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INTRODUCTION: Multiple sclerosis (MS) is a chronic neurodegenerative disease that leads to impaired cognitive function and accumulation of disability, with significant socioeconomic burden. Serious unmet need in the context of managing MS has given rise to ongoing research efforts, leading to the launch of new drugs planned for the near future, and subsequent concerns about the sustainability of healthcare systems. This study assessed the changes in the Italian MS market and their impact on the expenditures of the Italian National Healthcare Service between 2023 and 2028. METHODS: A horizon-scanning model was developed to estimate annual expenditure from 2023 to 2028. Annual expenditure for MS was calculated by combining the number of patients treated with each product (clinical inputs) and the yearly costs of therapy (economic inputs). Baseline inputs (2020-2022) were collected from IQVIA® real-world data, while input estimation for the 5-year forecast was integrated with analog analyses and the insights of clinicians and former payers. RESULTS: The number of equivalent patients treated in 2028 in Italy was estimated at around 67,000, with an increase of 10% versus 2022. In terms of treatment pattern evolution, first-line treatments are expected to reduce their shares from 47% in 2022 to 27% in 2028, and Bruton tyrosine kinase inhibitors are expected to reach 23% of patient shares. Overall, expenditure for MS is estimated to decrease from 721 million in 2022 to 551 million in 2028, mainly due to losses of exclusivity and renegotiation of drug prices. CONCLUSION: Despite the increase in the number of patients treated for MS and the launch of new molecules that will reach high market penetration, the model confirmed sustainability for the Italian National Healthcare Service.
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BACKGROUND: Cerebrospinal fluid myelin oligodendrocyte glycoprotein IgG (CSF MOG-IgG) are found in a proportion of patients with MOG antibody-associated disorder (MOGAD) and have been associated with severe disease presentations. However, most studies did not systematically investigate the role of MOG-IgG intrathecal synthesis (ITS). METHODS: We retrospectively studied 960 consecutive patients with paired serum and CSF samples screened for MOG-IgG using a live cell-based assays. MOG-IgG-specific antibody index (AIMOG) was systematically calculated using serum and CSF titres to assess MOG-IgG ITS, and clinical features were compared between MOG-IgG CSF+/CSF- and ITS+/ITS- patients. RESULTS: MOG-IgG were found in 55/960 patients (5.7%; serum+/CSF-: 58.2%, serum+/CSF+: 34.5%; serum-/CSF+: 7.3%). Serum/CSF MOG-IgG titres showed a moderate correlation in patients without ITS (ρ=0.47 (CI 0.18 to 0.68), p<0.001), but not in those with ITS (ρ=0.14 (CI -0.46 to -0.65), p=0.65). There were no clinical-paraclinical differences between MOG-IgG CSF+ vs CSF- patients. Conversely, patients with MOG-IgG ITS showed pyramidal symptoms (73% vs 32%, p=0.03), spinal cord involvement (82% vs 39%, p=0.02) and severe outcome at follow-up (36% vs 5%, p=0.02) more frequently than those without MOG-IgG ITS. A multivariate logistic regression model indicated that MOG-IgG ITS was an independent predictor of a poor outcome (OR: 14.93 (CI 1.40 to 19.1); p=0.03). AIMOG correlated with Expanded Disability Status Scale (EDSS) scores at disease nadir and at last follow-up (p=0.02 and p=0.01). CONCLUSIONS: Consistently with physiopathology, MOG-IgG ITS is a promising prognostic factor in MOGAD, and its calculation could enhance the clinical relevance of CSF MOG-IgG testing, making a case for its introduction in clinical practice.
