[The place of ciclosporin A cationic emulsion 0.1% in the therapy of xerophthalmia]. / Mesto kationnoi emul'sii tsiklosporina A 0,1% v terapii kseroftal'mii.

Dry eye disease (DED) is pathogenetically based on inflammation of the ocular surface. A step-by-step approach to DED treatment involves early initiation of anti-inflammatory therapy, including instillation of cyclosporine A (CsA). However, recommendations for the use of topical CsA in clinical practice are limited. This article presents an expert consensus on practical recommendations for the management of patients with DED, including indications, time of initiation and duration of CsA therapy, comparison of CsA forms currently registered in the Russian Federation, as well as issues of patient education.

Mitochondrial SIRT3 as a protective factor against cyclosporine A-induced nephrotoxicity.

Sirtuin3 (SIRT3), a mitochondrial deacetylase, has been shown to be involved in various kidney diseases. In this study, we aimed to clarify the role of SIRT3 in cyclosporine-induced nephrotoxicity and the associated mitochondrial dysfunction. Madin-Darby canine kidney (MDCK) cells were transfected with Flag-tagged SIRT3 for SIRT3 overexpression or SIRT3 siRNA for the inhibition of SIRT3. Subsequently, the cells were treated with cyclosporine A (CsA) or vehicle. Wild-type and SIRT3 knockout (KO) mice were randomly assigned to receive cyclosporine A or olive oil. Furthermore, SIRT3 activator, honokiol, was treated alongside CsA to wild type mice. Our results revealed that CsA treatment inhibited mitochondrial SIRT3 expression in MDCK cells. Inhibition of SIRT3 through siRNA transfection exacerbated apoptosis, impaired the expression of the AMP-activated protein kinase-peroxisome proliferator-activated receptor gamma coactivator 1 alpha (AMPK-PGC1α) pathway, and worsened mitochondrial dysfunction induced by CsA treatment. Conversely, overexpression of SIRT3 through Flag-tagged SIRT3 transfection ameliorated apoptosis, increased the expression of mitochondrial superoxide dismutase 2, and restored the mitochondrial regulator pathway, AMPK-PGC1α. In SIRT3 KO mice, CsA treatment led to aggravated kidney dysfunction, increased kidney tubular injury, and accumulation of oxidative end products indicative of oxidative stress injury. Meanwhile, SIRT3 activation in vivo significantly mitigated these adverse effects, improving kidney function, reducing oxidative stress markers, and enhancing mitochondrial health following CsA treatment. Overall, our findings suggest that SIRT3 plays a protective role in alleviating mitochondrial dysfunction caused by CsA through the activation of the AMPK-PGC1α pathway, thereby preventing further kidney injury.

Association Between FEV1 Decline Rate and Mortality in Long-Term Follow-Up of a 21-Patient Pilot Clinical Trial of Inhaled Liposomal Cyclosporine Plus Standard-of-Care Versus Standard-of-Care Alone for Bronchiolitis Obliterans Syndrome After Lung Transplantation.

BACKGROUND The association between forced expiratory volume in 1 second (FEV1) trajectory and mortality in bronchiolitis obliterans syndrome (BOS) is not well defined. Using long-term data from a prior clinical trial of inhaled liposomal cyclosporine A (L-CsA-I) for lung transplant patients with BOS, this study examined the association between longitudinal FEV1 change and mortality. MATERIAL AND METHODS We analyzed long-term data from a clinical trial which randomized 21 patients with BOS (³20% decrease in FEV1 from personal maximum) to receive L-CsA-I plus standard-of-care (n=11) or standard-of-care (SOC) alone (n=10) for 24 weeks. A joint statistical model, combining a linear mixed model for FEV1 change and Cox regression for mortality, was utilized to examine the overall association between FEV1 trajectory and mortality during follow-up. RESULTS The 21 trial participants (10 single, 11 double lung recipients) had a mean FEV1 of 1.7±0.6 Liters at randomization. Median follow-up post-randomization was 35 months. In joint model analysis, 1 percent FEV1 decline predicted 1.076-fold increased mortality risk (95% confidence interval: -0.998 to 1.160, p=0.058). FEV1 decline was reduced by 2.6% per year in L-CsA-I patients compared to SOC (p=0.210), and overall survival at 1/3/5 years was 91%/64%/27% vs 90%/20%/0% for L-CsA-I versus SOC, respectively (p=0.164). CONCLUSIONS In BOS patients, greater longitudinal FEV1 decline predicts increased mortality. Trends towards prolonged stabilization of FEV1 and improved survival were observed with L-CsA-I receipt. Further analyses will aid in evaluating the utility of FEV1 change as a survival predictor, having implications in BOS management and future trial design.

