Clinicopathologic and Dermoscopic Features of 20 Cases of Spark's Nevus, a Dermoscopic Simulator of Melanoma.

ABSTRACT: Spark's nevus is a particular type of melanocytic nevus, with histology that shows features of both Spitz and Clark nevus. Detailed dermoscopic features in a series of Spark nevi have not been described yet. We performed a monocentric retrospective observational study on 20 lesions of Spark nevus excised from 19 patients (M:F = 10:9; mean age: 37,6 years), reviewed by 5 experts in dermoscopy and 2 dermatopathologists. A histologic review confirmed that Spark nevi were mostly symmetric (80%), well circumscribed (100%), mainly compound (65%) melanocytic lesions with either epithelioid (55%) or spitzoid (45%) cell morphology and bridging of the nests (100%). Spark nevi were more frequently found on the trunk (85%) in patients with a history of sunburns in childhood (84%), with skin phototype III (79%), and with high nevus count (>100 nevi, 7 patients (36%)). On dermoscopy, we observed different general patterns: multicomponent (40%), reticular-globular-homogeneous (15%), globular homogeneous (15%), reticular (15%), reticular-globular (5%), homogeneous (5%), and globular (5%). Spark nevi showed frequently dermoscopic asymmetry (63%), brown color (90%) with areas of central hyperpigmentation (41%) and peripheral hypopigmentation (28%), atypical pigment network (48%), irregular globules (42%), irregular dots (31%), irregular blotches (16%), blue-whitish veil (13%), peripheral island (25%), irregular hyperpigmented areas (12%), and regression (33%). BRAF mutation was present in 7 of the 10 analyzed cases (70%); all these cases presented a history of evolution. In conclusion, Spark nevi occur on the trunk of young adults with high nevus count and history of sunburns; dermoscopic features are protean, often atypical and suspicious of melanoma.

The PRESTO study: awareness of stroke symptoms and time from onset to intervention.

Timely access to medical assistance is the first crucial step to improving clinical outcomes of stroke patients. Many educational campaigns have been organized with the purpose of making people aware of what a stroke is and what is necessary to do after its clinical onset. The PRESTO campaign was organized in Genoa (Italy) to spread easy messages regarding the management of the acute phase of stroke. Educational material was disseminated to educate people to call the emergency medical services as soon as symptoms appear. Data collected were analyzed in three different phases of the campaign: before the beginning, during, and after the end. We enrolled 1,132 patients with ischemic stroke admitted to hospital within 24 hours of symptoms onset. Our data showed a mild reduction in onset-to-door time (24 minutes) during the months following the end of the campaign and a slight increase in number of patients who arrived at hospitals, in particular with milder symptoms and transient ischemic attack, as opposed to the same period before the campaign. Interestingly, in the months after the end of the campaign, we observed a slight reduction of the percentage of patients who accessed hospitals after 4.5 hours from symptoms onset. In conclusion, our results may suggest that an informative campaign can be successful in making people rapidly aware of stroke onset, with the consequent rapid access to hospitals. Considering the changing of way of access to information, we think that an extensive multimedia campaign should be evaluated in the next future.

Effect of sex on psychological distress and fatigue over time in a prospective cohort of cancer survivors.

BACKGROUND: Studies indicate a higher level of distress in women than men with cancer, but whether this difference is retained over time is unknown. We studied the frequency and level of distress and fatigue during time according to gender in a cohort of cancer survivors. PATIENTS AND METHODS: In this prospective study, cancer survivors were invited to undergo a psychological session immediately before the medical visit. Distress was assessed by the distress thermometer, and fatigue was assessed by the ESAS-r scale. Patients underwent follow-up visits to assess changes over time. RESULTS: A total of 305 patients and 568 visits were performed with a median follow-up of 15.8 months. At baseline, females, young age, and breast cancer patients had significantly higher distress. However, there was an increase in distress of 0.29 points every 6 months in males (95% CI, 0.09-0.50) versus no change in females (0.03 points, 95% CI, - 0.09-0.15; p-interaction = 0.01). The different behavior of cancer distress during time according to gender was more evident in subjects aged 68 or older due to increasing physical problems in men (p-interaction = 0.005). There was no change in fatigue with time according to sex. CONCLUSIONS: Women, younger age, and breast cancer patients had increased cancer distress at the initial visit. However, women tend to stabilize during follow-up, whereas men tend to worsen their distress, especially because of physical and emotional problems, suggesting different coping capabilities. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov NCT05122052. IMPLICATIONS FOR CANCER SURVIVORS: Interventions aimed at improving recognition of emotions related to disease experience in male cancer survivors appear necessary.

