bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deucravacitinib in Plaque Psoriasis: Laboratory Parameters Through 4 Years of Treatment in the Phase 3 POETYK PSO-1, PSO-2, and LTE Trials
Authors: Korman Neil J. , Passeron Thierry , Okubo Yukari , Bagel Jerry , Warren Richard B. , Spelman Lynda , Winthrop Kevin , Hoyt Kim , Scharnitz Thomas , Banerjee Subhashis , Thaçi Diamant , Shahriari Mona , Stein Gold Linda 
Published: November 2024

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was efficacious versus placebo and apremilast and was well tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) parent trials. At Week 52, patients could enroll in the ongoing POETYK long-term extension (LTE) (NCT04036435) trial and receive open-label deucravacitinib. Changes in blood laboratory parameters known to be associated with Janus kinase (JAK) 1,2,3 inhibitors were evaluated through 4 years of deucravacitinib treatment.
Methods: Changes from baseline in lipid (cholesterol, triglycerides), chemistry (alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine, creatine phosphokinase [CPK]), and hematology (hemoglobin, lymphocytes, neutrophils, platelets) parameters in the blood known to be affected by JAK1,2,3 inhibitors in clinical trials were evaluated through Week 208 (4 years; data cutoff, November 1, 2023). Treatment discontinuations due to laboratory abnormalities were assessed.
Results: A total of 1519 patients received ≥1 deucravacitinib dose (total exposure, 4392.8 person-years); 1203 (79.2%) had ≥52 weeks and 542 (35.7%) had ≥208 weeks of continuous deucravacitinib exposure (median, 185 weeks). No trends or clinically meaningful mean changes from baseline were observed in any of the above laboratory parameters. In total, 3 patients discontinued treatment due to increased CPK, and 1 patient each discontinued due to lymphopenia, abnormal hepatic function, increased ALT, and increased AST. Discontinuations due to triglyceride elevations were not observed.
Conclusion: In PSO-1/PSO-2/LTE, no trends or clinically meaningful mean changes from baseline were observed in lipid, chemistry, or hematology parameters, in contrast to signature changes (eg, increased cholesterol, creatinine, serum transaminases, CPK, cytopenias) observed with JAK1,2,3 inhibitors. Discontinuations due to laboratory abnormalities noted above were rare (n=7 events) through 4 years of deucravacitinib treatment. Results suggest deucravacitinib treatment does not warrant routine laboratory testing for all patients, in contrast with the requirements for JAK1,2,3 inhibitors, reflecting its selectivity for TYK2.
Deucravacitinib, an Oral Selective Tyrosine Kinase 2 (TYK2) Inhibitor, in Patients with Moderate to Severe Scalp Psoriasis: Efficacy and Safety Results of a Phase 3b/4, Multicenter, Randomized, Double-blinded, Placebo-controlled Trial (PSORIATYK SCALP)
Authors: Duffin Kristina Callis , Griffiths Christopher E. M. , Hoffmann Matthias , Blauvelt Andrew , Balagula Eugene , Napoli Andrew , Jou Ying-Ming , Dyme Rachel , Hala Virginia , Pinter Andreas , Lebwohl Mark 
Published: November 2024

