Analysis of neutropenia as a predictive factor of the efficacy of trifluridine-tipiracil treatment.

OBJECTIVES: Trifluridine-tipiracil (TAS-102), an oral cytotoxic agent used in adult patients with refractory metastatic colorectal cancer (mCRC), has been associated with neutropenia (chemotherapy-induced neutropenia) (CIN)). MATERIALS AND METHODS: We evaluated the efficacy and safety of TAS-102 in a group of 45 mCRC patients (median age 66 years) in Huelva province, Spain, in a retrospective, multicenter observational study. RESULTS: We showed that the association between TAS-102 and CIN can be used as a predictor of efficacy. 20% (9/45) of patients with an Eastern Cooperative Oncology Group (ECOG) score of 2 had received at least one previous chemotherapy treatment. Overall, 75.5% (34/45) and 28.9% (13/45) had received anti-VEGF and anti-EGFR monoclonal antibodies, respectively. Additionally, 80% (36/45) of patients had received third-line treatment. The mean treatment period, duration of overall survival (OS), and duration of progression-free survival (PFS) were 3.4, 12, and 4 months, respectively. A partial response was seen in 2 patients (4.3%), and disease stabilization was observed in 10 patients (21.3%). Neutropenia was the most frequent grade 3 - 4 toxicity (46.7%; 21/45). Other findings were anemia (77.8%; 35/45), all grades of neutropenia (73.3%; 33/45), and gastrointestinal toxicity (53.3%; 24/45). The dose of TAS-102 needed to be reduced in 68.9% (31/45) of patients, whereas treatment needed to be interrupted in 80% (36/45) of patients. Grade 3 - 4 neutropenia was a positive prognostic factor for OS (p = 0.023). CONCLUSION: A retrospective evaluation shows that grade 3 - 4 neutropenia is an independent predictor of treatment response and survival in patients undergoing routine treatment for mCRC, but this finding needs confirmation in a prospective study.

Pulmonary embolism and COVID-19: A comparative analysis of different diagnostic models performance.

OBJECTIVE: Pulmonary embolism (PE) is a common complication of SARS-CoV-2 infection. Several diagnostic prediction rules based on pretest probability and D-dimer have been validated in non-COVID patients, but it remains unclear if they can be safely applied in COVID-19 patients. We aimed to compare the diagnostic accuracy of the standard approach based on Wells and Geneva scores combined with a standard D-dimer cut-off of 500 ng/mL with three alternative strategies (age-adjusted, YEARS and PEGeD algorithms) in COVID-19 patients. METHODS: This retrospective study included all COVID-19 patients admitted to the Emergency Department (ED) who underwent computed tomography pulmonary angiography (CTPA) due to PE suspicion. The diagnostic prediction rules for PE were compared between patients with and without PE. RESULTS: We included 300 patients and PE was confirmed in 15%. No differences were found regarding comorbidities, traditional risk factors for PE and signs and symptoms between patients with and without PE. Wells and Geneva scores showed no predictive value for PE occurrence, whether a standard or an age-adjusted cut-off was considered. YEARS and PEGeD algorithms were associated with increased specificity (19% CTPA reduction) but raising non-diagnosed PE. Despite elevated in all patients, those with PE had higher D-dimer levels. However, incrementing thresholds to select patients for CTPA was also associated with a substantial decrease in sensitivity. CONCLUSION: None of the diagnostic prediction rules are reliable predictors of PE in COVID-19. Our data favour the use of a D-dimer threshold of 500 ng/mL, considering that higher thresholds increase specificity but limits this strategy as a screening test.

Balance disorders as potential confounders associated with an increased risk of acute cerebrovascular accidents.