Prognostic value of texture analysis of the primary tumour in high-risk neuroblastoma: An 18 F-DOPA PET study.

PURPOSE: To evaluate the prognostic value of texture analysis of the primary tumour with 18 fluorine-dihydroxyphenylalanine positron emission tomography/X-ray computed tomography (18 F-DOPA PET/CT) in patients affected by high-risk neuroblastoma (HR-NBL). METHODS: We retrospectively analysed 18 patients with HR-NBL, which had been prospectively enrolled in the course of a previous trial investigating the diagnostic role of 18 F-DOPA PET/CT at the time of the first onset. Texture analysis of the primary tumour was carried out on the PET images using LifeX. Conventional indices, histogram parameters, grey level co-occurrence (GLCM), run-length (GLRLM), neighbouring difference (NGLDM) and zone-length (GLZLM) matrices parameter were extracted; their values were compared with the overall metastatic load, expressed by means of whole-body metabolic burden (WBMB) score and the progression-free/overall survival (PFS and OS). RESULTS: There was a direct correlation between WBMB and radiomics parameter describing uptake intensity (SUVmean : p = .004) and voxel heterogeneity (entropy: p = .026; GLCM_Contrast: p = .001). Conversely, texture indices of homogeneity showed an inverse correlation with WBMB (energy: p = .026; GLCM_Homogeneity: p = .006). On the multivariate model, WBMB (p < .01) and the first standardised uptake value (SUV) quartile (p < .001) predicted PFS; OS was predicted by WBMB and the N-myc proto-oncogene protein (MYCN) amplification (p < .05) for both. CONCLUSIONS: Textural parameters describing heterogeneity and metabolic intensity of the primary HR-NBL are closely associated with its overall metastatic burden. In turn, the whole-body tumour load appears to be one of the most relevant predictors of progression-free and overall survival.

Safety and Performance of POLYTECH Mesmo Breast Implants: A 5-Year Post-market Surveillance Study on 919 Patients.

Background: In 2007, POLYTECH Health & Aesthetics (POLYTECH, Dieburg, Germany) established an ongoing patient survey to improve the post-market surveillance of silicone gel-filled breast implants based on patient-reported outcomes in the context of the pioneering "Implants of Excellence" (IoE) program. Objectives: To disclose an update on safety and performance outcomes at 5 years for Mesmo breast implants. Methods: Between January 2014 and October 2019, 919 patients (for a total of 1816 implants) who underwent breast augmentation and reconstruction with Mesmo implants were asked to participate in the IoE program. Data were collected by mean of 1320 questionnaires received. A survival analysis assessed the onset of different complications. Results: Eight patients (0.9%) experienced capsular contracture Baker grade III or IV with a cumulative rate at 5 years of 1.2% (95% CI = 0.6-2.4). The proportion of revisional surgery was 0.5% with a 5-year rate of 0.6% (95% CI = 0.2-1.5). Additional adverse events such as hematoma, seroma, malposition, open wounds, and other complications were carefully monitored. Questionnaires showed that 93.9% (95% CI = 92.2-95.4) of the patients were satisfied or very satisfied with their aesthetic results with Mesmo implants. Conclusions: Post-market clinical follow-up revealed that the overall complications rate reported was low. Data demonstrated an excellent safety property on a large cohort of patients. This result allows the rating of Mesmo breast implants as highly competitive and a very safe choice for both surgeons and patients.

Internal carotid artery dissection related to abnormalities of styloid process: is it only a matter of length?

