IRIS UniSR (’Università Vita-Salute San Raffaele)
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Treatment of progressive locally advanced and metastatic basal cell carcinoma after two lines of treatment with hedgehog inhibitors and anti-PD1: The role of sonidegib rechallenge
No full textRobotic Surgery Is a Safe Treatment in Very Elderly Patients with Resectable Lung Cancer
No full text: Background: Lung cancer represents a significant health concern, particularly among the elderly population. With global life expectancy increasing, the number of very elderly patients is rising. Robotic-assisted thoracic surgery (RATS) offers potential advantages over both traditional and video-assisted thoracoscopic surgery (VATS). This study aims to evaluate the feasibility and safety of RATS in very elderly patients (VEP) diagnosed with lung cancer. Methods: This retrospective study included patients who underwent major lung resections using RATS between 2015 and 2022 at two specialized centers. Patients were divided into very elderly patients (VEP, ≥80 years) and non-elderly patients (NEP, <80 years). Demographic, clinical, and surgical data were analyzed. Propensity score matching (PSM) at a 1:3 ratio was performed using clinically relevant variables that were significantly different at baseline to balance the two groups. Results: This study included 340 patients: 28 VEP and 312 NEP. Before PSM, VEP had higher ASA scores, more advanced disease stages, and increased comorbidities. Despite these differences, postoperative outcomes were comparable. Complications occurred in 42.9% of VEP and 29.8% of NEP (p = 0.16), but grade III complications were observed in 14.3% of VEP and 6.4% of NEP (p = 0.12), and grade IV complications were observed in 0% of VEP and 0.9% of NEP (p = not estimable). The mean hospital stay was 4 days in both groups (p = 0.99). Even after PSM (26 VEP vs. 71 NEP), complications, hospital stay, and 90-day mortality (3.9% in VEP, 0% in NEP) were similar. Multivariable analysis identified reduced FEV1 as a predictor of complications, while pathological stage I and lobectomy were associated with a decreased risk of complications, both before and after PSM. Conclusions: RATS is a safe and feasible option for selected very elderly patients with lung cancer, yielding outcomes comparable to younger patients
The role of allogeneic stem cell transplantation in acute myeloid leukemia with translocation t(8;16)(p11;p13)
Get PDFAcute myeloid leukemia (AML) with translocation t(8;16)(p11;p13) represents a rare entity that has been categorized as a disease-defining recurring cytogenetic abnormality with adverse risk in the 2022 European LeukemiaNet classification. This rating was mainly based on a retrospective analysis comprising patients from several large clinical trials, which, however, included only 21 patients treated with allogeneic stem cell transplantation (alloSCT). Therefore, the European Society for Blood and Marrow Transplantation performed a registry study on a larger cohort to evaluate the role of alloSCT in t(8;16) AML. Sixty transplant recipients with t(8;16) AML were identified. Two-year overall and leukemia-free survival (OS/LFS) was 43/39%. Patients transplanted in first complete remission (CR1, n = 44) achieved a 2-year OS/LFS of 48%/48%. Following alloSCT in CR1, the multivariable analysis identified a complex karyotype (CK) as a major risk factor for relapse (HR 4.17, p =.016), lower LFS (HR 3.38, p =.01), and lower OS (HR 3.08, p =.017). Two-year OS/LFS of patients with CK was 19%/19%, in contrast to 67%/67% in patients with t(8;16) outside a CK. Other factors for inferior outcomes were older age and secondary AML. In summary, alloSCT could mitigate the adverse risk of patients with t(8;16) AML not harboring a CK, particularly when performed in CR1
Long-Term Effects of Atidarsagene Autotemcel for Metachromatic Leukodystrophy
