Immune Suppressive Treatment Research Articles

Clinical Characteristics and Outcomes in Patients with Chronic HBV Infection and Hospitalized for COVID-19 Pneumonia: A Retrospective Cohort Study

The effects of a concomitant infection of hepatitis B virus (HBV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are still debated, with a recognized major risk of HBV reactivation during immune-suppressive treatments. The aim of this study was to determine the prevalence and predictive factors of HBV reactivation in a cohort of hospitalized patients with coronavirus disease 2019 (COVID-19) and a current or past hepatitis B infection. In a monocentric retrospective observational study, we enrolled all consecutive hospital admitted patients with COVID-19 pneumonia and a positive HBV serology (N = 84) in our Infectious Diseases Unit from April 2021 to December 2023. We identified 18 (21%) HBsAg-positive/anti-HBc-positive, 41 (49%) HBsAg-negative/anti-HBc-positive/anti-HBs-positive, and 25 (30%) HBsAg-negative/anti-HBc-positive/anti-HBs-negative subjects. The overall rate of hepatitis flare was 10.7%, without any HBsAg seroreversion, severe HBV reactivation, and/or need for new HBV antiviral therapy introduction. Systemic corticosteroid treatment for COVID-19 and baseline anti-HBsAg status were associated with this risk of HBV reactivation. In conclusion, the overall risk of hepatitis flares in hospitalized COVID-19 was reasonably low, with higher doses of corticosteroids treatment being the major risk factor for HBV reactivation, and anti-HBs-positive serological status as a protective element.

Targeting CNS myeloid infiltrates provides neuroprotection in a progressive multiple sclerosis model

Demyelination and axonal injury in chronic-progressive Multiple Sclerosis (MS) are presumed to be driven by a neurotoxic bystander effect of meningeal-based myeloid infiltrates. There is an unmet clinical need to attenuate disease progression in such forms of CNS-compartmentalized MS. The failure of systemic immune suppressive treatments has highlighted the need for neuroprotective and repair-inducing strategies. Here, we examined whether direct targeting of CNS myeloid cells and modulating their toxicity may prevent irreversible tissue injury in chronic immune-mediated demyelinating disease. To that end, we utilized the experimental autoimmune encephalomyelitis (EAE) model in Biozzi mice, a clinically relevant MS model. We continuously delivered intracerebroventricularly (ICV) a retinoic acid receptor alpha agonist (RARα), as a potent regulator of myeloid cells, in the chronic phase of EAE. We assessed disease severity and performed pathological evaluations, functional analyses of immune cells, and single-cell RNA sequencing on isolated spinal CD11b+ cells. Although initiating treatment in the chronic phase of the disease, the RARα agonist successfully improved clinical outcomes and prevented axonal loss. ICV RARα agonist treatment inhibited pro-inflammatory pathways and shifted CNS myeloid cells toward neuroprotective phenotypes without affecting peripheral infiltrating myeloid cell phenotypes, or peripheral immunity. The treatment regulated cell-death pathways across multiple myeloid cell populations and suppressed apoptosis, resulting in paradoxically marked increased neuroinflammatory infiltrates, consisting mainly of microglia and CNS / border-associated macrophages. This work establishes the notion of bystander neurotoxicity by CNS immune infiltrates in chronic demyelinating disease. Furthermore, it shows that targeting compartmentalized neuroinflammation by selective regulation of CNS myeloid cell toxicity and survival reduces irreversible tissue injury, and may serve as a novel disease-modifying approach.

Inborn Errors of Immunity in Adults with Autoimmune Liver Diseases.

