Immunologic Predictors of Vaccine Responsiveness in Patients With Lymphoma and Chronic Lymphocytic Leukemia.

Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. Severe acute respiratory syndrome coronavirus 2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic messenger RNA vaccine response in retrospective and prospective cohorts with lymphoma and chronic lymphocytic leukemia, paired with clinical and research immune parameters.

Prior vaccination promotes early activation of memory T cells and enhances immune responses during SARS-CoV-2 breakthrough infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of vaccinated individuals is increasingly common but rarely results in severe disease, likely due to the enhanced potency and accelerated kinetics of memory immune responses. However, there have been few opportunities to rigorously study early recall responses during human viral infection. To better understand human immune memory and identify potential mediators of lasting vaccine efficacy, we used high-dimensional flow cytometry and SARS-CoV-2 antigen probes to examine immune responses in longitudinal samples from vaccinated individuals infected during the Omicron wave.

Prior vaccination enhances immune responses during SARS-CoV-2 breakthrough infection with early activation of memory T cells followed by production of potent neutralizing antibodies.

SARS-CoV-2 infection of vaccinated individuals is increasingly common but rarely results in severe disease, likely due to the enhanced potency and accelerated kinetics of memory immune responses. However, there have been few opportunities to rigorously study early recall responses during human viral infection. To better understand human immune memory and identify potential mediators of lasting vaccine efficacy, we used high-dimensional flow cytometry and SARS-CoV-2 antigen probes to examine immune responses in longitudinal samples from vaccinated individuals infected during the Omicron wave.

Deep learning automates bidimensional and volumetric tumor burden measurement from MRI in pre- and post-operative glioblastoma patients.

Tumor burden assessment by magnetic resonance imaging (MRI) is central to the evaluation of treatment response for glioblastoma. This assessment is, however, complex to perform and associated with high variability due to the high heterogeneity and complexity of the disease. In this work, we tackle this issue and propose a deep learning pipeline for the fully automated end-to-end analysis of glioblastoma patients.

Detecting liver cirrhosis in computed tomography scans using clinically-inspired and radiomic features.

Hepatic cirrhosis is an increasing cause of mortality in developed countries-it is the pathological sequela of chronic liver diseases, and the final liver fibrosis stage. Since cirrhosis evolves from the asymptomatic phase, it is of paramount importance to detect it as quickly as possible, because entering the symptomatic phase commonly leads to hospitalization and can be fatal. Understanding the state of the liver based on the abdominal computed tomography (CT) scans is tedious, user-dependent and lacks reproducibility.

Validating a Proteomic Signature of Severe COVID-19.

Unlabelled: COVID-19 is a heterogenous disease. Biomarker-based approaches may identify patients at risk for severe disease, who may be more likely to benefit from specific therapies. Our objective was to identify and validate a plasma protein signature for severe COVID-19.

PD-1 directed immunotherapy alters Tfh and humoral immune responses to seasonal influenza vaccine.

Anti-programmed death-1 (anti-PD-1) immunotherapy reinvigorates CD8 T cell responses in patients with cancer but PD-1 is also expressed by other immune cells, including follicular helper CD4 T cells (Tfh) which are involved in germinal centre responses. Little is known, however, about the effects of anti-PD-1 immunotherapy on noncancer immune responses in humans. To investigate this question, we examined the impact of anti-PD-1 immunotherapy on the Tfh-B cell axis responding to unrelated viral antigens.

Minimally invasive lateral occipitocervical fixation: case series and technique description.

Purpose: Occipitocervical junction (OCJ) instability is commonly treated with fixation via open posterior approach. The use of intraoperative navigation allows us to perform occipitocervical fixation via minimally invasive approach. We report a series of patients treated with percutaneous occipitocervical fixation, describing the surgical procedure in detail and discussing the technique.

Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine.

We examined antibody and memory B cell responses longitudinally for ∼9-10 months after primary 2-dose SARS-CoV-2 mRNA vaccination and 3 months after a 3rd dose. Antibody decay stabilized between 6 and 9 months, and antibody quality continued to improve for at least 9 months after 2-dose vaccination. Spike- and RBD-specific memory B cells remained durable over time, and 40%-50% of RBD-specific memory B cells simultaneously bound the Alpha, Beta, Delta, and Omicron variants.

Acute Stroke Care during COVID-19: National Data.

(1) Background: The pandemic of COVID-19 and subsequent lockdown strategies had a profound impact on many aspects of everyday life. During this time the world faced the unprecedented crisis of healthcare disrupting timely care delivery. This study was designed to evaluate the impact of the pandemic on the acute treatment of stroke in Poland.

Segmenting pediatric optic pathway gliomas from MRI using deep learning.

Optic pathway gliomas are low-grade neoplastic lesions that account for approximately 3-5% of brain tumors in children. Assessing tumor burden from magnetic resonance imaging (MRI) plays a central role in its efficient management, yet it is a challenging and human-dependent task due to the difficult and error-prone process of manual segmentation of such lesions, as they can easily manifest different location and appearance characteristics. In this paper, we tackle this issue and propose a fully-automatic and reproducible deep learning algorithm built upon the recent advances in the field which is capable of detecting and segmenting optical pathway gliomas from MRI.

mRNA Vaccination Induces Durable Immune Memory to SARS-CoV-2 with Continued Evolution to Variants of Concern.

SARS-CoV-2 mRNA vaccines have shown remarkable efficacy, especially in preventing severe illness and hospitalization. However, the emergence of several variants of concern and reports of declining antibody levels have raised uncertainty about the durability of immune memory following vaccination. In this study, we longitudinally profiled both antibody and cellular immune responses in SARS-CoV-2 naïve and recovered individuals from pre-vaccine baseline to 6 months post-mRNA vaccination.

