Utilization and outcome disparities in allogeneic hematopoietic stem cell transplant in the United States.

Allogeneic hematopoietic stem cell transplant (allo-HSCT) is increasingly being used in the United States (US) and across the world as a curative therapeutic option for patients with certain high-risk hematologic malignancies and non-malignant diseases. However, racial and ethnic disparities in utilization of the procedure and in outcome following transplant remain major problems. Racial and ethnic minority patients are consistently under-represented in the proportion of patients who undergo allo-HSCT in the US. The transplant outcomes in these patients are also inferior. The interrelated driving forces responsible for the differences in the utilization and transplant outcome of the medical intervention are socioeconomic status, complexity of the procedure, geographical barriers, and the results of differences in the genetics and comorbidities across different races. Bridging the disparity gaps is important not only to provide equity and inclusion in the utilization of this potentially life-saving procedure but also in ensuring that minority groups are well represented for research studies about allo-HSCT. This is required to determine interventions that may be more efficacious in particular racial and ethnic groups. Various strategies at the Federal, State, and Program levels have been designed to bridge the disparity gaps with varying successes. In this review paper, we will examine the disparities and discuss the strategies currently available to address the utilization and outcome gaps between patients of different races in the US.

Posterior reversible encephalopathy syndrome in a child following hypovolemic shock: a case report.

Introduction and importance: Posterior reversible encephalopathy syndrome (PRES) is a condition that causes a wide range of clinical neurological manifestations like headache, seizures, visual changes, and altered mental sensations. It is diagnosed with the help of sequential neuroimaging findings. Manifestations may occur a few hours to months after the initial precipitating cause. In the pediatric population, the most common cause is hypertension caused by renal disease or different drugs. Case presentation: Here, the authors present the case of a 4-year-old boy with a significant medical history of acute gastroenteritis following hypovolemic shock that later developed white matter edema of the brain on T2-weighted MRI scans along with symptoms such as headache and vomiting. Here, the patient was managed symptomatically with antiepileptic medication as prophylaxis. Clinical discussion: PRES is a rare neurological diagnosis made in the child that presents with headache, vomiting, blurring of vision, and abnormal body movements, which have several etiology like hypertension, glomerulonephritis, organ transplant, drugs, and very rarely with hypovolemic shock. It is an acute reversible condition in which a person presents with visual disturbances, headaches, and seizures. Seizures present as a life-threatening situation, so antiepileptic drugs are used as early prophylaxis. Conclusion: PRES is a reversible neurological condition, and prognosis is typically favorable if recognized and treated early, with symptom improvement or resolution in a few days to several weeks. Complications of PRES develop if the disease is not treated promptly. Complications include focal neurologic deficits from ischemic injury and epilepsy.

Intestinal barrier functions in hematologic and oncologic diseases.

The intestinal barrier is a complex structure that not only regulates the influx of luminal contents into the systemic circulation but is also involved in immune, microbial, and metabolic homeostasis. Evidence implicating disruption in intestinal barrier functions in the development of many systemic diseases, ranging from non-alcoholic steatohepatitis to autism, or systemic complications of intestinal disorders has increased rapidly in recent years, raising the possibility of the intestinal barrier as a potential target for therapeutic intervention to alter the course and mitigate the complications associated with these diseases. In addition to the disease process being associated with a breach in the intestinal barrier functions, patients with hematologic and oncologic diseases are particularly at high risks for the development of increased intestinal permeability, due to the frequent use of broad-spectrum antibiotics and chemoradiation. They also face a distinct challenge of being intermittently severely neutropenic due to treatment of the underlying conditions. In this review, we will discuss how hematologic and oncologic diseases are associated with disruption in the intestinal barrier and highlight the complications associated with an increase in the intestinal permeability. We will explore methods to modulate the complication. To provide a background for our discussion, we will first examine the structure and appraise the methods of evaluation of the intestinal barrier.

Post-Crash First Response by Traffic Police in Nepal: A Feasibility Study.

