Sequels of COVID-19 in nephrology. Chronic kidney patients are more prone to hemodialysis need and mortality.

Introduction: Acute kidney injury involves inflammation and intrinsic renal damage, and is a common complication of severe coronavirus disease 2019 (COVID-19). Baseline chronic kidney disease (CKD) confers an increased mortality risk. We determined the renal long-term outcomes of COVID-19 in patients with baseline CKD, and the risk factors prompting renal replacement therapy (RRT) initiation and mortality.

Antibody-based delivery of interleukin-2 modulates the immunosuppressive tumor microenvironment and achieves cure in pancreatic ductal adenocarcinoma syngeneic mice.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadly type of cancer, with an extremely low five-year overall survival rate. To date, current treatment options primarily involve various chemotherapies, which often prove ineffective and are associated with substantial toxicity. Furthermore, immunotherapies utilizing checkpoint inhibitors have shown limited efficacy in this context, highlighting an urgent need for novel therapeutic strategies.

Identifying risk factors for blood culture negative infective endocarditis: An international ID-IRI study.

Background: Blood culture-negative endocarditis (BCNE) is a diagnostic challenge, therefore our objective was to pinpoint high-risk cohorts for BCNE.

Methods: The study included adult patients with definite endocarditis. Data were collected via the Infectious Diseases International Research Initiative (ID-IRI).

Severe hypoglycemia induced by Tigecycline in a diabetic and hemodialysis patient.

Introduction: Tigecycline has a broad spectrum of activity, including activity against drug-resistant Gram-positive and -negative microorganisms. Its side effects are significant, but hypoglycemia is a rare finding during treatment. We aim to present an event of severe hypoglycemia in a patient with type 2 diabetes mellitus with replacement renal therapy, and hemodialysis after initiating tigecycline.

Multidrug-Resistant Acinetobacter baumannii mediastinitis.

Introduction: Mediastinitis remains one of the most serious complications of cardiac surgery. The reported incidence is 1-4%, while the related mortality varies from 10-47%.

Case Presentation: A patient with triple vessel disease (TVD) was hospitalized at our clinic for coronary artery bypass graft (CABG) surgery.

Cytokine Biopharmaceuticals with "Activity-on-Demand" for Cancer Therapy.

Cytokines are small proteins that modulate the activity of the immune system. Because of their potent immunomodulatory properties, some recombinant cytokines have undergone clinical development and have gained marketing authorization for the therapy of certain forms of cancer. Recombinant cytokines are typically administered at ultralow doses, as many of them can cause substantial toxicity even at submilligram quantities.

Optimizing the Design and Geometry of T Cell-Engaging Bispecific Antibodies Targeting CEA in Colorectal Cancer.

Metastatic colorectal cancer remains a leading cause of cancer-related deaths, with a 5-year survival rate of only 15%. T cell-engaging bispecific antibodies (TCBs) represent a class of biopharmaceuticals that redirect cytotoxic T cells toward tumor cells, thereby turning immunologically "cold" tumors into "hot" ones. The carcinoembryonic antigen (CEA) is an attractive tumor-associated antigen that is overexpressed in more than 98% of patients with colorectal cancer.

A novel strategy to generate immunocytokines with activity-on-demand using small molecule inhibitors.

Cytokine-based therapeutics have been shown to mediate objective responses in certain tumor entities but suffer from insufficient selectivity, causing limiting toxicity which prevents dose escalation to therapeutically active regimens. The antibody-based delivery of cytokines significantly increases the therapeutic index of the corresponding payload but still suffers from side effects associated with peak concentrations of the product in blood upon intravenous administration. Here we devise a general strategy (named "Intra-Cork") to mask systemic cytokine activity without impacting anti-cancer efficacy.

Middle Cerebral Artery Dissection: A Report of Two Cases With Treatments and Outcomes.

In the present report, we describe two cases of right-sided M1 segment middle cerebral artery dissection in a 51-year-old Asian female and in a 28-year-old Caucasian male patient with no previous history of ischemic stroke or known intracranial atherosclerosis presenting with acute unilateral headache progressing to severe multifocal hemispheric infarction with nearly complete one-sided motor paralysis. In both patients, a middle cerebral artery dissection was detected on angiography; they were given exclusively medical therapy: patient 1 was not eligible to reperfusive therapies and was treated with a three-month course of acetylsalicylic acid and clopidogrel combined with low-dose enoxaparin, while patient 2 was initially treated with intravenous alteplase with no hemorrhagic complications and was later shifted to single antiplatelet therapy. Despite an initial worsening of clinical severity and an extensive ischemic lesion in both patients, neurologic function improved over time, eventually allowing recovery of unaided gait.

Generation of a novel fully human non-superagonistic anti-CD28 antibody with efficient and safe T-cell co-stimulation properties.

