Real-world use of oral versus subcutaneous semaglutide in a cohort of type 2 diabetic patients: which option to which patient?

PURPOSE: To evaluate the variables influencing the therapeutic choice toward oral versus subcutaneous semaglutide in a cohort of diabetic subjects. METHODS: We retrospectively collected data of 292 patients followed at the Diabetes Unit of the University Hospital of Siena and the Hospital of Grosseto, who were prescribed oral (n = 115) or subcutaneous (n = 177) semaglutide between October 2021 and October 2022. RESULTS: Oral semaglutide was preferentially prescribed in older subjects with longer disease duration in replacement of other antidiabetic drugs, while subcutaneous semaglutide was preferentially prescribed in add-on to metformin in subjects with higher body weight and BMI. After 6 months, both formulations significantly improved glycemic control and body weight, however injectable semaglutide showed a greater efficacy on A1c levels, weight loss, BMI and waist circumference reduction. No differences were found in terms of adverse events. CONCLUSION: In our experience, injectable semaglutide is preferred in patients with excess weight and shorter disease duration, while the oral formulation was used later and especially after therapeutic failure of previous therapies. Follow-up data indicate similar tolerability and efficacy of both formulations, despite subcutaneous semaglutide demonstrated greater efficacy.

Stroke-like events after brain radiotherapy: a large series with long-term follow-up.

BACKGROUND AND PURPOSE: Patients with a history of brain radiotherapy can experience acute stroke-like syndromes related to the delayed effects of brain radiation, including stroke-like migraine attacks after radiation therapy syndrome, peri-ictal pseudoprogression and acute late-onset encephalopathy after radiation therapy syndrome. The aim of this study was to collect evidence on the long-term outcome and treatment of these conditions, whose knowledge is undermined by their rarity and fragmented description. METHODS: Cases were collected, both prospectively and retrospectively, amongst six neuro-oncology departments. Inclusion criteria were as follows: (i) history of brain radiotherapy (completed at least 6 months before the acute episode); (ii) new onset of acute/subacute neurological symptoms; (iii) exclusion of all etiologies unrelated to brain irradiation. A review of current literature on stroke-like syndromes was performed to corroborate our findings. RESULTS: Thirty-two patients with acute neurological conditions attributed to the delayed effects of radiation were identified, including 26 patients with stroke-like syndromes. Patients with stroke-like syndromes commonly presented with a mosaic of symptoms, including focal deficits (77%), encephalopathy (50%), seizures (35%) and headache (35%). Seventy-three percent of them had acute consistent magnetic resonance imaging alterations. Treatment included high-dose steroids in 65% of cases. Twenty-two patients recovered completely (85%). Sixteen patients (62%) experienced relapses (median follow-up 3.5 years). A literature review identified 87 additional stroke-like cases with similar characteristics. CONCLUSIONS: Stroke-like events related to brain irradiation may be associated with permanent sequelae. Steroids are often administered on empirical grounds, as they are thought to accelerate recovery. Relapses are common, highlighting the need to elaborate adequate prevention strategies.

Improvement in postoperative mortality in elective gastrectomy for gastric cancer: Analysis of predictive factors in 1066 patients from a single centre.