Inborn errors of immunity (IEI) may associate with autoimmune diseases, including autoimmune liver diseases (AILD). However, both the IEI frequency and secondary effects of immunosuppressives are unknown in patients with AILD due to the lack of data. We aimed to evaluate the ratio of IEI in AILD. A total of 82 patients with AILD (39 autoimmune hepatitis, 32 primary biliary cholangitis, 7 variant syndromes (VS), and 4 primary sclerosing cholangitis patients) were included in this single-center, cross-sectional, and descriptive study. The patients were evaluated and classified according to diagnostic criteria for IEI. Out of 82 patients with AILD, female/male ratio was 3.6. Median age of diagnosis of AILD was 45 years. We diagnosed 15 (18%) patients with immunodeficiency (ID). Inborn errors of immunity ratio was highest in VS patient group (29%). Out of 15 patients with ID, 4 (4.8%) patients had common variable immunodeficiency, 4 (4.8%) had partial immunoglobulin A deficiency, 4 (4.8%) had selective immunoglobulin M deficiency, and 3 (3.6%) had combined immunodeficiency. We detect ID in about one-fifth of the patients with AILD. The present study showed a significant risk of IEI that is blurred by the shadow of immune suppressive treatments. We suggest that the AILD patients with ID will benefit from the individualized and targeted therapeutic options used in IEI. Further research with larger patient groups and long-term follow-up are desperately needed to elucidate the diagnostic, therapeutic, and prognostic impacts of IEI-related individualized therapy on AILD patients.

Impact of bowel ischemia on mortality in gastrointestinal malignancies: A nationwide analysis.

e16370 Background: Bowel ischemia, characterized by reduced blood supply to the gastrointestinal (GI) tract, critically influences the pathogenesis and outcomes of GI malignancies through complex interactions involving vascular compromise, tumor biology, and systemic consequences. Despite this, the link between bowel ischemia and increased mortality in GI cancers remains unknown. This study aims to evaluate the impact of bowel ischemia on in-hospital mortality in GI cancer patients in the United States. Methods: This retrospective analysis utilized the 2016-2020 National Inpatient Survey (NIS) database. Adults aged 18 and above with esophageal, gastric, colon, cholangiocarcinoma, hepatocellular carcinoma, and pancreatic cancers were identified using the International Classification of Disease-10 (ICD-10) code. The cohort was stratified into patients with and without bowel ischemia. Hospital mortality was analyzed using STATA 18, adjusting for age, gender, race, insurance, Charlson’s index, baseline hospital characteristics, and comorbidities. Multivariate logistic regression analysis was performed, with all P values ≤ 0.05 considered statistically significant. Results: Among 2,133,465 adults with GI malignancies, 3,240 were hospitalized with bowel ischemia. Patients with bowel ischemia were older (mean age 68.10 vs. 67.07 years, P = 0.033), predominantly from the Southern region (33.49%, P = 0.019), and urban and teaching hospitals (76.83%; P = 0.006). Bowel ischemia was most associated with Pancreatic cancer (37.35%), Colon cancer (35.49%), and Hepatocellular carcinoma (11.57%). Within the cohort of patients with bowel ischemia, gastric cancer patients had the highest mortality rates of 45.83%. After adjusting for potential confounders, patients with gastric, esophageal, colon, and pancreatic cancers had significantly higher odds of in-hospital mortality of 11.90, 6.45, 4.14, 4.08, and 2.71, respectively. Conclusions: This study reveals an association between outcomes in hospitalized GI cancer patients and bowel ischemia, leading to increased mortality despite adjusting for potential confounders. Bowel ischemia significantly heightens the mortality risk in GI cancers through impaired nutrient and oxygen delivery, enhanced tumor aggressiveness, systemic inflammation, immune suppression, and compromised treatment efficacy. Understanding the intricate interplay between vascular compromise and cancer biology is crucial to improving patient care and outcomes in the face of these challenging malignancies.

Inflammation and Myocardial Blood Flow in Cardiac Sarcoidosis.

