JNK1 inhibitors target distal B cell receptor signaling and overcome BTK-inhibitor resistance in CLL.

Inhibition of the proximal B cell receptor (BCR) signaling pathway by BTK inhibitors is highly effective in the treatment of CLL, but drug resistance or intolerance occurs. Here, we investigated c-Jun N-terminal protein kinase 1 (JNK1) as an alternative drug target in the distal BCR pathway. JNK1 was preferentially overexpressed and activated in poor prognostic CLL with unmutated IGHV.

Activated granulocytes and inflammatory cytokine signaling drive T-cell lymphoma progression and disease symptoms.

Peripheral T-cell lymphomas (PTCLs), especially angioimmunoblastic and follicular TCLs, have a dismal prognosis because of the lack of efficient therapies, and patients' symptoms are often dominated by an inflammatory phenotype, including fever, night sweats, weight loss, and skin rash. In this study, we investigated the role of inflammatory granulocytes and activated cytokine signaling on T-cell follicular helper-type PTCL (TFH-PTCL) disease progression and symptoms. We showed that ITK-SYK-driven murine PTCLs and primary human TFH-PTCL xenografts both induced inflammation in mice, including murine neutrophil expansion and massive cytokine release.

Human β-defensin 2 ameliorates acute GVHD by limiting ileal neutrophil infiltration and restraining T cell receptor signaling.

Acute graft-versus-host disease (aGVHD), which is driven by allogeneic T cells, has a high mortality rate and limited treatment options. Human β-defensin 2 (hBD-2) is an endogenous epithelial cell-derived host-defense peptide. In addition to its antimicrobial effects, hBD-2 has immunomodulatory functions thought to be mediated by CCR2 and CCR6 in myeloid cells.

Impact of body size and body composition on bladder cancer outcomes: Risk stratification and opportunity for novel interventions.

Body size is emerging as a novel and clinically-relevant patient factor in bladder cancer research. Historically, a patient's body mass index (BMI) has been used as a proxy for obesity but it shows inconsistent associations with risk of developing the disease as well as with most clinical outcomes. More specific body composition features can be derived for patients using a variety of methods.

Variability in stone composition and metabolic correlation between kidneys in patients with bilateral nephrolithiasis.

Purpose: To evaluate the clinical significance of discordant stone analyses in patients undergoing bilateral ureteroscopy.

Materials And Methods: A retrospective chart review was performed for all patients undergoing stone extraction with bilateral ureteroscopy at our institution in an aim to identify patients who had bilateral stone analysis and 24-h urine chemistry data available. Stones were then classified based upon the dominant present (> 50%).

Optimized Xenograft Protocol for Chronic Lymphocytic Leukemia Results in High Engraftment Efficiency for All CLL Subgroups.

Preclinical drug development for human chronic lymphocytic leukemia (CLL) requires robust xenograft models recapitulating the entire spectrum of the disease, including all prognostic subgroups. Current CLL xenograft models are hampered by inefficient engraftment of good prognostic CLLs, overgrowth with co-transplanted T cells, and the need for allogeneic humanization or irradiation. Therefore, we aimed to establish an effective and reproducible xenograft protocol which allows engraftment of all CLL subtypes without the need of humanization or irradiation.

Tranexamic Acid in Civilian Trauma Care in the California Prehospital Antifibrinolytic Therapy Study.

Introduction: Hemorrhage is one of the leading causes of death in trauma victims. Historically, paramedics have not had access to medications that specifically target the reversal of trauma-induced coagulopathies. The California Prehospital Antifibrinolytic Therapy (Cal-PAT) study seeks to evaluate the safety and efficacy of tranexamic acid (TXA) use in the civilian prehospital setting in cases of traumatic hemorrhagic shock.

Efficacy and Safety of Tranexamic Acid in Prehospital Traumatic Hemorrhagic Shock: Outcomes of the Cal-PAT Study.

Introduction: The California Prehospital Antifibrinolytic Therapy (Cal-PAT) study seeks to assess the safety and impact on patient mortality of tranexamic acid (TXA) administration in cases of trauma-induced hemorrhagic shock. The current study further aimed to assess the feasibility of prehospital TXA administration by paramedics within the framework of North American emergency medicine standards and protocols.

Methods: This is an ongoing multi-centered, prospective, observational cohort study with a retrospective chart-review comparison.

Depletion of STAT5 blocks TEL-SYK-induced APMF-type leukemia with myelofibrosis and myelodysplasia in mice.

The spleen tyrosine kinase (SYK) was identified as an oncogenic driver in a broad spectrum of hematologic malignancies. The in vivo comparison of three SYK containing oncogenes, SYK(wt), TEL-SYK and IL-2-inducible T-cell kinase (ITK)-SYK revealed a general myeloexpansion and the establishment of three different hematologic (pre)diseases. SYK(wt) enhanced the myeloid and T-cell compartment, without leukemia/lymphoma development.

PIM kinases are essential for chronic lymphocytic leukemia cell survival (PIM2/3) and CXCR4-mediated microenvironmental interactions (PIM1).

Overexpression of the CXCR4 receptor is a hallmark of chronic lymphocytic leukemia (CLL) and is important for CLL cell survival, migration, and interaction with their protective microenvironment. In acute myelogenous leukemia (AML), PIM1 was shown to regulate the surface expression of the CXCR4 receptor. Here, we show that PIM (proviral integration site for Moloney murine leukemia virus) kinases 1-3 are overexpressed and that the CXCR4 receptor is hyperphosphorylated on Ser339 in CLL compared with normal lymphocytes.

First metatarsophalangeal joint arthrodiastasis and biologic resurfacing with external fixation: a case report.

The primary goal in the treatment of arthritic joints is elimination of pain associated with limited motion. Several surgical techniques have been developed to treat varying degrees of hallux rigidus of any cause. This case report details an alternative surgical approach to address hallux rigidus and associated hallux valgus deformity through a combination of joint debridement, resurfacing, and arthrodiastasis.

Periodontal treatment of an amalgam tattoo.

The amalgam tattoo can often result in an unsightly cosmetic appearance, especially in the maxillary anterior region. The predominant treatment for an amalgam tattoo is the free gingival graft, which also results in a poor cosmetic appearance. The authors would like to review the pathogenesis of the amalgam tattoo and present a new technique that leads to a pleasing cosmetic result.

Cognitive behavior therapy for depression in type 2 diabetes mellitus. A randomized, controlled trial.

Background: Psychotherapy is the principal nonpharmacologic method for the management of depression, but its usefulness for depressed patients with diabetes remains unknown.

Objective: To assess the efficacy of cognitive behavior therapy (CBT) for depression in patients with diabetes.

Design: Randomized, controlled trial.

Altered patterns of posttransplant urinary tract infections associated with perioperative antibiotics and curtailed catheterization.

Postoperative urinary tract infections (UTIs) in renal transplant patients were studied before and after introduction of a protocol requiring single-dose perioperative antibiotics and earlier catheter removal. The overall incidence of UTIs was reduced from 55.4% to 26%.