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. PSORIATYK SCALP, an ongoing, 52-week, phase 3b/4, multicenter, randomized, double-blinded, placebo-controlled trial, evaluated deucravacitinib efficacy/safety in patients with moderate to severe scalp psoriasis, including those with more limited overall psoriasis.
Methods: Adults with moderate to severe scalp psoriasis defined by more focused and objective inclusion criteria (ss-PGA ≥3, scalp surface area involvement ≥20%, and PSSI ≥12 at baseline) and BSA involvement ≥3% were randomized 1:2 to oral placebo or deucravacitinib 6 mg once daily through Week 16. The primary efficacy outcome was ss-PGA 0/1; key secondary outcomes were PSSI 90, change from baseline in scalp-specific itch numeric rating scale (NRS), and sPGA 0/1 at Week 16. Efficacy outcomes were evaluated at Week 16 for the overall population and the subpopulation with global sPGA ≥3. Nonresponder imputation and modified baseline observation carried forward were used for patients who discontinued or had missing data for binary and continuous outcomes, respectively.
Results: 154 patients were randomized (placebo, n=51; deucravacitinib, n=103). Baseline characteristics were similar in each group (placebo: mean BSA 10.0%, PASI 9.4, PSSI 32.2; deucravacitinib: mean BSA 10.5%, PASI 10.2, PSSI 33.5). In the overall population, a higher proportion of patients receiving deucravacitinib versus placebo achieved ss-PGA 0/1 at Week 16 (48.5% vs 13.7%; P<0.0001). Deucravacitinib was superior to placebo for PSSI 90 (38.8% vs 2.0%; P<0.0001) and mean change from baseline in scalp-specific itch NRS (−3.2 vs −0.7; P<0.0001). In the subpopulation (sPGA ≥3), a greater proportion achieved sPGA 0/1 with deucravacitinib versus placebo (51.0% vs 4.3%; P<0.0001). The most common adverse events (AEs) in the deucravacitinib group (≥5%) were nasopharyngitis (14.6%), upper respiratory tract infection (11.7%), acne (9.7%), headache (7.8%), COVID-19 (5.8%), and pustular acne (5.8%). Two serious AEs were reported (1/group); neither was considered treatment related or led to discontinuation.
Conclusion: Deucravacitinib was efficacious and well tolerated in patients with moderate to severe scalp psoriasis, including those with less extensive overall psoriasis (BSA ≥3%). The overall psoriasis response rate (sPGA 0/1) was consistent with POETYK trial results, despite including patients with more limited BSA involvement. Safety findings were consistent with the known deucravacitinib safety profile.
Long-Term Maintenance of Optimal Treatment Targets for Skin and Itch Outcomes With Upadacitinib in Moderate-to-Severe Atopic Dermatitis: 140-Week Results From the Phase 3 Measure Up 1 and 2 Studies
Authors: Issa Naiem T , Chovatiya Raj , Talia Jordan , Torres Tiago , Eyerich Kilian , Calimlim Brian M , Yang Yang , Pechonkina Alena , Moreira Alvaro , Grada Ayman , Bunick Christopher G 
Published: November 2024

Introduction: Despite undergoing prolonged systemic therapy, many patients with moderate-to-severe atopic dermatitis (AD) do not achieve optimal targets for skin and itch outcomes as defined by Aiming High in Eczema/AD (AHEAD) recommendations (eg, ≥90% improvement from baseline in Eczema Area and Severity Index [EASI 90] and Worst Pruritus Numerical Rating Scale [WP-NRS] score of 0/1 [no/minimal itch]). We evaluated long-term maintenance of optimal treatment targets with upadacitinib, an oral selective JAK inhibitor approved for moderate-to-severe AD in adolescents and adults.
Methods: This 140-week interim analysis included adolescents and adults with moderate-to-severe AD who were randomized at baseline to upadacitinib 15 mg (UPA15) or 30 mg (UPA30) in the ongoing, phase 3, double-blind Measure Up 1 and 2 studies. Assessments included the proportion of patients (at the population level) who maintained EASI 90, WP-NRS 0/1, or simultaneous achievement of EASI 90 + WP-NRS 0/1 responses from week 16 (end of the placebo-controlled period) onwards. Data are reported as observed cases with no imputation for missing data.
Results: Among patients who achieved EASI 90 at week 16 (UPA15, n=298; UPA30, n=384), EASI 90 was maintained by 79.8% (UPA15) and 83.7% (UPA30) at week 52, 76.7% (UPA15) and 83.0% (UPA30) at week 100, and 74.0% (UPA15) and 84.2% (UPA30) at week 140. Of patients achieving WP-NRS 0/1 at week 16 (UPA15, n=193; UPA30, n=281), WP-NRS 0/1 was maintained by 69.4% (UPA15) and 72.0% (UPA30) at week 52, 65.6% (UPA15) and 68.4% (UPA30) at week 100, and 62.3% (UPA15) and 66.0% (UPA30) at week 140. Of patients simultaneously achieving EASI 90 + WP-NRS 0/1 at week 16 (UPA15, n=156; UPA30, n=243), maintenance was achieved by 68.1% (UPA15) and 70.8% (UPA30) at week 52, 62.7% (UPA15) and 66.5% (UPA30) at week 100, and 58.7% (UPA15) and 64.4% (UPA30) at week 140. Among patients who did not maintain optimal outcomes, most still achieved clinically meaningful responses.
Conclusion: Most patients maintained optimal skin and itch outcomes through 140 weeks of upadacitinib treatment, demonstrating its potential to provide sustained long-term disease control in atopic dermatitis.
Efficacy of Ritlecitinib in Patients with Alopecia Areata by Extent of Hair Loss: Results from the Phase 2b/3 and Phase 3 ALLEGRO Clinical Trials
Authors: Mostaghimi Arash , Kindred Cheshana , Herranz Pinto Pedro , Mizuashi Masato , Wajsbrot Dalia , Adejumo Rahmat , Tran Helen , Takiya Liza 
Published: November 2024