Cardiac involvement in systemic sarcoidosis or isolated cardiac sarcoidosis plays a pivotal role in the clinical manifestation and prognostication. Active-inflammatory cardiac sarcoidosis is associated with a regional impairment of coronary microvascular function that may confer further detrimental effects on myocardial function needing further characterization. Clinical investigations with cardiac positron emission tomography/computed tomography in conjunction with 18F-fluorodeoxyglucose to determine myocardial inflammation and 13N-ammonia to quantify myocardial blood flow (MBF) in patients with known or suspected cardiac sarcoidosis outlined that sarcoidosis-induced myocardial inflammation was associated with adverse effects on corresponding regional coronary microvascular function. Notably, immune-suppressive treatment caused reductions in myocardial inflammation were paralleled by improvements of coronary microvascular dysfunction outlining direct adverse effect of inflammation on coronary arteriolar function. This review summarizes contributions of cardiac PET imaging in the identification and characterization of active-inflammatory cardiac sarcoidosis, its effect on coronary microvascular function, treatment responses, and prognostic implications.

Evaluating IgG Levels, Vaccination Effects, and COVID-19 Infection Severity in Renal Transplant Recipients

Several studies have reported that different factors play an important role in the production of IgG after VOVID-19 vaccination. This study aimed at studying COVID-19 infection rates and severity in renal transplant recipients and vaccine responsiveness. comorbidity hemodialysis requirements, and immune suppression treatment regimens. In this cross-sectional study, IgG levels was measured in renal transplant recipients using automated benchtop immunoanalyzer Vidas at the Duhok Center for Kidney Disease and Transplantation. In this study group, only 30 individuals experienced the SARS-COVID-2 infection, with only three cases being severe. The most frequently reported symptoms of SARS-COVID-2 virus infection were fatigue (18/30) 60%, high temperature (17/30) 56%, headache (12/30) 40%, and poor endurance (11/30) 36.6%. The IgG titers were significantly different between the vaccinated 33.067 ± 2.5 versus unvaccinated individuals 23.916 ± 3.31with p value = 0.025. On the other hand, demographic characteristics of the cohort including: comorbidities, hemodialysis, different age groups, gender, infection/no-infection differences had no statistically significant impact on the IgG titers. Vaccination significantly increased the levels of protective IgG level in kidney transplant recipients. It is crucial to focus on increasing the acceptance of vaccination among kidney transplant recipients to prevent infections from other COVID-19 variants or pathogen outbreaks.

Role of FoxP3+ Regulatory T Cells in Modulating Immune Responses to Adeno-Associated Virus Gene Therapy.

Adeno-associated virus (AAV) gene therapy is making rapid strides owing to its wide range of therapeutic applications. However, development of serious immune responses to the capsid antigen or the therapeutic transgene product hinders its full clinical impact. Immune suppressive (IS) drug treatments have been used in various clinical trials to prevent the deleterious effects of cytotoxic T cells to the viral vector or transgene, although there is no consensus on the best treatment regimen, dosage, or schedule. Regulatory T cells (Tregs) are crucial for maintaining tolerance against self or nonself antigens. Of importance, Tregs also play an important role in dampening immune responses to AAV gene therapy, including tolerance induction to the transgene product. Approaches to harness the tolerogenic effect of Tregs include the use of selective IS drugs that expand existing Tregs, and skew activated conventional T cells into antigen-specific peripherally induced Tregs. In addition, Tregs can be expanded ex vivo and delivered as cellular therapy. Furthermore, receptor engineering can be used to increase the potency and specificity of Tregs allowing for suppression at lower doses and reducing the risk of disrupting protective immunity. Because immune-mediated toxicities to AAV vectors are a concern in the clinic, strategies that can enhance or preserve Treg function should be considered to improve both the safety and efficacy of AAV gene therapy.

All-cause mortality of hospitalized inflammatory bowel disease patients: a multicenter study from Iran.

