Administration Of Biological Agents Research Articles

Autoimmunity and Cancer: Two Stations on the Same Continuum.

Autoimmunity has been associated with different types of cancer, including hematological malignancies like lymphomas, and solid tumors. Additionally, the potential role of medication-induced immunosuppression should be considered. Our study aimed to investigate the relationship between autoimmunity and the development of cancer, as well as the impact of immunosuppressive drugs on increasing cancer risk. The study sample was composed of patients who developed cancer after the administration of biological agents for the treatment of autoimmune disorders. Selected patients were treated in our hospital between 1st January 2011 and 31st December 2021 and followed up in internal medicine, gastroenterology, or dermatology consult. From 434 patients with autoimmune diseases using biological agents, only 20 developed cancer, which was our final study sample. The data analysis was performed using the IQVIR package version 2.0.2 (IQVIA, Durham, NC). A p-value of <0.05 was considered statistically significant. We found a significant correlation between long-term corticosteroid therapy and an increased risk of cancer. However, the effect of biological therapies on cancer risk was not statistically significant. It's worth noting that our sample size was small, so we cannot extrapolate these findings. Physicians need to be aware that treating autoimmune diseases with immunosuppressive therapies may contribute to the development of cancer. Further research is needed to determine the impact of such treatments on cancer prognosis.

Transition from intravenous to subcutaneous biological therapies in inflammatory bowel disease: An online survey of patients.

The transition from in-hospital intravenous administration to subcutaneous therapies to treat inflammatory bowel disease (IBD) can raise some concerns among patients due to the self-administration concerns, the management of potential side effects and the overall worries related to a change of treatment. This study aimed at evaluating patients' opinion about the switch from intravenous to subcutaneous formulations and their knowledge on new available therapeutic options. We conducted a survey using a questionnaire prepared by a team of gastroenterologists and nurses working at the IBD unit. It consists of 31 items and has been divided into four sections: descriptive, commitment, knowledge and passage mode opinion. The questions were formulated in Italian and conceived according to daily consultations with patients in everyday practice, without any previous piloting or specific medical literature reference. The survey was administered to consecutive IBD patients in intravenous biological treatment; patients currently or previously treated with subcutaneous therapy were excluded. Four hundred questionnaires were distributed to participants. As many as 311 patients (77.7%) completed the survey, while the remaining were excluded from the analysis; 155 (49.8%) patients were favorable to switch from intravenous to subcutaneous therapy, while only 78 (25.1%) disagreed. In univariate and multi-variate analysis, the approval rate for home therapy was significantly associated with the distance from the IBD center and work/family/personal commitments. Surprisingly, only a quarter of the IBD patients knew that almost all available therapeutic agents have a subcutaneous administration route. Regarding patients' opinion on the efficacy of subcutaneous administration of biological agents compared to intravenous drugs, 194 (63%) had no definite idea, while 44 (14%) believed that the effectiveness could be reduced. The transition from in-hospital to subcutaneous therapeutic management of biological therapy at home was generally viewed favorably by patients, especially if they have commitments or were residents far from the IBD center.