The long-term outcomes and safety of severe aplastic anemia treated with porcine antilymphocyte globulin plus cyclosporine, with or without thrombopoietin receptor agonists: a double-center retrospective study.

BACKGROUND: Porcine antilymphocyte globulin (p-ALG) combined with cyclosporine (CsA) has been commonly used for severe aplastic anemia (SAA) patients, but few studies on the combination of p-ALG and thrombopoietin receptor agonist (TPO-RA). RESEARCH DESIGN AND METHODS: We retrospectively analyzed the data of 85 people with diagnosed SAA who underwent p-ALG plus CsA, with or without TPO-RA from 2014 to 2023. RESULTS: The overall response rates were 55.3% and 65.9% at 3 and 6 months, and the TPO-RA group were 66.7% and 72.3% at 3 and 6 months, without TPO-RA group were 27.8% and 55.6%. In multivariate analysis, baseline platelet count of > 10 × 109/L was a simple predictor of favorable response at 6 months (p = 0.015). The median follow-up time for all patients was 39 months (range 0.4 ~ 104), the 5-year overall survival (OS) rate was 90.6% [95% CI = 82.1-95.2%], and the failure-free survival (FFS) rate was 68.9% [95% CI = 56.6-78.4%]. Having hematologic responses in 6 months was an independent positive predictor for FFS (p = 0.000). Twelve patients (14.1%) suffered from serum sickness, and 9.5% of patients had mild hepatic impairment. CONCLUSIONS: p-ALG along with CsA is an effective choice for patients with SAA. p-ALG combined with TPO-RA may contribute to the early restoration of hematopoiesis.

Supervivencia de la ciclosporina en el tratamiento de la dermatitis atópica moderada-grave: Registro Español de Dermatitis Atópica (BIOBADATOP) / Drug Survival in Cyclosporine Treatment for Moderate to Severe Atopic Dermatitis: Analysis of the Spanish Atopic Dermatitis Registry (BIOBADATOP)

Antecedentes: Debido a la eclosión en el último quinquenio de nuevas alternativas terapéuticas para la dermatitis atópica (DA), nos planteamos estudiar la supervivencia actual de la ciclosporina (CsA) en esta patología. La CsA, como paso necesario solicitado por el Sistema Nacional de Salud de España para la autorización de otros tratamientos sistémicos, podría presentar una supervivencia menor que en otras enfermedades. Material y método: Estudio multicéntrico, observacional, de cohortes prospectivo para el que se recogieron pacientes incluidos en el Registro Español de Dermatitis Atópica (BIOBADATOP). Como cohorte de comparación se emplearon los datos del Registro Español de tratamientos sistémicos en Psoriasis (BIOBADADERM). Resultados: Se incluyeron 130 pacientes diagnosticados de DA que habían recibido CsA (mediana de supervivencia de CsA: 1 año). En el grupo comparador se incluyeron 150 pacientes psoriásicos que habían recibido CsA (mediana de supervivencia: 0,37 años). Observamos una mayor supervivencia de la CsA en los pacientes con DA en comparación con los pacientes psoriásicos (p<0,001). Conclusión: La supervivencia de la CsA en BIOBADATOP es similar a la descrita en otras series de pacientes con DA, y superior a la observada en los pacientes con psoriasis en el registro BIOBADADERM.(AU)