Introduction: Ritlecitinib, a dual JAK3/TEC family kinase inhibitor, demonstrated efficacy and safety in patients ≥12 years old with AA and ≥50% scalp hair loss in the phase 2b/3 ALLEGRO study. This post hoc, pooled analysis of the ALLEGRO-2b/3 and phase 3 ALLEGRO-LT studies evaluated the efficacy of ritlecitinib in patients with alopecia areata (AA) by extent of baseline scalp hair loss through Month 24.
Methods: Patients aged ≥12 years with AA and ≥50% scalp hair loss who received ritlecitinib 50 mg daily in ALLEGRO-2b/3 and rolled over to ALLEGRO-LT (continued to receive 50 mg) were included. Outcomes included the proportions of patients achieving response based on Severity of Alopecia Tool [SALT] score ≤20 (≤20% scalp hair loss), ≥2-grade improvement in eyebrow assessment [EBA] score (among patients with abnormal score at baseline), and ≥2-grade improvement in eyelash assessment [ELA] score (among patients with abnormal score at baseline). Patients were stratified by extent of scalp hair loss at baseline, defined as severe AA (SALT score 50-94) or very severe AA (SALT score 95-100), as per the Alopecia Areata Investigator Global Assessment (AA-IGA). Data as observed and imputed (last observation carried forward [LOCF]) are reported at the cutoff date (December 9, 2022).
Results: Of 191 patients included, 66 (34.6%) had severe AA and 125 (65.4%) had very severe AA at baseline. At Month 12, 64.4% and 34.3% (observed) and 60.6% and 29.6% (LOCF) of patients with severe AA and very severe AA, respectively, achieved SALT ≤20. At Month 24, these proportions increased to 70.2% and 54.8% (observed) and 63.6% and 36.8% (LOCF), respectively. EBA response was achieved in 54.6% and 46.9% (observed) and 52.8% and 42.4% (LOCF) of patients with severe AA and very severe AA, respectively, at Month 12; at Month 24, the proportions were 60.9% and 56.5% (observed) and 50.0% and 45.8% (LOCF). ELA response was achieved in 60.7% and 40.5% (observed) and 61.3% and 38.0% (LOCF) of patients with severe AA and very severe AA, respectively, at Month 12; at Month 24, the proportions were 70.0% and 45.3% (observed) and 61.3% and 38.0% (LOCF).
Conclusion: Ritlecitinib 50 mg daily achieves scalp, eyebrow, and eyelash hair regrowth in patients with severe and very severe AA.
Funding: This study was funded by Pfizer Inc
To evaluate and compare the effect of diabetes and complete denture wearing on the occurrence of Mucor isolates in edentulous geriatric patients
Authors: Yadav Kanchan , Yadav Bhupender , Malhotra Taniya , Sardar Moumita , Nagpal Abhishek , Shetty Omkar 
Published: November 2024

Objectives:
The objective of this study was to explore the impact of diabetes and complete denture use on the presence of Mucor isolates in edentulous geriatric patients.