P16.05.B SAFETY AND EFFICACY OF INTRA-CSF BIOLOGIC AGENTS IN TREATMENT OF NEOPLASTIC MENINGITIS

Abstract BACKGROUND Neoplastic meningitis (NM) is an increasingly frequent, profoundly morbid, and almost invariably fatal complication of solid and hematologic malignancies. Despite multimodal therapy, median survival in randomized trials is approximately 4 months. Biologic agents are widely utilized in management of extra-CSF disease, but often have limited ability to penetrate the CSF. Intra-CSF administration of biologic agents has not been widely investigated. We describe the safety and efficacy of tumor-specific, intra-CSF biologic therapy in a large group of patients with neoplastic meningitis. MATERIAL AND METHODS We queried the database of a large, international neoplastic meningitis registry (NeMeRe) to identify patients with neoplastic meningitis who received at least one dose of neoplastic meningitis-directed therapy with a biologic agent. Detailed patient demographic, treatment, toxicity and outcome data was extracted and analyzed for the first 140 consecutive patients treated at our institution. RESULTS These 140 patients received an intrathecal biologic agent as part of a histology- and molecular profile-directed intraventricular chemotherapy treatment approach. Agents included rituximab (58 patients with lymphoma, 224 cycles), trastuzumab (42 patients with malignant primary brain tumors, 211 cycles; 15 patients with breast cancer, 149 cycles; 1 patient with esophageal cancer, 9 cycles), panitumumab (4 patients with lung cancer, 9 cycles), nivolumab (1 patient with melanoma, 5 cycles; 2 patients with breast cancer, 2 cycles; 2 patients with GBM 12 cycles; 2 patients with lung cancer, 4 cycles; 2 patients with gastric adenocarcinoma, 17 cycles; 2 patients with renal clear cell carcinoma, 17 cycles; 1 patient with AML, 2 cycles; 1 patient with multiple myeloma, 8 cycles) and alpha-interferon (10 patients with melanoma, 31 cycles; 2 patients with renal clear cell carcinoma, 18 cycles). Grade I/II toxicity occurred in 5.8% of rituximab, 3.2% of trastuzumab, 0% of panitumumab, 16.3% of nivolumab, and 3.2% of alpha-interferon containing cycles. There was no grade III toxicity. Median survivals in patients with lymphomatous meningitis (304 days), solid tumor NM from primary brain tumors (243 days), HER2 -positive breast cancer (not reached, &amp;gt;315 days), lung cancer (192 days), and melanoma (307 days) were encouraging. No difference in survival was seen between patients with and without treatment-related toxicity in any histologic group. CONCLUSION This large registry-based cohort study suggests that rituximab, trastuzumab, panitumumab, nivolumab, and alpha interferon may be safely administered into the CSF as part of a multi-agent intra-CSF treatment regimen. Survival, while very tentative, is encouraging. A prospective, multi-center evaluation of these agents in patients with neoplastic meningitis is warranted.

N04 How to manage the concerns of patients with inflammatory bowel disease due to the transition from in-hospital to home management with oral or subcutaneous therapies: results of a survey of a cohort of patients in intravenous biologic treatment

Abstract Background Therapeutic armamentarium of inflammatory bowel disease (IBD) has expanded, including several intravenous (IV) and subcutaneously administered biological agents and orally administered small molecules (SMs). Additionally, some biologics initially available only for IV administration also have subcutaneous (SC) formulations. However, transitioning from in-hospital IV treatment to SC or oral home therapy can lead to some patient concerns, mainly linked to the need for self-administration and managing side effects. This study aimed to evaluate the opinion of IBD patients on the transition to oral or SC treatment, considering multiple socio-demographic factors, the frequency of biologic agent infusion, and the commitments (personal, family, work) associated with the in-hospital administration of therapy. In addition, patients were asked about their knowledge of new therapeutic options and their expectations about this management modality. Methods We conducted a survey using a questionnaire prepared by a team of gastroenterologists and nurses working at the IBD Unit of the CEMAD-Policlinico Gemelli of Rome. The survey was administered to consecutive IBD patients in stable IV biological treatment from January to October 2022. It consists of 31 items and has been divided into four sections: descriptive, commitment, knowledge and passage mode opinion. Results 311 patients responded to the survey from 400 questionnaires (77.7%). 49.8% favored switching from IV to oral or SC therapy, and only 25.1% disagreed. In univariate and multivariate analysis, the home therapy approval rate was significantly associated with the distance from the IBD center (Fig. 1) and work/family/personal commitments. Surprisingly, only about a quarter of the IBD patients knew that almost all the following available therapeutic agents will have an SC administration route or will be SMs (Fig. 2). Regarding patients' opinion on the efficacy of SMs or SC administration of biological agents compared to IV drugs: 63% had no definite idea, while 14% believed that the effectiveness could be reduced. 23.8% of patients would like to be reassured by their gastroenterologist or nurse on the efficacy and safety of these new therapeutic options, and 7.7% would like to know the scientific data from studies on this issue. Conclusion The transition from in-hospital to the home therapeutic management of biological therapy with SC or oral agents was generally viewed favorably by patients, especially if they have commitments or are residents far from the IBD center. However, to reduce patient concerns and encourage this change, it is necessary to implement a patient training and information program involving all the IBD unit care figures, including IBD nurses.

