Administration Of Immunosuppressive Drugs Research Articles

Perspectives on the use of non-biological pharmacotherapy for adult-onset Still’s disease

Introduction The treatment of the patients with adult-onset Still’s disease (AOSD) remains largely empirical and it is based on the administration of immunosuppressive drugs. In this work, we described the use of non-biological pharmacotherapies for AOSD. Area covered Although nonsteroidal anti-inflammatory drugs (NSAIDs) are employed during the diagnostic phase, glucocorticoids (GCs) are the first-line therapy, administered at the beginning of the disease. As second-line therapy, conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) are used when GCs do not fully control the disease and/or to reduce the dosage of concomitant GCs. Methotrexate (MTX) is the most common administered csDMARDs whereas calcineurin inhibitors (CNIs) are used in severe patients. The lack of achievement of clinical response may lead to the administration of biologic DMARDs, with or without csDMARDs. Expert opinion The management of AOSD may benefit from the administration of non-biological pharmacotherapies, including GCs, MTX, and CNIs. These therapies showed efficacy in inducing a clinical response, in managing life-threatening complications, and may be well tolerated in combination with biologic DMARDs. However, further specific studies are needed to fully clarify the specific role of such drugs in clinical practice to improve the management of AOSD and to provide a more tailored treatment.

Fatal disseminated mucormycosis due to Cunninghamella bertholletiae infection after ABO-incompatible living donor liver transplantation: a case report

BackgroundFungal infection may develop because of immunosuppression after organ transplantation, in which invasive types, such as Aspergillus and Mucorales, fungi cause morbidity. We present a case of disseminated mucormycosis due to Cunninghamella bertholletiae after ABO-incompatible living donor liver transplantation (LDLT).Case presentationA 47-year-old man with decompensated liver cirrhosis and hepatocellular carcinoma underwent an ABO-incompatible LDLT using a graft procured from his son, who had a different blood type. Rituximab and mycophenolate mofetil were administered 3 weeks before LDLT as immunosuppressive therapy. Although liver graft function improved, mass-like infiltrates appeared in the lungs following intubation for > 1 week due to impaired consciousness. The brain magnetic resonance imaging findings were normal. Decreased ejection fraction and ST elevation were detected on echocardiography and electrocardiography, respectively. There was no dominant stenosis on coronary arteriography. The recipient underwent segmentectomy of the right lung 20 days after LDLT. C. bertholletiae was identified from a specimen using polymerase chain reaction, thus establishing a diagnosis of mucormycosis. Multiple infarctions in the brain, heart, and kidney developed within 2 weeks. Treatment with amphotericin B was ineffective. The patient developed circulatory collapse, and a temporary pacemaker and percutaneous coronary intervention were required for cardiac infarction. The recipient died of cardiac failure 27 days after the LDLT. Autopsy revealed disseminated mucormycosis involving the brain, thyroid, heart, lung, liver, gastrointestinal tract, and both kidneys. In addition, fungal endocarditis may have been responsible for septic emboli in multiple organs, resulting in multiple organ invasion. Hypothrombocytopenia was present since the pre-transplant period, and the recipient was diagnosed posthumously with myelodysplastic syndrome due to hereditary abnormalities. Multiple factors such as organ transplantation, bone marrow dysfunction, immunosuppression, and inadequate administration of antifungal reagents might have promoted mucormycosis development in our patient.ConclusionsMucormycosis by C. bertholletiae is a fatal complication; thus, early diagnosis and treatment are warranted before multiple organ invasion.