PURPOSE: There is a higher risk of stroke after suffering from balance disorders (BDs) such as vertigo or dizziness. The causal relationship remains unclear due to the limited scope of the existing studies and the high prevalence of cardiovascular risk factors (CVRFs) in BD patients. The objective of this study is to clarify the role that BDs seem to have in the development of acute cerebrovascular accidents (ACAs). METHODS: This is an observational prospective study. The CVRFs and demographic factors of a sample of our population were noted. Five clusters of patients were tracked over the course of 2 years to detect and diagnose BDs and ACAs. The causal relationships between the CVRFs, BDs and ACAs were analyzed in a univariate analysis. A logistic regression multivariant analysis was performed on those variables that reached statistical significance. RESULTS: The sample included 7886 participants and 31 ACAs were recorded. CVRFs that reached statistical significance included age ≥ 60, hypertension, diabetes mellitus, dyslipidemia, ischemic heart disease, atrial fibrillation and previous ACAs. The relationship between BDs and ACAs always reached statistical significance, regardless of how the BD variable was defined. Five different multivariate analyses were performed, but in none of them did the BD variables significantly reduce the deviance and thus, they were not taken into account when building the final model. CONCLUSION: This study shows that BDs are probably confounders that are closely linked to other CVRFs and they are also useful red flags to identify patients at a higher risk of suffering from ACAs.

Metalloproteinases 1 and 3 as Potential Biomarkers in Breast Cancer Development.

Breast cancer continues to be one of the main causes of morbidity and mortality globally and was the leading cause of cancer death in women in Spain in 2020. Early diagnosis is one of the most effective methods to lower the incidence and mortality rates of breast cancer. The human metalloproteinases (MMP) mainly function as proteolytic enzymes degrading the extracellular matrix and plays important roles in most steps of breast tumorigenesis. This retrospective cohort study shows the immunohistochemical expression levels of MMP-1, MMP-2, MMP-3, and MMP-9 in 154 women with breast cancer and 42 women without tumor disease. The samples of breast tissue are assessed using several tissue matrices (TMA). The percentages of staining (≤50%->50%) and intensity levels of staining (weak, moderate, or intense) are considered. The immunohistochemical expression of the MMP-1-intensity (p = 0.043) and MMP-3 percentage (p = 0.018) and intensity, (p = 0.025) present statistically significant associations with the variable group (control-case); therefore, expression in the tumor tissue samples of these MMPs may be related to the development of breast cancer. The relationships between these MMPs and some clinicopathological factors in breast cancer are also evaluated but no correlation is found. These results suggest the use of MMP-1 and MMP-3 as potential biomarkers of breast cancer diagnosis.

Matrix metalloproteases and TIMPs as prognostic biomarkers in breast cancer patients treated with radiotherapy: A pilot study.

Breast cancer (BC) is the most common tumour in women and one of the most important causes of cancer death worldwide. Radiation therapy (RT) is widely used for BC treatment. Some proteins have been identified as prognostic factors for BC (Ki67, p53, E-cadherin, HER2). In the last years, it has been shown that variations in the expression of MMPs and TIMPs may contribute to the development of BC. The aim of this pilot work was to study the effects of RT on different MMPs (-1, -2, -3, -7, -8, -9, -10, -12 and -13) and TIMPs (-1 to -4), as well as their relationship with other variables related to patient characteristics and tumour biology. A group of 20 BC patients treated with RT were recruited. MMP and TIMP serum levels were analysed by immunoassay before, during and after RT. Our pilot study showed a slight increase in the levels of most MMP and TIMP with RT. However, RT produced a significantly decrease in TIMP-1 and TIMP-3 levels. Significant correlations were found between MMP-3 and TIMP-4 levels, and some of the variables studied related to patient characteristics and tumour biology. Moreover, MMP-9 and TIMP-3 levels could be predictive of RT toxicity. For this reason, MMP-3, MMP-9, TIMP-3 and TIMP-4 could be used as potential prognostic and predictive biomarkers for BC patients treated with RT.

Prognostic Value of Secretoneurin in Patients With Severe Sepsis and Septic Shock: Data From the Albumin Italian Outcome Sepsis Study.

