Once-daily upadacitinib versus placebo in adults with extensive non-segmental vitiligo: a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study.

Background: Janus kinase (JAK) inhibition is a promising approach for treating vitiligo. We aimed to assess the efficacy and safety of upadacitinib, an oral selective JAK inhibitor, in adults with non-segmental vitiligo. Methods: This was a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study completed at 33 clinical centres in the United States, Canada, France, and Japan. Eligible patients were aged 18-65 years with non-segmental vitiligo and had a Facial Vitiligo Area Scoring Index (F-VASI) ≥0.5 and a Total Vitiligo Area Scoring Index (T-VASI) ≥5. Patients were randomly assigned (2:2:2:1:1) using an interactive response technology to receive upadacitinib 6 mg (UPA6), upadacitinib 11 mg (UPA11), upadacitinib 22 mg (UPA22), or placebo (PBO; preassigned to switch to either UPA11 or UPA22 in period 2) once daily for 24 weeks (period 1). For weeks 24-52 (period 2), patients randomly assigned to upadacitinib continued their treatment, and patients receiving PBO switched to their preassigned upadacitinib dose in a blinded fashion. The primary endpoint was the percent change from baseline in F-VASI at week 24. Efficacy was analysed in the intention-to-treat population, and safety was examined in all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT04927975. Findings: Between June 16, 2021, and June 27, 2022, 185 patients (including 115 [62%] who were female and 70 [38%] who were male) were randomly assigned to UPA6 (n = 49), UPA11 (n = 47), UPA22 (n = 43), or PBO (n = 46). At week 24, the LS mean difference versus PBO in the percent change from baseline in F-VASI was -7.60 (95% CI -22.18 to 6.97; p = 0.3037) for UPA6, -21.27 (95% CI -36.02 to -6.52; p = 0.0051) for UPA11, and -19.60 (95% CI -35.04 to -4.16; p = 0.0132) for UPA22. The LS mean difference versus PBO in the percent change from baseline in T-VASI was -7.45 (95% CI -16.86 to 1.96; p = 0.1198) for UPA6, -10.84 (95% CI -20.37 to -1.32; p = 0.0259) for UPA11 and -14.27 (95% CI -24.24 to -4.30; p = 0.0053) for UPA22. Ongoing treatment with upadacitinib induced continuous skin repigmentation over time without reaching a plateau through week 52. The rates for study drug discontinuation and serious treatment-emergent adverse events (TEAEs) were higher in the UPA22 group than in the UPA11 and UPA6 groups. Eight serious TEAEs, including one death of unknown cause and one case of infiltrating lobular breast carcinoma, were reported through 52 weeks; only two serious TEAEs (coronary artery arteriosclerosis [UPA6 (n = 1)] and non-fatal ischemic stroke [UPA11 (n = 1)]) were deemed by the investigator to have a reasonable possibility of being related to study drug. The one case of breast cancer in the UPA11 group was deemed unrelated to study drug, and the one death of unknown cause in the UPA22 group was reviewed and adjudicated and was deemed to be unrelated to study drug. The most common TEAEs were COVID-19, headache, acne, and fatigue. No new safety signals were observed. Interpretation: Upadacitinib monotherapy led to substantial repigmentation of both facial and total body vitiligo lesions and may offer an effective treatment option for adults with extensive non-segmental vitiligo. Based on these findings, upadacitinib 15 mg is being investigated in adults and adolescents with non-segmental vitiligo in an ongoing phase 3 randomised controlled trial. Funding: AbbVie Inc.

Treatment Discontinuation in Patients with Psoriasis Treated with Biologics: A Retrospective Analysis of German Health Claims Data.

INTRODUCTION: Plaque psoriasis is a common, often debilitating, chronic autoimmune inflammatory skin disease. Moderate-to-severe forms of psoriasis can be treated with biologics such as anti-interleukin and anti-tumor necrosis factor antibodies. We aimed to investigate treatment discontinuation among patients with psoriasis who initiated biologic treatment. METHODS: We conducted a retrospective, non-interventional cohort study based on anonymized claims data from the German statutory health insurance which covered the years from 2016 to 2021. We included adult patients with psoriasis who initiated biologic treatment in drug-specific cohorts. Over a 365-day follow-up period, we assessed the frequencies and the time until treatment discontinuation for different biologics. Differences in discontinuation rates were compared using a multivariate Cox proportional hazards model. RESULTS: A total of 2565 patients with psoriasis who initiated treatment with secukinumab (n = 612), adalimumab (n = 454), guselkumab (n = 354), ixekizumab (n = 259), ustekinumab (n = 241), tildrakizumab (n = 205), brodalumab (n = 166), risankizumab (n = 145), etanercept (n = 91), certolizumab (n = 29), and infliximab (n = 9) were included. A total of 1290 patients (50.29%) discontinued treatment during the follow-up period, ranging from 30.34% (risankizumab) to 69.23% (etanercept). Median time until discontinuation of treatment ranged from 102 days (etanercept) to 208 days (risankizumab). Once the biologic treatment was discontinued, 45.05% of patients restarted the treatment with the same agent, 23.10% of patients switched to another biologic, and 31.86% received no further biologic agent. Compared to patients treated with risankizumab, the treatment discontinuation rate was significantly higher (p < 0.05) in patients treated with the other biologics except ustekinumab (p = 0.12). CONCLUSIONS: Further research should explore reasons leading to treatment discontinuation in order to support treatment choices for patients with moderate-to-severe psoriasis.