Transdermal Delivery of Therapeutic Compounds With Nanotechnological Approaches in Psoriasis.

Psoriasis is a chronic, immune-mediated skin disorder involving hyperproliferation of the keratinocytes in the epidermis. As complex as its pathophysiology, the optimal treatment for psoriasis remains unsatisfactorily addressed. Though systemic administration of biological agents has made an impressive stride in moderate-to-severe psoriasis, a considerable portion of psoriatic conditions were left unresolved, mainly due to adverse effects from systemic drug administration or insufficient drug delivery across a highly packed stratum corneum via topical therapies. Along with the advances in nanotechnologies, the incorporation of nanomaterials as topical drug carriers opens an obvious prospect for the development of antipsoriatic topicals. Hence, this review aims to distinguish the benefits and weaknesses of individual nanostructures when applied as topical antipsoriatics in preclinical psoriatic models. In view of specific features of each nanostructure, we propose that a proper combination of distinctive nanomaterials according to the physicochemical properties of loaded drugs and clinical features of psoriatic patients is becoming a promising option that potentially drives the translation of nanomaterials from bench to bedside with improved transdermal drug delivery and consequently therapeutic effects.

S3327 Positive Attitudes Towards Telehealth During the COVID-19 Pandemic: A Strong Sign for Continued Use in the IBD Population

Introduction: At the University of Virginia (UVA), the arrival of the COVID19 pandemic caused the rapid implementation of telehealth following a three-week moratorium on non-urgent clinic appointments. This rapid implementation provided an opportunity to assess patient attitudes towards telemedicine, and evaluate its potential for continued use post-pandemic. Patients with inflammatory bowel disease (IBD) could benefit from this novel platform given their need for serial follow ups and, at times, urgent evaluations for concerning symptoms. Additionally, many patients with IBD require regular administration of biologic agents and the effect of the pandemic on patient adherence with these medications has yet to be fully identified. Methods: All patients in the UVA IBD clinic with a telehealth appointment between March 16 and August 31 received an invitation to complete a survey on their experience. The survey contained three instruments assessing demographics, attitudes and barriers to telehealth, and medication non-compliance. Invitations were provided at follow-up clinic visits, as well as through the Mychart app or physical mail. A retrospective chart review was also conducted to determine the disease state based on provider documentation or supporting results from endoscopic exams or laboratory testing. REDCap was used to administer the survey and store responses. Results: Of the forty patients who responded, 87% reported very little or no difficulty using telehealth, 95% rated their experience with telehealth as either the same or better than in-person care, and 78% said they would prefer a telehealth appointment over an in-person visit in the future. Of the 27 patients who reported being treated with a biologic agent, none reported any modifications to their medication schedule or missed doses. Conclusion: This patient survey demonstrated a favorable patient experience with telemedicine utilized in the care of patients with IBD. In this group of those who received telemedicine, medication non-adherence was not reported. It remains to be explored if this was the result of the continued access to providers that telehealth provided or due to other patient factors.Table 1.: Patient assessment of telehealth relative to in-person clinic visits.

Psoriasis as an adverse reaction to biologic agents beyond anti-TNF-α therapy.