OBJECTIVES: Secretoneurin directly influences cardiomyocyte calcium handling, and circulating secretoneurin levels seem to improve risk prediction in patients with myocardial dysfunction by integrating information on systemic stress, myocardial function, and renal function. Accordingly, in this study, we hypothesized that secretoneurin would improve risk prediction in patients with sepsis and especially in patients with septic shock as these patients are more hemodynamically unstable. DESIGN: Multicenter, interventional randomized clinical trial. SETTING: Multicenter, pragmatic, open-label, randomized, prospective clinical trial testing fluid administration with either 20% human albumin and crystalloids or crystalloid solutions alone in patients with severe sepsis or septic shock (The Albumin Italian Outcome Sepsis). PATIENTS OR SUBJECTS: In total, 540 patients with septic shock and 418 patients with severe sepsis. INTERVENTIONS: Either 20% human albumin and crystalloids or crystalloid solutions alone. MEASUREMENTS AND MAIN RESULTS: We measured secretoneurin on days 1, 2, and 7 after randomization and compared the prognostic value of secretoneurin for ICU and 90-day mortality with established risk indices and cardiac biomarkers in septic shock and severe sepsis. High secretoneurin levels on day 1 were associated with age and serum concentrations of lactate, bilirubin, creatinine, and N-terminal pro-B-type natriuretic peptide. Adjusting for established risk factors and cardiovascular biomarkers, secretoneurin levels on day 1 were associated with ICU (odds ratio, 2.27 [95% CI, 1.05-4.93]; p = 0.04) and 90-day mortality (2.04 [1.02-4.10]; p = 0.04) in patients with septic shock, but not severe sepsis without shock. Secretoneurin levels on day 2 were also associated with ICU (3.11 [1.34-7.20]; p = 0.008) and 90-day mortality (2.69 [1.26-5.78]; p = 0.01) in multivariate regression analyses and improved reclassification in patients with septic shock, as assessed by the net reclassification index. Randomized albumin administration did not influence the associations between secretoneurin and outcomes. CONCLUSIONS: Secretoneurin provides early and potent prognostic information in septic patients with cardiovascular instability.

Neuromotor and cognitive responses of adults with autism spectrum disorder compared to neurotypical adults.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder, whose core symptom domains include impaired social communication and narrowed interests and/or repetitive behaviors; in addition, deficits of general cognition, neuromotor function, and movement ability can be observed. This study was designed to examine differences in neuromotor and cognitive functions for a group of young adults with ASD and age-matched controls. It was also of interest to assess whether changes in the intra-individual variability (IIV) of these selected neuromotor and cognitive tasks also occurred. Increased IIV in persons with ASD may reveal important organizational features of their neuromotor system that differ from neurotypical controls. Twenty neurotypical adult individuals (24.3 ± 2.8 years) and twenty adults with a clinician-assigned diagnosis of ASD (21.2 ± 4.4 years) participated in this study. Specific cognitive and motor assessments included Trails Making Tests A&B, Symbol Digit Modalities Test, Purdue Pegboard Test, simple reaction time, finger tapping, hand grip strength, balance, and gait. Results revealed that the ASD adults exhibited decreased upper limb strength and slower responses for finger tapping, hand dexterity, reaction times, and gait compared to the non-ASD controls. The general slowing of motor responses for the persons with ASD was also associated with increased within-subject variability during the reaction time, finger tapping, hand grip, and gait assessments compared to neurotypical adults, illustrating that IIV measures may be a useful marker of widespread neuromotor dysfunction for adults with ASD. Overall, these findings are consistent with clinical observations that abnormalities of movement performance and cognitive performance are an associated feature of ASD in young adults.

A trial of d-cycloserine to treat the social deficit in older adolescents and young adults with autism spectrum disorders.

Autism spectrum disorders are difficult for older adolescents and young adults as impaired social communication affects the transition to adult life. d-Cycloserine, a partial glycine agonist at the N-methyl-d-aspartic acid receptor, was tested in a double-blind randomized trial in 20 older adolescents and young adults with autism spectrum disorders using two dosing strategies (50 mg daily versus 50 mg weekly) for 8 weeks with a 2-week follow-up after discontinuation. d-Cycloserine caused statistically and clinically significant improvement with no differentiation between dosing strategies on the Social Responsiveness Scale and the Aberrant Behavior Checklist before and after d-cycloserine administration.

Selective neck dissection as a therapeutic option in management of squamous cell carcinoma of unknown primary.

Carcinoma of unknown primary of the neck (CUP) is a metastasis presenting in one or more cervical lymph nodes, with no primary mucosal site identified. Retrospective case notes review of 25 consecutive patients (median age 55, 72% males) diagnosed as CUP who underwent neck dissection in a UK tertiary referral comprehensive cancer centre between 2000 and 2011. Median follow-up was 33 months. Nineteen patients underwent comprehensive neck dissections (six extended), six patients had selective neck dissection. Five year disease specific survival and regional recurrence free survival were 76 and 80% respectively. The overall rate of occult disease (disease not identified on preoperative evaluation, but found on histopathologic examination) was 8%, with rates of 0% in level I and 6% in level V. Our study suggests that in patients without preoperative evidence of disease in levels I or V selective neck dissection might be considered as an option, to facilitate preservation of the submandibular gland and accessory nerve without compromising oncological outcome. Larger studies should be performed before a change in practice can be advised.

