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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

The effectiveness and safety of ixekizumab in psoriasis patients under clinical practice conditions: A Spanish multicentre retrospective study.

The objective of the study was to evaluate efficacy and safety of ixekizumab in psoriasis patients under clinical practice conditions. Observational, retrospective, multicentre study that included patients with ixekizumab from March 2017 to March 2019. ≥ 90% reduction in the Psoriasis Area and Severity Index (PASI 90) and absolute PASI <2 were the parameters used to assess treatment response. Adverse events (AEs) were collected. Of the 301 patients included, 111 were women (36.9%), mean age was 48.5 (±13.5) years. Mean baseline PASI score was 13.5 (±7.7). More than half of the patients (68.5%) had received at least one biological drug before. At 3 months, 208 (76.5%) patients achieved PASI <2 and 156 (57.3%) PASI 90. At 12 months, 130 (73.4%) patients achieved absolute PASI <2 and 104 (58.7%) PASI 90. Multivariate analysis revealed that prior use of biologics was influential in achieving PASI <2 at both 3 and 12 months (OR 2.82, P = .006; OR 9.51, P < .001, respectively). Sixty-five patients (21.59%) exhibited at least one AE, injection site reaction was the most common (39; 36.8%). Likewise in trials, ixekizumab displayed an excellent profile of safety and efficacy also in real-life. Effectiveness appears superior in biologic-naive patients.

Inter- and Intra-rater Agreement of Dermatologic Ultrasound for the Diagnosis of Lobular and Septal Panniculitis.

OBJECTIVES: Dermatologic ultrasound (US) may aid in the diagnosis and classification of panniculitis. The purpose of this study was to assess the capability of dermatologic US for subtyping mainly septal/lobular panniculitis. METHODS: A multicentric and prospective study of the inter- and intra-rater agreement of dermatologic US for subtyping panniculitis was conducted among 4 clinicians with experience in dermatologic US and a radiologist specialized in dermatologic US. Clinicians recruited patients and performed dermatologic US examinations of the most substantial lesion and punch biopsies. A histologic study was considered the reference standard. Then the images were blindly evaluated by all researchers. For intra- and inter-rater agreement, Cohen and Fleiss κ values were calculated. RESULTS: Sixty-four patients were included. The Cohen intra-rater κ was 0.74. Sensitivity and specificity for lobular panniculitis were 85.19 and 88.57, respectively. The Fleiss inter-rater κ was 0.47. Limitations of the study included the small number of patients and differences in evaluators and their dermatologic US equipment. CONCLUSIONS: This study supports the use of US for diagnosing panniculitis. For subtyping panniculitis, the intra-rater correlation was good. Improvement of inter-rater agreement may depend on access to clinical information, dynamic images, a better definition of criteria, homogeneous configurations of the devices, and the expertise of dermatologic US operators.

A huge rectal ulcer due to argon plasma coagulation in a patient with radiation proctitis.

Radiation proctitis (RP) is a complication of radiotherapy in patients with pelvic cancer. A 64-year-old male underwent brachytherapy 2 years previously due to prostate cancer. Subsequently, he developed RP which was treated with argon plasma coagulation (APC). He was subsequently hospitalized due to rectal bleeding and underwent a colonoscopy. A large deep ulcer was seen in the anterior rectum wall, in the same place where APC was performed 3 months earlier. A perforated rectal ulcer was seen via pelvic MRI. However, it was contained by the mesorrectum. Rectal ulcers after APC are uncommon, but they can develop as a result of thermal damage to an ischemic mucosa due to radiotherapy. The treatment of choice of large ulcers is surgery, with a temporary colostomy in order to aid re-epithelialization.

An atypical bronchogenic cyst with yeast over-infection.

Bronchogenic cysts (BC) are rare congenital anomalies that result from abnormal budding of the tracheobronchial tree during fetal development. BC are usually located in the lung and the mediastinum, an abdominal location is unusual.

Evaluation of Cross-Validation Strategies in Sequence-Based Binding Prediction Using Deep Learning.

Binding prediction between targets and drug-like compounds through deep neural networks has generated promising results in recent years, outperforming traditional machine learning-based methods. However, the generalization capability of these classification models is still an issue to be addressed. In this work, we explored how different cross-validation strategies applied to data from different molecular databases affect to the performance of binding prediction proteochemometrics models. These strategies are (1) random splitting, (2) splitting based on K-means clustering (both of actives and inactives), (3) splitting based on source database, and (4) splitting based both in the clustering and in the source database. These schemas are applied to a deep learning proteochemometrics model and to a simple logistic regression model to be used as baseline. Additionally, two different ways of describing molecules in the model are tested: (1) by their SMILES and (2) by three fingerprints. The classification performance of our deep learning-based proteochemometrics model is comparable to the state of the art. Our results show that the lack of generalization of these models is due to a bias in public molecular databases and that a restrictive cross-validation schema based on compound clustering leads to worse but more robust and credible results. Our results also show better performance when representing molecules by their fingerprints.