No full textBACKGROUND: Metachromatic leukodystrophy (MLD) is an ultrarare, severe lysosomal storage disorder caused by a deficiency of arylsulfatase A (ARSA). METHODS: We treated patients who had MLD with atidarsagene autotemcel (arsa-cel), a hematopoietic stem-cell-based gene therapy, in two prospective open-label clinical studies and expanded-access programs. We compared their outcomes with those of untreated patients (natural history cohort). The primary end point was survival free from severe motor impairment (the time from birth to the first occurrence of loss of locomotion and of sitting without support or death from any cause). RESULTS: A total of 39 treated patients and 49 untreated patients were included. The median follow-up was 6.76 years (range, 0.64 to 12.19). Arsa-cel resulted in a significantly lower risk of severe motor impairment or death than no treatment among patients with presymptomatic late-infantile MLD (P<0.001), those with presymptomatic early-juvenile MLD (P = 0.04), and those with early-symptomatic early-juvenile MLD (P<0.001). The estimated percentage of patients surviving without severe motor impairment at 6 years of age was 0% (95% confidence interval [CI], not evaluable) among untreated patients with late-infantile MLD and 100% (95% CI, 100 to 100) among treated patients with presymptomatic late-infantile MLD. The estimated percentage of patients surviving without severe motor impairment at 10 years of age was 11.2% (95% CI, 0.9 to 36.4) among untreated patients with early-juvenile MLD and 87.5% (95% CI, 38.7 to 98.1) and 80.0% (95% CI, 40.9 to 94.6) among treated patients with presymptomatic and early-symptomatic early-juvenile MLD, respectively. No evidence of insertional oncogenesis was found. The most common grade 3 or higher adverse event was febrile neutropenia. Anti-ARSA antibodies were detected transiently in 6 of 39 patients (15%). Three deaths occurred, all of which were considered by the investigators to be unrelated to arsa-cel. CONCLUSIONS: Among patients with presymptomatic late-infantile or early-juvenile MLD and those with early-symptomatic early-juvenile MLD, the risk of severe motor impairment or death was significantly lower among those who received treatment with arsa-cel than in a natural history cohort that did not receive treatment. (Funded by Orchard Therapeutics and others; ClinicalTrials.gov numbers, NCT01560182 and NCT03392987.)
Tumour burden predicts outcomes after curative resection of multifocal intrahepatic cholangiocarcinoma
No full textBackground: Liver resection for multifocal intrahepatic cholangiocarcinoma (ICC) remains controversial due to a poor prognosis, driven by aggressive tumour biology. The aim of this study was to stratify multifocal ICC patients to identify those who are likely to benefit from resection. Methods: Patients who underwent upfront curative-intent hepatectomy for ICC were identified from an international multi-institutional database. Among patients with multifocal tumours, overall survival (OS) was analysed using multivariable Cox regression to identify prognostic factors. Tumour burden score (TBS) was used for stratification of multifocal ICC, with the optimal cut-off determined via restricted cubic spline (RCS) analysis. Results: Of 1502 patients, 208 (13.8%) had multifocal ICC. Among them, independent predictors of prognosis included TBS (HR 1.09), ASA grade >II (HR 1.48), cirrhosis (HR 2.05), periductal infiltrating/mass forming plus periductal infiltrating morphological subtype (HR 1.58), and receipt of adjuvant chemotherapy (HR 0.59). RCS analysis identified a TBS of 7.0 as the optimal cut-off. Notably, multifocal ICC patients with a low TBS (<7.0) demonstrated comparable 3-year OS to solitary ICC patients with AJCC stage II/III. In contrast, patients with a high TBS (≥7.0) and multifocal ICC exhibited the worst prognosis (3-year OS: stage I and solitary 67.1%, stage II/III and solitary 43.2%, low TBS and multifocal 43.4%, and high TBS and multifocal 17.8% (P < 0.001)). Conclusion: Whereas patients with high-TBS multifocal ICC had a poor prognosis, individuals with low-TBS multifocal ICC demonstrated survival outcomes comparable to solitary ICC patients. These findings emphasize the importance of stratifying patients by tumour burden to guide surgical decision-making and optimize treatment strategies for multifocal ICC
Hyaluronic Acid and Calcium Hydroxyapatite in the Context of Hypertrophic Photoaging. Evaluation by 2D, 3D Photographs and Reflectance Confocal Microscopy (RCM)
No full textAtypical Mid-Late Phase ICGA Hyperfluorescence in a Secondary MEWDS Case: A Distinct Disease or a Shift in Our Understanding of MEWDS?
