Ductal invasive carcinoma arising within atypical microglandular adenosis in a patient with BRCA-1 mutation: A case report

Abstract Microglandular adenosis (MGA) of the breast is a benign lesion that may mimic invasive carcinoma and which has been proposed to be a potential precursor of a well defined subset of triple-negative and basal-like breast carcinomas, characterized by specific expression of both basal and luminal markers (positive for EGFr and luminal cytokeratins such as CK 8/18, negative for high molecular weight cytokeratins such as CK 5/6), with a crucial role played by p53 mutation as "driver mutation" in the multistep model of cancerization. When an invasive carcinoma arises in a background of MGA, it is possible to identify a clear multistep transition from conventional MGA to atypical MGA (AMGA), Ductal Carcinoma In Situ (DCIS) arising within AMGA and invasive carcinoma. This is the first histological case report of an invasive carcinoma arising within MGA and AMGA in a patient carrying a germline BRCA-1 mutation, recognized as one of the most important genetic alterations correlated with the development of triple-negative carcinoma

An analysis of clinical, surgical, pathological and molecular characteristics of endometrial cancer according to mismatch repair status. A multidisciplinary approach

Since 2016, our hospital has applied tumor testing with immunohistochemistry (IHC) in endometrial cancer in order to detect mutations of mismatch repair genes (MMR). All cases with MMR deficiency proteins expression are sent for genetic testing, except those with MLH1 protein deficiency, in which case genetic testing is performed if negative for promoter hypermethylation. The primary aim of this study was to investigate the ability of our algorithm to identify Lynch syndrome (LS). The Secondary aims were to investigate the relationship between MMR status and clinicopathological features and prognosis of primary endometrial cancer (EC). From January 2016 to December 2018, 239 patients with EC were retrospectively analyzed and subdivided according to MMR status. Patients were divided in three groups: MMR proficient, LS and Lynch-like cancer (LLC). LS was characterized by a lower age and BMI, more use of contraceptive and less use of hormonal replacement therapy, nulliparity and a trend versus a better prognosis. LLC appeared more related to MMR proficient than LS and exhibited a more aggressive behavior. Our multidisciplinary approach permitted a correct diagnosis of germline mutation in patients with newly diagnosis EC and it confirmed clinicopathologic and prognostic characteristics of LS

BRCA-Associated Ovarian Cancer: From Molecular Genetics to Risk Management

Ovarian cancer (OC) mostly arises sporadically, but a fraction of cases are associated with mutations in BRCA1 and BRCA2 genes. The presence of a BRCA mutation in OC patients has been suggested as a prognostic and predictive factor. In addition, the identification of asymptomatic carriers of such mutations offers an unprecedented opportunity for OC prevention. This review is aimed at exploring the current knowledge on epidemiological and molecular aspects of BRCA-associated OC predisposition, on pathology and clinical behavior of OC occurring in BRCA mutation carriers, and on the available options for managing asymptomatic carriers

Characterization of BRCA Deficiency in Ovarian Cancer

BRCA testing is recommended in all Ovarian Cancer (OC) patients, but the optimal approach is debated. The landscape of BRCA alterations was explored in 30 consecutive OC patients: 6 (20.0%) carried germline pathogenic variants, 1 (3.3%) a somatic mutation of BRCA2, 2 (6.7%) unclassified germline variants in BRCA1, and 5 (16.7%) hypermethylation of the BRCA1 promoter. Overall, 12 patients (40.0%) showed BRCA deficit (BD), due to inactivation of both alleles of either BRCA1 or BRCA2, while 18 (60.0%) had undetected/unclear BRCA deficit (BU). Regarding sequence changes, analysis performed on Formalin-Fixed-Paraffin-Embedded tissue through a validated diagnostic protocol showed 100% accuracy, compared with 96.3% for Snap-Frozen tissue and 77.8% for the pre-diagnostic Formalin-Fixed-Paraffin-Embedded protocol. BD tumors, compared to BU, showed a significantly higher rate of small genomic rearrangements. After a median follow-up of 60.3 months, the mean PFS was 54.9 ± 27.2 months in BD patients and 34.6 ± 26.7 months in BU patients (p = 0.055). The analysis of other cancer genes in BU patients identified a carrier of a pathogenic germline variant in RAD51C. Thus, BRCA sequencing alone may miss tumors potentially responsive to specific treatments (due to BRCA1 promoter methylation or mutations in other genes) while unvalidated FFPE approaches may yield false-positive results

Electromechanical and robotic devices for gait and balance rehabilitation of children with neurological disability: a systematic review

