Effect of bariatric surgery on maternal cardiovascular system.

OBJECTIVE: Bariatric surgery is a successful treatment for sustainable weight loss and has been associated with improvement in cardiovascular function. Pregnancy after bariatric surgery is becoming increasingly common; however, little is known about the maternal cardiovascular system postsurgery. The aim of this study was to investigate maternal cardiovascular adaptation to pregnancy in women with previous bariatric surgery, compared with that in women with no history of weight-loss surgery and an early-pregnancy body mass index (BMI) similar to the presurgery BMI of the postbariatric women. METHODS: This was a prospective, observational, longitudinal study conducted from April 2018 to June 2020 including 30 pregnant women who had undergone bariatric surgery and 30 who had not, matched for presurgery BMI. Participants were seen at three timepoints during pregnancy: 12-14, 20-24 and 30-32 weeks' gestation. At all visits, maternal blood pressure (BP) was measured and cardiac geometry and function were assessed using two-dimensional (2D) transthoracic echocardiography. On a subset of patients (15 in each group), 2D speckle tracking was performed to assess global longitudinal and circumferential strain. Offline analysis was performed, and multilevel linear mixed-effects models were used for all comparisons. RESULTS: Compared with the no-surgery group, and across all trimesters, pregnant women with previous bariatric surgery had lower BP, heart rate and cardiac output and higher peripheral vascular resistance (P < 0.01 for all). Similarly, the postbariatric group demonstrated more favorable cardiac geometry and diastolic indices, including lower left ventricular mass, left atrial volume and relative wall thickness, together with higher E-wave/A-wave flow velocity across the mitral valve and higher mitral velocity (E') at the lateral and medial annulus on tissue Doppler imaging (P < 0.01 for all). There was no difference in ejection fraction, although global longitudinal strain was lower in postbariatric women (P < 0.01), indicating better systolic function. CONCLUSION: Our findings indicate better maternal cardiovascular adaptation in women with previous bariatric surgery compared with presurgery BMI-matched pregnant women with no history of weight-loss surgery. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

[Implementation of postgraduate and undergraduate teaching with simulated patients in Psychiatry]. / Implementación de docencia de postgrado y pregrado presencial y remota con pacientes simulados en psiquiatría.

BACKGROUND: Clinical simulation is a strategy with broad support especially when face-to-face medical attention is difficult. In Psychiatry, the use and availability of simulation is lower than in other medical specialties, even for remote teaching. AIM: To report a pedagogical experience whose objective was to develop and implement the simulated patient technique as a teaching strategy for psychopathology and face-to-face Psychiatry for Psychiatry residents and remote for undergraduate medical students. MATERIAL AND METHODS: Six residents and 115 medical students participated in the activity. A descriptive qualitative-quantitative study was designed. Surveys were used to measure the quality and satisfaction of clinical simulation and simulation in psychopathology and psychiatry. In addition, an opinion was requested about the activity. All residents and 104 students participated in the assessment. RESULTS: The simulations were satisfactorily evaluated. The participants perceived that the pedagogical activity favored the development of generic competencies and specific skills for general Psychiatry. CONCLUSIONS: Simulation in Psychiatry does not replace face-to-face practical teaching, but it is a transitional and complementary method for clinical activities.

[Initial assessment and management of the suicidal ideation and suicide attempts in primary care]. / Evaluación y manejo inicial de las ideas e intentos de suicidio en atención primaria.

Suicide and suicidal behaviors are a significant public health problem, for which several prevention modalities have been implemented. The identification and treatment of suicidal risk is a critical step in prevention, especially in primary health care, a level where most of the population consults. This article focuses fundamentally on the research on suicide risk in primary care by proposing an action guide for the assessment and management initial of suicide ideas and attempts.

De-escalated therapy for HR+/HER2+ breast cancer patients with Ki67 response after 2-week letrozole: results of the PerELISA neoadjuvant study.

