Psoriasis Severity, Health-Related Quality of Life, Work Productivity, and Activity Impairments Among Patients With Moderate to Severe Psoriasis Receiving Systemic Treatment: Real-World Data From Clinical Practice in Spain.

BACKGROUND AND OBJECTIVE: The treatment of psoriasis should not only focus on skin affectations but also weigh the parameters for health-related quality of life (HRQoL), thereby tackling the concept of cumulative life course impairment (CLCI) and treating the patient from a holistic perspective. The CRYSTAL study aimed to characterize psoriasis with real-word data from Spanish clinical practice in patients with moderate to severe disease who received continuous systemic treatment for at least 24 weeks by using the absolute Psoriasis Area and Severity Index (PASI) score and its correlation to HRQoL. MATERIAL AND METHODS: This was a non-interventional, cross-sectional study conducted in 30 centers in Spain, with 301 patients between the ages of 18 and 75 years. The study collected data regarding current treatment and absolute PASI and their relationship to HRQoL using the Dermatology Life Quality Index (DLQI), to activity impairment using the Work Productivity and Activity Impairment (WPAI) questionnaire, and to treatment satisfaction. RESULTS: The mean (SD) age was 50.5 (12.5) years, with a duration of disease of 14 (14.1) years. The mean (SD) absolute PASI reported was 2.3 (3.5), with 28.7% of patients presenting with PASI from >1 to ≤3 and 22.6% with PASI>3. Higher PASI scores were associated with higher DLQI (p<0.001) and WPAI scores and lower levels of treatment satisfaction (p<0.001). CONCLUSIONS: These data indicate that achieving lower absolute PASI values may correlate not only with better HRQoL but also with better work productivity and treatment satisfaction.

Psoriasis Severity, Health-Related Quality of Life, Work Productivity, and Activity Impairments Among Patients With Moderate to Severe Psoriasis Receiving Systemic Treatment: Real-World Data From Clinical Practice in Spain. / [Artículo traducido] Gravedad de la psoriasis, calidad de vida relacionada con la salud, productividad laboral y deterioro de la actividad en pacientes con psoriasis moderada a grave que reciben tratamiento sistémico: datos de la vida real de la práctica clínica en España.

BACKGROUND AND OBJECTIVE: The treatment of psoriasis should not only focus on skin affectations but also weigh the parameters for health-related quality of life (HRQoL), thereby tackling the concept of cumulative life course impairment (CLCI) and treating the patient from a holistic perspective. The CRYSTAL study aimed to characterize psoriasis with real-word data from Spanish clinical practice in patients with moderate to severe disease who received continuous systemic treatment for at least 24 weeks by using the absolute Psoriasis Area and Severity Index (PASI) score and its correlation to HRQoL. MATERIAL AND METHODS: This was a non-interventional, cross-sectional study conducted in 30 centers in Spain, with 301 patients between the ages of 18 and 75 years. The study collected data regarding current treatment and absolute PASI and their relationship to HRQoL using the Dermatology Life Quality Index (DLQI), to activity impairment using the Work Productivity and Activity Impairment (WPAI) questionnaire, and to treatment satisfaction. RESULTS: The mean (SD) age was 50.5 (12.5) years, with a duration of disease of 14 (14.1) years. The mean (SD) absolute PASI reported was 2.3 (3.5), with 28.7% of patients presenting with PASI from >1 to ≤3 and 22.6% with PASI>3. Higher PASI scores were associated with higher DLQI (p<0.001) and WPAI scores and lower levels of treatment satisfaction (p<0.001). CONCLUSIONS: These data indicate that achieving lower absolute PASI values may correlate not only with better HRQoL but also with better work productivity and treatment satisfaction.

Delayed immune-related adverse events with anti-PD-1-based immunotherapy in melanoma.