Transdiaphragmatic intercostal hernia induced by sternutation: A case report.

INTRODUCTION AND IMPORTANCE: Sternutation is, by definition, a situation that increases abdominal pressure. However, it has not been clearly linked to protrusion of abdominal content through weaknesses in the abdominal boundaries. CASE PRESENTATION: Here we present a case report in which the only trigger factor found for an abdominal content protrusion was a sternutation episode. The patient arrived in our institution with the diagnosis of a transdiaphragmatic intercostal hernia, proven in CT-scan. He was, then, submitted to emergent surgery, where through thoracotomy and subcostal laparotomy, hernia content was reduced. The patient had a favorable evolution. CLINICAL DISCUSSION: TDIH is a rare entity, for which there are still no consensus regarding its management. This makes clinical practice more challenging, leaving to the surgeon the therapeutic decision tailored to each patient. CONCLUSION: This entity should be further studied, and consensus reached regarding its management.

Clinical outcomes in patients with diabetes and stress hyperglycemia that developed SARS-CoV-2 infection / Desenlaces clínicos de los pacientes con diabetes e hiperglucemia de estrés que presentaron infección por SARS-CoV-2

INTRODUCTION: Diabetes and stress hyperglycemia have been related with poorer clinical outcomes in patients infected by SARS-CoV-2 and at risk for severe disease. OBJECTIVE: To evaluate clinical outcomes in three groups of patients (with diabetes, without diabetes and with stress hyperglycemia) with SARS-CoV-2 infection. MATERIALS AND METHODS: A retrospective cohort study was conducted in Cali (Colombia). We included patients 18 years old or older with a diagnosis of SARS-CoV-2 infection, managed in the emergency room, hospitalization, or intensive care unit between March 2020 and December 2021. Immunocompromised patients and pregnant women were excluded. Patients were classified into three groups: without diabetes, with diabetes, and with stress hyperglycemia. A comparison between the groups was performed. RESULTS: A total of 945 patients were included (59.6% without diabetes, 27% with diabetes, and 13.4% with stress hyperglycemia). Fifty-five-point three percent required intensive care unit management, with a higher need in patients with stress hyperglycemia (89.8%) and diabetes (67.1%), with no difference between these groups (p = 0.249). We identified a higher probability of death in the group with stress hyperglycemia versus the one without diabetes (adjusted OR = 8.12; 95% CI: 5.12-12.88; p < 0.01). Frequency of acute respiratory distress syndrome, need for invasive mechanical ventilation, use of vasopressors and inotropes, need for de novo renal replacement therapy, and mortality was higher in patients with metabolic alterations (diabetes and stress hyperglycemia). CONCLUSIONS: Diabetes and stress hyperglycemia were associated with worse clinical outcomes and mortality in patients with COVID-19. These patients should be identified early and considered them high risk at the COVID-19 diagnosis to mitigate adverse outcomes.

Introducción. La diabetes y la hiperglucemia de estrés se han relacionado con peores desenlaces clínicos en pacientes infectados por SARS-CoV-2 y con riesgo de enfermedad grave. Objetivo. Evaluar los resultados clínicos en tres grupos de pacientes (con diabetes, sin diabetes o con hiperglucemia de estrés) con infección por SARS-CoV-2. Materiales y métodos. Se llevó a cabo un estudio retrospectivo de cohorte en Cali (Colombia). Se incluyeron pacientes de 18 años o más, con diagnóstico de infección por SARS-CoV-2 atendidos en urgencias, hospitalización o unidad de cuidados intensivos entre marzo de 2020 y diciembre de 2021. Se excluyeron los pacientes inmunocomprometidos y las mujeres embarazadas. Los pacientes fueron clasificados en tres grupos: sin diabetes, con diabetes y con hiperglucemia de estrés. Se realizó una comparación entre los grupos. Resultados. Se incluyeron 945 pacientes (59,6 % sin diabetes, 27 % con diabetes y 13,4 % con hiperglucemia de estrés). El 55,3 % requirió manejo en la unidad de cuidados intensivos, con mayor necesidad por parte de los pacientes con hiperglucemia de estrés (89,8 %) y diabetes (67,1%), sin diferencia entre estos grupos (p = 0,249). Se observó una mayor probabilidad de muerte en el grupo con hiperglucemia de estrés versus sin diabetes (OR ajustado = 8,12; IC95%: 5,12-12,88; p < 0,01). La frecuencia de síndrome de distrés respiratorio agudo, necesidad de ventilación mecánica invasiva, uso de vasopresores e inotrópicos, necesidad de terapia de reemplazo renal de novo y mortalidad fue mayor en pacientes con alteraciones metabólicas (diabetes e hiperglucemia de estrés). Conclusiones. La diabetes y la hiperglucemia de estrés se asociaron a peores resultados clínicos y mortalidad en pacientes con COVID-19. Estos pacientes deben ser identificados tempranamente y considerados de alto riesgo al momento del diagnóstico de COVID-19 para mitigar los desenlaces adversos.