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BACKGROUND: Predicting disease progression in patients with the first clinical episode suggestive of multiple sclerosis (MS) is crucial for personalized therapeutic approaches. This study aimed to develop the EUMUS score for accurately estimating the risk of early evidence of disease activity and progression (EDA). METHODS: Retrospective analysis was conducted on data from 221 patients with a first clinical MS episode collected from four Italian MS centers. Various variables including socio-demographics, clinical features, cerebrospinal fluid analysis, evoked potentials, and brain MRI were considered. A prognostic multivariate regression model was identified to develop the EUMUS score. The optimal cutoff for predicting the transition from no evidence of disease activity (NEDA3) to EDA was determined. The accuracy of the prognostic model and score were tested in a separate UK MS cohort. RESULTS: After 12 months, 61.54% of patients experienced relapses and/or new MRI lesions. Younger age (OR 0.96, CI 0.93-0.99; p = 0.005), MRI infratentorial lesion(s) at baseline (OR 2.21, CI 1.27-3.87; p = 0.005), positive oligoclonal bands (OR 2.89, CI 1.47-5.69; p = 0.002), and abnormal lower limb somatosensory-evoked potentials (OR 2.77, CI 1.41-5.42; p = 0.003) were significantly associated with increased risk of EDA. The EUMUS score demonstrated good specificity (72%) and correctly classified 80% of patients with EDA in the independent UK cohort. CONCLUSIONS: The EUMUS score is a simple and useful tool for predicting MS evolution within 12 months of the first clinical episode. It has the potential to guide personalized therapeutic approaches and aid in clinical decision-making.
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Progresión de la Enfermedad , Imagen por Resonancia Magnética , Esclerosis Múltiple , Humanos , Masculino , Femenino , Adulto , Estudios Retrospectivos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/fisiopatología , Pronóstico , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Live cell-based assay (LCBA) is the gold standard for MOG-IgG detection, and fixed CBA (FCBA) is a widely used commercial alternative. Recent criteria attributed a diagnostic value to MOG-IgG titration with both LCBA and FCBA, with low-titre samples requiring additional supporting features for MOGAD diagnosis. However, FCBA titration is not validated. We aimed to assess the impact of the criteria-based MOG-IgG testing in MOGAD diagnosis. METHODS: Thirty-eight serum samples of LCBA MOG-IgG1-positive MOGAD patients were titred on MOG-IgG LCBA and FCBA, and the presence of supporting features for MOGAD assessed. MOGAD criteria were evaluated in four testing scenarios: (a) FCBA without titration; (b) FCBA with titration; c) LCBA without titration; (d) LCBA with titration. RESULTS: FCBA without titration failed to reach MOGAD diagnosis in 11/38 patients (28.9%, negative results in 5, lack of supporting features in 6). Patients with unconfirmed diagnosis had optic neuritis (ON, n = 8), or transverse myelitis (TM, n = 3). FCBA with titration allowed MOGAD diagnosis in 4 additional patients. Correlation between LCBA and FCBA titres was moderate (Spearman's rho 0.6, p < 0.001). CONCLUSIONS: FCBA yields high rate of misdiagnosis mainly due a lower analytical sensitivity. FCBA titration provides a moderate diagnostic advantage in FCBA positive patients.
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Enfermedades Autoinmunes , Inmunoglobulina G , Glicoproteína Mielina-Oligodendrócito , Adulto , Femenino , Humanos , Masculino , Autoanticuerpos/sangre , Inmunoglobulina G/sangre , Glicoproteína Mielina-Oligodendrócito/inmunología , Mielitis Transversa/diagnóstico , Mielitis Transversa/sangre , Neuritis Óptica/diagnóstico , Neuritis Óptica/sangre , Neuritis Óptica/inmunología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/inmunologíaRESUMEN
Bowel dysfunctions (BD) in multiple sclerosis (MS) are under reported despite their clinical relevance. Scales usually applied do not thoroughly assess constipation and fecal incontinence. Instead, a proper qualitative and quantitative description of these symptoms might have relevant clinical and scientific consequences. The aim of this project is to study the prevalence of BD in a cohort of persons with MS (pwMS). Four-hundred and forty-seven pwMS (330 relapsing-remitting MS-RRMS and 117 progressive MS-PMS) were recruited. Three different questionnaires were administered: the neurogenic bowel dysfunction score (NBDS), the Wexner constipation scale (WexCon) and the Wexner incontinence scale (WexInc). All the scales were divided in subscores according to symptom severity. The prevalence of BD, considered as NBDS > 0, was 53.7%. Mean scores in pwMS group were as follows: NBDS 2.6 (SD 3.5), WexInc 1.1 (SD 2.4), WexCon 4.4 (SD 5.9). NBDS, WexCon and WexInc were significantly higher in PMS vs RRMS (p < 0.001), and significantly associated with disease duration, EDSS, multiple sclerosis severity score (p < 0.001), as well as with each other (p < 0.001). Our study confirms the presence of bowel dysfunctions in a large group of pwMS with a wide range of disability and their association with progressive disease phenotype and clinical disability.
