Immune-modulating Medications Research Articles

Exploring Effective Therapeutic Approaches for COVID-19: A Review on Progress and Prospects

: Global health and economy have been severely impacted by the COVID-19 pandemic that was brought on by the SARS-CoV-2 coronavirus. This makes the creation of potent medications for the treatment of COVID-19 disease a top goal. In clinical trials, several medications that have been repurposed for the treatment of COVID-19 have shown promise. Nevertheless, there are a lot of obstacles to overcome in the creation of COVID-19 pharmacological therapy. The inability to pinpoint prospective treatment targets is one difficulty caused by the unclear etiology of COVID-19. Another difficulty is the virus' quick evolution, which can result in the creation of drug-resistant variants. Furthermore, the quick start of clinical trials has been prompted by the strong demand for effective therapies. A lack of reliable data on the safety and efficacy of medications can result from the early start of clinical trials that have been prompted by the strong demand for effective medicines. Despite these obstacles, the development of various promising pharmacological treatments for COVID-19 has advanced. These include immune-modulating medications, like dexamethasone and tocilizumab, as well as antiviral medicines, like remdesivir and favipiravir. Combination therapies using several medications may also be useful in enhancing outcomes for COVID-19 patients. Despite some encouraging advancements, there are still a lot of obstacles to be addressed in the development of pharmacological therapy for COVID-19. Further research is needed to identify the most effective treatment approaches for this disease.

Leflunomide-Associated Wound Complication After Cochlear Implantation: A Case Report.

Cochlear implantation has become an increasingly common strategy for aural rehabilitation in patients with severe to profound hearing loss who no longer benefit from conventional amplification. In conjunction, immunosuppressive therapies (e.g. disease-modifying anti rheumatic drugs (DMARDs) have become the keystone of management in numerous autoimmune conditions. Given the increasing prevalence of both, a greater proportion of patients will undergo cochlear implantation while on immune-modulating medications. While these medications are usually well tolerated, immunosuppression may put patients a higher risk for device infections. At present, this is not extensively studied within the cochlear implant literature. We conducted a retrospective chart review and review of the literature.Results:We present the case of an 81-year-old male who experienced wound dehiscence and infection secondary to leflunomide use for treatment of rheumatoid arthritis. Resolution of these issues was noted with a therapeutic drug holiday, and the patient has subsequently undergone re-implantation without issue.Conclusions:The case highlights a potential CI-associated wound complication in the setting of DMARD therapy. Given the increasing prevalence of both CIs and immunosuppressive therapy, future study on the potential for interaction is warranted to identify the best management strategy in the perioperative setting.

Subcutaneous (SC) nivolumab (NIVO) vs intravenous (IV) NIVO in patients with previously treated advanced or metastatic clear cell renal cell carcinoma (ccRCC): Safety and patient-reported outcomes (PROs) of the randomized phase 3 CheckMate 67T trial.

