Severity Scoring System Research Articles

Bimekizumab Efficacy and Safety Through 2 years in Patients with Hidradenitis Suppurativa: Results from the Phase 3 BE HEARD I&II trials and Open-Label Extension BE HEARD EXT

Introduction: Interleukin (IL)-17F and IL-17A play a role in the immunopathogenesis of hidradenitis suppurativa (HS).1–3 Bimekizumab (BKZ) is a humanized IgG1 monoclonal antibody that selectively inhibits IL-17F in addition to IL-17A leading to clinically meaningful improvements in patients (pts) with HS.4,5 Here, BKZ efficacy and safety data (OC) are presented over 2 years (96 weeks [wks]) for the pooled BE HEARD I&II (BHI&II) trials and BE HEARD EXT (BHEXT).5,6 Procedure/Study: In BHI&II, pts with moderate to severe HS were randomized 2:2:2:1 (16wk-initial/32wk-maintenance) to BKZ 320mg every 2 wks (Q2W)/Q2W, BKZQ2W/Q4W, BKZQ4W/Q4W or placebo/BKZQ2W.5 Wk48 completers could enroll in BHEXT and receive open-label BKZQ2W or BKZQ4W based on ≥90% HS Clinical Response (HiSCR90; averaged from Wks36/40/44). We report HiSCR50/75/90/100 rates, percentage change from baseline (%CfB, mean±SD) in International HS Severity Score System (IHS4) and draining tunnel (DT) count, and Dermatology Life Quality Index (DLQI) 0/1 achievement at Wks48/96 for patients randomized to BKZ in BHI&II and entered BHEXT (BKZ Total, observed case). Safety outcomes reported for pts who received ≥1 BKZ dose across BHI&II/BHEXT. Results: 556 pts randomized at baseline to BKZ in BHI&II completed Wk48 and entered BHEXT; 446 pts completed Wk96. At Wk48, HiSCR50/75/90/100 was achieved by 79.9/64.0/42.3/30.2% of pts; responses improved to Wk96: 85.4/77.1/57.6/44.2%. Baseline IHS4 was 35.6±31.5; %CfB at Wk48/96 was –70.3±39.6/−79.8±28.1%. Baseline DTs were 3.8±4.3; the %CfB at Wk48/96 was −57.5±72.9%/−73.7±45.7%. Baseline DLQI was 11.0±6.8; 27.4% (151/551) of pts achieved DLQI 0/1 at Wk48 and 33.9% (149/439) at Wk96. Over 2 years, 917/995 (248.9/100 pt years [PY]) pts experienced a treatment-emergent adverse event (TEAE). Serious TEAEs were reported in 122 (7.2/100 PY) pts; 109 (6.3/100 PY) pts discontinued due to a TEAE. Serious infections occurred in 33 (1.9/100 PY) pts. Safety data were comparable with BHI&II.5 Conclusion: In pts treated with BKZ, clinically meaningful improvements in efficacy outcomes observed at 1 year, including the HiSCR 75/90/100, IHS4, and DT count endpoints, were maintained to 2 years; improvements in quality of life were maintained. No new safety signals were observed; the safety profile over 2 years was consistent with BHI&II and BKZ studies in other indications.5,7–9

Gastrointestinal complaints after Roux-en-Y gastric bypass surgery. Impact of microbiota and its metabolites

Unexplainable gastrointestinal complaints occasionally occur after Roux-en-Y Gastric Bypass (RYGB) surgery. We therefor investigated the impact of microbiota composition and metabolites on gastrointestinal complaints after RYGB. In the BARICO study (Bariatric surgery Rijnstate and Radboudumc neuroimaging and Cognition in Obesity), microbiota and metabolites were measured before surgery, and 6, and 24 months after surgery. Gastrointestinal complaints were assessed with the Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) questionnaire 24 months after surgery. 65 participants (86.2 % female) with a mean age of 46.2 ± 6.0 years, and mean BMI of 41.2 ± 3.6 kg/m2 were included. According to the IBS-SSS questionnaire, 32.3 % had moderate/severe gastrointestinal complaints 24 months after surgery. Microbiota alpha diversity remained stable, while beta diversity significantly changed over time. Bile acids and short-chain fatty acids were significantly higher, and inflammatory markers significantly lower after surgery. Barnesiella sp., Escherichia/Shigella sp., and Faecalibacterium prausnitzii correlated positively, while Akkermansia sp correlated inversely with gastrointestinal complaints. Patients with mild and moderate/severe gastrointestinal complaints showed higher levels of GLC-3S. These findings suggest involvement of microbiota and metabolite changes in gastrointestinal complaints after surgery. However, it remains unclear whether bacteria influence gastrointestinal complaints directly or indirectly. Further exploration is required for development of interventions against gastrointestinal symptoms after surgery.