New onset or exacerbation of pre-existing psoriasis after therapeutic TNF-α inhibition is a well-described phenomenon. Over the last two decades, similar cases of paradoxical psoriasis have been reported following the administration of other biologic agents. We aimed to review all published cases of induced or exacerbated psoriasis after biologic therapy other than anti-TNF-α agents in order to further elucidate the pathophysiology of this phenomenon. A systematic literature review in the Medline database regarding any relevant case series or case reports on new onset or exacerbation of psoriasis after the administration of biologic agents targeting B cells, T cell co-stimulation, interleukin-1, interleukin-6, interleukin-17 and interleukin-12/23 was performed using appropriate key words. The literature search revealed nine articles (nine cases) of paradoxical psoriasis after ustekinumab and eight articles (nine cases) after secukinumab administration, both of which are approved therapies for psoriasis Moreover, 15 articles (23 cases) for rituximab, nine articles (12 cases) for abatacept, eight articles (nine cases) for tocilizumab, and one case report for anakinra have been published. In the majority of cases, patients had no prior history of psoriasis while 18 patients presented with exacerbation of pre-existing psoriatic lesions. Paradoxical psoriasis is not a specific adverse event of TNF-α inhibitors but is a possible side effect of any biologic agent interfering with the immune system. Awareness among physicians regarding early recognition is mandatory. Further clinical and experimental data are needed in order to unravel the pathophysiology of this unexpected phenomenon.

Approach to switching biologics in juvenile idiopathic arthritis: a real-life experience.

The primary aim of the treatment of juvenile idiopathic arthritis (JIA) is complete remission and minimizing the development of complications. Though biologic agents (BAs) provide better disease control, data related to BA switching patterns in JIA patients are scarce. This study aimed to determine the BA switching patterns in JIA patients. The study included children with JIA that received ≥ 1 BAs. Disease activity was evaluated based on the juvenile arthritis disease activity score 71 (JADAS71). Demographic data, clinical and laboratory findings, BA switching patterns, and the rationales for BA switching were recorded. The study included 177 (82 female and 95 male) JIA patients that received ≥ 1 BAs. Mean age at diagnosis of JIA was 9.1 ± 4.9years. BAs were prescribed a median of 14months (range: 3-66months) after diagnosis. Among the 177 patients, 31 (17.5%) required BA switching a median 10.5months (range: 3-38months) after initiation of the first BA. Among all the BAs that were switched to after administration of the first BA, tocilizumab was the most commonly switched (n = 15). The most common reason for BA switching was inadequate response (n = 29). BAs were switched 2 times in 5 patients and 3 times in 1 patient. When patients that switched BAs 1 time were compared to those that switched 2 and 3 times there were not any differences in terms of JIA types, whereas those that switched 2 and 3 times had a higher active joint count and JADAS71 score after 6months of initiation of the first BA. As some of the JIA patients could not achieve remission despite using the prescribed BA, BA switching was required. Herein, we provide data on both BA switching patterns and requirements, which may improve the management of JIA patients.

Biologic Agents Preserve the C-2 Pedicle in Patients with Rheumatoid Arthritis: A Comparative Imaging Study Using Three-Dimensional Computed Tomography

To investigate whether biologic agents (BAs) reduce a narrow C-2 pedicle screw trajectory, which is often a key stabilizer in surgical treatment, in patients with rheumatoid arthritis (RA). A total of 100 patients with RA treated with and without BAs (BA [+] group [n= 50] and BA [-] group [n= 50]), respectively, were included in the present study. Computed tomography (CT) images of their cervical spine, including C-2, were analyzed. The maximum screw diameter at C-2 that could be inserted without breaching the cortex, measured on 3-dimensional images using a CT-based navigation system, was compared between the groups with and without BA administration. Furthermore, the destruction of the atlantoaxial joint was examined using CT images. The risk factors for a narrow C-2 pedicle were elucidated among the patients treated with BAs. The pedicle in the BA (+) group had a significantly larger C-2 maximum screw diameter than the BA (-) group (6.00 mm vs. 5.13 mm, P < 0.001), with less destruction of the atlantoaxial joint. Among the BA (+) group, a longer period until the initial administration of BAs and RA disease duration were associated with a narrow C-2 pedicle. This study suggests that BAs can maintain the trajectory for C-2 pedicle screws, which acts as a key stabilizer in surgical management for the rheumatoid cervical spine, by halting the destruction of the atlantoaxial joint. Early introduction of BAs can be especially important to prevent the narrowing of the C-2 pedicle.