414.3: Review of the Safety and Efficacy of Immunosuppression in the Pig-To-Nonhuman Primate Islet Xenotransplantation Model

Background: With the recent progress of xenotransplantation moving to the clinic there is renewed enthusiasm in the field of xenotransplantation, but the need for strong immunosuppressive and anti-inflammatory agents remains. The effects and safety of these agents need to be reviewed in detail to allow progress to the clinic. This project aimed to evaluate the short-term (100 days) effects of immunosuppression on haematological and immunological parameters following neonatal porcine islet cell cluster (NICC) xenotransplantation in a diabetic non-human primate model. Methods: Four baboons received 5 doses of anti-CD2 at 5mg/kg from day -3 to day 21 along with fortnightly anti-CD154 administration at 20-30mg/kg and belatacept administration at20mg/kg. This was followed by daily maintenance immunosuppression of tacrolimus at 5mg/kg or sirolimus at 2mg/kg. Prior to immunosuppression administration, blood was collected to establish baseline haematological and immunological parameters. Full haematological parameters were assayed and immunological parameters including B cells, T cells, monocytes, and granulocytes were assessed by flow cytometry. Results: The immunosuppressive therapy was highly effective in suppressing total white cell counts in all recipients. By day 100, B and T cells were depleted by 50-60% compared to baseline. In the 14-day gap between treatment with anti-CD154+belatacept, the immune cells (particularly B and T cells) recovered but were suppressed at each subsequent time point as compared to previous levels. There was a gradual reversal of the CD4:CD8 ratio, with a reduction of CD4+ cells and an increase in CD8+ cells over the 100 days. Tregs, a key component of achieving tolerance, gradually increased from day 30-60. Other hematological parameters such as mean corpuscular hemoglobin concentration (MCHC) and red cell count (RCC) remained unaffected by immunosuppression. Conclusion: This novel combination of immunosuppressive agents is effective and safe in baboons receiving neonatal porcine islet cell cluster xenotransplantation.

Autoimmunity to acetylcholine receptor channels

AbstractAnti‐acetylcholine receptor antibody (AChRAb) targets nicotinic acetylcholine receptors (AChRs) of the neuromuscular junction (NMJ). AChRAb induces degradation of AChRs, which causes a decrease in the efficacy of neuromuscular transmission. The clinical condition induced by this process is myasthenia gravis (MG). Transmission failure at the NMJ is detectable by a repetitive nerve stimulation test. AChRAb may be complicated with thymic abnormalities (thymoma and/or lymphoreticular hyperplasia [LFH]). Moreover, autoimmune thyroid disease may accompany MG. Thymoma and LFH have etiological roles in AChRAb production, and the removal of thymoma and LFH improve MG symptoms. MG therapies, such as acetylcholine esterase inhibitor (AChEI), aim to increase the efficacy of NMJ transmission; however, the effect of AChEI is limited. The primary therapy aims to decrease AChRAb and is combined with thymectomy. There are two methods to remove AChRAb from the patients' blood: (1) reduce the production of immunoglobulins by administration of corticosteroid and/or immunosuppressants and (2) remove immunoglobulin by blood purification. In some patients, long‐lasting immunosuppression is necessary, which causes adverse events. Combinatory use of other immunosuppressants reduces the adverse events of corticosteroids. In addition, intravenous immunoglobulin is available to modify the proportion of immunoglobulin in patients' blood. Recently, humanized monoclonal antibodies against specific molecules have been introduced for immunoglobulin modification; however, they are not AChRAb specific. Thus, it is necessary to consider the safety and cost‐effectiveness of therapies.

Autoimmune hepatitis in pediatrics, a review by the Working Group of the Latin American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver characterized by a complex interaction among genetic factors, immune response to antigens present in hepatocytes, and immune regulation alterations. Its distribution is global and there is a female predominance. AIH is divided into 2 groups, depending on the type of serum autoantibodies detected. The most common presentation is acute hepatitis (40%), with non-specific symptoms, high aminotransferase levels, and hypergammaglobulinemia. Standard treatment consists of the administration of immunosuppressive drugs. It is a complex condition, often difficult to diagnose. If not managed adequately, the 5-year mortality rate may reach 75%.

