Long-term drug survival of risankizumab in psoriasis: insights from a real-life multicenter study on hard-to-treat areas.

Psoriasis, a chronic inflammatory condition, often presents challenges in treatment, particularly in areas such as nails, palms/soles, scalp/face, and genitalia. Monoclonal antibodies (mAb) like risankizumab targeting interleukin-23 (IL-23) have emerged as promising treatments, yet data on long-term efficacy remain limited. This multicenter retrospective study aimed to evaluate the drug survival at 12 and 36 months of 191 psoriasis patients treated with risankizumab, focusing on critical areas. Patients, previously unresponsive to first-line therapies, were treated according to Italian Guidelines. Survival analysis revealed a 97.6% one-year and 95% three-year drug survival rate. Secondary ineffectiveness was the primary reason for discontinuation, particularly in palmoplantar involvement cases. Factors such as BMI, gender, age, disease duration, baseline severity, and previous biologic exposure did not significantly impact drug survival, except for palmoplantar psoriasis (HR 4.72). Risankizumab demonstrated prolonged response with low treatment switch requirements, especially notable in challenging areas. Understanding such factors can aid in optimizing therapeutic approaches for improved patient care and long-term outcomes in managing psoriasis. Further research is warranted to refine treatment strategies in difficult-to-treat areas.

Validation of the Predisposition Infection Response Organ (PIRO) dysfunction score for the prognostic stratification of patients with sepsis in the Emergency Department / Validación del sistema PIRO (predisposición, infección, respuesta, fallo orgánico) para la estratificación del pronóstico en pacientes con sepsis en el servicio de urgencias

Objective: There are many different methods for computing the Predisposition Infection Response Organ (PIRO) dysfunction score. We compared three PIRO methods (PIRO1 (Howell), PIRO2 (Rubulotta) and PIRO3 (Rathour)) for the stratification of mortality and high level of care admission in septic patients arriving at the Emergency Department (ED) of an Italian Hospital. Design, setting and participants We prospectively collected clinical data of 470 patients admitted due to infection in the ED to compute PIRO according to three different methods. We tested PIRO variables for the prediction of mortality in the univariate analysis. Calculation and comparison were made of the area under the receiver operating curve (AUC) for the three PIRO methods, SOFA and qSOFA. Results Most of the variables included in PIRO were related to mortality in the univariate analysis. Increased PIRO scores were related to higher mortality. In relation to mortality, PIRO 1 performed better than PIRO2 at 30 d ((AUC 0.77 (0.716–0.824) vs. AUC 0.699 (0.64–0.758) (p=0.03) and similarly at 60 d (AUC 0.767 (0.715–0.819) vs AUC 0.709 (0.656–0.763)(p=0.55)); PIRO1 performed similarly to PIRO3 (AUC 0.765 (0.71–0.82) at 30 d, AUC 0.754 (0.701–0.806) at 60 d, p=ns). Both PIRO1 and PIRO3 were as good as SOFA referred to mortality (AUC 0.758 (0.699, 0.816) at 30 d vs. AUC 0.738 (0.681, 0.795) at 60 d; p=ns). For high level of care admission, PIRO proved inferior to SOFA. Conclusions We support the use of PIRO1, which combines ease of use and the best performance referred to mortality over the short term. PIRO2 proved to be less accurate and more complex to use, suffering from missing microbiological data in the ED setting. (AU)