Early impairment of endothelial and myocardial function in patients with hidradenitis suppurativa

Abstract Background/Introduction Hidradenitis suppurativa (HS) is a chronic, recurrent, debilitating, inflammatory skin disease manifested by painful, deep-seated, inflamed lesions of the apocrine gland-bearing areas of the body (axillae, submammary folds, inguinal and anogenital region). HS has been associated, among others, with an increased cardiovascular risk. Purpose We aimed to investigate the endothelial, arterial and left ventricular (LV) myocardial function in patients with severe HS. Methods Twenty-eight, not previously treated patients (mean age: 36 ± 13 years) with Hurley stage III disease and a mean score of 19±8 on the International Hidradenitis Suppurativa Severity Score System (IHS4) scale, were studied. Twenty healthy sex-, age- and body mass index -matched individuals, who were also weighted for common cardiovascular risk factors, served as the control group. Both patients and controls were evaluated for: a) perfused boundary region (PBR) of the sublingual microvessels with a diameter of 5-25 μm (an increased PBR value is considered as an indicator of a decrease in thickness of the endothelial glycocalyx), using a dedicated camera (Microscan, GlycoCheck), b) carotid-femoral pulse wave velocity (PWV-Complior), c) flow-mediated dilation (FMD) of the brachial artery and d) LV global longitudinal strain (GLS) using the speckle-tracking echocardiography. Results Compared to healthy controls, HS patients had increased PBR value (2.32 ± 0.19 vs. 1.99 ± 0.14 μm, p < 0.001) and decreased FMD (5.7 ± 2.9 vs. 10.3 ± 1.9 %, p < 0.001) and GLS values (-18.6 ± 2.8 vs. -22.5 ± 2.3 %, p < 0.001). In contrast, similar PWV values (9.2 ± 2 vs. 9.1 ± 1.9 m/s, p = 0.937) were recorded between patients and controls (Table). Increased IHS4 score (more severe disease) was associated with increased PBR values (r = 0.42, p = 0.026) and decreased FMD values (r = -0.37, p = 0.045). Conclusion Patients with HS show early impairment of endothelial and LV myocardial function, which correlates with the severity of the underlying systemic inflammation.Table

Secukinumab efficacy in patients with hidradenitis suppurativa assessed by the International Hidradenitis Suppurativa Severity Score System (IHS4): A post hoc analysis of the SUNSHINE and SUNRISE trials.

The International Hidradenitis Suppurativa Severity Score System (IHS4) is a validated tool that measures inflammatory lesions, including draining tunnels, in hidradenitis suppurativa (HS). To evaluate secukinumab efficacy using IHS4 in patients with moderate to severe HS. Data from the SUNSHINE and SUNRISE trials, which assessed subcutaneous secukinumab 300 mg every 2 (SECQ2W) and 4 (SECQ4W) weeks in adults with moderate to severe HS, were analyzed. Assessments included changes from baseline in IHS4 and severity classification up to Week 52; IHS4-55, IHS4-75, IHS4-90 responses (55%, 75% and 90% reduction in IHS4) and concordance between IHS4-55 and HS clinical response (HiSCR), at Weeks 16 and 52. In total, 1084 patients (SECQ2W = 361; SECQ4W = 360; placebo = 363) were analyzed. At Week 16, SECQ2W and SECQ4W demonstrated a numerically higher reduction in IHS4 from baseline versus placebo (adjusted mean [95% CI]: -10.80 [-12.30 to -9.30] and -9.46 [-10.96 to -7.96] vs. -4.92 [-6.43 to -3.41]); the reduction was maintained until Week 52 in both dose regimens. A greater proportion of patients achieved IHS4-55 with SECQ2W (43.4%) and SECQ4W (39.5%) versus placebo (31.5%) at Week 16, with further improvement at Week 52. Similar trends were observed for IHS4-75 and IHS4-90 responses. While no patients had mild disease based on IHS4 (80.7% had severe and 19.3% had moderate HS) at baseline, a greater proportion of patients were categorized as having mild disease at Week 16 in the SECQ2W (25.9%) and SECQ4W (24.0%) groups versus placebo (16.4%); this trend continued up to Week 52 in both dose regimens. Strong concordance (>85%) was observed between IHS4-55 and HiSCR. Both SECQ2W and SECQ4W demonstrated efficacy in improving treatment response as measured by IHS4 and reducing disease severity versus placebo at Week 16 and these improvements were sustained through Week 52. These findings support that the dynamic and dichotomous IHS4 can efficiently detect treatment response changes in clinical trial settings.

