Oral arsenic trioxide incorporation into frontline treatment with all-trans retinoic acid and chemotherapy in newly diagnosed acute promyelocytic leukemia: A 5-year prospective study.

BACKGROUND: Strategies using oral arsenic trioxide (As2 O3 ) are efficacious in relapsed acute promyelocytic leukemia (APL), but they have not been examined in newly diagnosed cases. METHODS: Sixty-two consecutive patients (24 men and 38 women) with a median age of 52 years (range, 22-85 years), 36% of whom had high-risk features, underwent induction with all-trans retinoic acid at 45 mg/m2 /d, oral As2 O3 at 10 mg/d, and ascorbic acid at 1 g/d (the all-trans retinoic acid-arsenic trioxide-ascorbic acid [AAA] regimen) for 6 weeks (with patients younger than 70 years additionally receiving daunorubicin at 50 mg/m2 /d × 3); they then underwent consolidation with 2 monthly cycles of daunorubicin (50 mg/m2 /d × 2) and cytarabine (100 mg/m2 /d × 5) and received AAA maintenance (2 weeks every 8 weeks) for 2 years. A contemporaneous cohort of 37 newly diagnosed patients (15 men and 22 women) with a median age of 51 years (range, 23-78 years), not consenting to oral As2 O3 induction but receiving similar induction, consolidation, and AAA maintenance, served as a comparator group; 46% of these patients had high-risk features. RESULTS: The oral As2 O3 induction cohort showed a complete remission (CR) rate of 100%. After a median of 37 months (range, 13-82 months), there were no relapses, so conventional risks (age, leukocyte and platelet counts, and Fms-like tyrosine kinase 3 [FLT3] mutations) were not relevant. The leukemia-free survival (LFS) and overall survival (OS) rates were 100% at 3 years and 94.1% at 5 years. The non-As2 O3 induction cohort showed a CR rate of 100%. After a median of 52 months (range, 14-77 months), there were 3 relapses (8%). Comparable patients in the oral As2 O3 induction and non-As2 O3 induction cohorts showed similar OS, but LFS was significantly superior in the oral As2 O3 induction cohort. CONCLUSIONS: The incorporation of oral As2 O3 into induction for newly diagnosed APL was safe and decreased relapses.

Transfusion of pathogen-reduced platelet components without leukoreduction.

BACKGROUND: Leukoreduction (LR) of platelet concentrate (PC) has evolved as the standard to mitigate risks of alloimmunization, clinical refractoriness, acute transfusion reactions (ATRs), and cytomegalovirus infection, but does not prevent transfusion-associated graft-versus-host disease (TA-GVHD). Amotosalen-ultraviolet A pathogen reduction (A-PR) of PC reduces risk of transfusion-transmitted infection and TA-GVHD. In vitro data indicate that A-PR effectively inactivates WBCs and infectious pathogens. STUDY DESIGN AND METHODS: A sequential cohort study evaluated A-PR without LR, gamma irradiation, and bacterial screening in hematopoietic stem cell transplant (HSCT) recipients. The first cohort received conventional PC (control) processed without LR, but with gamma irradiation and bacterial screening. The second cohort received A-PR PC (test) processed without: LR, bacterial screening, or gamma irradiation. The primary efficacy outcome was the 1-hour corrected count increment. The primary safety outcome was treatment-emergent ATR. Secondary outcomes included clinical refractoriness, and 100-day status for engraftment, TA-GVHD, HSCT-GVHD, infections, and mortality. RESULTS: Mean corrected count increment (× 103 ) of 33 test PC recipients was similar (18.9 ± 8.8 vs. 16.6 ± 8.4; p = 0.296) to that of 31 control PC recipients. Test recipients had a reduced, but nonsignificant, incidence of ATR (test = 9.1%, Control = 19.4%; p = 0.296). The frequencies of clinical refractoriness (0 of 33 vs. 4 of 31 patients) and refractory transfusions (6.6% vs. 19.3%) were lower in the test cohort (p = 0.05 and 0.02), respectively. No patient in either cohort had TA-GVHD. Day 100 engraftment, HSCT-GVHD, mortality, and infectious disease complications were similar between cohorts. CONCLUSIONS: This study indicated that A-PR PC without LR, gamma irradiation, or bacterial screening is feasible for support of HSCT.

Next-generation sequencing with a 54-gene panel identified unique mutational profile and prognostic markers in Chinese patients with myelofibrosis.

