Use Of Conventional Therapy Research Articles

The temporal association between hospital admissions, biological therapy usage and direct healthcare costs in rheumatoid arthritis patients.

TheAustralian Pharmaceutical Benefits Scheme (PBS) hassubsidised biological therapy since 2003. We investigated the association between biological therapy for RA hospitalisation rates and health-care costs.Hospital admissions for RA patients between 1995 and 2014 were identified in the Western Australia (WA) Hospital Morbidity Data Collection (ICD codes 714 and M05.00-M06.99). State-specific dispensing data for conventional and biological therapies for RA was obtained from Statistics Australia and expressed as defined daily doses/1000 population/day (DDD) using WA population census. Principal component analysis (PCA) was applied to determine the relationship between DMARDs use and hospital admission rates.A total of 17,125 patients had 50,353 admissions with a diagnostic code for RA. Between 1995 and 2002, the number of RA admissions fell from 7.9 to 2.6/1000 admissions, while conventional therapy use rose from 1.45 to 1.84 DDD. Between 2003 and 2014, RA admissions decreased further to 1.9/1000 hospital admissions, while conventional therapy use increased to 2.19 DDD and biological therapy from 0.01 to 1.0 DDD. In PCA, conventional and biological therapies use had an inverse relationship with hospital admission rates. Annual costs of biological therapy utilisation was 22.5 million in 2003-2014, while theannual cost saving of RA hospital admissions was 9.2 million.The increased use of conventional therapy use for RA has coincided with a significant decline in hospital admissions for RA patients in WA, while a more modest further decline followed biological therapy introduction. Biological therapy was not as cost-effective as conventional in relation to RA hospital admissions costs.

Exploring the Role of Nutraceuticals in Major Depressive Disorder (MDD): Rationale, State of the Art and Future Prospects.

Major depressive disorder (MDD) is a complex and common disorder, with many factors involved in its onset and development. The clinical management of this condition is frequently based on the use of some pharmacological antidepressant agents, together with psychotherapy and other alternatives in most severe cases. However, an important percentage of depressed patients fail to respond to the use of conventional therapies. This has created the urgency of finding novel approaches to help in the clinical management of those individuals. Nutraceuticals are natural compounds contained in food with proven benefits either in health promotion or disease prevention and therapy. A growing interest and economical sources are being placed in the development and understanding of multiple nutraceutical products. Here, we summarize some of the most relevant nutraceutical agents evaluated in preclinical and clinical models of depression. In addition, we will also explore less frequent but interest nutraceutical products which are starting to be tested, also evaluating future roads to cover in order to maximize the benefits of nutraceuticals in MDD.

Use of repetitive transcranial magnetic stimulation in an adolescent with autism spectrum disorder and comorbid major depression disorder with anxiety symptoms: A case study

IntroductionPsychiatric comorbidities, including depressive and anxiety disorders, are common in individuals with autism spectrum disorder (ASD). Use of conventional therapies for treating depression and anxiety are of limited efficacy in individuals with ASD making treatment a challenging field. Repetitive Transcranial Magnetic Stimulation (rTMS) is a safe and efficacious technique in major depressive disorder, and a similar approach could yield therapeutic benefits in ASD.ObjectivesThe aim of this case study is to present the effectiveness of rTMS in a 17 year old patient diagnosed with ASD and comorbid major depression disorder with anxiety symptoms.MethodsThis is a case study of a male adolescent aged 17, diagnosed with ASD and comorbid major depression disorder with anxiety symptoms, suicidal ideation and aggressive behavior. The protocol applied was 4 weeks of daily rTMS sessions. This involved rTMS to the left dorsomedial prefrontal cortex (10 Hz, 3.000 pulses/120% motor threshold) to treat depressive symptoms and to the right (50Hz, 600 pulses/ 120%motor threshold) to treat anxiety symptoms. Assessments were conducted using the BDI, PHQ-9 and GAD-7 scales at baseline and one month follow up. Suicidal ideation and aggressive behavior were assessed by a clinician at same intervals.ResultsPatient showed overall improvement in scores both in depression and anxiety scales. Suicidal Ideation and aggressive behavior showed significant reduction. No side effects were recorded during therapy.ConclusionsOur findings suggest that the use of rTMS therapy in adolescents in the autistic spectrum and comorbid major depression disorder and anxiety symptoms is an efficacious and safe therapeutic treatment option.