Inflammatory Prostatitis Plus IBS-D Subtype and Correlation with Immunomodulating Agent Imbalance in Seminal Plasma: Novel Combined Treatment.

We recently demonstrated the effectiveness of long-term treatment with rifaximin and the probiotic DSF (De Simone formulation) in improving urogenital and gastrointestinal symptoms in patients with both chronic inflammatory prostatitis (IIIa prostatitis) and diarrhea-predominant irritable bowel syndrome (IBS-D), relative to patients with IBS-D alone. Because the low-grade inflammation of the intestine and prostate may be one of the reasons for co-developing both IIIa prostatitis and IBS-D, we designed the present study to once again evaluate the efficacy of combined rifaximin and DSF treatment in patients affected by IIIa prostatitis plus IBS-D, but we also measured seminal plasma pro-inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines before and after treatment. Methods: We consecutively enrolled 124 patients with IIIa prostatitis and IBS-D (diagnosed using the Rome III criteria). Patients were randomized into two groups: group A (n = 64) was treated with rifaximin (seven days per month for three months) followed by DSF, and group B (n = 60) was treated with a placebo. By the end of the intervention, 68.7% and 62.5% of patients from group A reported improved NIH-CPSI (National Institute of Health's Chronic Prostatitis Symptom Index) and IBS-SSS (Irritable Bowel Syndrome Severity Scoring System) scores, respectively, compared to only 3.3% and 5% of the placebo group. Group A patients also had significantly lower mean seminal plasma levels of IL-6 (11.3 vs. 32.4 pg/mL) and significantly higher mean levels of IL-10 (7.9 vs. 4.4 pg/mL) relative to baseline, whereas the levels of IL-6 and IL-10 did not change in the placebo group. Conclusions: The combined treatment with rifaximin and DSF appears to represent the optimal approach for addressing a syndrome such as irritable bowel syndrome (IBS-D plus), which frequently co-occurs with prostatitis (IIIa prostatitis). This approach is particularly beneficial in cases where the symptoms are not always clearly delineated, the etiology is multifactorial, and the diagnosis is multilevel.

Impact of HADS Anxiety and Depression Scores on the Efficacy of Dietary Interventions for Irritable Bowel Syndrome.

Anxiety and depression are associated strongly with irritable bowel syndrome (IBS). Dietary therapies are used increasingly in the management of IBS, but the impact of common mental disorders on response to these has not been well studied. To examine whether symptoms compatible with common mental disorders influence response to dietary interventions. Prospective cohort study of adults, with either diarrhoea-predominant or mixed bowel habits, IBS Severity Scoring System [IBS-SSS] score ≥ 75 points. Participants completed the Hospital Anxiety and Depression score (HADS) and attended initially for British Dietary Association advice for IBS. IBS-SSS was re-checked 3 months later to assess response. If primary endpoint (≥ 50 point decrease in IBS-SSS) was not achieved, patients were offered low fermentable oligo-, di- and monosaccharides and polyol diet and repeated IBS-SSS after another 3 months. Secondary endpoints included of change in IBS-SSS and effect of symptom severity on response. In total, 448 patients took part, average age of 42 years and 79.0% were female. 69.9% of participants had HADS-A scores ≥ 8 and 39.3% with HADS-D scores ≥ 8. Average IBS-SSS score at baseline was 290 (SD 86). No significant difference was noted in achievement of the primary endpoint according to HADS-A scores (53.4% vs. 62.2% by ITT in those with HADS-A ≥ 8 vs. HADS-A < 8, p = 0.09). Patients with HADS-D ≥ 8 were significantly less likely to achieve the primary endpoint compared with those with HADS-D < 8 (43.8% vs. 64.0% by ITT, p < 0.01). Understanding psychological profile of patients can help predicting their response to IBS dietary interventions.

