Excess shed mesothelin disrupts pancreatic cancer cell clustering to impair peritoneal colonization.

Peritoneum is the second most common site of metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Peritoneal colonization is impaired in PDAC cells with knockout (KO) of the cancer surface antigen mesothelin (MSLN) or by introducing Y318A mutation in MSLN to prevent binding to mucin-16 (MUC-16). MSLN has a membrane-bound form but is also shed to release soluble MSLN (sMSLN).

Different ECLS Pump Configurations for Temporary Right Ventricular Assist Device in LVAD Patients: A Retrospective Case-Control Study.

Background: Acute right ventricular failure is a critical complication after left ventricular assist device (LVAD) implantation, often managed with a temporary paracorporeal right ventricular assist device (RVAD). This study examined three extracorporeal life support (ECLS) systems regarding mortality, bleeding complications, and intensive care unit (ICU) stay duration.

Methods: This monocentric, retrospective case-control study included all patients receiving LVAD with paracorporeal RVAD between 2009 and 2020.

Vaccination generates functional progenitor tumor-specific CD8 T cells and long-term tumor control.

Background: Immune checkpoint blockade (ICB) therapies are an important treatment for patients with advanced cancers; however, only a subset of patients with certain types of cancer achieve durable remission. Cancer vaccines are an attractive strategy to boost patient immune responses, but less is known about whether and how immunization can induce long-term tumor immune reprogramming and arrest cancer progression. We developed a clinically relevant genetic cancer mouse model in which hepatocytes sporadically undergo oncogenic transformation.

Practical training concept for perfusionists at the heart and diabetes center Nordrhein-Westfalen.

Background: Increasing regulations and requirements of advisory bodies, in particular the Joint Federal Committee and the Medical Service of the health insurance funds, make it necessary to employ only demonstrably well-trained perfusionists. The minimum requirement for this staff is EBCP certification. Currently there is limited availability of such specialists on the German market.

Vaccination generates functional progenitor tumor-specific CD8 T cells and long-term tumor control.

Background: Immune checkpoint blockade (ICB) therapies are an important treatment for patients with advanced cancers; however only a subset of patients with certain types of cancer achieves durable remissions. Cancer vaccines are an attractive strategy to boost patient immune responses, but less is known about whether and how immunization can induce long-term tumor immune reprogramming and arrest cancer progression. We developed a clinically-relevant genetic cancer mouse model in which hepatocytes sporadically undergo oncogenic transformation.

Tumor-Reactive CD8+ T Cells Enter a TCF1+PD-1- Dysfunctional State.

T cells recognize several types of antigens in tumors, including aberrantly expressed, nonmutated proteins, which are therefore shared with normal tissue and referred to as self/shared-antigens (SSA), and mutated proteins or oncogenic viral proteins, which are referred to as tumor-specific antigens (TSA). Immunotherapies such as immune checkpoint blockade (ICB) can activate T-cell responses against TSA, leading to tumor control, and also against SSA, causing immune-related adverse events (irAE). To improve anti-TSA immunity while limiting anti-SSA autoreactivity, we need to understand how tumor-specific CD8+ T cells (TST) and SSA-specific CD8+ T (SST) cells differentiate in response to cognate antigens during tumorigenesis.

Hallmarks of CD8 T cell dysfunction are established within hours of tumor antigen encounter before cell division.

Tumor-specific CD8+ T cells (TST) in patients with cancer are dysfunctional and unable to halt cancer progression. TST dysfunction, also known as exhaustion, is thought to be driven by chronic T cell antigen receptor (TCR) stimulation over days to weeks. However, we know little about the interplay between CD8 T cell function, cell division and epigenetic remodeling within hours of activation.

Functional Status and Quality of Life 6 Months After Extracorporeal Membrane Oxygenation Therapy for COVID-19-Related Pulmonary Failure.