JARID1-targeted histone H3 demethylase inhibitors exhibit anti-proliferative activity and overcome cisplatin resistance in canine oral melanoma cell lines.

Histone demethylases are overexpressed or display altered activity in numerous human cancers leading to alterations in cell cycle dynamics, DNA repair kinetics, and therapeutic resistance. Consequently, therapeutic targeting of histone demethylases has become an active and promising area of research in human oncology. However, the role of histone demethylases and the potential efficacy of demethylase inhibition in canine cancers remains largely unknown. In the present work, we addressed this knowledge gap by exploring the therapeutic potential of histone demethylase inhibitors (HDIs) in canine oral melanoma. Using canine melanoma cell lines, we determined that broad spectrum HDIs result in decreased cell survival and prolonged DNA damage repair kinetics. We then showed that JARID1B, a histone H3 demethylase implicated in proliferation-dormancy regulation and drug sensitivity in human cancers, is highly expressed in canine tumour tissues. HDIs targeting JARID1B, and related JARID1 family members, significantly reduced survival fractions in canine melanoma cell lines, but did not appear to modulate DNA damage repair kinetics like broad spectrum HDI treatments. Importantly, we found that the anti-proliferative effects of JARID1-targeted HDIs are preserved in cell lines resistant to platinum-based chemotherapeutics, suggesting that HDIs may serve as a viable therapeutic strategy when faced with oral melanomas that progress despite the use of conventional therapies.

From Conventional to Precision Therapy in Canine Mammary Cancer: A Comprehensive Review.

Canine mammary tumors (CMTs) are the most common neoplasm in intact female dogs. Canine mammary cancer (CMC) represents 50% of CMTs, and besides surgery, which is the elective treatment, additional targeted and non-targeted therapies could offer benefits in terms of survival to these patients. Also, CMC is considered a good spontaneous intermediate animal model for the research of human breast cancer (HBC), and therefore, the study of new treatments for CMC is a promising field in comparative oncology. Dogs with CMC have a comparable disease, an intact immune system, and a much shorter life span, which allows the achievement of results in a relatively short time. Besides conventional chemotherapy, innovative therapies have a large niche of opportunities. In this article, a comprehensive review of the current research in adjuvant therapies for CMC is conducted to gather available information and evaluate the perspectives. Firstly, updates are provided on the clinical–pathological approach and the use of conventional therapies, to delve later into precision therapies against therapeutic targets such as hormone receptors, tyrosine kinase receptors, p53 tumor suppressor gene, cyclooxygenases, the signaling pathways involved in epithelial–mesenchymal transition, and immunotherapy in different approaches. A comparison of the different investigations on targeted therapies in HBC is also carried out. In the last years, the increasing number of basic research studies of new promising therapeutic agents on CMC cell lines and CMC mouse xenografts is outstanding. As the main conclusion of this review, the lack of effort to bring the in vitro studies into the field of applied clinical research emerges. There is a great need for well-planned large prospective randomized clinical trials in dogs with CMC to obtain valid results for both species, humans and dogs, on the use of new therapies. Following the One Health concept, human and veterinary oncology will have to join forces to take advantage of both the economic and technological resources that are invested in HBC research, together with the innumerable advantages of dogs with CMC as a spontaneous animal model.

IDENTIFYING INADEQUATE RESPONSE AMONG CROHN’S DISEASE PATIENTS ON A BIOLOGIC IN A REAL-WORLD ADMINISTRATIVE CLAIMS DATABASE