Enthesitis and Dactylitis Resolution with Risankizumab for Active Psoriatic Arthritis: Integrated Analysis of the Randomized KEEPsAKE 1 and 2 Trials.

INTRODUCTION: The presence (vs absence) of enthesitis/dactylitis is associated with greater psoriatic arthritis (PsA) activity and reduced health-related quality of life. Risankizumab, an interleukin 23 antagonist, demonstrated superior treatment efficacy over placebo in patients with PsA, including enthesitis/dactylitis. Herein, we report the efficacy of risankizumab on complete resolution of enthesitis and/or dactylitis and improvements in patient-reported outcomes in patients with PsA. METHODS: This integrated post hoc analysis of data from KEEPsAKE 1 and KEEPsAKE 2 included patients with baseline enthesitis (Leeds Enthesitis Index > 0) and/or dactylitis (Leeds Dactylitis Index > 0). Efficacy outcomes at weeks 24 and 52 included proportion of patients achieving enthesitis and/or dactylitis resolution and minimal clinically important differences (MCID) in pain, Health Assessment Questionnaire-Disability Index, and Functional Assessment of Chronic Illness Therapy-Fatigue. RESULTS: Of 1407 patients, approximately 63%, 28%, and 20% had baseline enthesitis, dactylitis, and both enthesitis/dactylitis, respectively. At week 24, higher response rates were observed for risankizumab vs placebo for resolution of enthesitis, dactylitis, and both enthesitis/dactylitis (differences of 13.9%, 16.9%, and 13.3%, respectively; p < 0.05). By week 52, risankizumab treatment resulted in complete resolution of enthesitis, dactylitis, and both enthesitis and dactylitis in 55.0%, 76.1%, and 52.3% of patients; similar resolution rates occurred among patients who switched from placebo to risankizumab. Among risankizumab-treated patients who achieved resolution of enthesitis and/or dactylitis, MCIDs were also attained in patient-reported pain, disability, and fatigue at week 24 (all p < 0.05; except fatigue in patients with resolution of both enthesitis/dactylitis); responses were sustained through week 52. CONCLUSIONS: Higher proportions of risankizumab-treated (vs placebo-treated) patients achieved enthesitis and/or dactylitis resolution and meaningful improvements in patient-reported outcomes at week 24 and generally sustained responses at week 52. Thus, risankizumab may result in sustained alleviation of PsA-related pathognomonic musculoskeletal lesions of enthesitis/dactylitis. GOV IDENTIFIERS: NCT03675308, and NCT03671148.

Early automated detection system for skin cancer diagnosis using artificial intelligent techniques.

Recently, skin cancer is one of the spread and dangerous cancers around the world. Early detection of skin cancer can reduce mortality. Traditional methods for skin cancer detection are painful, time-consuming, expensive, and may cause the disease to spread out. Dermoscopy is used for noninvasive diagnosis of skin cancer. Artificial Intelligence (AI) plays a vital role in diseases' diagnosis especially in biomedical engineering field. The automated detection systems based on AI reduce the complications in the traditional methods and can improve skin cancer's diagnosis rate. In this paper, automated early detection system for skin cancer dermoscopic images using artificial intelligent is presented. Adaptive snake (AS) and region growing (RG) algorithms are used for automated segmentation and compared with each other. The results show that AS is accurate and efficient (accuracy = 96%) more than RG algorithm (accuracy = 90%). Artificial Neural networks (ANN) and support vector machine (SVM) algorithms are used for automated classification compared with each other. The proposed system with ANN algorithm shows high accuracy (94%), precision (96%), specificity (95.83%), sensitivity (recall) (92.30%), and F1-score (0.94). The proposed system is easy to use, time consuming, enables patients to make early detection for skin cancer and has high efficiency.

Efficacy and Safety of Risankizumab for Active Psoriatic Arthritis: 100-Week Results from the KEEPsAKE 2 Randomized Clinical Trial.