INTRODUCTION: Vascular Eagle syndrome, due to impingement of the extracranial internal carotid artery (ICA) by the styloid process (SP), is an uncommon and not yet widely recognized cause of ICA dissection. Up to now, this diagnosis is still presumptive, based mainly on the length of the SP. However, given the discrepancy between the much higher prevalence of an elongated SP in the population compared to the reported rate of Eagle syndrome, other anatomical factors beyond the length itself of this bony structure seem to be involved. MATERIAL AND METHODS: We performed a retrospective single center case-control study of ICA dissection related to abnormalities of styloid process and age- and sex-matched controls affected by ICA dissection not related to abnormal relationship with the styloid process. In our work instead of considering SP length as the main criteria to differentiate the two groups, we decided to consider styloid process-internal carotid artery distance (at the dissection point) as the main factor to define a styloid process related dissection (SPRD). In fact in some patients, the distance between the dissected artery and the bony prominence was virtual. RESULTS: Our study showed that in patients with SPRD the styloid process angulation on the coronal plane tends to be more acute and that styloid process-C1 distance is significantly shorter at the side of the dissection. This data reinforces the idea that ICA dissection risk in the vascular Eagle syndrome has probably a multifactorial pathogenesis.

Head CT in centenarians: emergency and non-emergency findings.

INTRODUCTION: Our retrospective study evaluates head CTs performed in our Hospital in the last 11 years (2009-2019) in centenarian patients. OBJECTIVES: To estimate the correlation between reasons for examination and CT findings in emergency and to evaluate if there was the expected involution of the brain by analyzing some non-emergency neuroradiological parameters (NENP). MATERIAL AND METHODS: 62 Head CTs performed on patients aged 100 and over were reviewed. They were evaluated emergency CT findings and NENP (leukoencephalopathy, enlargement of the ventricular volume, presence of vascular calcifications). For comparison, NENP were also assessed in two relatively younger populations of 62 patients aged between 65-70 (called "65-70") and 85-90 ("85-90"). RESULTS: In cases of suspected traumatic brain lesions, 11.9% (n = 5/42) of centenarians showed a cerebral bleeding; as concerns suspected stroke we found a higher concordance between clinical suspicion and CT features, 46.6% (n = 7/15). As regards NENP, no significant differences were found with respect to the "85-90" population in terms of severity of leukoencephalopathy, enlargement of the ventricular volume and presence of vascular calcifications. CONCLUSIONS: In emergency, CT plays a pivotal role in defining an immediate diagnosis and from a medico-legal point of view, resulting together with clinical observation the main strategy in the management of centenarians. By the analysis of NENP we may support that centenarians' brains on CT are similar to those of "85-90".

Multidimensional Frailty Predicts Mortality Better than Physical Frailty in Community-Dwelling Older People: A Five-Year Longitudinal Cohort Study.

Frailty is a common syndrome in older people that carries an increased risk of mortality. Two main models describe frailty, either as a loss of physical functions or as an accumulation of multiple deficits. The aim of our study was to compare the physical frailty index developed in the Cardiovascular Health Study (CHS) with a multidimensional frailty tool, the Multidimensional Prognostic Index (MPI), in predicting death in community-dwelling older subjects. Four hundred and seven community-dwelling older subjects were enrolled. Each subject underwent a comprehensive geriatric assessment (CGA) with calculation of the MPI and CHS index. Mortality was recorded over the following 5 years. In the overall sample (mean age of 77.9 ± 4.5 years; 51.6% female), 53 subjects (13%) died during the 5-year follow-up period. Both the MPI and CHS index were able to predict mortality; however, the MPI was significantly more accurate than the CHS index in predicting mortality (C-index = 0.69 and 0.59, respectively; p < 0.001), with a statistically significant difference of 10%. In conclusion, multidimensional frailty, assessed by the MPI, predicts five-year mortality in community-dwelling older people better than physical frailty, as assessed by the CHS index. These findings suggest the usefulness of assessing frailty by means of CGA-based tools to predict relevant health-negative outcomes in older people.

Predictors of poor seroconversion and adverse events to SARS-CoV-2 mRNA BNT162b2 vaccine in cancer patients on active treatment.