In this multicenter study, we investigated all causes of mortality in hospitalized inflammatory bowel disease (IBD) patients. The widespread use of biologics and immune suppressive treatments, along with the longer lifespan of patients with IBD, may have changed the cause of death in this population. Knowing this may lead to better preventive and therapeutic strategies for IBD patients. This cross-sectional study reviewed records of 1926 IBD patients hospitalized in referral hospitals in Isfahan and Shiraz during 2013-2021. In nine years, 84 patients, 39 from Isfahan and 45 from Shiraz, died. We retrospectively gathered data on demographic, clinical, and laboratory information, as well as the cause of death. We extracted the cause of death from the death sheets and classified it using the International Classification of Diseases (ICD-10). Using the Kaplan-Meier model, we estimated the median survival time from disease diagnosis to death. Males accounted for 47 (55%) of the deceased patients. The mean age of the patients was 48.63 ± 18.7 years. The mortality rates among hospitalized UC and CD patients were 7.2% and 7.8%, respectively. The median duration of admission to death was 8 days, with 19 (22.6%) of IBD patients dying on the first day of their hospital admission. Half of the cohort of deceased IBD patients had survived for 8 years following their disease diagnosis. 32.7% of all recorded causes of death were due to certain infectious diseases. The second and third most common causes of death were diseases of the digestive system and diseases of the circulatory system, including pulmonary embolism, accounting for 30.1% and 14.2%, respectively. According to this study from Iran, infectious diseases are the leading cause of death among hospitalized IBD patients. Prevention and clinical management of pulmonary embolism in IBD patients require more careful consideration. We strongly encourage population-based cohort studies to enhance the findings.

Awareness and experiences of side effects and infections during chemotherapy treatment: a cross sectional survey among family caregivers of cancer patients in India

Background: Adequate understanding of side effects and infections is essential for family caregivers to ensure proper management for cancer patients during chemotherapy. The present paper describes the family caregivers' awareness of the symptoms of possible side effects and infections during chemotherapy treatment. Methods: Family caregivers were identified through the lodging facilities near the cancer treatment centres in Thiruvananthapuram and Mumbai. The cross-sectional survey was conducted using a structured interview schedule formulated in the Kobo-collect toolbox and analyzed using IBM-SPSS-Statistics-25. Results: Among the 217 family caregivers aged between 19 to 76 years, 83% were close relatives of the patients. The majority of the family caregivers were able to identify conditions such as hair loss (95%), appetite change (88%), and nausea/vomiting (88%) as side effects of chemotherapy. At the same time, participants recognized the symptoms of infections were less. Unusual vaginal discharge/irritation (57%) and burning/pain with urination (55%) were the commonly recognized symptoms of infections. From the list of symptoms, more than six out of the thirteen side effects and more than three out of seven infections were correctly identified by 82% and 42% of family caregivers, respectively. Conclusions: The family caregivers were largely aware of side effects but not much about infections. Since chemotherapy is an immune suppressive treatment, infection awareness among family caregivers is essential to avoid any serious complications during the treatment period. Communication with family caregivers on 'the symptoms and management' of 'side effects and infections' and when to seek treatment is crucial for cancer treatment success.

Subclinical atherosclerosis in Behcet's disease and its inverse relation to azathioprine use: an updated meta-analysis.

To evaluate the intima media thickness of carotid arteries (IMT) and its clinical, laboratory and treatment correlates in Behcet's disease (BD). Systematic search of EMBASE and PubMed databases from January 2016 to October 2022; we employed random effect meta-analyses for continuous outcomes and Peto's odds ratio for rare events. The meta-analysis included 36 case control studies: the IMT was greater in BD (n = 1103) than in controls (n = 832) (p < 0.0001) with wide heterogeneity (I2 = 86.9%); a sensitivity analysis that included mean age of BD participants, gender, disease duration and activity, atherogenic index of plasma, blood pressure, C-reactive protein, ethnicity, smoking status, anti-inflammatory and immune suppressive agents, revealed that male gender, mean age of participants and azathioprine use (the latter two in inverse fashion) partly explained the heterogeneity variance (p = 0.02, p = 0.005, and p = 0.01). The IMT was greater in vascular (n = 114) than in non-vascular BD (n = 214) (p = 0.006). BD patients (n = 782) had a greater pooled prevalence of carotid plaques than controls (n = 537) (13.1% vs. 2.97%, p < 0.0001). Subclinical carotid artery atherosclerosis represents a vascular feature of BD, independently of the traditional cardiovascular risk factors. The inverse correlations between IMT, age and azathioprine use suggest that thicker carotid arteries at disease onset eventually regress with immune suppressive treatment: this assumption needs verification on adequately designed clinical trials.