Background: The past 5 years have seen a proliferation of new treatments for atopic dermatitis (AD). We analyzed recent drug survival data for cyclosporine in this setting. Because the Spanish National Healthcare system requires patients with AD to be treated with cyclosporine before they can be prescribed other systemic treatments, drug survival for cyclosporine may be shorter than in other diseases. Material and method: Multicenter, observational, prospective cohort study using data from the Spanish Atopic Dermatitis Registry (BIOBADATOP). Data from the Spanish Registry of Systemic Treatments in Psoriasis (BIOBADADERM) were used to create a comparison cohort. Results: We analyzed data for 130 patients with AD treated with cyclosporine (median drug survival, 1 year). Median cyclosporine survival in the psoriasis comparison group (150 patients) was 0.37 years. Drug survival was significantly longer in AD than in psoriasis (P<.001). Conclusion: Drug survival of cyclosporine in the BIOBADATOP registry is similar to that described in other series of patients with AD and longer than that observed in the BIOBADADERM psoriasis registry.(AU)

[Translated article] Drug Survival in Cyclosporine Treatment for Moderate to Severe Atopic Dermatitis: Analysis of the Spanish Atopic Dermatitis Registry (BIOBADATOP) / Supervivencia de la ciclosporina en el tratamiento de la dermatitis atópica moderada-grave: Registro Español de Dermatitis Atópica (BIOBADATOP)

Antecedentes: Debido a la eclosión en el último quinquenio de nuevas alternativas terapéuticas para la dermatitis atópica (DA), nos planteamos estudiar la supervivencia actual de la ciclosporina (CsA) en esta patología. La CsA, como paso necesario solicitado por el Sistema Nacional de Salud de España para la autorización de otros tratamientos sistémicos, podría presentar una supervivencia menor que en otras enfermedades. Material y método: Estudio multicéntrico, observacional, de cohortes prospectivo para el que se recogieron pacientes incluidos en el Registro Español de Dermatitis Atópica (BIOBADATOP). Como cohorte de comparación se emplearon los datos del Registro Español de tratamientos sistémicos en Psoriasis (BIOBADADERM). Resultados: Se incluyeron 130 pacientes diagnosticados de DA que habían recibido CsA (mediana de supervivencia de CsA: 1 año). En el grupo comparador se incluyeron 150 pacientes psoriásicos que habían recibido CsA (mediana de supervivencia: 0,37 años). Observamos una mayor supervivencia de la CsA en los pacientes con DA en comparación con los pacientes psoriásicos (p<0,001). Conclusión: La supervivencia de la CsA en BIOBADATOP es similar a la descrita en otras series de pacientes con DA, y superior a la observada en los pacientes con psoriasis en el registro BIOBADADERM.(AU)

Background: The past 5 years have seen a proliferation of new treatments for atopic dermatitis (AD). We analyzed recent drug survival data for cyclosporine in this setting. Because the Spanish National Healthcare system requires patients with AD to be treated with cyclosporine before they can be prescribed other systemic treatments, drug survival for cyclosporine may be shorter than in other diseases. Material and method: Multicenter, observational, prospective cohort study using data from the Spanish Atopic Dermatitis Registry (BIOBADATOP). Data from the Spanish Registry of Systemic Treatments in Psoriasis (BIOBADADERM) were used to create a comparison cohort. Results: We analyzed data for 130 patients with AD treated with cyclosporine (median drug survival, 1 year). Median cyclosporine survival in the psoriasis comparison group (150 patients) was 0.37 years. Drug survival was significantly longer in AD than in psoriasis (P<.001). Conclusion: Drug survival of cyclosporine in the BIOBADATOP registry is similar to that described in other series of patients with AD and longer than that observed in the BIOBADADERM psoriasis registry.(AU)

Prognostic model on pregnancy outcomes for women with recurrent spontaneous abortions treated with cyclosporin A: A single-institution experience.

BACKGROUND: This study aimed to identify prognostic factors for pregnancy outcomes and construct a prognostic model for pregnancy outcomes in women with Recurrent Spontaneous Abortions (RSA) treated with cyclosporin A. METHODS: A total of 154 RSA patients treated with cyclosporin A between October 2016 and October 2018 were retrospectively recruited. Multivariate logistic regression was applied to identify the prognostic factors for pregnancy success in RSA women treated with cyclosporin A. The Receiver Operating Characteristic (ROC) curve was applied to construct prognostic value, and the prognostic performance was assessed using area under the ROC. RESULTS: After adjusting potential confounding factors, the authors noted increased age (OR = 0.771; 95 % CI 0.693‒0.858; p < 0.001) and positive antinuclear antibodies (OR = 0.204; 95 % CI 0.079‒0.526; p = 0.001) were associated with a reduced incidence of pregnancy success, while positive anti-ß2 glycoprotein-I-antibody (OR = 21.941; 95 % CI 1.176‒409.281; p = 0.039) was associated with an increased incidence of pregnancy success after treated with cyclosporin A. The AUC of combining these variables for predicting pregnancy failure was 0.809 (95 % CI 0.735‒0.880). CONCLUSIONS: This study systematically identified the prognostic factors for pregnancy success in women treated with cyclosporin A, and the constructed prognostic model based on these factors with relatively higher prognostic value. Further large-scale prospective studies should be performed to validate the prognostic value of the constructed model.

