Dose reduction is a feasible strategy in patients with plaque psoriasis who achieve sustained response with secukinumab: a retrospective, multicenter cohort study in daily practice setting.

BACKGROUND: Biological therapy dose modification is a common practice in the long-term treatment of plaque psoriasis. OBJECTIVE: The objective of the study was to determine prevalence, characteristics of patients, effectiveness, treatment survival of secukinumab dose reduction (SEC-DR) strategy and assess its safety and cost implications. METHODS: A retrospective, observational, multicenter cohort study was conducted in patients with plaque psoriasis treated with secukinumab and up to 2 years of follow-up. RESULTS: In 63/347 patients with an initial standard dose regimen, SEC-DR was tried at any moment in 18.2% of them after sustained response. In 51 patients, the interval between administrations was increased while in 12 patients, monthly dose was reduced to 150 mg. Successful SEC-DR was achieved in 77.8% of the patients, with sustained PASI response to the end of the study. Survival of secukinumab treatment and safety profile were not compromised by DR. The use of DR saved 33% of the cost, including failures in which standard treatment was resumed. LIMITATIONS: The proper of the study designed and the arbitrary definition of "DR success." CONCLUSION: Off-label SEC-DR strategy was used in patients with sustained response to standard dose regimen; this strategy showed long-term efficacy without compromising treatment survival or worsening the safety profile while also being cost saving.

Artificial intelligence in medicine - dermatology compared to other medical specialties in FDA-cleared software as medical device.

Artificial intelligence (AI) and machine learning (ML) have occupied the center stage in healthcare as research groups and institutions investigate their capabilities and risks. Dermatology is often cited as one of the medical specialties most ripe for disruption with AI technology due to the heavy incorporation of visual information into clinical decisions and treatments. Although the literature on AI in dermatology is rapidly growing, there has been a noticeable absence of mature AI solutions utilized by dermatology departments or patients. This commentary provides insight into the regulatory challenges facing AI solutions for the specialty of dermatology and the unique considerations that should be factored into AI development and deployment.

Características de las intervenciones en cirugía cardiaca en un hospital general de Lima, Perú

Objetivos: Describir las características epidemiológicas, clínicas y quirúrgicas de las intervenciones en cirugía cardiaca en un hospital general de Lima - Perú. Material y métodos: Estudio observacional, descriptivo y retrospectivo. La población estudiada fue de pacientes operados de cirugía cardiaca electivamente entre 2009 y 2019 en el Hospital María Auxiliadora. Se incluyeron 41 pacientes. Resultados: La mediana de edad fue 44 (rango intercuartílico: 26,5 - 58,5) años y el sexo femenino fue 75,6%. Los principales antecedentes patológicos fueron: arritmia cardiaca (56,1%), hipertensión arterial (36,6%), accidente cerebrovascular (24,4%) y diabetes mellitus tipo 2 (14,6%). La cirugía realizada con más frecuencia fue el reemplazo valvular con válvula protésica (39%), principalmente de la válvula mitral; en segundo lugar, cirugías correctivas de defecto de tabique (26,8%), principalmente comunicación interauricular. Las complicaciones postoperatorias más frecuentes fueron: neumonía intrahospitalaria (14%), arritmia cardiaca nueva (14%) y síndrome de bajo gasto cardiaco (12%). Las medias de los tiempos de circulación extracorpórea y tiempo de pinzamiento aórtico fueron de 97,5 ± 39,0 min y 68,1 ± 35,5 min, respectivamente. La media de la estancia en unidad de cuidados intensivos fue 4,1 ± 2,9 días y la media de la estancia hospitalaria fue 22,3 ± 10,9 días. No hubo mortalidad hasta 30 días del postoperatorio. Conclusiones: Los pacientes intervenidos fueron principalmente adultos jóvenes y a predominio del sexo femenino, con comorbilidades cardiovasculares importantes. La principal cirugía realizada fue el reemplazo de válvula cardiaca y las demás características clínico-quirúrgicas fueron similares a lo reportado en Latinoamérica.