Improved Mayo Endoscopic Score has a higher value for evaluating clinical severity of ulcerative colitis

To assess the value of Improved Mayo Endoscopic Score (IMES) for evaluation of the clinical severity of ulcerative colitis (UC). We retrospectively analyzed the clinical and endoscopic data of 167 patients diagnosed with UC in Beijing Tsinghua Changgung Hospital from January, 2015 to November, 2021. The severity of endoscopic lesions was determined by Mayo Endoscopic Score (MES, 0-3 points) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score (0-8 points), and the scope of endoscopic lesions was evaluated based on the Montreal classification system. The IMES was established by combining the MES with the Montreal classification. The IMSE showed stronger correlations with modified Truelove and Witts Disease Severity, Mayo score and partial Mayo score (r=0.712, 0.784, and 0.703, respectively) than MES (r=0.642, 0.754, and 0.604, respectively), Montreal classification (r=0.598, 0.628, and 0.603, respectively) and UCEIS (r= 0.670, 0.767, and 0.677, respectively). ROC curve analysis showed that IMES was superior to MES, Montreal and UCEIS in diagnosis of severe and moderate- to-severe UC. IMES also showed stronger correlations with the laboratory indicators including CRP (r=0.583), WBC (r=0.235), HB (r=-0.280), PLT (r=0.352), ALB (r=-0.396) and ESR (r=0.471) than MES and Montreal classification. An IMES score of 5 was of greater value than a MES score of 3, E3, and UCEIS≥6 for predicting the administration of systemic hormones, immunosuppressants, or surgery in the near future. IMES can better reflect the clinical severity of UC and has good correlations with the laboratory indicators of the patients.

Single Case Experience of Immunosuppressant Administration to Systemic Sclerosis-ILD Patients with Aspergilloma

Background: Systemic sclerosis (SSc) is a chronic autoimmune disease that still poses a great challenge to clinicians. SSc is characterized by immune dysregulation and progressive fibrosis that typically affects variable internal organ involvement such as lungs. Interstitial lung disease (ILD) is a common manifestation of SSc and a leading cause of death. The immunosuppressive drug is the main treatment to suppress the inflammation process in SSc.
 Case presentation: In this case we report a 40-year-old female to suffer ILD-SSc. According to High-Resolution Computed Tomography (HRCT) thorax, we found that it was interstitial lung disease with aspergilloma. She got methylprednisolone 3x8 mg and azathioprine 2x50 mg. At the end of the treatment, the patient showed improvement in her clinical condition and showed no worsening condition in the HRCT evaluation for her fungal aspergilloma.
 Conclusion: Systemic sclerosis (SSc) is a rare autoimmune disease involving the skin and internal organs. The immunosuppressive agent is still the drug of choice for most autoimmune diseases. Immunosuppressive may promote fungal growth and have been associated with increased risk in most serious fungal diseases including aspergilloma.

Extracorporeal photopheresis in the treatment of chronic graft-versus-host-disease

Introduction. Chronic graft versus host disease (GVHD) is a frequently occurring complication after transplantation of allogeneic hematopoietic cells associated with a decrease in the quality of life and long-term administration of immunosuppressive drugs. Extracorporeal photopheresis (ECP) is a second line of therapy after treatment failure with glucocorticoids.Aim — to evaluate the effects of ECP treatment in patients with glucocorticosteroids (GCS)-refractory, GCS-dependent or GCS -intolerant chronic GVHD.Materials and methods. 24 patients with GCS-refractory, GCS-dependent or GCS-intolerant chronic GVHD were included in the therapy with ECP. Nine patients had moderate chronic GVHD, and 15 had a severe chronic GVHD. Skin and mucous membranes were the most frequently targeted organs, 21 and 20 of 24 patients respectively, liver damage was detected in 8 patients. The maximum duration of treatment was 33 months (median — 8.5 months). The number of procedures of ECP ranged from 6 to 48 (median — 22).Results. A response was determined in 23 patients with one patient being excluded from the assessment due to a relapse of acute leukemia. 16 (69.5 %) patients achieved an overall response to ECP treatment. Three patients had complete response and full reduction of immunosuppressive therapy. When assessing organ-specific response, the most notable improvement was observed in the mucous membranes of 17 patients (89.4 %), skin — 17 (85 %), and liver — 7 (75 %). Along with achieving a general overall response, 78.2 % of patients partly reduced or completely canceled immunosuppressive therapy.Conclusion. ECP is an effective and promising second line treatment method for chronic GVHD in patients with GCS-refractory, GCS-dependent or GCS-intolerant forms.

