFC with yogurt failed all OFC with processed CM forms other than yogurt that tested vs. 4/8 among those who failed OFC with yogurt (p = 0.006). The rub test with yogurt was negative in 1/3 (33%) of the patients with ICU CMA. Conclusions: The results of our study are placed alongside others already present in the literature and concerning other methods of processing CM proteins and help to reduce the dietary restrictions of the majority of children with systemic IgE-CMA

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The NUMEN project: Heavy-Ion Double Charge Exchange reactions towards 0νββ NME determination / El proyecto NUMEN: reacciones de intercambio de cargas dobles de iones pesados hacia la determinación de 0νββ NME

Abstract NUMEN proposes cross sections measurements of Heavy-Ion double charge exchange reactions as an innovative tool to access the nuclear matrix elements, entering the expression of the life time of Neutrinoless double beta decay (0νββ). A key aspect of the projectis the use at INFN-Laboratori Nazionali del Sud (LNS) of the Superconducting Cyclotron (CS) for the acceleration of the required high resolution and low emittance heavy-ion beams and of MAGNEX large acceptance magnetic spectrometer for the detection of the ejectiles. The experimental measurements of double charge exchange reactions induced by heavy ions present a number of challenging aspects, since such reactions are characterized by very low cross sections. First experimental results give encouraging indication on the capability to access quantitative information towards the determination of the Nuclear Matrix Elements for 0νββ decay.

Resumen NUMEN propone mediciones de secciones eficaces de reacciones de intercambio de carga doble de iones pesados como una herramienta innovadora para acceder a los elementos de la matriz nuclear, entrando en la expresión del tiempo de vida de la desintegración beta doble sin neutrino (0νββ). Un aspecto clave del proyecto es el uso en INFN-Laboratori Nazionali del Sud (LNS) del ciclotrón superconductor (CS) para la aceleración de los haces de iones pesados de alta resolución y baja emitancia requeridos y del espectrómetro magnético de gran aceptación MAGNEX para la detección de los residuos eyectados. Las mediciones experimentales de reacciones de intercambio de carga doble inducidas por iones pesados presentan una serie de aspectos desafiantes, ya que tales reacciones se caracterizan por secciones eficaces muy bajas. Los primeros resultados experimentales dan una indicación alentadora sobre la capacidad de acceder a información cuantitativa para la determinación de los Elementos de la Matriz Nuclear para la descomposición de 0νββ.

Metastatic neuroblastoma in infants: are survival rates excellent only within the stringent framework of clinical trials?

Introduction. SIOPEN INES protocol yielded excellent 5-year survival rates for MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to lack or delay of MYCN status or late registration were treated, but not included in the study. Our goal was to analyse survival at 10 years among the whole population. Materials and methods. Italian and Spanish metastatic INES patients’ data are reported. SPSS 20.0 was used for statistical analysis. Results. Among 98 infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and 74 %, respectively. MYCN status was significant for EFS, but not for OS in multivariate analysis. Conclusions. The survival rates of patients who complied with all the inclusion criteria for INES trials are higher compared to those that included also not registered patients. Five-year EFS and OS for INES 99.2 were 87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning 99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61 and 68 %. MYCN amplification had a strong impact on prognosis and therefore we consider it unacceptable that many patients were not studied for MYCN and probably inadequately treated. Ten-year survival rates were shown to decrease: EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events, particularly in stage 4s. Population-based registries like European ENCCA WP 11-task 11 will possibly clarify these data (AU)

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Relactacao - I. Proposta de uma tecnica para facilitar a estimulacao da lactacao / Relactation - I. Proposal of a technic to facilitate the stimulation of lactation

Os autores propoem uma tecnica de relactacao em maes de criancas reinternadas na Maternidade de Campinas, nos Ambulatorios da Faculdade de Medicina da UNICAMP e do Instituto de Pediatria da UNICAMP e que haviam deixado de amamentar por varios motivos. Aplicam um metodo simples de estimulacao de succao ao seio com sonda nasogastrica tipo adulto, adaptada ao mamilo materno por onde se faz complementacao alimentar com leite humano de Banco, ou leite de vaca, enquanto nao se restabelece a producao lactea. Baseiam sua tecnica fundamentalmente em apoio e assessoria psicologica intensa, succoes frequentes e repetidas do mamilo, para estimular a producao de prolactina, e complementacao alimentar concomitante para reforcar a succao