Current prognostication in myelofibrosis (MF) is based on clinicopathological features and mutations in a limited number of driver genes. The impact of other genetic mutations remains unclear. We evaluated for mutations in a myeloid panel of 54 genes using next-generation sequencing. Multivariate Cox regression analysis was used to determine prognostic factors for overall survival (OS) and leukaemia-free survival (LFS), based on mutations of these genes and relevant clinical and haematological features. One hundred and one patients (primary MF, N = 70; secondary MF, N = 31) with a median follow-up of 49 (1-256) months were studied. For the entire cohort, inferior OS was associated with male gender (P = 0.04), age > 65 years (P = 0.04), haemoglobin < 10 g/dL (P = 0.001), CUX1 mutation (P = 0.003) and TP53 mutation (P = 0.049); and inferior LFS was associated with male gender (P = 0.03), haemoglobin < 10 g/dL (P = 0.04) and SRSF2 mutations (P = 0.008). In primary MF, inferior OS was associated with male gender (P = 0.03), haemoglobin < 10 g/dL (P = 0.002), platelet count < 100 × 109/L (P = 0.02), TET2 mutation (P = 0.01) and CUX1 mutation (P = 0.01); and inferior LFS was associated with haemoglobin < 10 g/dL (P = 0.02), platelet count < 100 × 109/L (P = 0.02), TET2 mutations (P = 0.01) and CUX1 mutations (P = 0.04). These results showed that clinical and haematological features and genetic mutations should be considered in MF prognostication.

Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services Task Force.

BACKGROUND: Screening can detect prostate cancer at earlier, asymptomatic stages, when treatments might be more effective. PURPOSE: To update the 2002 and 2008 U.S. Preventive Services Task Force evidence reviews on screening and treatments for prostate cancer. DATA SOURCES: MEDLINE (2002 to July 2011) and the Cochrane Library Database (through second quarter of 2011). STUDY SELECTION: Randomized trials of prostate-specific antigen-based screening, randomized trials and cohort studies of prostatectomy or radiation therapy versus watchful waiting, and large observational studies of perioperative harms. DATA EXTRACTION: Investigators abstracted and checked study details and quality using predefined criteria. DATA SYNTHESIS: Of 5 screening trials, the 2 largest and highest-quality studies reported conflicting results. One found that screening was associated with reduced prostate cancer-specific mortality compared with no screening in a subgroup of men aged 55 to 69 years after 9 years (relative risk, 0.80 [95% CI, 0.65 to 0.98]; absolute risk reduction, 0.07 percentage point). The other found no statistically significant effect after 10 years (relative risk, 1.1 [CI, 0.80 to 1.5]). After 3 or 4 screening rounds, 12% to 13% of screened men had false-positive results. Serious infections or urine retention occurred after 0.5% to 1.0% of prostate biopsies. There were 3 randomized trials and 23 cohort studies of treatments. One good-quality trial found that prostatectomy for localized prostate cancer decreased risk for prostate cancer-specific mortality compared with watchful waiting through 13 years of follow-up (relative risk, 0.62 [CI, 0.44 to 0.87]; absolute risk reduction, 6.1%). Benefits seemed to be limited to men younger than 65 years. Treating approximately 3 men with prostatectomy or 7 men with radiation therapy instead of watchful waiting would each result in 1 additional case of erectile dysfunction. Treating approximately 5 men with prostatectomy would result in 1 additional case of urinary incontinence. Prostatectomy was associated with perioperative death (about 0.5%) and cardiovascular events (0.6% to 3%), and radiation therapy was associated with bowel dysfunction. LIMITATIONS: Only English-language articles were included. Few studies evaluated newer therapies. CONCLUSION: Prostate-specific antigen-based screening results in small or no reduction in prostate cancer-specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Virtual blood banking in Hong Kong.

OBJECTIVE. To review our experience in virtual blood banking for intra-operative transfusion in Hong Kong. DESIGN. Retrospective study. SETTING. Three major acute hospitals and a specialised centre for joint replacement surgery with installation of an Operating Theatre Blood Transaction System. PATIENTS. Patients undergoing surgery under anaesthesia and requiring intra-operative transfusion for the period from the implementation of the system in individual institutes (Queen Elizabeth Hospital: June 1997; Princess Margaret Hospital: May 2001; Queen Mary Hospital: October 2009; and Hong Kong Buddhist Hospital: December 2010) till September 2011. RESULTS. Under the system, 58 923 units of red cells were released intra-operatively for 18 264 patients (11% of the total number of blood units issued by the blood banks in these institutes during the study period). About 1% of them (613 units) entailed unmatched red cells given to 183 patients for emergency transfusions during surgery. The mean time required for the issue of the first unit of red cells was less than 1 minute. A total of 1231 units of red cells were returned unused after being released. Among them, 95 units were deemed unfit for re-issue because they had left the temperature-monitored blood storage refrigerators in the operating theatres for more than 30 minutes. There was no delay in transfusion or postponement of surgery due to problems or downtime of the Operating Theatre Blood Transaction System. CONCLUSION. Our experience has shown that our virtual blood banking system was efficient and effective, and helped ensure that the right patient received the right amount of the right blood at the right time. The system can be implemented either locally in the same hospital with a central blood bank, or in a more remote and networked site without a nearby supporting blood bank.