Evaluation of tuberculosis infection in COVID-19 patients: a case of tuberculosis and COVID-19 co-infection

The COVID-19 pandemic affected millions of people worldwide, becoming a challenge of every nation. Since the COVID-19 can present wide spectrum of clinical signs and symptoms, patients with symptoms similar to that of COVID-19 may be misdiagnosed during the context of COVID-19 pandemic. In this regard, various co-infections may affect the outcome of COVID-19 patients if it lefts undiagnosed, especially during the administration of immunosuppressive drugs. Similar to COVID-19, TB affect the lungs and respiratory airways primarily. These two diseases have resembling symptoms, including dry cough, fever, and dyspnea. Due to the importance of early COVID-19 diagnosis, many other respiratory infectious diseases such as tuberculosis (TB) may be missed. Herein, a case of COVID-19 and tuberculosis co-infection is presented.

Frequency of Hepatitis B Markers in Systemic Lupus Erythematosus Patients in Iran.

Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Hepatitis B virus is the causative agent for chronic, acute, cirrhosis, and hepatocellular carcinoma. SLE patients with chronic or occult hepatitis B infection undergoing immunosuppressive drugs may become reactive and develop fatal hepatitis. Therefore, this study was conducted to determine HBV markers in SLE patients before the administration of immunosuppressive drugs in Ahvaz city, Iran. Materials and methods:The sera of 92 SLE patients were tested for HBs Ag and anti-HBc using ELISA, HBV DNA (by Nested PCR) testes. Real-time PCR was performed for the patients with positive anti-HBc and negative HBsAg. The positive HBV DNA samples were checked for HBV genotype and HBV subtypes. Results: Among the 92 SLE patients, three (3.3%) were males and 89 (96.7%) females . The patients’ ages ranged from 14 to 70 years [mean age of 38.9±10.1]. Three of 92 (3.26%) subjects [2/3 males and 1/89 female] were positive for HBsAg, anti-HBc Ab, and HBV DNA detected with PCR (p=0.000003)]. Five of 89 (5.61%) subjects [1 male and 4/88 females were only positive for anti-HBc and negative for HBs Ag, HBV DNA(PCR) using Real-time PCR (p=0.05). The results of the nucleotide data and phylogenetic tree showed all three HBV patients were genotype D1. The results of amino acid sequencing revealed all three HBV patients were HBV subtype ayw2. Conclusion:This study proved that 3.26% of SLE patients were positive for overt HBV infection (positive for anti-HBc, HBsAg and HBV-DNA using PCR). All the three isolated HBV were genotype D1 and subtype ayw2. The fact that 5.61% of the patients were only positive for anti-HBc characterized the occult hepatitis B infection (OBI) although further investigation is needed. To prevent HBV or OBI reactivation for SLE patients before immunosuppression treatment, HBV markers including anti-HBc, HBsAg, HBV-DNA should be implemented using PCR and Real-time PCR .

In-ICU-acquired infections in flare-up systemic rheumatic disease patients receiving immunosuppressant.