Pseudomonas aeruginosa Bloodstream Infections in SARS-CoV-2 Infected Patients: A Systematic Review.

Bacterial co-infections increase the severity of respiratory viral infections and are frequent causes of mortality in COVID-19 infected subjects. During the COVID-19 period, especially at the beginning of the pandemic, an inappropriate use of broad-spectrum antibiotic treatments has been frequently described, mainly due to prolonged hospitalization, especially in intensive care unit departments, and the use of immune-suppressive treatments as steroids. This misuse has finally led to the occurrence of infections by multi-drug resistant (MDR) bacteria in hospitalized COVID-19 patients. Although different reports assessed the prevalence of Gram-negative infections in COVID-19 infected patients, scarce data are currently available on bloodstream infections caused by Pseudomonas aeruginosa in hospitalized COVID-19 patients. The aim of our systematic review is to describe data on this specific population and to discuss the possible implications that these co-infections could have in the management of COVID-19 pandemics in the future. We systematically analysed the current literature to find all the relevant articles that describe the occurrence of P. aeruginosa bloodstream infections in COVID-19 patients. We found 40 papers that described in detail P. aeruginosa HAIs-BSI in COVID-19 patients, including 756,067 patients overall. The occurrence of severe infections due to MDR bacteria had a significant impact in the management of hospitalized patients with COVID-19 infections, leading to a prolonged time of hospitalization and to a consequent increase in mortality. In the near future, the increased burden of MDR bacteria due to the COVID-19 pandemic might partially be reduced by maintaining the preventive measures of infection control implemented during the acute phase of the COVID-19 pandemic. Finally, we discuss how the COVID-19 pandemic changed the role of antimicrobial stewardship in healthcare settings, according to the isolation of MDR bacteria and how to restore on a large scale the optimization of antibiotic strategies in COVID-19 patients.

Risk factors for a severe disease course in children with SARS-COV-2 infection following hematopoietic cell transplantation in the pre-Omicron period: a prospective multinational Infectious Disease Working Party from the European Society for Blood and Marrow Transplantation group (EBMT) and the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH) study.

Risk factors for severe SARS-Cov-2 infection course are poorly described in children following hematopoietic cell transplantation (HCT). In this international study, we analyzed factors associated with a severe course (intensive care unit (ICU) admission and/or mortality) in post-HCT children. Eighty-nine children (58% male; median age 9 years (min-max 1-18)) who received an allogeneic (85; 96%) or an autologous (4; 4%) HCT were reported from 28 centers (18 countries). Median time from HCT to SARS-Cov-2 infection was 7 months (min-max 0-181). The most common clinical manifestations included fever (37; 42%) and cough (26; 29%); 37 (42%) were asymptomatic. Nine (10%) children following allo-HCT required ICU care. Seven children (8%) following allo-HCT, died at a median of 22 days after SARS-Cov-2 diagnosis. In a univariate analysis, the probability of a severe disease course was higher in allo-HCT children with chronic GVHD, non-malignant disease, immune suppressive treatment (specifically, mycophenolate), moderate immunodeficiency score, low Lansky score, fever, cough, coinfection, pulmonary radiological findings, and high C-reactive protein. In conclusion, SARS-Cov-2 infection in children following HCT was frequently asymptomatic. Despite this, 10% needed ICU admission and 8% died in our cohort. Certain HCT, underlying disease, and SARS-Cov-2 related factors were associated with a severe disease course.