Rapid induction of antigen-specific CD4 T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination.

SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses on healthy SARS-CoV-2-naive and recovered individuals prior to and following mRNA prime and boost vaccination. Vaccination induced rapid antigen-specific CD4 T cell responses in naive subjects after the first dose, whereas CD8 T cell responses developed gradually and were variable in magnitude.

CD8 T cells contribute to survival in patients with COVID-19 and hematologic cancer.

Patients with cancer have high mortality from coronavirus disease 2019 (COVID-19), and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 patients with cancer who were hospitalized for COVID-19, patients with hematologic cancer had higher mortality relative to patients with solid cancer. In two additional cohorts, flow cytometric and serologic analyses demonstrated that patients with solid cancer and patients without cancer had a similar immune phenotype during acute COVID-19, whereas patients with hematologic cancer had impairment of B cells and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses.

Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination.

Novel mRNA vaccines for SARS-CoV-2 have been authorized for emergency use. Despite their efficacy in clinical trials, data on mRNA vaccine-induced immune responses are mostly limited to serological analyses. Here, we interrogated antibody and antigen-specific memory B cells over time in 33 SARS-CoV-2 naïve and 11 SARS-CoV-2 recovered subjects.

Longitudinal Analysis Reveals Distinct Antibody and Memory B Cell Responses in SARS-CoV2 Naïve and Recovered Individuals Following mRNA Vaccination.

Novel mRNA vaccines for SARS-CoV2 have been authorized for emergency use and are currently being administered to millions of individuals worldwide. Despite their efficacy in clinical trials, there is limited data on vaccine-induced immune responses in individuals with a prior SARS-CoV2 infection compared to SARS-CoV2 naïve subjects. Moreover, how mRNA vaccines impact the development of antibodies as well as memory B cells in COVID-19 experienced versus COVID-19 naïve subjects remains poorly understood.

CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer.

Cancer patients have increased morbidity and mortality from Coronavirus Disease 2019 (COVID-19), but the underlying immune mechanisms are unknown. In a cohort of 100 cancer patients hospitalized for COVID-19 at the University of Pennsylvania Health System, we found that patients with hematologic cancers had a significantly higher mortality relative to patients with solid cancers after accounting for confounders including ECOG performance status and active cancer status. We performed flow cytometric and serologic analyses of 106 cancer patients and 113 non-cancer controls from two additional cohorts at Penn and Memorial Sloan Kettering Cancer Center.

From magnifying glass to operative microscopy - the historical and modern role of the microscope in microsurgery.

The modern computer-assisted microscope, being a hallmark of microsurgery, has become a standard piece of equipment in the operating theatre. Its introduction enabled visualisation of fine anatomical structures, obscure to the unaided eye, and revolutionised many surgical specialties, such as neurological, ophthalmological, or vascular. These astounding achievements have been the culmination of a century of constant progress in optical engineering and microsurgery, since 1921, when a microscope was first used during surgery.

Determination of in Vivo Enzyme Occupancy Utilizing Inhibitor Dissociation Kinetics.

During drug discovery, assessment of in vivo target occupancy by therapeutic candidates is often required for predicting clinical efficacy. Current strategies for determining target occupancy include using radiolabeled or irreversible surrogates, which can be technically challenging, and the results are often not sufficiently quantitative. We developed a straightforward method by applying slow-dissociation kinetics to quantitatively determine enzyme occupancy without using specialized reagents.

Increased muscle force production and bone mineral density in ActRIIB-Fc-treated mature rodents.

Myostatin is a highly conserved member of the transforming growth factor-β ligand family known to regulate muscle growth via activation of activin receptors. A fusion protein consisting of the extracellular ligand-binding domain of activin type IIB receptor with the Fc portion of human immunoglobulin G (ActRIIB-Fc) was used to inhibit signaling through this pathway. Here, we study the effects of this fusion protein in adult, 18-month-old, and orchidectomized mice.

Intraoperative Neurophysiologic Monitoring (INM) in scoliosis surgery.

Even among skilled spinal deformity surgeons, neurologic deficits are inherent potential complications of spine surgery. The aim was to assess the meaning of changes and to evaluate the critical rates of Somatosensory Evoked Potentials (SEP) and Motor Evoked Potentials (MEP) for Neurologic Deficit (ND) occurrence associated with scoliosis surgery. A Group of 30 patients with idiopathic scoliosis treated surgically by posterior correction and stabilisation were included.

Operative treatment of isthmic spondylolisthesis with posterior stabilization and ALIF. Cages versus autogenous bone grafts.

In the following study the use of cages and autogenous bone grafts were compared in the operative treatment of isthmic spondylolisthesis with the posterior stabilization and Anterior Lumbosacral Interbody Fusion (ALIF). 55 patients were divided into two groups. Autogenous bone grafts were used in the first group (34 patients) and titanium interbody implants (cages) in the second group (21 patients).

Secondary scoliosis after thoracotomy in patients with aortic coarctation and patent ductus arteriosus.

The aim of this study was to determine the influence of lateral thoracotomy on the development of scoliosis in subjects undergoing repair of coarctation of the aorta (CoAo) and patent ductus arteriosus (PDA). A group of 133 patients with CoAo and PDA was evaluated. Forty-five patients with CoAo and 38 with PDA were operated on using lateral thoracotomy (operative group) while 12 patients with CoAo and 31 with PDA were treated using balloon dilatation and stent or coil implantation (non-operative group).