BACKGROUND: Road traffic injuries are a significant and increasing public health burden in Nepal, but there is no national coverage of regulated and standardized emergency medical service systems. Therefore, this study was designed to develop a first responder trauma training program for the Nepal traffic police and to evaluate the feasibility of its delivery and follow up. METHODS: A training needs assessment with traffic-police officers in a single district of Nepal informed the development of a 3-day first-response course which was provided to officers in May 2019. Participants were supplied with a trauma-pack and asked to complete a report form when first-responder skills were used. Knowledge and confidence face-to-face surveys were used before and after training to assess learning, and were repeated at 6 months to assess retention of knowledge. The surveys at 6 months assessed the factors affecting application of first response skills. RESULTS: Most (97%) participants believed giving first-aid was part of their responsibilities and 95% had experience of transporting road crash victims to hospital with a range of injuries. Low levels of first-aid training and variable course content were reported. Knowledge and confidence scores improved post-intervention but were reduced at 6-months. During attendance at 303 road crashes in the 6-months follow-up period, 44% of the participants self-reported using at least one skill from the course; applying them on 92 occasions. Incident report-forms were frequently not completed. Barriers to providing treatment included: the patient already en-route to hospital when police arrived at scene; resistance to providing care from relatives or bystanders; and competing police duties (e.g., traffic management). CONCLUSIONS: Delivering a first-response training program for traffic-police in Nepal is feasible. Knowledge was retained and used, and skills were in frequent demand. A study of effectiveness and cost-effectiveness appears warranted to determine if extending the training to other districts can improve outcomes in road traffic injury patients in the absence of formal emergency medical services.

Adapting Agriculture to Climate Change: A Synopsis of Coordinated National Crop Wild Relative Seed Collecting Programs across Five Continents.

The Adapting Agriculture to Climate Change Project set out to improve the diversity, quantity, and accessibility of germplasm collections of crop wild relatives (CWR). Between 2013 and 2018, partners in 25 countries, heirs to the globetrotting legacy of Nikolai Vavilov, undertook seed collecting expeditions targeting CWR of 28 crops of global significance for agriculture. Here, we describe the implementation of the 25 national collecting programs and present the key results. A total of 4587 unique seed samples from at least 355 CWR taxa were collected, conserved ex situ, safety duplicated in national and international genebanks, and made available through the Multilateral System (MLS) of the International Treaty on Plant Genetic Resources for Food and Agriculture (Plant Treaty). Collections of CWR were made for all 28 targeted crops. Potato and eggplant were the most collected genepools, although the greatest number of primary genepool collections were made for rice. Overall, alfalfa, Bambara groundnut, grass pea and wheat were the genepools for which targets were best achieved. Several of the newly collected samples have already been used in pre-breeding programs to adapt crops to future challenges.

State of Post-injury First Response Systems in Nepal-A Nationwide Survey.

Injuries account for 9.2% of all deaths and 9.9% of the total disability-adjusted life years in Nepal. To date, there has not been a systematic assessment of the status of first response systems in Nepal. An online survey was cascaded through government, non-governmental organisations and academic networks to identify first response providers across Nepal. Identified organisations were invited to complete a questionnaire to explore the services, personnel, equipment, and resources in these organisations, their first aid training activities and whether the organisation evaluated their first response services and training. Of 28 organisations identified, 17 (61%) completed the questionnaire. The range of services offered varied considerably; 15 (88.2%) provided first aid training, 9 (52.9%) provided treatment at the scene and 5 (29.4%) provided full emergency medical services with assessment, treatment and transport to a health facility. Only 8 (47.1%) of providers had an ambulance, with 6 (35.3%) offering transportation without an ambulance. Of 13 first aid training providers, 7 (53.8%) evaluated skill retention and 6 (46.2%) assessed health outcomes of patients. The length of a training course varied from 1 to 16 days and costs from US$4.0 to 430.0 per participant. There was a variation among training providers in who they train, how they train, and whether they evaluate that training. No standardisation existed for either first aid training or provision of care at the scene of an injury. This survey suggests that coordination and leadership will be required to develop an effective first response system across the country.

Improved health care utilization and costs in transplanted versus non-transplanted adults with sickle cell disease.

Patients with sickle cell disease (SCD) have access to fewer health care resources and therapies compared to other diseases, which contributes to increased morbidity and health care utilization. We compared health care utilization (inpatient hospital days, emergency care visits) and health care-related costs between SCD adults that underwent hematopoietic stem cell transplantation (HSCT) using a nonmyeloblative conditioning regimen versus those referred for HSCT but did not proceed due to lack of an HLA-matched sibling donor, denial by insurance, red blood cell antibodies to the potential donor, or declining further evaluation. Between 8/2011 and 4/2016, 83 SCD patients were referred for allogeneic HSCT and 16 underwent the procedure. The HSCT and non-HSCT groups were similar by age, sex, prior SCD-related therapy and complications. Compared to pre HSCT, significantly fewer inpatient hospital days (median of 1 versus 22 days, P = 0.003) and emergency care visits (median of 1 versus 4 visits, P = 0.04) were observed by the 2nd year post-HSCT. Similar results were observed in comparison to the standard-of-care group (median of 1 versus 12 hospital days, P = 0.002; median of 1 versus 3 emergency visits, P = 0.03). Lower health care costs were observed by the 2nd year post-HSCT (median of $16,281 versus $64,634 pre-HSCT (P = 0.01) and versus $54,082 in the standard-of-care group (P = 0.05). A median reduction of -$20,833/patient/year (IQR, -$67,078-+$4,442/patient/year) in health care costs compared to pre-HSCT was observed in the 2nd year post-HSCT. In conclusion, allogeneic HSCT leads to improvements in health care utilization and costs compared to standard-of-care therapy in high-risk SCD adults.