Systemic rheumatic diseases (SRDs) are a group of inflammatory disorders that can need intensive care unit (ICU) admission during a flare-up, requiring administration of immunosuppressants. We undertook this study to determine the frequency, outcome, and occurrence associated factors of infections in flare-up SRD patients receiving immunosuppressant. Monocenter, a retrospective study including SRD patients admitted to ICU for a flare-up requiring immunosuppressant from 2004 to 2019. The primary endpoint was in-ICU-acquired infections. Ninety-eight patients (female/male ratio: 1.6; mean age at admission: 39.5 ± 17.4 years) were admitted to the ICU for a SRD flare-up, inaugural in 61.2% cases. A specific treatment was given to every patient: corticosteroids 100%, cyclophosphamide 45.9%, plasma exchange 46.9%. Ninety-five infections occurred in 35 (36%) patients mainly pneumonias. The overall in-hospital mortality was 17.3%, and 46% of patients with a nosocomial infection died during their ICU stay. The logistic regression multivariable model retained renal replacement therapy and mechanical ventilation as independent predictors of infection. In-ICU-acquired infection in SRD flare-up is a frequent event associated with organ failures but not with in-ICU use of immunosuppressants. These data suggest that the fear of infection should not withhold a careful in-ICU use of immunosuppressive drugs. Key Points • In-ICU infections are frequent in flare-up systemic rheumatic disease patients. • Infections are associated with increased mortality. • Cyclophosphamide given in ICU was not independently associated with infection. • Severe neutropenia occurred in 27% of patients receiving cyclophosphamide in ICU.

The Cytokine Storm in COVID-19: The Strongest Link to Morbidity and Mortality in the Current Epidemic

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. The clinical presentations of the SARS-CoV-2 infection are widely variable and treatment strategies for COVID-19 are dependent on the infection phase. Timing the right treatment for the right phase of this disease is paramount, with correlations detected between the phase of the infection and the type of drug used to treat. The immune system activation following COVID-19 infection can further develop to a fulminant cytokine storm which can progress to acute respiratory distress syndrome. The inflammatory phase, or the hyperinflammation phase, is a later stage when patients develop acute respiratory distress syndrome (ARDS), sepsis, and kidney and other organ failure. In this stage, the virus is probably not necessary and all the damage is due to the immune system’s cytokine storm. Immunosuppressive or immunomodulatory agent administration is the major strategy in treating COVID-19 patients at this stage. On the other hand, immunodeficient patients who are treated with immunomodulator agents have attenuated immune systems that do not produce enough cytokines. Current data do not show an increased risk of severe COVID-19 in patients taking biologic therapies or targeted disease-modifying antirheumatic drugs. However, more comprehensive studies are needed to assess the effect of these medications, and whether they may actually be protective of the severe type of disease. Although medications for COVID-19 and for the cytokine storm are important, the main breakthrough in slowing down the pandemic was developing effective vaccines. These vaccines showed a dramatic result in reducing morbidity and mortality up to the Delta variant’s spread. However, the emergence of the new variant, Omicron, influenced the successful results we had before. This variant is more contagious but less dangerous than Delta. The aim now is to develop vaccines based on the Omicron and Delta immunogens in the future for broad protection against different variants.

A patient with eosinophilic granulomatosis with polyangiitis successfully weaned from corticosteroids through remission induction therapy with mepolizumab

The patient was a 74-year-old man who was admitted to our hospital for fever, purpura, abdominal pain, and bilateral numbness. Although the patient tested negative for anti-neutrophil cytoplasmic antibody (ANCA), he presented with an elevated peripheral eosinophil count, increased inflammatory responses, duodenitis, cholecystitis, lung lesions, renal disorder, and peripheral neuropathy. The skin biopsy findings revealed vasculitis. Thus, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA). Given the advanced age of the patient, in addition to the poor general condition and hepatic and renal dysfunction, administration of immunosuppressants was considered to pose a high risk. After obtaining informed consent, remission induction therapy was initiated with mepolizumab (MPZ; 300 mg/M) in combination with high-dose corticosteroid therapy (equivalent to 70 mg/day of prednisolone). After treatment initiation, eosinophil counts and inflammatory responses decreased. Moreover, the abdominal pain and purpura resolved, and renal/hepatic dysfunction and peripheral neuropathy also improved. While the corticosteroid dose was subsequently reduced, no relapse was observed. Approximately 2 years later, the corticosteroid was discontinued. After the discontinuation of the corticosteroid, the patient continued treatment with MPZ alone and has remained in remission for approximately 6 months. Therefore, MPZ may be useful as a remission induction therapy in ANCA-negative EGPA resistant to steroids.