BACKGROUND: Gastrectomy represents the main treatment for gastric adenocarcinoma. This procedure is associated with substantial morbidity and mortality. The aim of this study was to evaluate the postoperative mortality changes across the study period and to identify predictive factors of 30-day mortality after elective gastrectomy for gastric cancer. METHODS: This was a retrospective cohort study of a prospective database from a single centre. Patients treated with an elective gastrectomy from 1996 to 2014 for gastric adenocarcinoma were included. We compared postoperative mortality between four time periods: 1996-2000, 2001-2005, 2006-2010, and 2011-2014. Univariate and multivariate analyses were applied to identify predictors of 30-day postoperative mortality. RESULTS: We included 1066 patients (median age 65 years; 67% male). The 30-day mortality rate was 4.7%. Mortality decreased across the four time periods; from 6.5% to 1.8% (P = 0.022). In the univariate analysis, age, ASA score, albumin <3.5, multivisceral resection, splenectomy, intrathoracic esophagojejunal anastomosis, R status, and T status were significantly associated with postoperative mortality. In the multivariate analysis, ASA class 3 (OR 10.06; CI 1.97-51.3; P = 0.005) and multivisceral resection (OR 1.6; CI 1.09-2.36; P = 0.016) were associated with higher postoperative 30-day mortality; surgery between 2011 and 2014 was associated with lower postoperative 30-day mortality (OR 0.55; CI 0.33-0.15; P = 0.030). CONCLUSION: There was a decrease in postoperative 30-day mortality during this 18-year period at our institution. We have identified ASA score and multivisceral resection as predictors of 30-day mortality for elective gastrectomy for cancer.

Combined central and peripheral demyelination: Clinical features, diagnostic findings, and treatment.

Combined central and peripheral demyelination (CCPD) is rare, and current knowledge is based on case reports and small case series. The aim of our study was to describe the clinical features, diagnostic results, treatment and outcomes in a large cohort of patients with CCPD. Thirty-one patients entered this retrospective, observational, two-center study. In 20 patients (65%) CCPD presented, after an infection, as myeloradiculoneuropathy, encephalopathy, cranial neuropathy, length-dependent peripheral neuropathy, or pseudo-Guillain-Barré syndrome. Demyelinating features of peripheral nerve damage fulfilling European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria for CIDP were found in 23 patients (74%), and spatial dissemination of demyelinating lesions on brain MRI fulfilling the 2010 McDonald criteria for multiple sclerosis (MS) in 11 (46%). Two thirds of the patients had a relapsing or progressive disease course, usually related to the appearance of new spinal cord lesions or worsening of the peripheral neuropathy, and showed unsatisfactory responses to high-dose corticosteroids and intravenous immunoglobulins. The clinical presentation of CCPD was severe in 22 patients (71%), who were left significantly disabled. Our data suggest that CCPD has heterogeneous features and shows frequent post-infectious onset, primary peripheral nervous system or central nervous system involvement, a monophasic or chronic disease course, inadequate response to treatments, and a generally poor outcome. We therefore conclude that the current diagnostic criteria for MS and CIDP may not fully encompass the spectrum of possible manifestations of CCPD, whose pathogenesis remains largely unknown.

Postoperative adjuvant treatment for gastric cancer improves long-term survival after curative resection and D2 lymphadenectomy. Results from a Latin American Center.

BACKGROUND: The benefits of adjuvant treatment in the context of a D2 lymph node dissection are controversial. The aim was to investigate the effects of postoperative adjuvant treatment on the survival of patients with a curative resection for gastric cancer and a D2 lymph node dissection. METHODS: We performed a retrospective cohort study. Patients operated from 1996 to 2013 were selected. We compared long term survival of patients treated with surgery alone and those with surgery plus postoperative adjuvant treatment. A multivariate analysis for survival was applied in every stage. RESULTS: The study included 580 patients. Two-hundred and four patients received postoperative adjuvant treatment (AD) and 376 patients were treated only with surgery (SU). Patients in the AD group were younger (60 versus 68, p < 0.001), had a lower rate of multiple organ resection (21% versus 39%, p < 0.001) and had less postoperative complications (14% versus 32%, p < 0.001). In the AD group, patients had more advanced disease (stage III; 77% versus 66%, p < 0.001). No difference was found in lymph nodes resected (31 versus 30, p = ns). The median survival with adjuvant treatment was 33 months (39% 5 year survival) and 22 months (31% 5 year survival) for patients without adjuvant treatment (p = 0.003). On multivariate analysis, patients with stage IIIB and IIIC had significantly better overall and disease specific long-term survival with adjuvant treatment. CONCLUSIONS: These results suggest that there is a long-term survival benefit for patients treated with postoperative adjuvant treatment for stages IIIB and IIIC gastric cancer after D2 lymph node dissection.