Objetivo: Existen muchos métodos diferentes para calcular la escala PIRO (predisposición, infección respuesta, fallo orgánico). Comparamos 3 métodos (PIRO1 [Howell], PIRO2 [Rubolotta] y PIRO3 [Rathour]) para estratificar la mortalidad y el ingreso con alto nivel de cuidados en pacientes con sepsis atendidos en el servicio de urgencias (SU) de un hospital italiano. Diseño, entorno y participantes Recopilamos datos clínicos prospectivos de 470 pacientes que llegaban con una infección al SU, con el fin de calcular la puntuación PIRO, de acuerdo con 3 métodos diferentes. Evaluamos las variables PIRO para la predicción de la mortalidad en un análisis monovariable. Calculamos y comparamos el área bajo la curva (AUC) característica de operación del receptor (ROC) de los 3 métodos PIRO, SOFA y qSOFA. Resultados La mayoría de las variables incluidas en las puntuaciones PIRO estaban relacionadas con la mortalidad en un análisis de una sola variable. El aumento de la puntuación PIRO se relacionó con una mortalidad más elevada. En cuanto a la mortalidad, PIRO1 presentó un rendimiento mejor que PIRO2 a los 30 días (AUC 0,77 [0,716-0,824] frente a AUC 0,699 [0,64-0,758]; p=0,03) y similares a los 60 días (AUC 0,767 [0,715-0,819] frente a AUC 0,709 [0,656-0,763]; p=0,55); PIRO1 presentó un rendimiento similar al de PIRO3 (AUC 0,765 [0,71-0,82] a los 30 días, AUC 0,754 [0,701-0,806] a los 60 días; p=NS). Tanto PIRO1 como PIRO3 presentaron un rendimiento similar al de SOFA para la mortalidad (AUC 0,758 [0,699-0,816) al cabo de 30 días y AUC 0,738 [0,681-0,795] al cabo de 60 días; p=NS). En cuanto al ingreso con alto nivel de cuidados, las puntuaciones PIRO resultaron ser inferiores a SOFA. Conclusiones Apoyamos el uso de la puntuación PIRO1, que resulta fácil de usar, y presenta el mejor rendimiento en cuanto a la mortalidad a largo plazo. PIRO2 resultó ser menos precisa y más compleja de usar ... (AU)

Validation of the Predisposition Infection Response Organ (PIRO) dysfunction score for the prognostic stratification of patients with sepsis in the Emergency Department.

OBJECTIVE: There are many different methods for computing the Predisposition Infection Response Organ (PIRO) dysfunction score. We compared three PIRO methods (PIRO1 (Howell), PIRO2 (Rubulotta) and PIRO3 (Rathour)) for the stratification of mortality and high level of care admission in septic patients arriving at the Emergency Department (ED) of an Italian Hospital. DESIGN, SETTING AND PARTICIPANTS: We prospectively collected clinical data of 470 patients admitted due to infection in the ED to compute PIRO according to three different methods. We tested PIRO variables for the prediction of mortality in the univariate analysis. Calculation and comparison were made of the area under the receiver operating curve (AUC) for the three PIRO methods, SOFA and qSOFA. RESULTS: Most of the variables included in PIRO were related to mortality in the univariate analysis. Increased PIRO scores were related to higher mortality. In relation to mortality, PIRO 1 performed better than PIRO2 at 30 d ((AUC 0.77 (0.716-0.824) vs. AUC 0.699 (0.64-0.758) (p=0.03) and similarly at 60 d (AUC 0.767 (0.715-0.819) vs AUC 0.709 (0.656-0.763)(p=0.55)); PIRO1 performed similarly to PIRO3 (AUC 0.765 (0.71-0.82) at 30 d, AUC 0.754 (0.701-0.806) at 60 d, p=ns). Both PIRO1 and PIRO3 were as good as SOFA referred to mortality (AUC 0.758 (0.699, 0.816) at 30 d vs. AUC 0.738 (0.681, 0.795) at 60 d; p=ns). For high level of care admission, PIRO proved inferior to SOFA. CONCLUSIONS: We support the use of PIRO1, which combines ease of use and the best performance referred to mortality over the short term. PIRO2 proved to be less accurate and more complex to use, suffering from missing microbiological data in the ED setting.

False-negative real-time polymerase chain reaction tests in COVID-19 patients: an epidemiological analysis of 302 patients.