Biomarkers to predict therapeutic response in chronic spontaneous urticaria: a review.

Chronic spontaneous urticaria (CSU) is a relatively common dermatological disorder characterized by sudden and unpredictable onset of pruritic wheals and/or angioedema, for more than six weeks. It is a mast cell-mediated histaminergic disorder, considerably worsening patients' quality of life. Current treatment options include anti-histamines, omalizumab and cyclosporine, in a step-wise algorithmic approach, aimed at complete symptom control. Patients do not respond uniformly to these therapeutic options due to phenotypic and endotypic heterogeneity, and often remain uncontrolled/poorly controlled. Recent research is focused on identifying certain biomarkers to predict therapeutic response and facilitate patient-targeted personalized treatment, for maximum benefit. The current article summarizes various biomarkers explored to date, and also elaborates their role in predicting therapeutic response to anti-histamines, omalizumab and cyclosporine, in CSU patients. High disease activity, elevated CRP/ESR and elevated D-dimer are the most important predictors of non/poor-response to antihistamines. Low and very low baseline IgE, elevated CRP/ESR, ASST+, BAT/BHRA+, basopenia, eosinopenia, and elevated D-dimer are predictors of poor and good response to omalizumab and cyclosporine, respectively. Additionally, normal or slightly elevated baseline IgE and FceR1 overexpression are predictors of a faster response with omalizumab. However, none of these predictors have so far been completely validated and are not yet recommended for routine use. Thus, large-scale prospective studies are needed to confirm these predictive biomarkers and identify new ones to achieve the goal of personalized medicine for CSU.

Silk Fibroin Formed Bioadhesive Ophthalmic Gel for Dry Eye Syndrome Treatment.

PURPOSE: Dry eye syndrome (DES), arising from various etiologic factors, leads to tear film instability and ocular surface damage. Given its anti-inflammatory effects, cyclosporine A (CsA) has been widely used as a short-term treatment option for DES. However, poor bioavailability and solubility of CsA in aqueous phase make the development of a cyclosporine A-based eye drop for ocular topical application a huge challenge. METHODS: In this study, a novel strategy for preparing cyclosporine A-loaded silk fibroin nanoemulsion gel (CsA NBGs) was proposed to address these barriers. Additionally, the rheological properties, ocular irritation potential, tear elimination kinetics, and pharmacodynamics based on a rabbit dry eye model were investigated for the prepared CsA NBGs. Furthermore, the transcorneal mechanism across the ocular barrier was also investigated. RESULTS: The pharmacodynamics and pharmacokinetics of CsA NBGs exhibited superior performance compared to cyclosporine eye drops, leading to a significant enhancement in the bioavailability of CsA NBGs. Furthermore, our investigation into the transcorneal mechanism of CsA NBGs revealed their ability to be absorbed by corneal epithelial cells via the paracellular pathway. CONCLUSION: The CsA NBG formulation exhibits promising potential for intraocular drug delivery, enabling safe, effective, and controlled administration of hydrophobic drugs into the eye. Moreover, it enhances drug retention within the ocular tissues and improves systemic bioavailability, thereby demonstrating significant clinical translational prospects.

Resveratrol attenuates cyclosporin A-induced upregulation of the thromboxane A2 receptor and hypertension via the AMPK/SIRT1 and MAPK/NF-κB pathways in the rat mesenteric artery.