Delayed Neutropenia in Heart Transplant Recipients Following COVID-19 Diagnosis

Introduction`Neutropenia is observed after heart transplantation due to medication effects and viral infections. SARS-CoV-2 infection, which causes Covid-19 illness, can uncommonly cause neutropenia in non-transplant recipients. Delayed neutropenia following SARS-CoV-2 infection in heart transplant recipients (HTRs) has not been described.Case ReportCase 1: A 45 year old male combined heart and liver transplant recipient was diagnosed with Covid-19 17 months after transplant. Neutropenia had been noted six months after transplant in the setting of valganciclovir and mycophenolate mofetil (MMF) use, which resolved with discontinuation of those medications. At the time of his Covid-19 diagnosis, his immunosuppression regimen included tacrolimus with a target level 8-10 ng/mL and prednisone 5 mg once daily, and he had an asymptomatic course. His absolute neutrophil count (ANC) four weeks prior to Covid-19 diagnosis was 1,690/uL. The ANC obtained nine weeks after Covid-19 diagnosis was 890/uL. Testing for cytomegalovirus was negative and no neutrophil-depleting medications were identified. He received two doses of granulocyte colony stimulating factor (G-CSF). The subsequent ANC two days after the second dose was 3,600/uL. Case 2: A 66 year old male HTR was diagnosed with Covid-19 31 months after transplant. His symptoms included fever, cough, and diarrhea and he was admitted for inpatient care. Immunosuppression at the time of diagnosis included tacrolimus with a target level of 8-10 ng/mL and MMF 1000 mg twice daily, which was later decreased to 500 mg twice daily. The ANC nadir during his acute illness was 1310/uL. Six weeks after Covid-19 diagnosis, his ANC was 420/uL. Testing for cytomegalovirus was negative. The patient required a total of six doses of G-CSF over six weeks due to persistent neutropenia. MMF was discontinued. He was referred to a hematologist for persistent neutropenia. A bone marrow biopsy showed normal neutrophil production, and increased peripheral neutrophil consumption was hypothesized.SummaryAcute viral infections including SARS-CoV-2 can cause neutropenia, but delayed neutropenia is rare and has not been described in HTRs. Careful monitoring of the complete blood count (with differential) may be useful in this population following a Covid-19 diagnosis. Modulation of immunosuppression and G-CSF administration can support neutrophil recovery.

Клинический случай пациентки с увеитом, ассоциированным с ювенильным идиопатическим артритом

The prevalence of juvenile idiopathic arthritis is 0.05–0.6% in different countries, and in the territory of the Russian Federation it reaches 62.3 100 thousand children. The incidence of uveitis associated with juvenile idiopathic arthritis is 10–30%. Uveitis in juvenile idiopathic arthritis occurs in 80–93% of the type of chronic iridocyclitis. In 3–19.6% of cases, recurrent macular edema develops. In order to treat uveitis associated with juvenile idiopathic arthritis, systemic immunosuppressive therapy, local and systemic administration of antiinflammatory drugs are used. Uveitis in juvenile idiopathic arthritis is asymptomatic in the early stages of the disease, so screening ophthalmological examination of children 2–4 times a year is recommended. Purpose. Description of a clinical case of a patient with uveitis associated with juvenile idiopathic arthritis. Material and methods. A clinical observation of a patient with uveitis associated with juvenile idiopathic arthritis was described. Patient Z., 10 years old, underwent a standard ophthalmological examination, ultrasound examination, optical coherence tomography. Results. The patient had a low-symptomatic course of chronic persistent anterior uveitis, the development of cystic macular edema of the left eye. Anti-inflammatory treatment was carried out in the conditions of the academician S.N. Fyodorov Federal State Institution National Medical Research Center “Intersectoral Research and Technology Complex “Eye microsurgery” Ministry of Health of the Russian Federation”, Novosibirsk Branch. The rheumatologist recommended intensification of systemic immunosuppressive therapy. The prescribed treatment made it possible to preserve visual functions, reduce the frequency and severity of the development of relapses of the disease. Conclusions.Uveitis associated with juvenile idiopathic arthritis is a serious pathology, often accompanied by the development of complications, requires a multidisciplinary approach, regular monitoring and timely adequate treatment. Key words: uveitis, macular edema, juvenile idiopathic arthritis.