SUMMARY Objective: To describe the clinical, epidemiological, and surgical characteristics of cardiac interventions in a general hospital in Lima, Peru. Methods : a retrospective and descriptive study was carried-out at Hospital Maria Auxiliadora from 2009-2019, 41 patients were included. Results: Median age was 44 years (IQR: 26.5-58.5); 75.6% were females. Underlying conditions were arrhythmias (56.1%); blood hypertension (36.6%); strokes (24.4%) and diabetes (14.6%). Valve replacement using prosthetic valves was the most frequent procedure (39%), mainly mitral valve replacement; followed by surgical repairs of septum abnormalities, mainly atrial defects (26.8%). The most common post-operative complications were nosocomial pneumonia (14%), new arrhythmia (14%) and low output syndrome (12%). Mean times of extracorporeal circulation and aortic clamping were 97.5 ± 39.0 min and 68.1 ± 35.5 min, respectively. Mean ICU and hospital stays were 4.1 ± 2.9 and 22.3 ± 10.9 days, respectively. No fatalities were recorded 30-days after the procedures. Conclusions: Young, predominantly female adults with significant comorbidities were surgically intervened in this setting. The main surgical procedure was valve replacement, no differences with reports from Latin America were found.

Secukinumab is effective and safe in the long-term treatment of plaque psoriasis in a daily practice setting: Multicenter study in 384 Spanish patients.

The aim of the study was to assess the long-term effectiveness and safety of secukinumab in Spanish patients with moderate-to-severe psoriasis in a daily practice setting. Nationwide multicenter, observational, retrospective, non-interventional, single-cohort study including patients who initiated treatment with secukinumab in daily clinical practice conditions. Subjects were followed for a minimum of 3 months and a maximum of 24 months. Psoriasis Area Severity Index (PASI), Body Surface Area and Physician's Global Assessments were collected at baseline and months 3, 6, 12, 18 and 24 during treatment. Adverse events and reasons for secukinumab withdrawal were collected and classified for analyses. A total of 384 patients were enrolled in the study. Median PASI declined rapidly from 14.3 at baseline to 2.7 at month 3, 2.1 at month 12, and remained low (2.8) at month 24. Within the group of patients with PASI ≥10 at baseline (n = 278), 58.3%, 60.4% and 56.5% achieved a PASI90 response at months 3, 12 and 24, respectively. As for absolute PASI, 86.5%, 69.5%, 42.7% and 37% achieved PASI <5, < 3, < 1 and 0, respectively, at month 3. Secukinumab was more effective in biologic-naïve patients and in those with lower Body Mass Index. Secukinumab presented a good long-term safety profile. Secukinumab was effective and safe in a routine clinical setting, in a large cohort of patients with moderate-to-severe plaque psoriasis, in the short-, medium- and long-term (up to 24 months).

Guselkumab effectiveness and survival in patients with psoriasis and psoriatic arthritis: Multicenter analysis in daily clinical practice by the Spanish Psoriasis Group.

Guselkumab is a monoclonal antibody that selectively blocks the p19 subunit of interleukin 23 and has been approved for the treatment of moderate to severe psoriasis and active psoriatic arthritis in adult patients due to its efficacy in different clinical trials. Therefore, itis important to know the performance of guselkumab in this setting of patients in clinical practice given that a high percentage of them are not represented in these clinical trials. Our objective was to evaluate the effectiveness and tolerability of guselkumab in clinical practice in the first patients with psoriasis and psoriatic arthritis treated since the date of its approval for psoriasis in Spain, in joint dermatology-rheumatology clinics. A multicenter retrospective data collection was carried out, in which 14 hospitals participated, including a total of 90 patients with psoriatic arthritis confirmed by a rheumatologist. Data collection was recorded at baseline and at weeks 12, 24, and 52 for both the articular and cutaneous domains. Ninety PsA patients started treatment with guselkumab and therefore were included in this study. The vast majority had already failed to at least to one biologic therapyprior guselkumab prescription. The median age was 55 years, 61% were female and 46% had a BMI ≥ 30 kg/m2 . Sixty-nine percent suffered from peripheral arthritis, and in 34% an axial involvement was also detected; dactylitis or enthesitis was present in 24% and 29% of patients, respectively. Guselkumab was effective in controlling both articular and skin manifestations of PsA patients. Absolute PASI significantly decreased from 10.5 to 4.8, 1.9 and 1.3 at weeks 12, 24, and 52, respectively. In 29 out of 61 (48%) of cases, DAPSA was moderate or high, and patients showed a significant reduction in DAPSA at 12, 24, and 52 weeks of treatment (mean DAPSA values at baseline and follow up were 29, 20, 16, and 14, respectively). Patients with DAPSA in low activity or in remission at the time of initiation of guselkumab maintained response at the end of the study period. No new safety concerns were detected. Seventy-eight out of 90 patients (84.4%) persisted on treatment after 2 years follow-up. Our experience suggests that guselkumab isan effective drug for PsA and PsO patients in clinical practice with good tolerability and no additional safety signals, making it a new therapeutic alternative for the treatment of PsA and PsO patients.