Cyclosporin A, an immunosuppressive agent, is extensively utilized for the prevention of transplant rejection and treat autoimmune disease in the clinic, despite its association with a high risk of hypertension development among patients. Resveratrol is a kind of non-flavonoid phenolic compound that widely exists in many plants. The aim of the present study was to investigate the mechanism by which resveratrol ameliorates cyclosporin A-induced hypertension. The arterial rings of the mesentery were incubated with cyclosporin A and resveratrol in vitro. Rats were administered cyclosporin A and/or resveratrol for 3 weeks in vivo. Blood pressure was measured via the tail arteries. Vasoconstriction curves were recorded using a sensitive myograph. The protein expression was evaluated through Western blotting. This study demonstrated that resveratrol mitigated the cyclosporin A-induced increase in blood pressure in rats. Furthermore, resveratrol markedly inhibited the cyclosporin A-induced upregulation of thromboxane A2 receptor-mediated vasoconstriction in the rat mesenteric artery both in vitro and in vivo. Moreover, resveratrol activated AMPK/SIRT1 and inhibited the MAPK/NF-κB signaling pathway. In conclusion, resveratrol restored the cyclosporin A-induced upregulation of the thromboxane A2 receptor and hypertension via the AMPK/SIRT1 and MAPK/NF-κB pathways in rats.

Effects of Topical 0.05% Cyclosporine A on Dry Eye Symptoms and Parameters Following Small Incision Lenticule Extraction.

PURPOSE: To evaluate the effects of topical 0.05% cyclosporine A on Ocular Surface Disease Index (OSDI) score and ocular surface parameters after small incision lenticule extraction (SMILE) for myopia. METHODS: In this study, 151 patients who underwent SMILE were randomized into the control group (71 eyes) and the 0.05% cyclosporine A group (80 eyes). Both groups received standard treatment during the 1 month after SMILE. Over the next 3 months, The control group continued standard therapy (0.3% sodium hyaluronate) and the 0.05% cyclosporine A group received additional 0.05% cyclosporine A. OSDI total and subscale scores, non-invasive tear break-up time (NIBUT), tear lipid layer thickness (LLT), and tear meniscus height (TMH) were assessed preoperatively and postoperatively. RESULTS: Compared to baseline, the OSDI scores significantly increased in both groups (P < .001). The 0.05% cyclosporine A group exhibited lower OSDI total scores after administering 0.05% cyclosporine A versus the control group (P = .026). At 1 month of follow-up, NIBUT, LLT, and TMH values significantly decreased in both groups compared to baseline (P < .05). The 0.05% cyclosporine A group exhibited higher NIBUT, LLT, and TMH versus the control group, returning to preoperative values after 2 months. Overall, the OSDI total score and NIBUT values during follow-up were not significantly different between the two groups; however, the LLT and TMH values were significantly different between the two groups (P < .001 and .041, respectively) by repeated measures analysis of variance. CONCLUSIONS: Topical 0.05% cyclosporine A was effective in relieving subjective dry eye symptoms and maintaining ocular surface stability in the early postoperative period of SMILE. [J Refract Surg. 2024;40(4):e229-e238.].

Adaptative Strategy of Immunosuppressive Drugs Dosage Adjustments When Combined With Nirmatrelvir/Ritonavir in Solid Organ Transplant Recipients With COVID-19.

Nirmatrelvir/ritonavir is a promising option for preventing severe COVID-19 in solid organ transplant recipients with SARS-CoV-2 infection. However, concerns have arisen regarding potential drug interactions with calcineurin inhibitors (CNI). This two-phase multicentre retrospective study, involving 113 patients on tacrolimus and 13 on cyclosporine A, aimed to assess the feasibility and outcomes of recommendations issued by The French societies of transplantation (SFT) and pharmacology (SFPT) for CNI management in this context. The study first evaluated adherence to recommendations, CNI exposure, and clinical outcomes. Notably, 96.5% of patients on tacrolimus adhered to the recommendations, maintaining stable tacrolimus trough concentrations (C0) during nirmatrelvir/ritonavir treatment. After reintroduction, most patients experienced increased C0, with 42.9% surpassing 15 ng/mL, including three patients exceeding 40 ng/mL. Similar trends were observed in cyclosporine A patients, with no COVID-19-related hospitalizations. Moreover, data from 22 patients were used to refine the reintroduction strategy. Modelling analyses suggested reintroducing tacrolimus at 50% of the initial dose on day 8, and then at 100% from day 9 as the optimal approach. In conclusion, the current strategy effectively maintains consistent tacrolimus exposure during nirmatrelvir/ritonavir treatment, and a stepwise reintroduction of tacrolimus may be better suited to the low CYP3A recovery.