4532 Background: CheckMate 67T (NCT04810078), a multicenter, randomized, open-label, phase 3 study, evaluated pharmacokinetics and objective response rate (ORR) noninferiority of NIVO SC vs IV in previously treated patients with advanced/metastatic ccRCC. Noninferiority endpoints of exposure (time-averaged serum concentration over the first 28 days and trough serum concentration at steady state) and efficacy (ORR by BICR) were met. Safety was comparable in the SC vs IV arms. NIVO-related immunogenicity was as expected for SC administration and further assessments did not identify apparent clinically meaningful impact. This report focuses on additional safety analyses and PROs. Methods: Patients were randomized 1:1 to NIVO SC 1200 mg + recombinant human hyaluronidase PH20 Q4W (n = 248) or NIVO IV 3 mg/kg Q2W (n = 247). Eligibility criteria were previously reported. Safety analyses were performed for all-causality adverse events (AEs) across weight categories (< 50 kg, ≥ 50 kg–< 70 kg, ≥ 70–< 90 kg, ≥ 90 kg–< 110 kg, and ≥ 110 kg). The onset, management, and resolution of treatment-related select AEs were studied; duration and grade of local site reactions and the effect of immunogenicity on local site reactions were reported. PROs were assessed using the Functional Assessment of Chronic Illness Therapy (FACIT) GP5 item. Results: The overall AE incidence rates in the SC arm were generally comparable to or lower than in the IV arm across weight categories, but limited by small sample sizes in the < 50 kg and ≥110 kg subgroups. Across the treatment-related select AE categories, most events were manageable with established algorithms and resolved with immune-modulating medications. Local site reactions were mild to moderate with a median duration of 2.0 and 0.01 days in the SC and the IV arms, respectively; most resolved without treatment. The proportion of patients with a local site reaction of any grade was 8.1% in the SC arm and 2.0% in the IV arm. In patients testing NIVO-specific anti-drug antibody (ADA)-positive, 15.2% of patients in the SC arm reported a local site reaction, but all were grade 1–2 and most resolved without treatment. No hypersensitivity/infusion reaction select AEs were reported in ADA-positive patients in either arm. A majority of patients in SC and IV arms reported minimal bother by treatment side effects in their FACIT GP5 scores. Conclusions: The safety profile of SC was consistent with IV, supporting the use of NIVO SC as an option improving patient experience. This aligns with patient preference for SC administration over IV. Analyses based on weight and ADA subgroups were consistent with the known NIVO safety profile. Toxicity was manageable with immune-modulating medications. FACIT GP5 scores indicated no bother by treatment side effects. Clinical trial information: NCT04810078 .

Investigating the risk of deep vein thrombosis with JAK inhibitors: a disproportionality analysis using FDA Adverse Event Reporting System Database (FAERS)

ABSTRACT Background Janus kinase (JAK) inhibitors are immune-modulating medications used to treat conditions including rheumatoid arthritis, COVID-19, ulcerative colitis, atopic dermatitis, myelofibrosis, and polycythemia Vera. However, these medications have been associated with higher incidence of deep vein thrombosis. The objective of this study was to investigate potential safety signals for DVT associated with JAK inhibitors using disproportionality analysis from the FDA Adverse Event Reporting System (FAERS) database. Research design and methods The authors retrospectively investigated case/non-case analysis using Openvigil 2.1-MedDRA-v24 (2004Q1 to 2022Q4). The preferred term used was ‘deep vein thrombosis,’ and the drugs included were baricitinib, tofacitinib, and upadacitinib. Reporting odds ratio, proportional reporting ratio, and information component were used to detect signals. Results Overall 114,005 AE reports related to JAK inhibitors were identified, of which 647 reports (baricitinib − 169, tofacitinib − 425, and upadacitinib − 53) associated with DVT were obtained from FAERS. On analysis, baricitinib and tofacitinib had greater signal strength for age group of 65–100 years and all three had the highest signal strength for male gender. Conclusions Our study identified signals for DVT with baricitinib, tofacitinib, and upadacitinib. Further research using well-designed epidemiological data is needed to validate these results.

First-line nivolumab plus ipilimumab for metastatic non-small cell lung cancer, including patients with ECOG performance status 2 and other special populations: CheckMate 817

BackgroundCheckMate 817, a phase 3B study, evaluated flat-dose nivolumab plus weight-based ipilimumab in patients with metastatic non-small cell lung cancer (NSCLC). Here, in this research, we report on first-line treatment...

Linking Genetic Diagnosis to Therapeutic Approach in Very Early Onset Inflammatory Bowel Disease: Pharmacologic Considerations.

Very early onset inflammatory bowel disease (VEO-IBD) is diagnosed in children <6 years of age, and in rare cases may be due to an identifiable monogenic cause. Recent advances in genetic testing have allowed for more accurate diagnosis, with as many as 100 genes now known to be associated with monogenic inflammatory bowel disease. These genes are involved in many immune pathways and thus may represent potential avenues for targeted precision medicine with pharmacologic treatments aimed at these. This review describes the broad classifications of monogenic disorders known to cause VEO-IBD, as well as empiric and disease-specific medical therapies. These include immune-modulating or immunosuppressant medications, nutritional therapy, surgery, and hematopoietic stem cell transplantation. We aim to provide an overview of the current state of targeted therapy for VEO-IBD.