INTRODUCTION: Long-term therapeutic options providing durable response and tolerability are needed for psoriatic arthritis (PsA). The ongoing KEEPsAKE 2 trial is evaluating risankizumab treatment in patients with active PsA who previously had inadequate response/intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) and/or 1-2 biologic DMARDs (bDMARD-IR). Herein, we report results through 100 weeks of treatment. METHODS: KEEPsAKE 2 is a global phase 3 trial. Patients with active PsA were randomized 1:1 to double-blind subcutaneous risankizumab 150 mg or placebo (weeks 0, 4, and 16). At week 24, all patients received open-label risankizumab every 12 weeks until end of study. Efficacy endpoints included achieving ≥ 20% improvement in PsA symptoms using American College of Rheumatology criteria (ACR20), attaining minimal disease activity (MDA; meeting ≥ 5/7 criteria of low disease activity and extent), and improving in other measures. RESULTS: At the cutoff date, 345/443 (77.9%) patients were ongoing in the study. ACR20 was achieved in 57.1% and 52.5% of the continuous risankizumab and placebo/risankizumab cohorts, respectively, at week 100 and in 60.0% and 55.8%, respectively, at week 52. In week 52 responders, maintenance of ACR20 at week 100 was achieved in 74.8% (continuous risankizumab) and 78.7% (placebo/risankizumab) of patients. In the continuous risankizumab and placebo/risankizumab cohorts, respectively, MDA was achieved by 33.0% and 33.3% of patients at week 100 and by 27.2% and 33.8% at week 52. Among MDA responders at week 52, maintenance of MDA response was achieved by 83.6% and 73.0% of the continuous risankizumab and placebo/risankizumab cohorts, respectively. Risankizumab was well tolerated through week 100. CONCLUSIONS: Risankizumab demonstrated durable efficacy and tolerability through 100 weeks; most patients who achieved ACR20 and MDA responses at week 52 maintained this achievement through week 100. There were no new safety signals in patients who had csDMARD-IR and bDMARD-IR. TRIAL REGISTRATION: ClinicalTrials.gov NCT03671148.

Risankizumab, a biologic disease-modifying antirheumatic drug, helps control the body's immune system to reduce symptoms of psoriatic arthritis (a disease that inflames the joints of people who have the skin condition psoriasis). The ongoing KEEPsAKE 2 study is evaluating how well risankizumab works and how safe it is for treating adult patients with active psoriatic arthritis who previously experienced inadequate response to one or more specific types of disease-modifying anti-arthritis drugs. Patients were randomly assigned to receive either risankizumab or an inactive drug; after 24 weeks, all patients received risankizumab. At study week 100, 57% of patients who were assigned to receive continuous risankizumab since the start of the study experienced a 20% or more improvement in a measure of psoriatic arthritis symptoms using criteria established by the American College of Rheumatology (ACR20); a similar proportion of patients achieved a 20% improvement at both weeks 24 and 52. Similarly, 56% and 53% of patients who switched from inactive drug to risankizumab achieved ACR20 at weeks 52 and 100 (more than before switching to risankizumab at week 24). Minimal disease activity (MDA) was evaluated by assessing joint and skin symptoms, affected body surface area, pain, and physical function. At week 100, 33% of patients achieved MDA (both groups), which was similar to week 52. Most patients who achieved ACR20 or MDA at week 52 maintained responses at week 100. Improvements with risankizumab were seen in several other measures of treatment outcomes through week 100. Risankizumab was generally safe through 100 weeks.

Efficacy and Safety of Risankizumab for Active Psoriatic Arthritis: 100-Week Results from the Phase 3 KEEPsAKE 1 Randomized Clinical Trial.

INTRODUCTION: Patients with psoriatic arthritis (PsA) require treatment providing durable long-term efficacy in different disease domains as well as safety. We present 100-week efficacy and safety results of risankizumab in patients with active PsA and previous inadequate response/intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR). METHODS: KEEPsAKE 1 (NCT03675308) is a global phase 3 study, including a 24-week, double-blind, placebo-controlled and ongoing open-label extension periods. Patients were randomized 1:1 to receive risankizumab 150 mg or placebo at baseline and weeks 4 and 16. After week 24, all patients received open-label risankizumab every 12 weeks thereafter. Patients were evaluated through 100 weeks. Endpoints included achieving ≥ 20% reduction in American College of Rheumatology criteria for symptoms of rheumatoid arthritis (ACR20), minimal disease activity (MDA; defined as ≥ 5/7 criteria of low disease activity and extent), and other measures. RESULTS: Overall, 828/964 (85.9%) patients completed week 100. For patients receiving continuous risankizumab, 57.3%, 70.6%, and 64.3% achieved ACR20 at weeks 24, 52, and 100, respectively. For the placebo/risankizumab cohort, 33.5% achieved ACR20 at week 24 but increased after switching to active treatment at weeks 52 (63.7%) and 100 (62.1%). In ACR20 responders at week 52, 81.2% of both treatment cohorts maintained response at week 100. MDA was achieved by 25.0%, 38.3%, and 38.2% of the continuous risankizumab cohort at weeks 24, 52, and 100. In the placebo/risankizumab cohort, 10.2% achieved MDA at week 24, increasing at weeks 52 (28.0%) and 100 (35.2%). MDA response was maintained at week 100 in week 52 responders in the continuous risankizumab (75.5%) and placebo/risankizumab cohorts (78.2%). Similar trends were observed for other efficacy measures. Risankizumab was generally well tolerated through 100 weeks. CONCLUSIONS: For patients with active PsA who are csDMARD-IR, risankizumab demonstrated durable long-term efficacy and was generally well tolerated, with a consistent long-term safety profile. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03675308.