BACKGROUND: In human epidermal growth factor receptor 2 (HER2+) breast cancers, neoadjuvant trials of chemotherapy plus anti-HER2 treatment consistently showed lower pathologic complete response (pCR) rates in hormone receptor (HR) positive versus negative tumors. The PerELISA study was aimed to evaluate the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen in HR+/HER2+ breast cancer patients selected on the basis of Ki67 inhibition after 2-week letrozole. PATIENTS AND METHODS: PerELISA is a phase II, multicentric study for postmenopausal patients with HR+/HER2+ operable breast cancer. Patients received 2-week letrozole, and then underwent re-biopsy for Ki67 evaluation. Patients classified as molecular responders (Ki67 relative reduction >20% from baseline) continued letrozole and started trastuzumab-pertuzumab for five cycles. Patients classified as molecular non-responders started weekly paclitaxel for 13 weeks combined with trastuzumab-pertuzumab. Primary aim was breast and axillary pCR. According to a two-stage Simon's design, to reject the null hypothesis, at least 8/43 pCR had to be documented. RESULTS: Sixty-four patients were enrolled, 44 were classified as molecular responders. All these patients completed the assigned treatment with letrozole-trastuzumab-pertuzumab and underwent surgery. A pCR was observed in 9/44 cases (20.5%, 95% confidence interval 11.1% to 34.5%). Among molecular non-responders, 16/17 completed treatment and underwent surgery, with pCR observed in 81.3% of the cases. PAM50 intrinsic subtype was significantly associated with Ki67 response and pCR. Among molecular responders, the pCR rate was significantly higher in HER2-enriched than in other subtypes (45.5% versus 13.8%, P = 0.042). CONCLUSIONS: The primary end point of the study was met, by reaching the pre-specified pCRs. In patients selected using Ki67 reduction after short-term letrozole exposure, a meaningful pCR rate can be achieved without chemotherapy. PAM50 intrinsic subtyping further refines our ability to identify a subset of patients for whom chemotherapy might be spared. EUDRACT NUMBER: 2013-002662-40. CLINICALTRIALS.GOV IDENTIFIER: NCT02411344.

Multicentre randomized clinical trial of colonic J pouch or straight stapled colorectal reconstruction after low anterior resection for rectal cancer.

BACKGROUND: Colonic J pouch reconstruction has been found to be associated with a lower incidence of anastomotic leakage than straight anastomosis. However, studies on this topic are underpowered and retrospective. This randomized trial evaluated whether the incidence of anastomotic leakage was reduced after colonic J pouch reconstruction compared with straight colorectal anastomosis following anterior resection for rectal cancer. METHODS: This multicentre RCT included patients with rectal carcinoma who underwent low anterior resection followed by colorectal anastomosis. Patients were assigned randomly to receive a colonic J pouch or straight colorectal anastomosis. The main outcome measure was the occurrence of major anastomotic leakage. The incidence of global (major plus minor) anastomotic leakage and general complications were secondary outcomes. Risk factors for anastomotic leakage were identified by regression analysis. RESULTS: Of 457 patients enrolled, 379 were evaluable (colonic J pouch arm 190, straight colorectal arm 189). The incidence of major and global anastomotic leakage, and general complications was 14·2, 19·5 and 34·2 per cent respectively in the colonic J pouch group, and 12·2, 19·0 and 27·0 per cent in the straight colorectal anastomosis group. No statistically significant differences were observed between the two arms. In multivariable logistic regression analysis, male sex (odds ratio 1·79, 95 per cent c.i. 1·02 to 3·15; P = 0·042) and high ASA fitness grade (odds ratio 2·06, 1·15 to 3·71; P = 0·015) were independently associated with the occurrence of anastomotic leakage. CONCLUSION: Colonic J pouch reconstruction does not reduce the incidence of anastomotic leakage and postoperative complications compared with conventional straight colorectal anastomosis. Registration number NCT01110798 (http://www.clinicaltrials.gov).