OBJECTIVES: Patients who arrive at the emergency department (ED) with COVID-19, who test negative at the first real-time polymerase chain reaction (RT-PCR), represent a clinical challenge. This study aimed to evaluate if the clinical manifestation at presentation, the laboratory and imaging results, and the prognosis of COVID-19 differ in patients who tested negative at the first RT-PCR compared with those who tested positive and also to evaluate if comorbid conditions patient-related or the period of arrival are associated with negative testing. STUDY DESIGN: We retrospectively collected clinical data of patients who accessed the ED from March 1 to May 15, 2020. METHODS: We compared clinical variables, comorbid conditions, and clinical outcomes in the two groups by univariate analysis and logistic regression. RESULTS: Patients who tested negative at the first RT-PCR showed a higher prevalence of cardiopathy, immunosuppression, and diabetes, as well as a higher leukocyte and lower lymphocyte counts compared with patients who tested positive. A bilateral interstitial syndrome and a typical pattern at computed tomography scan were prevalent in the test-negative group. Test-negative patients were more likely to be admitted to the hospital but less likely to need admission in a high level of care ward. The false-negative rate increased from March to May. CONCLUSION: False-negative RT-PCR COVID-19 patients present a similar spectrum of symptoms compared with positive cohort, but more comorbidities. Imaging helps to identify them. True positives had a higher risk of serious complications.

Validation of the Predisposition Infection Response Organ (PIRO) dysfunction score for the prognostic stratification of patients with sepsis in the Emergency Department.

OBJECTIVE: There are many different methods for computing the Predisposition Infection Response Organ (PIRO) dysfunction score. We compared three PIRO methods (PIRO1 (Howell), PIRO2 (Rubulotta) and PIRO3 (Rathour)) for the stratification of mortality and high level of care admission in septic patients arriving at the Emergency Department (ED) of an Italian Hospital. DESIGN, SETTING AND PARTICIPANTS: We prospectively collected clinical data of 470 patients admitted due to infection in the ED to compute PIRO according to three different methods. We tested PIRO variables for the prediction of mortality in the univariate analysis. Calculation and comparison were made of the area under the receiver operating curve (AUC) for the three PIRO methods, SOFA and qSOFA. RESULTS: Most of the variables included in PIRO were related to mortality in the univariate analysis. Increased PIRO scores were related to higher mortality. In relation to mortality, PIRO 1 performed better than PIRO2 at 30 d ((AUC 0.77 (0.716-0.824) vs. AUC 0.699 (0.64-0.758) (p=0.03) and similarly at 60 d (AUC 0.767 (0.715-0.819) vs AUC 0.709 (0.656-0.763)(p=0.55)); PIRO1 performed similarly to PIRO3 (AUC 0.765 (0.71-0.82) at 30 d, AUC 0.754 (0.701-0.806) at 60 d, p=ns). Both PIRO1 and PIRO3 were as good as SOFA referred to mortality (AUC 0.758 (0.699, 0.816) at 30 d vs. AUC 0.738 (0.681, 0.795) at 60 d; p=ns). For high level of care admission, PIRO proved inferior to SOFA. CONCLUSIONS: We support the use of PIRO1, which combines ease of use and the best performance referred to mortality over the short term. PIRO2 proved to be less accurate and more complex to use, suffering from missing microbiological data in the ED setting.

Dietary intake of advanced glycation end products (AGEs) and changes in body weight in European adults.