Abstract Objectives The purpose of this analysis was to assess the frequency of inadequate response (IR) over 1 year from biologic initiation among Crohn’s disease (CD) patients in the United States using a claims-based algorithm. Baseline factors associated with IR to a biologic were also analyzed. Methods This was a retrospective cohort study using claims data from the HealthCore Integrated Research Database. Adult patients with CD who initiated a biologic (TNFi: adalimumab, certolizumab, infliximab; non-TNFi: natalizumab, ustekinumab, and vedolizumab) from 7/1/2016 to 8/31/2018 and had continuous enrollment ≥6 months before and ≥12 months after index date (date of first biologic claim) were included. The index biologic was defined as the first biologic prescribed during the study time period. The claims-based algorithm used in this study to identify IR was originally developed and validated in rheumatoid arthritis and was modified for CD patients. Patients were identified as having IR to their index biologic if during the 12 months after index date they had one or more of the following: low adherence (defined as proportion of days covered (PDC)<80%), switched/added new biologic, added a new conventional therapy, increased dose/frequency of biologic, addition or dose increase of oral glucocorticoids, used a new pain medication, or had surgery for CD. Baseline patient characteristics were compared between responders and IRs using Chi-square tests for categorical variables and t-tests for continuous variables. A multivariable logistic regression model was constructed to identify baseline characteristics associated with IR to the index biologic. Results A total of 2,437 CD patients were included in this analysis. Mean age was 41 years, 53% were female, 81% initiated a TNFi, and 19% initiated a non-TNFi as their index biologic (Table 1). Over the 1-year follow-up period, 62% of CD patients had an IR to their biologic: 41% of patients had low adherence, 14% switched/added a new biologic, 13% added a new conventional therapy, 12% had a dose/frequency increase of their index biologic, 12% had an addition/dose increase of oral glucocorticoids, 8% used a new pain medication, and 5% had surgery. Inadequate responders were more likely to be female (odds ratio (OR)=1.36; p<0.001), have historical use of TNFi (OR=1.94; p<0.001), and be on a consumer-driven health plan (OR=1.28; p<0.001); while patients with baseline use of conventional therapy were more likely to be responders (OR=0.72; p<0.001) (Table 2). Conclusion Over 62% of CD patients had an inadequate response to their index biologic within 1 year after initiation, mostly driven by low adherence. This modified claims-based algorithm for CD appears useful to classify inadequate responders in health plan claims data. Additional research is needed to further validate this algorithm in a clinical setting.

Design, synthesis, and biological evaluation of tetrahydroisoquinolines derivatives as novel, selective PDE4 inhibitors for antipsoriasis treatment.

Psoriasis is a kind of chronic inflammatory skin disorder, while the long-term use of conventional therapies for this disease are limited by severe adverse effects. Novel small molecules associated with new therapeutic mechanisms are greatly needed. It is known that phosphodiesterase 4 (PDE4) plays a central role in regulating inflammatory responses through hydrolyzing intracellular cyclic adenosine monophosphate (cAMP), making PDE4 to be an important target for the treatment of inflammatory diseases (e.g. psoriasis). In our previous work, we identified a series of novel PDE4 inhibitors with a tetrahydroisoquinoline scaffold through structure-based drug design, among which compound 1 showed moderate inhibition activity against PDE4. In this study, a series of novel tetrahydroisoquinoline derivatives were developed based on the crystal structure of PDE4D in complex with compound 1. Anti-inflammatory effects of these compounds were evaluated, and compound 36, with high safety, permeability and selectivity, exhibited significant inhibitory potency against the enzymatic activity of PDE4D and the TNF-α release from the LPS-stimulated RAW 264.7 and hPBMCs. Moreover, an invivo study demonstrated that a topical administration of 36 achieved more significant efficacy than calcipotriol to improve the features of psoriasis-like skin inflammation. Overall, our study provides a basis for further development of tetrahydroisoquinoline-based PDE4 inhibitors against psoriasis.

Therapeutic Efficacy of Urinile Against Gouty Arthritis.

