NCCN Guidelines® Insights: Systemic Mastocytosis, Version 3.2024.

Mastocytosis is a heterogeneous group of disorders comprising cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. It is associated with a variety of symptoms related to the release of mast cell mediators and mast cell tissue infiltration. Referral to specialized centers with expertise in the management of mastocytosis and multidisciplinary collaboration with subspecialists (eg, allergists for the management of anaphylaxis and drug hypersensitivities, anesthesiologists for invasive procedures or surgery, high-risk obstetrician for pregnancy) is recommended. The NCCN Guidelines for Systemic Mastocytosis provide evidence- and consensus-based recommendations for the diagnosis and comprehensive care of patients with systemic mastocytosis. The multidisciplinary panel of experts convenes at least once a year to review requested changes to the guidelines from both internal and external entities as well as to discuss data on existing and new therapies. These NCCN Guidelines Insights focus on some of the recent updates to the guidelines.

Innovation in Resident Core Oncology Education: Switching from an Inpatient Ward Rotation to a Hybrid Model of Inpatient Consultations and Outpatient Clinics.

Interest in an oncology career has decreased among internal medicine residents completing an inpatient hematology-oncology rotation. Over years, our institutional data at Indiana University School of Medicine reflected lower satisfaction with the oncology inpatient ward rotation as compared to other rotations. We hypothesized that a switch from an inpatient ward rotation to a hybrid model of inpatient consultations and outpatient clinics would improve resident satisfaction with their educational experience in oncology. Over the 6-month periods preceding and following the change in rotation format, residents were asked to complete anonymous rotation evaluations and rate their experiences on a 5-point Likert scale (poor 1 to excellent 5). Areas assessed included patient load, educational value of patient mix, quality of didactics and teaching, quality of patient care delivery, adequacy of time for reading, and overall rotation quality. The hybrid oncology rotation was rated as significantly superior to the traditional ward format in six out of eight areas including patient load, educational value of patient mix, time for study, teaching quality, relevance of material, and overall rating. Improvements in the perceived quality of patient care delivery (p = 0.139) and quality of didactics (p = 0.058) were also observed without reaching statistical significance. The balance of inpatient and outpatient experiences with the hybrid rotation was highly rated (4.5 ± 0.5). The implementation of a hybrid oncology rotation was associated with perceived improvement in educational value, patient mix, and time for reflection and study without apparent compromise in the quality of patient care delivery.

Inflammation and autoimmunity are interrelated in patients with sickle cell disease at a steady-state condition: implications for vaso-occlusive crisis, pain, and sensory sensitivity.

This study aimed to comprehensively analyze inflammatory and autoimmune characteristics of patients with sickle cell disease (SCD) at a steady-state condition (StSt) compared to healthy controls (HCs) to explore the pathogenesis of StSt and its impact on patients' well-being. The study cohort consisted of 40 StSt participants and 23 HCs enrolled between July 2021 and April 2023. StSt participants showed elevated white blood cell (WBC) counts and altered hematological measurements when compared to HCs. A multiplex immunoassay was used to profile 80 inflammatory cytokines/chemokines/growth factors in plasma samples from these SCD participants and HCs. Significantly higher plasma levels of 35 analytes were observed in SCD participants, with HGF, IL-18, IP-10, and MCP-2 being among the most significantly affected analytes. Additionally, autoantibody profiles were also altered, with elevated levels of anti-SSA/Ro60, anti-Ribosomal P, anti-Myeloperoxidase (MPO), and anti-PM/Scl-100 observed in SCD participants. Flow cytometric analysis revealed higher rates of red blood cell (RBC)/reticulocyte-leukocyte aggregation in SCD participants, predominantly involving monocytes. Notably, correlation analysis identified associations between inflammatory mediator levels, autoantibodies, RBC/reticulocyte-leukocyte aggregation, clinical lab test results, and pain crisis/sensitivity, shedding light on the intricate interactions between these factors. The findings underscore the potential significance of specific biomarkers and therapeutic targets that may hold promise for future investigations and clinical interventions tailored to the unique challenges posed by SCD. In addition, the correlations between vaso-occlusive crisis (VOC)/pain/sensory sensitivity and inflammation/immune dysregulation offer valuable insights into the pathogenesis of SCD and may lead to more targeted and effective therapeutic strategies. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT05045820.