Synovial sarcoma in children and adolescents: the European Pediatric Soft Tissue Sarcoma Study Group prospective trial (EpSSG NRSTS 2005).

BACKGROUND: To report the results of the first European prospective nonrandomized trial dedicated to pediatric synovial sarcoma. PATIENTS AND METHODS: From August 2005 to August 2012, 138 patients <21 years old with nonmetastatic synovial sarcoma were registered in 9 different countries (and 60 centers). Patients were treated with a multimodal therapy including ifosfamide-doxorubicin chemotherapy and radiotherapy, according to a risk stratification based on surgical stage, tumor size and site, and nodal involvement. RESULTS: With a median follow-up of 52.1 months (range 13.8-104.4 months), event-free survival (EFS) was 81.9% and 80.7%, and overall survival (OS) was 97.2% and 90.7%, at 3 and 5 years, respectively. The only significant prognostic variable at univariate analysis was the risk group: 3-year EFS was 91.7% for low-risk, 91.2% for intermediate-risk, and 74.4% for high-risk cases. In 24 low-risk patients (completely resected tumor ≤5 cm in size) treated with surgery alone, there were two local relapses and no metastatic recurrences. Among 67 high-risk patients (unresected, or axial tumor or nodal involvement), 66 underwent surgery after neoadjuvant chemotherapy. Response to chemotherapy was 55.2%, including 22.4% cases with complete or major partial remissions, and 32.8% with minor partial remissions. CONCLUSION: This study demonstrates that collaborative prospective studies on rare pediatric sarcomas are feasible even on a European scale, with excellent treatment compliance. The overall results of treatment were satisfactory, with higher survival rates than those previously published by pediatric groups. Nonetheless, larger, international projects are needed, based on a cooperative effort of pediatric and adult oncologists. CLINICAL TRIALS NUMBER: European Union Drug Regulating Authorities Clinical Trials No. 2005-001139-31.

Prognostic significance of AMPK activation in advanced stage colorectal cancer treated with chemotherapy plus bevacizumab.

BACKGROUND: AMP-activated protein kinase (AMPK) has a central role in cellular energy sensing and is activated in preclinical tumour models following anti-vascular endothelial growth factor (VEGF) therapy. The possible predictive or prognostic role of AMPK status in cancer patients treated with anti-VEGF drugs has not been investigated so far. METHODS: Expression of components of the AMPK pathway including phosphorylated AMPK (pAMPK), phosphorylated acetyl-Coa carboxylase (pACC) and liver kinase B1 (LKB1) was investigated by immunohistochemistry in 48 colorectal cancers treated with FOLFIRI plus bevacizumab. Correlation between pAMPK and pACC and associations between the AMPK pathway scores and clinico-pathological characteristics were assessed. Overall survival (OS) was estimated through Kaplan-Meier method, whereas hazard ratios were computed to identify prognostic factors. RESULTS: Fourteen patients (29.2%) were included in the pAMPK-negative group (score ≤5), whereas 34 patients (70.8%) were included in the pAMPK-positive group (score >5). The Spearman's coefficient for the correlation between pAMPK and pACC scores in primary tumour samples was 0.514 (P=0.0002). Low pAMPK levels were associated with worse OS (P-value 0.0002) but not with PFS, whereas low pACC levels were associated both with worse OS and PFS (P-value 0.0007 and 0.01, respectively). CONCLUSIONS: Our findings suggest that high tissue AMPK activation is a prognostic biomarker in this cohort of metastatic colorectal cancer patients.

Parameningeal rhabdomyosarcoma in pediatric age: results of a pooled analysis from North American and European cooperative groups.