PURPOSE: Advanced glycation end products (AGEs) can be formed in foods by the reaction of reducing sugars with proteins, and have been shown to induce insulin resistance and obesity in experimental studies. We examined the association between dietary AGEs intake and changes in body weight in adults over an average of 5 years of follow-up. METHODS: A total of 255,170 participants aged 25-70 years were recruited in ten European countries (1992-2000) in the PANACEA study (Physical Activity, Nutrition, Alcohol, Cessation of smoking, Eating out of home in relation to Anthropometry), a sub-cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition). Body weight was measured at recruitment and self-reported between 2 and 11 years later depending on the study center. A reference database for AGEs was used containing UPLC-MS/MS-measured Nε-(carboxymethyl)-lysine (CML), Nε-(1-carboxyethyl)-lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) in 200 common European foods. This reference database was matched to foods and decomposed recipes obtained from country-specific validated dietary questionnaires in EPIC and intake levels of CEL, CML, and MG-H1 were estimated. Associations between dietary AGEs intake and body weight change were estimated separately for each of the three AGEs using multilevel mixed linear regression models with center as random effect and dietary AGEs intake and relevant confounders as fixed effects. RESULTS: A one-SD increment in CEL intake was associated with 0.111 kg (95% CI 0.087-0.135) additional weight gain over 5 years. The corresponding additional weight gain for CML and MG-H1 was 0.065 kg (0.041-0.089) and 0.034 kg (0.012, 0.057), respectively. The top six food groups contributing to AGEs intake, with varying proportions across the AGEs, were cereals/cereal products, meat/processed meat, cakes/biscuits, dairy, sugar and confectionary, and fish/shellfish. CONCLUSION: In this study of European adults, higher intakes of AGEs were associated with marginally greater weight gain over an average of 5 years of follow-up.

The role of plasma microseminoprotein-beta in prostate cancer: an observational nested case-control and Mendelian randomization study in the European prospective investigation into cancer and nutrition.

BACKGROUND: Microseminoprotein-beta (MSP), a protein secreted by the prostate epithelium, may have a protective role in the development of prostate cancer. The only previous prospective study found a 2% reduced prostate cancer risk per unit increase in MSP. This work investigates the association of MSP with prostate cancer risk using observational and Mendelian randomization (MR) methods. PATIENTS AND METHODS: A nested case-control study was conducted with the European Prospective Investigation into Cancer and Nutrition (EPIC) with 1871 cases and 1871 matched controls. Conditional logistic regression analysis was used to investigate the association of pre-diagnostic circulating MSP with risk of incident prostate cancer overall and by tumour subtype. EPIC-derived estimates were combined with published data to calculate an MR estimate using two-sample inverse-variance method. RESULTS: Plasma MSP concentrations were inversely associated with prostate cancer risk after adjusting for total prostate-specific antigen concentration [odds ratio (OR) highest versus lowest fourth of MSP = 0.65, 95% confidence interval (CI) 0.51-0.84, Ptrend = 0.001]. No heterogeneity in this association was observed by tumour stage or histological grade. Plasma MSP concentrations were 66% lower in rs10993994 TT compared with CC homozygotes (per allele difference in MSP: 6.09 ng/ml, 95% CI 5.56-6.61, r2=0.42). MR analyses supported a potentially causal protective association of MSP with prostate cancer risk (OR per 1 ng/ml increase in MSP for MR: 0.96, 95% CI 0.95-0.97 versus EPIC observational: 0.98, 95% CI 0.97-0.99). Limitations include lack of complete tumour subtype information and more complete information on the biological function of MSP. CONCLUSIONS: In this large prospective European study and using MR analyses, men with high circulating MSP concentration have a lower risk of prostate cancer. MSP may play a causally protective role in prostate cancer.

Clinical experience with the etanercept biosimilar SB4 in psoriatic patients.

Background After the expiry of the patent of reference etanercept, several biosimilars have been developed, including SB4. Objective To study safety and efficacy of SB4 in psoriatic patients previously treated with etanercept and in the etanercept naive ones. Method Patients affected by moderate to severe psoriasis and/or psoriatic arthritis attending the Psoriasis Center of Florence University, treated with SB4 were enrolled in the study. Patients were divided in two cohorts. Cohort 1 included 32 patients who were switched from previous etanercept, cohort 2 included 12 patients who were naive to etanercept. Results Evaluation of the efficacy of SB4 in cohort 1 patients revealed rates of clinical remission (defined as both PASI and/or DAS28 increase < 10%) of 92% and 64% for psoriasis and psoriatic arthritis respectively. In cohort 2 at week 24 PASI 75 was observed in 75% of patients. Conclusion In our experience switching from originator to SB4 in psoriatic patients seems not to influence efficacy, especially cutaneous manifestations, over a median observational period of 24 weeks.