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Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Intestino Neurogénico , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple Crónica Progresiva/complicaciones , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Estreñimiento , Intestino Neurogénico/complicaciones , Italia/epidemiologíaRESUMEN
Background: Pregnancy-associated cancer (PAC) occurs during pregnancy or within 12 months after the delivery. Head and neck cancer (HNC) during pregnancy is infrequent, therefore diagnosis and personalized therapy are intricate. Methods: We investigated outcomes of 15 PAC patients (5 salivary, 4 nasopharyngeal, 3 thyroid, 2 oral cavity, one HPV-related carcinoma) diagnosed in the period 2005-2019. A literature review on PAC is provided. Results: Median gestational age at PAC diagnosis was 28 weeks (range: 16-40 weeks) in ten cases, at 5 months after delivery (range: 1 week-6 months) in the remaining five. Treatments included surgery (3 during pregnancy, 5 after childbirth), chemoradiation (8), and 3 patients with upfront metastatic disease received chemotherapy. Median survival was 6.6 years (eight women remain with no evidence of disease six years after diagnosis). Conclusion: All patients received state-of-the-art therapy, with encouraging long-term results, highlighting treatment safety in women with HNC during pregnancy.
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The design of an open zero-gradient hardware is proposed in this work. The hardware is thought for characterizing single Polymer Electrolyte Membrane Fuel Cells (PEMFCs), specifically Membrane Electrode Assemblies (MEAs), with a focus on transport application. The objective of the proposed design is to minimize both operation and degradation heterogeneities over the cell active area in order to evaluate material properties only. It is indeed specifically intended to quantify the PEMFC materials performance without accounting for any interdependency between the layers of the MEA and the cell hardware design (e.g. heating/cooling system and flow field features). This is granted by combining high stoichiometry ratios of the gas reactants and limited pressure drops: they indeed keep uniform operating conditions (concentration in the gas phase, relative humidity, pressure and temperature), as verified by the electrochemical and operational characterization. With such characteristics, accurate information about both the performance and the degradation of the MEA materials can be provided. This tool is powerful for assessing the ranking in terms of performance and durability of different PEMFCs, as well as for application in the field of the materials local diagnostics.
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Optic neuritis (ON) is the most common cause of vision loss in young adults. It manifests as acute or subacute vision loss, often accompanied by retrobulbar discomfort or pain during eye movements. Typical ON is associated with Multiple Sclerosis (MS) and is generally mild and steroid-responsive. Atypical forms are characterized by unusual features, such as prominent optic disc edema, poor treatment response, and bilateral involvement, and they are often associated with autoantibodies against aquaporin-4 (AQP4) or Myelin Oligodendrocyte Glycoprotein (MOG). However, in some cases, AQP4 and MOG antibodies will return as negative, plunging the clinician into a diagnostic conundrum. AQP4- and MOG-seronegative ON warrants a broad differential diagnosis, including autoantibody-associated, granulomatous, and systemic disorders. These rare forms need to be identified promptly, as their management and prognosis are greatly different. The aim of this review is to describe the possible rarer etiologies of non-MS-related and AQP4- and MOG-IgG-seronegative inflammatory ON and discuss their diagnoses and treatments.