PURPOSE: Initial findings in patients with cancer suggest a lower seroconversion to SARS-CoV-2 vaccination possibly related to myelo-immunosuppressive therapies. We conducted a prospective study to assess factors predicting poor seroconversion and adverse events following immunisation (AEFI) to the BNT162b2 vaccine in patients on active treatment. PATIENTS AND METHODS: Cancer patients, candidates to two doses of BNT162b2 SARS-CoV-2 vaccination, were enrolled. Patients on active surveillance served as controls. The primary endpoint was poor seroconversion (anti S1/S2 IgG < 25 AU/mL) after 21 days from the second dose. RESULTS: Between March and July 2021, 320 subjects were recruited, and 291 were assessable. The lack of seroconversion at 21 days from the second dose was 1.6% (95% CI, 0.4-8.7) on active surveillance, 13.9% (8.2-21.6) on chemotherapy, 11.4% (5.1-21.3) on hormone therapy, 21.7% (7.5-43.7) on targeted therapy and 4.8% (0.12-23.8) on immune-checkpoint-inhibitors (ICI). Compared to controls, the risk of no IgG response was greater for chemotherapy (p = 0.033), targeted therapy (0.005) and hormonotherapy (p = 0.051). Lymphocyte count < 1 × 109/L (p = 0.04) and older age (p = 0.03) also significantly predicted poor seroconversion. Overall, 43 patients (14.8%) complained of AEFI, mostly of mild grade. Risk of AEFI was greater in females (p = 0.001) and younger patients (p = 0.009). CONCLUSION: Chemotherapy, targeted therapy, hormone therapy, lymphocyte count < 1 × 109/L, and increasing age predict poor seroconversion after two doses of BNT162b2 in up to 20% of patients, indicating the need for a third dose and long-term serological testing in non-responders. AEFI occur much more frequently in women and younger subjects who may benefit from preventive medications. CLINICALTRIALS. GOV IDENTIFIER: NCT04932863.

A Presurgical Study of Curcumin Combined with Anthocyanin Supplements in Patients with Colorectal Adenomatous Polyps.

Adenomatous polyps are precancerous lesions associated with a higher risk of colorectal cancer (CRC). Curcumin and anthocyanins have shown promising CRC-preventive activity in preclinical and epidemiological studies. The objective of this window-of-opportunity, proof-of principle trial was to evaluate the effect of curcumin combined with anthocyanin supplements on tissue biomarkers of colorectal adenomatous polyps. Eligible patients received either anthocyanin and curcumin supplementation or related matching placebo for 4-6 weeks before polyp removal. Adenomatous polyps and adjacent tissue biopsies were collected at baseline and after supplementation for immunohistochemical assessment of ß-catenin, NF-kappa B (NF-κB), Ki-67, P53, and dysplasia. No differences were observed in baseline biomarker expression between normal and dysplastic tissues. The combination of anthocyanins and curcumin resulted in a significant borderline reduction of NF-κB immunohistochemistry (IHC) expression in adenoma tissue (geometric mean ratio (GMR): 0.72; 95% confidence interval (CI): 0.51-1.00; p-value: 0.05) and a trend to a reduction of Ki-67 (GMR: 0.73; 95% CI: 0.50-1.08; p-value: 0.11). No significant modulation of biomarkers in normal adjacent mucosa was observed. We concluded that the combined supplementation of anthocyanins and curcumin seems to lead to a potentially favorable modulation of tissue biomarkers of inflammation and proliferation in colon adenomas.

A Three-Domain Scoring System to Customize the Risk of Relapse of Differentiated Thyroid Carcinoma.

PURPOSE: the validation of a new scoring model considering the principal risk factors of differentiated thyroid cancer (DTC) relapse. METHODS: we evaluated all DTC patients treated with thyroidectomy and radioactive iodine (RAI) therapy. Three domains were considered: the demographic domain (age and gender), the surgical domain (histology and the American Thyroid Association risk categories), and the RAI-related domain (pre-RAI thyroglobulin and post-therapeutic 131I whole-body scan). The progression-free survival was assessed. The patients' sample was randomly split into a training and validation set. The three-domain score was calculated as the weighted sum of the levels of each significant factor, then scaled to an integer range (0-100) and, finally, stratified into terciles: mild risk 0-33, moderate risk 34-66, and severe risk 67-100. RESULTS: 907 DTC patients were included. The RAI-related domain was the most relevant factor in the score calculation. The tercile stratification identified significantly different survival curves: patients within the two upper terciles showed approximately 6 to 30 times more progressive risk than patients at mild risk. CONCLUSION: we have validated a three-domain scoring system and the principal impact on this score is provided by the peri-RAI findings, whose prognostic role seems to be essential in risk identification.

Heterogeneity of bone metastases as an important prognostic factor in patients affected by oestrogen receptor-positive breast cancer. The role of combined [18F]Fluoroestradiol PET/CT and [18F]Fluorodeoxyglucose PET/CT.