Sigle Agent of Posttransplant Cyclophosphamide Without Calcineurin Inhibitor Controls Severity of Experimental Chronic GVHD.

Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HCT), but its pathogenesis remains unclear. Recently, haplo-identical HCT with post-transplant cyclophosphamide (Haplo-HCT with PTCY) was found to achieve a low incidence rate of acute GVHD and chronic GVHD. However, while the pathogenesis of acute GVHD following Haplo-HCT with PTCY has been well investigated, that of chronic GVHD remains to be elucidated, especially in HLA-matched HCT with PTCY. Based on its safety profile, PTCY is currently applied for the human leucocyte antigen (HLA)-matched HCT setting. Here, we investigated the mechanisms of chronic GVHD following HLA-matched HCT with PTCY using a well-defined mouse chronic GVHD model. PTCY attenuated clinical and pathological chronic GVHD by suppressing effector T-cells and preserving regulatory T-cells compared with a control group. Additionally, we demonstrated that cyclosporine A (CsA) did not show any additional positive effects on attenuation of GVHD in PTCY-treated recipients. These results suggest that monotherapy with PTCY without CsA could be a promising strategy for the prevention of chronic GVHD following HLA-matched HCT.

Nanoceria-Mediated Cyclosporin A Delivery for Dry Eye Disease Management through Modulating Immune-Epithelial Crosstalk.

Dry eye disease (DED) affects a substantial worldwide population with increasing frequency. Current single-targeting DED management is severely hindered by the existence of an oxidative stress-inflammation vicious cycle and complicated intercellular crosstalk within the ocular microenvironment. Here, a nanozyme-based eye drop, namely nanoceria loading cyclosporin A (Cs@P/CeO2), is developed, which possesses long-term antioxidative and anti-inflammatory capacities due to its regenerative antioxidative activity and sustained release of cyclosporin A (CsA). In vitro studies showed that the dual-functional Cs@P/CeO2 not only inhibits cellular reactive oxygen species production, sequentially maintaining mitochondrial integrity, but also downregulates inflammatory processes and repolarizes macrophages. Moreover, using flow cytometric and single-cell sequencing data, the in vivo therapeutic effect of Cs@P/CeO2 was systemically demonstrated, which rebalances the immune-epithelial communication in the corneal microenvironment with less inflammatory macrophage polarization, restrained oxidative stress, and enhanced epithelium regeneration. Collectively, our data proved that the antioxidative and anti-inflammatory Cs@P/CeO2 may provide therapeutic insights into DED management.

[Translated article] Approach to the Epidemiology, Disease Management, and Current Challenges in the Management of Generalized Pustular Psoriasis Through a Survey Conducted Among Spanish Dermatologists.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin disease characterised by recurrent or intermittent flares. Epidemiological and disease management data in Spain are limited. Our goal was to estimate the epidemiology of GPP, explore its management, and reach consensus on the current challenges faced in Spain. METHODS: An electronic survey was submitted to dermatologists from the Spanish Academy of Dermatology and Venereology Psoriasis Working Group. This group is experienced in the management of GPP. It included a Delphi consensus to establish the current challenges. RESULTS: A total of 33 dermatologists responded to the survey. A 5-year prevalence and incidence of 13.05 and 7.01 cases per million inhabitants, respectively, were estimated. According to respondents, the most common GPP symptoms are pustules, erythema, and desquamation, while 45% of patients present > 1 annual flares. A total of 45% of respondents indicated that flares often require a length of stay between 1 and 2 weeks. In the presence of a flare, 67% of respondents often or always prescribe a non-biological systemic treatment as the first-line therapy [cyclosporine (55%); oral retinoid (30%)], and 45% a biological treatment [anti-TNFα (52%); anti-IL-17 (39%)]. The dermatologists agreed that the main challenges are to define and establish specific therapeutic goals to treat the disease including the patients' perspective on the management of the disease. CONCLUSION: Our study describes the current situation on the management of GPP in Spain, increasing the present knowledge on the disease, and highlighting the current challenges faced at the moment.