Extracorporeal membrane oxygenation (ECMO) is increasingly used in COVID-19-related pulmonary failure and the number of patients recovering from COVID-19 is growing. Here, we assess survival and recovery 6 months after ECMO for COVID-19. From April 2020 to September 2021, n = 60 (60.

Mesothelin Enhances Tumor Vascularity in Newly Forming Pancreatic Peritoneal Metastases.

Over 90% of pancreatic ductal adenocarcinomas (PDAC) express mesothelin (MSLN). Overexpression or knockdown of MSLN has been implicated in PDAC aggressiveness. This activity has been ascribed to MSLN-induced activation of MAPK or NF-κB signaling pathways and to interaction of MSLN with its only known binding partner, MUC16.

Posttraumatic Arthritis After Intra-Articular Distal Femur and Proximal Tibia Fractures.

Posttraumatic arthritis (PTA) is a form of joint degeneration that occurs after physical trauma to a synovial joint. Development of PTA is multifactorial and results from mechanical damage at the time of trauma, a cell-mediated inflammatory response, and abnormal articulation due to persistent malalignment or joint instability. Although some risk factors may be unavoidable, preventing the development of PTA of the knee after intra-articular fracture (IAF) requires restoring anatomic articulation and alignment.

Protein Synthesis Inhibition Activity of Mesothelin Targeting Immunotoxin LMB-100 Decreases Concentrations of Oncogenic Signaling Molecules and Secreted Growth Factors.

LMB-100 is a mesothelin-targeted recombinant immunotoxin (iTox) that carries a modified exotoxin A (PE) payload. PE kills cells by inhibiting synthesis of new proteins. We found that treatment of pancreatic cancer cells with LMB-100 for 24⁻48 h did not change total protein level despite inducing protein synthesis inhibition (PSI).

Novel obscurins mediate cardiomyocyte adhesion and size via the PI3K/AKT/mTOR signaling pathway.

The intercalated disc of cardiac muscle embodies a highly-ordered, multifunctional network, essential for the synchronous contraction of the heart. Over 200 known proteins localize to the intercalated disc. The challenge now lies in their characterization as it relates to the coupling of neighboring cells and whole heart function.

Mesothelin-targeted immunotoxin RG7787 has synergistic anti-tumor activity when combined with taxanes.

Recombinant immunotoxins (RITs) are antibody-based therapeutics that carry a toxin payload. The RG7787 RIT targets the cancer antigen mesothelin to deliver a recombinantly-engineered, reduced immunogenicity variant of Pseudomonas exotoxin A (PE) to the cytosol where it inhibits protein synthesis. Here we demonstrate that maximal doses of RG7787 temporarily halt growth of pancreatic cancer tumor xenografts, similar to the approved drugs gemcitabine and nab-paclitaxel, however, combination of the RIT with nab-paclitaxel produces durable complete regressions in most mice.

Management of Pelvic Ring Injuries in Unstable Patients.

High-energy pelvic ring injuries can represent life-threatening injuries in the polytraumatized patient, particularly when presenting with hemodynamic instability. These injuries mandate a systematic multidisciplinary approach to evaluation, and timely intervention to address hemorrhage while concomitantly addressing mechanical instability. These pelvic injuries are associated with potentially lethal hemorrhage originating from venous, arterial, and osseous sources.

Biophysical characterization of naturally occurring titin M10 mutations.

The giant proteins titin and obscurin are important for sarcomeric organization, stretch response, and sarcomerogenesis in myofibrils. The extreme C-terminus of titin (the M10 domain) binds to the N-terminus of obscurin (the Ig1 domain) in the M-band. The high-resolution structure of human M10 has been solved, along with M10 bound to one of its two known molecular targets, the Ig1 domain of obscurin-like.

Charge transfer tuning by chemical substitution and uniaxial pressure in the organic complex tetramethoxypyrene-tetracyanoquinodimethane.

