Analysis of factors influencing target PASI responses and side effects of methotrexate monotherapy in plaque psoriasis: a multicenter study of 1521 patients.

Methotrexate (MTX) is commonly used as first-line systemic treatment agent in psoriasis. We aimed to evaluate the clinical characteristics and treatment responses of patients with psoriasis undergoing MTX monotherapy. Data from adult patients with plaque psoriasis who received MTX monotherapy for at least 3 months between April 2012 and April 2022 were retrospectively evaluated in 19 tertiary care centers. Our study included 722 female and 799 male patients, a total of 1521 participants. The average age of the patients was 44.3 ± 15.5 years. Mode of treatment was oral in 20.4% of patients while in 79.4% it was subcutaneous. The median treatment duration was 8 months (IQR = 5-15). The median weekly dose was 15 mg (IQR = 11-15). 1448 (95.2%) patients were taking folic acid supplementation. At week 12, 16.3% of the patients achieved PASI (Psoriasis Area and Severity Index) 90 response while at week 24, 37.3% achieved it. Logistic regression analysis for week 12 identified the following independent factors affecting PASI 90 achievement positively: median weekly MTX dose ≤ 15 mg (P = 0.011), subcutaneous administration (P = 0.005), no prior systemic treatment (< 0.001) and folic acid use (0.021). In logistic regression analysis for week 24; median weekly MTX dose ≤ 15 mg (P = 0.001), baseline PASI ≥ 10 (P < 0.001), no prior systemic treatment (P < 0.004), folic acid use (P = 0.001) and absence of comorbidities (P = 0.009) were determined as independent factors affecting the achievement of PASI 90. Adverse effects were observed in 38.8% of the patients, with nausea/vomiting (23.9%) and transaminase elevation (13%) being the most common. The most common reasons for interruptions (15.3%) and discontinuations (27.1%) of the treatment were patient related individual factors. The use of MTX as the first systemic treatment agent, at doses ≤ 15 mg/week and concurrent folic acid application are positive predictive factors for achieving the target PASI response both at weeks 12 and 24. In our study, which is one of the most comprehensive studies on MTX treatment in psoriasis, we observed that MTX is an effective and safe treatment option.

Effectiveness and safety of ustekinumab for the treatment of psoriasis; six years of clinical experience.

BACKGROUND: This work aimed to investigate the long-term clinical experience with ustekinumab in cases with psoriasis. MATERIALS AND METHODS: This retrospective cohort research group consisted of cases who presented to the dermatology outpatient clinics between January 2015 and January 2021, diagnosed with psoriasis, and were treated with ustekinumab. Data including gender, age, weight, disease duration, naïve and non-naïve status, psoriasis type, duration of medication, comorbidities, psoriasis area and severity index scores, the causes of treatment discontinuation, and previous treatments were retrospectively reviewed and analyzed. RESULTS: 160 cases with psoriasis were treated with ustekinumab during the research period. Twenty-four patients were excluded. Among 136 cases, 84 (61.8%) were male and 52 (38.2%) were female. We determined 80.55% of the non-naïve cases responded to ustekinumab. CONCLUSION: Ustekinumab can be a suitable treatment option for non-naïve and resistant patients. Our data suggest the positive effect persists in cases with favorable responses to the first or second dose of ustekinumab. Also, we determined male cases gave more rapid and more robust responses than female cases, and patients were more willing about continuing the treatment.

A prospective dual-centre intra-individual controlled study for the treatment of burns comparing dermis graft with split-thickness skin auto-graft.