B-068 Plasma calprotectin as an index of draining tunnel formation in Hidradenitis suppurativa

Abstract Background Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease which affects areas rich in apocrine glands. The main disease manifestations are inflammatory nodules (IN) and draining tunnels (dT). The course and progression of the disease are difficult to predict. There is currently lack of any broadly accepted biomarker which may inform on the activity of hidradenitis suppurativa (HS). Draining tunnel (dT) formation is the hallmark of HS in the affected skin. The existence of a biomarker which may predict dT formation before dTs appear in skin may become a tool for early biological treatment. Calprotectin, also known as S100 A8/A9 protein has been shown to be involved in various inflammatory conditions, including HS. Aim of this study was to evaluate circulating calprotectin as an index of dTs in the affected skin. Methods The study group consisted of 40 patients with confirmed HS and varying disease activity, assessed by number of dTs and International Hidradenitis Suppurativa Severity Score System (IHS 4 score) . Plasma samples were collected and stored at -80°C until analysis. Calprotectin was measured with GCAL® turbidimetric assay (Gentian AS, Norway). Results Fifteen patients had mild HS and 25 patients had moderate/severe HS. Positive association was found between circulating calprotectin and the absolute dT count (Pearson’s r2 = +0.750; p&amp;lt;0.0001) and the IHS4 (International HS 4 score) (Pearson’s r2 = +0.671; p&amp;lt;0.0001). Circulating calprotectin was significantly increased in patients with more than 2 dTs. Plasma calprotectin greater than 0.5 mg/L was associated with odds ratio 8.00 (1.87 to 34.22; p = 0.005) for 2 or more dTs. Conclusions Calprotectin is presented, for the first time, as a biomarker which indicates the formation of dTs in the skin. Its use as surrogate of early start of biologicals and response to treatment remains to be explored.

Low-dose titrated amitriptyline as second-line treatment for adults with irritable bowel syndrome in primary care: the ATLANTIS RCT.

Irritable bowel syndrome, characterised by abdominal pain and a change in stool form or frequency, is most often managed in primary care. When first-line therapies are ineffective, National Institute for Health and Care Excellence guidelines suggest considering low-dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown and they are infrequently prescribed by general practitioners. To evaluate the clinical and cost-effectiveness of low-dose titrated amitriptyline as a second-line treatment for irritable bowel syndrome in primary care. A pragmatic, randomised, multicentre, two-arm, double-blind, placebo-controlled trial. A nested, qualitative study explored participant and general practitioner experiences of treatments and trial participation, and implications for wider use of amitriptyline for irritable bowel syndrome in primary care. Participants, clinicians, investigators and analysts were masked to allocation. Fifty-five general practices in three regions in England (Wessex, West of England, West Yorkshire). Patients aged ≥ 18 years meeting Rome IV criteria for irritable bowel syndrome with ongoing symptoms after trying first-line treatments and no contraindications to TCAs. Amitriptyline 10 mg once-daily, self-titrated by participants to a maximum of 30 mg once-daily or matched placebo for 6 months. Participants randomised 1 : 1 with most having the option to continue blinded treatment for a further 6 months. The primary participant-reported outcome was the effect of amitriptyline on global irritable bowel syndrome symptoms at 6 months, measured using the irritable bowel syndrome Severity Scoring System, with a 35-point between-group difference defined as the minimum clinically important difference. The key secondary outcome was the proportion of participants reporting subjective global assessment of relief at 6 months, defined as somewhat, considerable, or complete relief of symptoms. Other secondary outcomes included: effect on global symptoms, via the irritable bowel syndrome Severity Scoring System, and subjective global assessment of relief of irritable bowel syndrome symptoms at 3 and 12 months; effect on somatic symptom-reporting at 6 months; anxiety an-d depression scores; ability to work and participate in other activities at 3, 6 and 12 months; acceptability, tolerability and adherence to trial medication. Four hundred and sixty-three participants were randomised to amitriptyline (232) or placebo (231). An intention-to-treat analysis of the primary outcome showed a significant difference in favour of amitriptyline for irritable bowel syndrome Severity Scoring System score between arms at 6 months [-27.0, 95% confidence interval (CI) -46.9 to -7.10; p = 0.008]. For the key secondary outcome of subjective global assessment of relief of irritable bowel syndrome symptoms, amitriptyline was superior to placebo at 6 months (odds ratio 1.78, 95% CI 1.19 to 2.66; p = 0.005). Amitriptyline was superior to placebo across a range of other irritable bowel syndrome symptom measures but had no impact on somatoform symptom-reporting, anxiety, depression, or work and social adjustment scores. Adverse event trial withdrawals were more common with amitriptyline (12.9% vs. 8.7% for placebo) but most adverse events were mild. The qualitative study thematically analysed 77 semistructured interviews with 42 participants and 16 GPs. Most participants found the self-titration process acceptable and empowering. General practitioners should offer low-dose amitriptyline to patients with irritable bowel syndrome whose symptoms do not improve with first-line therapies. Guidance and resources should support GP-patient communication to distinguish amitriptyline for irritable bowel syndrome from use as an antidepressant and to support patients managing their own dose titration. This trial is registered as ISRCTN48075063. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/162/01) and is published in full in Health Technology Assessment Vol. 28, No. 66. See the NIHR Funding and Awards website for further award information.