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Esclerosis Múltiple , Neuritis Óptica , Humanos , Glicoproteína Mielina-Oligodendrócito , Estudios Retrospectivos , Neuritis Óptica/diagnóstico , Neuritis Óptica/etiología , Acuaporina 4 , AutoanticuerposRESUMEN
OBJECTIVES: Cisplatin is essential in the curative treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients. The assessment of risk factors to predict an early cisplatin-induced nephrotoxicity could help in better managing one of the most relevant cisplatin-related dose-limiting factors. MATERIAL AND METHODS: We retrospectively collected data of LA-HNSCC patients treated at our Institution from 2008 to 2019. Patients received cisplatin in a curative setting concurrently with radiation. Acute Kidney Injury (AKI) was assessed as a dichotomous variable (CreaIncr) based on pre-treatment values, and values recorded at days 6-20 post-first cycle of cisplatin. Univariable logistic regression models were performed to investigate associations between CreaIncr and clinical characteristics. A multivariable logistic model on a priori selected putative covariates was performed. RESULTS: Of the 350 LA-HNSCC treated patients, 204 were analyzed. Ninety (44 %) suffered from any grade AKI (grade I 51.1 %): out of them, 84.4 % received high-dose cisplatin (100 mg/m2 q21). On the univariable logistic regression model, male sex, age, serum uric acid, creatinine, concomitant drugs, and cisplatin schedule were significantly associated with a higher rate of AKI. At multivariable model, age (p = 0.034), baseline creatinine (p = 0.027), concomitant drugs (p = 0.043), and cisplatin schedule (one-day bolus or fractionated high-dose vs. weekly; p = 0.001) maintained their significant association. CONCLUSIONS: Identifying pre-treatment risk factors in LA-HNSCC patients may improve decision-making in a setting where cisplatin has a curative significance. A strict monitoring of AKI could avoid cisplatin dose adjustments, interruptions, and treatment delays, thus limiting a negative impact on outcomes.
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Lesión Renal Aguda , Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Masculino , Cisplatino/efectos adversos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Antineoplásicos/efectos adversos , Estudios Retrospectivos , Creatinina/efectos adversos , Ácido Úrico/efectos adversos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Quimioradioterapia/efectos adversos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Factores de RiesgoRESUMEN
BACKGROUND: NUT carcinoma (NUTc) is a rare and aggressive malignant epithelial tumor characterized by rearrangement of the NUT gene on chromosome 15q14. METHODS: In this article, we present the fifth case worldwide of a young woman affected by a NUTc arising from a submandibular gland, presenting as a rapidly evolving mass. She underwent a right scialoadenectomy and received the initial diagnosis of high-grade mucoepidermoid carcinoma. Due to evidence of local recurrence at magnetic resonance imaging 1 month later, a subsequent right radical neck dissection was performed. The patient then sought a second opinion at our cancer center and finally received the correct diagnosis of NUT carcinoma. Given the well-known aggressive behavior of this neoplasm, as well as clinical and radiological features, she underwent adjuvant chemo-radiation (intensity-modulated radiotherapy + concurrent chemotherapy with cisplatin). RESULTS: After a disease-free interval of 2.6 months, a widespread metastatic disease led to rapid deterioration of performance status and patient death in a few weeks after metastatic onset. CONCLUSIONS: We presented a case of NUTc arising from salivary gland aiming to improve the knowledge of this rare malignancy. First, we pointed out that in the setting of rare tumors like salivary gland cancers, the diagnosis should be obtained by expert pathologists, and patients should be referred to tertiary cancer centers for their clinical management. Second, molecular profiling may help to identify possible druggable targets that may be exploited to treat patients suffering from this aggressive malignancy. Sharing the molecular data provided in this case will be useful for further research.