Effect of the 50 bp deletion polymorphism in the SOD1 promoter on SOD1 mRNA levels in Italian ALS patients.

The genetic association between homozygosity for a 50 bp deletion polymorphism in the SOD1 promoter, 1684 bp upstream of the ATG, and an increased age of symptom onset was observed in various populations of ALS patients. Moreover, it has been demonstrated that this deletion reduces SOD1 expression in vitro. The objective of the present study was to test whether the observed association is replicated in patients from an Italian population and to check whether the deletion correlates with reduced SOD1 mRNA expression in vivo. Genomic DNA from 235 Italian SALS cases and 245 age- and sex-matched donors from the same ethnic background was screened for the 50 bp SOD1 promoter deletion by real time PCR assays. No differences were observed between ALS patients and controls for the frequency of both the alleles (D=deleted, N=non-deleted; p=0.95) and genotypes (p=0.90). Furthermore, stratification of the ALS samples showed that this variation was not associated with increased age of onset in ND and DD patients in comparison to NN patients (p=0.48). Finally, we performed real-time RT-PCR to quantify SOD1 mRNA levels in 48 patients and we did not find a relevant difference among the three sub-groups of genotypes (p=0.30). Our data suggest that the studied polymorphism does not modulate SOD1 mRNA level and disease phenotype in an Italian population.

Neuropsychological evaluation and follow up in jcv- and non-jcv-related leukoencephalopathies in HIV infection.

The introduction of highly active antiretroviral therapy does not seem to have altered the incidence of progressive multifocal leukoencephalopathy (PML) in HIV infection. Moreover, the occurrence of a HIV-related leukoencephalopathy, called not determined leukoencephalopaties (NDLE), has been reported. As neuropsychological impairment remains highly prevalent in HIV infection, the aim of this study is to describe the neuropsychological profile of PML and NDLE patients, analyzing the time-related changes. Clinical and neuropsychological data from 32 patients (17 PML, 15 NDLE) were compared with two control groups: (1) asymptomatic HIV+ patients without magnetic resonance imaging evidence of leukoencephalopathy; (2) age-/gender-/education-matched healthy subjects. Patients with rapidly worsening PML were significantly impaired on all neuropsychological tests, while PML with more benign course and NDLE groups showed a dysexecutive pattern of impairment. Asymptomatic HIV+ subjects showed mild and isolated cognitive deficits, without functional impact. Cognitive impairment should therefore be considered a key feature from HIV infection diagnosis.

HIV-related acute inflammatory leukoencephalopathy of undetermined origin: review of the literature.

HIV-related acute inflammatory leukoencephalopathy of undetermined origin (AIL) has been anecdotally described in literature as being responsible for cognitive and motor deficits. We carried out a review of all the cases of AIL published in literature. Articles were selected according to 2 criteria: acute onset of symptoms; undetermined aetiology and non-fulfilment of multiple sclerosis diagnostic criteria. They were then analyzed in terms of clinical, biological and instrumental features, therapy, diagnostic classification and prognosis. Although rare (21 patients out of about 4,000 publications), AIL is of particular interest, as the comprehension of its mechanisms could give some insight into the direct and immune-mediated actions of HIV within the brain. All the reported patients share several clinical, histopathological, radiological and CSF features, leading to hypothesize a similar aetiopathogenetic mechanism. Conversely, we observed a high heterogeneity of treatment and diagnostic classification, which could have conditioned the broad prognostic variability. The absence of a defined aetiology leads to consider these forms as a particular subgroup of not determined leucoencephalopathies (NDLE), with both MRI and histological pattern dominated by inflammation as distinctive feature.

NMO-IgG-negative relapsing myelitis.