Results From a Psychometric Validation Study: Patients With Irritable Bowel Syndrome Report Higher Symptom Burden Using End-of-Day Vs Real-Time Assessment.

Real-time assessment of gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS) using the experience sampling method (ESM) is suggested as a more appropriate approach than currently used end-of-day or end-of-week reports. This psychometric evaluation study assesses the validity and reliability of a previously developed ESM-based patient-reported outcome measure (PROM) for real-time GI symptom assessment in IBS. This multicenter validation study included 230 Rome IV patients with IBS (80% female; mean age 41.2 years) in 3 European countries. Patients completed the electronic ESM-PROM (up to 10 random moments daily, with a weekly minimum completion rate of 33%) and an end-of-day symptom diary for 7 consecutive days. End-of-week questionnaires (Gastrointestinal Symptom Rating Scale for IBS, IBS Severity Scoring System, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7) were completed at the end of the 7-day period. The ESM assessment had a mean completion rate of 71%. Strong and significant correlations (0.651-0.956) with moderate-to-good consistency (intra-class correlation coefficients 0.580-0.779) were observed between ESM and end-of-day scores. However, end-of-day scores were significantly higher (Δ0.790-1.758, P < 0.001) than mean daily ESM scores. Differences with end-of-week scores were more pronounced, with weaker correlations (Pearson's r 0.393-0.802). ESM-PROM exhibited moderate-to-good internal consistency (Cronbach's α 0.585-0.887) across 5 symptom domains. First and second half-week scores demonstrated good-to-excellent consistency (intraclass correlation coefficients 0.871-0.958). Psychometric evaluation demonstrated strong validity and reliability of the ESM-PROM for real-time GI symptom assessment in IBS. In addition, the ESM-PROM provides a precise and reliable ascertainment of individual symptom pattern and trigger interactions, without the bias of peak reporting when compared with retrospective methods. This highlights its potential as a valuable tool for personalized healthcare in monitoring disease course and treatment response in patients with IBS.

Factors Associated With Successful Withdrawal of Biologic Agents in Children With Colchicine-Resistant Familial Mediterranean Fever.

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease, and colchicine is the mainstay of treatment. Approximately 5%-10% of patients may respond inadequately to colchicine, and anti-interleukin-1 (anti-IL-1) agents are important treatment options in these patients. The aim of this study was to see whether there is any factor associated with the withdrawal of these anti-IL-1 agents and to investigate the characteristics of colchicine-resistant FMF patients who needed biological therapy. Demographic, clinical characteristics, and disease severity of patients, at 2 referral centers, between 2012 and 2022, in whom anti-IL-1 treatment was continued and discontinued, were compared in this study. The international severity scoring system for FMF (ISSF) was used for disease severity assessment. In 64 colchicine-resistant FMF patients, the median (interquartile range) duration of biological treatment was 39 (45) months. Treatment of 26 patients (40.6%) was started with anakinra and 38 (59.4%) with canakinumab. During follow-up, anti-IL-1 treatment was discontinued in 23 patients (35.9%). High ISSF scores before biological treatment, presence of exertional leg pain, subclinical inflammation, and comorbidity were found to be statistically more frequent in the group whose biological therapy could not be discontinued (p = 0.009, p = 0.006, p = 0.026, p = 0.001, respectively). Low ISSF scores before biological treatment with no accompanying exertional leg pain, subclinical inflammation, and comorbidities may be stated as an associated factors in terms of the discontinuation of biological agents in colchicine-resistant pediatric FMF patients.

Risk factors analysis for severe acute kidney injury in septic patients and establishment and validation of an hour-specific prediction model

