Determination of phenytoin at trace levels in domestic wastewater and synthetic urine samples by gas chromatography-mass spectrometry after its preconcentration by simple liquid-phase microextraction.

This work presents a sensitive and accurate analytical method for the determination of phenytoin at trace levels in domestic wastewater and synthetic urine samples by gas chromatography-mass spectrometry (GC-MS) after the metal sieve-linked double syringe liquid-phase microextraction (MSLDS-LPME) method. A metal sieve was produced in our laboratory in order to disperse water-immiscible extraction solvents into aqueous media. Univariate optimization studies for the selection of proper extraction solvent, extraction solvent volume, mixing cycle, and initial sample volume were carried out. Under the optimum MSLDS-LPME conditions, mass-based dynamic range, limit of quantitation (LOQ), limit of detection (LOD), and percent relative standard deviation (%RSD) for the lowest concentration in calibration plot were figured out to be 100.5-10964.2 µg kg-1, 150.6 µg kg-1, 45.2 µg kg-1, and 9.4%, respectively. Detection power was improved as 187.7-folds by the developed MSLDS-LPME-GC-MS system while enhancement in calibration sensitivity was recorded as 188.0-folds. In the final step of this study, the accuracy and applicability of the proposed system were tested by matrix matching calibration strategy. Percent recovery results for domestic wastewater and synthetic urine samples were calculated as 95.6-110.3% and 91.7-106.6%, respectively. These results proved the accuracy and applicability of the proposed preconcentration method, and the obtained analytical results showed the efficiency of the lab-made metal sieve apparatus.

Survival in systemic sclerosis associated pulmonary arterial hypertension in the current treatment era-results from a nationwide study.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a leading cause of mortality in systemic sclerosis (SSc). This nationwide study aims to describe real world treatment characteristics and assess survival rates of patients with SSc-PAH. METHODS: In this retrospective cohort study, patients with SSc-PAH were identified from Turkish Ministry of Health National Electronic Database (from January 2016 to September 2022), using ICD-10 codes. Data on demographics, treatment characteristics, and death was collected. Kaplan-Meier curves were used to calculate cumulative probabilities of survival at 1, 3, and 5 years. RESULTS: Five hundred forty-seven patients (90.7% female) with SSc-PAH were identified. Median age at PAH diagnosis was 59.9 (50.0-67.4) years. During a median follow-up duration of 3.2 (1.5-4.8) years, 199 (36.4%) deaths occurred. Estimated survival rates at 1, 3, and 5 years were 90.2%, 73.2%, and 56.6%, respectively. Survival was similar among patients with and without interstitial lung disease (p = 0.20). Patients who used immunosuppressives had better survival than those who did not (p < 0.001). No difference was observed in survival rates according to initial PAH-specific treatment regimen (monotherapy or combination) (p = 0.49). CONCLUSION: Compared to most of historical cohorts, higher survival rates for SSc-PAH were observed in this study. Early diagnosis of PAH may have contributed to these findings. The impact of immunosuppressive therapy on prognosis of SSc-PAH needs to be further investigated in prospective studies. Key Points • Early diagnosis is pivotal for better outcomes in SSc-PAH. • Implementation of PAH treatment guidelines in routine clinical practice is still poor and should be improved. • Effect of immunosuppressive therapies on disease course has to be defined in SSc-PAH.

Unveiling cancer risk in ANCA-associated vasculitis: result from the Turkish Vasculitis Study Group (TRVaS).