CD19-Targeted CAR-T Cells in Refractory Systemic Lupus Erythematosus: Safety, Efficacy, and Mechanistic Insights from the First Five Patients

Background: Systemic lupus erythematosus (SLE) is an auto-immune disease that is based on dysregulation of the adaptive immune system, autoantibody production and immune complex-mediated tissue damage. While treatment of SLE has substantially improved, a subset of patients experiences severe progressive disease despite T- and B-cell targeted therapy. Aim: For patients with refractory SLE, we aimed to achieve deep depletion of B cells using autologous CD19-CAR T cells with the goal of achieving an immunological reset and drug free remission. Methods: Five patients (4 women, 1 men) with SLE refractory to several immune-suppressive drugs including pulsed steroids, hydroxychloroquine, mycophenolate, cyclophosphamide, intravenous immunoglobulins, rituximab, and belimumab were treated with CD19 CAR T cells in a compassionate use program. Mean patient age was 21.8 ± 2.3 years, mean disease duration was 4.6 ± 3.0 years and mean SLE disease activity index (SLEDAI) was 11.8±3.8. Autologous T cells were transduced with a lentiviral anti-CD19 CAR vector composed of the FMC63 scFv, a CD8-derived hinge region, TNFRSF19-derived transmembrane domain, CD3ζ intracellular domain, and 4-1BB co-stimulatory domain and expanded within the local GMP facility utilizing the closed automated CliniMACS Prodigy® system (Miltenyi Biotec, Bergisch Gladbach, Germany). CAR T cells were re-infused at a dose of 1x106 CAR T cells/kg body weight after lymphodepletion with fludarabine/ cyclophosphamide. All SLE treatments with the exception of low dose prednisolone was stopped before CAR-T cell administration. After CAR-T cell treatment, no other immune-modulatory or immune-suppressive treatment was given. Tolerability was assessed following international guidelines. Results: Despite long-lasting high dose steroid treatment, sufficient numbers of CD19 CAR-T cells could be generated from 5/5 SLE patients. Lymphodepletion led to expected reduction of white blood cells. Following lymphodepletion, CAR T cells expanded in vivo with a peak on day 9 and a deep depletion of B cells was achieved in all patients. Bone marrow toxicity towards non-B cells was short and all patients recovered neutrophils (>500/nL) before day 14 post CAR T cells. Only mild CRS of °I occurred in all five patients. One patient received a single dose of tocilizumab due to persisting fever >24 hours. There were no ICANS, no CRS of any organ, and no infections. Remission of SLE according to DORIS criteria was achieved in all 5 patients after 3 months and the mean (±SD) SLEDAI score after 3 months was 0.4±0.9. Laboratory parameters normalized in all SLE patients after CAR-T transfer including seroconversion of anti-dsDNA antibodies and all patients were free of immune-suppressive drugs by month 3. One patient presented with proteinuria at month 4. Kidney biopsy as well as serum diagnostics showed no signs of SLE. After a steroid pulse, proteinuria went back to normal. Despite reconstitution of B cells no relapse of SLE was observed in the follow up of any of the patients which are now 17, 12, 8, 7, and 5 months after CAR T cell therapy. Reappearing B cells were naïve and showed non-class switched B cell receptors. While pre-existing vaccine-specific antibodies towards measles or VZV persisted, several auto-reactive antibodies were abrogated. Quality of life was poor at decision to treatment and improved substantially at month three. Improvement was mostly driven by abrogation of joint pain and of fatigue. Conclusions: Taken together, the preliminary data from this pilot study show that CD19 CAR T-cell therapy is very well tolerated in patients with a non-malignant B cell derived autoimmune disease and induce rapid remission of severe refractory SLE. Longer follow-up and higher patient numbers from controlled clinical trials are needed to confirm these promising results.

Vaccination Opportunities in Multiple Sclerosis Patients Treated with Cladribine Tablets.