Preserved SARS-CoV-2 Vaccine Cell-Mediated Immunogenicity in Patients With Inflammatory Bowel Disease on Immune-Modulating Therapies.

Immune-modulating medications for inflammatory bowel diseases (IBDs) have been associated with suboptimal vaccine responses. There are conflicting data with SARS-CoV-2 vaccination. We therefore assessed SARS-CoV-2 vaccine immunogenicity at 2 weeks after second mRNA vaccination in 29 patients with IBD compared with 12 normal healthy donors. We observed reduced humoral immunity in patients with IBD on infliximab. However, we observed no difference in humoral and cell-mediated immunity in patients with IBD on infliximab with a thiopurine or vedolizumab compared with normal healthy donors. This is the first study to demonstrate comparable cell-mediated immunity with SARS-CoV-2 vaccination in patients with IBD treated with different immune-modulating medications.

Antibody Response to BNT162b2 Vaccine in Immune Modifiers-Treated Psoriatic Patients.

Data regarding anti-COVID-19 vaccination efficacy in psoriasis patients treated with immune-modulatory medications are scarce. This study aims to examine the rate of positive antibody response following BNT162b2 vaccine in those patients. BNT162b2-vaccinated and immune modifier-treated psoriatic patients were assigned to serological testing of IgG antibodies to protein S of SARS-CoV-2 after the second vaccination dose by Abbott Architect or Beckman Coulter. Levels ≥ 1 S1 units/mL (S/ml) and > 150 arbitrary units/ml (AU/ml) are considered a positive antibody response, respectively. The antibody levels further analyzed according to the patient's characteristics and compared to health workers' controls. Forty-nine of the 51 patients had a positive antibody response. Overall, patients treated with immune-modulatory medications had antibody levels similar to the control group. Immune modifier-treated psoriasis patients seem to develop a positive antibody response to the full BNT162b2 vaccination in the vast majority of cases.

Immune-related hepatitis in a patient with hepatocellular carcinoma treated with nivolumab

SummaryWe present a case of a male patient with advanced hepatocellular carcinoma who developed hepatic and dermatological immune-related adverse events during treatment with the immune checkpoint inhibitor nivolumab. We discuss relevant aspects regarding the management of immune-related hepatic adverse events, including the incidence and onset of the event, the requirement for immune-modulating medication, resuming of immunotherapy, and the association between the occurrence of immune-related adverse events and the outcome.

Nasal Microbiota and Infectious Complications After Elective Surgical Procedures

The association of the nasal microbiome with outcomes in surgical patients is poorly understood. To characterize the composition of nasal microbiota in patients undergoing clean elective surgical procedures and to examine the association between characteristics of preoperative nasal microbiota and occurrence of postoperative infection. Using a nested matched case-control design, 53 individuals who developed postoperative infection were matched (approximately 3:1 by age, sex, and surgical procedure) with 144 individuals who were not infected (ie, the control group). The 2 groups were selected from a prospective cohort of patients undergoing surgical procedures at 2 tertiary care university hospitals in Baltimore, Maryland, who were at high risk for postoperative infectious complications. Included individuals were aged 40 years or older; had no history of autoimmune disease, immunocompromised state, immune-modulating medication, or active infection; and were scheduled to undergo elective cardiac, vascular, spinal, or intracranial surgical procedure. Data were analyzed from October 2015 through September 2020. Nasal microbiome cluster class served as the main exposure. An unsupervised clustering method (ie, grades of membership modeling) was used to classify nasal microbial samples into 2 groups based on features derived from 16S ribosomal RNA gene sequencing. The microbiome cluster groups were derived independently and agnostic of baseline clinical characteristics and infection status. Composite of surgical site infection, bacteremia, and pneumonia occurring within 6 months after surgical procedure. Among 197 participants (mean [SD] age, 64.1 [10.6] years; 63 [37.7%] women), 553 bacterial taxa were identified from preoperative nasal swab samples. A 2-cluster model (with 167 patients in cluster 1 and 30 patients in cluster 2) accounted for the largest proportion of variance in microbial profiles using grades of membership modeling and was most parsimonious. After adjusting for potential confounders, the probability of assignment to cluster 2 was associated with 6-fold higher odds of infection after surgical procedure (odds ratio [OR], 6.18; 95% CI, 3.33-11.7; P < .001) independent of baseline clinical characteristics, including nasal carriage of Staphylococcus aureus. Intrasample (ie, α) diversity was inversely associated with infectious outcome in both clusters (OR, 0.57; 95% CI, 0.42-0.75; P < .001); however, probability of assignment to cluster 2 was associated with higher odds of infection independent of α diversity (OR, 4.61; 95% CI, 2.78-7.86; P < .001). These findings suggest that the nasal microbiome was an independent risk factor associated with infectious outcomes among individuals who underwent elective surgical procedures and may serve as a biomarker associated with infection susceptibility in this population.

