Validation of a Hematopoietic Cell Transplant-Composite Risk (HCT-CR) Model for Post-Transplant Survival Prediction in Patients with Hematologic Malignancies.

PURPOSE: Allogeneic hematopoietic stem cell transplantation (AHCT) outcomes depend on disease and patient characteristics. We previously developed a novel prognostic model, hematopoietic cell transplant composite-risk (HCT-CR) by incorporating the refined disease risk index (DRI-R) and hematopoietic cell transplant-comorbidity/age index (HCT-CI/Age) to predict post-transplant survival in patients with acute myeloid leukemia and myelodysplastic syndrome. Here we aimed to validate and prove the generalizability of the HCT-CR model in an independent cohort of patients with hematologic malignancies receiving AHCT. EXPERIMENTAL DESIGN: Data of consecutive adult patients receiving AHCT for various hematologic malignancies were analyzed. Patients were stratified into four HCT-CR risk groups. The discrimination, calibration performance, and clinical net benefit of the HCT-CR model were tested. RESULTS: The HCT-CR model stratified patients into four risk groups with significantly different overall survival (OS). Three-year OS was 67.4%, 50%, 37.5%, and 29.9% for low, intermediate, high, and very high-risk group, respectively (P < 0.001). The HCT-CR model had better discrimination on OS prediction when compared with the DRI-R and HCT-CI/Age (C-index was 0.69 vs. 0.59 and 0.56, respectively, P < 0.001). The decision curve analysis showed that HCT-CR model provided better clinical utility for patient selection for post-transplant clinical trial than the "treat all" or "treat none" strategy and the use of the DRI-R and HCT-CI/Age model separately. CONCLUSIONS: The HCT-CR can be effectively used to predict post-transplant survival in patients with various hematologic malignancies. This composite model can identify patients who will benefit the most from transplantation and helps physicians in making decisions regarding post-transplant therapy to improve outcomes.

Outcome of Multiple Myeloma with Chromosome 1q Gain and 1p Deletion after Autologous Hematopoietic Stem Cell Transplantation: Propensity Score Matched Analysis.

The gain/amplification CKS1B gene at chromosome region 1q21 (1q+) is one of the most common genetic aberrations in multiple myeloma (MM). Amplification of CKS1B is frequently associated with the deletion of the CDKN2C gene at chromosome region 1p32 (1p-), which is also associated with inferior outcomes. In this retrospective study, we evaluated the outcomes of patients with 1q+ and/or 1p- after high-dose therapy and autologous hematopoietic cell transplantation (auto-HCT). From January 2006 to December 2015, 1491 newly diagnosed patients with MM underwent upfront high-dose therapy and auto-HCT at our institution. Of those, 899 had the fluorescent in situ hybridization (FISH) data available. FISH was performed at diagnosis and before the start of induction in 686 (76%) patients and after the initiation of induction therapy in 213 (24%) patients. We identified 100 patients with 1q+ and/or 1p- by FISH from the cohort of 899 patients. A control group (n = 287) with diploid cytogenetics and normal FISH panel was selected from the same cohort. From the above 2 cohorts, using a propensity score matched analysis, we identified matched controls for 85 of the 100 patients with 1q+/1p-. Patients were matched for age at auto-HCT, sex, International Staging System stage, induction regimen, creatinine level, disease status at auto-HCT, conditioning regimen, and maintenance therapy. Sixty-seven (79%), 4 (5%), and 14 (16%) patients had 1q+, 1p-, or both 1q+ and 1p-, respectively. There was no significant difference in induction therapy, preparative regimen, or maintenance therapy between the 1q+/1p- and the control group. The median follow-up time for all patients was 29.2 months (range, 0.29 to 84.96). The cumulative incidence of 100-day nonrelapse mortality was 1.2% and 0% for the 1q+/1p- and the control group, respectively. Forty-two patients (50%) in the 1q+/1p- group achieved complete response compared with 40 patients (47%) in the control group. The estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 41% and 79% for the 1q+/1p- group and 56% and 86% for the control group. Patients in the 1q+/1p- group were at significantly increased risk of progression or death compared to the control group (hazard ratio [HR], 2.21; confidence interval [CI], 1.18 to 4.16; P = .014). No significant association between OS in the 2 groups was observed. The outcome of the 1q+/1p- alone (with no additional high-risk cytogenetics) and the propensity score matched control groups was also compared. Median PFS for the 1q+/1p- alone subgroup was 26.6 months, compared with 38.8 months for the control group (HR, 1.9; CI, 0.9 to 4.08; P = .09). The median OS had not been reached for the 1q+/1p- alone subgroup and was 81.1 months for the control group (HR, 1.25; CI, 0.3 to 4.6; P= .73). 1q+/1p- abnormalities with amplification of CKS1B and deletion ofCDKN2Cgenes were associated with shorter PFS compared with a propensity score matched group of patients with diploid cytogenetics and normal a FISH panel. The outcomes of 1q+/1p- patients with MM have improved with the use of more effective induction, conditioning, and maintenance therapy compared with historical controls, but we still need more effective therapeutic approaches to fully overcome the negative impact of 1q+/1p-.

