The impact of cytotoxic therapy on the risk of progression and death in clonal cytopenia(s) of undetermined significance.

ABSTRACT: Clonal cytopenia of undetermined significance (CCUS) is defined by a myeloid driver mutation in the context of otherwise unexplained cytopenia. CCUS has an inherent risk of progressing to myeloid neoplasm. However, it is unknown how exposure to previous cytotoxic therapy may impact the risk of progression and survival. We stratified patients with CCUS by prior exposure to DNA-damaging therapy. Of 151 patients, 46 (30%) had received cytotoxic therapy and were classified as therapy-related CCUS (t-CCUS), whereas 105 (70%) had de novo CCUS. A lower proportion of t-CCUS had hypercellular marrows (17.8% vs 44.8%, P = .002) but had higher median bone marrow blast percentages. After a median follow-up of 2.2 years, t-CCUS had significantly shorter progression-free survival (PFS, 1.8 vs 6.3 years; hazard ratio [HR], 2.1; P = .007) and median overall survival (OS; 3.6 years vs not reached; HR, 2.3; P = .007) compared with CCUS. Univariable and multivariable time-to-event analyses showed that exposure to cytotoxic therapy independently accounted for inferior PFS and OS. Despite the similarities in clinical presentation between CCUS and t-CCUS, we show that exposure to prior cytotoxic therapies was an independent risk factor for inferior outcomes. This suggests that t-CCUS represents a unique clinical entity that needs more stringent monitoring or earlier intervention strategies.

Is pathogen reduction an acceptable alternative to irradiation for risk mitigation of transfusion-associated graft versus host disease?

Transfusion-associated graft versus host disease (TA-GVHD) is a highly morbid and often fatal adverse event associated with transfusion of cellular blood products [platelets, red blood cells (RBCs) and whole blood] and more rarely with never-frozen plasma products. It is caused by residual viable donor T-lymphocytes that proliferate and actively target recipient tissues. Selective or universal irradiation of blood components using gamma-irradiation and more recently, X-ray irradiation, are the most commonly applied interventions and have been validated by the demonstration of in vitro T-lymphocyte inactivation, in murine models of TA-GVHD and by years of clinical experience. Irradiation, however, has multiple limitations including a sharp dose-response curve that renders quality control of dosage critically important, the use of radioactive radiation sources that are a terrorism risk, and selective implementation in many countries that leads to inadvertent omission and patient risk exposure. Certain pathogen reduction technologies (PRT) for platelets have been approved by regulatory authorities and endorsed by professional societies as an alternative to irradiation for reducing the risk of TA-GVHD, and PRT for RBCs and whole blood are in development. While the mechanism of action of T-lymphocyte inactivation differs from gamma/X-ray irradiation, the impact on T-lymphocyte inactivation for PRT is equivalent or superior to that of irradiation as demonstrated by sensitive in vitro lymphocyte proliferation assays and in vivo mouse models that approximate human TA-GVHD. Clinical trials and cumulative routine-use experience attest to the efficacy of PRT when used as an alternative to irradiation. While T-lymphocyte inactivation efficacy varies between PRT platforms, the implementation of PRT for platelets increases blood safety for patients beyond the mitigation of TA-GVHD, by decreasing the risk of transfusion transmitted infections with known viruses, bacteria and parasites as well as emerging pathogens.

Lord of the "rings": A case of Plasmodium falciparum.

Plasmodium falciparum is the most common species to result in severe malaria infection. Examination of blood sample with thick and thin smear is the gold standard diagnostic test and repeat peripheral smear monitoring every 12-24 h should be performed after initiation of treatment to ensure parasite clearance in severe infection. Treatment for severe P. falciparum infection should be initiated without delay, and if artemisinin products are not available, atovaquone-proguanil can be used as an alternative.

Novel cannabidiol aspartame combination treatment (JW-100) significantly reduces ISGA score in atopic dermatitis: Results from a randomized double-blinded placebo-controlled interventional study.