To investigate cancer incidence in patients with ANCA-associated vasculitis (AAV), compare it with the age/sex-specific cancer risk of the Turkish population, and explore independent risk factors associated with cancer. This multicenter, incidence case-control study was conducted using the TRVaS registry. AAV patients without cancer history before AAV diagnosis were included. Demographic and AAV-related data of patients with and without an incident cancer were compared. Standardized cancer incidence rates were calculated using age-/sex-specific 2017 Turkish National Cancer Registry data for cancers (excluding non-melanoma skin cancers). Cox regression was performed to find factors related to incident cancers in AAV patients. Of 461 AAV patients (236 [51.2%] male), 19 had incident cancers after 2022.8 patient-years follow-up. Median (IQR) disease duration was 3.4 (5.5) years, and 58 (12.6%) patients died [7 with cancer and one without cancer (log-rank, p = 0.04)]. Cancer-diagnosed patients were older, mostly male, and more likely to have anti-PR3-ANCA positivity. The cumulative cyclophosphamide dose was similar in patients with and without cancer. Overall cancer risk in AAV was 2.1 (SIR) ((1.3-3.2), p = 0.004); lung and head-neck [primary target sites for AAV] cancers were the most common. In Cox regression, male sex and ≥ 60 years of age at AAV diagnosis were associated with increased cancer risk, while receiving rituximab was associated with decreased cancer risk. Cancer risk was 2.1 times higher in AAV patients than the age-/sex-specific cancer risk of the Turkish population population, despite a high rate of rituximab use and lower dose of cyclophosphamide doses. Vigilance in cancer screening for AAV patients covering lung, genitourinary, and head-neck regions, particularly in males and the elderly, is vital.

Clinical Characteristics and Outcomes of Polyarteritis Nodosa: An International Study.

OBJECTIVE: We describe the demographics, clinical features, disease course, and survival of polyarteritis nodosa (PAN) through an international collaboration (GLOBAL-PAN). METHODS: Patients with PAN were recruited between 1990 and 2020 from observational cohorts of nine countries across Europe, Japan, and North America. Eligibility was retrospectively defined using the European Medicines Agency classification algorithm. Patients with PAN related to hepatitis B virus (n = 12) and two monogenic diseases mimicking PAN, deficiency of adenosine deaminase 2 enzyme (n = 16) or familial Mediterranean fever (n = 11), were excluded. Data regarding organ involvement, relapse, disease-related damage, and survival were analyzed. RESULTS: Three hundred fifty-eight patients (female:male ratio 174:184), including those with systemic PAN (sPAN, n = 282) and cutaneous PAN (n = 76), were included. Twenty-five were pediatric onset. Mean ± SD age at diagnosis was 44.3 ± 18.1 years. Constitutional symptoms (71.5%), cutaneous involvement (70.5%), musculoskeletal findings (69.1%), and neurologic features (48.0%) were common manifestations. Among patients with sPAN, gastrointestinal involvement and proteinuria over 400 mg/day were reported in 52.2% and 11.2%, respectively. During a median (interquartile range) 59.6 (99.5) months of follow-up, relapse occurred in 48.5% of patients. One, 5- and 10-year survival rates for sPAN were 97.1%, 94.0%, and 89.0%, respectively. Predictors of death for sPAN included age ≥65 years at diagnosis, serum creatinine at diagnosis >140 µmol/L, gastrointestinal manifestations, and central nervous system (CNS) involvement. CONCLUSION: The spectrum of PAN remains a complex, multifaceted disease. Relapse is common. Age ≥65 years and serum creatinine >140 µmol/L at diagnosis, as well as gastrointestinal and CNS involvement, are independent predictors of death in sPAN.

Factors that predict development of chronic kidney disease in patients with rheumatoid arthritis receiving biologic DMARDs and mortality rates.