Psoriatic arthritis (PsA) often affects individuals with the skin condition psoriasis. A biologic disease-modifying antirheumatic drug can help control inflammation and regulate the immune system to ease symptoms and slow progression of PsA. The ongoing KEEPsAKE 1 study is evaluating the efficacy and safety of risankizumab in patients with active PsA who previously have not had success with ≥ 1 conventional disease-modifying antirheumatic drug. Patients were initially treated with risankizumab 150 mg (continuous risankizumab group) or inactive drug (inactive drug/risankizumab group). After 24 weeks, all received risankizumab for the rest of the study. At week 100, 64% (continuous risankizumab group) and 62% (inactive drug/risankizumab group) of patients had ≥ 20% improvement in PsA symptoms (measured using American College of Rheumatology [ACR20] criteria). Both groups showed similar percentages at week 52 and improvement from week 24. In patients who achieved ACR20 at week 52, 81% maintained their ACR20 response at week 100. Minimal disease activity was defined as a combination of joint and skin symptoms, affected body surface area, pain, and physical functioning. At week 100, 38% of the continuous risankizumab group and 35% of the inactive drug/risankizumab group achieved minimal disease activity. Percentages were similar at week 52 and higher than week 24 in both groups. In patients who achieved minimal disease activity at week 52, 81% maintained response at week 100. All other measures of treatment responses showed similar patterns from the start of risankizumab through week 100. Risankizumab was considered generally safe by the treating physicians.

Influence of titanium dioxide nanoparticles and/or cadmium chloride oral exposure on testicular morphology, oxidative stress, and apoptosis in rats: Ameliorative role of co-enzyme Q10.

Background and objectives: Little is known about the implications of titanium dioxide nanoparticles (TiO2NPs) and cadmium chloride (Cd) co-exposure on the male reproductive system in mammals. As a result, this study researched the effects of oral TiO2NPs and/or Cd exposure on male reproduction and testicular functions. Additionally, a mitigation trial with co-enzyme Q10 (CoQ10) has also been conducted. Methods: In a 60-day experiment, seven experimental groups, each containing 10 male Sprague Dawley rats, were orally given distilled water (control), corn oil (vehicle control), CoQ10 (10 mg/kg b.wt), TiO2NPs (50 mg/kg b.wt), Cd (5 mg/kg b.wt), TiO2NPs + Cd, and TiO2NPs + Cd + CoQ10. Then, sperm quality, male sex hormones, oxidative stress indications, Ti and Cd testicular residues, testes and accessory gland architecture, and apoptotic and inflammatory markers in rat testes were assessed. Results: TiO2NPs and/or Cd exposure negatively impacted body weight, weight gain, testicular weights, semen quality, serum reproductive hormones, oxidative stress parameters, and Caspase-3 and tumor necrosis factor (TNF-α) immunoreactions. Histopathological changes were recorded in testicular, seminal vesicle, and prostatic tissues. Yet, co-administration of CoQ10 with TiO2NPs and Cd substantially mitigated these adverse consequences. The most notable aspect is that it effectively lowered testicular tissue Ti and Cd levels. It also improved oxidant status, hormonal profile, and sperm picture. CoQ10 minimized the testicular damage implied by histological examination. Furthermore, CoQ10 significantly diminished TiO2NPs and Cd-induced Caspase-3 and TNF-α immunoexpression in testicular tissue. Conclusion: As a result, CoQ10 could be utilized as a safe remedy to protect male reproductive physiology from TiO2NPs and Cd damage.

Interactive effects of cadmium and titanium dioxide nanoparticles on hepatic tissue in rats: Ameliorative role of coenzyme 10 via modulation of the NF-κB and TNFα pathway.

This study investigated the effect of oral dosing of titanium dioxide nanoparticles (TNPs) and cadmium (Cd2+) on rat liver and the potential protective role of coenzyme Q10 (CQ10) against TNPs and Cd2+-induced hepatic injury. Seventy male Sprague Dawley rats were divided into seven groups and orally given distilled water, corn oil, CQ10 (10 mg/kg b.wt), TNPs (50 mg/kg b.wt), Cd2+ (5 mg/kg b.wt), TNPs + Cd2+, or TNPs + Cd2++CQ10 by gastric gavage for 60 successive days. The results showed that individual or mutual exposure to TNPs and Cd2+ significantly increased the serum levels of various hepatic enzymes and lipids, depleted the hepatic content of antioxidant enzymes, and increased malondialdehyde. Moreover, the hepatic titanium and Cd2+ content were increased considerably in TNPs and/or Cd2+-exposed rats. Furthermore, marked histopathological perturbations with increased immunoexpression of tumor necrosis factor-alpha and nuclear factor kappa B were evident in TNPs and/or Cd2+-exposed rats. However, CQ10 significantly counteracted the damaging effect of combined exposure of TNPs and Cd2+ on the liver. The study concluded that TNPs and Cd2+ exposure harm hepatic function and its architecture, particularly at their mutual exposure, but CQ10 could be a candidate protective agent against TNPs and Cd2+ hepatotoxic impacts.