BACKGROUND: Atopic dermatitis (AD) is a common and chronic inflammatory skin disease that erupts periodically. Although the negative impact of the disorder on overall quality of life has been well established, new treatments for AD are still needed. Various studies have reported on cannabidiol's effectiveness in relieving pain and easing inflammation while not presenting major health risks. AIMS: In this communication, we aim to demonstrate the effectiveness of a novel cannabidiol (CBD) and aspartame formulation, JW-100, in relieving signs and symptoms of AD. PATIENTS/METHODS: We conducted a double-blinded placebo-controlled interventional study randomizing patients to one of three treatment groups: JW-100 (CBD plus aspartame), CBD only, or placebo topical formulations. The Investigator's Static Global Assessment (ISGA) score was used to document any changes in AD resulting from the applied interventions at 14 days. RESULTS: Fifty-seven patients completed the trial and were included in the final analysis. The ISGA score of the patients at baseline was 2.56, 2.24, and 2.24, for the JW-100, CBD, and placebo groups, respectively. After two weeks of treatment, the ISGA score reduced by 1.28, 0.81, and 0.71, for the JW-100, CBD, and placebo groups, respectively. The JW-100 cohorts demonstrated statistically significant ISGA score reduction (p = 0.042). 50% of patients in the JW-100 group achieved ISGA score of clear or almost clear (0 or 1) with at least a 2-grade improvement from baseline after treatment (p = 0.028). Only 20% and 15% of patients in the CBD only and placebo groups reported ISGA score of clear or almost clear (0 or 1). CONCLUSIONS: JW-100, a novel topical formulation containing CBD and aspartame, was demonstrated to produce statistically significant improvements in AD following 14 days of topical application.

Addressing Decision Making in Progesterone Treatment for History of Preterm Delivery.

Introduction The United States ranks 27th among nations worldwide for infant mortality with a rate of 6.1 deaths per 1,000 live births. The majority of perinatal morbidity and mortality is related to preterm birth, defined as delivery prior to 37 weeks' gestation. Among the risk factors for preterm birth is prior preterm birth, which is associated with a 1.5- to 2.0-fold increase in risk. At the present time, there is only one Food and Drug Administration approved treatment for the prevention of preterm birth among women with a history of prior spontaneous premature delivery, intramuscular 17-α-hydroxyprogesterone caproate (17-OHP), administered once weekly from 20 to 36 weeks' gestation. However, many eligible pregnant patients decline this therapy. Methods This was a prospective, cohort study involving patients who were identified as candidates for 17-OHP treatment at their first obstetric visit and asked to complete a short survey regarding their history of preterm birth. Those patients who consented to a follow-up phone call were asked to participate in a focus group discussion regarding their experience with progesterone and the health care system. Results During the 1-year study period, 55 progesterone candidates were identified, 43 accepted treatment, 7 refused, and 5 either initiated prenatal care too late to receive injections or did not follow-up. Those who accepted treatment appeared to cope better with treatment side effects, and/or had traumatic emotional reactions regarding their prior premature birth outcomes. Women who declined treatment often cited pain with injection, had fatalistic beliefs regarding their care, and/or had personal concerns related to full-term pregnancy. Discussion Maternal health care providers should always discuss the implications of prematurity at the time of the index premature delivery and again at the first prenatal visit of the subsequent pregnancy. Providers need to be prepared to employ various techniques for patient counseling and education. Small changes in office practice, like having fewer care providers involved in patient care or providing distractions for children, may make the difference between a patient who is open or closed to treatment options.

The Las Vegas mass shooting: An analysis of blood component administration and blood bank donations.

BACKGROUND: The deadliest mass shooting in modern United States history occurred on October 1, 2017, in Las Vegas, killing 58 and overwhelming hospitals with more than 600 injured. The scope of the tragedy offers insight into medical demands, which may help guide preparedness for future mass shooting incidents. METHODS: Retrospective, deidentified, health care institution-provided data from all hospitals and blood banks providing care to Las Vegas shooting victims were gathered. Study authors independently reviewed all data and cross-referenced it for verification. Main outcomes and measures include the number of victims requiring hospital and intensive care admission, the amount and types of blood components transfused during the first 24 hours, and the amount of blood donated to local blood banks following the Las Vegas mass shooting. RESULTS: Two hundred twenty patients required hospital admission, 68 of them to critical care. Nearly 500 blood components were transfused during the first 24 hours in a red blood cell-to-plasma-to-platelet ratio of 1:0.54:0.81. Public citizens donated almost 800 units of blood immediately after the shooting; greater than 17% of this donated blood went unused. CONCLUSIONS: The amount of blood components transfused per patient admitted was similar in magnitude to other mass casualty events, and available blood supply met patient demand. The public call for blood donors was not necessary to meet immediate demand and led to resource waste. Preparation for future mass shooting incidents should include training the community in hemorrhage control, encouraging routine blood donation, and avoiding public calls for blood donation unless approved by local blood suppliers. LEVEL OF EVIDENCE: Therapeutic study, level V.