Material and Methods:
Intraoral swab samples were collected using a sterile culture device, focusing on the center of the hard palate for all patient groups. Immediately after collection, each sample was immersed in a sterile culture-collecting device containing normal saline to prevent swab drying. Subsequently, these swabs were isolated and cultured in Sabouraud’s dextrose agar medium at a temperature range of 25–30°C.

Results:
Statistical analysis using the Chi-square test revealed no Mucor isolates in any of the four groups. However, the combination of diabetes and complete denture use led to the isolation of other commensal fungi in 65% of samples, contrasting with the non-diabetic, non-denture-wearing group where this occurrence was only 5%.

Conclusion:
The study concluded that there was no observable correlation between the occurrence of Mucor isolates in edentulous geriatric patients, irrespective of complete denture use, or diabetic status. Nevertheless, the coexistence of diabetes and complete denture use significantly increased the presence of opportunistic fungi in the oral cavity compared to non-diabetic, non-denture-wearing patients.
A rare case of spinal myeloid sarcoma
Authors: Deconinck Wouter , Bamps Sven , Steelandt Thomas , Wissels Maarten , Plazier Mark , Put Eric , Achahbar Salah-Eddine , Vanvolsem Steven , Meeuws Sacha , Klein Sam , Roosen Gert 
Published: November 2024

Background:
Myeloid sarcoma (MS), a rare extramedullary tumor composed of myeloid blast cells, is classified by the World Health Organization as a subtype of acute myeloid leukemia (AML). Isolated, primary, or nonleukemic MS has an incidence of 2/1,000,000 adults and constitutes only 0.7% of all AML cases. MS presentations vary widely, with spinal involvement being rare.

Case Description:
A-year-old male presented with interscapular pain radiating to the right upper arm/neck but was neurologically intact. Once diagnosed with isolated spinal MS, he underwent a surgical decompression followed by local irradiation, systemic chemotherapy, and bone marrow transplantation. Eight months postoperatively, however, he experienced a graft-versus-host rejection and required additional therapies.

Conclusion:
Establishing the diagnosis of MS is challenging and typically requires histological confirmation (i.e., the presence of myeloblasts and granulocytic cells). However, optimal treatment strategies remain elusive; despite radiation, chemotherapy, bone marrow transplant/other local therapies, the overall long-term prognosis for MS remains poor.
Giant cerebellar neurocysticercosis masquerading a primary central nervous system neoplasm – A case report with review of literature
Authors: Singh Kavindra , Singh Rahul , Sihag Rakesh K. , Kumar Arvind 
Published: November 2024

Background:
Neurocysticercosis (NCC) is one of the leading parasitic infections of the brain. Giant NCC is rare, with only two cases of cerebellar involvement reported till now. In the presence of a host immune response, these giant NCCs can mimic primary central nervous system neoplasms. The objective of this article is to report a rare case of giant cerebellar NCC and its management strategy with a literature review.

Case Description:
A young male presented with a giant cerebellar ring-enhancing mass with features of raised intracranial pressure, and surgical excision was done. The patient made an uneventful recovery.

Conclusion:
Surgical excision is safe for NCC, especially in the presence of a diagnostic dilemma.
Drug-resistant BRAF V600E-mutant recurrent pleomorphic xanthoastrocytoma, CNS WHO Grade 3 successfully resolved with incidental discontinuation of combined BRAF and MEK inhibitor therapy
Authors: Inoue Hirotaka , Kuroda Jun-Ichiro , Fujioka Yutaka , Hata Nobuhiro , Mizoguchi Masahiro , Yoshii Daiki , Sueyoshi Hiroyuki , Takeshima Yuki , Fujimoto Kenji , Shinojima Naoki , Sunami Kuniko , Mikami Yoshiki , Nakamura Hideo , Mukasa Akitake 
Published: November 2024

Background:
Combination therapy with BRAF and MEK inhibitor holds promise for treating gliomas harboring the BRAF V600E mutation; however, the development of acquired resistance remains a challenge.