Closure of Tracheocutaneous Fistulae in Patients With Challenged Wound Healing.

OBJECTIVE: To describe and evaluate the surgical outcomes of multilayered closure of persistent tracheocutaneous fistulae (TCF) in patients with challenged wound healing. METHODS: A retrospective chart review of all patients who underwent closure of TCF by the senior author between October 2011 and December 2021 was performed. Age, body mass index (BMI), time between decannulation and TCF repair, medical comorbidities, procedure duration, length of hospitalization, and postoperative complications were recorded. The primary outcomes were closure of the fistula, postoperative subcutaneous emphysema, pneumomediastinum, pneumothorax, wound infection, or breakdown. Outcomes of patients with and without challenged wound healing were compared. RESULTS: Thirty-five patients who underwent TCF repair during the study period were identified. The mean age and BMI were 62.9 years and 28.43 respectively. Twenty-six (74%) patients met criteria for challenged wound healing at the time of the TCF repair. There was 1 (3.84%) minor complication in the challenged wound healing group and none (0%) in the control group (P = 1.00). No patients experienced wound breakdown or air leak noted on exam or chest radiography. CONCLUSION: Multilayered closure of persistent tracheocutaneous fistulae is a simple technique which is safe and effective even in patients with challenged wound healing.

Synthesis, characterization and protective efficiency of novel polybenzoxazine precursor as an anticorrosive coating for mild steel.

In this study, 2-[(E)-(hexylimino)methyl] phenol (SA-Hex-SF) was synthesized by adding salicylaldehyde (SA) and n-hexylamine (Hex-NH2), which was subsequently reduced by sodium borohydride to produce 2-[(hexylamino)methyl] phenol (SA-Hex-NH). Finally, the SA-Hex-NH reacted with formaldehyde to give a benzoxazine monomer (SA-Hex-BZ). Then, the monomer was thermally polymerized at 210 °C to produce the poly(SA-Hex-BZ). The chemical composition of SA-Hex-BZ was examined using FT-IR, 1H, and 13C NMR spectroscopy. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and X-ray Diffraction (XRD), respectively, were used to examine the thermal behavior, surface morphology, and crystallinity of the SA-Hex-BZ and its PBZ polymer. Mild steel (MS) was coated by poly(SA-Hex-BZ) which was quickly prepared using spray coating and thermal curing techniques (MS). Finally, the electrochemical tests were used to evaluate the poly(SA-Hex-BZ)-coating on MS as anti-corrosion capabilities. According to this study, the poly(SA-Hex-BZ) coating was hydrophobic, and corrosion efficiency reached 91.7%.

Risankizumab improved health-related quality of life, fatigue, pain and work productivity in psoriatic arthritis: results of KEEPsAKE 1.

OBJECTIVES: PsA is a heterogeneous disease that impacts many aspects of social and mental life, including quality of life. Risankizumab, an antagonist specific for IL-23, is currently under investigation for the treatment of adults with active PsA. This study evaluated the impact of risankizumab vs placebo on health-related quality of life (HRQoL) and other patient-reported outcomes (PROs) among patients with active PsA and inadequate response or intolerance to conventional synthetic DMARD (csDMARD-IR) in the KEEPsAKE 1 trial. METHODS: Adult patients with active PsA (n = 964) were randomized (1:1) to receive risankizumab 150 mg or placebo. PROs assessed included the 36-Item Short-Form Health Survey (SF-36, v2), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), EuroQoL-5 Dimension-5 Level (EQ-5D-5L), Patient's Assessment of Pain, Patient's Global Assessment (PtGA) of Disease Activity, and Work Productivity and Activity Impairment-PsA (WPAI-PsA) questionnaire. Least squares (LS) mean change from baseline at week 24 was compared between risankizumab and placebo. RESULTS: At week 24, differences between groups were observed using LS mean changes from baseline in SF-36 physical component summary and mental component summary; FACIT-Fatigue; EQ-5D-5L; Patient's Assessment of Pain; PtGA; all eight SF-36 domains (all nominal P < 0.001); and the WPAI-PsA domains of impairment while working (presenteeism), overall work impairment and activity impairment (all nominal P < 0.01). CONCLUSION: Risankizumab treatment resulted in greater improvements in HRQoL, fatigue, pain and work productivity in patients with active PsA who have csDMARD-IR, when compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03675308.

Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from the KEEPsAKE 1 study.