Inoculation Method Impacts Symptom Development Associated with Diaporthe aspalathi, D. caulivora, and D. longicolla on Soybean (Glycine max).

One hundred fifty-two Diaporthe isolates were recovered from symptomatic soybean (Glycine max) stems sampled from the U.S. states of Iowa, Indiana, Kentucky, Michigan, and South Dakota. Using morphology and DNA sequencing, isolates were identified as D. aspalathi (8.6%), D. caulivora (24.3%), and D. longicolla (67.1%). Aggressiveness of five isolates each of the three pathogens was studied on cultivars Hawkeye (D. caulivora and D. longicolla) and Bragg (D. aspalathi) using toothpick, stem-wound, mycelium contact, and spore injection inoculation methods in the greenhouse. For D. aspalathi, methods significantly affected disease severity (P < 0.001) and pathogen recovery (P < 0.001). The relative treatment effects (RTE) of stem-wound and toothpick methods were significantly greater than for the other methods. For D. caulivora and D. longicolla, a significant isolate × method interaction affected disease severity (P < 0.05) and pathogen recovery (P < 0.001). Significant differences in RTEs were observed among D. caulivora and D. longicolla isolates only when the stem-wound and toothpick methods were used. Our study has determined that the stem-wound and toothpick methods are reliable to evaluate the three pathogens; however, the significant isolate × method interactions for D. caulivora and D. longicolla indicate that multiple isolates should also be considered for future pathogenicity studies.

Neuroprotective effect of solanesol against 3-nitropropionic acid-induced Huntington's disease-like behavioral, biochemical, and cellular alterations: Restoration of coenzyme-Q10-mediated mitochondrial dysfunction.

OBJECTIVE: The aim of the present study was to evaluate the solanesol (SNL)-mediated coenzyme-Q10 restoration to ameliorate 3-nitropropionic (3-NP)-induced behavioral, biochemical, and histological changes which resemble Huntington's disease (HD)-like symptoms in men. MATERIALS AND METHODS: Various behavioral and biochemical parameters were carried out to evaluate the activity of SNL on 3-NP-treated rats. To determine the therapeutic significance of SNL on HD, different behavioral tests such as memory task, locomotor activity, grip strength, and beam cross and some biochemical test along with histopathological findings were done. RESULTS: Chronic 3-NP, 10 mg/kg i.p., caused physical and mental abnormalities in animals, including memory impairment, weak grip strength, abnormal posture, and cognitive deficit. Biochemical analysis of brain homogenate in 3-NP-treated rats showed altered mitochondrial complexes, oxidative stress, and elevated lipid biomarkers. Neurohistological alterations of hippocampus, basal ganglia, and cerebral cortex of 3-NP-treated rats exhibit severe neuronal space, irregular damaged cells, and dense pyknotic nuclei-associated marked focal diffused gliosis. SNL administered for 15 days significantly improved motor performance and cognitive behavior task and restored the histopathological changes. Further, SNL treatment significantly improved mitochondrial complexes such as coenzyme-Q10 enzyme activity and attenuated inflammatory and oxidative damage of rat brain. CONCLUSION: In the present research work, SNL (5, 10, and 15 mg/kg p.o.) provided notable neuroprotective effect, which was confirmed by behavioral paradigms and biochemical test. It restored the behavioral and biochemical alteration caused by 3-NP and confirmed the strong neuroprotective mechanism of SNL in 3-NP-intoxicated memory and cognitive abnormalities.

Survival trends among patients with advanced renal cell carcinoma in the United States.