Gout is arthritis caused due to Monosodium urate (MSU) crystals deposition occurring particularly in patients with associated comorbidities limiting the use of conventional therapies. This study was planned to evaluate the therapeutic efficacy of urinile (a herbal drug) for the treatment of gouty arthritis. Allopurinol was used as standard drug (positive control). The study population of 250 volunteers (gouty arthritis patients) were divided into 2 groups as test and control group (n = 125 each). Gouty arthritis patients in test and control group were treated with 300 mg each of urinile and allopurinol, respectively. Clinical symptoms of all the study volunteers were recorded and serum uric acid was determined. Significant (p < 0.05) reduction in serum uric acid level toward normal was found in test group individuals. Clinical symptoms of gouty arthritis patients were also improved in test group compared to control group. Results showed that urinile has the potential to decrease serum uric acid level in gouty arthritis patients probably because of its antioxidant potential and xanthine oxidase inhibitory activity. It can be concluded that the tested herbal drug urinile is more potent in treating gouty arthritis patients and can be used as an effective alternative to the most commonly used allopathic drugs.

Uterus duplex bicornis cum vagina subsepta infrasimplici или uterus didelphys cum vagina subseptainfra simplici?

The various deformities found in the area of ​​female genital organs are of interest to us not only as a deviation from the laws according to which the forms of individual creatures develop, but also according to those functional features that are completely dependent on the properties, location and degree of development of the existing defect. They are interesting for the practicing physician in the sense that the morbid phenomena and functional deviations that have developed as a result of their morbidity require special individual therapy based on a comprehensive study of this defect. The developed diseases on the basis of a viciously developed organ require the careful use of conventional therapy. Finally, in the diagnostic sense, they sometimes present such difficulties that are not always even resolved positively on the sectional table.

Regeneration of hyaline cartilage in osteochondral lesion model using L-lysine magnetic nanoparticles labeled mesenchymal stem cells and their in vivo imaging.

Treatment of osteochondral defects continues to pose a major challenge for patients and orthopedic surgeons due to the limited healing potential of articular cartilage. Mesenchymal stem cells (MSCs) possess therapeutic potential for the treatment of osteochondral pain and pathology. However, it is necessary to use proper labeling and imaging agent of stem cells that can decipher its role posttransplantation. A major limitation of routinely used contrast agents is signal dilution over a period of time which limits its use for further studies. At the same time, regeneration of fibrocartilage over native hyaline cartilage also limits the use of conventional therapies. The present study evaluates the efficacy of bone marrow-derived mesenchymal stem cells (BMSCs) for the treatment of osteochondral defect in rats with the regeneration of hyaline cartilage in situ and in vivo monitoring of the stem cells using L-lysine functionalized magnetic iron oxide nanoparticles (lys-IONPs). L-lysine stabilizes the iron oxide nanoparticles, enhances the biocompatibility, and provides functionalities for efficient stem cell labeling. in vitro toxic effects of lys-IONPs on mitochondrial impairment, morphological alterations, and actin cytoskeleton reveal minimum damage to BM-MSCs. Histological data (H and E, Masson's trichrome and immunohistochemistry) describe the early initiation of healing and regeneration of hyaline-like cartilage over fibrocartilage in stem cell treated groups. MR scans demonstrate generation of hypointense signals in lys-IONPs-BMSCs with improved signal intensity and minimum loss over 28 days revealing its use as a long-term stem cell labeling and imaging agent.

Complementary and Alternative Medicine Use in Pediatric Functional Abdominal Pain Disorders at a Large Academic Center

To describe the use of complementary and alternative medicine (CAM) in pediatric functional abdominal pain disorders at a large Midwestern pediatric gastroenterology center. A survey of patients attending a follow-up visit for functional abdominal pain disorders was completed. Data were collected on demographics, quality of life, use of conventional therapies, patient's opinions, and perception of provider's knowledge of CAM. Of 100 respondents (mean age, 13.3±3.5years), 47 (60% female) had irritable bowel syndrome, 29 (83% female) had functional dyspepsia, 18 (67% female) had functional abdominal pain, and 6 (83% female) had abdominal migraine (Rome III criteria). Ninety-six percent reported using at least 1 CAM modality. Dietary changes were undertaken by 69%. Multivitamins and probiotics were the most common supplements used by 48% and 33% of respondents, respectively. One-quarter had seen a psychologist. Children with self-reported severe disease were more likely to use exercise (P<.05); those with active symptoms (P<.01) or in a high-income group (P<.05) were more likely to make dietary changes; and those without private insurance (P<.05), or who felt poorly informed regarding CAM (P<.05), were more likely to use vitamins and supplements. Seventy-seven percent of patients described their quality of life as very good or excellent. The use of CAM in children with functional abdominal pain disorders is common, with a majority reporting a high quality of life. Our study underscores the importance of asking about CAM use and patient/family knowledge of these treatments.