To investigate if donor and recipient site morbidity (healing time and cosmesis) could be reduced by a novel, modified split-thickness skin grafting (STSG) technique using a dermal component in the STSG procedure (DG). The STSG technique has been used for 150 years in surgery with limited improvements. Its drawbacks are well known and relate to donor site morbidity and recipient site cosmetic shortcomings (especially mesh patterns, wound contracture, and scarring). The Dermal graft technique (DG) has emerged as an interesting alternative, which reduces donor site morbidity, increases graft yield, and has the potential to avoid the mesh procedure in the STSG procedure due to its elastic properties. A prospective, dual-centre, intra-individual controlled comparison study. Twenty-one patients received both an unmeshed dermis graft and a regular 1:1.5 meshed STSG. Aesthetic and scar assessments were done using The Patient and Observer Scar Assessment Scale (POSAS) and a Cutometer Dual MPA 580 on both donor and recipient sites. These were also examined histologically for remodelling and scar formation. Dermal graft donor sites and the STSG donor sites healed in 8 and 14 days, respectively (p < 0.005). Patient-reported POSAS showed better values for colour for all three measurements, i.e., 3, 6, and 12 months, and the observers rated both vascularity and pigmentation better on these occasions (p < 0.01). At the recipient site, (n = 21) the mesh patterns were avoided as the DG covered the donor site due to its elastic properties and rendered the meshing procedure unnecessary. Scar formation was seen at the dermal donor and recipient sites after 6 months as in the standard scar healing process. The dermis graft technique, besides potentially rendering a larger graft yield, reduced donor site morbidity, as it healed faster than the standard STSG. Due to its elastic properties, the DG procedure eliminated the meshing requirement (when compared to a 1:1.5 meshed STSG). This promising outcome presented for the DG technique needs to be further explored, especially regarding the elasticity of the dermal graft and its ability to reduce mesh patterns.Trial registration: ClinicalTrials.gov Identifier (NCT05189743) 12/01/2022.

Real-life efficacy and drug continuation of secukinumab in treating moderate to severe plaque psoriasis in Aegean region of Turkey: a multicenter retrospective study and systematic review of the literature.

BACKGROUND: Secukinumab was demonstrated to be efficient in the treatment of moderate to severe plaque psoriasis in the phase studies. Real-life treatment experiences obtained from patients that do not meet the inclusion criteria of phase studies can provide valuable information on efficacy and safety results. Results may also differ in different ethnic populations. OBJECTIVE: To investigate short and long-term efficacy and drug continuation of secukinumab in Turkish population. METHODS: The study conducted in three tertiary care psoriasis centers. Patients' demographic characteristics and week 0 / 4th week / 12th week / 1st year PASI values were analyzed. For systematic review of the literature a PubMed search using the keywords "secukinumab and real and psoriasis" from inception to April 2021 was performed. RESULTS: Mean PASI scores improved the compared to baseline at all assessment weeks (p = 0.000). In multivariate model, we found that bioexperience have negative influence on the PASI90 response at week 4. Univariate analysis showed significant relationship only between PASI90 response rate and gender at week 12 and year 1. Approximately 85% of patients remained on secukinumab treatment at the end of one year. CONCLUSIONS: Secukinumab seems to be an effective treatment option for plaque psoriasis. According to our knowledge, this is the first study concerning about long-term efficacy and drug continuation of secukinumab from Turkey.

Ixekizumab for the treatment of the patients with moderate to severe plaque psoriasis: Clinical data from a real-world experience.

Real-life data about any particular treatment is very helpful for clinicians, particularly when managing a chronic disease such as psoriasis. In our study, we aimed to reflect our clinical experience during 48 weeks with an IL-17 antagonist ixekizumab. This study was designed as a retrospective multi-center study. Four tertiary referral centers participated into the study. The patients who did not present to the clinics for 3rd month follow-up were excluded. Data including gender, age, weight, type of psoriasis, additional sites on the body, disease duration, previous treatments, duration of medication of ixekizumab, psoriasis area and severity index scores, previous treatments, and comorbidities, the reasons for drug discontinuation, adverse effects and the patients' naïve or non-naïve status were retrieved from electronic patient folders. Although 267 patients met the inclusion criteria, 28 patients were excluded since they did not present to the clinic for 3rd month follow-up so 239 cases were included mmüne research. We determined significant correlations between naive and non-naive cases about getting PASI 75 and PASI 90 responses for all cases (p = 0.005 and p = 0.028, respectively) and between comorbid and non-comorbid cases about getting PASI 90 and PASI 100 responses for all cases (p = 0.021 and p = 0.029, respectively). When we investigate as female and male patients separately, non-comorbid female cases can achieve PASI 100 response significantly easier than comorbid female patients (p = 0.019). Clinicians can use ixekizumab safely mmüne treatment of their patients with psoriasis and get PASI 75-90-100 responses quickly. Ixekizumab is more effective for naive cases but it may also be a treatment option for biologic experienced patients. The ratio of PASI 75-90-100 responses are better in non-comorbid cases than comorbid patients nevertheless ixekizumab is a quite effective agent mmüne treatment of comorbid cases.