Response of soil and vegetation in a warm-temperate Pine forest to intensive biomass harvests, phosphorus fertilisation, and wood ash application.

The objective of this study was to assess the effects of different intensities of biomass harvesting, and the possible effects of compensation methods, on forest functioning. To do so, we carried out a split-plot experiment (SW France) crossing four different intensities of biomass harvesting (Stem-Only Harvest [SOH], Aboveground Additional Harvest [AAH], Belowground Additional Harvest [BAH], and Whole-Tree Harvest [WTH]) and three compensation methods (control [C], wood ash application [A] and phosphorus fertilisation [P]). The experimental treatments were followed by the plantation of pines (Pinus pinaster). The environmental consequences of treatments on soil and vegetation were evaluated 11 years after the tree plantation. Despite their low additional biomass exports (+10 % for AAH to +34 % for WTH), the non-conventional harvest practices exported much higher quantities of nutrients than the conventional SOH technique (+145 % of exported N in WTH). Additional biomass harvests impacted the soil organic matter content, with negative effects on P-organic, soil cation exchange capacity, exchangeable Ca, and most extractible nutrients. However, tree nutritional status was improved by P-fertiliser or wood ash. We observed a positive effect of wood ash application on soil pH and nutrient content but, like additional harvests, wood ash application decreased the pool of soil organic carbon (~10 %). Overall, the experiment showed that exporting more forest biomass due to the additional harvesting of biomass had negative consequences on the ecosystem biogeochemistry. Additional harvests have impoverished the soil, and decreased the soil organic carbon content. Importantly, applying nutrients as fertiliser or wood ash did not compensate for all the negative impacts of biomass exports and the method of wood ash recycling in forests could even decrease the soil organic carbon.

Fast and sustained improvement of patient-reported outcomes in psoriatic patients treated with secukinumab in a daily practice setting.

Psoriasis is a chronic dermatological disease with great impact on patients' quality of life (QoL). The main objective of this study was to assess the impact of secukinumab treatment on different patient-reported outcomes (PROs) during a long-term follow-up in Spanish patients with moderate-to-severe psoriasis under real-world conditions. Retrospective, observational, open-label, nationwide multicenter cohort study that included patients who initiated treatment with secukinumab in daily clinical practice conditions. PROs assessing disease impact and QoL included Dermatology Life Quality Index (DLQI), Patient's Global Psoriasis Assessment, Itch Numerical Rating Scale and EuroQoL Thermometer Visual Analogue Scale. Outcomes, including PROs and Psoriasis Area and Severity Index (PASI), were assessed at months 3, 6, 12, 18, and 24 during treatment. A total of 238 patients were enrolled in the study. Patients had a mean DLQI score of 14.9 at baseline; 78.3%, 73.7%, and 71.7% of them achieved a DLQI 0/1 response at months 6, 12, and 24, respectively. DLQI score was lower in the long term for naïve patients. A sharp decrease in mean DLQI was observed during the first 3 months, reaching a plateau that was maintained until the end of follow-up. Similar findings were observed for the rest of QoL assessments. There was a close association between improvement in QoL and skin clearance (PASI), which progressively increased during follow-up. In this study, secukinumab sustainably improved patient's QoL during a 24-month follow-up, with strongest effects in patients naïve to biological therapies and with a direct correlation with PASI improvement.

Synthesis and SAR of novel GPR39 agonists and positive allosteric modulators.

We report a significant decrease in transcription of the G protein-coupled receptor GPR39 in striatal neurons of Parkinson's disease patients compared to healthy controls, suggesting that a positive modulator of GPR39 may beneficially impact neuroprotection. To test this notion, we developed various structurally diverse tool molecules. While we elaborated on previously reported starting points, we also performed an in silico screen which led to completely novel pharmacophores. In vitro studies indicated that GPR39 agonism does not have a profound effect on neuroprotection.