BACKGROUND: Parameningeal (PM) site is a well-known adverse prognostic factor in children with localized rhabdomyosarcoma (RMS). To identify risk factors associated with outcome at this site, we pooled data from 1105 patients treated in 10 studies conducted by European and North American cooperative groups between 1984 and 2004. PATIENTS AND METHODS: Clinical factors including age, histology, size, invasiveness, nodal involvement, Intergroup Rhabdomyosarcoma Study (IRS) clinical group, site, risk factors for meningeal involvement (MI), study group, and application of radiotherapy (RT) were studied for their impact on event-free and overall survival (EFS and OS). RESULTS: Ten-year EFS and OS were 62.6 and 66.1% for the whole group. Patients without initial RT showed worse survival (10-year OS 40.8% versus 68.5% for RT treated patients). Multivariate analysis focusing on 862 patients who received RT as part of their initial treatment revealed four unfavorable prognostic factors: age <3 or >10 years, signs of MI, unfavorable site, and tumor size. Utilizing these prognostic factors, patients could be classified into different risk groups with 10-year OS ranging between 51.1 and 80.9%. CONCLUSIONS: While, in general, PM localization is regarded as an adverse prognostic factor, the current analysis differentiates those with good prognosis (36% patients with 0-1 risk factor: 10-year OS 80.9%) from high-risk PM patients (28% with 3-4 factors: 10-year OS 51.1%). Furthermore, this analysis reinforces the necessity for RT in PM RMS.

[Magnitude, impact and recommended management strategies for depression, with reference to Chile]. / Magnitud, impacto y estrategias de enfrentamiento de la depresión, con referencia a Chile.

Depression is a global public health priority. Intervention strategies at different levels of care must be implemented. Research is needed in the areas of depression prevention, treatment and rehabilitation. This paper reports a literature review, focused in Chile, on the magnitude, impact, recommended management strategies and new research on depression.

New fracture patterns distal epiphysis femur in youth: Update of current classification.

INTRO: Distal growth core fractures of the femur are the third most common fracture in patients older than 10 years. These fractures result from high-energy trauma and have a high risk of evolving into growth disorders. The classification most used to describe these types of fractures is that described by Salter and Harris. Special clinical cases often occur in clinical practice that are not described in the classifications used. In our study, we analyzed and further focused on new fracture patterns related to pediatric epiphyseal detachments not easily described by the normal classifications currently used in the literature. MATERIALS AND METHODS: From January 2020 to December 2022, we treated 2 male clinical cases with epiphyseal detachments of the distal femur that could not be classified according to the Salter and Harris classification. age of the patients was 10 and 11 years, respectively; for both patients, the traumatic mechanism was a direct trauma to the right knee at high speed using an electric scooter; Serious clinical and radiographic follow-ups were performed at month 1, month 3, month 6, month 12, and month 24 from the date of surgery. DISCUSSION: Distal femur fractures represent a challenge for the orthopedics because they have a high incidence of complications. In our experience, there has been an increase in this type of injury caused using recently developed electric vehicles, which can reach considerable speeds. The Salter Harris classification is among the most widely used for fractures involving the growth physis. This classification proved to be rather limiting in the present case, so we decided to classify the fracture as 'Salter Harris III equivalent'. CONCLUSIONS: The fracture examined is a very rare fracture of the distal femur and is not reflected in the classifications currently in use. The patient presented an excellent clinical and radiographic result after surgery with the presence of a shortening of the affected femur in relation to the contralateral one, which suggests that the growth deficit may continue and increase over time for which reason future studies until skeletal maturity will be necessary to quantify the damage to the growth physis.

REGOMA-OSS: a large, Italian, multicenter, prospective, observational study evaluating the efficacy and safety of regorafenib in patients with recurrent glioblastoma.