Case Description:
We describe a case of repeated recurrent BRAF-mutant pleomorphic xanthoastrocytoma (central nervous system World Health Organization grade 3) treated with combination therapy with BRAF and MEK inhibitor. The patient received dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor); however, she developed resistance to the combination therapy. Remarkably, incidental drug discontinuation contributed to the disappearance of the resistant tumor. The same phenomenon was repeatedly observed after that. Genetic analysis demonstrated that the resistant tumor had BRAF V600E amplification; the resistant tumor remained BRAF→MEK→ERK pathway dependent, and drug resistance might be due to elevated BRAF V600E expression. We speculated that ERK1/2 signal extremes caused by the discontinuation of the combination therapy affected the resistant tumor survival.

Conclusion:
This case study provides important insights into novel treatment strategies and their underlying mechanisms for gliomas with BRAF mutations.
Combined transpetrosal-transtentorial approach with occipital artery – anterior inferior cerebellar artery bypass and aneurysm clipping for a lower basilar artery aneurysm involving anterior inferior cerebellar artery: Two-dimensional operative video
Authors: Duangprasert Gahn , Ota Nakao , Noda Kosumo , Tanikawa Rokuya 
Published: November 2024

Background:
Aneurysms of the lower basilar artery (BA) are rare, accounting for <1% of all intracranial aneurysms. This location has been described as “No man’s land” since it poses a potential challenge for microsurgery. Recently, endovascular treatment has become an alternative option; however, there are some disadvantages regarding the obliteration rate, patency of the parent, and perforating arteries.

Case Description:
We present the case of a 69-year-old female with an incidentally found lower BA aneurysm. The imaging examinations revealed a wide-neck aneurysm size of 8.5 mm arising just distal to the vertebrobasilar junction, with involvement of the left anterior inferior cerebellar artery (AICA). After a discussion with the patient, she opted to undergo the surgical treatment. We described the detailed steps of our surgical techniques in performing a combined transpetrosal-transtentorial approach. First, the occipital artery (OA) was harvested. Then, the posterior transpetrosal (retrolabyrinthine) and a far-lateral suboccipital approach were conducted with tentorial sectioning to expose the aneurysm. After AICA was confirmed to arise from the aneurysm sac, the OAAICA bypass was established to ensure AICA patency, followed by complete aneurysm clipping. The approach provided both the presigmoid and retrosigmoid corridors for bypass and clipping procedures, respectively. The patient tolerated the procedure well. Postoperative imaging examinations showed complete aneurysm obliteration and bypass patency without complications. She was discharged without neurological deficits (modified Rankin Scale 0).

Conclusion:
The combined transpetrosal approach is safe and effective for revascularization and clipping procedure for a lower BA aneurysm.
Вопросы кадрового обеспечения и финансирования инновационной деятельности малых предприятий
Authors: Ю.С. Коробова , С.Н. Яшин 
Published: November 2024

В качестве целей исследования выступает анализ современных тенденций и разработка комплекса мер по решению проблем кадрового обеспечения и финансирования инновационного развития малых предприятий. В статье обосновывается значимость малого предпринимательства в экономике, инновационном развитии страны и решении проблемы безработицы. Обозначены основные стратегические ориентиры государственной политики России в сфере малого и среднего предпринимательства. Проводится анализ динамики численности инновационно ориентированных работников и структуры затрат на реализацию инновационных товаров и услуг малых предприятий по видам инновационной деятельности и источникам финансирования. По результатам исследования, полученным на базе использования общелогических методов теоретического обобщения, выявлены негативные тенденции, сдерживающие инновационное развитие малых предприятий. Предлагаются пути повышения занятости населения в секторе малого инновационного бизнеса, а также комплекс мероприятий по созданию благоприятных условий для повышения кадрового потенциала и инновационного развития малого предпринимательства. Полученные в ходе исследования результаты могут быть полезны федеральным и региональным органам власти при принятии стратегических решений по поддержке малых предприятий.
POSSIBLE ERRORS IN THE DIAGNOSIS OF INTRAOCULAR TUMORS
Authors: Stoyukhina A. S. 
Published: November 2024

