Integrated care pathways and the hub-and-spoke model for the management of non-melanoma skin cancer: A proposal of the Italian Association of Hospital Dermatologists (ADOI).

The term non-melanoma skin cancer (NMSC) refers to skin cancer different from melanoma, and it is usually restricted to basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and their pre-cancerous lesions, e.g., actinic keratosis. These conditions represent the most frequent tumors in Caucasians and are characterized by an increasing incidence worldwide and a high socio-economic impact. The term Integrated Care Pathway (ICP) refers to "a complex intervention for the mutual decision making and organization of care processes for a well-defined group of patients during a well-defined period". The purpose of this paper is to present a proposal from the Italian Association of Hospital Dermatologists (ADOI) for an ICP organization of care of NMSC, considering the hub-and-spoke model in the different geographical areas. This proposal is based on the most recent literature and on documents from the Italian Association of Medical Oncology (AIOM), the European consensus-based interdisciplinary guidelines from the European Association of Dermato- Oncology (EADO), and the National Comprehensive Cancer Network (NCCN). We initially discuss the NMSC outpatient clinic, the role of the multidisciplinary working groups, and the hub-and-spoke model regarding this topic. Then, we define the ICP processes specific for BCC and SCC. The ICP for NMSC is an innovative strategy to guarantee the highest possible quality of health care while the hub-andspoke model is crucial for the organization of different health care structures. Considering the importance on this topic, it is essential to create a valid ICP together with an efficient organization within the different geographical areas.

Hypothalamitis and pituitary atrophy.

Hypothalamitis is a rare inflammatory disorder involving the hypothalamus and classified as primary, or isolated, and secondary hypothalamitis. Secondary hypothalamitis although very rare is more common than the primary one and may occur in patients affected by autoimmune diseases such as autoimmune hypophysitis, systemic autoimmune diseases, infective diseases in patients affected by immune-deficit, paraneoplastic encephalitis, or in patients treated with immune checkpoint inhibitors. In accordance with the rarity of this disease, diagnosis and management of hypothalamitis prove to be challenging. The diagnosis requires a high index of clinical suspicion. The main symptoms may be: various degrees of hypopituitarism, neuropsychiatric and behavioral disorders, and disturbances of autonomic and metabolic regulation. Magnetic resonance images play a crucial role in the diagnosis of hypothalamitis and in the exclusion of a neoplastic lesion. Therapeutic management should be oriented according to the disease etiology. In most cases, after ruling out infective hypothalamitis, the mainstay of therapy consists of immunosuppressive treatment. Great attention should be paid to hormonal replacement therapy, if partial or total hypopituitarism is present, in particular in patients affected by diabetes insipidus, central hypoadrenalism and hypothyroidism. According to the complexity of this disease, a multidisciplinary approach is strongly advocated to reach an early diagnosis and an integrated therapy.

[The integrated care pathway for non melanoma skin cancer: the Istituto Dermopatico dell'Immacolata - IRCCS experience in Rome.] / Il percorso diagnostico-terapeutico e assistenziale nella gestione del paziente affetto da tumore cutaneo non melanocitario: l'esperienza dell'IDI - IRCCS di Roma.

The incidence of non-melanoma skin cancers (NMSC) is increasing worldwide and these skin cancers have become an important health issue. An integrated care pathway (ICP) is a multidisciplinary outline of anticipated care, placed in an appropriate timeframe, to help a patient with a specific condition. The aim of this paper is to define the ICP for patients affected by NMSC referring to the Istituto Dermopatico dell'Immacolata - IRCCS of Rome and Villa Paola, Italy. This ICP is multidisciplinary and included various specialists like dermatologist, oncologist, general surgeon, plastic surgeon, anatomopathologist, molecular biologist and epidemiologist. This ICP is based on the most recent acquisitions in the literature, referring in particular to the national (EADO and SIDEMAST) and international guidelines (EDF and NCCN). We firstly valued the current practice for patients affected by NMSC referring to our Institute to define the multidisciplinary process map. This process delineated the activities and the responsibilities performed during delivery of care to the patients and the potential problem areas or opportunities for improvements. Subsequently, we defined the final ICP process. This ICP of NMSC represents an innovative strategy to provide high quality healthcare. This allows to ensure all the necessary procedures for the patient, optimizing the "continuum" of care and the use of health services, and improving the organization of the Institute regarding an important health issue.

Sleep-potentiated epileptiform activity in early thalamic injuries: Study in a large series (60 cases).