Common association of haemolytic uraemic syndrome with invasive Streptococcus pneumoniae infection in five Chinese paediatric patients.

Haemolytic uraemic syndrome is an important cause of acute renal impairment in childhood. We review the incidence, and clinical and laboratory features of haemolytic uraemic syndrome in a Chinese population. Five patients were identified from 2006 to 2008. All patients were young children with associated invasive Streptococcus pneumoniae pulmonary infection. Serotypes 3, 14, and 19A were confirmed in four patients. The classical post-diarrhoeal form associated with Escherichia coli (O157:H7) infection was not seen. One patient died of acute respiratory failure. Streptococcus pneumoniae infection, as an associated condition in haemolytic uraemic syndrome, is important and relatively common in Chinese patients, especially among children. The acute clinical picture is similar to that reported in the western literature, except for an uncommon association with meningitis. The medium-term renal outcome of the Chinese population appears to be more favourable than the Caucasians. Widespread vaccination against Streptococcus pneumoniae may have resulted in changes in bacterial epidemiology and clinicians should be continuously aware of this severe disease. The use of washed blood components for transfusion in the acute stage requires further study.

Standardizing the Accommodations Process for Health Care Workers During COVID-19.

ABSTRACT: The COVID-19 pandemic has resulted in a significant increase in accommodation requests from employees seeking temporary alterations to or relief from their job demands. To maintain consistency and ensure a standard approach, Johns Hopkins Medicine established a COVID-19 Accommodation Review committee that includes experts from the occupational health, legal, and human resources departments, as well as an Americans with Disabilities Act coordinator. In this article, the authors describe the workflow and various components of their institution's accommodations review process, which has resulted in a more consistent and equitable approach to granting requests.

Community Culinary Workshops as a Nutrition Curriculum in a Preventive Medicine Residency Program.

Introduction: Obesity and diabetes are common diagnoses in the primary care population, especially in urban settings. Physicians providing preventive culinary and nutrition education to patients may be able to uniquely address these medical issues; however, culinary and nutrition education among medical residency programs is insufficient. Methods: We describe a pilot of a novel interactive approach to culinary and nutrition education focused on preventive medicine residents who were trained to provide culinary and nutrition skills to community members in three separate workshops. We developed and implemented a series of three culinary education workshops with 11, eight, and nine preventive medicine residents in each respective workshop. A total of 16 residents were invited to participate. A physician-chef facilitated each workshop with the residents within a community church kitchen and meeting area. We evaluated self-reported data on confidence level with culinary education and resident attitudes toward effects of culinary education on patient behaviors, as well as frequency of home-cooked meals and personal cooking competency, as indicators of resident proficiency. Results: A significant increase was noted in self-reported cooking competency after culinary workshops when evaluating change from the first workshop to the final workshop ( p = .038). Increases in home-cooking frequency and belief that lifestyle medicine impacts patient behavior were also observed but did not achieve statistical significance. Discussion: Culinary workshops are a useful tool to enhance nutrition education in a residency curriculum and may be an effective way to improve resident perceptions regarding the impact of nutrition education in the community.

Regional approaches to hospital preparedness.

This article describes issues related to the engagement of hospitals and other community partners in a coordinated regional healthcare preparedness and response effort. The report is based on interviews with public health and hospital representatives from 13 regions or states across the country. It aims to identify key ingredients for building successful regional partnerships for healthcare preparedness as well as critical challenges and policy and practical recommendations for their development and sustainability.

Billions for biodefense: Federal Agency biodefense funding, FY2006-FY2007.

Since 2001, the United States government has spent substantial resources on preparing the nation against a bioterrorist attack. Earlier articles in this series analyzed the civilian biodefense funding by the federal government from fiscal years 2001 through 2006. This article updates those figures with budgeted amounts for fiscal year 2007, specifically analyzing the budgets and allocations for biodefense at the Department of Health and Human Services, the Department of Homeland Security, the Department of Agriculture, the Environmental Protection Agency, the Department of State, and the National Science Foundation.

The prospect of using alternative medical care facilities in an influenza pandemic.

Alternative care facilities (ACFs) have been widely proposed in state, local, and national pandemic preparedness plans as a way to address the expected shortage of available medical facilities during an influenza pandemic. These plans describe many types of ACFs, but their function and roles are unclear and need to be carefully considered because of the limited resources available and the reduced treatment options likely to be provided in a pandemic. Federal and state pandemic plans and the medical literature were reviewed, and models for ACFs being considered were defined and categorized. Applicability of these models to an influenza pandemic was analyzed, and recommendations are offered for future ACF use. ACFs may be best suited to function as primary triage sites, providing limited supportive care, offering alternative isolation locations to influenza patients, and serving as recovery clinics to assist in expediting the discharge of patients from hospitals.