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Carcinoma , Neoplasias de las Glándulas Salivales , Femenino , Humanos , Glándula Submandibular/patología , Carcinoma/patología , Neoplasias de las Glándulas Salivales/patología , Neoplasias de las Glándulas Salivales/terapia , Radioterapia AdyuvanteRESUMEN
BACKGROUND AND OBJECTIVES: Glial fibrillary acidic protein (GFAP) antibodies can associate with an astrocytopathy often presenting as a meningoencephalitis. Visual involvement has been reported but scarcely defined. We describe 2 cases of GFAP astrocytopathy with predominant visual symptoms and present a systematic review of the literature. METHODS: We describe 2 patients with GFAP astrocytopathy from our neurology department. We performed a systematic review of the literature according to PRISMA guidelines, including all patients with this disease and available clinical data, focusing on visual involvement. RESULTS: Patient 1 presented with bilateral optic disc edema and severe sudden bilateral loss of vision poorly responsive to therapy. Patient 2 showed bilateral optic disc edema, headache, and mild visual loss with complete recovery after steroids. We screened 275 records and included 84 articles (62 case reports and 22 case series) for a total of 592 patients. Visual involvement was reported in 149/592 (25%), with either clinical symptoms or paraclinical test-restricted abnormalities. Bilateral optic disc edema was found in 80/159 (50%) of patients investigated with fundoscopy, among which 49/80 (61%) were asymptomatic. One hundred (100/592, 17%) reported visual symptoms, often described as blurred vision or transient visual obscurations. Optic neuritis was rare and diagnosed in only 6% of all patients with GFAP astrocytopathy, often without consistent clinical and paraclinical evidence to support the diagnosis. Four patients (including patient 1) manifested a severe, bilateral optic neuritis with poor treatment response. In patients with follow-up information, a relapsing disease course was more frequently observed in those with vs without visual involvement (35% vs 11%, p = 0.0035, OR 3.6 [CI 1.44-8.88]). DISCUSSION: Visual system involvement in GFAP astrocytopathy is common and heterogeneous, ranging from asymptomatic bilateral optic disc edema to severe bilateral loss of vision, but optic neuritis is rare. GFAP CSF antibody testing should be considered in patients with encephalitis/meningoencephalitis or myelitis and bilateral optic disc edema, even without visual symptoms, and in patients with severe bilateral optic neuritis, especially when AQP4 antibodies are negative. Visual symptoms might associate with a higher relapse risk and help to identify patients who may require chronic immunosuppression.
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Meningoencefalitis , Neuritis Óptica , Papiledema , Humanos , Proteína Ácida Fibrilar de la Glía , Neuritis Óptica/diagnóstico , AnticuerposRESUMEN
The recent SARS-CoV-2 pandemic and related vaccines have raised several issues. Among them, the potential role of the viral infection (COVID-19) or anti-SARS-CoV-2 vaccines as causal factors of dysimmune CNS disorders, as well as the safety and efficacy of vaccines in patients affected by such diseases and on immune-active treatments have been analyzed. The aim is to better understand the relationship between SARS-CoV-2 infection/vaccines with dysimmune CNS diseases by describing 12 cases of multiple sclerosis/myelitis onset or reactivation after exposure to SARS-CoV-2 infection/vaccines and reviewing all published case reports or case series in which MS onset or reactivation was temporally associated with either COVID-19 (8 case reports, 3 case series) or anti-SARS-CoV-2 vaccines (13 case reports, 6 case series). All the cases share a temporal association between viral/vaccine exposure and symptoms onset. This finding, together with direct or immune-based mechanisms described both during COVID-19 and MS, claims in favor of a role for SARS-CoV-2 infection/vaccines in unmasking dysimmune CNS disorders. The most common clinical presentations involve the optic nerve, brainstem and spinal cord. The preferential tropism of the virus together with the presence of some host-related genetic/immune factors might predispose to the involvement of specific CNS districts.