BACKGROUND: Immune-related adverse events (irAEs) typically occur within 4 months of starting anti-programmed cell death protein 1 (PD-1)-based therapy [anti-PD-1 ± anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4)], but delayed irAEs (onset >12 months after commencement) can also occur. This study describes the incidence, nature and management of delayed irAEs in patients receiving anti-PD-1-based immunotherapy. PATIENTS AND METHODS: Patients with delayed irAEs from 20 centres were studied. The incidence of delayed irAEs was estimated as a proportion of melanoma patients treated with anti-PD-1-based therapy and surviving >1 year. Onset, clinical features, management and outcomes of irAEs were examined. RESULTS: One hundred and eighteen patients developed a total of 140 delayed irAEs (20 after initial combination with anti-CTLA4), with an estimated incidence of 5.3% (95% confidence interval 4.0-6.9, 53/999 patients at sites with available data). The median onset of delayed irAE was 16 months (range 12-53 months). Eighty-seven patients (74%) were on anti-PD-1 at irAE onset, 15 patients (12%) were <3 months from the last dose and 16 patients (14%) were >3 months from the last dose of anti-PD-1. The most common delayed irAEs were colitis, rash and pneumonitis; 55 of all irAEs (39%) were ≥grade 3. Steroids were required in 80 patients (68%), as well as an additional immunosuppressive agent in 27 patients (23%). There were two irAE-related deaths: encephalitis with onset during anti-PD-1 and a multiple-organ irAE with onset 11 months after ceasing anti-PD-1. Early irAEs (<12 months) had also occurred in 69 patients (58%), affecting a different organ from the delayed irAE in 59 patients (86%). CONCLUSIONS: Delayed irAEs occur in a small but relevant subset of patients. Delayed irAEs are often different from previous irAEs, may be high grade and can lead to death. They mostly occur in patients still receiving anti-PD-1. The risk of delayed irAE should be considered when deciding the duration of treatment in responding patients. However, patients who stop treatment may also rarely develop delayed irAE.

Peripheral microcirculatory alterations are associated with the severity of acute respiratory distress syndrome in COVID-19 patients admitted to intermediate respiratory and intensive care units.

BACKGROUND: COVID-19 is primarily a respiratory disease; however, there is also evidence that it causes endothelial damage in the microvasculature of several organs. The aim of the present study is to characterize in vivo the microvascular reactivity in peripheral skeletal muscle of severe COVID-19 patients. METHODS: This is a prospective observational study carried out in Spain, Mexico and Brazil. Healthy subjects and severe COVID-19 patients admitted to the intermediate respiratory (IRCU) and intensive care units (ICU) due to hypoxemia were studied. Local tissue/blood oxygen saturation (StO2) and local hemoglobin concentration (THC) were non-invasively measured on the forearm by near-infrared spectroscopy (NIRS). A vascular occlusion test (VOT), a three-minute induced ischemia, was performed in order to obtain dynamic StO2 parameters: deoxygenation rate (DeO2), reoxygenation rate (ReO2), and hyperemic response (HAUC). In COVID-19 patients, the severity of ARDS was evaluated by the ratio between peripheral arterial oxygen saturation (SpO2) and the fraction of inspired oxygen (FiO2) (SF ratio). RESULTS: Healthy controls (32) and COVID-19 patients (73) were studied. Baseline StO2 and THC did not differ between the two groups. Dynamic VOT-derived parameters were significantly impaired in COVID-19 patients showing lower metabolic rate (DeO2) and diminished endothelial reactivity. At enrollment, most COVID-19 patients were receiving invasive mechanical ventilation (MV) (53%) or high-flow nasal cannula support (32%). Patients on MV were also receiving sedative agents (100%) and vasopressors (29%). Baseline StO2 and DeO2 negatively correlated with SF ratio, while ReO2 showed a positive correlation with SF ratio. There were significant differences in baseline StO2 and ReO2 among the different ARDS groups according to SF ratio, but not among different respiratory support therapies. CONCLUSION: Patients with severe COVID-19 show systemic microcirculatory alterations suggestive of endothelial dysfunction, and these alterations are associated with the severity of ARDS. Further evaluation is needed to determine whether these observations have prognostic implications. These results represent interim findings of the ongoing HEMOCOVID-19 trial. Trial registration ClinicalTrials.gov NCT04689477 . Retrospectively registered 30 December 2020.

Spanish Society of Allergology and Clinical Immunology (SEAIC) Vision of Drug Provocation Tests.