Chinese Medicine for Psoriasis Vulgaris Based on Syndrome Pattern: A Network Pharmacological Study.

Background The long-term use of conventional therapy for psoriasis vulgaris remains a challenge due to limited or no patient response and severe side effects. Complementary and alternative treatments such as traditional Chinese medicine (TCM) are widely used in East Asia. TCM treatment is based on individual syndrome types. Three TCM formulae, Compound Qingdai Pills (F1), Yujin Yinxie Tablets (F2), and Xiaoyin Tablets (F3), are used for blood heat, blood stasis, and blood dryness type of psoriasis vulgaris, respectively. Objectives To explore the mechanism of three TCM formulae for three syndrome types of psoriasis vulgaris. Methods The compounds of the three TCM formulae were retrieved from the Psoriasis Database of Traditional Chinese Medicine (PDTCM). Their molecular properties of absorption, distribution, metabolism, excretion and toxicity (ADME/T), and drug-likeness were compared by analyzing the distribution of compounds in the chemical space. The cellular targets of the compounds were predicted by molecular docking. By constructing the compound-target network and analyzing network centrality, key targets and compounds for each formula were screened. Three syndrome types of psoriasis vulgaris related pathways and biological processes (BPs) were enriched by the Database for Annotation, Visualization, and Integrated Discovery (DAVID) v6.8. Results The compounds of the three formulae exhibited structural diversity, good drug-like properties, and ADME/T properties. A total of 72, 97 and 85 targets were found to have interactions with compounds of F1, F2, and F3, respectively. The three formulae were all related to 53 targets, 8 pathways, 9 biological processes, and 10 molecular functions (MFs). In addition, each formula had unique targets and regulated different pathways and BPs. Conclusion The three TCM formulae exhibited common mechanisms to some extent. The differences at molecular and systems levels may contribute to their unique applications in individualized treatment.

Immunogenic cell death by neoadjuvant oxaliplatin and radiation protects against metastatic failure in high-risk rectal cancer

ObjectiveHigh rates of systemic failure in locally advanced rectal cancer call for a rational use of conventional therapies to foster tumor-defeating immunity.MethodsWe analyzed the high-mobility group box-1 (HMGB1) protein, a measure of immunogenic cell death (ICD), in plasma sampled from 50 patients at the time of diagnosis and following 4 weeks of induction chemotherapy and 5 weeks of sequential chemoradiotherapy, both neoadjuvant modalities containing oxaliplatin. The patients had the residual tumor resected and were followed for long-term outcome.ResultsPatients who met the main study end point—freedom from distant recurrence—showed a significant rise in HMGB1 during the induction chemotherapy and consolidation over the chemoradiotherapy. The higher the ICD increase, the lower was the metastatic failure risk (hazard ratio 0.26, 95% confidence interval 0.11–0.62, P = 0.002). However, patients who received the full-planned oxaliplatin dose of the chemoradiotherapy regimen had poorer metastasis-free survival (P = 0.020) than those who had the oxaliplatin dose reduced to avert breach of the radiation delivery, which is critical to maintain efficient tumor cell kill and in the present case, probably also protected the ongoing radiation-dependent ICD response from systemic oxaliplatin toxicity.ConclusionThe findings indicated that full-dose induction oxaliplatin followed by an adapted oxaliplatin dose that was compliant with full-intensity radiation caused induction and maintenance of ICD and as a result, durable disease-free outcome for a patient population prone to metastatic progression.

Tissue engineering and regenerative medicine strategies for the female breast.

