Săpături arheologice la biserica reformată din Tăuții Măgheruși (jud. Maramureș)

A Máramaros megyei Miszmogyorós (rom. Tăuții Măgherăuș) Nagybányától nyugatra, 11 km távolságra helyezkedik el. Református temploma a város központi részén található, a régi Tótfalu/Misztótfalu részen. A templomot a Nagybánya-Szatmár DN 1C nemzeti út veszi körül. A 2009 tavaszán a templom alapozása mellett végzett drénezési munkálatok kapcsán került sor megelőző régészeti feltárásra. A kutatás célja a templom építéstörténetének és a hozzá tartozó temető kapcsolatának megállapítása, annak időrendjének tisztázása volt. A régészeti kutatás során két szelvényt jelöltek ki: az SI/2009 felületet a templom déli falával merőlegesen nyitották, a templomhajó és a szentély találkozásánál, míg az S II/2009-est a szentély északi külső falával párhuzamosan nyitották a 16. században elfalazott sekrestyeajtó előtt. A kutatás során megállapították, hogy az S I/2009 szelvényben a templomhajó és a szentély alapozása és felmenő fala között létezik egy falelválás, ami arra utal, hogy ezek különböző fázisokban épültek. Mindezt a megállapítást alátámasztja az alapozás mélysége, a falszövet összetétele és a habarcs állaga. A falak környeztéből nem került elő leletanyag, amely alapján keltezni lehetne ezeket az építési periódusokat. Az \ud ásatás a templom körüli temető 27 temetkezését tárta fel. Figyelembe véve azt, hogy a temető csak részben kutatott, így a feltárt temetőrészlet alapján jelen elemzés csak részeredményeket tartalmaz és tájékoztató jellegű. Kiemelném azt a tényt is, hogy egy katolikus eredetű templomról és közösségről van szó, amely áttért a református vallásra, így a feltárt temetkezések elkülönítése és keltezése viszonylag nehéz feladatot jelent. Más temetőfeltárásokhoz hasonlóan, ahol sikerült elkülöníteni a katolikus és protestáns temetkezésket (lásd. Szentábrahám, Telekfalva, Teke), a miszmogyorósi református templom esetében ez nem volt lehetséges. A szegényes leletanyag alapján a temető használatának periódusát a 16-18. századra határozhatjuk meg

IL-4Rα Blockade by Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Atopic Dermatitis.

Dupilumab is a fully human antibody to interleukin-4 receptor α that improves the signs and symptoms of moderate to severe atopic dermatitis (AD). To determine the effects of dupilumab on Staphylococcus aureus colonization and microbial diversity on the skin, bacterial DNA was analyzed from swabs collected from lesional and nonlesional skin in a double-blind, placebo-controlled study of 54 patients with moderate to severe AD randomized (1:1) and treated with either dupilumab (200 mg weekly) or placebo for 16 weeks. Microbial diversity and relative abundance of Staphylococcus were assessed by DNA sequencing of 16S ribosomal RNA, and absolute S. aureus abundance was measured by quantitative PCR. Before treatment, lesional skin had lower microbial diversity and higher overall abundance of S. aureus than nonlesional skin. During dupilumab treatment, microbial diversity increased and the abundance of S. aureus decreased. Pronounced changes were seen in nonlesional and lesional skin. Decreased S. aureus abundance during dupilumab treatment correlated with clinical improvement of AD and biomarkers of type 2 immunity. We conclude that clinical improvement of AD that is mediated by interleukin-4 receptor α inhibition and the subsequent suppression of type 2 inflammation is correlated with increased microbial diversity and reduced abundance of S. aureus

Use of systemic therapies in adults with atopic dermatitis:12-month results from the European prospective observational study in patients eligible for systemic therapy for atopic dermatitis (EUROSTAD)

Background The European Prospective Observational Study in Patients Eligible for Systemic Therapy for Atopic Dermatitis (EUROSTAD) is an ongoing observational study aiming to describe characteristics of patients with atopic dermatitis (AD) treated with systemic therapy over time and the management of their disease in a real-world setting. Methods Data from patients enrolled in EUROSTAD between March 2017 and April 2019 were analyzed for systemic therapy use and treatment change over 12 months. Results 288 patients reported taking systemic medications; 42.7% received cyclosporine, 35.3% dupilumab, 28.1% methotrexate, 25.4% oral corticosteroids, 6.8% azathioprine, 6.1% injectable corticosteroids, and 3.4% mycophenolate. The median duration of treatment was 1.1 months for oral systemic corticosteroids, 3.2 months for injectable corticosteroids, 4.8 months for cyclosporine, 7.3 months for methotrexate, and 14.9 months for dupilumab. The most frequent reasons for stopping treatment included lack of efficacy, patient decision, adverse events, and disease well controlled. Conclusion The 12-month interim EUROSTAD study analysis highlights the current trends and outcomes of systemic treatments for moderate-to-severe AD. Among all systemic treatments for AD, dupilumab was the least likely to be discontinued, whereas cyclosporine and corticosteroids, whilst effective, were primarily limited to episodic flare management consistent with treatment guidelines