The controlled drug provocation test (DPT) is currently considered the gold standard for the diagnosis of drug allergy. Adverse drug reactions (ADRs) are an increasingly common presenting complaint in both primary and specialized care. In Spain, ADRs are usually assessed via the allergology department, which rules out immunological mechanisms in up to 90% of cases. An adequate approach to ADRs clearly impacts the costs and efficacy of the treatments prescribed by other specialists. Consequently, if we did not use DPTs, patients would require more expensive, more toxic, and less effective treatments in many cases. In recent years, many new drugs have been developed. This document is intended to be a practical guideline for the management of DPTs according to the vision of the Spanish Allergology Society. The diagnostic work-up begins with a detailed clinical history. Skin tests are only useful for some medications, and in most cases the diagnosis can only be confirmed by DPT. Although cross-reactivity is common, DPTs can confirm the diagnosis and help to find an alternative drug. Programmed individualized patient management based on the type of drug to be studied and the patient´s comorbidities usually enables a solution to be found in most cases.

A real world analysis of recurrence risk factors for early colorectal cancer T1 treated with standard endoscopic resection.

BACKGROUND AND STUDY AIM: Currently, endoscopic resection of early colorectal cancer defined as carcinoma with limited invasion of the mucosa (Tis) and submucosa (T1) is possible. However, lymph node spreading increases to 16.2% of cases when tumor invades the submucosa. We analyzed the previously identified factors for lymph node dissemination and recurrence, in our population. PATIENTS AND METHODS: We analyzed retrospectively all patients with T1 tumors, treated at our center with endoscopic resection and some with additional surgery between January 2006 and January 2018. Statistical analysis was performed using IBM SPSS Statistics 25.0. RESULTS: One hundred fifty-nine patients were treated with endoscopic resection, 56.6% with additional surgery. The mean age was 68.74 years and 69. 9% were male. All patients who underwent additional surgery presented negative margins and 8.8% presented positive lymph nodes. In a mean follow-up of 23.36 months, 13 patients had relapsed. The risk of relapse did not differ between patients treated with additional surgery from those who only underwent endoscopic resection (p = 0.506). On the other hand, lymph node dissemination (p = 0.007) and a positive endoscopic margin (p = 0.01) were independent risk factors for relapse. There was a positive association between lymph node dissemination and lymphatic (p = 0.07), vascular (p = 0.007), and perineural (p = 0.001) invasion and also with degree of histological differentiation (p = 0.001). CONCLUSION: In our study, lymphatic, vascular, and perineural invasion and also the degree of histological differentiation were associated with lymph node dissemination. However, the only independent risk factors for long-term recurrence were a positive margin and lymph node dissemination.

Sharing the sidewalk: A case of E-scooter related pedestrian injury.

The popularity of rideshare electric scooters is due to their availability, accessibility, and low cost. The recent increase in electric scooter use has raised concerns regarding the safety of both riders and pedestrians. Previous studies characterize the incidence and pattern of injury for riders, but there is a lack of literature concerning electric scooters' impact on pedestrians. Pedestrians injured by electric scooters face potential financial burdens from hospitalization costs, medical interventions, taking time off from work, and rehabilitation therapies. Based on prior studies, pedestrians who are most prone to injuries sustained by pedestrian transportation include individuals with vision and/or hearing impairment, young children, the elderly, and people distracted by mobile devices. We present a case involving a sixty-year-old female pedestrian who presented to the emergency department with an acute lumbar compression fracture after a collision with an electric scooter. This study highlights the safety risks and incidence of injuries for pedestrians associated with electric scooters, which can help shape public policy to ensure the safety of both riders and pedestrians.

Correction to: Persistent major alopecia following adjuvant docetaxel for breast cancer: incidence, characteristics, and prevention with scalp cooling.

In the original publication of the article, Table 1 was published with incorrect caption and values. The Table 1 with corrected caption and values is given in this Correction.

Persistent major alopecia following adjuvant docetaxel for breast cancer: incidence, characteristics, and prevention with scalp cooling.