The complexity of mammary tissue and the variety of cells involved make tissue regeneration an ambitious goal. This review, supported by both detailed macro and micro anatomy, illustrates the potential of regenerative medicine in terms of mammary gland reconstruction to restore breast physiology and morphology, damaged by mastectomy. Despite the widespread use of conventional therapies, many critical issues have been solved using the potential of stem cells resident in adipose tissue, leading to commercial products. in vitro research has reported that adipose stem cells are the principal cellular source for reconstructing adipose tissue, ductal epithelium, and nipple structures. In addition to simple cell injection, construct made by cells seeded on a suitable biodegradable scaffold is a viable alternative from a long‐term perspective. Preclinical studies on mice and clinical studies, most of which have reached Phase II, are essential in the commercialization of cellular therapy products. Recent studies have revealed that the enrichment of fat grafting with stromal vascular fraction cells is a viable alternative to breast reconstruction. Although in the future, organ‐on‐a‐chip can be envisioned, for the moment researchers are still focusing on therapies that are a long way from regenerating the whole organ, but which nevertheless prevent complications, such as relapse and loss in terms of morphology.

Parental use of conventional and complementary therapy for autism in Jordan

ObjectiveWe investigated parental use of conventional therapies and complementary and alternative medicine (CAM) for children with autism in Jordan. MethodThis prospective cross-sectional study was conducted from February 2018 through December 2018 at the paediatric neurology clinics of three tertiary referral hospitals in Jordan. The accompanying parent was interviewed to complete a structured questionnaire. Results274 parents were interviewed. The most common medications used were those to treat hyperactivity (150; 54.7 %), anticonvulsants (60; 21.9 %), and sleep aids (6; 2.1 %). CAM was used by 129 parents (47.0 %). A casein-free diet was the most commonly used dietary modification (24; 8.7 %), while fish oil (Omega-3) was the most common supplement used (96; 35.0 %). Hyperbaric oxygen, chelation therapy, and antifungal treatment were also occasionally used. Higher parental education levels and access to rehabilitation services correlated with higher CAM use (p < 0.05).

Change in the Expression of BAK، FAS، BAX، TNF-A، BCL-2 and Survivin Apoptosis Genes of the Human Breast Adenocarcinoma Cells (MCF-7) by Staphylococcal Enterotoxin B

Introduction: Breast cancer is one of the most prevalent malignancies among women. Patients whose suffering from this condition, as a result of the use of conventional therapies often have a poor response to treatment and the relapse among them is frequent. In this study, the effects of staphylococcal enterotoxin type B on BAK، FAS، BAX، TNF-a، BCL-2 و Survivin genes expression in human breast adenocarcinoma cells (MCF-7) was examined. Staphylococcal enterotoxin B is a powerful member of the Staphylococcus aureus toxins family, which is known as an anticancer agent with potential for killing cancer cells. Methods: The experimental study was carried out at the Biotechnology Research Center of Islamic Azad University, Shahrekord Branch. By using Lipofectamine 2000 reagent, MCF-7 cells transfected with the pcDNA3.1(+)-seb (recombinant) and pcDNA3.1(+) (non-recombinant) plasmids and were selected by culturing in a selective medium of RPMI- 1640 containing 600 μg / mL antibiotic G418. Then, the expression of BAK, FAS, BAX, TNF-a, BCL-2, and Survivin genes in transfected cells were analyzed by real time PCR. Student's t-test, SPSS Inc., Chicago, IL; Version 16 and also Excel program for statistical analysis were used. Results: The results of this study indicated that staphylococcal enterotoxin type B (SEB) remarkably changes the expression of apoptotic related genes in MCF-7 cell line. It was observed a significant increase in the expression of BAK, FAS, BAX, and TNF-a genes, the expression of BCL-2 and Survivin genes significantly decreased compared to the control group (P=0/032). Conclusion: Staphylococcal enterotoxin type B has an inhibitory effect on the growth, proliferation and invasion of breast adenocarcinoma cells through altering the expression of the genes involved in the apoptosis process. Therefore, it seems that there is a good research field for the use of this toxin in the control and treatment of human breast adenocarcinoma.