OBJECTIVE: PsA is a chronic disease with heterogeneous clinical manifestations requiring treatment options with long-term efficacy and safety. In this follow-up analysis, the 52-week efficacy and safety of risankizumab 150 mg in patients with active PsA who had previous inadequate response/intolerance to one or more conventional synthetic DMARDs (csDMARD-IR) were evaluated. METHODS: KEEPsAKE 1 is an ongoing, global, phase 3 study with a 24-week, double-blind, placebo-controlled period (period 1) and an open-label extension period (period 2). In period 1, eligible patients were randomized 1:1 to receive subcutaneous risankizumab 150 mg or placebo at weeks 0, 4 and 16. At week 24 (period 2), all continuing patients received open-label risankizumab 150 mg every 12 weeks through week 208. RESULTS: At week 24, 57.3% of risankizumab-treated patients (n = 483) achieved ≥20% improvement in ACR criteria (ACR20) vs 33.5% of placebo-treated patients (n = 481; P < 0.001). At week 52, 70.0% of patients who were randomized to receive continuous risankizumab therapy and 63.0% of patients who were randomized to receive placebo in period 1 and then receive risankizumab at week 24 achieved ACR20. Similar result trends were observed for other efficacy measures. Risankizumab was well tolerated through 52 weeks of treatment with a consistent safety profile from week 24 through week 52. CONCLUSION: In patients with active PsA who were csDMARD-IR, continuous risankizumab treatment demonstrated robust long-term efficacy and was well tolerated through 52 weeks of treatment. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, KEEPsAKE1, NCT03675308.

Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from the KEEPsAKE 2 study.

OBJECTIVE: PsA is a chronic inflammatory disease in which the skin and joints are affected. In this follow-up analysis, the 52-week efficacy and safety of risankizumab 150 mg in patients with active PsA who had previous inadequate response/intolerance to one or two biologic therapies (Bio-IR) or one or more conventional synthetic DMARDs (csDMARD-IR) were evaluated. METHODS: In the ongoing, phase 3, KEEPsAKE 2 trial, patients with active PsA were randomized 1:1 to receive subcutaneous risankizumab 150 mg or placebo at weeks 0, 4 and 16 (period 1). At week 24 (period 2), patients who received placebo were switched to risankizumab, and all patients received risankizumab 150 mg every 12 weeks from weeks 28 to 208. RESULTS: At week 24, 51.3% of risankizumab-treated patients (n = 224) achieved ≥20% improvement in ACR criteria (ACR 20) vs 26.5% of placebo-treated patients (n = 220; P < 0.001). At week 52, 58.5% of patients randomized to receive continuous risankizumab achieved ACR20, and 55.7% of patients who switched from placebo to risankizumab at week 24 achieved ACR20. Similar trends were observed for other efficacy measures. Rates of serious treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation remained stable through week 52, and no deaths were reported. CONCLUSION: Risankizumab was well tolerated and improved symptoms of PsA in Bio-IR/csDMARD-IR patients, with a consistent long-term safety profile from weeks 24 to 52. TRIAL REGISTRATION: United States National Library of Medicine clinical trials database www.clinicaltrials.gov; KEEPsAKE 2; NCT03671148.

A Novel Low-Cost Technique to Allow for Jet Ventilation.

BACKGROUND/OBJECTIVE: Traditional jet ventilation requires the use of a catheter that is inserted either through an endotracheal tube or laryngoscope. Specially designed laryngoscopes with a built-in luer lock adapter to which the high-pressure tubing may be attached exist but are not always available. We present our experience with an adapter which allows connection of the high-pressure tubing to the suction side port of suitable laryngoscopes that is easily assembled using readily available materials in the operating room. METHOD: We designed a jet ventilator adapter using a high-pressure jet ventilation tubing assembly and a 3-way stopcock extension set which we have used for the past 13 years. A retrospective case series of all adult patients who underwent direct laryngoscopy and/or bronchoscopy using this jet ventilation adapter between January 2017 and August 2021 was performed. RESULT: A total of 100 consecutive patients underwent laryngoscopy and bronchoscopy using jet ventilation between January 2017 and August 2021 was identified. The mean age was 56.3 years, and the mean BMI was 31.2. The most common diagnoses were idiopathic subglottic/tracheal stenosis (46.4%), acquired tracheal stenosis (34.1%), and acquired subglottic stenosis (14.8%). The median duration of the surgical procedure was 53 minutes with an interquartile range of 23. The CO2 laser was used in all cases. There was no disconnection of the adapter, episodes of postoperative respiratory compromise, or extraluminal air on chest radiography for any of our cases. Oxygen saturations remained above 90% intraoperatively for all cases. CONCLUSION: Our simple jet ventilator adapter connects the jet ventilator to the suction side port of suitable laryngoscopes and eliminates the need for a jet ventilation catheter or specialized laryngoscope at a minimal cost.

Reversible Bevacizumab Induced Vocal Fold Necrosis.