BACKGROUND: Persistent alopecia (PA) after docetaxel has been recently described. The aim of our study is to establish the incidence and characteristics of PA following adjuvant docetaxel for breast cancer (BC) and to test the ability of scalp cooling in prevention. PATIENTS AND METHODS: BC patients receiving adjuvant chemotherapy followed or not by endocrine therapy (and a control group receiving only endocrine therapy) were interviewed in a single institution at 1.5 to 5 years following primary diagnosis searching for PA. A confirmatory prevalence study was later performed in other two institutions. Finally, a prevention study using prophylactic scalp cooling (PSC) with ELASTO-GEL hypothermia caps in patients receiving adjuvant docetaxel was performed. RESULTS: In the initial prevalence study (492 patients), minor forms of PA (grade 1) were recorded with all chemotherapy regimens and aromatase inhibitors. Patients receiving docetaxel regimens at cumulative dose (CD) ≥ 400 mmg/m2 presented a significantly higher prevalence of grades 1 PA (33-52%) and 2 PA (5-12%). Prevalence of grade 2 PA with docetaxel CD ≥ 400 mmg/m2 was confirmed in two other institutions. Overall, grade 2 PA was seen in 10.06% (95% CI 7.36-13.61) of 358 patients with docetaxel regimens reaching CD ≥ 400 mmg/m2, but not in patients with lower docetaxel CD, other chemotherapy regimens, or endocrine therapy alone. In prevention trial, no grade 2 PA occurred among 116 patients receiving adjuvant docetaxel (≥ 400 mmg/m2) and PSC followed-up after a 96 months median time. PSC was well tolerated. No scalp relapses were seen among 30 patients (22% of all inclusions) having disease relapse. CONCLUSION: Adjuvant treatment with docetaxel (CD ≥ 400 mmg/m2) is associated with a significant rate of grade 2 PA, leading to wearing a wig, in around 10% of patients. This toxicity was completely prevented with scalp cooling. Clinical Trial Reference: NCT00515762.

Inhibitor development after switching of FVIII concentrate in multitransfused patients with severe haemophilia A.

Switching between different therapeutic FVIII concentrate types has been postulated as a possible cause of inhibitor development in patient with haemophilia A. In this single-centre, retrospective study, the incidence, titre and duration of inhibitor development in multitransfused patients, defined as patients with more than 150 exposure days (ED), were analysed from January 1970 to December 2007 in relation to ED and the number of switches between different products. Inhibitor titre was assessed by Bethesda assay (before 1998) or Nijmegen assay (after 1998). Medical records of 167 patients were screened, of which 97 patients met the inclusion criteria. Fourteen products of plasmatic origin (different purities) and five recombinant (three generations) were used. Nine patients (9%) developed inhibitors, all transient, low-titre (1.41 ± 0.54 BU) after 323 ± 287 ED in average. Seventeen patients had no product switches of which four patients (23%) developed inhibitors (97 ED in average), whereas 13 patients (77%) did not (ED: 230). Fifty patients switched between plasmatic products only (median: 10 changes) of which five patients (10%) developed inhibitors (ED: 503), whereas 45 patients did not (ED: 932). Five patients switched between recombinant products only (seven changes) of which no patient developed inhibitors (748 ED). Twenty-five patients switched between plasmatic and recombinant products (13 changes) of which no patient developed inhibitors (ED: 1654). No statistically significant differences between patient groups were observed. Neither the number of different FVIII products administered nor the switching of products influenced the incidence of inhibitor in multitransfused patients.

Assessment of the thrombin generation assay in haemophilia: comparative study between fresh and frozen platelet-rich plasma.

The severity of haemophilia A has traditionally been classified by the dosage of factor VIII (FVIII) by one-step coagulation tests. However, an homogeneous group of patients with similar FVIII levels show clinical heterogeneity and 10-15% of the patients classified as severe haemophilia do not have a severe bleeding phenotype. Traditional tests used for measuring FVIII are not capable of detecting other prohaemorrhagic or prothrombotic factors. Global tests as the thrombin generation assay (TGA) may detect these haemostatic factors. So TGA may be an additional tool for classifying the actual severity of haemophilia. Our group is carrying out correlation tests between FVIII and TGA in platelet-poor and -rich plasmas (PPP and PRP, respectively). PRP has the inconvenience that must be done freshly soon after blood extraction. Our aim is to study the differences between TGA performed with fresh and frozen PRP and PPP and its implementation in multicenter studies. We included 70 patients with severe haemophilia A in prophylactic treatment. Venous blood drawing was obtained prior to administration of FVIII, at the trough levels. FVIII measurement and TGA were performed in fresh and frozen PRP and PPP. The platelet absence caused a significant decrease in TGA although PPP and PRP correlated well. Frozen samples gave different results in PPP, but there were no significant differences between fresh and frozen PRP. This fact enables using frozen PRP in multicenter studies with a TGA-specialized laboratory for reclassifying haemophilia severity and for pharmacokinetic studies with TGA.