To explore the risk factors of severe acute kidney injury (AKI) in septic patients, and to establish an hour-specific prediction model. Based on the information of septic patients in the Medical Information Mart for Intensive Care- IV (MIMIC- IV) database, general information, comorbidities, vital signs, severity scoring system, laboratory indicators, invasive operations and medication use were recorded. The enrolled patients were randomized into a training set and a validation set according to a ratio of 7 : 3. AKI was diagnosed according to the guidelines of Kidney Disease: Improving Global Outcome (KDIGO). Based on Lasso regression and Cox regression, the risk factors of severe AKI (AKI stage 2 and stage 3) in septic patients were analyzed and hour-specific prediction model were established. Consistency index (C-index), area under the receiver operator characteristic curve (AUC) and calibration curve were used to assess the predictive efficacy of the model. A total of 20 551 septic patients were enrolled, including 14 385 patients in the training set and 6 166 patients in the validation set. Multivariate Cox regression analysis showed that atrial fibrillation [hazard ratio (HR) = 1.266, 95% confidence interval (95%CI) was 1.150-1.393], heart failure (HR = 1.348, 95%CI was 1.217-1.493), respiratory failure (HR = 1.565, 95%CI was 1.428-1.715), heart rate (HR = 1.004, 95%CI was 1.002-1.007), mean arterial pressure (HR = 1.245, 95%CI was 1.126-1.377), lactic acid (HR = 1.051, 95%CI was 1.025-1.077), simplified acute physiology score II (SAPS II, HR = 1.019, 95%CI was 1.016-1.023), serum creatinine (HR = 1.171, 95%CI was 1.127-1.216), anion gap (HR = 1.024, 95%CI was 1.010-1.038), serum potassium (HR = 1.155, 95%CI was 1.079-1.236), white blood cell count (HR = 1.006, 95%CI was 1.003-1.009) and furosemide use (HR = 0.414, 95%CI was 0.368-0.467) were independently associated with severe AKI in septic patients (all P < 0.01). The above predictors were applied to construct an hour-specific prediction model for the occurrence of severe AKI in septic patients. The C-index of the prediction model was 0.723 and 0.735 in the training and validation sets, respectively. The AUC for the occurrence of severe AKI at 12, 24, and 48 hours were 0.795 (95%CI was 0.782-0.808), 0.792 (95%CI was 0.780-0.805), and 0.775 (95%CI was 0.762-0.788) in the training set, and the AUC were 0.803 (95%CI was 0.784-0.823), 0.791 (95%CI was 0.772-0.810), and 0.773 (95%CI was 0.752-0.793) in the validation set, respectively. The calibration curves of the two cohorts were in good agreement. The hour-specific prediction model effectively identifies high-risk septic patients for developing severe AKI within 48 hours, aiding clinicians in stratifying patients for early therapeutic interventions to improve outcomes.

Interleukin-1 family cytokines and soluble receptors in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic skin disease, characterized by clinical inflammation of the hair follicle with the recurrence of abscesses, nodules, and tunnels. Recently, several studies suggested a role of IL-1 family (IL-1F) cytokines in eliciting and sustaining the disease. The aim of this work is to perform a comprehensive analysis of IL-1F cytokines, soluble inhibitors and receptors in a cohort of HS patients not treated with biological agents. Sixteen patients affected by HS and 16 healthy controls were recruited; clinical data were collected and disease severity evaluated by means of the International HS Severity Score System (IHS4). Serum levels of IL-1F cytokines, inhibitors and receptors were measured using a Multiplex Assays. IL-18 and free IL-18 levels were significantly higher in patients vs controls. Among soluble inhibitors, IL-1Ra, IL-1R2 and ST2/IL-1R4 were significantly increased. IL-18, free IL-18 and IL-33 levels are strongly correlated with IHS4. Also the inhibitors IL-1Ra and IL-18BP show a correlation with IHS4. The data obtained in this study confirm the involvement of IL-1F cytokines in mediating the disease and determining its severity and suggest a possible role for IL-18 as novel serum biomarker of active disease.

53303 Repurposing the Composite Assessment of Index Lesion Severity Scoring System in Cutaneous Lichen Planus

53303 Repurposing the Composite Assessment of Index Lesion Severity Scoring System in Cutaneous Lichen Planus

Assessing the Role of Adalimumab in Treating Hidradenitis Suppurativa: Findings from a Retrospective Study at a Reference Center.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by inflammatory lesions, often leading to scarring. Managing HS can be difficult, requiring biological therapy, specifically adalimumab. A retrospective study was conducted on patients diagnosed with HS and treated with the TNF-α inhibitor adalimumab. Data from 21 patients were included in this study. International Hidradenitis Suppurativa Severity Score System (IHS4); Dermatology Life Quality Index (DLQI); pain intensity according to the Visual Analogue Scale (VAS); and number of nodules, abscesses, and fistulas were assessed. Notably, 47.62% of patients achieved Hidradenitis Suppurativa Clinical Response. The mean number of inflamed nodules decreased from 5.62 ± 4.12 to 3 ± 3.46, abscesses decreased from 1.76 ± 2.63 to 0.81 ± 1.4, and fistulas decreased from 2.62 ± 1.86 to 2 ± 1.9 (p < 0.05). The IHS4 score decreased from 19 ± 10.78 to 12.62 ± 11.13 (p = 0.001), DLQI from 15.76 ± 7.73 to 7.43 ± 7.76 (p < 0.001), and VAS from 6.69 ± 1.56 to 3.64 ± 2.65 (p < 0.001). There was a significant difference in the baseline IHS4 scores between patients who had prior surgery with a mean score of 23.86 ± 9.4 versus non-surgical patients with a mean IHS4 score of 9.29 ± 5.53 (p = 0.001). About half of HS patients responded positively to adalimumab treatment; the use of the drug reduces inflammatory lesions, and pain, and improves quality of life.