In the last two decades, a growing interest has been focused on gait and balance robot-assisted rehabilitation in children with neurological disabilities. Robotic devices allow the implementation of intensive, task-specific training fostering functional recovery and neuroplasticity phenomena. However, limited attention has been paid to the protocols used in this research framework. This systematic review aims to provide an overview of the existing literature on robotic systems for the rehabilitation of gait and balance in children with neurological disabilities and their rehabilitation applications. The literature search was carried out independently and synchronously by three authors on the following databases: MEDLINE, Cochrane Library, PeDro, Institute of Electrical and Electronics Engineers, ScienceDirect, and Google Scholar. The data collected included three subsections referring to clinical, technical, and regulatory aspects. Thirty-one articles out of 81 found on the primary literature search were included in the systematic review. Most studies involved children with cerebral palsy. Only one-third of the studies were randomized controlled trials. Overall, 17 devices (nine end-effector systems and eight exoskeletons) were investigated, among which only 4 (24%) were bore the CE mark. Studies differ on rehabilitation protocols duration, intensity, and outcome measures. Future research should improve both rehabilitation protocols\u2019 and devices\u2019 descriptions

Robot-assisted upper limb training for patients with multiple sclerosis: an evidence-based review of clinical applications and effectiveness

Upper extremities limitation is a common functional impairment in patients with Multiple Sclerosis (PwMS). Novel technological devices are increasingly used in neurorehabilitation to support motor function improvement and the quantitative assessment of motor performance during training in patients with neurological diseases. In this review, we systematically report the evidence on clinical applications and robotic-assisted arm training (RAT) in functional recovery in PwMS. PubMed/MEDLINE, the Cochrane Library, and the Physiotherapy Evidence Database (PEDro) databases were systematically searched from inception to March 2021. The 10-item PEDro scale assessed the study quality for the RCT, and the AMSTAR-2 was used to assess the quality of the systematic review. The 5-item Oxford CEBM scale was used to rate the level of evidence. A total of 10 studies (161 subjects) were included. The selected studies included one systematic review, four RCTs, one randomized crossover, and four case series. The RCTs were scored as high-quality studies, while the systematic review was determined to be of low quality. Shoulder range of motion, handgrip strength, and proximal arm impairment improved after RAT. Manual dexterity, arm function, and use in daily life also ameliorated arm function. The high clinical heterogeneity of treatment programs and the variety of robot devices affects the generalizability of the study results; therefore, we emphasize the need to standardize the intervention type in future studies that evaluate the role of robotic-assisted training in PwMS. Robot-assisted treatment seems safe and useful to increase manual dexterity and the quality of movement execution in PwMS with moderate to severe disability. Additional studies with an adequate sample size and methodological rigour are warranted to drive definite conclusion

Upper limb robotic rehabilitation for patients with cervical spinal cord injury: a comprehensive review

The upper extremities limitation represents one of the essential functional impairments in patients with cervical spinal cord injury. Electromechanics assisted devices and robots are increasingly used in neurorehabilitation to help functional improvement in patients with neurological diseases. This review aimed to systematically report the evidence-based, state-of-art on clinical applications and robotic-assisted arm training (RAT) in motor and functional recovery in subjects affected by cervical spinal cord injury. The present study has been carried out within the framework of the Italian Consensus Conference on "Rehabilitation assisted by robotic and electromechanical devices for persons with disability of neurological origin" (CICERONE). PubMed/MEDLINE, Cochrane Library, and Physiotherapy Evidence Database (PEDro) databases were systematically searched from inception to September 2021. The 10-item PEDro scale assessed the study quality for the RCT and the AMSTAR-2 for the systematic review. Two different authors rated the studies included in this review. If consensus was not achieved after discussion, a third reviewer was interrogated. The five-item Oxford CEBM scale was used to rate the level of evidence. A total of 11 studies were included. The selected studies were: two systematic reviews, two RCTs, one parallel-group controlled trial, one longitudinal intervention study and five case series. One RCT was scored as a high-quality study, while the systematic review was of low quality. RAT was reported as feasible and safe. Initial positive effects of RAT were found for arm function and quality of movement in addition to conventional therapy. The high clinical heterogeneity of treatment programs and the variety of robot devices could severely affect the generalizability of the study results. Therefore, future studies are warranted to standardize the type of intervention and evaluate the role of robotic-assisted training in subjects affected by cervical spinal cord injury

Effects of robotic upper limb treatment after stroke on cognitive patterns: A systematic review

Background: Robotic therapy (RT) has been internationally recognized for the motor rehabilitation of the upper limb. Although it seems that RT can stimulate and promote neuroplasticity, the effectiveness of robotics in restoring cognitive deficits has been considered only in a few recent studies. Objective: To verify whether, in the current state of the literature, cognitive measures are used as inclusion or exclusion criteria and/or outcomes measures in robotic upper limb rehabilitation in stroke patients. Methods: The systematic review was conducted according to PRISMA guidelines. Studies eligible were identified through PubMed/MEDLINE and Web of Science from inception to March 2021. Results: Eighty-one studies were considered in this systematic review. Seventy-three studies have at least a cognitive inclusion or exclusion criteria, while only seven studies assessed cognitive outcomes. Conclusion: Despite the high presence of cognitive instruments used for inclusion/exclusion criteria their heterogeneity did not allow the identification of a guideline for the evaluation of patients in different stroke stages. Therefore, although the heterogeneity and the low percentage of studies that included cognitive outcomes, seemed that the latter were positively influenced by RT in post-stroke rehabilitation. Future larger RCTs are needed to outline which cognitive scales are most suitable and their cut-off, as well as what cognitive outcome measures to use in the various stages of post-stroke rehabilitation