Spasticity in multiple sclerosis: results of a patient survey.

Information regarding the epidemiology of spasticity in patients with multiple sclerosis (MS) in Spain is limited. This cross-sectional survey-based study was undertaken to evaluate the symptoms, severity and consequences of MS-related spasticity (MSS) and to estimate the prevalence of MSS overall and according to the degree of severity (mild/moderate/severe). Adult MS patients (n = 8463) from the two main Spanish MS patients' associations were asked to complete a web-based questionnaire. Two thousand six hundred twenty seven responses were received, of which 2029 were valid for analysis. Two thirds were for women. The mean age of respondents was 40.2 years and the mean MS duration was 8.7 years. MSS was reported by 65.7% of respondents with 40% of these rating it as moderate/severe. MS patients with spasticity experienced more symptoms (including greater difficulty walking), consumed more healthcare resources (including care and rehabilitation sessions), and had a higher degree of disability than patients without spasticity. There was a significant correlation between increasing severity of spasticity and worsening of symptoms. Only 42.4% of patients with moderate spasticity and 52.6% of patients with severe spasticity were currently receiving antispasticity medication compared with 69% and 79%, respectively, reported in a similar survey-based study from the United States; this is likely to reflect regional variations in practice. Early and effective treatment of MSS is important to minimise the consequences of spasticity-related symptoms on patients' quality of life and the economic burden on healthcare systems. In appropriate patients, antispastic treatment, including pharmacotherapy and physiotherapy/rehabilitation, may provide such benefits.

Exploratory analysis of clinical benefit of ipilimumab and nivolumab treatment in patients with metastatic melanoma from a single institution.

PURPOSE: We retrospectively analysed overall survival (OS) and potential predictive biomarkers of OS in patients with metastatic melanoma treated with ipilimumab plus nivolumab in a single institution. METHODS AND PATIENTS: Electronic medical records of patients with advanced melanoma receiving ≥ 1 dose of a combined ipilimumab plus nivolumab regimen between March 3, 2016 and March 7, 2020 in a single institution, were reviewed. OS was analysed using the Kaplan-Meier method. Sub-group analyses were conducted to examine several endpoints according to relevant clinical, molecular and pathological variables using logistic and Cox models. RESULTS: Forty-four cases were reviewed, 38 (86.4%), of whom had cutaneous melanoma, 21 (47.7%) were BRAF mutant, 21 (47.7%) presented high lactate dehydrogenase (LDH) values, 23 (52.3%) had ≥ 3 disease sites, and 10 (22.7%) patients had brain metastases. The median follow-up was 37.7 months, and the median OS was 21.1 months (95% CI 8.2-NR). In the multivariate analysis, the OS was significantly longer in patients with an Eastern Cooperative Oncology Group (ECOG) score of 0, LDH ≤ upper limit of normal, absence of liver metastases and neutrophil-to-lymphocyte ratio (NLR) < 5 (all p ≤ 0.05, log-rank test). These factors allowed the classification of patients into three prognostic risk groups (low/intermediate/high risk) for death. CONCLUSION: Overall survival of real-world patients from our cohort receiving ipilimumab plus nivolumab was lower than in previous studies. The ECOG score, LDH values, the presence of liver metastases and the NLR were independent prognostic factors for survival.

Real-world outcomes with ipilimumab and nivolumab in advanced melanoma: a multicentre retrospective study.