OBJECTIVE: Idiopathic transverse myelitis (I-TM) is typically monophasic, while relapsing forms are usually referred to spinal cord-restricted neuromyelitis optica (NMO), atypical multiple sclerosis (MS), or myelitis during the course of infections and connectivitis. Our objective was to evaluate the frequency of recurrent I-TM; to clarify the nosology of these forms through comparison with NMO and post-infectious TM (P-TM). DESIGN: Prospective cohort study on patients presenting with I-TM was carried out inpatients of Infectious and Neurologic Disease Clinics, Italy. METHODS: Over an 8-year period, we recruited 13 patients with I-TM and 16 with P-TM. The patients were followed-up for at least 3 years with repeated brain and spinal cord magnetic resonance imaging (MRI) examinations, multimodal evoked potentials and serum screen for connectivitis. Relapses were defined on clinical and imaging criteria. RESULTS: Four patients with I-TM (31%) had a relapsing course . They were all males with age >50, and severe at-onset disability. The final outcome was poor in three out of four patients. Serum NMO-immunoglobulin G was undetectable in all patients. Longitudinally extensive myelitis was not predictive of relapses. I-TM and P-TM shared clinical, cerebrospinal fluid (CSF) and MRI features, as well as a similar rate (54 vs 38%) of peripheral nervous system involvement (polyradiculoneuritis), and an identical rate of relapses (31% for both forms). CONCLUSIONS: Our series support the existence of relapsing I-TM as a disease entity that does not appear related to NMO, nor to MS, cannot be further specified and shares many features with P-TM. The likelihood of relapses was unpredictable based on clinical, CSF and MRI findings.

Immunohistochemical evaluation of minichromosome maintenance protein 7 in astrocytoma grading.

The minichromosome maintenance (MCM) proteins, which play an important role in eukaryotic DNA replication, represent a group of proteins that are currently under investigation as novel diagnostic tumor markers. Several studies have proved a greater reliability of MCM proteins to stain proliferating cells compared to Ki67 protein, a routinely used proliferation marker in histopathology. In the present study, the expressions of MCM7 and Ki67 were estimated in 66 primary human astrocytomas in relation to tumor grade (Grade I-IV, WHO). MCM7 significantly stained more nuclei compared to Ki67 in all the histopathological grades investigated. In addition, a stronger increase of the MCM7 labelling index, in relation to the tumor aggressiveness, was observed.

Effect of nitric oxide on lymphocytes from sporadic amyotrophic lateral sclerosis patients: toxic or protective role?

Markers of oxidative and nitrosative stress have been found in spinal cord, cortex, cerebrospinal fluid and plasma of patients affected by amyotrophic lateral sclerosis (ALS), a fatal disorder characterised by progressive motor neuron degeneration. In this study, we investigated the effect of the NO-releasing agent, diethylamine NONOate (NONO), on lymphocytes from patients affected by the sporadic form of ALS (SALS) and controls by flow cytometry. In the same experimental conditions we investigated the expression of the antioxidant proteins, Bcl-2 and SOD1. Incubation with NONO induced cell damage in control lymphocytes but did not further damage the already affected untreated SALS lymphocytes. The incubation with NONO induced a time-dependent decrease of Bcl-2 and SOD1 in control lymphocytes. Surprisingly, in SALS lymphocytes the NONO treatment increased the expression of these proteins, which in basal conditions was depressed compared to control lymphocytes.

A randomized phase III study: comparison between intravenous and intraarterial ACNU administration in newly diagnosed primary glioblastomas.