OBJECTIVES: We aimed to determine the choice of biologic/targeted synthetic disease-modifying anti-rheumatic drugs (b/ts-DMARDs), factors associated with the development of chronic kidney disease (CKD), and mortality in RA patients with CKD receiving b/ts-DMARDs. METHODS: Two thousand one hundred forty-one RA (79.4% female) patients were included in the analysis from the HUR-BIO prospective registry. Patients were divided into the CKD group and the non-CKD group. Age and gender-matched patients were selected from the non-CKD group, and then three main groups were determined. CKD was staged according to the glomerular filtration rate criteria. The clinical characteristics of the patients, disease activities, treatment choices, drug retention rate, and mortality rates were compared between the groups. RESULTS: CKD was detected in 90/2141 (4.2%) RA patients on b/ts-DMARDs. Forty patients (2.3%) developed CKD during follow-up after the initiation of b/ts-DMARDs. In the CKD group, anti-TNF agents were chosen as the first-line b/ts-DMARDs therapy in 64.4% of patients, with etanercept leading in 31 (34.4%) patients. In multivariate analysis, age at the start of treatment, DAS-28-ESR at last visit, amyloidosis, hypertension, and history of smoking were the factors associated with the development of CKD in RA patients receiving b/ts-DMARDs. The mortality rate in RA-CKD patients until the onset of the pandemic was 15.41 per 1000 patient years, whereas it was 85.9 per 1000 patient years after the pandemic. CONCLUSION: Comorbidities and control of disease activity are critical in the development of CKD in RA patients receiving b/ts-DMARDs. While there was no significant difference in mortality rate between CKD and non-CKD patients, the overall mortality rate increased after the COVID-19 pandemic duration in both groups.

Apical fibrobullous lung disease in spondyloarthritis patients with biologic DMARDs indication.

OBJECTIVE: The rate of pleuroparenchymal involvement in patients with SpA varies widely, from 0% to 85%. The most common form is apical fibrobullous disease (AFLD). The aim of this study was to determine the incidence of AFLD and associated factors in SpA patients under and/or planned to start biologic DMARDs (bDMARDs) therapy. METHODS: The records of 3021 SPA patients registered with HUR-BIO who had indication of bDMARDs between 2010 and 2021 were scanned. The study included 2489 patients with at least one chest radiograph (X-ray). Patient demographics, comorbidities, laboratory data, bDMARDs used, baseline DASs, and purified protein derivative and/or QuantiFERON test results before initiation of bDMARDs were recorded. RESULTS: Of the 2489 patients, 36 (1.4%) were found to have AFLD by X-ray and/or CT. The mean disease duration was 11.7 (7.1) years. Patients with AFLD were more likely to be male [28 (77.8%) vs 1321 (53.9%), P = 0.004], older [56.3 (10.5) years vs 44.8 (11.4) years, P < 0.001], heavy smokers [27 (79.4%) vs 1468 (60.9%), P = 0.028] and have had longer disease duration [17. 7 (9.7) years vs 11.6 (7) years, P = 0.001]. QuantiFERON positivity was higher in the AFLD group [9 (36%) vs 309 (16.1%), P = 0.013]. While treatment with adalimumab was less preferred in those with AFLD, treatment with etanercept was more frequently preferred. CONCLUSION: As the radiological findings of AFLD can be confused with those of tuberculosis, special attention should be paid to differentiating between tuberculosis and the disease in males and in patients who have had long disease duration.

The dietary acid load is associated with disease severity in psoriatic arthritis (PsA).

OBJECTIVES: An acidogenic diet, by disrupting the blood pH equilibrium, can contribute to metabolic acidosis and lead to inflammation. Therefore, we hypothesized that dietary acid load (DAL) increases disease activity and inflammation in PsA patients. METHODS: This study was conducted with 58 obese/overweight patients, aged 20-65 years. Dietary intake was assessed using a 3-consecutive-day 24-hour recall. The DAL was evaluated through the PRAL (potential renal acid load) and NEAP (net endogenous acid production) and divided into the low and high groups by their median values. The disease activity assessments, anthropometric measurements, dietary data and blood parameters of patients were recorded and compared at the low and high DAL groups. RESULTS: We observed that patients in the high NEAP and PRAL groups had worse PsA pattern scores (p<0.05). Also, PRAL and NEAP scores were positively associated with DAPSA, HAQ, and PSAID-12 scores. After adjusting age, sex, smoking, and BMI, 1 mEq increase in PRAL and NEAP was associated with an elevation of DAPSA (0.506 and 0.486 points, respectively). CONCLUSIONS: These results showed a close relationship between DAL and PsA symptoms. An acidogenic diet may negatively affect PsA prognosis. Healthy eating recommendations should be part of the management of the disease.