COVID 19 pandemic and mass vaccination campaigns have revealed the situation of the most vulnerable patients. In this work, we focused our attention to patients who have Multiple Sclerosis (MS), particularly in treatment with cladribine tablets, trying to understand if and when it is possible to administer the vaccine successfully. In light of the novel topic, we studied the existing literature and analysed experiences with previous vaccinations, such as influenza and VZV, as well as data from countries where vaccination campaigns had already begun. Overall, we have taken into account the mechanism of action, the pharmacokinetic/pharmacodynamic of cladribine, and the changes in the immune system after its administration, together with the preliminary data about the humoral response to influenza, VZV, and SARS-CoV-2 vaccinations in cladribine treated patients. In conclusion, data showed that the use of cladribine tablets seems to permit flexibility regarding vaccination timing and we suggest that vaccination in those patients should be safe and effective. The current COVID 19 pandemic has re-ignited the interest in vaccines and vaccination procedures. The importance of including fragile individuals has increased as a result of mass vaccination. Millions of patients with multiple sclerosis (MS) around the world are debating whether they can safely receive their vaccine shot with the same efficacy despite receiving immune-modulating or immune-suppressive treatments. In the absence of conclusive empirical data, we will review and discuss the available evidence and the reasonable conclusions for one specific treatment, namely cladribine tablets (Mavenclad).

Risk factors for early death or euthanasia within 100 days of diagnosis in dogs with meningoencephalitis of unknown origin

Meningoencephalitis of unknown origin (MUO) in the dog is an inflammatory condition of the central nervous system with variable short- and long-term prognosis. Previous studies have attempted to identify risk factors for early death; however, the findings were inconsistent and prognostication and treatment selection remain difficult for cases of MUO. The aim of this study was to compare the influence of putative prognostic factors on early survival in dogs with MUO. Logistic regression was used to analyse the effect of clinical and magnetic resonance imaging (MRI) features at diagnosis and type of immune-suppressive treatment received on survival at three-time points; 7 days, 30 days, and 100 days post-diagnosis. Ninety eight dogs were included.Dogs that were obtunded at presentation had a 6.6 times increased odds of death in the first 7 days after diagnosis, a 2.1 times increased risk of death 8–30 days after diagnosis, and a 1.9 times increased risk of death 31–100 days after diagnosis. No other clinical, MRI feature, or treatment was found to have a significant influence on survival. Obtundation at presentation was found to increase risk of early euthanasia in dogs with MUO, while the addition of an IV infusion of cytarabine to immune-suppressive corticosteroid therapy (prednisolone and/or dexamethasone) at initial treatment did not improve the odds of survival at 7, 30, or 100 days after diagnosis.

Dynamics of the Immune response in Hospitalized SARS-CoV-2 Infected Cancer Patients

Seroconversion rates were compared between oncological and non-oncological patients infected with SARS-CoV-2 during a 14-day hospitalization time. All COVID-19 non-oncological and solid malignancies patients reached 100% seroconversion at day 14, while less than half of the hematological patients were seroconverted at the same time point. Despite the limited number and variability of the patient’s cohort, we conclude that there is a delayed seroconversion in the hematological malignancies group, which may be linked to changes in the hematological parameters, immune suppression and/or oncological treatments that are typically associated with these patients.

A Single Center's Experience with BK-Virus Frequency in Post-Renal Transplant Patients in IKD Peshawar

Objective: To measure the incidence of BK-Virus infection, treatment, and complications among patients who had kidney transplants at the Institute of Kidney Diseases (IKD) in Peshawar, Pakistan. Methodology: The single center experience retrospective study was conducted in IKD Peshawar, Pakistan from January to December 2021. Clinical and analytical data was gathered. Blood samples were tested for BK virus load using quantitative DNA-polymerase chain reaction (PCR). Results: A total of 131 patients were examined. Of the 131 participants, 117 (89.4%) were males and 14 (10.6%) were females, with a mean age of 30.04 5.41. All of the patients received a transplant from a blood relative. After six months, the BK-Virus plasma PCR was found to be positive in eight patients (6.2%) who had had kidney transplantation. Conclusion: Patients who have had a kidney transplant and are on induction treatment or other forms of immune-suppression are at an increased risk of contracting the BK-Virus infection. Immunosuppressive medicines should be reduced to the barest minimum for effective treatment. Keywords: Transplanted Kidneys, BK Virus.