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Vacunas contra la COVID-19 , COVID-19 , Esclerosis Múltiple , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , SARS-CoV-2 , Vacunas ViralesRESUMEN
PURPOSE: The investigation of multiple molecular targets with next-generation sequencing (NGS) has entered clinical practice in oncology, yielding to a paradigm shift from the histology-centric approach to the mutational model for personalized treatment. Accordingly, most of the drugs recently approved in oncology are coupled to specific biomarkers. One potential tool for implementing the mutational model of precision oncology in daily practice is represented by the Molecular Tumor Board (MTB), a multidisciplinary team whereby molecular pathologists, biologists, bioinformaticians, geneticists, medical oncologists, and pharmacists cooperate to generate, interpret, and match molecular data with personalized treatments. PATIENTS AND METHODS: Since May 2020, the institutional MTB set at Fondazione IRCCS Istituto Nazionale Tumori of Milan met weekly via teleconference to discuss molecular data and potential therapeutic options for patients with advanced/metastatic solid tumors. RESULTS: Up to October 2021, among 1,996 patients evaluated, we identified >10,000 variants, 43.2% of which were functionally relevant (pathogenic or likely pathogenic). On the basis of functionally relevant variants, 711 patients (35.6%) were potentially eligible to targeted therapy according to European Society of Medical Oncology Scale for Clinical Actionability of Molecular Targets tiers, and 9.4% received a personalized treatment. Overall, larger NGS panels (containing >50 genes) significantly outperformed small panels (up to 50 genes) in detecting actionable gene targets across different tumor types. CONCLUSION: Our real-world data provide evidence that MTB is a valuable tool for matching NGS data with targeted treatments, eventually implementing precision oncology in clinical practice.
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Neoplasias , Humanos , Medicina de Precisión , Atención al Paciente , Oncología Médica , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
Postinfectious neurological syndromes (PINS), among which acute disseminated encephalomyelitis (ADEM), are inflammatory and mostly monophasic disorders. We previously reported that PINS patients can show relapses, or even disease progression. Here we describe a cohort of patients with progressive-PINS and >5 years of follow-up, that developed a progressive worsening without radiological/cerebrospinal fluid analysis evidence of inflammation. At onset 5 patients fulfilled diagnostic criteria for ADEM and none for MS. Progression occurred after a median of 22 months from onset (in 4/7 after 1/more relapses), manifesting as ascending tetraparesis with bulbar functions involvement in 5/7. Five/7 patients received high dose steroids and/or IvIG and 6/7 Rituximab(n = 4) and/or cyclophosphamide(n = 2), with no impact on disease progression in 6/7. NfL levels were higher in patients with progressive-PINS compared to monophasic-ADEM (p = 0.023) and healthy controls (p = 0.004). Progression is rare, but possible, in PINS. Immunotherapy seems to be ineffective in these patients, and elevated serum NfL in serum suggest persistent axonal damage.
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Encefalomielitis Aguda Diseminada , Filamentos Intermedios , Humanos , Estudios de Seguimiento , Encefalomielitis Aguda Diseminada/diagnóstico , Progresión de la Enfermedad , RecurrenciaRESUMEN
As life expectancy rises, more elderly people undergo spinal fusion surgery to treat lumbar degenerative diseases. The MIS-TLIF technique, which minimizes soft tissue manipulation, is a promising fusion technique for frailer patients. The aim of this study was to investigate if older age is a significant factor in the clinical outcome of single- or double-level MIS-TLIF. A cross-sectional study was conducted on 103 consecutive patients. Data were compared between younger (<65 y.o.) and older (≥65 y.o.) patients. We observed no significant differences between baseline characteristics of the two groups apart from the frequency of disk space treated, with a relative predominance of L3-L4 space treated in the elderly (10% vs. 28%, p = 0.01) and L5-S1 space in younger patients (36% vs. 5%, p = 0.006). There was no significant difference in complication rate, surgical satisfaction, EQ 5D-5L, or Oswestry Disability Index (ODI) global or specific scores, with the exception of the EQ 5D-5L "mobility" score, where older patients fared worse (1.8 ± 1.1 vs. 2.3 ± 1.4; p = 0.05). The minimal invasiveness of the surgical technique, age-related specific outcome expectations, and biomechanical issues are all potential factors influencing the lack of age group differences in outcome scores.