Use of remote blood releasing system for red cell transfusion in hospice care center.

OBJECTIVES: It is quite common to have advanced cancer or end-stage renal disease patients for regular or even frequent blood transfusion in palliative care. However, due to geographical reason in some hospice centers, blood transfusion is sometimes difficult if blood bank is closed during non-office hour or not available. METHODS: Here, we reported a new blood releasing system, that is, remote blood releasing system, that could be used safely by nursing staff alone when the blood bank was closed during the night time and holiday. RESULTS: On-call nursing staff could collect red cells successful in these two cases. CONCLUSION: The new blood releasing system seems useful. However, larger sample sizes and longer period of study are required to estimate its efficacy and safety. The provision of antibody-positive red cells and platelet remained a limitation of this system.

Alemtuzumab induced complete remission of therapy-resistant pure red cell aplasia.

Two patients with pure red cell aplasia (PRCA) refractory to anti-thymocyte globulin, prednisolone, cyclophosphamide, fludarabine, mitoxantrone, dexamethasone and cyclosporine, were treated with alemtuzumab (anti-CD52 antibody). Case 1, a 35-year-old man with idiopathic PRCA, remitted completely with 130 mg of alemtuzumab. Case 2, a 42-year-old man with PRCA due to T-cell large granular lymphocyte (T-LGL) leukaemia, achieved complete remission of the PRCA with 490 mg of alemtuzumab, although the T-LGL leukaemia responded only transiently. There were no significant side effects, and normalization of erythropoiesis was durable. Alemtuzumab is active in PRCA that is idiopathic or secondary to T-cell lymphoproliferative diseases.

Hepatitis C virus infection in adult Chinese hemophilia patients negative for the human immunodeficiency virus: treatment results with interferon and ribavirin.

Hepatitis C virus (HCV) eradication in hemophilia patients depends on viral and patient factors. We report the treatment results with interferon 3 (5 megaunits, 3 times per week) and ribavirin (1 g daily) for 1 year in 17 Chinese patients who were negative for the human immunodeficiency virus. The HCV genotype consisted of a mixture of Western (genotypes 1, 2, and 3) and Chinese (genotypes 1 and 6) patterns. Quasi species were common (29%). Seven patients (41%) stopped treatment because of complications. Sustained HCV eradication was achieved until the end of treatment or for 24 months in 7 of 17 patients, respectively. A sustained response occurred in 50% of the patients completing treatment and occurred only in patients with genotypes 1, 3, and 6 but not with quasi species.

Teaching Integrative Medicine to Residents: A Focus on Populations Rather Than Individual Patients.

INTRODUCTION: Integrative medicine (IM) is by its very definition patient centric: "It reaffirms the importance of the relationship between practitioner and patient, focuses on the whole person, is informed by evidence, and makes use of all appropriate therapeutic approaches." Best methods for teaching IM in residency have not been well described. METHODS: An IM curriculum for preventive medicine (PM) residents was thoughtfully developed and iteratively revised using Kern's six-step approach. The centerpiece of this curriculum was to have learners work collaboratively within teams on projects that would facilitate IM-focused care within primary care practices. Before embarking on specific IM-related projects, residents immersed themselves within the practices to understand the needs of the community. RESULTS: Forty-eight PM residents have participated in the curriculum in the last 3 years, and 27 unique physician preceptors served as mentors for the projects. Both residents and preceptors enjoyed working on the projects, and both groups considered the work to be a valuable educational pursuit. Common IM content areas covered by the projects dealt with interprofessional collaboration, health promotion, and population-based prevention. Although there were challenges associated with implementation of the projects, overcoming these enhanced the PM residents' confidence and ability to serve as agents of change. CONCLUSIONS: An IM curriculum was successfully incorporated into a PM residency program. The focus on serving the community, or a population health approach, may not be the most common approach in IM, but it worked effectively to enhance the IM knowledge and skills of PM residents.

Plasmablastic transformation of multiple myeloma.

We describe morphological, immunophenotypic, and cytogenetic characterization of a case of multiple myeloma (MM) that showed plasmablastic transformation at the terminal phase with a picture resembling acute leukemia. The plasmablasts expressed monotypic cytoplasmic immunoglobulin together with myeloid and megakaryocytic markers at disease transformation. Conventional cytogenetic study of bone marrow cells showed coexistence of hypodiploid and hyperdiploid cells, with the former being the predominant clone as evidenced by an interphase fluorescence in situ hybridization study. The clinical course in our case shows that plasmablastic transformation should be considered in the differential diagnoses of disease progression in MM. Whether de novo plasmablastic myeloma and plasmablastic transformation can be distinguished as a progression from underlying MM merits further investigation, especially in terms of biologic features and relevance to prognosis.