Novel Disease Risk Model for Patients with Acute Myeloid Leukemia Receiving Allogeneic Hematopoietic Cell Transplantation.

Molecular data and minimal residual disease (MRD) have been shown to influence outcomes in acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic cell transplantation (AHCT). Here we developed and validated a novel AML-specific disease risk group (AML-DRG) and revised our previously developed hematopoietic cell transplant-composite risk (HCT-CR) model by incorporating molecular data and MRD status to predict outcomes of patients with AML. The study included 1414 consecutively treated adult AML patients who received a first AHCT. Patients were randomly assigned into training (n = 944) and validation (n = 470) sets. To develop the AML-DRG model, the coefficient of all significant AML-related variables in multivariable Cox regression analysis in a training dataset was converted into scores, whereas the AML-HCT-CR was the sum of disease-related factors assessed by the AML-DRG model with the addition of weighted scores from patient-related factors. The AML-DRG was developed by assigning the following scores: 1 point to secondary AML, 1 point to the European LeukaemiaNet adverse genetic risk, 2 points to complete remission with MRD positive/unknown, and 4 points to active disease. These scores were used to generate 3 risk groups of the AML-DRG with significantly different overall survivals. By adding the score for significant patient-related factors (HCT-specific comorbidity index/age), we created 4 risk groups of AML-HCT-CR with distinct survival outcomes. Both the AML-DRG and AML-HCT-CR provided significantly better discriminative capacity compared with the disease risk index, European LeukaemiaNet genetic risk model, and cytogenetic risk model. Prognostic models incorporating molecular data and MRD status allow better stratification and improved survival estimates of AML patients post-transplant.

Aberrant arc between the common hepatic artery and a replaced right hepatic artery resulting in misperfusion in a patient with a hepatic arterial infusion pump.

Hepatic arterial infusion pumps are increasingly utilized as an option for liver directed therapy in the treatment of metastatic colorectal carcinoma. After skeletonization of the hepatic artery through the ligation of extra-hepatic branches, these pumps are implanted surgically with their tip placed in the common hepatic artery. Subsequently, a nuclear medicine pump study is performed to ensure homogeneous perfusion of the liver and detect any extrahepatic perfusion. We report a peripheral arc between the superior mesenteric artery and celiac axis, which caused misperfusion on the SPECT nuclear medicine scan.

Diffusion Tensor Imaging of the Superior Thalamic Radiation and Cerebrospinal Fluid Distribution in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND AND PURPOSE: Ventricular enlargement in elderly raises a challenging differential diagnosis to physicians. While Alzheimer's disease is the most common form of dementia, idiopathic normal pressure hydrocephalus (iNPH) constitutes a potentially reversible syndrome. iNPH has a unique pathophysiology pertaining to cerebrospinal fluid (CSF) dynamics and periventricular white matter. We aimed to determine the effects of iNPH on periventricular white matter bundles and to further characterize its ventricular and sulcal CSF distribution by using diffusion tensor tractography (DTT) and CSF volumetrics on high resolution T1-weighted magnetic resonance imaging data. METHODS: Deterministic DTT and validated volumetric parcellation were performed on 20 healthy elderly, 13 Alzheimer's disease (AD), and 9 iNPH patients. The superior thalamic radiation, corticospinal tract, and dentatorubrothalamic tract were traced and quantified using DTI studio software. Cloud-based volumetric parcellation was also performed on 138 healthy subjects across the lifespan, 13 AD, and 9 iNPH-patients. Ventricular and sulcal CSF volumes in the three groups were compared. RESULTS: Combining increased mean diffusivity of the superior thalamic radiation with ventricular volume resulted in clear separation of iNPH from the AD and age-matched healthy subject groups. Additionally, ventricular to sulcal CSF ratio, utilizing fully automated methods, was significantly greater in the iNPH patients compared to AD and healthy age-matched controls. CONCLUSIONS: Combined microstructural (DTT) and macrostructural (ventricular volume) changes is a promising radiological approach in studying ventriculomegaly. Automated estimation of the disproportionate ventricular and sulcal CSF ratio in patients presenting with ventriculomegaly may be important as radiologic markers in differentiating iNPH from other causes of ventriculomegaly.

A novel combined interventional radiologic and hepatobiliary surgical approach to a complex traumatic hilar biliary stricture.

INTRODUCTION: Benign strictures of the biliary system are challenging and uncommon conditions requiring a multidisciplinary team for appropriate management. PRESENTATION OF CASE: The patient is a 32-year-old male that developed a hilar stricture as sequelae of a gunshot wound. Due to the complex nature of the stricture and scarring at the porta hepatis a combined interventional radiologic and surgical approach was carried out to approach the hilum of the right and left hepatic ducts. The location of this stricture was found by ultrasound guidance intraoperatively using a balloon tipped catheter placed under fluoroscopy in the interventional radiology suite prior to surgery. This allowed the surgeons to select the line of parenchymal transection for best visualization of the stricture. A left hepatectomy was performed, the internal stent located and the right hepatic duct opened tangentially to allow a side-to-side Roux-en-Y hepaticojejunostomy (a Puestow-like anastomosis). DISCUSSION: Injury to the intrahepatic biliary ductal confluence is rarely fatal, however, the associated injuries lead to severe morbidity as seen in this example. Management of these injuries poses a considerable challenge to the surgeon and treating physicians. CONCLUSION: Here we describe an innovative multi-disciplinary approach to the repair of this rare injury.