Misplacement of the PEG tube through the transverse colon, an uncommon but possible complication.

Misplacement of the Percutaneous Endoscopic Gastrostomy (PEG) tube through the transverse colon mainly by traction is an uncommon complication probably due to inadvertent puncture of colon during PEG placement, resulting in gastrocolocutaneous fistula. Stool drainage through the stoma is usually the only symptom. We report a 52-year-old male with Wernicke-Korsakoff syndrome and PEG tube placement 7 months earlier and replacement one month ago. Due to stool drainage through the stoma was observed, he was performed a computed tomography (CT) in which PEG tube was visualized lodged in transverse colon without pneumoperitoneum associated. Due to important morbility, endoscopic management was decided. Balloon was removed through cutaneous orifice and Ovesco clip was placed simultaneously, achieving a complete closure of wall defect. Although spontaneous closure of the fistula usually happens, surgery is sometimes required, with endoscopic treatment being a less invasive and effective alternative to solve this complication.

Effectiveness and safety of guselkumab for the treatment of psoriasis in real-world settings at 24 weeks: A retrospective, observational, multicentre study by the Spanish Psoriasis Group.

Data on the effectiveness and safety of a drug in real-world clinical practice complement the evidence from clinical trials, which are carried out in a different setting. Little has been published on the effectiveness and safety of guselkumab in the treatment of psoriasis in clinical practice. The ojective of this study was to assess the effectiveness and safety of guselkumab at 24 weeks in patients with moderate to severe plaque psoriasis in routine clinical practice. A retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis treated with guselkumab for at least 24 weeks was carried out in Spain. We studied 343 patients, 249 of whom were followed for 24 weeks. By week 24, the mean (SD) psoriasis area severity index (PASI) had decreased from 11.1 (7.3) to 1.7 (2.8) (-9.3; [-10.2;-8.4]), 85.9% of the patients had achieved PASI score of 4 or less and 77.9% a PASI score of 2 or less. In terms of relative PASI response, 59.4% of the patients achieved a PASI-90 response and 49.0% a PASI-100 response. On multivariate analysis, two factors reduced the probability of a PASI of 2 or less at 24 weeks: a BMI ≥30 (OR, 0.44; 95% CI, 0.22-0.88) and a greater previous exposure to biologic therapy (OR, 0.69; 95% CI, [0.56-0.84]). Adverse events were rare (9.9%) and led to withdrawal from treatment in only nine patients (2.6%) by the end of the follow-up period. The results of this study confirm the high efficacy and safety of guselkumab indicated by the clinical trial data. In clinical practice, the absolute PASI score appears to be a better marker of response to treatment than the relative value.

Multicentric Study on High-Frequency Ultrasound Characterization of Calcium Deposits in Dermal and Subcutaneous Calciphylaxis and Calcinosis.

OBJECTIVES: Calcium depositions are frequent in multiple inflammatory dermatosis, they can be explored by ultrasound (US) but the patterns of these depositions have not yet been described. The aim of this study is to describe different patterns of calcium deposition in inflammatory dermatoses. METHODS: The clinical and US data of 58 patients from 7 different centers with inflammatory dermatosis showing ultrasonography-detected calcium depositions was retrospectively reviewed. RESULTS: Dystrophic calcinosis represented 86.2%, calciphylaxis 8.6%, and metastatic calcinosis 5.2%. Three different sonographic patterns of calcium deposition were found: 1) thin hyperechoic bands, parallel to the surface of the epidermis, generating a strong and wide posterior acoustic shadow; 2) hyperechoic spots or lumps with a narrow acoustic shadow; and 3) a linear hyperechoic band parallel to the walls of a blood vessel with also a narrow acoustic shadow. The predominant pattern in metastatic calcifications was type 1, in dystrophic calcifications type 2, and in calciphylaxis type 3. In dystrophic calcinosis, cutis deposits were longer and wider than in calciphylaxis (P < .05). CONCLUSION: New data on inflammatory dermatoses with calcium deposition may be useful for the diagnosis and monitoring of calcium deposits and could avoid the performance of more invasive tests, such as a skin biopsy.

Personalized Therapy Approach for Hospitalized Patients with Coronavirus Disease 2019.