BACKGROUND: In the randomized phase II REGOMA trial, regorafenib showed promising activity in patients with recurrent glioblastoma. We conducted a large, multicenter, prospective, observational study to confirm the REGOMA data in a real-world setting. PATIENTS AND METHODS: The major inclusion criteria were histologically confirmed diagnosis of glioblastoma according to the World Health Organization (WHO) 2016 classification and relapse after radiotherapy with concurrent/adjuvant temozolomide treatment, good performance status [Eastern Cooperative Oncology Group performance status (ECOG PS 0-1)] and good liver function. Regorafenib was administered at the standard dose of 160 mg/day for 3 weeks on/1 week off. Brain magnetic resonance imaging was carried out within 14 days before starting regorafenib and every 8-12 weeks. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate, disease control rate (DCR), safety and health-related quality of life. The Response Assessment in Neuro-Oncology (RANO) criteria were used for response evaluation and Common Terminology Criteria for Adverse Events (CTCAE) version 5 for assessment of adverse events (AEs). RESULTS: From September 2020 to October 2022, 190 patients with recurrent glioblastoma were enrolled from 30 cancer centers in Italy: their median age was 58.5 years [interquartile range (IQR) 53-67 years], 68% were male and 85 (44.7%) were in optimal clinical condition (ECOG PS 0). The number of patients taking steroids at baseline was 113 (60%); the second surgery was carried out in 39 (20.5%). O6-methylguanine-DNA methyltransferase (MGMT) was methylated in 80 patients (50.3%) and 147 (92.4%) of the patients analyzed had isocitrate dehydrogenase (IDH) wild type. The median follow-up period was 20 months (IQR 15.6-25.5 months). The median OS was 7.9 months ([95% confidence interval (CI) 6.5-9.2 months] and the median PFS was 2.6 months (95% CI 2.3-2.9 months). Radiological response was partial response and stable disease in 13 (7.3%) and 26 (14.6%) patients, respectively, with a DCR of 21.9%. The median number of regorafenib cycles per patient was 3 (IQR 2.0-4.0). Grade 3-4 drug-related adverse events were reported in 22.6% of patients. A dose reduction due to AEs was required in 36% of patients. No deaths were considered as treatment-related AEs. CONCLUSIONS: This large, real-world observational study showed similar OS with better tolerability of regorafenib in patients with relapsed glioblastoma compared with the REGOMA study.

Subclinical hypothyroidism and myocardial function in obese children.

BACKGROUND AND AIMS: Pediatric obesity is an important health problem representing a major public health concern worldwide in the last decades. An isolated elevation of Thyroid Stimulating Hormone (TSH) with normal levels of thyroid hormones is frequently found in obese children. It has been named Isolated Hyperthyreotropinemia or Subclinical Hypothyroidism (SCH) and may be considered a consequence of obesity. Evidence exists that SCH is related to impairment of both systolic and diastolic myocardial function in the adult population. The aim of our study is to establish if obesity-related SCH influences myocardial function in children. METHODS AND RESULTS: We examined 34 obese children and adolescents with SCH and 60 obese children with normal TSH levels who underwent Doppler echocardiographic to evaluate myocardial function. Global systolic function as assessed by Ejection Fraction (EF) was comparable between groups, however Right Ventricle pressure global systolic function and pressure were significantly reduced in SCH group. Mitral annulus peak systolic (MAPSE) excursion lateral and MAPSE septum resulted significantly reduced in SCH group. Tissue Doppler imaging peak systolic motion (TDI-S) was reduced in SCH group. Diastolic function also showed significant modifications in SCH group. CONCLUSION: These results suggest possible involvement of cardiac function in obese children with SCH resulting in both abnormal diastolic function and reduced longitudinal systolic function. This new insight into cardiovascular consequences of obesity-related SCH in children could influence clinical approach to such patients by pediatric endocrinologists.

Rare cardiomyopathies: diagnostic features.

Cardiomyopathies (CM) are an important and heterogeneous group of diseases affecting the myocardium. They can induce mechanical and/or electrical disorders and are due to a variety of causes, they frequently are genetic. However, since their high number and their clinical complexity, the identification is still a challenge. Echocardiography is a very useful tool in the assessment of CM. In this review we aim to define the typical clinical features and to discuss the main diagnostic tool, above all echocardiography that can help physicians in the correct assessment of CM.