Success and failure of additional immune modulators in steroid-refractory/resistant pneumonitis related to immune checkpoint blockade

BackgroundPneumonitis related to immune checkpoint blockade is uncommon but can be severe, fatal or chronic. Steroids are first-line treatment, however, some patients are refractory or become resistant to steroids. Like...

Monosexual Cercariae of Schistosoma japonicum Infection Protects Against DSS-Induced Colitis by Shifting the Th1/Th2 Balance and Modulating the Gut Microbiota

Inflammatory bowel disease (IBD)-related inflammation is closely associated with the initiation and progression of colorectal cancer. IBD is generally treated with 5-aminosalicylic acid and immune-modulating medication, but side effects and limitations of these therapies are emerging. Thus, the development of novel preventative or therapeutic approaches is imperative. Here, we constructed a dextran sodium sulphate (DSS)-induced IBD mouse model that was infected with monosexual Schistosoma japonicum cercariae (mSjci) at day 1 or administered dexamethasone (DXM) from days 3 to 5 as a positive control. The protective effect of mSjci on IBD mice was evaluated through their assessments of their clinical signs, histopathological lesions and intestinal permeability. To uncover the underlying mechanism, the Th1/Th2 balance and Treg cell population were also examined. Additionally, the alterations in the gut microbiota were assessed to investigate the interaction between the mSjci-modulated immune response and pathogenic microbiome. Mice treated with DSS and mSjci showed fewer IBD clinical signs and less impaired intestinal permeability than DSS-treated mice. Mechanistically, mSjci modulated the Th1/Th2 balance by repressing IFN-γ production, promoting IL-10 expression and enhancing the Treg subset population. Moreover, mSjci notably reshaped the structure, diversity and richness of the gut microbiota community and subsequently exerted immune-modulating effects. Our findings provide evidence showing that mSjci might serve as a novel and effective protective strategy and that the gut microbiota might be a new therapeutic target in IBD.

Nivolumab in Advanced Hepatocellular Carcinoma: Safety Profile and Select Treatment-Related Adverse Events From the CheckMate 040 Study.