Understanding and Minimising Injection-Site Pain Following Subcutaneous Administration of Biologics: A Narrative Review.

Injection-site pain (ISP) is a subjective side effect that is commonly reported with the subcutaneous administration of biological agents, yet it may only be a concern to some. Multiple factors related to the product formulation, such as pH, volume and excipients, and/or to the injection process have the potential to contribute to ISP, while patient-related factors, such as low body weight, gender and age, can make an individual more susceptible to experiencing ISP. While total elimination of ISP remains unlikely with any subcutaneously administered agent, it can be minimised by helping the patient to develop a confident and competent injection technique via robust and effective training. Careful management of patient expectations along with open discussion regarding the potential risk of ISP may serve to minimise treatment-related anxieties and, importantly, allow the patient to remain in control of his/her treatment. Other interventions to help minimise ISP include psychological interventions, allowing biologics to reach room temperature prior to injection, using the most suitable injection device for the individual patient and selecting an alternative drug formulation, when available. Productive patient–physician communication remains important in order to support and optimise treatment experience and adherence, while also providing the opportunity for patients to discuss any ISP-related issues.

IVIG ameliorate inflammation in collagen-induced arthritis: projection for IVIG therapy in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease that leads to joint destruction and disability. Despite a significant progress in administration of biological agents for RA patients, there is still a need for improved therapy. Intravenous immunoglobulins (IVIG), a pooled polyspecific immunoglobulin (Ig)G extracted from 5000 to 20 000 healthy subjects, showed beneficial therapeutic effect in patients with immune deficiency, sepsis and autoimmune diseases. The current study aimed to investigate the beneficial effect of treatment with IVIG in established collagen-induced arthritis in DBA/1j mice. Murine arthritis was induced in DBA/1j mice. Treatment with IVIG began when the disease was established. The clinical score was followed twice a week until day 48. The mice were bled for plasma and the paws were hematoxylin and eosin (H&E)-stained. Cytokine profile in the plasma was analyzed by Luminex technology and titers of circulating anti-collagen antibodies in the plasma was tested by enzyme-linked immunosorbent assay. Our results show that treatment with IVIG in murine significantly reduced the clinical arthritis score (P<0·001). Moreover, mode of action showed that IVIG significantly reduced circulating levels of inflammatory cytokines [interferon (IFN)-γ, interleukin (IL)-1β, IL-17, IL-6, tumor necrosis factor (TNF)-α, P<0·001], inhibiting anti-collagen antibodies (P<0·001) in the plasma of collagen-induced arthritis mice. Importantly, histopathological examination revealed that IVIG treatment prevented the migration of inflammatory immune cells into the cartilage and synovium, reduced the extent of joint damage and preserved joint architecture. Our results proved for the first time the valuable anti-inflammatory treatment of IVIG in experimental RA. We propose IVIG therapy for a subgroup of patients with rheumatologically related diseases.

Le choix thérapeutique: médicaments du psoriasis et grossesse avant, pendant et après la grossesse.

Psoriasis typically affects young adults and therefore many women with a desire to become pregnant or already pregnant. In this particular situation, treatment can be a real challenge for some patients, especially in the case of severe forms. In addition to local treatments, which are generally well tolerated, UVB phototherapy and cyclosporin remain the first-line systemic treatments. Acitretin and methotrexate are contraindicated. Safety data regarding the administration of biologic agents during pregnancy, are reassuring, the main adverse event being immunosuppression of the newborn if treatment is not discontinued. Biologic agents should ideally be discontinued before pregnancy, but in case of absolute necessity, they can be maintained or even initiated during pregnancy. Overall, it is recommended that biologic agents should not be continued beyond the second trimester because of the risk of maternal-fetal infection. If a biologic agent should be initiated during pregnancy, tanercept or certolizumab will be preferred, because of their low transplacental passage and more extensive safety data.

Administration sequence for multi-agent oncolytic regimens.