Elderly psoriatic patients under biological therapies: an Italian experience.

BACKGROUND: The number of elderly patients with psoriasis is steadily increasing in the Western world; nevertheless, they are frequently excluded from biological clinical trials and described as a high-risk group for adverse events. Thus, there is lack of information concerning safety and effectiveness of available treatments for psoriasis in the elderly, particularly about new biological systemic drugs. OBJECTIVE: Our aim was to describe our experience with all biological therapies currently used in the elderly (>65 years) psoriatic patients. METHODS: A retrospective multicentric review of clinical records of all psoriatic patient aged 65 years or older actually receiving biological drugs (etanercept, adalimumab, infliximab, golimumab, certolizumab pegol, ustekinumab or secukinumab) was undertaken. RESULTS: Our study population included 266 elderly psoriatic patients actually receiving any biological therapy (adalimumab 31.2%, ustekinumab 28.9%, etanercept 20.3%, secukinumab 15%, infliximab 3%, golimumab 1% and certolizumab pegol 0.6%). The PASI score at the baseline (week 0) ranged from 4 to 54; mean ± SD, 16.5 ± 7.1, which changed after biological administration to 3.7 ± 8 at week 16, 1.6 ± 2.1 at week 28 and 1.2 ± 2.1 at week 52. Among 266 elderly psoriatic patients, 25 adverse events were reported during the observation period. The most frequent events were infections with 12 (48%) reports, followed by malignancies with four (16%) reports. CONCLUSIONS: To date, our study represents the widest experience on the use of biological drugs in elderly psoriatic patients. We found that all biologics for psoriasis showed a great efficacy also in elderly people, and the rate and the type of adverse effects were similar to the younger patients. In conclusion, the age alone should not limit our therapeutic options. Further observational study using multiple data sources is needed to evaluate long-term effectiveness and safety for elderly psoriatic patients.

Randomized, placebo-controlled, double-blind trial of clobetasol propionate 0.05% in the treatment of oral lichen planus.

OBJECTIVE: To perform a randomized, placebo-controlled, double-blind study, with a follow-up period of 6 months, for the use of topical clobetasol in cases of symptomatic oral lichen planus (OLP). SUBJECTS AND METHODS: Thirty-two participants were analyzed, with the aims of: (I) to compare the usefulness of topically applied clobetasol propionate 0.05% (mixed with 4% hydroxyethyl cellulose gel) and 4% hydroxyethyl cellulose gel alone (considered as placebo) in the management of OLP; (II) to describe which of them is quicker in decreasing signs and reported symptoms, and (III) which is able to give the proper longer remission in the follow-up. RESULTS: Symptoms improved in all clobetasol-treated patients during the first 2 months of therapy, while only 50% of placebo control group (p = .005) displayed similar results; of the remaining half, 12.5% did experienced a worsening while 37.5% remained stable. Regarding clinical signs, 87.5% of clobetasol-treated patients improved, while only 62.5% of the placebo-treated patients had a positive response (p = .229). CONCLUSIONS: It is possible to report that clobetasol, at this dosage, has been more effective than a placebo at provoking symptoms improvement in subjects affected by atrophic-erosive oral lesions.

Can atrophic-erosive oral lichen planus promote cardiovascular diseases? A population-based study.