Certolizumab pegol in the treatment of psoriasis: Real-life data.

Certolizumab pegol (CZP), the only Fc-free, PEGylated anti-tumor necrosis factor biologic agent. This study aims to investigate the effect and safety of CZP in moderate-to-severe chronic plaque psoriasis. We performed a retrospective observational analysis of the moderate-to-severe psoriasis patients under ceratolizumab pegol therapy. Primer endpoints were efficacy of CZP, defined as statistically significant improvement of Psoriasis Area and Severity Index (PASI), Physician's Global Assessment (PGA), and clinical Disease Activity index for Psoriatic Arthritis (cDAPSA) in the 24 week of therapy. Secondary endpoints were safety of CZP especially during COVID-19 pandemic. Fifty-six moderate-to-severe psoriasis patients treated with CZP were evaluated retrospectively. We observed a rapid and significant reduction of PASI, PGA, and cDAPSA scores in W4. After loading dose, we observed loss of clinical efficacy of CZP in eight patients and optimized therapy by increasing the dosing of CZP. Dose escalation of CZP permitted the achievement and long-term maintenance of clinical improvement in these patients. We compare the clinical efficacy of CZP between naive and patients who has been treated with other biologic agents. There were no statistical differences in efficacy between these two groups. No side effects were observed during CZP treatment. There were no cases of death from COVID-related disease in our study population or patients hospitalized for COVID-19 related disease. Our results demonstrate that CZP is an effective and safe therapeutic option for patients with moderate-to-severe chronic plaque psoriasis.

Metabolic Response to Claudication in Peripheral Arterial Disease: A Microdialysis Pilot Study.

OBJECTIVES: This is a pilot study, and the objective of the study was to investigate the possible uses of microdialysis in the calf muscle to assess the metabolic response to intermittent claudication (IC) and in addition evaluate the simultaneous systemic inflammatory reaction. METHODS: Dialysate and venous blood sampling was performed before, during and after walking on a treadmill to maximal tolerable claudication (controls 10 min) using 1 microdialysis catheter inserted in the gastrocnemius muscle, 1 subcutaneously in the pectoral region (as a reference), and a peripheral venous catheter. RESULTS: A total of 9 participants were recruited, 6 patients with IC and 3 healthy control subjects. At baseline, patients with IC and control subjects did not differ in metabolic findings (glucose, lactate, pyruvate, and glycerol) in the gastrocnemius muscle. Subcutaneous glucose concentration was higher in control subjects. After physical exertion, gastrocnemius and subcutaneous glycerol, lactate, and pyruvate concentrations increased in patients with IC. Plasma concentrations of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), hepatocyte growth factor, and vascular endothelial growth factor were higher in IC subjects at baseline, and TNF-α, IL-6, and IL-18 increased after walking as did IL-6 and IL-1ß in control subjects. The muscle catheters did not show any signs of harm. CONCLUSIONS: Microdialysis can be used to study the ongoing metabolic response during walking and claudication. Our results suggest both an acute local and a systemic inflammatory reaction during development of claudication.

Simultaneous common bile duct clearance and laparoscopic cholecystectomy: experience of a one-stage approach.

INTRODUCTION: The timing and optimal method for common bile duct (CBD) clearance and laparoscopic cholecystectomy remains controversial. Several different approaches are available in clinical practice. The current study presents the experience of two European hospitals of simultaneous laparoscopic cholecystectomy (LC) and intra-operative endoscopic retrograde cholangiopacreatography (IO-ERCP) done by surgeons. METHODS: Retrospective analysis of all consecutive patients subjected to LC + IO-ERCP during their index admission between 4/2014 and 9/2016. Data accrued included patient demographics, laboratory markers, operation time (min) reported as mean (± SD) and hospital length of stay (LOS) reported as median (lower quartile, upper quartile). RESULTS: During the 29-month study, a total of 201 consecutive LC + IO-ERCPs were performed. The mean age of patients was 55 ± 19 years and 67% were female. The mean intervention time was 105 ± 44 min. The total LOS was 4 (3,  7) days and the post-operative LOS was 2 (1,  3) days. A total of 6 (3%) patients experienced post-interventional pancreatitis and two (1%) patients suffered a Strasberg type A bile leak. All patients were successfully discharged. CONCLUSION: Simultaneous LC + IO-ERCP is associated with few complications. Further studies investigating cost-benefit and patient satisfaction are warranted.