Comparison of the accuracy of four diagnostic prediction rules for pulmonary embolism in patients admitted to the emergency department.

INTRODUCTION AND OBJECTIVES: Ruling out pulmonary embolism (PE) through a combination of clinical assessment and D-dimer level can potentially avoid excessive use of computed tomography pulmonary angiography (CTPA). We aimed to compare the diagnostic accuracy of the standard approach based on the Wells and Geneva scores combined with a standard D-dimer cut-off (500 ng/ml), with three alternative strategies (age-adjusted and the YEARS and PEGeD algorithms) in patients admitted to the emergency department (ED) with suspected PE. METHODS: Consecutive outpatients admitted to the ED who underwent CTPA due to suspected PE were retrospectively assessed. Sensitivity, specificity, positive and negative predictive values, likelihood ratios and diagnostic odds ratios were calculated and compared between the different diagnostic prediction rules. RESULTS: We included 1402 patients (mean age 69±18 years, 54% female), and PE was confirmed in 25%. Compared to the standard approach (p<0.001), an age-adjusted strategy increased specificity with a non-significant decrease in sensitivity only in patients older than 70 years. Compared to the standard and age-adjusted approaches, the YEARS and PEGeD algorithms had the highest specificity across all ages, but were associated with a significant decrease in sensitivity (p<0.001), particularly in patients aged under 60 years (sensitivity of 81% in patients aged between 51 and 60 years). CONCLUSION: Compared to the standard approach, all algorithms were associated with increased specificity. The age-adjusted strategy was the only one not associated with a significant decrease in sensitivity compared to the standard approach, enabling CTPA requests to be reduced safely.

The Role of TOMM40 in Cardiovascular Mortality and Conduction Disorders: An Observational Study.