PURPOSE: To assess the prognostic role of different inter and intralesional expression (heterogeneity) of oestrogen receptor (ER) in bone metastases, as identified by the combined use of [18F]FES PET/CT and [18F]FDG PET/CT in patients with oestrogen receptor-positive (ER+) metastatic breast cancer (BC). METHODS: We analysed patients with a new diagnosis of bone metastases who were candidates for first-line systemic endocrine therapy. Before starting therapy, patients underwent baseline [18F]FES PET/CT and [18]FDG PET/CT. Semi-quantitative evaluation of whole-body bone metabolic burden (WB-B-MB) was performed on [18F]FES and [18F]FDG PET/CT in order to evaluate disease extent, tumour metabolism and ER heterogeneity. We used time-to-event analyses (Kaplan-Meier and Cox proportional-hazards methods) to estimate progression-free (PFS) and overall survival (OS), in order to assess the independent prognostic value of [18F]FES PET/CT and [18F]FDG PET/CT, alone and in combination. RESULTS: According to our criteria, we enrolled 49 patients. Over a median follow-up of 44.7 months, 35 patients suffered disease progression (71.4 %) and 15 died of disease (30.6 %). When the risk of disease progression was calculated by means of the Cox model, only [18F]FDG WB-B-MB was independently and directly associated to PFS (p = 0.02). On analysing the association between all prognostic parameters and survival, the Cox model showed that the only parameter associated with OS was the WB-B-MB FES/FDG ratio (p = 0.01). CONCLUSION: The combined use of [18F]FES-PET/CT and [18F]FDG-PET/CT can identify ER heterogeneity in BC bone metastases. This heterogeneity is significantly associated with survival. Moreover, the extension of the FDG-avid component correlates with the risk of disease progression.

Association Between the Multidimensional Prognostic Index and Mortality During 15 Years of Follow-up in the InCHIANTI Study.

BACKGROUND: Multidimensional Prognostic Index (MPI) is recognized as a prognostic tool in hospitalized patients, but data on the value of MPI in community-dwelling older persons are limited. Using data from a representative cohort of community-dwelling persons, we tested the hypothesis that MPI explains mortality during 15 years of follow-up. METHODS: A standardized comprehensive geriatric assessment was used to calculate the MPI and to categorize participants in low-, moderate-, and high-risk classes. The results were reported as hazard ratios (HRs) and the accuracy was evaluated with the area under the curve (AUC), with 95% confidence intervals (CIs) and the C-index. We also reported the median survival time by standard age groups. RESULTS: All 1453 participants (mean age 68.9 years, women = 55.8%) enrolled in the InCHIANTI study at baseline were included. Compared to low-risk group, participants in moderate (HR = 2.10; 95% CI: 1.73-2.55) and high-risk MPI group (HR = 4.94; 95% CI: 3.91-6.24) had significantly higher mortality risk. The C-index of the model containing age, sex, and MPI was 82.1, indicating a very good accuracy of this model in explaining mortality. Additionally, the time-dependent AUC indicated that the accuracy of the model incorporating MPI to age and sex was excellent (>85.0) during the whole follow-up period. Compared to participants in the low-risk MPI group across different age groups, those in moderate- and high-risk groups survived 2.9-7.0 years less and 4.3-8.9 years less, respectively. CONCLUSIONS: In community-dwelling individuals, higher MPI values are associated with higher risk of all-cause mortality with a dose-response effect.

Multidimensional prognostic index (MPI) predicts successful application for disability social benefits in older people.

AIM: The economic recognition of disability is of importance in daily practice, but the tools used in older people are still limited. Therefore, we aimed to investigate the effectiveness of the multidimensional prognostic index (MPI) to identify frail older subjects to be submitted to civil invalidity application for disability benefits including Attendance Allowance (AA) indemnity, Carer's Leave (Law 104) and/or Parking Card for people with disabilities. METHODS: From March 2018 to January 2019, 80 older people were included. The MPI was calculated from comprehensive geriatric assessment information including eight different domains. Civil benefits included attendance allowance (AA) indemnity by the Local Medico-Legal Committee (MLC-NHS) and by the National Institute of Social Security Committee (INPS), Carer's Leave (Law 104), and Parking Card for people with disabilities. RESULTS: MPI values were associated with an increased probability to obtain a 100% civil disability, AA indemnity, Carer's Leave and a parking card for people with disabilities. MPI score showed a very good accuracy in predicting the civil invalidity benefits with a area-under-curve (AUC) of 87.3 (95% CI 80.6-97.4) to predict the release of AA indemnity, 81.3 (95% CI 68.5-91.1) to predict Care's leave and 70.7 (95% CI 59.4-84.7) to predict the Parking Card release. Moreover, data showed that a cut-off score of MPI ≥ 0.75 could identify the 100% of older subjects who successfully obtained the indemnity release. CONCLUSION: MPI is an excellent predictor of social benefits' release by local and national agencies.