BackgroundCheckMate 040 assessed the efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is needed to support the management of treatment‐related adverse events (TRAEs). This analysis assessed the safety of nivolumab monotherapy in the phase I/II, open‐label CheckMate 040 study.Materials and MethodsSelect TRAEs (sTRAEs; TRAEs with potential immunologic etiology requiring more frequent monitoring) occurring between first dose and 30 days after last dose were analyzed in patients in the dose‐escalation and ‐expansion phases. Time to onset (TTO), time to resolution (TTR), and recurrence of sTRAEs were assessed, and the outcome of treatment with immune‐modulating medication (IMM) was evaluated.ResultsThe analysis included 262 patients. The most common sTRAE was skin (35.5%), followed by gastrointestinal (14.5%) and hepatic (14.1%) events; the majority were grade 1/2, with 10.7% of patients experiencing grade 3/4 events. One patient had grade 5 pneumonitis. Median (range) TTO ranged from 3.6 (0.1–59.9) weeks for skin sTRAEs to 47.6 (47.1–48.0) weeks for renal sTRAEs. Overall, 68% of sTRAEs resolved, with median (range) TTR ranging from 3.7 (0.1–123.3+) weeks for gastrointestinal sTRAEs to 28.4 (0.1–79.1) weeks for endocrine sTRAEs. Most gastrointestinal and all hepatic events resolved with treatment in accordance with established toxicity management algorithms. In 57 patients (40%), sTRAEs were managed with IMM. Reoccurrence of sTRAEs was uncommon following rechallenge with nivolumab.ConclusionNivolumab demonstrated a manageable safety profile in this analysis of patients with advanced HCC. A majority of sTRAEs resolved with treatment.Implications for PracticeNivolumab is a viable treatment option for patients with previously treated advanced hepatocellular carcinoma as it has demonstrated durable tumor responses and promising survival. Nivolumab has a manageable safety profile. The most common select treatment‐related adverse events (sTRAEs) in this analysis were skin related (35%). Gastrointestinal and hepatic sTRAEs were observed in approximately 14% of patients. The majority of sTRAEs resolved (68%). Safety events are easier to manage if addressed early. Patient education on signs and symptoms to watch out for and the importance of early reporting and consultation should be emphasized.

Cogan's Syndrome: Clinical Presentations and Update on Treatment.

Cogan's syndrome (CS) is a rare systemic vasculitis that can severely affect vision and hearing, which may also have significant systemic effects. Early recognition of this autoimmune disorder and intervention can minimize disabling and irreversible damage. This article will review the varying clinical presentations of CS and emerging information of systemic disease associated with CS. We will also review recently published promising treatment outcomes using immune modulating medications. As our framework for recognizing the markers of CS and the associated systemic disorders expands, more effective guidelines and treatment options may emerge.

Expression of SARS-CoV-2 Entry Molecules ACE2 and TMPRSS2 in the Gut of Patients With IBD.

BackgroundPatients with inflammatory bowel disease (IBD) have intestinal inflammation and are treated with immune-modulating medications. In the face of the coronavirus disease-19 pandemic, we do not know whether patients with IBD will be more susceptible to infection or disease. We hypothesized that the viral entry molecules angiotensin I converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are expressed in the intestine. We further hypothesized that their expression could be affected by inflammation or medication usage.MethodsWe examined the expression of Ace2 and Tmprss2 by quantitative polymerase chain reacion in animal models of IBD. Publicly available data from organoids and mucosal biopsies from patients with IBD were examined for expression of ACE2 and TMPRSS2. We conducted RNA sequencing for CD11b-enriched cells and peripheral and lamina propria T-cells from well-annotated patient samples.Results ACE2 and TMPRSS2 were abundantly expressed in the ileum and colon and had high expression in intestinal epithelial cells. In animal models, inflammation led to downregulation of epithelial Ace2. Expression of ACE2 and TMPRSS2 was not increased in samples from patients with compared with those of control patients. In CD11b-enriched cells but not T-cells, the level of expression of ACE2 and TMPRSS2 in the mucosa was comparable to other functional mucosal genes and was not affected by inflammation. Anti-tumor necrosis factor drugs, vedolizumab, ustekinumab, and steroids were linked to significantly lower expression of ACE2 in CD11b-enriched cells.ConclusionsThe viral entry molecules ACE2 and TMPRSS2 are expressed in the ileum and colon. Patients with IBD do not have higher expression during inflammation; medical therapy is associated with lower levels of ACE2. These data provide reassurance for patients with IBD.