Antibody-based therapeutics represent an important class of biopharmaceuticals in cancer immunotherapy. CD3 bispecific T-cell engagers activate cytotoxic T-cells and have shown remarkable clinical outcomes against several hematological malignancies. The absence of a costimulatory signal through CD28 typically leads to insufficient T-cell activation and early exhaustion.

Generation and characterization of a novel high-affinity human antibody targeting carcinoembryonic antigen.

There are no effective treatment options for most patients with metastatic colorectal cancer (mCRC). mCRC remains a leading cause of tumor-related death, with a five-year survival rate of only 15%, highlighting the urgent need for novel pharmacological products. Current standard drugs are based on cytotoxic chemotherapy, VEGF inhibitors, EGFR antibodies, and multikinase inhibitors.

Targeted delivery of tumor necrosis factor in combination with CCNU induces a T cell-dependent regression of glioblastoma.

Glioblastoma is the most aggressive primary brain tumor with an unmet need for more effective therapies. Here, we investigated combination therapies based on L19TNF, an antibody-cytokine fusion protein based on tumor necrosis factor that selectively localizes to cancer neovasculature. Using immunocompetent orthotopic glioma mouse models, we identified strong anti-glioma activity of L19TNF in combination with the alkylating agent CCNU, which cured the majority of tumor-bearing mice, whereas monotherapies only had limited efficacy.

Predictors of mortality in hemodialysis patients with COVID-19: A single-center experience.

Introduction: The COVID-19 pandemic has disproportionately affected patients with preexisting comorbidities, particularly dialysis patients. The aim of this study was to determine predictors of mortality in this population.

Methodology: We conducted an observational, retrospective, cohort study collecting data from pre and post-vaccine from the electronic medical records of a single dialysis center at Hygeia International Hospital Tirana, Albania.

An Antibody Targeting Fibroblast Activation Protein Simultaneously Fused to Interleukin-2 and Tumor Necrosis Factor Selectively Localizes to Neoplastic Lesions.

The delivery of specific cytokine payloads to a neoplastic environment employing antibodies able to selectively accumulate at the tumor site represents an attractive strategy to stimulate an immune response to cancer. Whilst conventional antibody-cytokine fusions based on a single payload have shown potent anticancer activity, the concomitant delivery of two cytokine payloads may further improve the therapeutic outcome as the immune system typically adopts multiple signals to reinforce an antitumor strategy. We here describe a potency-matched dual-cytokine antibody fusion protein containing a tumor-targeting antibody fragment specific to human fibroblast activation protein (FAP), simultaneously linked to both interleukin-2 (IL2) and a tumor necrosis factor (TNF) mutant.

An Engineered IFNγ-Antibody Fusion Protein with Improved Tumor-Homing Properties.

Interferon-gamma (IFNγ) is one of the central cytokines produced by the innate and adaptive immune systems. IFNγ directly favors tumor growth control by enhancing the immunogenicity of tumor cells, induces IP-10 secretion facilitating (CXCR3+) immune cell infiltration, and can prime macrophages to an M1-like phenotype inducing proinflammatory cytokine release. We had previously reported that the targeted delivery of IFNγ to neoplastic lesions may be limited by the trapping of IFNγ-based products by cognate receptors found in different organs.

Albanian university students' knowledge, attitudes, and practices regarding COVID-19 infection and vaccine: A cross-sectional study.

Introduction: COVID-19 pandemic remains a public health concern worldwide. Given that, students represent a subgroup of the population with an impact on the pandemic.

Aim: The aim of this study is to evaluate the knowledge, attitudes, and practices of Albanian students about COVID-19, and to provide a database to plan and implement preventive evidence-based interventions.

A Case of Anti-Leucine-Rich Glioma-Inactivated Protein 1 (Anti-LGI1) Encephalitis With an Unusual Frontomesial Motor Cortex T2 MRI Hyperintensity.

Anti-leucine-rich glioma-inactivated protein 1 (anti-LGI1) encephalitis is a rare autoimmune disorder, classified within limbic encephalitides, and characterized by seizures and subacute cognitive-behavioral impairment, mainly affecting short-term memory and usually involving temporo-mesial lobe structures. We present a case of anti-LGI1 encephalitis characterized by focal right lower limb motor seizures and pyramidal signs and responsive to high-dose methylprednisolone. The patient developed an atypical left frontal lobe parasagittal T2 hyperintense lesion on MRI within one month of hospital admission, which has not been described previously in this disease to the best of our knowledge.

Selection of a PD-1 blocking antibody from a novel fully human phage display library.

Programmed cell death protein 1 (PD-1) is an immunoregulatory target which is recognized by different monoclonal antibodies, approved for the therapy of multiple types of cancer. Different anti-PD-1 antibodies display different therapeutic properties and there is a pharmaceutical interest to generate and characterize novel anti-PD-1 antibodies. We screened multiple human antibody phage display libraries to target novel epitopes on the PD-1 surface and we discovered a unique and previously undescribed binding specificity (termed D12) from a new antibody library (termed AMG).