BACKGROUND: In this randomized phase III study, the effectiveness as well as the side-effects of intraarterial [i.a.] (17 patients) versus intravenous [i.v.] (16 patients) ACNU [Nimustine] administration in newly diagnosed glioblastoma, were compared. PATIENTS AND METHODS: All patients undenwent extensive surgical resection, and both groups were homogeneous for the other known risk factors. Thirty-three patients with glioblastoma were treated with ACNU at the dose of 80-100 mg/m2. Treatment was repeated every 5-8 weeks for a minimum of 2 and maximum of 14 cycles. Total survival time (TST) and to time to progression were chosen as outcome variables. RESULTS AND CONCLUSION: No significant differences in systemic and hematological toxicity between the i.a. and iv. ACNU administration routes were detected. In both groups, tolerance of the procedure was excellent. Analysis of the main outcome measured showed no significant differences between i.a. and i.v. ACNU administration: time to progression was 6 months for i.a. ACNU and 4 months for i.v. ACNU and total survival time was 17 months for i.a. ACNU and 20 months for i.v. ACNU. In spite of ACNU dose incrementation, obtained through i.a. route administration, and subsequent higher concentration in the tumor bed, no improvement could be achieved in effectiveness.

Minichromosome maintenance protein 7: a reliable tool for glioblastoma proliferation index.

At present there is increasing evidence concerning the value of minichromosome maintenance (MCM) protein expression as a novel indicator of proliferation. In the present study, 15 glioblastoma samples, classified according to WHO, were analysed to evaluate the expression of the principal proliferation markers. The samples examined were subdivided into 2 cytological subsets, small cell (SC) or multiforme cell (MC) glioblastoma, according to the predominant cell type defined in individual specimens. MCM7 detected more cells in the cycle than Ki67 and PCNA and all cases of SC glioblastoma, the most aggressive subset, displayed a significant increase of MCM7-stained nuclei versus those stained with Ki67. These results suggest that the cell cycle-associated proteins MCM are not only useful markers of proliferation, but also valid aids for diagnosis in cerebral glioblastoma.

Factores pronósticos en carcinoma de células renales: ¿son adecuadas las variables definidas por el actual TNM? / Prognosis factors in renal cells carcinoma: are the variables defined by TNM adequate?

Objetivo: Identificar aquellos factores pronósticos que influyen de manera independiente en la sobrevida y en caso de ser significativo el tamaño de la lesión, determinar cuál es el mejor punto de corte para esta variable. Materiales y métodos: Se revisaron los registros de 420 pacientes con diagnóstico de carcinoma de células renales estudiados entre enero de 1994 y junio de 2004 en dos centros. El análisis de sobrevida se efectuó a través de curvas de Kaplan-Meier. Se realizó estudio univariado y multivariado para determinar qué factores, clínicos e histológicos, tienen un impacto directo en la sobrevida de los pacientes con cáncer renal. El mejor punto de corte para el tamaño tumoral se determinó por medio de curvas ROC. Resultados: La sobrevida global de la serie fue 76,4 por ciento, con un seguimiento promedio de 30,8 meses (DS±24,5). El análisis demostró una tasa de sobrevida de 95,7 por ciento para T1, 58,5 por ciento para T2, 65,2 por ciento, 49,4 por ciento, 35,4 por ciento para T3 a, b y c, respectivamente y 44,4 porciento para T4. El análisis univariado mostró que la edad, al momento del diagnóstico, el valor del hematocrito y VHS preoperatorios, la presencia de fosfatasas alcalinas elevadas y el tamaño de la lesión influyen en la sobrevida (p <0,05). El análisis multivariado reveló que la presencia de fosfatasas alcalinas elevadas, el tamaño, la invasión de la vena renal (p <0,01) y la invasión de la cápsula renal (p <0,05) son variables con significativo valor pronóstico. El mejor punto de corte para el tamaño entregado por la curva ROC fue 6 cm, tanto para recidiva como para muerte por cáncer, alcanzado una sensibilidad de 80,6 por ciento y una especificidad de 68,1 por ciento.Conclusión: La actual etapificación TNM no se correlaciona certeramente con las sobrevidas obtenidas en esta serie de pacientes. En contraste con lo mencionado en la literatura internacional, el grado de Fuhrman, la invasión de la glándula suprarrenal y el tipo histológico...