Persistent hemolytic disease of the fetus and newborn (HDFN) associated with passive acquisition of anti-D in maternal breast milk.

BACKGROUND: Anti-D is a well-documented, significant cause of hemolytic disease of the fetus and newborn (HDFN), but its presence in breast milk is not routinely described. Theoretically, breast milk containing anti-D could have the potential to exacerbate HDFN if ingested by the affected infant. STUDY DESIGN AND METHODS: This is a case report of a 28-week premature male neonate with hydrops fetalis born to a 32-year-old woman (gravidity 3/parity 3) with anti-D and anti-G. The male neonate experienced prolonged HDFN due to passive acquisition of anti-D in the mother's breast milk. RESULTS: The mother's breast milk reacted strongly (4+) with the D-positive cells in the antibody screen test. Discontinuation of breast milk feeding and addition of total parenteral nutrition led to the cessation of clinically significant HDFN. CONCLUSION: Although anti-D is a significant cause of HDFN through placental transfer of antibody, exacerbation of the condition through breast milk antibodies is rarely described. The current case highlights the possibility of this occurring. Discontinuation of maternal breast milk feedings should be considered in infants with HDFN who do not respond to standard treatment.

Ki-67 proliferative index predicts progression-free survival of patients with well-differentiated ileal neuroendocrine tumors.

Ki-67 proliferative index (Ki-67 index) is suggested to be an important prognostic variable and is included as one of the grading parameters for neuroendocrine tumors. The present study was undertaken to determine the usefulness of the Ki-67 index and the corresponding tumor grade in predicting progression-free survival (PFS) of patients with ileal well-differentiated neuroendocrine tumors (wNETs). Tumors from 57 patients with ileal wNETs were studied. Immunohistochemical staining for Ki-67 was performed on the primary as well as selected metastatic tumors and quantitated by computer-assisted image analysis using the Ariol system. The tumors were graded based on mitotic activity and Ki-67 index. Clinical and pathological variables affecting the PFS were analyzed. There were 29 women and 28 men, with a mean age of 59 years. At the time of initial presentation, 8 patients (14%) had localized disease (stages I and II), 29 patients (51%) had regional (nodal/mesenteric) spread (stage III), and 20 patients (35%) had distant metastasis (stage IV). Twelve patients experienced disease progression during subsequent follow-up. Patients with initial stage IV disease were more likely to experience disease progression (P = .005). Additionally, higher histological grade (as determined by Ki-67 index >2%) was associated with a decreased PFS (P = .001). Ki-67 index greater than 2% at either the primary site or the metastatic site was found to be the only significant predictor of PFS after consideration of all other variables in an adjusted analysis. In conclusion, the Ki-67 index predicts PFS of patients with ileal wNETs.

Autoimmune hemolytic anemia in pediatric liver or combined liver and small bowel transplant patients: a case series and review of the literature.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) occurring after solid organ transplantation is an infrequently reported entity. We describe in this report six cases of AIHA in pediatric liver or combined liver and small bowel transplant patients. STUDY DESIGN AND METHODS: We retrospectively identified and reviewed the records of pediatric liver or combined liver and small bowel transplant patients with both serologic and clinical evidence of AIHA. We also performed an English language literature review for prior publications of AIHA occurring after solid organ transplantation. RESULTS: We identified six patients presenting with severe hemolysis 9 months to 14 years after transplantation. All six developed warm AIHA, and two had concomitant cold agglutinins. All except one patient received various therapeutic combinations including steroids, intravenous immune globulin, rituximab, plasmapheresis, splenectomy, and vincristine. Five patients achieved remission 2 weeks to 3 months after presentation. Although tacrolimus has been speculated to play a causative role in the development of AIHA after organ transplantation, our case series demonstrated slightly better outcomes despite continuing tacrolimus compared to published cases where most patients either received significantly reduced doses of tacrolimus or were switched to a different immunosuppressant (83% vs. 76% cumulative literature remission rate). CONCLUSION: AIHA may occur in solid organ transplant patients at a much higher frequency than previously believed. Hemolysis is often severe and resistant to steroid treatment alone. Thus early diagnosis and institution of aggressive multimodality treatment, including the use of rituximab, may be needed to achieve remission.