Short course of immune-suppressive doses of prednisolone, evaluated through a prospective double-masked placebo-controlled clinical trial in healthy Beagles, is associated with sustained modifications in renal, hydration, and electrolytic status.

To investigate the effects and duration of orally administered prednisolone on renal function evaluated by glomerular filtration rate (GFR) determination and creatinine (Cr) and symmetric dimethylarginine (SDMA) concentrations as well as on urinalysis, electrolytes, and hydric status in healthy dogs. 14 healthy Beagles. In this prospective double-masked placebo-controlled study, dogs were randomized after baseline evaluation to receive a 7-day course of either prednisolone (1.5 to 2.0 mg/kg, PO, q 12 h) or a placebo. A repeated-measure design was performed, each dog participating in 4 successive sampling sessions. Clinical data, systolic blood pressure, CBC, and biochemical analyses including serum SDMA concentration, GFR determination, urine output quantification, and complete urinalysis were performed for all dogs the day before (D0) and at the end of steroid administration (D7) as well as 2 weeks (D21) and 4 weeks (D35) after the end of treatment. At D7, when compared with baseline, GFR increased significantly in treated dogs, whereas creatinine and SDMA concentrations decreased significantly. GFR and Cr but not SDMA modifications persisted significantly at D21. None of the variables differed significantly from baseline at D35. The OR of presenting an albumin band on urine electrophoresis was 2.4 times as high in treated versus control dogs (OR, 36; 95% CI, 1.8 to 719.4; P = 0.02). A short-term course of immune-suppressive prednisolone treatment in healthy dogs leads to a sustained but reversible renal hyperfiltration state. Modification in electrolytic variables can affect the clinical interpretation of blood work in such patients.

Effects of temporarily suspending low-dose methotrexate treatment for 2 weeks after SARS-CoV-2 vaccine booster on vaccine response in immunosuppressed adults with inflammatory conditions: protocol for a multicentre randomised controlled trial and nested mechanistic substudy (Vaccine Response On/Off Methotrexate (VROOM) study)

IntroductionIt is unknown if a temporary break in long-term immune-suppressive treatment after vaccination against COVID-19 improves vaccine response. The objective of this study was to evaluate if a 2-week interruption...

Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia and Ventilator-Associated Tracheobronchitis in COVID-19.

Although few studies evaluated the incidence of hospital-acquired pneumonia (HAP) or ventilator-associated tracheobronchitis in COVID-19 patients, several studies evaluated the incidence of ventilator-associated pneumonia (VAP) in these patients. Based on the results of a large multicenter European study, VAP incidence is higher in patients with SARS-CoV-2 pneumonia (36.1%), as compared with those with influenza pneumonia (22.2%), or no viral infection at intensive care unit (ICU) admission (16.5%). Potential explanation for the high incidence of VAP in COVID-19 patients includes long duration of invasive mechanical ventilation, high incidence of acute respiratory distress syndrome, and immune-suppressive treatment. Specific risk factors for VAP, including SARS-CoV-2-related pulmonary lesions, and bacteria-virus interaction in lung microbiota might also play a role in VAP pathogenesis. VAP is associated with increased mortality, duration of mechanical ventilation, and ICU length of stay in COVID-19 patients. Further studies should focus on the incidence of HAP especially in ICU non-ventilated patients, better determine the pathophysiology of these infections, and evaluate the accuracy of currently available treatment guidelines in COVID-19 patients.