The existence of a multitude of oncolytics regimens containing two or more agents (combination) outlines the need to define their most adequate sequence of administration. However, limited resources are currently available to specify a particular sequence, presenting challenges potentially impacting on patient safety, and Pharmacy & Infusion Nursing workflows. A comprehensive literature search was performed leading to the compilation of a document containing drug administration sequencing instructions for our Nursing, Pharmacy, and Oncology providers to follow. Regimens prioritized in our literature review represented regimens selected as part of our approved Clinical Pathways, regimens inquiries from Pharmacy or Nursing, as well as less frequently used regimens. We stratified the regimens by tumor type and arranged them alphabetically by indication. A table was compiled containing all the supporting literature for the recommended drug administration sequences. If, in certain instances, no literature support was identified outlining rationale such as enhanced management of adverse effects, a specific institutional decision was made by our enterprise Medical Oncology Committee with recommendations from Pharmacy experts. The primary guiding principles for outlining our recommendations were the following: administration of vesicant agents first; administration of biologic agents first; administration of taxanes prior to platinum agents; and duration of infusion (shorter infusions prioritized). This guideline is not exhaustive. The compilation provided here is intended to be utilized as guidance for oncolytics administration sequence. We will continue to review and incorporate treatment sequencing recommendations for additional regimens.

Rheumatoid arthritis in real clinical practice: initiation of therapy with biological agents. Results of the «Computer Terminals of Self-Assessment for Patients with Rheumatic Diseases» («TERMINAL-II») project

Objective : to assess quality-of-life (QoL) dynamics in patients with rheumatoid arthritis (RA) when initiating therapy with biological agents (BAs) in real clinical practice. Patients and methods . The investigation enrolled patients with RA from the patient cohort participating in the TERMINAL-II multicenter Russian study, who newly initiated BA therapy. In the self-assessment terminal, the patient completed HAQ, EQ-5D, and RAPID-3 questionnaires. DAS28, SDAI, CDAI, and RAPID-3 were used to determine disease activity. The patient's functional status and QoL were assessed using the HAQ index and the EQ-5D questionnaire, respectively. The efficiency of the therapy was analyzed 6 months after the start of the study according to the standard procedures. Results and discussion . The investigation enrolled 156 RA patients: 79.6% females; mean age, 45.8±13.2 years; disease duration, 7.6±5.6 years. The patients had high RA activity (a mean DAS28 of 5.2±1.2, a mean SDAI of 39.5±16.4, a mean CDAI of 27.5±10.4, and a mean RAPID-3 of 15.1±3.6) and previous inefficacy of synthetic disease-modifying antirheumatic drugs (DMARDs) after at least 6 months of therapy. Only 1.2% of patients had a good functional status comparable to the population-based control (HAQ 40.5). 70% of patients needed to take non-steroidal anti-inflammatory drugs (NSAIDs). The first BA was chosen in accordance with the recommendations for administration of BAs and in terms of their availability in a specific region of the Russian Federation. The first prescribed BA was tumor necrosis factor-a (TNF-a) inhibitors in 112 (71.8%)patients, anti-B-cell therapy in 14 (9.0%), an interleukin-6 receptor inhibitor in 16 (10.3%), and a leukocyte costimulatory inhibitor in 14 (9.0%). Comparison of the patients receiving newly initiated therapy with TNF-a inhibitors and drugs with other mechanisms of action showed that the patients who had abatacept received higher doses of methotrexate (MTX), but lower doses of glucocorticoids (GCs) than those who were prescribed rituximab and tocilizumab. A statistically significant decrease in DAS28, SDAI, CDAI, and RAPID-3 scores was achieved after 6 months of therapy. Improvements of functional status and QoL in patients were also noted (p<0.0001). The patients continued to receive MTX. During the follow-up period, its dose remained almost unchanged: it averaged 15.7±3.8 and 15.7±3.7 mg/week at the beginning and the end of the study, respectively. Due to decreased inflammation, the dose of CS was reduced (on average, from 5.8±2.5 to 5.1±2.6 mg/day; p=0.02), the number of patients requiring NSAIDs declined (from 72.4 to 63.8%). DAS28, SDAI, and CDAI remission and low disease activity were achieved in 38.1, 16.5, and 20% of patients, respectively. The functional status improved in most patients with RA: 20, 50, and 70% improvements in HAQ were observed in 59.4, 46.9, and 28.7% of cases, respectively. QoL improvements were seen in two thirds of the patients: 30, 50, and 70% improvements in 58.3, 29.5, and in 23.7%. After 6-month follow-up, GC therapy was completely discontinued in 4.6% of patients; their dose was reduced in 5.3%, and 8.6% completely refused to take NSAIDs. Conclusion . Biologic therapy was shown to be effective in RA patients with an inadequate response to synthetic NSAIDs in real clinical practice. The patients preferred the subcutaneous injection of BAs. Biologic treatment in most patients was initiated with TNF-a inhibitors, mainly with adalimumab. Six-month therapy could reduce disease activity and improve functional status and health-related QoL in two thirds of severe patients.