[Association of loneliness, impulsivity and alcohol use with suicidal behavior in adolescents]. / Soledad, impulsividad, consumo de alcohol y su relación con suicidalidad en adolescentes.

BACKGROUND: Suicide and suicide attempts are public health problems. Their prevention requives the detection of predictor factors. AIM: To determine the predictive valué of loneliness, impulsivity and alcohol use on suicidal behavior in adolescents. SUBJECTS AND METHODS: Suicidal behavior, Loneliness (UCLA), Impulsivity (Barratt) scales and the Alcohol Use Disorders Identification Test (AUDIT), were applied to 763 high school students aged 14 to 19 years (49% males), living in Chillan, Chile. RESULTS: Nineteen percent of participants had attempted suicide and 34.3% had suicidal ideation. Loneliness, impulsivity and alcohol use were directly related to suicidal behavior. These predictors explained 31 % of the suicidal behavior. The most important risk factor was loneliness, followed by femóle gender, impulsivity and alcohol use. CONCLUSIONS: Loneliness, impulsivity and alcohol use are risk factors for suicide among adolescents. Women are at higher risk than men.

Clinical and molecular detection of inherited colorectal cancers in northeast Italy: a first prospective study of incidence of Lynch syndrome and MUTYH-related colorectal cancer in Italy.

The reported incidence of hereditary colorectal cancers (CRCs) is widely variable. The principal aim of the study was to prospectively evaluate the incidence of familial CRCs in a region of northern Italy using a standardized method. Consecutive CRC patients were prospectively enrolled from October 2002 to December 2003. Patients underwent a structured family history, the microsatellite instability (MSI) test and a screen for MUTYH mutations. Following family history patients were classified as belonging to high, moderate and mild risk families. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 proteins and investigation for MLH1/MSH2 mutations, for MLH1 promoter methylation and for the V600E hotspot BRAF mutation were performed in high MSI (MSI-H) cases. Of the 430 patients enrolled, 17 (4%) were high risk [4 hereditary non-polyposis colorectal cancer (HNPCC), 12 suspected HNPCC and 1 MUTYH-associated adenomatous polyposis coli (MAP)], 53 moderate risk and 360 mild risk cases. The MSI test was performed on 393 tumours, and 46 (12%) of them showed MSI-H. In these patients, one MLH1 pathogenetic mutations and two MSH2 pathogenetic mutations were found. Thirty-two (70%) MSI-H cases demonstrated MLH1 methylation and/or BRAF mutation: None of them showed MLH1/MSH2 mutation. Two biallelic germline MUTYH mutations were found, one with clinical features of MAP. A strong family history of CRC was present in 4% of the enrolled cases; incidence of MLH1/MSH2 or MUTHY mutations was 1.3% and of MSI-H phenotype was 12%. MLH1 methylation and BRAF mutation can exclude 70% of MSI-H cases from gene sequencing.

Administration of Samital® in children with oral mucositis: a feasibility study.

OBJECTIVE: SAMITAL®, a botanical drug containing three highly standardized extracts (Vaccinium myrtillus, Macleaya cordata and Echinacea angustifolia), has shown promising results in treating or preventing oral mucositis (OM) in adult patients, but it has not been fully investigated in children. In this study, we assessed the feasibility of SAMITAL administration in pediatric patients receiving anticancer treatment to prevent or treat OM, focusing on identifying an appropriate dose and evaluating safety and tolerability and palatability and treatment compliance. PATIENTS AND METHODS: We conducted an open-label, monocentric, prospective study on 18 children receiving anticancer therapy to prevent or treat OM. RESULTS: No SAMITAL®-related side effects were observed or reported during the study; moreover, no systemic absorption of SAMITAL® metabolites was detected in the bloodstream. However, compliance to SAMITAL® was unsatisfactory and variable (from 2 to 100%), and patients reported low palatability (median taste of 4.8; range 1.0-8.0). CONCLUSIONS: SAMITAL® administration appears to be safe in the pediatric population, as it is not absorbed in the bloodstream and does not cause any local or systemic side effects. However, the current formulation is only partially suitable for children, and future studies on SAMITAL® in children would need an adapted formulation to increase compliance.