Dupilumab significantly improves sleep in adults with atopic dermatitis: results from the 12-week placebo-controlled period of the 24-week phase 4 randomized double-blinded placebo-controlled DUPISTAD study

BACKGROUND Sleep disturbance is a prominent symptom of atopic dermatitis (AD) and can result in insomnia, daytime fatigue, drowsiness, reduced productivity and impaired quality of life (QoL). OBJECTIVES The Dupilumab Effect on Sleep in AD Patients (DUPISTAD) phase IV randomized double-blinded placebo-controlled study evaluated the impact of dupilumab treatment on sleep and other patient- and physician-reported outcomes. METHODS Adults with moderate-to-severe AD were randomized 2 : 1 to dupilumab 300 mg once every 2 weeks (q2w) or placebo for 12 weeks; concomitant topical corticosteroids were permitted. Patients subsequently entered an open-label phase and received dupilumab 300 mg q2w for a further 12 weeks. The primary endpoint was the percentage change in sleep quality from baseline to week 12, assessed using a novel numeric rating scale (NRS). Secondary and exploratory endpoints included percentage change in peak pruritus NRS (PP NRS), change in SCORing Atopic Dermatitis (SCORAD), SCORAD sleep visual analogue scale (VAS), Eczema Area and Severity Index, Patient-Reported Outcomes Measurement Information System (PROMIS) sleep-related impairment T-score and the Epworth Sleepiness Scale. Sleep diary and wrist actigraphy measurements were recorded throughout the study. RESULTS In total, 127 patients received dupilumab and 61 patients received placebo. Demographic and baseline disease characteristics were balanced between groups. Sleep quality NRS significantly improved in patients treated with dupilumab by week 12 vs. placebo [least squares mean of the difference (LSMD) -15.5%, P < 0.001]. PP NRS (LSMD -27.9%, P < 0.001), SCORAD (LSMD -15.1, P < 0.001), SCORAD sleep VAS (LSMD -2.1, P < 0.001) and PROMIS T-score (LSMD -3.6, P < 0.001) were also significantly improved at week 12 with dupilumab vs. placebo. The overall percentage of patients reporting treatment-emergent adverse events was lower in the dupilumab group (56.7%) than in the placebo group (67.2%). CONCLUSIONS Dupilumab significantly improved sleep quality and perception of sleep continuity, itch, metrics of AD severity and QoL in adults with moderate-to-severe AD, with an acceptable safety profile compared with placebo

IL-4R alpha blockade by dupilumab decreases Staphylococcus aureus colonization and increases microbial diversity in atopic dermatitis

Dupilumab is a fully human antibody to interleukin-4 receptor alpha that improves the signs and symptoms of moderate to severe atopic dermatitis (AD). To determine the effects of dupilumab on Staphylococcus aureus colonization and microbial diversity on the skin, bacterial DNA was analyzed from swabs collected from lesional and nonlesional skin in a double-blind, placebo-controlled study of 54 patients with moderate to severe AD randomized (1:1) and treated with either dupilumab (200 mg weekly) or placebo for 16 weeks. Microbial diversity and relative abundance of Staphylococcus were assessed by DNA sequencing of 16S ribosomal RNA, and absolute S. aureus abundance was measured by quantitative PCR. Before treatment, lesional skin had lower microbial diversity and higher overall abundance of S. aureus than nonlesional skin. During dupilumab treatment, microbial diversity increased and the abundance of S. aureus decreased. Pronounced changes were seen in nonlesional and lesional skin. Decreased S. aureus abundance during dupilumab treatment correlated with clinical improvement of AD and biomarkers of type 2 immunity. We conclude that clinical improvement of AD that is mediated by interleukin-4 receptor alpha inhibition and the subsequent suppression of type 2 inflammation is correlated with increased microbial diversity and reduced abundance of S. aureus

Dupilumab improves patient-reported symptoms of atopic dermatitis, symptoms of anxiety and depression, and health-related quality of life in moderate-to-severe atopic dermatitis : analysis of pooled data from the randomized trials SOLO 1 and SOLO 2