Proceedings of the GRAPPA 2022 Executive Retreat.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) leadership congregated for a strategic planning meeting before the 2022 GRAPPA annual meeting in New York, USA. Meeting aims were to review GRAPPA's performance in relation to its 2016 goals and identify successes and areas for further improvement, identify key GRAPPA priorities and activities for the next 5 years, and explore committee structures to best support these aims.

Young-GRAPPA (Y-GRAPPA) at the 2022 GRAPPA Annual Meeting: One Year in Y-GRAPPA. Where Do We Stand, Where Do We Go?

Young-GRAPPA (Y-GRAPPA) was introduced at the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting. Here we present the 1-year progress of Y-GRAPPA and future plans of this enthusiastic group of young clinicians and early career researchers interested in psoriasis and psoriatic arthritis.

Hematologic Malignancy Risk in Inflammatory Arthritis Patients Treated with TNF Inhibitors: The Real-Life Data from the HUR-BIO Registry.

INTRODUCTION: This study aimed to assess the incidence of hematologic malignancy (HM) among inflammatory arthritis (IA) patients receiving tumor necrosis factor inhibitors (TNFi) compared with the general Turkish population. METHODS: HUR-BIO (Hacettepe University Rheumatology Biologic Registry) is a single-center biological disease-modifying anti-rheumatic drug (bDMARD) registry since 2005. Patients with IA, including rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis who had at least one visit after the TNFi were screened from 2005 to November 2021. Standardized incidence rates (SIR) were calculated after adjustment for age and gender and compared with the 2017 Turkish National Cancer Registry (TNCR). RESULTS: Of the 6139 patients registered in the HUR-BIO, 5355 used any TNFi at least once. The median follow-up duration was 2.6 years for patients receiving TNFi. Thirteen patients developed a HM on follow-up. In these patients, the median age at the IA onset was 38 (range, 26-67), and the median age at the HM diagnosis was 55.5 (range, 38-76). Patients using TNFi had an increased HM incidence (SIR 4.23, 95% confidence interval (CI) 2.35-7.05). Ten patients with HM were under 65 years of age. In this group, there was a higher incidence of HM in both men (SIR 5.15, 95% CI 1.88-11.43) and women (SIR 4.76, 95% CI 1.74-10.55). CONCLUSIONS: The risk of HMs in inflammatory arthritis patients receiving TNFi was four times higher than in the general Turkish population.

Evaluation of plaque index, gingival index and oral health-related quality of life in obese patients / Evaluación del índice de placa, índice gingival y calidad de vida relacionada con la salud bucal en pacientes obesos

Obesity is a chronic disease that may be related to caries, periodontitis, xerostomia, and dental erosion, as well as increasing morbidity and mortality. The aim of this study was to evaluate the plaque index (Silness & Löe, 1964), the gingival index (Löe & Silness, 1963), and the oral health-related quality of life (OHRQoL) in obese patients. The study included 45 extremely obese, 45 obese, and 45 normal-weight individuals between the ages of 18 and 58. The plaque index and gingival index of the individuals were determined by clinical examination by probing. In addition, the Oral Health Impact Profile-14 (OHIP-14) questionnaire was used for the OHRQoL. The IBM SPSS Statistic 22.0 software program was used for the statistical evaluation of the study data. The plaque index and gingival index values were statistically higher in obese compared to normal weight individuals (p0.05). There was no statistically significant difference between the OHIP-14 total scores of the groups (p>0.05). Increased apparent plaque index and gingival index values in obese patients may adversely affect periodontal health.