PURPOSE: To assess efficacy and toxicity of combination immunotherapy with ipilimumab plus nivolumab in routine practice in a retrospective multicentre cohort of patients with advanced melanoma. PATIENTS AND METHODS: This retrospective analysis included patients with advanced melanoma treated with ipilimumab and nivolumab between October 2015 and January 2020 at six centres in Australia, Europe and the United States of America. We describe efficacy outcomes (overall survival [OS], progression-free survival [PFS] and objective response rate [ORR]) in treatment-naïve and pre-treated patients, with and without brain metastases, plus treatment-related adverse events (trAEs) in all patients treated. RESULTS: A total of 697 patients were identified; 472 were treatment-naïve of which 138 (29.2%) had brain metastases, and 225 were previously treated of which 102 (45.3%) had brain metastases. At baseline, 32.3% had stage M1c and 34.4% stage M1d disease. Lactate dehydrogenase was high in 280 patients (40.2%). With a median follow-up of 25.9 months, median OS in the 334 treatment-naïve patients without brain metastases was 53.7 months (95% confidence interval [CI] 40.8-NR) and 38.7 months (95% CI 18.6-NR) for the 138 treatment-naïve patients with brain metastases. For the entire cohort the ORR was 48%, for treatment-naïve patients without brain metastases ORR was 56.6% with a median PFS of was 13.7 months (95% CI 9.6-26.5). Median PFS was 7.9 months (95% CI 5.8-10.4) and OS 38 months (95% CI 31-NR) for the entire cohort. Grade 3-4 trAE were reported in 44% of patients, and 4 (0.7%) treatment-related deaths (1 pneumonitis, 2 myocarditis and 1 colitis) were recorded. CONCLUSION: The outcome and toxicity of combination immunotherapy with ipilimumab and nivolumab in a real-world patient population are similar to those reported in pivotal trials.

Correlates of species richness in the largest Neotropical amphibian radiation.

Although tropical environments are often considered biodiversity hotspots, it is precisely in such environments where least is known about the factors that drive species richness. Here, we use phylogenetic comparative analyses to study correlates of species richness for the largest Neotropical amphibian radiation: New World direct-developing frogs. Clade-age and species richness were nonsignificantly, negatively correlated, suggesting that clade age alone does not explain among-clade variation in species richness. A combination of ecological and morphological traits explained 65% of the variance in species richness. A more vascularized ventral skin, the ability to colonize high-altitude ranges, encompassing a large variety of vegetation types, correlated significantly with species richness, whereas larger body size was marginally correlated with species richness. Hence, whereas high-altitude ranges play a role in shaping clade diversity in the Neotropics, intrinsic factors, such as skin structures and possibly body size, might ultimately determine which clades are more speciose than others.

The impact of allodynia on the efficacy of almotriptan when given early in migraine: data from the "Act when mild" study.

The objective of this study was to evaluate the impact of allodynia on treatment outcomes in the patients with acute migraine treated in the "Act when Mild" (AwM) study. AwM, a randomized placebo-controlled trial, studied almotriptan 12.5 mg in the early treatment (within 1 hr) of acute migraine when the pain was still mild, and investigated clinical outcomes in the presence or absence of allodynia, which was prospectively recorded using patient questionnaires. Of the total population, 39% (n = 404) reported allodynia that did not alter the efficacy of almotriptan administered for early/mild pain in terms of 2-hr pain-free rates (53.9% for allodynic patients vs. 52.5% for nonallodynic patients). Similarly, sustained pain-free rates were 47.2% versus 45.5%, and migraine duration 1.40 versus 1.54 hr, respectively. However, allodynia impaired the effectiveness of almotriptan in the patients with moderate/severe pain in terms of longer migraine duration, fewer patients achieving pain-free status, and more requiring rescue medication. In conclusion, the lack of effect of allodynia on the efficacy of almotriptan given for early/mild migraine pain might help explain the improved outcomes associated with the early-treatment strategy in AwM. Moreover, the data suggest that pain intensity is the main driver of triptan response, and not the presence or absence of allodynia.

Organosolv processing of vine shoots: Fractionation and conversion of hemicellulosic sugars into platform chemicals by microwave irradiation.

Vine shoots were subjected to a mild aqueous extraction (to remove water-soluble extractives), and the extracted solids were reacted in catalyzed media (containing water and 1-butanol) to achieve the one-stage solubilization of lignin and hemicelluloses, yielding a cellulose-rich solid. Operating in a microwave-heated reactor under optimized conditions (190 °C in media containing 2% of catalyst and 52% 1-butanol), 67.8% lignin was dissolved, and solids containing 75% cellulose were obtained. Lignin was recovered from the reaction medium and characterized, whereas the hemicellulose-derived products present in the aqueous phase (obtained under conditions leading to maximum concentrations of 17.7 g pentoses/L) were converted into furfural at 64.6% molar yield by acidic processing in the presence of recycled 1-butanol.