Integrated clinicopathologic and molecular analysis of endometrial carcinoma: Prognostic impact of the new ESGO-ESTRO-ESP endometrial cancer risk classification and proposal of histopathologic algorithm for its implementation in clinical practice

IntroductionThe European Society of Gynecologic Oncology/European Society of Radiation Therapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) committee recently proposed a new risk stratification system for endometrial carcinoma (EC) patients that incorporates clinicopathologic and molecular features. The aim of the study is to compare the new ESGO/ESTRO/ESP risk classification system with the previous 2016 recommendations, evaluating the impact of molecular classification and defining a new algorithm for selecting cases for molecular analysis to assign the appropriate risk class.MethodsThe cohort included 211 consecutive EC patients. Immunohistochemistry and next-generation sequencing were used to assign molecular subgroups of EC: POLE mutant (POLE), mismatch repair deficient (MMRd), p53 mutant (p53abn), and no specific molecular profile (NSMP).ResultsImmuno-molecular analysis was successful in all cases, identifying the four molecular subgroups: 7.6% POLE, 32.2% MMRd, 20.9% p53abn, and 39.3% NSMP. The recent 2020 guidelines showed a 32.7% risk group change compared with the previous 2016 classification system: the reassignment is due to POLE mutations, abnormal p53 expression, and a better definition of lymphovascular space invasion. The 2020 system assigns more patients to lower-risk groups (42.2%) than the 2016 recommendation (25.6%). Considering the 2020 risk classification system that includes the difference between “unknown molecular classification” and “known,” the integration of molecular subgroups allowed 6.6% of patients to be recategorized into a different risk class. In addition, the use of the proposed algorithm based on histopathologic parameters would have resulted in a 62.6% reduction in molecular analysis, compared to applying molecular classification to all patients.ConclusionApplication of the new 2020 risk classification integrating clinicopathologic and molecular parameters provided more accurate identification of low-and high-risk patients, potentially allowing a more specific selection of patients for post-operative adjuvant therapy. The proposed histopathologic algorithm significantly decreases the number of tests needed and could be a promising tool for cost reduction without compromising prognostic stratification

The characteristics and activities of child and adolescent mental health services in Italy: a regional survey

<p>Abstract</p> <p>Background</p> <p>To date, no studies have assessed in detail the characteristics, organisation, and functioning of Child and Adolescent Mental Health Services (CAMHS). This information gap represents a major limitation for researchers and clinicians because most mental disorders have their onset in childhood or adolescence, and effective interventions can therefore represent a major factor in avoiding chronicity. Interventions and mental health care are delivered by and through services, and not by individual, private clinicians, and drawbacks or limitations of services generally translate in inappropriateness and ineffectiveness of treatments and interventions: therefore information about services is essential to improve the quality of care and ultimately the course and outcome of mental disorders in childhood and adolescence.</p> <p>The present paper reports the results of the first study aimed at providing detailed, updated and comprehensive data on CAMHS of a densely populated Italian region (over 4 million inhabitants) with a target population of 633,725 subjects aged 0-17 years.</p> <p>Methods</p> <p>Unit Chiefs of all the CAMHS filled in a structured 'Facility Form', with activity data referring to 2008 (data for inpatient facilities referred to 2009), which were then analysed in detail.</p> <p>Results</p> <p>Eleven CAMHS were operative, including 110 outpatient units, with a ratio of approximately 20 child psychiatrists and 23 psychologists per 100,000 inhabitants aged 0-17 years. All outpatient units were well equipped and organized and all granted free service access. In 2008, approximately 6% of the target population was in contact with outpatient CAMHS, showing substantial homogeneity across the eleven areas thereby. Most patients in contact in 2008 received a language disorder- or learning disability diagnosis (41%). First-ever contacts accounted for 30% of annual visits across all units. Hospital bed availability was 5 per 100,000 inhabitants aged 0-17 years.</p> <p>Conclusion</p> <p>The percentage of young people in contact with CAMHS for mental disorders is in line with those observed in previous epidemiological studies. The overall number of child psychiatrists per 100,000 inhabitants is one of the highest in Europe and it is comparable with the most well equipped areas in the US. This comparison should be interpreted with caution, however, because in Italy, child psychiatrists also treat neurological disorders. Critical areas requiring improvement are: the uneven utilisation of standardised assessment procedures and the limited availability of dedicated emergency services during non-office hours (e.g., nights and holidays).</p