EBV-Gastritis Preceded the Development of Nasopharyngeal EBV (+) Diffuse Large B Cell Lymphoma in a Patient With Ruxolitinib-Induced Immunosuppression.

Epstein-Barr virus (EBV) is acquired early in life as asymptomatic or symptomatic infectious mononucleosis (IM) and remains latent in a few B cells in most individuals. Pathologic EBV-reactivation affects immunosuppressed individuals and manifests as IM-like syndromes, polyclonal lymphoproliferative disorders, EBV-related lymphomas, and carcinomas. EBV-associated gastritis is an underrecognized and very rarely reported entity. We report a case of a 65-year-old woman with ruxolitinib-treated polycythemia vera, who developed EBV viremia and EBV gastritis. The patient improved after the ruxolitinib dose reduction and administration of antiviral therapy. A few months after discontinuation of the antiviral therapy the gastric symptoms recurred, numerous gastric ulcers were identified, and a nasopharyngeal mass was detected. A biopsy of the nasopharynx showed an EBV (+) diffuse large B cell lymphoma. Ruxolitinib was discontinued and the patient was started on rituximab monotherapy with a resolution of symptoms and pathologic improvement. Our case supports earlier reports of an association of ruxolitinib therapy with EBV complications. An early diagnosis of EBV gastritis in immunocompromised patients is important since the gastric infection may precede or co-exist with a developing EBV-associated malignancy. Our case and existing literature suggest that EBV gastritis in symptomatic patients with iatrogenic immunosuppression requires discontinuation of immunosuppressive therapy if feasible, treatment with antivirals, and close surveillance for possible evolving/concurrent EBV (+) malignancy.

Inflammation and autoimmunity are interrelated in patients with sickle cell disease at a steady-state condition: implications for vaso-occlusive crisis, pain, and sensory sensitivity.

This study aimed to comprehensively analyze inflammatory and autoimmune characteristics of patients with sickle cell disease (SCD) at a steady-state condition (StSt) compared to healthy controls (HCs) to explore the pathogenesis of StSt and its impact on patients' well-being. The study cohort consisted of 40 StSt participants and 23 HCs enrolled between July 2021 and April 2023. StSt participants showed elevated white blood cell (WBC) counts and altered hematological measurements when compared to HCs. A multiplex immunoassay was used to profile 80 inflammatory cytokines/chemokines/growth factors in plasma samples from these SCD participants and HCs. Significantly higher plasma levels of 37 analytes were observed in SCD participants, with HGF, IL-18, IP-10, and MCP-2 being among the most significantly affected analytes. Additionally, autoantibody profiles were also altered, with elevated levels of anti-SSA/Ro60, anti-Ribosomal P, anti-Myeloperoxidase (MPO), and anti-PM/Scl-100 observed in SCD participants. Flow cytometric analysis revealed higher rates of red blood cell (RBC)/reticulocyte-leukocyte aggregation in SCD participants, predominantly involving monocytes. Notably, correlation analysis identified associations between inflammatory mediator levels, autoantibodies, RBC/reticulocyte-leukocyte aggregation, clinical lab test results, and pain crisis/sensitivity, shedding light on the intricate interactions between these factors. The findings underscore the potential significance of specific biomarkers and therapeutic targets that may hold promise for future investigations and clinical interventions tailored to the unique challenges posed by SCD. In addition, the correlations between vaso-occlusive crisis (VOC)/pain/sensory sensitivity and inflammation/immune dysregulation offer valuable insights into the pathogenesis of SCD and may lead to more targeted and effective therapeutic strategies.

A cleavage-resistant urokinase plasminogen activator receptor exhibits dysregulated cell-surface clearance.