Aims: TOMM40 single nucleotide polymorphism (SNP) rs2075650 consists of allelic variation c.275-31A > G and it has been linked to Alzheimer disease, apolipoprotein and cholesterol levels and other risk factors. However, data on its role in cardiovascular disorders are lacking. The first aim of the study is to evaluate mortality according to TOMM40 genotype in a cohort of selected patients affected by advanced atherosclerosis. Second aim was to investigate the relationship between Xg and AA alleles and the presence of conduction disorders and implantation of defibrillator (ICD) or pacemaker (PM) in our cohort. Materials and Methods: We enrolled 276 patients (mean age 70.16 ± 7.96 years) affected by hemodynamic significant carotid stenosis and/or ischemia of the lower limbs of II or III stadium Fontaine. We divided the population into two groups according to the genotype (Xg and AA carriers). We evaluated several electrocardiographic and echocardiographic parameters, including heart rate, rhythm, presence of right and left bundle branch block (LBBB and RBBB), PR interval, QRS duration and morphology, QTc interval, and left ventricular ejection fraction (LVEF). We clinically followed these patients for 82.53 ± 30.02 months and we evaluated the incidence of cardiovascular events, number of deaths and PM/ICD implantations. Results: We did not find a difference in total mortality between Xg and AA carriers (16.3 % vs. 19.4%; p = 0.62). However, we found a higher mortality for fatal cardiovascular events in Xg carriers (8.2% vs. 4.4%; HR = 4.53, 95% CI 1.179-17.367; p = 0.04) with respect to AA carriers. We noted a higher percentage of LBBB in Xg carriers (10.2% vs. 3.1%, p = 0.027), which was statistically significant. Presence of right bundle branch block (RBBB) was also higher in Xg (10.2% vs. 4.4%, p = 0.10), but without reaching statistically significant difference compared to AA patients. We did not observe significant differences in heart rate, presence of sinus rhythm, number of device implantations, PR and QTc intervals, QRS duration and LVEF between the two groups. At the time of enrolment, we observed a tendency for device implant in Xg carriers at a younger age compared to AA carriers (58.50 ± 0.71 y vs. 72.14 ± 11.11 y, p = 0.10). During the follow-up, we noted no statistical difference for new device implantations in Xg respect to AA carriers (8.2% vs. 3.5%; HR = 2.384, 95% CI 0.718-7.922; p = 0.156). The tendency to implant Xg at a younger age compared to AA patients was confirmed during follow-up, but without reaching a significant difference(69.50 ± 2.89 y vs. 75.63 ± 8.35 y, p = 0.074). Finally, we pointed out that Xg carriers underwent device implantation 7.27 ± 4.43 years before AA (65.83 ± 6.11 years vs. 73.10 ± 10.39 years) and that difference reached a statistically significant difference (p = 0.049) when we considered all patients, from enrollment to follow-up. Conclusions: In our study we observed that TOMM40 Xg patients affected by advanced atherosclerosis have a higher incidence of developing fatal cardiovascular events, higher incidence of LBBB and an earlier age of PM or ICD implantations, as compared to AA carriers. Further studies will be needed to evaluate the genomic contribution of TOMM40 SNPs to cardiovascular deaths and cardiac conduction diseases.

Association between Ustekinumab Trough Levels, Serum IL-22, and Oncostatin M Levels and Clinical and Biochemical Outcomes in Patients with Crohn's Disease.

Background: Ustekinumab (UST) has demonstrated effectiveness in treating patients with Crohn's disease. Monitoring treatment response can improve disease management and reduce healthcare costs. We investigated whether UST trough levels (TLs), serum IL22, and Oncostatin M (OSM) levels could be early indicators of non-response by analysing their correlation with clinical and biochemical outcomes in CD. Methods: Patients with CD initiating UST treatment from October 2018 to September 2020 were enrolled at six Italian centres for inflammatory bowel disease (IBD). Clinical and biochemical data were collected at four time points: baseline, second subcutaneous (SC) dose, fourth SC dose, and 52 weeks. TLs were measured during maintenance, at the second SC dose, and at the fourth SC dose. IL-22 and OSM serum levels were assessed at baseline and the second SC dose. We analysed whether TLs, IL22 levels, and OSM serum levels were associated with clinical response, clinical remission, biochemical remission, and endoscopic remission using the appropriate statistical tests. Results: Out of eighty-four initially enrolled patients, five were lost to follow-up, and eleven discontinued the drug before 52 weeks. At the 52-week time point, 47% achieved biochemical remission based on faecal calprotectin levels, and 61.8% achieved clinical remission. TLs at the second SC dose significantly correlated with biochemical remission at the same time point (p = 0.011). However, TLs did not correlate with clinical remission. Baseline OSM levels did not correlate with biochemical or clinical remission or response. IL22 levels notably decreased during UST therapy (p = 0.000), but its values did not correlate with biochemical or clinical remission. Conclusions: UST is an effective therapy for patients with CD. TLs measured at the second SC dose significantly correlated with biochemical remission, emphasising their potential role in treatment monitoring. Levels of OSM and IL-22, despite a significant decrease in the latter during therapy, did not exhibit correlations with clinical or biochemical outcomes in our study. Further studies are needed to confirm these findings.

Vedolizumab is superior to infliximab in biologic naïve patients with ulcerative colitis.