2774 Gastritis After Combination Ipilimumab and Nivolumab: A Rare Adverse Event After Immunotherapy

INTRODUCTION: Immunotherapies are commonplace in the treatment of many neoplasms, and have an array of commonly reported toxicities. Among the reported gastrointestinal side effects, diarrhea and colitis are most frequently cited. However, there have only been a rare handful of reported cases of Immune-checkpoint modulator toxicity affecting only the upper GI tract. In this paper we report a case of Ipilimumab-Nivolumab associated Gastritis in a patient treated with these medications at our facility. CASE DESCRIPTION/METHODS: The patient is a 78-year-old male with Stage IV Melanoma who presented to the hospital with nausea, vomiting, weight loss, and reduced oral intake for two weeks. The patient had most recently received 2 rounds of Ipilimumab and Nivolumab for his Melanoma 2 weeks prior to his presentation to our hospital, concurrent with the start of his symptoms. There had been no history of NSAID usage during this time, and physical exam was notable for mild epigastric tenderness. A Computed Tomography scan of the Chest/Abdomen/Pelvis showed diffuse thickening of the stomach, compatible with gastritis. Upper Endoscopy revealed diffuse severely erythematous mucosa with bleeding on contact in the entire examined stomach, and patchy, mildly erythematous mucosa without bleeding was found in the duodenal bulb, with the second portion of the duodenum being normal. The pathology report revealed subacute gastritis with acute inflammatory exudate consistent with an area of mucosal ulceration, with other etiologies of gastritis ruled out. The patient was begun on glucocorticoid therapy, with rapid resolution of his symptoms. Repeat endoscopy 2 weeks later revealed resolution of the previously noted gastritis and inflammation. Pathologic examination of biopsies confirmed resolution of the inflammatory process. DISCUSSION: On review of the literature, gastritis resulting from immune-checkpoint modulators has rarely been reported on. Some common side effects associated with these immune modulating medications, colloquially called immune-related adverse events (irAEs), include diarrhea, colitis, and hepatitis. However, there are a few case reports concerning the development gastritis without enterocolitis after Nivolumab treatment alone. Approximately 3 case reports and 1 case series of 20 patients describe such a side effect, To date, there are no reported cases of a patient treated with both Nivolumab and Ipilimumab who developed gastritis as the only adverse event.

Infliximab for the treatment of refractory polyarteritis nodosa.

Polyarteritis nodosa (PAN) is a necrotizing vasculitis predominantly affecting medium and small size arteries. Cyclophosphamide, a drug with narrow therapeutic range and poor safety profile, constitutes the treatment of choice for PAN vasculitis with major organ involvement. To describe our clinical experience in treating refractory PAN with infliximab (a TNF inhibitor), a drug with good tolerability and better safety profile than cyclophosphamide. Twenty-six PAN patients were admitted to our rheumatology unit between 2006 and 2017, of whom nine patients, with severe and refractory disease, were treated with infliximab after failure of standard treatment. We describe herein the patients' characteristics, clinical manifestations, severity and response to infliximab treatment and review the current literature. Complete remission was defined as the absence of features of active disease and withdrawal of prednisone therapy. Significant improvement was defined as clinical improvement and prednisone dose reduction of at least 50% or a 50% reduction in immune modulatory medications other than prednisone. After 4months of treatment, 8/9 (89%) patients achieved significant improvement, with two of them achieving complete remission. We suggest that anti-TNF agents, and in particular infliximab, are relatively safe and efficacious treatment options in refractory PAN. A randomized controlled trial should be done in order to objectively evaluate infliximab in PAN.

DYSPNEA, DYSPHAGIA, AND URTICARIA WITH ANGIOEDEMA AFTER CHILDBIRTH

Introduction Our case highlights the challenge in differentiating between hypereosinophilic syndrome (HES) and eosinophilia exacerbating atopic disease. Case Description A 29-year-old woman presents with dyspnea, dysphagia, urticaria and angioedema after childbirth. Evaluation revealed an eosinophil count of 3800/mcL. Infectious, cardiac, and chest imaging studies were normal. Lung function demonstrated FEV1/FVC at 0.85. Bronchial challenge with methacholine was positive. Bone marrow was normocellular with eosinophilia without evidence of PDGFRA, CHIC2, and FIP1L1 rearrangement. Upper endoscopy demonstrated esophageal eosinophilia. She improved on prednisone 40 mg daily, mometasone-formoterol, and montelukast. Dysphagia improved after esophageal dilation. Eosinophil counts remained elevated at 1500/mcL, with difficulty tapering prednisone due to dyspnea. She started interferon-alpha and continued prednisone 20 mg daily for 6 years with significant weight gain. She presented to our center and started mycophenolate-mofetil, discontinued interferon-alpha, and tapered prednisone to 5 mg daily. She then started mepolizumab and stopped prednisone. Six months later she developed dyspnea and urticaria. She switched to omalizumab with improvement and is stable on omalizumab, mycophenolate-mofetil, mometasone-formoterol, and montelukast. Discussion Asthma endotyping prompts checking eosinophil counts to assess for potential benefit with anti-IL5 therapy. Recent data demonstrates mepolizumab improves glucocorticoid sensitive HES, yet our patient responded better to omalizumab. The different biologics can help delineate the differential pathophysiology behind a patient's clinical presentation. Given the emerging overlap in therapeutic management, our case emphasizes the importance to shift the paradigm of understanding eosinophilic inflammation as a spectrum of disease rather than isolated entities, in consideration of both biologic and immune modulating medications.