The impact of oral health on prognosis of older multimorbid inpatients: the 6-month follow up MPI oral health study (MPIOH).

PURPOSE: There is clear evidence for an association between oral health and systemic illnesses, geriatric syndromes, and mortality. Frail and multimorbid older people often suffer from insufficient oral health care, but standardized dental examinations are not routinely performed in clinical settings. The aim of this study was to verify the practicability of in-hospital oral health examinations and to identify their association with patients' prognosis as assessed by means of the Comprehensive Geriatric Assessment (CGA)-based Multidimensional Prognostic Index (MPI). METHODS: One hundred hospitalized patients aged 65 years and older (mean age 76.9 years (SD 6.4); 58.2% male, 41.8% female) underwent a CGA-based MPI calculation at discharge with subdivision into three mortality risk groups (MPI-1, low risk, score 0-0.33; MPI-2, moderate risk, score 0.34-0.66; MPI-3, high risk, score 0.67-1). To identify the current oral health status and the Oral Health-related Quality of Life (OHRQoL), three oral health examinations were performed. Information on survival, the incidence of oral diseases, dental appointments, and treatments up to 6 months after discharge were collected. RESULTS: All oral health examinations were feasible during hospitalization and were associated with MPI prognosis, even though they were not associated with 6-month mortality. The MPI could not predict the use of dental health care or treatment, as, irrespective of MPI and oral health examinations, dental services were underutilized during follow up. CONCLUSION: Besides MPI evaluation, oral health examinations should be implemented into an inhospital course to improve clinical decision-making as well as secondary and tertiary prevention of oral health- and related systemic diseases. TRIAL REGISTRATION NUMBER: German Clinical Trials Register: DRKS00013607 (07.02.2019, retrospectively registered).

How to better stratify the risk of differentiated thyroid carcinomas: the key role of radioactive iodine therapy, age, and gender.

PURPOSE: The risk of relapse of differentiated thyroid carcinomas (DTC) and their indication for radioactive iodine therapy (RAI) are assessed according to ATA risk stratification system principally based on tumor-nodes-metastasis (TNM) staging. However, while establishing the indication for RAI may be a "dilemma," performing it can improve the risk stratification. We aimed to evaluate whether (1) the stratification of risk of recurrence differs when TNM is considered with or without peri-RAI findings and (2) the assessment of the risk of disease-specific mortality is improved by adding age and gender. METHODS: From our database, all DTC patients treated with thyroidectomy and RAI from 1992 to 2017 were included. Subjects with a follow-up shorter than 1 year and positive thyroid antibodies were excluded. Patients were classified into (1) a three-category ATA model based on TNM (basic model) and (2) a five-category model based on TNM plus peri-RAI findings, i.e., thyroglobulin and 131I whole-body scan (advanced model). Relapse was proven by histology and/or imaging. Differences in disease-free survival (DFS) and overall survival (OS) were assessed. RESULTS: We enrolled 907 patients; of these, 4.4% died and 21% suffered recurrence. According to the basic model, there were 11.8% high-risk, 32.9% intermediate-risk, and 55.3% low-risk patients. According to the advanced model, 29.9% of patients were re-classified in a higher risk category and the five categories of this model displayed significantly different risks of relapse and death. The estimate of DFS was significantly higher in the advanced model than in the basic one (ΔC-index = + 6.8%, P < .001). By adding age and gender to the advanced model, the highest performance in predicting death was achieved (ΔC-index = + 5.1%, P < .001). CONCLUSIONS: The peri-RAI findings are essential in order to carefully stratify the risk of DTC recurrence. Integrating these data with age and gender enables those cases at highest risk of death to be identified.

Immediate Breast Reconstruction after mastectomy with polyurethane implants versus textured implants: A retrospective study with focus on capsular contracture.