La obesidad es una enfermedad crónica que puede estar relacionada con caries, periodontitis, xerostomía y erosión dental, además de aumentar la morbimortalidad. El objetivo de este estudio fue evaluar el índice de placa, el índice gingival y la calidad de vida relacionada con la salud bucal (CVSB) en pacientes obesos. El estudio incluyó a 45 individuos extremadamente obesos, 45 obesos y 45 de peso normal entre las edades de 18 y 58 años. El índice de placa y el índice gingival de los individuos se determinaron mediante examen clínico y sondaje periodontal. Además, se utilizó el cuestionario Oral Health Impact Profile-14 (OHIP-14) para la evaluación CVSB. Se utilizó el programa informático IBM SPSS Statistic 22.0 para la evaluación estadística. Los valores del índice de placa y del índice gingival fueron estadísticamente más altos en obesos en comparación con los individuos de peso normal (p0,05). No hubo diferencia estadísticamente significativa entre las puntuaciones totales de OHIP-14 de los grupos (p>0,05). El aumento del índice de placa aparente y los valores del índice gingival en pacientes obesos pueden afectar negativamente la salud periodontal.

Mortality in psoriatic arthritis patients, changes over time, and the impact of COVID-19: results from a multicenter Psoriatic Arthritis Registry (PsART-ID).

BACKGROUND: This study aimed to assess the mortality of PsA before and during the COVID-19 pandemic. METHODS: From the prospective, multicenter PsART-ID (Psoriatic Arthritis Registry-International Database), patients from Turkey were analyzed by linking the registry to the Turkish Cause of Death Registry. The outcome of interest was death from any cause, pre-pandemic (since the onset of registry-March 2014-March 2020), and during the pandemic (March 2020-May 2021). The crude mortality rate and standardized mortality ratio (SMR) were determined. RESULTS: There were 1216 PsA patients with a follow-up of 7500 patient-years. Overall, 46 deaths (26 males) were observed. In the pre-pandemic period, SMR for PsA vs the general population was 0.95 (0.61-1.49), being higher in males [1.56 (0.92-2.63)] than females [0.62 (0.33-1.17)]. The crude mortality rate in PsA doubled during the pandemic (pre-pandemic crude mortality rate: 5.07 vs 10.76 during the pandemic) with a higher increase in females (2.9 vs 8.72) than males (9.07 vs 14.73). CONCLUSION: The mortality in PsA was found similar to the general population in the pre-pandemic era. The mortality rates in PsA doubled during the pandemic. Whether PsA patients have more risk of mortality than the general population due to COVID-19 needs further studies. Key Points • Decrease in mortality in PsA might be expected with the more effective treatment options and better disease control. • A crude mortality rate is comparable to the general population and not increased until the pandemic. • Currently, there is a 2-fold increase in crude mortality rate possibly due to the COVID-19.

Translation and cross-cultural adaptation of the modified Short QUestionnaire to Assess Health-enhancing physical activity (mSQUASH) into Turkish.

Aims The aim was to translate and cross-culturally adapt the modified Short Questionnaire to Assess Health-enhancing physical activity (mSQUASH) into Turkish Methods The mSQUASH was translated into Turkish and backward-translation into Dutch was performed afterwards using the Beaton method. After the Turkish version was reviewed and revised by an expert committee that included translators, two patients and the research team a pre-final version was produced. The-pre final version then entered a field-test with cognitive debriefing in 10 patients with axSpA. The final result was the Turkish mSQUASH version. Results The translation process went without difficulties. Small discrepancies were either resolved during the synthesis or expert consensus meetings. Mean (SD) time to complete the mSQUASH was 6.1 (2.4) minutes in field-test procedure. The cognitive debriefing showed that the items of the Turkish mSQUASH were clear, relevant, easy to understand and easy to complete. None of the patients reported that an important aspect of physical activity was missing from the questionnaire items. Patients raised the concern that not all sport examples were culturally suitable; tennis was replaced by volleyball and basketball after the cognitive debriefing, to make it more appropriate to the Turkish culture. Conclusion The final Turkish version of the mSQUASH showed acceptable linguistic and field validity for use in both clinical practice and research. However, further assessment of the psychometric properties (validity and reliability) of the Turkish version of the mSQUASH is needed before it can be implemented.