SY23-5 - Immune checkpoint inhibitors and neuromuscular adverse events

Neuromuscular adverse events (AEs) associated with cancer treatment with immune checkpoint inhibitors (ICIs) include diverse clinical subsets. The general features of neuromuscular AEs have not been elucidated because the frequency is generally low, ranging from 1%-2% of cancer patients undergoing ICIs therapy. The diseases affect the central nervous system, peripheral nerves, neuromuscular junction, and muscle. Disease onset and progression may be rapid with a critical clinical course. The clinical presentation may be different from that of patients unrelated to drugs. Brain MRI images or laboratory findings do not always yield useful information, even if cancer patients suffer from severe neurological symptoms. Prior treatment including cytotoxic chemotherapies and radiation may have been factors in causing neuromuscular damage. Metastatic lesions potentially produce new neurological symptoms. In addition, paraneoplastic syndrome, a remote effect of malignancy on neuromuscular organs, is always considered as a differential diagnosis. Stroke and epilepsy are serious events requiring the permanent termination of ICIs treatment. Headache, dizziness, and dysgeusia were relatively common and mild treatment-related AEs. In contrast, representative immune-related AEs such as autoimmune encephalitis, demyelinating polyneuropathy, myasthenia, and myositis were serious. There was a tight association between myasthenia, myositis, and myocarditis. There are guidelines for the treatment of neuromuscular immune-mediated AEs. For all but the minimum neurological symptoms, checkpoint inhibitor therapy should be withheld until the nature of the AEs is identified. Immune-modulating medication is generally effective for neuromuscular AEs. Both CD8+ cytotoxic T-cells and autoantibodies are involved in the pathogenesis of neuromuscular AEs. Correct understanding of neuromuscular AEs is required for the best management of cancer patients.

Patients with a fast progression profile in geographic atrophy have increased CD200 expression on circulating monocytes.

Geographic atrophy (GA) is a progressing atrophy of the neuroretina with no treatment option. Age-related malfunction of retinal microglia amplifies response towards age-related tissue stress in age-related macular degeneration. Here, we investigated monocyte CD200 expression - the circulating middleman negotiating retinal microglial activity - in a poorly understood subtype of age-related macular degeneration. Prospective case-control study. Forty-six patients with GA and 26 healthy controls were included. All participants were subjected to a structured interview and detailed retinal examination. Controls were recruited from patient's spouses accompanying them in the clinic to match the groups best possibly. Participants had no history of immune disorders or cancer, and did not receive any immune-modulating medication. Patients did not have any history or sign of choroidal neovascularization in either eye. Fresh drawn blood was stained with monoclonal antibodies and prepared for flow cytometry to evaluate CD200 expression in monocytes and their functional subsets. The percentage of CD200+ monocytes in patients and controls. We found that monocytes were more CD200 positive in patients with GA compared to healthy age-matched controls. Then, we explored the potential relationship between CD200 expression and important fundus autofluorescence patterns that predict disease progression. Patients with a high risk of progression (patients with high degree of hyperautofluorescence) had distinctly increased CD200 expression compared to other patients with GA. Our data reveals that abnormal monocytic CD200 expression is present in GA, and in particular among those identified as fast progressors.