Influence of exposure to microbial ligands, immunosuppressive drugs and chronic kidney disease on endogenous immunomodulatory gene expression in feline adipose-derived mesenchymal stem cells.

Feline autologous mesenchymal stem cells (MSCs) show promise for immunomodulatory activity, but the functional impact of chronic kidney disease (CKD), concurrent immunosuppressive drug administration or infection is unknown. The study objectives compare endogenous cytokine gene expression (interleukin [IL]-6, IL-10, IL-12p40, IL-18 and transforming growth factor beta [TGF-β]) in adipose-derived MSCs (aMSCs) from cats with and without CKD, following in vitro exposure to microbial ligands and treatment with common immunosuppressive drugs. Previously obtained aMSCs, phenotype CD44+, CD90+, CD105+ and MHCII-, from cats with (n = 6) and without (n = 6) CKD were compared via real-time PCR (RT-PCR) for immunomodulatory gene expression. aMSCs were exposed in vitro to lipopolysaccharide (LPS), peptidoglycan or polyinosinic:polycytidylic acid (Poly I:C), simulating bacterial or viral exposure, respectively. aMSCs were also exposed to ciclosporin, dexamethasone or methotrexate. Gene expression was measured using RT-PCR, and Cq was utilized after each run to calculate the delta cycle threshold. aMSCs isolated from healthy and CKD cats showed no significant differences in gene expression in the five measured cytokines. No significant changes in measured gene expression after drug treatment or microbial ligand stimulation were observed between normal or CKD affected cats. Proinflammatory genes (IL-6, IL-12p40 and IL-18) showed altered expression in aMSCs from both groups when compared with the same cells in standard culture after exposure to methotrexate. Poly I:C altered IL-6 and TGF-β gene expression in aMSCs from both healthy and CKD cats when compared with the same cells in standard culture. The five genes tested showed no statistical differences between aMSCs from healthy or CKD cats. There was altered cytokine gene expression between the control and treatment groups of both healthy and CKD cats suggesting feline aMSCs have altered function with immunosuppressive treatment or microbial ligand exposure. Although the current clinical relevance of this pilot study comparing brief exposure to select agents in vitro in aMSCs from a small number of cats is unknown, the study highlights a need for continued investigation into the effects of disease and concurrent therapies on use of cell-based therapies in feline patients.

Pluripotent Stem Cell-derived Strategies to Treat Acute Liver Failure: Current Status and Future Directions.

Liver disease has long been a heavy health and economic burden worldwide. Once the disease is out of control and progresses to end-stage or acute organ failure, orthotopic liver transplantation (OLT) is the only therapeutic alternative, and it requires appropriate donors and aggressive administration of immunosuppressive drugs. Therefore, hepatocyte transplantation (HT) and bioartificial livers (BALs) have been proposed as effective treatments for acute liver failure (ALF) in clinics. Although human primary hepatocytes (PHs) are an ideal cell source to support these methods, the large demand and superior viability of PH is needed, which restrains its wide usage. Thus, a finding alternative to meet the quantity and quality of hepatocytes is urgent. In this context, human pluripotent stem cells (PSC), which have unlimited proliferative and differential potential, derived hepatocytes are a promising renewable cell source. Recent studies of the differentiation of PSC into hepatocytes has provided evidence that supports their clinical application. In this review, we discuss the recent status and future directions of the potential use of PSC-derived hepatocytes in treating ALF. We also discuss opportunities and challenges of how to promote such strategies in the common applications in clinical treatments.