Background: Atopic dermatitis (AD) profoundly affects quality of life (QoL). Dupilumab significantly improves clinical outcomes, is well tolerated, and approved to treat inadequately controlled moderate-to-severe AD in adults; however, its effect on patient-reported outcomes (PROs) is not fully characterized. Objective: To evaluate the impact of dupilumab on patient-reported AD symptoms and QoL. Methods: Pooled data were analyzed from two identically designed phase 3 studies, LIBERTY AD SOLO 1 (NCT02277743) and SOLO 2 (NCT02277769), assessing the following PROs: Peak Pruritus Numerical Rating Scale (NRS), Pruritus Categorical Scale, SCORing AD (SCORAD), Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), Hospital Anxiety and Depression Scale (HADS), five-dimension EuroQoL questionnaire (EQ-5D), and patient-assessed disease status and treatment effectiveness. Results: Dupilumab rapidly improved (vs. placebo) Peak Pruritus NRS scores by day 2 (p <.05), anxiety and depression (HADS), and QoL (DLQI) by week 2, and maintained through week 16 (p <.0001). At week 16, more dupilumab-treated than placebo-treated patients reported improvement in SCORAD itch and sleep, and no pain/discomfort (EQ-5D) (p <.0001). Limitations: Cultural differences of translated PROs. Conclusion: Dupilumab had a significant, positive impact on AD symptoms, including itch, sleep, pain, anxiety and depression, and QoL in adults with moderate-to-severe AD.Peer reviewe

Baseline Demographics, Comorbidities, Treatment Patterns and Burden of Atopic Dermatitis in Adults and Adolescents from the GLOBOSTAD Long-Term Observational Study

Introduction - Insights into real-world treatment of atopic dermatitis (AD) are relevant to clinical decision making. The aim of this analysis was to characterize patients who receive dupilumab for AD in a real-world setting. Methods - The GLOBOSTAD registry is an ongoing, longitudinal, prospective, observational study of patients with AD who receive dupilumab according to country-specific prescribing information. We report baseline characteristics, comorbidities and treatment patterns for patients enrolled from July 11, 2019 to March 31, 2022. Analyses are descriptive; no formal statistical comparisons were performed. Results - Nine hundred fifty-two adults and adolescents were enrolled in GLOBOSTAD. Patients had a high disease burden before starting dupilumab: (mean [standard deviation]) percent body surface area affected (44.8 [24.42]), Eczema Area and Severity Index total score (24.8 [12.95]), SCORing Atopic Dermatitis total score (60.5 [16.34]), Patient-Oriented Eczema Measure total score (19.7 [6.37]) and Dermatology Life Quality Index total score (13.7 [7.02]). Overall, 741 (77.8%) patients reported ≥ 1 type 2 inflammatory comorbidities, most frequently allergic rhinitis (492 [51.7%]), asthma (323 [33.9%]), food allergy (294 [30.9%]) or another allergy (274 [28.8%]). In the previous 12 months, 310 (32.6%) patients had received systemic non-steroidal immunosuppressants and 169 (17.8%) systemic corticosteroids; 449 (47.2%) had received topical corticosteroids, most commonly potent topical corticosteroids; 141 (14.8%) had received topical calcineurin inhibitors and 32 (3.4%) ultraviolet therapy. Most (713 [74.9%]) patients started dupilumab because of prior treatment failure. Conclusion - Patients enrolled in GLOBOSTAD demonstrated considerable multidimensional burden of disease across AD signs, symptoms and quality of life despite previous use of systemic and non-systemic AD treatments

Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study

BACKGROUND: Significant unmet need exists for long-term treatment of moderate to severe atopic dermatitis (AD). OBJECTIVE: To assess the long-term safety and efficacy of dupilumab in patients with AD. METHODS: This ongoing, multicenter, open-label extension study (NCT01949311) evaluated long-term dupilumab treatment in adults who had previously participated in phase 1 through 3 clinical trials of dupilumab for AD. This analysis examined patients given 300 mg dupilumab weekly for up to 76 weeks at data cutoff (April 2016). Safety was the primary outcome; efficacy was also evaluated. RESULTS: Of 1491 enrolled patients (1042.9 patient-years), 92.9% were receiving treatment at cutoff. The safety profile was consistent with previously reported trials (420.4 adverse events/100 patient-years and 8.5 serious adverse events/100 patient-years), with no new safety signals; common adverse events included nasopharyngitis, conjunctivitis, and injection-site reactions. Sustained improvement was seen up to 76 weeks in all efficacy outcomes, including measures of skin inflammation, pruritus, and quality of life. LIMITATIONS: Lack of control arm, limited number of patients with 76 weeks or longer of treatment (median follow-up, 24 weeks), and patients not receiving the approved dose regimen of 300 mg every 2 weeks. CONCLUSION: The safety and efficacy profile from this study supports the role of dupilumab as continuous long-term treatment for patients with moderate to severe AD