INTRODUCTION: Since the approval of sorafenib in December 2005, several targeted therapeutic agents have been approved by the FDA for the treatment of advanced renal cell carcinoma (RCC). This study was conducted to find out whether the improvements in survival of advanced RCC patients with targeted agents have translated into a survival benefit in a population-based cohort. METHODS: We analyzed the SEER 18 (Surveillance, Epidemiology and End RESULTS) registry database to calculate the relative survival rates for advanced RCC patients during 2001-2009, 2001-2005, 2006-2007 and 2008-2009. We also evaluated the survival rates by age (<65 and ≥65 years) and sex. RESULTS: The total number of advanced RCC patients during 2001-2009, 2001-2005, 2006-2007 and 2008-2009 were 7,047, 4,059, 1,548 and 1,440, respectively. During 2001-2009, the 1- and 3-year relative survival rates were 26.7±0.6 and 10.0±0.4%, respectively. There was no significant difference in 1-year relative survival rates for patients diagnosed during 2006-2007 and 2008-2009 compared to those diagnosed during 2001-2005. Similarly, the 3-year survival rates for patients diagnosed during 2006-2007 were similar to those diagnosed during 2001-2005. CONCLUSIONS: This population-based study showed that there was no significant improvement in relative survival rates among advanced RCC patients in the era of targeted agents.

Second primary malignancies in chronic myeloid leukemia.

Survival of patients with chronic myeloid leukemia (CML) has improved with the use of imatinib and other tyrosine kinase inhibitors. There is limited data on second primary malignancies (SPM) in CML. We analyzed the SPMs rates among CML patients reported to Surveillance, Epidemiology, and End Results (SEER) database during pre-(1992-2000) and post-(2002-2009) era. We used SEER Multiple Primary-Standardized Incidence Ratio session to calculate standardized incidence ratios (SIRs). Among 8,511 adult CML patients, 446 patients developed 473 SPMs. The SIR for SPMs in CML patients was significantly higher with observed/expected ratio:1.27, P < 0.05 and absolute excess risk of 32.09 per 10,000 person years compared to general population. The rate of SPMs for cancers of all sites in post-imatinib era were significantly higher compared to pre-imatinib era with observed/expected ratio of 1.48 versus 1.06, P = 0.03. This study showed that risk of SPMs is higher among CML patients. The risk of SPMs is significantly higher in post-imatinib era compared to pre-imatinib era.

Second primary malignancies in adult acute myeloid leukemia--A US population-based study.

BACKGROUND: Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Long-term survivors from AML may be at higher risk of second primary malignancies. PATIENTS AND METHODS: We selected adult patients with AML aged≥18 years from the National Cancer Institute's Surveillance, Epidemiology and End RESULTS (SEER 13) database. We used the multiple primary standardized incidence ratio session of SEER*stat software to calculate the risk of second primary malignancies in patients with AML. RESULTS: Among 5,091 patients, 148 patients developed a total of 160 second primary malignancies, with an observed/expected (O/E) ratio of 1.17, (95% confidence interval=0.99-1.36), and an excess risk of 15.47 per 10,000 population. The risk of all-site cancer, cancer of gastrointestinal system, and oral and pharyngeal cancer in different age groups was found to be significantly higher among patients with AML compared to that of general US population. CONCLUSION: Adult patients with AML have a significantly higher risk of second primary malignancies compared to the general population.

Improved survival among older acute myeloid leukemia patients - a population-based study.

BACKGROUND: Survival in acute myeloid leukemia (AML) has improved in younger patients over the last decade. This study was conducted to evaluate the relative survival rates in older AML patients over two decades in the US. MATERIAL AND METHODS: We analyzed Surveillance, Epidemiology, and End Results (SEER) registry database to evaluate relative survival rate in older (≥ 75 years) AML population diagnosed during 1992-2009. We selected AML patients from 13 registries of SEER 18 database to compare RS during 1992-2000 and 2001-2009. RESULTS: The relative survival rates improved significantly during 2001-2009 compared to 1992-2000 for all age groups and sex. For young elderly patients (75-84 years) RS increased from 13.1 ± 0.8% to 17.4 ± 0.9% at one year Z-value = 3.98, p < 0.0001 and from 2.0 ± 0.4 to 2.6 ± 0.5%, Z-value = 3.61, p < 0.0005 at five years. Similarly, for very elderly (≥ 85 years) patients RS increased from 5.3 ± 1.0% to 8.0 ± 1.0%, Z-value = 3.03, p < 0.005 at one year, but no improvement seen at five years. CONCLUSION: The relative survival in elderly AML has increased significantly during 2001-2009 compared to 1992-2000.