Topical administration of tacrolimus and corticosteroids in tapering doses is effective in preventing immune rejection\xa0in high-risk keratoplasty: a 5-year follow-up study

BackgroundTo evaluate the efficacy of the topical administration of immunosuppressants and corticosteroids in tapering doses in the management of patients with high-risk keratoplasty.MethodsOne hundred and six patients treated with topical immunosuppressants (50 eyes in the FK506 group and 56 eyes in the CsA group) and corticosteroid eye drops in tapering doses were enrolled in the study. The rates of rejection episodes, irreversible rejection, graft survival, and related influential factors were evaluated.ResultsThe mean follow-up period was 48.1 ± 7.9 months (range, 36–60 months). The rates of rejection episodes and irreversible rejection were 14.0% and 6.00% in the FK506 group and 37.5% and 7.1% in the CsA group, respectively. Kaplan-Meier survival analysis demonstrated a significantly higher graft survival rate in the FK506 group (81.6%±5.3%, 71.1%±6.3%) compared with that in the CsA group (71.1%±6.3%, 57.5%±7.5%) at 3 and 5 years after surgery (P = 0.006). Multivariate logistic regression revealed that preoperative risk score ≥ 3 (P = 0.016) and endothelial immune rejection (P = 0.033) were risk factors associated with graft survival.ConclusionsTopical administration of tacrolimus and corticosteroids in tapering doses is effective in decreasing the incidence of immune rejection in high-risk keratoplasty. Careful instruction of patients on the reasonable use of topical tacrolimus is critical to avoid immune rejection induced by sudden discontinuation of medication.

Estudio de casos-controles de la infección por Clostridioides difficile en un área sanitaria rural

ObjectiveTo determine the risk and prognostic factors for Clostridioides difficile infection (CDI). Patients and methodsProspective, case-control study with 61 cases and 64 controls, aged ≥2 years with diarrhoea, carried out in Castilla-La Mancha Health Care Area for 14 months. The diagnosis was made by immunochromatography technics (glutamate dehydrogenase and toxin A/B), confirming discordant cases by isothermal amplification. Demographic variables, comorbidities, type of acquisition, previous administration of antibiotics, antacids and immunosuppressants, and evolution were collected. The data were analysed using the chi-square test and the effect of risk and prognostic factors was quantified using an odds ratio with 95% confidence intervals. ResultsHospital admission 4 weeks prior to infection, hypoalbuminemia, and previous administration of antibiotics were identified as independent risk factors for CDI. Presenting these 3 factors constitutes nearly 3-fold increase in the risk of becoming infected. A greater number of hospital admissions in the 4-12 weeks prior to CDI were found in the group of nosocomial acquisition. Although there was a greater tendency to recurrence and an unfavourable prognosis among nosocomial cases, these differences were not significant. We found that fever and hospital admission in the 4 weeks prior to infection were unfavourable prognostic factors of CDI. ConclusionsThe independent risk factors for CDI were: Hospital admission in the 4 weeks prior to infection, hypoalbuminemia, and previous administration of antibiotics. Fever and hospitalisation in the previous 4 weeks were also identified as prognostic factors of unfavourable evolution.

Kimura Disease with Colli Dextra Tumor Manifestation: A Case Report

Abstract Kimura disease (KD) is a rare chronic inflammatory disease characterized by a triad of painless head and subcutaneous neck masses with regional lymphadenopathy, tissue and serum eosinophil infiltration, and elevated serum immunoglobulin E (IgE). It is a benign condition of unknown aetiology that usually affects young Asian men.1,2 We report a case of a 19-year-old woman with a neck lump for the past 3 months said to be enlarged. A less characteristic manifestation with a rare prevalence, Kimura disease, can be considered a differential diagnosis in a colli tumour. In this case, it was established after histopathological biopsy. Treatment for Kimura disease is still under observation in several studies. The treatments that have been tested include surgery, radiotherapy, and administration of corticosteroids and immunosuppressants, or a combination. In this case, surgical therapy was initiated, followed by steroids and radiotherapy.