BACKGROUND: Capsular contracture (CC) is the most common complication following Immediate Breast Reconstruction (IBR) with breast implants. Different implant surfaces were developed aiming to reduce the incidence of CC. We evaluated the incidence and degree of CC after Direct-to-Implant (DTI) IBR with insertion of textured (TE) or polyurethane (PU) covered implants. METHODS: A retrospective review of consecutive patients treated at our Institution with mastectomy and one-stage IBR and implant reconstruction between 2013 and 2018, with or without post mastectomy radiation therapy (PMRT), was conducted. Immediate breast reconstruction was performed by implanting 186 PU covered implants and 172 TE implants. RESULTS: Three-hundred-twelve women underwent 358 DTI IBR with PU or TE implants, were analyzed with a median follow-up time of 2.3 years (range 1.0-3.0). The overall rate of CC Baker grade III and IV was 11.8% (95%CI: 8.4-16.3), while, after PU and TE implant placement it was 8.1% (95% CI: 4.1-15.7) and 15.8% (95% CI: 4.1-15.7) [p = 0.009]), respectively. Irradiated breasts developed CC more frequently rather than non-irradiated breasts (HR = 12.5, p < 0.001), and the relative risk was higher in the TE group compared with the PU group (HR = 0.3, p = 0.003). CONCLUSIONS: After mastectomy and one-stage IBR, the use of PU covered implants is associated with a lower incidence of CC compared to TE implants. This advantage is amplified several folds for patients who necessitate PMRT. Footnote: Capsular contracture (CC); Immediate Breast Reconstruction (IBR); Directto- Implant (DTI); Textured (TE); Polyurethane (PU); Post mastectomy radiation therapy (PMRT); Nipple Sparing mastectomy (NSM).

Pharmacokinetics, safety, and activity of trabectedin as first-line treatment in elderly patients who are affected by advanced sarcoma and are unfit to receive standard chemotherapy: A phase 2 study (TR1US study) from the Italian Sarcoma Group.

BACKGROUND: Although elderly patients (≥70 years) represent 30% of new diagnoses of soft tissue sarcoma (STS), they are underrepresented in clinical trials and are often unfit to receive standard anthracycline-based chemotherapy. Trabectedin is registered as a second-line treatment for advanced STS and is characterized by a favorable safety profile. METHODS: The aim of this single-arm, phase 2 study was to investigate trabectedin (scheduled dose, 1.3-1.5 mg/m2 ) as a first-line treatment in elderly patients with advanced stage STS who are inoperable and are unfit to receive standard anthracycline-based chemotherapy. The coprimary endpoints were progression-free survival at 3 months (PFS3) and the rate of clinically limiting toxicities (CLTs). We also conducted an ancillary study on pharmacokinetics. RESULTS: Twenty-four patients (12 men and 12 women) with a median age of 79 years (interquartile range [IQR], 74-83 years) were enrolled. The histological subtype was leiomyosarcoma in 46%, liposarcoma in 33%, and other histotypes in 21%. The median number of trabectedin courses was 4 (IQR, 3-6), with 7 patients (29%) receiving ≥6 cycles. Eight patients (33%) required dose reductions. The most frequent grade 3/4 adverse events were neutropenia in 9 patients (38%), fatigue in 5 patients (21%), and aminotransferase elevation in 5 patients (21%). PFS3, median PFS, and overall survival were 71% (80% CI, 57%-81%), 4 months, and 12 months, respectively. Ten patients (42% [80% CI, 28%-57%]) experienced CLTs. Trabectedin Cmax , half-life, clearance, and distribution volume were 1.28 ng/mL (standard deviation [SD], 0.58 ng/mL), 26.70 hours (SD, 9.09 hours), 39.98 L/h/m2 (SD, 14.08 L/h/m2 ), and 1460 L/m2 (SD, 561 L/m2 ), respectively. CONCLUSION: Trabectedin can be administered safely to elderly patients with STS who are unfit to receive anthracyclines. Pharmacokinetics in the elderly population was superimposable to historical data.

Development and validation of a robotic multifactorial fall-risk predictive model: A one-year prospective study in community-dwelling older adults.