Exploring the Effects of Cyclosporin A to Isocyclosporin A Rearrangement on Ion Mobility Separation.

Cyclosporin A (CycA) is a peptide secondary metabolite derived from fungi that plays a crucial role in transplantation surgery. Cyclic traveling wave ion mobility mass spectrometry (IM-MS) revealed an N → O peptidyl shift in singly protonated CycA to isocyclosporin A (isoA), whereas no such isomerization was observed for doubly protonated and sodiated molecules. CycA and isoA were able to be separated by considering doubly protonated precursors using a specific ion fragment. In parallel, sodium ion stabilization facilitated the simultaneous separation and quantitation of singly charged cyclosporin isomers with the limit of detection and coefficient of determination of 1.3% and 0.9908 for CycA in isoA and 1.0% and 0.9830 for isoA in CycA, respectively. Finally, 1H-13C gHSQC NMR experiments permitted parallel recording of up to 11 cyclosporin conformers. The ratios were determined by integrating the volume of cross-peaks of the upfield resonating hydrogen in the diastereotopic methylene group of sarcosine-3.

UCOMB-real life data: treatment strategies for chronic urticaria patients with comorbidities.

BACKGROUND: There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities. METHODS: We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines. RESULTS: Of 212 patients, 108 (mean age 48.9 years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6 months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9 months (SD ± 3.2) and one quadruple therapy (2.1 months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria. CONCLUSIONS: Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile.

A retrospective analysis of 65 patients with acrodermatitis continua of Hallopeau.

There are limited data on acrodermatitis continua of Hallopeau (ACH), particularly among Asian populations. The primary aim was to evaluate the clinical features of ACH and treatment approaches in a sizeable multicentre Asian cohort. We analysed data from adult patients diagnosed with ACH. Of 65 patients with ACH, seven patients had ACH with GPP. Females were more frequently affected in both conditions. Five (71.4%) developed GPP 5-33 years after ACH onset, while two (28.6%) developed GPP concurrently with ACH. The onset age for ACH with GPP (27.9 ± 13.6 years) was earlier than that of isolated ACH (39.8 ± 17.3 years). Metabolic comorbidities were common. ACH exhibited a chronic persistent course. Among systemic non-biologics, acitretin was the most frequently prescribed, followed by ciclosporin and methotrexate. Acitretin and ciclosporin demonstrated similar marked response rates, which surpassed that of methotrexate. Regarding biologics, a marked response was more commonly observed with interleukin-17 inhibitors than with tumour necrosis factor inhibitors. Females are predominant in both conditions. The onset age for ACH among Asian patients is earlier (late 30s) than that for Caucasian patients (late 40s). Interleukin-17 inhibitors may be more effective than tumour necrosis factor inhibitors in managing ACH.

Pancytopenia with aplastic anemia in systemic lupus erythematosus: case series and literature review.

Aplastic anemia (AA) is a rare, potentially catastrophic hematopoiesis failure manifested by pancytopenia and bone marrow aplasia. AA occurrence in Systemic Lupus Erythematosus (SLE) patients is extremely rare. The diagnosis may be delayed due to other possible pancytopenia etiologies. Confirmation of peripheral cytopenias diagnosis necessitates a bone marrow aspiration. The management of AA is challenging, and the literature reported using glucocorticoids, danazol, plasmapheresis, cyclophosphamide, intravenous immunoglobulin, and cyclosporine. We report two cases of SLE patients who presented with pancytopenia, with bone marrow biopsy confirmed AA. One case was treated with cyclophosphamide but unfortunately succumbed to Acute Respiratory Distress Syndrome (ARDS), while the other case was managed with rituximab with a good response. Interestingly, both patients were on azathioprine before the diagnosis of AA. A comprehensive search for reported cases of AA in PubMed, Scopus, and the Directory of Open Access Journals databases was performed to enhance the understanding of the diagnostic and management challenges associated with AA in SLE, facilitating ongoing exploration and research in this field. The decision to do a BM aspiration and biopsy is recommended for SLE patients with an abrupt decline in blood counts and previously stable blood counts.