Squamous Cell Carcinoma In Situ-The Importance of Early Diagnosis in Bowen Disease, Vulvar Intraepithelial Neoplasia, Penile Intraepithelial Neoplasia, and Erythroplasia of Queyrat.

Cutaneous squamous cell carcinoma (cSCC) is the second-most-prevalent malignancy in humans. A delayed diagnosis of cSCC leads to heightened invasiveness and positive surgical margins. Bowen's disease (BD) represents an early form of cSCC and presents as a small erythematous, photo-distributed, psoriasiform plaque. Although certain dermoscopy features in BD are quite characteristic, histopathology remains the gold standard for diagnosis and provides a severity-scoring system that assists in guiding appropriate treatment strategies. The classification of precancerous lesions of the vulva and penis has undergone multifarious transformations due to variations in clinical and histopathological characteristics. Presently, erythroplasia of Queyrat is categorized as a clinical variant of penile intraepithelial neoplasia (PeIN). The diagnoses of vulvar intraepithelial neoplasia (VIN) and PeIN present significant challenges and typically necessitate one or more biopsies, potentially guided by dermoscopy. Aceto-white testing demonstrates a notably high negative predictive value for genital precancerous lesions. Histopathological examination represents the gold-standard diagnosis in VIN and PeIN, while p16 and p53 immunostainings alongside HPV testing provide crucial diagnostic clues. The histopathologic features, degree of differentiation, and associations with lichen planus, lichen sclerosus, and HPV guide the selection of conservative treatments or surgical excision.

Assessment of Clinician-Reported Outcome Measures for Alopecia Areata: A Systematic Scoping Review.

Clinician-reported outcome measures (ClinROMs) are an important part of disease assessment in daily practice and clinical trials. There is a broad disagreement on the most appropriate ClinROM for a comprehensive assessment of alopecia areata (AA) severity. This paper aims to identify the currently available ClinROMs for AA through a systematic literature search, address their practical strengths and weaknesses, and identify the road ahead for future research. A search was conducted of the published, peer-reviewed literature via PubMed (Medline) and EMBASE (via Ovid) databases. Articles published in English within the last 23 years (post-2000) that objectively measured AA severity were included. We did not select scoring systems that were solely based on patient-reported outcomes (PROs). The literature search identified 1376 articles, of which 27 were chosen for full-text review. Based on our eligibility criteria, fourteen articles were identified, describing sixteen different ClinROMs. Five ClinROMs solely measured scalp hair loss (SALT, SALTⅡ, ALODEX, pSALT, and AA-IGA). Three trichoscopy-based ClinROMs assessed disease activity (AAPI, AAPS, and Coudability hair score). Six ClinROMs exclusively assessed non-scalp areas (BETA, BELA, ALBAS, ClinRO for Eyelash, Eyebrow, and Nail assessment). Two ClinROMs assessed both the scalp and beyond-scalp areas (AASI and AASc). The practical strengths and weaknesses of each assessment tool were described. Various practical limitations associated with established tools have impeded their universal implementation in routine clinical practice. There is a significant need for a holistic clinical severity scoring system to capture all the key severity identifiers beyond the involvement of the scalp.

CORR Insights®: What Is the Risk of Irrigation and Debridement Following Foot and Ankle Surgery? Development of a Risk Severity Scoring System.

CORR Insights®: What Is the Risk of Irrigation and Debridement Following Foot and Ankle Surgery? Development of a Risk Severity Scoring System.

Severity of child neglect among acutely poisoned children in Egypt.