BACKGROUND: As the use of anti-angiogenic treatments is gaining scope in the treatment of various malignancies, there are increasing reports of laryngeal side effects. We report two cases of laryngeal necrosis and dysphonia. METHODS: Two patients with gynecological malignancies presented with severe dysphonia 11-24 months after initiation of bevacizumab therapy. Videostroboscopic examination of the larynx revealed bilateral ulcerations and eschar of the superior surface with absent mucosal waves. RESULTS: Patients were treated with discontinuation of the bevacizumab, vocal rest, and proton pump inhibitors. Both had improvement in voice and resolution of the eschar and ulceration. Shallow sulci and mild breathiness persisted in one patient. CONCLUSION: With increasing use of potent systemic anti-angiogenic compounds, clinicians should be vigilant of this important complication of therapy. Time to onset of symptoms and reversibility of symptoms vary by patient and require further study. There may be long-term voice sequelae.

Postoperative management of Zenker's diverticulum: Results of the American Bronchoesophagological Association survey.

INTRODUCTION: Although treatment of Zenker's diverticulum (ZD) is commonly performed by otolaryngologists using a variety of surgical techniques, there is little published data on the postoperative management of patients. We sought to determine practice patterns among members of the American Bronchoesophagological Association (ABEA) after surgery for ZD. METHODS: An online questionnaire was designed via JotForm™ and subsequently sent to active members of the ABEA. Responses were analyzed using descriptive statistics. RESULTS: Twenty-three members (6.6 %) completed the survey. Most (73.9 %) were fellowship trained in laryngology and reported performing >5 procedures per year. Most laryngologists reported employing multiple techniques including transcervical (TC) (73.9 %), endoscopic stapling (ES) (65.2 %), endoscopic CO2 laser (EL) (56.5 %), and endoscopic harmonic scalpel (EH) (4.3 %). Postoperatively, 52.3 % of respondents placed patients in 23-hour observation after TC, 66.7 % after ES, 69.2 % after EL, and 100 % after EH. 47.1 % of respondents used standard overnight admission after TC, as compared to 13.3 % after ES, 23.1 % after EL and 0 % after EH. Postoperative esophagography was utilized by 70.6 % of respondents after TC, 20 % after ES, 38.5 % after EL, and 100 % after EH. A peroral diet was started postoperatively on the day of surgery by 26.7 % respondents after ES but not after any of the other techniques. CONCLUSION: Most laryngology trained respondents employ multiple techniques for the treatment of ZD including at least 1 endoscopic technique. Respondents were more likely to hospitalize patients after a transcervical than endoscopic approach. Postoperative esophagography was utilized in most patients after TC, but not after ES or EL. Most respondents admit patients for 23-hour observation and start a peroral diet on postoperative day 1 regardless of technique.

Improved patient-reported outcomes in patients with psoriatic arthritis treated with risankizumab: analysis of the Phase 3 trial KEEPsAKE 2.

OBJECTIVES: Determine the impact of 24-week risankizumab (RZB) versus placebo (PBO) on patient-reported outcomes (PROs) in patients with psoriatic arthritis (PsA) and inadequate response to one or two biologics (Bio-IR) and/or ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR). METHODS: Patients in the Phase 3 trial, KEEPsAKE 2, were randomised (1:1) to RZB 150 mg or PBO by subcutaneous injection. PROs assessed: 36-Item Short-Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), Patient's Assessment of Pain by visual analogue scale (VAS), Patient's global assessment of disease activity (PtGA), EuroQoL-5 Dimension-5 Level (EQ-5D-5L) and Work Productivity and Activity Impairment-PsA (WPAI-PsA). Least squares mean change from baseline at week 24 was compared between RZB versus PBO by mixed-effects repeated regression modelling. RESULTS: At week 24, RZB versus PBO treatment resulted in significant differences (95% CIs) in mean change from baseline in ranked secondary endpoints SF-36 physical component summary score (3.9 (2.4 to 5.3); p<0.001) and FACIT-Fatigue (2.2 (0.6 to 3.9); p=0.009) and improvements in pain (-8.1 (-12.8 to -3.5)), PtGA (-8.8 (-13.5 to -4.2)) and EQ-5D-5L index (0.08 (0.04 to 0.11)) and VAS (5.9 (1.9 to 9.8)) (all nominal p<0.01). More RZB-treated versus PBO-treated patients reported improvements from baseline at week 24 in 7 of 8 SF-36 subdomains (nominal p<0.05). At week 24, more RZB-treated versus PBO-treated patients reported improvements in 3 of 4 WPAI-PsA domains (nominal p≤0.01). CONCLUSION: Overall, RBZ treatment resulted in improvements in pain, fatigue, health-related quality of life and ability to perform work in Bio-IR and/or csDMARD-IR patients with PsA. TRIAL REGISTRATION NUMBER: NCT03671148.

Effective Range of FSSW Parameters for High Load-Carrying Capacity of Dissimilar Steel A283M-C/Brass CuZn40 Joints.