Predicting In-Hospital and 1-Year Mortality in Geriatric Trauma Patients Using Geriatric Trauma Outcome Score.

BACKGROUND: The Geriatric Trauma Outcome Score (GTOS; [age] + [2.5 × Injury Severity Score] + 22 [if packed RBC transfused within ≤24 hours of admission]), was developed and validated as a prognostic indicator for in-hospital mortality in elderly trauma patients. However, GTOS neither provides information about post-discharge outcomes nor discriminates between patients dying with and without care restrictions. Isolating the latter, GTOS prediction performance was examined during admission and 1-year post discharge in a mature European trauma registry. STUDY DESIGN: All trauma admissions 65 years of age and older in a university hospital during 2007 to 2011 were considered. Data on age, Injury Severity Score, packed RBC transfusion within ≤24 hours, therapy restrictions, discharge disposition, and mortality were collected. In-hospital deaths with therapy restrictions and patients discharged to hospice were excluded. The GTOS was the sole predictor in a logistic regression model estimating mortality probabilities. Performance of the model was assessed by misclassification rate, Brier score, Tjur R2, and area under the curve. RESULTS: The study population was 1,080 patients with a median age of 75 years, mean Injury Severity Score of 10, and packed RBCs transfused in 8.2%. In-hospital mortality was 14.9% and 7.7% after exclusions. Misclassification rate fell from 14% to 6.5% and Brier score from 0.09 to 0.05, and area under the curve increased from 0.87 to 0.88. Equivalent values for the original GTOS sample were 9.8%, 0.07, and 0.82, respectively. One-year mortality follow-up showed a misclassification rate of 17.6% and Brier score of 0.13. CONCLUSIONS: Excluding patients with care restrictions and discharged to hospice improved GTOS performance for in-hospital mortality prediction. The GTOS is not adept at predicting 1-year mortality.

A versatile atomic force microscope for three-dimensional nanomanipulation and nanoassembly.

A conventional atomic force microscope (AFM) has been successfully applied to manipulating nanoparticles (zero-dimensional), nanowires (one-dimensional) or nanotubes (one- or two-dimensional) by widely used pushing or pulling operations on a single surface. However, pick-and-place nanomanipulation in air is still a challenge. In this research, a modified AFM, called a three-dimensional (3D) manipulation force microscope (3DMFM), was developed to realize 3D nanomanipulation in air. This system consists of two individually actuated cantilevers with protruding tips that are facing each other, constructing a nanotweezer for the pick-and-place nanomanipulation. Before manipulation, one of the cantilevers is employed to position nano-objects and locate the tip of the other cantilever by image scanning. During the manipulation, these two cantilevers work collaboratively as a nanotweezer to grasp, transport and place the nano-objects with real-time force sensing. The manipulation capabilities of the nanotweezer were demonstrated by grabbing and manipulating silicon nanowires to build 3D nanowire crosses. 3D nanomanipulation and nanoassembly performed in air could become feasible through this newly developed 3DMFM.

[The skin manifestations in patients with lung cancers]. / Akciger Kanserli Hastalarda Deri Bulgulari.

It is also common to observe skin manifestations in many internal malignancies. The lung cancer is a frequently seen internal cancer. Due to its gradually increasing incidence, it has become the first reason of death from cancer also in women by overtaking the breast cancer. Although pathognomonic skin manifestations are not reported in lung cancers, it is emphasized that lung cancer must be remembered when non specific signs such as digital clubbing, hypertrophic osteoatropathy, cyanosis due to superior vena cava syndrome, oedema, telengiectasia, acanthosis nigricans are observed. Because a few reports are present about this subject in literature, 44 patients which had the diagnosis of lung cancer in Cumhuriyet University Faculty of Medicine were evaluated according to the their dermatological manifestations. 47.7% of these patients had digital clubbing; meanwhile 25% telengiectasia of the chest forewall, 22.7% lip cyanosis, 9% long eyelash, 2.27% pruritus, 2.27% hypertrophic pulmonary osteoarthropathy and 2.27% Leser Trelat sign were established.