No full textPurpose: To report a secondary multiple evanescent white dot syndrome (MEWDS) case with peculiar indocyanine green angiography (ICGA) findings. Method: Report of a patient with sickle cell disease (SCD) and a longstanding macular hole who developed an atypical form of secondary MEWDS. Analysis of multimodal imaging findings was performed. Results: A 33-year-old female with SCD presented with a longstanding full-thickness macular hole in the left eye, but then was lost to follow-up. Upon her return nine months later, fundus examination revealed new, asymptomatic, yellowish lesions at the level of the outer retina or retinal pigment epithelium (RPE). ICGA showed a peculiar hyperfluorescence in mid-to-late phases, while fundus autofluorescence (FAF) highlighted distinct temporal patterns of hyper-autofluorescence. Some of the ICGA hyperfluorescent lesions displayed a central hypofluorescent core. The multimodal imaging findings suggest a distinct disease or a sequential mechanism in MEWDS pathophysiology. The process may begin with an initial photoreceptoritis, marked by primary self-resolving hyper-autofluorescence on FAF, followed by an early RPE dysfunction with choroidal hyperpermeability evidenced by mid-late phase ICGA hyperfluorescence, then more marked RPE dysfunction shown by late-phase ICGA hypofluorescence and FAF hyper-autofluorescence. Conclusion: This case describes an unusual secondary MEWDS presentation with unique imaging findings. The peculiar ICGA behavior and evolving FAF patterns may suggest either a distinct disease or a shift in our understanding of MEWDS involving photoreceptoritis, early RPE dysfunction, followed by more advanced RPE damage. The findings underscore the need for a nuanced approach to interpreting white-dot syndromes
The mediating role of adult attachment insecure style on the relationship between mentalization and adverse childhood experiences in a sample of community-dwelling adults
No full textdverse childhood experiences (ACEs) refer to any stressful or potentially traumatic events that happen before age 18 years. Early neglect and an early high–emotional environment seem to impair the normal acquisition of the understanding of the self and others (mentalization) and have an impact on the attachment relationship that persists into adulthood. Few studies have evaluated the associations between ACEs, attachment and mentalization in adult community samples. The present study aims to evaluate the associations among ACEs, adult attachment style in peer relationships and mentalization in a sample of 403 community–dwelling adults. Participants were administered the Childhood Abuse and Trauma Scale, the Attachment Style Questionnaire, and the Mentalization Questionnaire. The results showed significant associations between ACEs, mentalization, and adult insecure attachment style. Moreover, the insecure attachment styles Discomfort with Closeness and Need for Approval fully mediated the observed associations between ACEs and mentalization deficit. These data suggested that ACEs impact on mentalization via its effect on avoidant and preoccupied attachment style and that an adult insecure attachment style in individuals who experienced early adverse events could impair mentalization ability. Furthermore, they seem to present relevant clinical implications highlighting the importance of the development of a secure attachment relationship in the therapeutic context
Marcatori di sonno per la fenoconversione all'interno dello spettro delle alfa-sinucleinopatie
No full textIl disturbo comportamentale in sonno REM isolato (iRBD) è classificato come una parasonnia del sonno REM, che si colloca all'inizio dello spettro delle α-sinucleinopatie. Dato il suo ruolo come importante fattore di rischio di fenoconversione all’interno di questo ambito, l'identificazione di biomarcatori precoci, così come di fattori protettivi contro la neurodegenerazione, rappresenta un obiettivo primario. Tramite tre differenti studi, la mia tesi di dottorato ha cercato di esplorare il ruolo di diverse misure comportamentali, neuropsicologiche e neurofisiologiche, quali possibili marcatori precoci di fenoconversione nei pazienti affetti da iRBD. Il primo studio ha esplorato il ruolo della riserva cognitiva (CR) nell'iRBD in due modi. Innanzitutto, abbiamo valutato l'impatto della CR sul funzionamento cognitivo dei pazienti con iRBD, fornendo le prime evidenze a sostegno della CR come possibile fattore protettivo. In secondo luogo, abbiamo combinato misure di CR e riserva cerebrale (BR) per valutarne l'interazione e l'influenza sul carico patologico e sulle prestazioni cognitive nei pazienti con iRBD. In questo contesto, non solo abbiamo replicato le evidenze precedenti che collegano le alterazioni delle onde lente (SW) al deterioramento cognitivo, ma abbiamo anche suggerito una nuova interazione tra carico patologico e dinamiche del sonno a onde lente nell'iRBD. Il secondo studio aveva l’obiettivo di esplorare la possibile presenza di una disfunzione colinergica precoce a livello periferico nell'iRBD. I risultati hanno dimostrato la presenza di alterazioni nel riflesso pupillare alla luce, associate a prestazioni inferiori nell'elaborazione visuospaziale e visuopercettiva, fornendo prove a supporto della presenza di una disfunzione colinergica sottostante e supportando il ruolo della pupillometria in questo contesto. Infine, il terzo è uno studio pilota che aveva lo scopo di valutare la possibile presenza di disfunzioni nell’elaborazione temporale e nella sincronizzazione sensorimotoria nell'iRBD e indagare i ritmi elettroencefalografici a riposo. I risultati hanno suggerito la presenza di una disfunzione esecutiva che potrebbe sottostare alle alterazioni nell’elaborazione temporale e nella sincronizzazione sensorimotoria nei pazienti affetti da iRBD e hanno fornito ulteriori intuizioni rispetto alla natura della ritmicità intrinseca dell'individuo.