Evolution of echocardiographic and cardiac magnetic resonance imaging abnormalities during follow-up in patients with multisystem inflammatory syndrome in children.

AIMS: Multisystem inflammatory syndrome in children (MIS-C) with cardiovascular manifestations are frequent. However, there is lacking evidence regarding cardiological follow-up of this cohort of patients. The aim of our study was to describe the early and mid-term cardiac abnormalities assessed by standard and speckle-tracking echocardiography (STE), and cardiac MRI (CMR). METHODS AND RESULTS: We enrolled 32 patients (21 male, 11 female), mean age 8.25 ± 4years, with diagnosis of MIS-C. During admission, all children underwent TTE, STE with analysis of left ventricle global longitudinal strain (GLS) and CMR. Patients underwent cardiological evaluation at 2 (T1) and 6 months (T2) after discharge. Cardiac MRI was repeated at 6 months after discharge. Mean left ventricular ejection fraction (LVEF) at baseline was 58.8 ± 10% with 10 patients (31%) below 55%. Speckle-tracking echocardiography showed reduced mean LV GLS (-17.4 ± 4%). On CMR, late gadolinium enhancement (LGE) with non-ischaemic pattern was evident in 8 of 23 patients (35%). Follow-up data showed rapid improvement of LVEF at T1 (62.5 ± 7.5 vs. 58.8 ± 10.6%, P-value 0.044) with only three patients (10%) below ≤ 55% at T1. Left ventricular (LV) GLS remained impaired at T1 (-17.2 ± 2.7 vs.-17.4 ± 4, P-value 0.71) and significantly improved at T2 (-19 ± 2.6% vs. -17.4 ± 4%, P-value 0.009). LV GLS was impaired (>-18%) in 53% of patients at baseline and T1, whereas only 13% showed persistent LV GLS reduction at T2. Follow-up CMR showed LGE persistence in 33.4% of cases. CONCLUSION: Early cardiac involvement significantly improves during follow-up of MIS-C patients. However, subclinical myocardial dysfunction seems to be still detectable after 6 months of follow-up in a not negligible proportion of them.

Central nervous system failure in melanoma patients: results of a randomised, multicentre phase 3 study of temozolomide- and dacarbazine- based regimens.

BACKGROUND: This study compared the central nervous system (CNS) metastasis incidence between a temozolomide- and a dacarbazine-based regimen in untreated stage IV melanoma patients. METHODS: A total of 150 patients were randomly assigned to receive either oral temozolomide (200 mg m(-2) per day; days 1-5) or intravenous dacarbazine (800 mg m(-2); day 1), in combination with intravenous cisplatin (75 mg m(-2); day 1) and subcutaneous interleukin-2 (3 MU twice daily; days 9-18), every 28 days (CTI and CDI). RESULTS: A total of 149 patients were eligible for an intention-to-treat analysis (CTI: n=74, CDI: n=75). The 1-year cumulative CNS incidence failure was 20.6% for CTI and 31.1% for CDI (P=0.22). In all 24 patients in CTI (32%) and 34 (45%) in CDI developed CNS metastases; 31 patients died of early systemic progression, before CNS evaluation. Median survival time was 8.4 months in the CTI and 8.7 in the CDI arm; in patients with CNS metastases the median survival time was 13.5 months in the CTI and 11.5 in the CDI arm. No difference in toxicity was observed between the two arms. CONCLUSION: The incidence of CNS failures in metastatic melanoma was not significantly reduced and the clinical course was not modified substituting a dacarbazine-based regimen with a temozolomide-based regimen. Patients who developed CNS metastases did not have a worse prognosis than patients progressing in other sites and should not be excluded from new investigational studies.