Degenerative and Inflammatory Osteoproliferations in Lumbar Radiographs in Psoriatic Arthritis Patients.

The aim of this study was to determine the distribution different types of osteoproliferative lesions on the lumbar spine and their relations in patients with psoriatic arthritis (PsA) under biologic-disease-modifying anti-rheumatic drug therapy. T12-S1 corners were evaluated in 182/274 (66.4%) patients with lumbar radiographs. Lesions were determined as osteophyte (grade 0-3), erosion, sclerosis, squaring, corner syndesmophyte, and bridging syndesmophyte. Lesions with no clear distinction were defined as ambiguous. The mean (SD) age of 182 PsA (69.2% female) patients was 47.6 years (12.7), the mean age at diagnosis of PsA was 39.7 years (12.7). Of the patients, 112 (61.5%) met the criteria for mNY. Osteophytes were the most frequently detected lesions (42.3%), with 18.1% of patients having osteophyte grade 2 and above (mostly on L2-L4). Syndesmophytes were present in 24.2% of all patients (mostly on T12-L4), and ambiguous lesions were detected in 13 (4.7%) patients. Changes were observed in five ambiguous lesions in patients with follow-up lumbar radiography, four of them transformed into corner syndesmophytes at follow-up, and one was evaluated as osteophyte grade 2. Approximately one fifth of patients presented with significant degenerative new bone formation, and syndesmophytes were found in one fourth. In approximately 7% of all patients, lesions were ambiguous. The nature of these lesions needs to be evaluated in further imaging studies.

Young-GRAPPA at the Annual GRAPPA Meeting: Presentation of a New Group Within GRAPPA and Its Vision.

At the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, a separate group was created (Young-GRAPPA) to address the challenges of young researchers and physicians beginning their careers. This paper presents the initial organizational framework and different components and aims of this group. We were able to enroll over 50 young researchers as a result of this meeting.

Anxiety levels before biologic initiation and changes with treatment in patients with psoriatic arthritis: HUR-BIO biologic registry results.

OBJECTIVES: Psoriatic arthritis (PsA) is an inflammatory musculoskeletal disease related to several comorbidities. Anxiety is an important comorbidity in PsA and the data is scarce. We aimed to understand the rates before biologic agents and change in anxiety with the treatment. METHODS: PsA patients from the Hacettepe University biologic database (HUR-BIO) were assessed for the high anxiety level (score ≥ 4) using the patient self-reported measure of anxiety on a 0-10 numerical scale, included in the Psoriatic Arthritis Impact of Disease questionnaire (PSAID-12). The rate and scores of anxiety were determined before starting biologic agents, at the first visit within 6 months. Changes in anxiety scores were assessed according to favorable treatment responses, and the correlation was evaluated by Spearman correlation analysis. RESULTS: From 520 patients registered, 147 [mean (SD) age 43.3 (12.4) years, 70.7% female] had anxiety score both at baseline and first visit within 6 months. Both the frequency of high anxiety level and mean (SD) scores decreased at the first visit [63.9% vs. 41.4%, 4.8 (3.4) vs. 3.2 (3.1) respectively, p < 0.001 for both] after a mean (SD) follow-up of 105.7 (22.2) days. There was also a positive correlation between the change in anxiety scores and all parameters tested for treatment response: pain, PGA, BASDAI, HAQ-DI, DAS-28, and also PsAID-12. CONCLUSION: Anxiety is a more frequent problem at biologic initiation than rates observed in the general PsA population. The rates show a decreasing trend and correlates with treatment response but is still high within 6 months under treatment. KEY POINTS: • As high as 65% of patients had a high anxiety levels before the initiation of bDMARDs. • The disease activity control is essential in reducing anxiety; however, rates are still high within 6 months. • Decreased anxiety scores and rates of the high anxiety level are linked to better outcomes.