Conjunctivitis in Dupilumab Clinical Trials for Adolescents with Atopic Dermatitis or Asthma

Background: Conjunctivitis is a known comorbidity of atopic dermatitis. Dupilumab clinical trials for moderate-to-severe atopic dermatitis in adults showed a higher conjunctivitis incidence for dupilumab-treated patients than placebo-treated patients, whereas trials for uncontrolled asthma reported lower rates for both dupilumab and placebo. Objective: The objective of this study was to evaluate the incidence and severity of conjunctivitis in dupilumab clinical trials in adolescents with moderate-to-severe atopic dermatitis or uncontrolled asthma. Methods: We evaluated the incidence of conjunctivitis in adolescents (aged 12 to < 18 years) in three phase III trials. Ocular events were diagnosed and treated based on patient-reported symptoms and an external eye examination by study investigators, in most cases without an ophthalmologic referral. In LIBERTY AD ADOL (16-week, randomized, placebo-controlled, double-blinded trial), adolescents with moderate-to-severe atopic dermatitis were randomized to subcutaneous placebo, dupilumab 300 mg every 4 weeks, or dupilumab every 2 weeks (200 mg, patients < 60 kg at baseline; 300 mg, ≥ 60 kg at baseline). In LIBERTY AD PED-OLE (open-label extension), pediatric patients from previous dupilumab atopic dermatitis trials received dupilumab 2 mg/kg or 4 mg/kg weekly (up to 300 mg) or 300 mg every 4 weeks. In LIBERTY ASTHMA QUEST (randomized, double-blinded, placebo-controlled trial), patients with uncontrolled moderate-to-severe asthma were randomized to 52 weeks of add-on therapy with dupilumab 200 or 300 mg every 2 weeks or matched-volume placebo. Results: In ADOL, more dupilumab-treated (17/165; 10.3%) than placebo-treated patients (4/85; 4.7%) reported one or more conjunctivitis event. All events were mild to moderate in severity; 12 (7.3%) dupilumab-treated and 4 (4.7%) placebo-treated patients received treatment. Most patients with conjunctivitis (dupilumab, 12/17; placebo, 4/4) recovered/resolved during the treatment period. The risk of conjunctivitis showed no relationship with dupilumab serum concentration. In PED-OLE, 12/275 adolescents (4.4%) reported one or more conjunctivitis event. Most conjunctivitis events were mild to moderate. Ten patients received treatment for conjunctivitis. Ten patients recovered/resolved during the study. In QUEST, similar low proportions of dupilumab-treated (2/68, 2.9%) and placebo-treated (1/39, 2.6%) adolescents reported one or more conjunctivitis event. All events were mild to moderate. One dupilumab-treated patient received treatment for conjunctivitis. All cases recovered/resolved during the study. No patients in these trials discontinued study treatment temporarily or permanently because of conjunctivitis. In ADOL, one case of unspecified viral keratitis (specific viral etiology not known) in the dupilumab 300-mg every 4 weeks group and one case of allergic blepharitis in the placebo group were reported; both events resolved during the treatment period, and neither led to treatment discontinuation. Conclusions: Dupilumab-treated adolescents in atopic dermatitis trials had a higher incidence of conjunctivitis than placebo-treated patients, whereas overall rates of conjunctivitis among adolescents in the asthma trial were lower than in atopic dermatitis trials and were similar for dupilumab- and placebo-treated patients. Most events were mild to moderate, most recovered/resolved, and none prompted study withdrawal. These results are similar to those reported in adult trials and support a drug–disease interaction. ClinicalTrials.gov Identifiers: NCT03054428, NCT02612454, NCT02414854. [MediaObject not available: see fulltext.

The Omnis Barbaria Experimental Archaeology Camp for Children – First Edition

Like in many other European countries, during the past 15 years, Romania has seen an increased interest by archaeologists and history enthusiasts towards the reconstruction of artefacts and certain phenomenal aspects of the past. Whether the study approached a theoretical (Sima 2002, 77-82; Barbu 2015, 779-793) or practical aspect, such as reconstruction of housing (Cotiugă 2009, 303-342), workshops (Ardeleanu 2012, 72-73), ritual pits (Ardeleanu 2015, 59-96), textiles (Torcică 2015, 219-230), stonework (Zăgreanu 2010, 361-363) or weapons (Borangic 2007-2008, 44-62; Borangic 2013, 821-836; Borangic, Barbu 2013, 22-47) all these archaeological experiments were conducted in order to find out and partially explain some issues of history that would otherwise remain unknown to researchers or to the general public