Urokinase plasminogen activator receptor (u-PAR) binds urokinase plasminogen activator (u-PA) and participates in plasminogen activation in addition to modulating several cellular processes such as adhesion, proliferation, and migration. u-PAR is susceptible to proteolysis by its cognate ligand and several other proteases. To elucidate the biological significance of receptor cleavage by u-PA, we engineered and expressed a two-chain urokinase plasminogen activator (tcu-PA) cleavage-resistant u-PAR (cr-u-PAR). This mutated receptor was similar to wild-type u-PAR in binding u-PA and initiating plasminogen activation. However, cr-u-PAR exhibited accelerated internalization and resurfacing due to direct association with the endocytic receptor alpha(2)-macroglobulin receptor/low density lipoprotein receptor-related protein in the absence of the enzyme x inhibitor complex of tcu-PA and plasminogen activator inhibitor-1 (tcu-PA.PAI-1). cr-u-PAR-expressing cells had enhanced migration compared with wild-type u-PAR-expressing cells, and cr-u-PAR was less sensitive to chymotrypsin cleavage as compared with wt u-PAR. Our studies suggest that these mutations in the linker region result in a rearrangement within the cr-u-PAR structure that makes it resemble its ligand-bound form. This constitutively active variant may mimic highly glycosylated cleavage-resistant u-PAR expressed in certain highly malignant cancer-cells.

The Mini-Gastric Bypass original technique.

INTRODUCTION: Mini-Gastric Bypass (MGB) is becoming more and more popular as shown by the numerous articles published over the past 15 years, supporting the operation as a short and simple procedure with excellent outcomes and low complication rates. There is still confusion amongst surgeons on the technique of the operation. The purpose of this paper is to review and describe the technique of MGB by its originators. METHODS: With 20 years of experience of performing the original MGB, the authors present the details of the MGB. RESULTS: The MGB consists of a long conduit from below the crow's foot extending up to the left of the angle of His. It is similar to, but importantly, not the same as the pouch of the Sleeve Gastrectomy. MGB has a wide gastro-jejunal anastomosis to an anti-colic loop of jejunum 150-200 cm distal to the ligament of Trietz. The power of MGB comes from the fact that it is both a "Non-Obstructive" restrictive procedure and it also has a significant fatty food intolerance component with minimal malabsorption. CONCLUSION: In this article we describe the original Rutledge technique of Mini-Gastric Bypass. Notably this is neither a "Single Anastomosis bypass", nor an "Omega Loop Bypass" and also not the "One Anastomosis Bypass of Carbajo". It is a particular technique first created by Rutledge in 1997 and associated with low risk and excellent outcomes. The goal of this manuscript is to help avoid complications and problems seen when the operation deviates from some of the basic principles of general surgery used in the original operation.

Seven Years of Mini-Gastric Bypass in Type II Diabetes Patients with a Body Mass Index <35 kg/m(2).

BACKGROUND: Mini-gastric bypass (MGB) is a safe, effective, and reversible procedure for patients with type II diabetes mellitus (T2DM) and morbid obesity. Less is known, however, about its long-term effects in patients with a body mass index (BMI) <35 kg/m(2). METHODS: From February 2007 to February 2014, 1468 patients underwent MGB at our institution, including 983 with T2DM. Of these, 128 (82 women), of mean age 41.6 ± 10.2 years, had a BMI of 30-35 kg/m(2). Prospectively collected data were analyzed retrospectively. Factors assessed included disease duration, family history, medication use, remission, and biochemical indicators, including fasting plasma glucose, glycosylated hemoglobin (HbA1c), serum insulin, and C-peptide concentrations. Remission of T2DM was defined as HbA1c <6.0 % without medication. RESULTS: Prior to surgery, patients had a mean BMI of 33.4 ± 3.3 kg/m(2), mean waist circumference of 104.5 ± 8.2 cm, mean C-peptide concentration of 3.4 ± 1.2 ng/ml, and mean T2DM duration of 6.5 ± 3.1 years. Within 6 months of MGB, 95 % of these patients had attained HbA1c <7 %. Complete remission rates at 1, 2, and 7 years were 64, 66, and 53 %, respectively. Mean HbA1c decreased from 10.7 ± 1.5 % at baseline to 6.2 ± 0.5% at 1 year, 5.4 ± 1.2 % at 3 years, and 5.7 ± 1.8 % at 7 years. No deaths occurred, but two (1.6 %) patients experienced major complications. CONCLUSIONS: MGB provides good, long-term control of T2DM in patients with class I obesity. Early intervention results in higher remission rates.