Child abuse and neglect pose significant public health challenges, contributing to compromised development and adverse health outcomes. Neglect is the most frequent type of child abuse, presenting substantial challenges for paediatricians. To identify types of neglect associated with poisoned children, analyse potential risk factors and develop a novel severity scoring system to assess child neglect in Alexandria, Egypt. Using a simple random sampling technique, with an observational checklist we collected data on children aged 2 months to 17 years admitted for poisoning at the poison centre of Alexandria Main University Hospital from October to December 2022. We analysed the data using SPSS version 20.0 and tested the associations between neglect score and child data, current condition and carer data using the χ2 test, the Monte Carlo simulation and Fisher's exact P. The study enrolled 147 children, male-to-female ratio 1:1.17. Pesticides were the most common cause of poisoning. Lack of supervision was noted in 83% of cases and the neglect severity score showed that 27.9% of the children experienced severe neglect. There was significant association between severity of neglect and caregiver's education level and between severity of neglect and child's residence; severe neglect cases were significantly higher among children whose caregivers had no formal education (70.7%) and among those from rural areas (61%). These findings highlight the critical need to address educational disparities among caregivers and improve supervision for children, especially in rural areas.

What Is the Risk of Irrigation and Debridement Following Foot and Ankle Surgery? Development of a Risk Severity Scoring System.

Surgical site infection (SSI) after foot and ankle surgery has serious negative effects on patient health and quality of life. While previous studies have looked at predisposing factors for SSI, to our knowledge, no study has proposed a risk severity score. Can a risk severity score, based on patient demographic characteristics and surgical variables, be developed for preoperative use in patients undergoing foot and ankle surgery that will calculate the risk of an irrigation and debridement (I&D) procedure within 90 days of surgery utilizing data from previous surgeries? A retrospective chart study was performed on patients undergoing foot and ankle surgery. Data on demographic characteristics including age, sex, and BMI were recorded. Data on patient factors including diabetes and smoking history were also recorded. Surgical details including length of surgery, procedure type, surgeon, antibiotic delivery time, antibiotic type, and antibiotic dose were analyzed. Of 2979 procedures, 1% (36) of I&Ds were performed within 90 days. The mean age at surgery was 49 ± 17 years, and 57% (1702) of patients were female. The mean BMI was 28 ± 6 kg/m2. The primary outcome was I&D within 90 days postoperatively. Descriptive statistics of differences in patient characteristics between those who underwent I&D and those who did not were examined using chi-square tests and t-tests (p < 0.05 was taken as significant). Significant variables from a simple regression analysis were included in a multiple logistic regression model with a forward stepwise procedure for variable selection. We required all data in the model to be categorical; thus, continuous variables such as time were dichotomized. We factored odds ratios determined by multiple regression for significant variables into the final risk severity score, and an easy-to-use tool based on this risk severity score was created in Excel (Microsoft). Current tobacco use, diabetes, and longer operative times were the only factors associated with I&D within 90 days postoperatively. A risk severity score was developed using current tobacco use, diabetes, and length of surgery greater than 60 minutes as factors. A patient with a severity score of 0 (no risk factors) had a 0.6% chance of I&D within 90 days, while a severity score of 1 indicated a 1.1% chance, a score of 2 indicated a 2.1% chance, a score of 3 indicated a 4.0% chance, and a score of 4 (all risk factors) indicated a 7.5% chance of I&D within 90 days. A spreadsheet that can be used at the point of care was created based on these findings. Our risk severity score may help inform preoperative patient guidance and operative planning. Calculating the score in the office setting during preoperative visits can also improve communication between physician and patient. Future research should focus on validation of this risk severity score at multiple institutions. Level III, prognostic study.

What can impact on the presence of carious lesions in first permanent molars? Revisiting the association between MIH and caries.

Assess whether the independent variables (IV) such as number of MIH-affected molars, MIH severity, past caries experience, visible plaque index (VPI), gingival bleeding index (GBI), age, and gender affect the presence of caries lesion (DMF_s) in first permanent molars, considering or not atypical restoration in MIH-affected molars as a previous caries lesion. A sample of 476 schoolchildren, aged 6-10years, were evaluated for MIH and caries diagnosis, using the Severity Scoring System (MIH-SSS) and the International Caries Detection and Assessment System (ICDAS), respectively. From the ICDAS, the DF-s/ D-s and df-s were calculated. The Zero-inflated Negative Binomial Regression was used to evaluate the impact of the IV on the dependent variable, considering or not the restorative component in MIH-affected molars. When the presence of caries was evaluated with the restorative component, age, MIH severity and past caries experience had a significant impact on the dependent variable (R2 = 0.176). Without the restorative component in MIH-affected molars, only age and past caries experience were statistically significant (R2 = 0.167). Since in the case of MIH teeth restoration may be attributed to post-eruptive breakdown rather than previous caries lesions, in the present study MIH did not influence the presence of caries lesions in the MIH-affected molars showing that restoration is not an adequate parameter for measuring the historical occurrence of caries. The first permanent molars may not necessarily be at an increased risk of caries due to MIH if the etiological factors for caries development are effectively managed.