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Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequent cancers in humans, with cumulative ultraviolet radiation exposure, aging, and immunodepression as the main risk factors. In most cases, these malignancies arise in the head and neck area, and they can be treated with locoregional therapies. A minority of cases require systemic therapy. Currently, Sonic Hedgehog inhibitors (i.e., vismodegib and sonidegib) have been approved for advanced BCC, while the PD-1 checkpoint inhibitor cemiplimab has been approved as a first-line treatment for cSCC and as a second-line treatment for BCC. Nevertheless, there is a clinical need for an effective and safe systemic therapies for advanced synchronous (syn) BCC/cSCC not amenable to local treatments. International guidelines do not provide specific recommendations for patients affected by this condition, and no case reports on the full-dose association of these medications have been previously reported. Here, we present the cases of two elderly patients affected by synBCC/cSCC of the head and neck, who received combined therapy with cemiplimab and sonidegib at full dose and standard schedule, achieving remarkable clinical benefit and long-term responses, without major adverse events. The instance of a feasible treatment for patients with advanced synBCC/cSCC will become increasingly frequent with the advancement of life expectancy in the global population, and the synergistic activity of targeted therapies and immunotherapy-administered either in association or sequentially-deserves to be further explored.
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BACKGROUND: The aim of this study was to achieve a consensus on the minimum set of outcome measures and predictors to be used in the neurosurgical practice and on the timing of outcome assessment. METHODS: A consensus building approach was employed. All neurosurgical departments in Lombardy (Italy) were invited to participate by the Carlo Besta Neurologic Institute IRCCS Foundation. Three workshops were organized during which a multidisciplinary group called Neurosurgical Outcome Network (NEON) was created and the methodology to select outcome measures, predictors, and timing of outcome assessment was established. Eight working groups were created for the different neurosurgical diseases (neuro-oncological, skull base, vascular, traumatic, spinal, peripheral nervous system, malformation, functional) and 8 workshops were organized to identify the outcome measures and predictors specific for each of the neurosurgical diseases based on the experts' clinical practice and the existing literature. RESULTS: A total of 20 neurosurgical departments participated in this study. Specific outcome measures, predictors and the timing of outcome assessment were identified for each of the 8 neurosurgical diseases. Moreover, a list of variables common to all pathologies were identified by the NEON group as further data to be collected. CONCLUSIONS: A consensus on the minimum set of outcome measures and predictors and the timing of outcome assessments for 8 neurosurgical diseases was achieved by a group of neurosurgeons of the Lombardy region, called NEON. These sets could be used in future studies for a more homogeneous data collection and as a starting point to reach further agreement also at national and international level.
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Neurocirujanos , Evaluación de Resultado en la Atención de Salud , Humanos , Neón , ItaliaRESUMEN
Background: Vertebral arthrodesis for degenerative pathology of the lumbar spine still remains burdened by clinical problems with significant negative results. The introduction of the sagittal balance assessment with the evaluation of the meaning of pelvic parameters and spinopelvic (PI-LL) mismatch offered new evaluation criteria for this widespread pathology, but there is a lack of consistent evidence on long-term outcome. Methods: The authors performed an extensive systematic review of literature, with the aim to identify all potentially relevant studies about the role and usefulness of the restoration or the assessment of Sagittal balance in lumbar degenerative disease. They present the study protocol RELApSE (NCT05448092 ID) and discuss the rationale through a comprehensive literature review. Results: From the 237 papers on this topic, a total of 176 articles were selected in this review. The analysis of these literature data shows sparse and variable evidence. There are no observations or guidelines about the value of lordosis restoration or PI-LL mismatch. Most of the works in the literature are retrospective, monocentric, based on small populations, and often address the topic evaluation partially. Conclusions: The RELApSE study is based on the possibility of comparing a heterogeneous population by pathology and different surgical technical options on some homogeneous clinical and anatomic-radiological measures aiming to understanding the value that global lumbar and segmental lordosis, distribution of lordosis, pelvic tilt, and PI-LL mismatch may have on clinical outcome in lumbar degenerative pathology and on the occurrence of adjacent segment disease.