Potential Regenerative Capacity of physiological serum, L-arginine and IGF-1 on Skeletal Muscle

In post–mitotic tissues such as skeletal muscles there are no significant cell replacements throughout life; the cells sustain local damage through its pool of specified stem cells. Muscle satellite cells are mononuclear cells that remain in a quiescent state till be activated; when they proliferate and fuse with muscle fibers to donate myonuclei, a process necessary for post-embryonic growth, hypertrophy and tissue repair in this post-mitotic tissue.Modern trends in using (autologous) biological agents ininitiation of regenerative process encourage us to evaluate the efficacy of some of these agents.In this study muscle damage was induced by cardiotoxin; followed by administration of biological agents; autologous physiological serum, L-arginine and IGF-1as a stimulating factors of myogenic satellite cells to initiate the myogenic regenerative process.Our study refers to variable degrees of efficacy in stimulation of myogenic stem cells differentiation and the outcome of the regenerative process. Although the physiological serum had marked ability to stimulate MSC but high number of newly formed myotubules are split. L-arginine despite had delayed regenerating time, but more organization of newly formed myotubules was retained. IGF-1 had rapid effect but associated with considerable number of newly formed split myotubules.We could conclude that for perfect regenerative myogenic tissue not main just formation muscle fibers, but theses fibers must be organized and functional. Healthy functional regenerative process need synchronization of several agents should be considered

Behçet's disease, VKH, sarcoidosis

SummaryOcular involvement associated with Behçet disease is characterized by a relapsing remitting panuveitis with diffuse vitritis, retinal infiltrates, and occlusive vasculitis. Proper management relies on the early use of immunosuppressive drugs in combination with corticosteroids and administration of biologic agents in resistant and severe posterior segment involvement. VKH disease is a bilateral panuveitis that may be associated with extraocular manifestations. Exudative retinal detachment, associated with typical imaging findings, is the most specific feature to acute VKH disease. Sunset glow fundus is typical to chronic VKH disease. Complications are more likely to occur in the chronic recurrent phase. Treatment for acute VKH disease relies on systemic corticosteroids for at least 6 months. Immunosuppressive therapy is mainly used in chronic recurrent disease. Main ocular features of sarcoidosis include bilateral granulomatous anterior uveitis, vitritis with snowballs, multifocal chorioretinitis, and segmental periphlebitis. Diagnosis is challenging in the absence of apparent systemic involvement. Treatment of sarcoidosis relies on corticosteroids and immunosuppressive agents, in severe cases.

Clinical characteristics and treatment outcomes of patients with colorectal cancer who develop brain metastasis: a single institution experience.