OBJECTIVE: The study aims at a better definition of continuous spike-waves during sleep (CSWS) with an early thalamic lesion, focusing on various grades of sleep-potentiated epileptiform activity (SPEA). Their possible relationship with different clinical features was studied to try to define prognostic factors of the epileptic disorder, especially relating to behavior/cognitive outcome, in order to improve prevention and treatment strategies. METHODS: Sixty patients with early thalamic injury were followed since the first registration of SPEA with serial neurological, long term EEG monitoring and neuropsychological examinations, as well as neuroimaging and a detailed clinical history. They were classified in three different groups according to the sleep spike-waves (SW) quantification: electrical status epilepticus during sleep (ESES), more than 85% of slow sleep; overactivation between 50% and 85% and simple activation between 10 and 50%). Results were then examined also with a statistical analysis. RESULTS: In our series of CSWS occurring in early brain injured children with unilateral thalamic involvement there is a common neuropathologic origin but with various grades of SPEA severity. Statistical analysis showed that patients evolving toward ESES presented more commonly the involvement of the mediodorsal part of thalamus nuclei and a bilateral cortico-subcortical brain injury, epilepsy was more severe with a delayed onset; moreover, in the acute stage .ESES patients presented the worst behavior/cognitive performances. As to cognitive and behavior outcome, longer SPEA duration as well as bilateral brain injury and cognitive/behavior impairment in acute phase appear linked to a poor outcome; some particular neuropathology (ischemic stroke and haemorrhagic infarction) as well as hydrocephalus shunting are associated with behavior disorders. CONCLUSIONS: Discrete features seem to support different underlying mechanisms in ESES patients in comparison with less severe SPEA; they represent negative prognostic factors. Longer SPEA duration as well as bilateral brain injury and cognitive/behavior impairment in acute phase seem predictive of a worse cognitive/behavior outcome.

Insertion of 16 amino acids in the BAR domain of the oligophrenin 1 protein causes mental retardation and cerebellar hypoplasia in an Italian family.

We observed a three-generation family with two maternal cousins and an uncle affected by mental retardation (MR) with cerebellar hypoplasia. X-linked inheritance and the presence of cerebellar malformation suggested a mutation in the OPHN1 gene. In fact, mutational screening revealed a 2-bp deletion that abolishes a donor splicing site, resulting in the inclusion of the initial 48 nucleotides of intron 7 in the mRNA. This mutation determines the production of a mutant oligophrenin 1 protein with 16 extra amino acids inserted in-frame in the N-terminal BAR (Bin1/amphiphysin/Rvs167) domain. This is the first case of a mutation in OPHN1 that does not result in the production of a truncated protein or in its complete loss. OPHN1 (ARHGAP41) encodes a GTPase-activating (GAP) protein belonging to the GRAF subfamily characterized by an N-terminal BAR domain, followed by a pleckstrin-homology (PH) domain and the GAP domain. GRAF proteins play a role in endocytosis and are supposed to dimerize via their BAR domain, that induces membrane curvature. The extra 16 amino acids cause the insertion of 4.4 turns in the third alpha-helix of the BAR domain and apparently impair the protein function. In fact, the clinical phenotype of these patients is identical to that of patients with loss-of-function mutations.

Early thalamic injury associated with epilepsy and continuous spike-wave during slow sleep.

PURPOSE: Mechanisms inducing continuous spike-wave during slow sleep (CSWS) in encephalopathy with electrical status epilepticus during sleep are still unclear. Recently, some sporadic cases with early thalamic injury associated with CSWS have been reported. The aim of the study was to investigate in a population of patients with an early thalamic injury the presence of an activation of paroxysmal activities during sleep, their characteristics, and possible relations to neuroimaging and neuropsychological features. METHODS: Thirty-two patients with prenatal or perinatal thalamic injuries, mostly due to a vascular mechanisms, were fully examined, including neuroimaging, EEG monitoring, and cognitive follow-up. RESULTS AND CONCLUSIONS: Twenty-nine of 32 patients showed major sleep EEG activation. Among these 29 patients, two different groups were distinguished: the first included the more or less typical CSWS (12 cases), generally with symmetry of spike and waves (SWs) and often with no spindle at all. The other cases had an usual asymmetry of SWs and presence or reduction of spindles, plus other atypical features concerning synchronism and morphology of SWs. Behavioral disorders were significantly more present in patients with a true CSWS; their improvement (and in one case of the three thoroughly followed the improvement of cognitive competence) paralleled the disappearance of CSWS. The generally predominant injury of the lateral aspect of the thalamus included reticular nucleus and ventral nuclei. An imbalance of gamma-aminobutyric acid (GABA)(B)--versus GABA(A)--mediated receptors may be evoked as a cofactor predisposing to CSWS.

Neuroimaging of thalamic tumors in children.

INTRODUCTION: Thalamic tumors are typical deep brain tumors; their incidence is not precisely known because of the different definition criteria. However, taking only lesions arising in the thalami into consideration (and excluding those secondarily involving the thalami from adjacent structures) approximately 40% of thalamic tumors affect patients under 18 years of age and thalamic neoplasms account for 2-5% of all intracranial tumors in children. MATERIALS AND METHODS: In the present paper we have focused attention on the neuroimaging features of thalamic tumors in a pediatric population; based upon personal experience, we suggest a rational neuroradiological approach to the diagnostic evaluation, describe CT and MRI findings of the most common tumors, and attempt to define basic patterns in order to provide the most reliable "pathological" diagnosis.