Rationale: The article discusses difficulties in the differential diagnosis of intraocular tumors (IOT), particularly in cases of small choroidal melanoma. Despite a substantial number of publications dedicated to the diagnosis of intraocular tumors, difficulties in interpreting imaging methods, such as optical coherence tomography (OCT), persist.Objective: to analyze the OCT patterns that have led to diagnostic errors.Methods: We analyzed the OCT results of 15 patients whose diagnosis of «choroidal hemangioma» was revised to «choroidal melanoma» in 11 cases or «progressive nevus» in 4 cases. The mean age at the time of IOT detection was 50.20±13.08 years (range: 35–79 years); the average tumor prominence was 2.22±0.82 mm (range: 1-3.6 mm), and the average diameter was 8.01±2.72 mm (range: 3.11–11.5 mm). A detailed analysis of the specific OCT patterns that led to diagnostic errors was conducted.Results and discussion: The characteristics of the identified OCT patterns that frequently caused diagnostic difficulties were thoroughly examined, such as cystic changes and the «subretinal cleft» phenomenon. Cases in which complex OCT patterns overlapped with both melanoma and hemangioma were also analyzed, reinforcing the need for a multimodal approach to the interpretation of imaging data. Conclusion: for accurate diagnosis and to avoid erroneous planning of treatment strategies, OCT should be evaluated within the context of the clinical picture and patient history.
THE RELATIONSHIP BETWEEN RETINAL PERFUSION AND FUNCTIONAL RECOVERING OF FOVEA IN DIFFERENT TYPES OF SURGICAL CLOSURE OF FULL-THICKNESS MACULAR HOLES
Authors: Doktorova T. А. , Boiko E. V. , Suetov A. A. , Sosnovskiy S. V. 
Published: November 2024

Rationale: The effect of retinal perfusion on functional recovery of the fovea, as well as the value of quantitative perfusion parameters as predictors of functional outcome in the surgical treatment of full-thickness macular holes (FTMH) remains poorly understood.Objective: To study the relationship between changes in retinal perfusion and functional parameters of the fovea in the postoperative period at 1 and 2 types of FTMH closure.Methods: A prospective study including 93 patients (93 eyes) with idiopathic FTMH stage 2-4 according to D. Gass after surgical treatment. In subgroups with type 1 and type 2 of FTMH closure, changes in the foveal avascular zone (FAZ) area and vessel density in the superficial and deep capillary plexuses (SCP and DCP) in the fovea, changes in BCVA, retinal sensitivity (RS) at the fixation point, and P1 amplitude in the fovea were studied. Studies were performed preoperatively, 1 and 6 months after surgery. A significant correlation was found between the changes in BCVA, RS at the fixation point, P1 amplitude in the fovea, and changes in vessel density in the SCP and DCP, which was more pronounced in the period from 1 to 6 months after surgery. The correlation of the changes in the parameters is higher in type 2 of FTMH closure than in type 1 of FTMH closure.Results:. Subgroups with type 1 and type 2 FTMH closure included 67 and 26 eyes, respectively. Type 2 FTMH closure showed lower vascular density in the DCP before (p=0.02) and 6 months after surgery (p=0.03), lower BCVA before surgery (p=0.03), 1 and 6 months after surgery (p <0.001), lower RS at the fixation point before and after surgery (p<0.002).Conclusion. In type 2 macular hole closure, postoperative changes in retinal perfusion have a more pronounced impact on functional recovery of the fovea, especially in the late postoperative period.