Linitis plastica of the colon due to metastases of invasive lobular breast carcinoma.

Colon metastases from breast carcinoma are relatively rare and the invasive lobular subtype tends to metastasize more frequently due to its peritoneal dissemination. A 67-year-old female with a lobular subtype breast neoplasm was treated via a surgical resection ten years previously, with subsequent radiotherapy and adjuvant chemotherapy. She is currently in clinical remission. A colonoscopy was performed due to a recent onset cachexia syndrome, which identified diffuse linitis plastica of the colon. Biopsies confirmed that it was secondary to infiltration by cancer cells of invasive lobular breast carcinoma (ILBC). In conclusion, linitis plastica of the colon may be a new presentation of colon metastases from ILBC.

Serrated Lesions in patients with Inflammatory Bowel Disease.

BACKGROUND: a new serrated histologic finding has recently been discovered in patients with inflammatory bowel disease (IBD), known as serrated epithelial change (SEC). Recent studies suggest that SEC is strongly associated with dysplasia. CASE REPORT: the case was a 62-year-old male in a dysplasia-colorectal cancer screening program with periodic chromoendoscopies, with CES findings in the previous chromoendoscopy studies. DISCUSSION: a prophylactic colectomy seems a reasonable option for patients with several serrated lesions identified via chromoendoscopy screening. Particularly, if they are extensive and poorly defined, due to the possibility of developing high-grade dysplasia or colorectal cancer (CRC) during surveillance.

Soil parent material-A major driver of plant nutrient limitations in terrestrial ecosystems.

Because the capability of terrestrial ecosystems to fix carbon is constrained by nutrient availability, understanding how nutrients limit plant growth is a key contemporary question. However, what drives nutrient limitations at global scale remains to be clarified. Using global data on plant growth, plant nutritive status, and soil fertility, we investigated to which extent soil parent materials explain nutrient limitations. We found that N limitation was not linked to soil parent materials, but was best explained by climate: ecosystems under harsh (i.e., cold and or dry) climates were more N-limited than ecosystems under more favourable climates. Contrary to N limitation, P limitation was not driven by climate, but by soil parent materials. The influence of soil parent materials was the result of the tight link between actual P pools of soils and physical-chemical properties (acidity, P richness) of soil parent materials. Some other ground-related factors (i.e., soil weathering stage, landform) had a noticeable influence on P limitation, but their role appeared to be relatively smaller than that of geology. The relative importance of N limitation versus P limitation was explained by a combination of climate and soil parent material: at global scale, N limitation became prominent with increasing climatic constraints, but this global trend was modulated at lower scales by the effect of parent materials on P limitation, particularly under climates favourable to biological activity. As compared with soil parent materials, atmospheric deposition had only a weak influence on the global distribution of actual nutrient limitation. Our work advances our understanding of the distribution of nutrient limitation at global scale. In particular, it stresses the need to take soil parent materials into account when investigating plant growth response to environment changes.

The In Vitro Pharmacological Profile of Drugs as a Proxy Indicator of Potential In Vivo Organ Toxicities.

The potential of a drug to cause certain organ toxicities is somehow implicitly contained in its full pharmacological profile, provided the drug reaches and accumulates at the various organs where the different interacting proteins in its profile, both targets and off-targets, are expressed. Under this assumption, a computational approach was implemented to obtain a projected anatomical profile of a drug from its in vitro pharmacological profile linked to protein expression data across 47 organs. It was observed that the anatomical profiles obtained when using only the known primary targets of the drugs reflected roughly the intended organ targets. However, when both known and predicted secondary pharmacology was considered, the projected anatomical profiles of the drugs were able to clearly highlight potential organ off-targets. Accordingly, when applied to sets of drugs known to cause cardiotoxicity and hepatotoxicity, the approach is able to identify heart and liver, respectively, as the organs where the proteins in the pharmacological profile of the corresponding drugs are specifically expressed. When applied to a set of drugs linked to a risk of Torsades de Pointes, heart is again the organ clearly standing out from the rest and a potential protein profile hazard is proposed. The approach can be used as a proxy indicator of potential in vivo organ toxicities.