In the current study, a 2 mm thick low-carbon steel sheet (A283M-Grade C) was joined with a brass sheet (CuZn40) of 1 mm thickness using friction stir spot welding (FSSW). Different welding parameters including rotational speeds of 1000, 1250, and 1500 rpm, and dwell times of 5, 10, 20, and 30 s were applied to explore the effective range of parameters to have FSSW joints with high load-carrying capacity. The joint quality of the friction stir spot-welded (FSSWed) dissimilar materials was evaluated via visual examination, tensile lap shear test, hardness test, and macro- and microstructural investigation using SEM. Moreover, EDS analysis was applied to examine the mixing at the interfaces of the dissimilar materials. Heat input calculation for the FSSW of steel-brass was found to be linearly proportional with the number of revolutions per spot joint, with maximum heat input obtained of 11 kJ at the number of revolutions of 500. The temperature measurement during FSSW showed agreement with the heat input dependence on the number of revolution. However, at the same revolutions of 500, it was found that the higher rotation speed of 1500 rpm resulted in higher temperature of 583 °C compared to 535 °C at rotation speed of 1000 rpm. This implies the significant effect for the rotation speed in the increase of temperature. The macro investigations of the friction stir spot-welded joints transverse sections showed sound joints at the different investigated parameters with significant joint ligament between the steel and brass. FSSW of steel/brass joints with a number of revolutions ranging between 250 to 500 revolutions per spot at appropriate tool speed range (1000-1500 rpm) produces joints with high load-carrying capacity from 4 kN to 7.5 kN. The hardness showed an increase in the carbon steel (lower sheet) with maximum of 248 HV and an increase of brass hardness at mixed interface between brass and steel with significant reduction in the stir zone hardness. Microstructural investigation of the joint zone showed mechanical mixing between steel and brass with the steel extruded from the lower sheet into the upper brass sheet.

COVID-19 Tracheostomy Outcomes.

OBJECTIVES: (1) Assess overall COVID-19 mortality in ventilated patients with and without tracheostomy. (2) Determine the impact of tracheostomy on mechanical ventilation duration, overall length of stay (LOS), and intensive care unit (ICU) LOS for patients with COVID-19. STUDY DESIGN: Case series with planned chart review. SETTING: Single-institution tertiary care center. METHODS: Patients with COVID-19 who were ≥18 years old and requiring invasive positive pressure ventilation (IPPV) met inclusion criteria. Patients were stratified into 2 cohorts: IPPV with tracheostomy and IPPV with intubation only. Cohorts were analyzed for the following primary outcome measures: mortality, LOS, ICU LOS, and IPPV duration. RESULTS: An overall 258 patients with IPPV met inclusion criteria: 46 (18%) with tracheostomy and 212 (82%) without (66% male; median age, 63 years [interquartile range, 18.75]). Average LOS, time in ICU, and time receiving IPPV were longer in the tracheostomy cohort (P < .01). Ability to wean from IPPV was similar between cohorts (P > .05). The number of deaths in the nontracheostomy cohort (54%) was significantly higher than the tracheostomy cohort (29%, P < .01). CONCLUSIONS: While tracheostomy placement in patients with COVID-19 did not shorten overall LOS, mechanical ventilation duration, or ICU LOS, patients with a tracheostomy experienced a significantly lower number of deaths vs those without. One goal for tracheostomy is improved pulmonary toilet with associated shortened IPPV requirements. Our study did not identify this advantage among the COVID-19 population. However, this study demonstrates that the need for tracheostomy in the COVID-19 setting does not portent a poor prognostic factor, as patients with a tracheostomy experienced a significantly higher survival rate than their nontracheostomy counterparts.

Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial.

OBJECTIVES: Risankizumab is an interleukin-23 inhibitor under study for the treatment of patients with psoriatic arthritis (PsA). The phase 3 KEEPsAKE 2 trial investigated the efficacy and safety of risankizumab versus placebo in patients with active PsA who had previous inadequate response or intolerance to ≤2 biological therapies (Bio-IR) and/or ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR). Results through week 24 are reported here. METHODS: Adults with PsA who were Bio-IR and/or csDMARD-IR were randomised to receive subcutaneously administered risankizumab 150 mg or placebo at weeks 0, 4 and 16 during a 24-week, double-blind treatment period. The primary endpoint was the proportion of patients who achieved ≥20% improvement in American College of Rheumatology score (ACR20) at week 24. Secondary endpoints assessed key domains of PsA and patient-reported outcomes. RESULTS: A total of 444 patients (median age 53 years, range 23-84 years) were randomised to risankizumab (n=224) or placebo (n=220); 206 patients (46.5%) were Bio-IR. At week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (51.3% vs 26.5%, p<0.001) and all secondary endpoints (p<0.05) compared with placebo. Serious adverse events were reported for 4.0% and 5.5% of risankizumab-treated and placebo-treated patients, respectively; serious infections were reported for 0.9% and 2.3%, respectively. CONCLUSION: Treatment with risankizumab resulted in significant improvements versus placebo in key disease outcomes and was well tolerated in patients with PsA who were Bio-IR and/or csDMARD-IR. TRIAL REGISTRATION NUMBER: NCT03671148.