There are no prospective, head-to-head, controlled trials comparing the efficacy and safety of Infliximab (IFX) and Vedolizumab (VDZ) for the treatment of moderate-to-severe ulcerative colitis (UC), while only a few real-life retrospective studies have been published so far. We assessed the efficacy of IFX vs. VDZ in two cohorts of biologic-naïve outpatients with moderate-to-severe UC or mild, but refractory, disease. Data were extracted from patients' files and reviewed. The duration of follow-up (FU) was 52 weeks. The primary endpoint was the clinical remission (CR) at the end of FU. Secondary endpoints were: drug persistency, time to obtain CR, clinical response at the end of the induction phase (IP), steroid-free CR (compared to patients who used steroids at baseline) at the end of FU, need for drug optimization, adverse events (AEs), and normalization of C-reactive protein (CRP). We also analyzed the causes of dropping out (primary non-response), or secondary loss of response (immunogenic or not), for each group. We enrolled 82 patients (50 IFX and 32 VDZ) who met the inclusion criteria. At the end of FU, CR was obtained in 32% of the patients on IFX and 75% on VDZ (p = 0.0003). Drug persistency was superior for VDZ compared to IFX (78% vs. 52%, p = 0.033). Clinical response at the end of induction was reached in 54% and in 81% in the IFX and VDZ group, respectively (p = 0.014). Steroid-free clinical remission at the end of FU was 62% and 94% in the IFX vs. VDZ group, respectively (p = 0.036). The need for drug optimization was higher for VDZ than for IFX (28% vs. 57%, p = 0.009), while the time to obtain CR, the incidence of AEs, mean duration of FU, and rate of CRP normalization at the end of IP were comparable between the two groups. There was a prevalence of patients dropping out because of primary non-response in IFX group (p = 0.027), while the incidence of secondary loss of response was similar in the two groups. At the multivariate analysis, CRP and Partial Mayo Score (PMS) at T0 did not correlate with CR at the end of FU in both groups. In this retrospective, real world data study in biologic-naïve patients, VDZ was superior to IFX in CR, clinical response rate at the end of IP, drug persistency, steroid-free remission, and need for optimization at the end of FU.

Involvement of APOE in Incidence of Revascularization in Patients Affected by Peripheral Arterial Disease: A Prospective Study from Southern Italy.

INTRODUCTION: Atherosclerosis is a complex multifactorial disease and apolipoprotein E (APOE) polymorphism has been associated with cardiovascular events. The APOE gene, located on chromosome 19q13.2, has an important role in lipid metabolism, in particular on circulating cholesterol levels, implying further pleiotropic effects; from its polymorphism are derived three alleles (ε2, ε3 and ε4), which induce different phenotypes, while its impact on carotid and femoral atherosclerosis is still controversial. OBJECTIVES: The aim of the study is to investigate the relationship between APOE genotypes and peripheral revascularization in a cohort of patients affected by advanced peripheral arterial disease (PAD) at a prolonged follow-up. MATERIALS AND METHODS: Some 332 patients (259 males and 73 females; mean age 70.86 ± 7.95 years) with severe PAD were enrolled in a longitudinal study, with a 90.75 ± 32.25 month follow-up, assessing major adverse cardiovascular events (MACE). RESULTS: As compared with ε3/ε3, in ε4 patients we observed a significant higher incidence of carotid (13.2% vs. 5.6%; HR = 2.485, 95% CI 1.062-5.814; p = 0.036) and lower limb (11.8% vs. 4.3%; HR = 2.765, 95% CI 1.091-7.008; p = 0.032) revascularizations and, accordingly, a higher incidence of total peripheral revascularizations (13.5% vs. 9.5%; HR = 2.705, 95% CI 1.420-5.151; p = 0.002). HR remained statistically significant even when adjusted for classic cardiovascular risk factors. CONCLUSIONS: In our observational study, we confirm that the ε4 allele is associated with higher total peripheral revascularization in patients with advanced atherosclerotic vascular disease at prolonged follow-up.

Adrenal Neuroblastoma Producing Catecholamines Diagnosed in Adults: Case Report.

Neuroblastoma is a solid tumor considered almost exclusively pediatric, with more than 95% of patients diagnosed before 10 years of age, with a mostly benign clinical course and with encouraging survival rates in these age ranges. It occurs rarely in adolescents, and the presentation in young adults or older people is even rarer; consequently, a more severe prognosis and higher mortality rates have been documented within this population. This is also due to a great limitation within the treatment since the chemotherapeutic regimens proposed so far are valid for pediatric patients, with low tolerance to it within the adult population. We present the case of a 24-year-old female patient with catecholamine-secreting neuroblastoma who obtained surgical management, with subsequent local tumor recurrence, with subsequent need for onco-specific and symptomatic management.