Inhibition of dendritic cells and Th17 cells by a flavonoid compound attenuates clinical severities in a murine collagen-induced arthritis model

Abstract Rheumatoid arthritis is a common autoimmune disease, which leads to severe disabilities and affecting approximately one percent of the worldwide population. It is manifested with significant infiltration of immune cells, synovial inflammation, bone erosion and progressive disability. Despite the use of conventional therapies and biological agents, there are still some unmet needs and concerns. We aimed to develop novel therapeutic agents for the treatment of rheumatoid arthritis. We first identified that flavonoid compound CD001 derived from plants possesses suppressive effects on the maturation of dendritic cells and reduced the production of cytokines by dendritic cells. CD001 inhibited the Th17 differentiation in a dose-dependent manner in vitro. CD001 also inhibited the IL-6 secretion by SW982 synovial cells stimulated by IL-17 in vitro. Furthermore, in a murine model of collagen-induced arthritis, administration of CD001 significantly ameliorated paw edema and clinical scores in a dose-dependent manner. IL-17, IL-22 and TNF-a production of CD4 T cells decreased after treatment with CD001, while the percentage of Tregs increased. Immunohistochemistry stains also showed that CD001 decreased IL-17+ cells in the joints. In summary, pharmacological approach to inhibit dendritic cells and Th17 cells may be a promising intervention to treat rheumatoid arthritis.

Topical Treatment of Persistent Epithelial Defects with a Matrix Regenerating Agent.

The aim of the study was to assess the efficacy of a topical regenerating agent (RGTA) for management of persistent epithelial defects (PEDs) resistant to conventional therapy. Twenty-one patients (23 eyes) with PEDs despite the use of conventional therapy for lagophthalmos (n = 4), neurotrophic ulcer (n = 9), chemical burn (n = 3), Stevens-Johnson syndrome (n = 1), atopic keratoconjunctivitis (n = 1), severe dry eye (n = 2), peripheral ulcerative keratitis (n = 1), fungal keratitis (n = 1), and bacterial keratitis (n = 1) were enrolled in the study. Patients were treated with RGTA (Cacicol; Thea, Paris, France) instilled at a dosage of one drop on alternate days. Patients were evaluated by slit-lamp examination, anterior segment photography, and fluorescein-dye testing. Ulcer areas were noted on alternate days starting from the first day of instillation. Twenty of 23 eyes (86.9%) displayed complete corneal healing after a mean period of ∼7.2 days (range, 2-20 days). Mean decrease ratio of ulcer area observed was 61.2% (range, 8.8%-100%, n = 19) on the 2nd day, 74.4% (range, 36%-100%, n = 16) on the 4th day, 80.2% (range, 43.7%-100%, n = 12) on the 6th day, 88.5% (range, 55.9%-100%, n = 9) on the 8th day, and 85.5% (range, 58.3%-100%, n = 7) on the 10th day. No significant differences were found in the epithelialization speed between eyes with and without bandage contact lenses in any postoperative day (P > 0.05). There were no treatment-related local or systemic side effects during the study. RGTA seems to be an effective therapeutic alternative in the treatment of persistent corneal epithelial defects.

Rapid glucocorticoid tapering therapy to reduce mortality from pneumocystis pneumonia in patients with rheumatic disease

Objective: Pneumocystis pneumonia (PCP) is a serious complication in patients with rheumatic diseases who are receiving immunosuppressive therapy. These patients have a higher mortality from PCP than those with human immunodeficiency virus. We examined factors associated with poor prognosis in patients with rheumatic diseases and evaluated PCP treatment in this population.Methods: This retrospective, single-center, observational cohort study included 31 patients with rheumatic diseases who were admitted to Juntendo University Hospital for PCP treatment from June 2006 to December 2017. The primary outcome was non–disease-specific mortality at discharge.Results: The median age at PCP diagnosis was 64 years. The survival rate was 61.3% (19/31). Twelve patients died, in all cases due to respiratory failure due to PCP. Among variables at PCP diagnosis and those related to PCP treatment, the presence of coexisting pulmonary diseases and greater glucocorticoid dose at PCP diagnosis were associated with higher mortality. The mortality related to biological agents for PCP was low. Rapid tapering of glucocorticoids improved survivability.Conclusion: In the treatment of PCP in patients with rheumatic diseases, rapid tapering of glucocorticoids was associated with a higher survival rate than the use of conventional therapy.

A Beacon in the Dark: Canakinumab. A New Therapeutic Perspective in Chronic Tophaceous Gout.

Novartis Farma, Italy.