Nel complesso, questi diversi aspetti hanno permesso di delineare un puzzle complesso riguardante le varie disfunzioni, le cause fisiopatologiche, i meccanismi del disturbo e le possibili traiettorie cliniche che i pazienti affetti da iRBD possono incontrare nel loro percorso di malattia. La presente tesi di dottorato aggiunge un piccolo tassello al puzzle della conoscenza attuale in questo campo, con la speranza che possa contribuire ad aprire la strada a future ricerche terapeutiche.Isolated rapid eye-movement (REM) sleep behavior disorder (iRBD) is classified as a REM sleep parasomnia, that takes its stand at the beginning of the α-synucleinopathies spectrum. Since its role as an important risk factor of conversion within this field, the identification of timely biomarkers, but also protective factors against neurodegeneration is a leading objective. By means of three different studies, my PhD dissertation aimed to explore the role of behavioral, neuropsychological and neurophysiological measures, as possible early markers for disease progression in iRBD patients. The first study explored the role of cognitive reserve (CR) in iRBD in two ways. First, we evaluated the impact of CR on the cognitive functioning of iRBD patients and provided the first preliminary findings supporting CR as a possible protective factor in iRBD. Second, we combined CR and brain reserve (BR) measures in order to evaluate their interaction and influence on pathological burden and cognitive performance in iRBD. In this context, we not only replicated previous evidence linking slow waves (SW) disruption to cognitive impairment, but we also suggested a novel interaction between pathological burden and SW sleep dynamics in iRBD. The second study aimed to explore the possible presence of early peripheric cholinergic dysfunction in iRBD. The results demonstrated the presence of pupillary light reflex alterations which were associated with poorer performances in visuospatial and visuoperceptive processing, further indicating the presence of an underlying cholinergic dysfunction and supporting the role of pupillometry in this context. Finally, the third was a pilot study with the aim of evaluating the possible presence of temporal processing and sensorimotor synchronization dysfunctions in iRBD and to investigate resting-state electroencephalographic rhythms. The results suggested the presence of an executive-based dysfunction underlying timing-related impairments in iRBD and provided further insights into the nature of individual’s intrinsic rhythmicity.
Altogether these different aspects of iRBD pathology shaped a complex puzzle concerning the different dysfunctions, pathophysiological causes, disease mechanisms and future clinical trajectories that these patients may come across in their path. The present PhD dissertation adds a little piece to the puzzle of the current knowledge in this field, but I hope that this will contribute to paving the way for future therapeutic research
The posterior mitral leaflet overhang: A rare yet possible complication of percutaneous mitral valve procedures
No full text: The two surgical options for mitral valve regurgitation are replacement and repair, with annuloplasty being the cornerstone of correction. In cases of repair failure, especially in high surgical risk patients, transcatheter mitral valve-in-ring (MViR) procedures represent emerging and challenging options. Among the several complications linked to this treatment, this paper delves into the role that native mitral leaflets may play in precipitating acute bioprosthesis dysfunction in the MViR procedure. The literature extensively covers complications related to the anterior leaflet, including risks such as outflow tract obstruction and residual mitral insufficiency due to interaction between native and prosthetic leaflets. Conversely, complications involving the posterior leaflet are less understood and often overlooked. In this gap in the literature, we present a clinical case highlighting how a redundant native posterior mitral leaflet can unexpectedly lead to acute severe mitral insufficiency by interfering with prosthetic leaflets.The two surgical options for mitral valve regurgitation are replacement and repair, with annuloplasty being the cornerstone of correction. In cases of repair failure, especially in high surgical risk patients, transcatheter mitral valve-in-ring (MViR) procedures represent emerging and challenging options. Among the several complications linked to this treatment, this paper delves into the role that native mitral leaflets may play in precipitating acute bioprosthesis dysfunction in the MViR procedure. The literature extensively covers complications related to the anterior leaflet, including risks such as outflow tract obstruction and residual mitral insufficiency due to interaction between native and prosthetic leaflets. Conversely, complications involving the posterior leaflet are less understood and often overlooked. In this gap in the literature, we present a clinical case highlighting how a redundant native posterior mitral leaflet can unexpectedly lead to acute severe mitral insufficiency by interfering with prosthetic leaflets