Hospitalized patients with coronavirus disease 2019 (COVID-19) experiencing respiratory symptoms have different complications (inflammatory, co-infection, and thrombotic) that are identifiable by analytics patterns. Personalized treatment decisions decreased early mortality (odds ratio [OR] .144; 95% confidence interval [CI] .03-.686; P = .015). Increasing age (OR 1.06; P = .038) and therapeutic effort limitation (OR 9.684; P < .001) were associated with higher mortality.

Multicenter Retrospective Study of Secukinumab Drug Survival in Psoriasis Patients in a Daily Practice Setting: A Long-Term Experience in Spain.

INTRODUCTION: There is limited and conflicting evidence over the real-world drug survival of secukinumab (SEC) in patients with psoriasis, especially in the long term. Our objective was to analyze the short- and long-term survival of SEC (S-SEC) and its predictive factors for the treatment of psoriasis. METHODS:  Patients clinically diagnosed with plaque psoriasis and under treatment with secukinumab (n = 384) in a daily practice setting were analyzed in a retrospective, multicenter study performed in a nationwide cohort and followed up for a period of 2 years. Kaplan-Meier curve was plotted to analyze drug survival time, and log-rank test was performed to compare several groups. Factors related to speed of treatment discontinuation were studied with a Cox regression model. RESULTS: The overall cumulative secukinumab drug survival rates observed at 6, 12, 18, and 24 months were 97.1%, 89.0%, 81.1%, and 74.3%, respectively. Obesity [hazard ratio (HR), 1.809, CI 95% 1.114-2.962; p = 0.004] and previous experience with biological therapies, particularly those who had been treated with ≥ 2 biologicals with different mechanisms of action (HR 3.476, CI 95% 1.875-6.444; p = 0.017) were associated with an early discontinuation, whereas psoriatic arthritis was associated with delayed discontinuation, (HR 0.493, CI 95% 0.265-0.917; p = 0.025). CONCLUSIONS: In our study, we found that cumulative secukinumab drug survival for psoriasis patients for the period 6-18 months was in the range of real-world evidence studies. Additionally, we observed a relatively high long-term survival rate at 24 months (74.3%).

Apremilast improves quality of life and ultrasonography parameters in patients with nail psoriasis: A prospective cohort study.

Specific studies on apremilast for nail psoriasis are lacking. Our objective was to evaluate the nail-specific patient-reported outcomes, clinical efficacy, ultrasound (US) parameters, and safety of apremilast for nail psoriasis. We conducted a prospective cohort study including adult patients with plaque and nail psoriasis with a fingernail Nail Psoriasis Severity Index (NAPSI) score of 12 or more. Patients were treated with apremilast 30 mg b.i.d. for 52 weeks. Forty-five patients were included. At week 52, the Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) Patient Benefit Index global weighted score was 2 or more in 52% of patients and NAPPA Quality of Life and fingernail NAPSI improved by 57% and 53%, respectively. US parameters improved from week 16 onwards. Target nail NAPSI improvements were higher for nail matrix scores (60%) than for nail bed scores (38%, p < 0.001). Baseline target nail bed NAPSI was associated with not achieving a target nail 50% reduction in NAPSI score at week 52 in the bivariate analysis (p = 0.024). Safety was consistent with the known apremilast profile. Results from apremilast therapy for 52 weeks in patients with psoriasis and predominant nail disease show significant improvements in nail-specific quality of life, clinical signs, and structural restoration on US, suggesting that apremilast may be considered in the treatment of nail psoriasis.

Ultrasonographic Patterns of Cutaneous Sarcoidosis.

Sarcoidosis is a multiorgan disease characterized by the formation of noncaseating granulomas and possible skin involvement. Cutaneous sarcoidosis (CS) can be explored by ultrasonography when deep dermal or subcutaneous nodules are the clinical presentation. We reviewed the ultrasound characteristics of 14 patients (86% female; mean age, 55 years) with CS. Ultrasonography revealed dermal or subcutaneous hypoechoic areas with increased echogenicity and hypervascularity of the neighboring subcutaneous tissue. In 42.9% of cases a cobblestone pattern of the subcutaneous tissue suggestive of septal involvement was detected. These US features can support the detection of dermal and subcutaneous abnormalities in CS and its early diagnosis.