OBJECTIVE: Lichen planus has been recently associated with an increased risk of cardiovascular diseases (CVDs). The oral manifestations can be divided into white hyperkeratotic lesions (WL) and atrophic and erosive lesions (RL). The aim of this report was to compare the presence of CVDs between patients affected by WL or RL, to test the hypothesis that RL are associated with an increased incidence of CVDs. SUBJECTS AND METHODS: Patients were analysed through a complete collection of all the risk factors for CVDs. The primary endpoint was the occurrence of a cardiovascular event-acute coronary syndrome (ACS), any revascularization or stroke/TIA. A multivariable logistic regression model, adjusted for age at diagnosis, body mass index, smoking, alcohol consumption, diabetes, hypertension, CVDs familiarity and periodontitis, was performed. RESULTS: A prospective cohort of 307 patients has been evaluated; 185 (60.3%) had WL and 122 RL (39.7%). Twenty-four patients had a CVD. ACS occurred more frequently in RL (adjusted odds ratio 5.83; 95% CI: 1.16-29.39), mainly due to the higher risk of it after the histological diagnosis of Oral lichen planus OLP (odds ratio 4.23; 95% CI: 0.66-27.23). CONCLUSION: Patients with RL could possibly have a higher risk of developing ACS. Further analysis on larger cohort is however warranted.

Dietary glycemic index, glycemic load, and cancer risk: results from the EPIC-Italy study.

Factors linked to glucose metabolism are involved in the etiology of several cancers. High glycemic index (GI) or high glycemic load (GL) diets, which chronically raise postprandial blood glucose, may increase cancer risk by affecting insulin-like growth factor. We prospectively investigated cancer risk and dietary GI/GL in the EPIC-Italy cohort. After a median 14.9 years, 5112 incident cancers and 2460 deaths were identified among 45,148 recruited adults. High GI was associated with increased risk of colon and bladder cancer. High GL was associated with: increased risk of colon cancer; increased risk of diabetes-related cancers; and decreased risk of rectal cancer. High intake of carbohydrate from high GI foods was significantly associated with increased risk of colon and diabetes-related cancers, but decreased risk of stomach cancer; whereas high intake of carbohydrates from low GI foods was associated with reduced colon cancer risk. In a Mediterranean population with high and varied carbohydrate intake, carbohydrates that strongly raise postprandial blood glucose may increase colon and bladder cancer risk, while the quantity of carbohydrate consumed may be involved in diabetes-related cancers. Further studies are needed to confirm the opposing effects of high dietary GL on risks of colon and rectal cancers.

Eating at restaurants, at work or at home. Is there a difference? A study among adults of 11 European countries in the context of the HECTOR* project.

BACKGROUND/OBJECTIVES: To compare macronutrient intakes out of home-by location-to those at home and to investigate differences in total daily intakes between individuals consuming more than half of their daily energy out of home and those eating only at home. SUBJECTS/METHODS: Data collected through 24-h recalls or diaries among 23 766 European adults. Participants were grouped as 'non-substantial', 'intermediate' and 'very substantial out-of-home' eaters based on energy intake out of home. Mean macronutrient intakes were estimated at home and out of home (overall, at restaurants, at work). Study/cohort-specific mean differences in total intakes between the 'very substantial out-of-home' and the 'at-home' eaters were estimated through linear regression and pooled estimates were derived. RESULTS: At restaurants, men consumed 29% of their energy as fat, 15% as protein, 45% as carbohydrates and 11% as alcohol. Among women, fat contributed 33% of energy intake at restaurants, protein 16%, carbohydrates 45% and alcohol 6%. When eating at work, both sexes reported 30% of energy from fat and 55% from carbohydrates. Intakes at home were higher in fat and lower in carbohydrates and alcohol. Total daily intakes of the 'very substantial out-of-home' eaters were generally similar to those of individuals eating only at home, apart from lower carbohydrate and higher alcohol intakes among individuals eating at restaurants. CONCLUSIONS: In a large population of adults from 11 European countries, eating at work was generally similar to eating at home. Alcoholic drinks were the primary contributors of higher daily energy intakes among individuals eating substantially at restaurants.

Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort.

Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1 = 1.26; 95% CI 1.00-1.58; Ptrend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1 = 1.29; 95% CI 1.02-1.62; Ptrend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.