BACKGROUND: Falls in the elderly are a major public health concern because of their high incidence, the involvement of many risk factors, the considerable post-fall morbidity and mortality, and the health-related and social costs. Given that many falls are preventable, the early identification of older adults at risk of falling is crucial in order to develop tailored interventions to prevent such falls. To date, however, the fall-risk assessment tools currently used in the elderly have not shown sufficiently high predictive validity to distinguish between subjects at high and low fall risk. Consequently, predicting the risk of falling remains an unsolved issue in geriatric medicine. This one-year prospective study aims to develop and validate, by means of a cross-validation method, a multifactorial fall-risk model based on clinical and robotic parameters in older adults. METHODS: Community-dwelling subjects aged ≥ 65 years were enrolled. At the baseline, all subjects were evaluated for history of falling and number of drugs taken daily, and their gait and balance were evaluated by means of the Timed "Up & Go" test (TUG), Gait Speed (GS), Short Physical Performance Battery (SPPB) and Performance-Oriented Mobility Assessment (POMA). They also underwent robotic assessment by means of the hunova robotic device to evaluate the various components of balance. All subjects were followed up for one-year and the number of falls was recorded. The models that best predicted falls-on the basis of: i) only clinical parameters; ii) only robotic parameters; iii) clinical plus robotic parameters-were identified by means of a cross-validation method. RESULTS: Of the 100 subjects initially enrolled, 96 (62 females, mean age 77.17±.49 years) completed the follow-up and were included. Within one year, 32 participants (33%) experienced at least one fall ("fallers"), while 64 (67%) did not ("non-fallers"). The best classifier model to emerge from cross-validated fall-risk estimation included eight clinical variables (age, sex, history of falling in the previous 12 months, TUG, Tinetti, SPPB, Low GS, number of drugs) and 20 robotic parameters, and displayed an area under the receiver operator characteristic (ROC) curve of 0.81 (95% CI: 0.72-0.90). Notably, the model that included only three of these clinical variables (age, history of falls and low GS) plus the robotic parameters showed similar accuracy (ROC AUC 0.80, 95% CI: 0.71-0.89). In comparison with the best classifier model that comprised only clinical parameters (ROC AUC: 0.67; 95% CI: 0.55-0.79), both models performed better in predicting fall risk, with an estimated Net Reclassification Improvement (NRI) of 0.30 and 0.31 (p = 0.02), respectively, and an estimated Integrated Discrimination Improvement (IDI) of 0.32 and 0.27 (p<0.001), respectively. The best model that comprised only robotic parameters (the 20 parameters identified in the final model) achieved a better performance than the clinical parameters alone, but worse than the combination of both clinical and robotic variables (ROC AUC: 0.73, 95% CI 0.63-0.83). CONCLUSION: A multifactorial fall-risk assessment that includes clinical and hunova robotic variables significantly improves the accuracy of predicting the risk of falling in community-dwelling older people. Our data suggest that combining clinical and robotic assessments can more accurately identify older people at high risk of falls, thereby enabling personalized fall-prevention interventions to be undertaken.

Testing longitudinal data for prognostication in ambulatory heart failure patients with reduced ejection fraction. A proof of principle from the GISSI-HF database.

BACKGROUND: Variability of parameter measurements in heart failure with reduced ejection fraction (HFrEF) may contribute to reducing the prediction accuracy of available prognostic models. We investigated whether the use of longitudinal versus cross-sectional measurements of established predictors of mortality in patients with HFrEF would increase the accuracy of prognostication. METHODS: We used longitudinal measurements of systolic blood pressure (SBP), heart rate, hemoglobin, creatinine and uric acid from HFrEF patients enrolled in the GISSI-HF trial. We performed linear mixed models to investigate the difference in first 6-month trajectories of these parameters between patients alive and dead at 4-year follow-up, and examined the change in prediction accuracy by comparing area under the curve (AUC) and net reclassification index (NRI) values obtained using a traditional cross-sectional survival model versus a longitudinal joint model using information up to 6-month follow-up. RESULTS: We included 5469 patients with 32,206 repeated visits and measurements. We demonstrated a significant difference in the first 6-month change of each one of the selected parameters between those alive and dead at the end of follow-up (p-value for time∗mortality interaction ≤0.01). The comparison of prediction accuracy of the two models revealed a significant increase of about 2% in the AUCs when using longitudinal values of each parameter of interest up to 6 months, with significant concomitant increase in NRI. The greatest increase in accuracy was noticed when using longitudinal SBP measurements in patients with baseline SBP ≤ 110 mmHg. CONCLUSIONS: Our findings support the use of longitudinal data to improve prognostication in patients with HFrEF, and warrant validation in external cohorts and creation of new prognostic tools.