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Anaplastic thyroid carcinoma (ATC) is a rare cancer accounting for 40% of thyroid cancer-specific deaths. In the last 5 years, improved insights into molecular pathways led the Food and Drug Administration to license BRAF/MEK inhibitors (B/Mi) in BRAFV600E-mutant ATC, and pembrolizumab in solid cancer with high tumour mutational burden (TMB-H) (≥10 mutations/megabase) (mut/Mb). In Europe, clinicians face challenges in prescribing novel treatments, as the European Medical Association (EMA) has not licensed B/Mi nor immunotherapy (IO) for ATC so far. Some patients manage to receive these drugs through alternative ways. We investigated the extent of this phenomenon launching an online survey from March 12th to 19th 2021 open to 239 Institutions in the EORTC Endocrine and Head & Neck Cancer Groups. Questions enquired about the number of ATC patients evaluated/year, feasibility of BRAF assessment, accessibility to B/Mi-IO, availability of clinical trials and interest in new studies. Colleagues from 94 Institutions (20 Countries) joined: 30 centres evaluated ≥5 ATC patients/year, with an overall incidence >200 patients/year. 80.8% tested BRAF status, 43.6% by next-generation sequencing. 62.7% and 70% of responders reported limitations in prescribing B/Mi and IO, respectively: either the impossibility of offering them, or drugs accessibility exclusively under certain conditions (e.g. health insurance, clinical trials, compassionate use, off-label). Only 13.8% had clinical trials ongoing while 91.5% of sites claimed ATC-dedicated trials. Disparities in access to novel treatments are diffuse. Access to cutting-edge therapies is an urgent issue in this setting, and clinical trials seem feasible within an appropriate network.
Asunto(s)
Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Humanos , Carcinoma Anaplásico de Tiroides/genética , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/terapia , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genética , Europa (Continente) , MutaciónRESUMEN
BACKGROUND: IgG antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) define a subset of associated disorders (myelin oligodendrocyte glycoprotein associated disorders (MOGAD)) that can have a relapsing course. However, information on relapse predictors is scarce. The utility of retesting MOG-IgG over time and measuring their titres is uncertain. We aimed to evaluate the clinical relevance of longitudinal MOG-IgG titre measurement to predict relapses in patients with MOGAD. METHODS: In this retrospective multicentre Italian cohort study, we recruited patients with MOGAD and available longitudinal samples (at least one >3 months after disease onset) and tested them with a live cell-based assay with endpoint titration (1:160 cut-off). Samples were classified as 'attack' (within 30 days since a disease attack (n=59, 17%)) and 'remission' (≥31 days after attack (n=295, 83%)). RESULTS: We included 102 patients with MOGAD (57% adult and 43% paediatric) with a total of 354 samples (83% from remission and 17% from attack). Median titres were higher during attacks (1:1280 vs 1:640, p=0.001). Median onset titres did not correlate with attack-related disability, age or relapses. Remission titres were higher in relapsing patients (p=0.02). When considering the first remission sample available for each patient, titres >1:2560 were predictors of relapsing course in survival (log rank, p<0.001) and multivariate analysis (p<0.001, HR: 10.9, 95% CI 3.4 to 35.2). MOG-IgG seroconversion to negative was associated with a 95% relapse incidence rate reduction (incidence rate ratio: 0.05, p<0.001). CONCLUSIONS: Persistent MOG-IgG positivity and high remission titres are associated with an increased relapse risk. Longitudinal MOG-IgG titres could be useful to stratify patients to be treated with long term immunosuppression.