In the search for novel organic charge transfer salts with variable degrees of charge transfer we have studied the effects of two modifications of the recently synthesized donor-acceptor system [tetramethoxypyrene (TMP)]-[tetracyanoquinodimethane (TCNQ)]. One is of chemical nature by substituting the acceptor TCNQ molecules by F4TCNQ molecules. The second consists in simulating the application of uniaxial pressure along the stacking axis of the system.

Protamine overdose and its impact on coagulation, bleeding, and transfusions after cardiopulmonary bypass: results of a randomized double-blind controlled pilot study.

Background: We assessed the effects of protamine overdosing on thrombelastometry, bleeding, and transfusions in patients after cardiopulmonary bypass (CPB).

Methods: In group 1 (n = 15), representing the clinical standard, the protamine dose was based on the initial heparin dose, and group 2 (n = 15) received protamine based on the heparin concentration measured after CPB. Primary end points were thromboelastometric parameters.

Fulminate heparin-induced thrombocytopenia and surgery with deep hypothermic circulatory arrest using bivalirudin.

After on-pump coronary artery bypass graft surgery, a patient had acute heparin-induced thrombocytopenia with thoracic arterial and venous thrombus formations. Complex emergency surgery with cardiopulmonary bypass and deep hypothermic circulatory arrest using bivalirudin anticoagulation was performed.

Photo- and auger-electron recoil induced dynamics of interatomic Coulombic decay.

At photon energies near the Ne K edge it is shown that for 1s ionization the Auger electron, and for 2s ionization the fast photoelectron, launch vibrational wave packets in a Ne dimer. These wave packets then decay by emission of a slow electron via interatomic Coulombic decay (ICD). The measured and computed ICD electron spectra are shown to be significantly modified by the recoil induced nuclear motion.

Intramedullary nailing of the femur: current concepts concerning reaming.

Intramedullary fixation has advanced to the standard of care for fractures of the femoral shaft. Current controversies center on whether to prepare the intramedullary canal by reaming, particularly in certain subsets of patients. As understanding of the local and systemic effects of reaming deepens, there is a role for maximizing the benefits of intramedullary preparation before nail fixation, while attempting to minimize the major disadvantages of this technique.

The Ivemark syndrome: prenatal diagnosis of an uncommon cystic renal lesion with heterogeneous associations.

Renal dysplasia has been reported in association with a number of anatomical abnormalities, including pancreatic dysgenesis and hepatic anomalies. The combination of renal, hepatic, and pancreatic dysplasia (RHPD), also known as Ivemark syndrome, is rare and uniformly fatal. We report here the gross and histological findings in 4 cases of combined RHPD, 2 of which were detected by prenatal ultrasonography.

Mammographic appearance following implant removal.

Potential complications of augmentation mammaplasty with silicone gel breast implants have been the subject of much recent debate in the medical and lay communities. Some women have undergone implant removal, and others may follow. The mammographic appearance following submammary implant removal in four women and the histologic appearance in one case are described.

Flow cytometric analysis of breast needle aspirates.

This study investigated two hypotheses: (1) sufficient cells may be obtained by needle aspiration of breast nodules to produce good flow cytometric DNA profiles; and (2) benign breast lesions do not produce aneuploid G0G1 peaks, and therefore a distinct aneuploid peak is sufficient for a diagnosis of malignancy. Breast specimens received in Surgical Pathology between December 1985 and February 1987 were aspirated, and the cells stained with propidium iodide for flow cytometric DNA analysis. A total of 344 specimens were aspirated, of which 204 (59%) were malignant and 140 (41%) benign.

Small-cell undifferentiated carcinoma of the cervix. A clinicopathologic, ultrastructural, and immunocytochemical study of 15 cases.

The clinicopathologic, immunocytochemical, and ultrastructural features of 15 small-cell undifferentiated carcinomas (SCUC) of the uterine cervix are reported. Patients ranged in age from 25 to 87 (median, 42 years) and presented as stages IB (nine patients), IIA (one patient), IIB (two patients), IIIB (two patients), and IV (one patient). A variety of treatment regimens were employed.