Comparison of 5 acute pulmonary embolism mortality risk scores in patients with COVID-19.

OBJECTIVE: Pulmonary embolism (PE) is a common complication of SARS-CoV-2 infection. We aimed to explore the short-term outcomes among patients with acute PE and COVID-19 and to further determine and compare the performance of the different prognostic scores (PESI, sPESI, BOVA, FAST and ESC scores) for risk-stratification in this scenario. METHODS: Retrospective single-centre study of 85 patients with SARS-CoV-2 infection and PE admitted to the Emergency Department (ED). The diagnostic accuracy of each above-mentioned prognostic score was calculated post hoc, and their discriminative power was evaluated through an AUC curve. RESULTS: Among the 85 patients, all-cause death occurred within 7 days for 6 patients (7.1%) and within 30 days for 14 patients (16.5%). Despite being older and having a higher percentage of altered mental status on presentation, non-survivors patients did not differ from survivors regarding comorbidities, traditional risk factors for venous thromboembolism and signs and symptoms at the ED presentation.Each risk stratification tool had modest discriminative power for 7-day mortality (AUC range, 0.601-0.730) with slightly lower discrimination for 30-day mortality (AUC range, 0.543-0.638). The pair-wise comparison of ROC curves showed that PESI had better predictive value for short-term mortality than ESC score (z test = 3.92, p = 0.001) and sPESI (z test = 2.43, p = 0.015); there is no significant difference between PESI and BOVA score (z test = 1.05, p = 0.295) and FAST score (z test = 0.986, p = 0.324). CONCLUSION: The most common risk-stratification tools for PE had modest discriminative power to predict short-term mortality in patients with acute PE and COVID-19.

Analysis of Blood Biochemistry and Pituitary-Gonadal Histology after Chronic Exposure to Bisphenol-A of Mice.

Bisphenol-A is an emerging pollutant that is widespread in the environment, and to which live beings are continuously and inadvertently exposed. It is a substance with an endocrine-disrupting capacity, causing alterations in the reproductive, immunological, and neurological systems, among others, as well as metabolic alterations. Our study aimed to assess its clinical signs, and effects on the most relevant blood biochemical parameters, and to evaluate pituitary and gonadal histology after a chronic exposure of adult mice to different BPA doses (0.5, 2, 4, 50 and 100 µg/kg BW/day) through their drinking water. The biochemical results showed that a marked significant reduction (p < 0.05) was produced in the levels of serum glucose, hypoproteinaemia and hypoalbuminemia in the groups exposed to the highest doses, whereas in the group exposed to 50 µg/kg BW/day the glucose and total protein levels dropped, and the animals exposed to 100 µg/kg BW/day experienced a diminution in albumin levels. In the case of the group exposed to 50 µg/kg BW/day, however, hypertriglyceridemia and hypercholesterolemia were determined, and the blood parameters indicating kidney alterations such as urea and creatinine experienced a significant increase (p < 0.05) with respect to the controls. Regarding the pituitary and gonads, none of the animals exposed presented histological alterations at the doses tested, giving similar images to those of the control group. These results suggest that continuous exposure to low BPA doses could trigger an inhibition of hepatic gluconeogenesis, which would result in a hypoglycaemic state, together with an induction of the enzymes responsible for lipidic synthesis, a mechanism by which the increase in the lipid and serum cholesterol levels could be explained. Likewise, the decline in the protein and albumin levels would be indicative of a possible hepatic alteration, and the increase in urea and creatinine would point to a possible renal perturbation, derived from continuous exposure to this xenobiotic. Based on our results, it could be said that chronic exposure to low BPA doses would not produce any clinical signs or histological pituitary-gonadal effects, but it could cause modifications in some blood biochemical parameters, that could initially indicate a possible hepatic and renal effect.

Italian Case Report with a Double Mutation in PSEN1 (K311R and E318G).

Alzheimer's disease (AD) is the most common cause of dementia worldwide. The clinical spectrum of suspected AD has been extended from mild cognitive impairment (MCI) to preclinical AD which includes people who have typical cognitive function but harbor the underlying biological features of AD. We report the first case of an Italian patient affected by MCI (MMSE 24\30), characterized by a double mutation p.Lys311Arg (K311R) and p.Glu318Gly (E318G) in Presenilin-1 but with the absence of abnormal accumulation of amyloid beta.