The development of brain metastasis (BM) in patients with colorectal cancer (CRC) is a rare and late event. We sought to investigate the clinical characteristics, disease course and safety using biologic agents in our patients with CRC who develop brain metastases. A retrospective review of patients with CRC with brain metastases treated at our institution from 01/2005-01/2015 was performed. Survival analysis was performed using the Kaplan-Meier method. Forty patients were included in the analysis. Median age was 55.5 years, 67.5% were males, and 28% had a KRAS mutation. Twenty-four percent were treatment-naive at the time of BM diagnosis. Patients had a median of two brain lesions. Sixty-five percent of the patients were treated with radiotherapy alone, 22.5% had both surgical resection and brain radiotherapy. Median overall survival was 3.2 months after development of BM. Overall survival was longer in patients who received combined modality local therapy compared to patients treated with surgical resection or radiotherapy alone. Patients who received systemic treatment incorporating biologics following development of BM had a median overall survival of 18.6 months. Overall, the administration of biologic agents was safe and well tolerated. In summary, BM is an uncommon and late event in the natural history of metastatic CRC. The ability to deliver combined-modality local brain therapy as well as availability of more systemic therapy options appear to lead to improved outcomes.

Behçet's disease, VKH, sarcoidosis

SummaryOcular involvement associated with Behçet disease is characterized by a relapsing remitting panuveitis with diffuse vitritis, retinal infiltrates, and occlusive vasculitis. Proper management relies on the early use of immunosuppressive drugs in combination with corticosteroids and administration of biologic agent in resistant and severe posterior segment involvement. VKH disease is a bilateral panuveitis that may be associated with extraocular manifestations. Exudative retinal detachment, associated with typical imaging findings, is the most specific feature to acute VKH disease. Sunset glow fundus is typical to chronic VKH disease. Complications are more likely to occur in the chronic recurrent phase. The mainstay of treatment for acute VKH disease relies on systemic corticosteroid therapy for at least 6 months. Immunosuppressive therapy is mainly used in chronic recurrent disease.Main ocular features of sarcoidosis include bilateral granulomatous anterior uveitis, vitritis with snowballs, multifocal chorioretinitis, and segmental periphlebitis. Diagnosis may be challenging in the absence of apparent systemic involvement. Treatment of sarcoidosis relies on corticosteroids and immunosuppressive agents, in severe cases.

Behçet's disease, VKH, sarcoidosis

SummaryOcular involvement associated with Behçet disease is characterized by a relapsing remitting panuveitis with diffuse vitritis, retinal infiltrates, and occlusive vasculitis. Proper management relies on the early use of immunosuppressive drugs in combination with corticosteroids and administration of biologic agent in resistant and severe posterior segment involvement. VKH disease is a bilateral panuveitis that may be associated with extraocular manifestations. Exudative retinal detachment, associated with typical imaging findings, is the most specific feature to acute VKH disease. Sunset glow fundus is typical to chronic VKH disease. Complications are more likely to occur in the chronic recurrent phase. The mainstay of treatment for acute VKH disease relies on systemic corticosteroid therapy for at least 6 months. Immunosuppressive therapy is mainly used in chronic recurrent disease. Main ocular features of sarcoidosis include bilateral granulomatous anterior uveitis, vitritis with snowballs, multifocal chorioretinitis, and segmental periphlebitis. Diagnosis may be challenging in the absence of apparent systemic involvement. Treatment of ocular sarcoidosis relies on corticosteroids and immunosuppressive agents, in severe cases.

Investigating the potential side effects of anti-TNF therapy for rheumatoid arthritis: cause for concern?

There are now five anti-TNF drugs available for clinical use, and it will not be long before they are joined by biosimilar drugs. Some patients treated with selective TNF drugs may develop adverse events such as infections, malignancies, acute infusion and injection reactions, autoimmunity and cardiovascular effects. Registry data consistently show that, particularly during the first 6 months, anti-TNF drugs slightly increase the risk of serious infections of the skin, soft tissues and joints, but it does not seem to increase the risk of cancer other than nonmelanoma skin cancers. A number of studies have shown that the administration of biological agents can lead to the formation of neutralizing and nonneutralizing antibodies. Lipid levels increase, but the atherogenic index remains stable and qualitative changes to lipid particles may reduce the risk of cardiovascular diseases. Patients treated with anti-TNF drugs therefore need to be monitored regularly.