Bronchoscopy Education: An Experiential Learning Theory Perspective.

Bronchoscopy programs implementing the experiential learning model address different learning styles. Problem-based learning improves knowledge retention, critical decision making, and communication. These modalities are preferred by learners and contribute to their engagement, in turn leading to durable learning. Follow-up after live events is warranted through spaced education strategies. The objectives of this article are to (1) summarize and illustrate the implementation of experiential learning theory for bronchoscopy courses, (2) discuss the flipped classroom model and problem-based learning, (3) illustrate bronchoscopy checklists implementation in simulation, and (4) discuss the importance of feedback and spaced learning for bronchoscopy education programs.

Assessment of the Albumin-Bilirubin (ALBI) Grade as a Prognostic Indicator for Hepatocellular Carcinoma Patients Treated With Radioembolization.

OBJECTIVE: As the utility of Child-Pugh (C-P) class is limited by the subjectivity of ascites and encephalopathy, we evaluated a previously established objective method, the albumin-bilirubin (ALBI) grade, as a prognosticator for yttrium-90 radioembolization (RE) treatment for patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 117 patients who received RE for HCC from 2 academic centers were reviewed and stratified by ALBI grade, C-P class, and Barcelona Clinic Liver Cancer stage. The overall survival (OS) according to these 3 criteria was evaluated by Kaplan-Meier survival analysis. The utilities of C-P class and ALBI grade as prognostic indicators were compared using the log-rank test. Multivariate Cox regression analysis was performed to identify additional predictive factors. RESULTS: Patients with ALBI grade 1 (n=49) had superior OS than those with ALBI grade 2 (n=65) (P=0.01). Meanwhile, no significant difference was observed in OS between C-P class A (n=100) and C-P class B (n=14) (P=0.11). For C-P class A patients, the ALBI grade (1 vs. 2) was able to stratify 2 clear and nonoverlapping subgroups with differing OS curves (P=0.03). Multivariate Cox regression test identified alanine transaminase, Barcelona Clinic Liver Cancer stage, and ALBI grade as the strongest prognostic factors for OS (P<0.10). CONCLUSIONS: ALBI grade as a prognosticator has demonstrated clear survival discrimination that is superior to C-P class among HCC patients treated with RE, particularly within the subgroup of C-P class A patients. ALBI grade is useful for clinicians to make decisions as to whether RE should be recommended to patients with HCC.

High expression of LMO2 predicts a favorable outcome in adult patients with BCR/ABL negative B-cell acute lymphoblastic leukemia.

The LIM domain only protein 2 (LMO2) is a key regulator of hematopoietic stem cell development. Expression of LMO2 has been evaluated in B-cell lymphoma, T-cell acute lymphoblastic leukemia and acute myeloid leukemia; however, information concerning its role in breakpoint cluster region/Abelson murine leukemia viral oncogene homolog 1 (BCR/ABL) negative B-cell acute lymphoblastic leukemia (B-ALL) remains limited. The present study investigated LMO2 expression using quantitative polymerase chain reaction in 85 adult patients with BCR/ABL negative B-ALL, and associated the expression of LMO2 with established prognostic factors. LMO2 expression levels in patients with BCR/ABL negative B-ALL was not significantly different compared with control individuals (P=0.25). However, LMO2 expression levels were associated with the immunophenotypical features of the patients; a high LMO2 expression was associated with a higher incidence of complete remission (P=0.03) and lower rate of relapse (P=0.01), and patients with a high LMO2 expression had a significantly improved overall survival rate (P=0.01) and disease-free survival (P=0.01). The present results suggest that LMO2 expression is a favorable prognostic marker in adult patients with BCR/ABL negative B-ALL and may be used as a diagnostic marker and therapeutic target. However, additional studies regarding its prognostic role in patients with BCR/ABL negative B-ALL are required.

Diagnostic error in medicine: analysis of 583 physician-reported errors.

BACKGROUND: Missed or delayed diagnoses are a common but understudied area in patient safety research. To better understand the types, causes, and prevention of such errors, we surveyed clinicians to solicit perceived cases of missed and delayed diagnoses. METHODS: A 6-item written survey was administered at 20 grand rounds presentations across the United States and by mail at 2 collaborating institutions. Respondents were asked to report 3 cases of diagnostic errors and to describe their perceived causes, seriousness, and frequency. RESULTS: A total of 669 cases were reported by 310 clinicians from 22 institutions. After cases without diagnostic errors or lacking sufficient details were excluded, 583 remained. Of these, 162 errors (28%) were rated as major, 241 (41%) as moderate, and 180 (31%) as minor or insignificant. The most common missed or delayed diagnoses were pulmonary embolism (26 cases [4.5% of total]), drug reactions or overdose (26 cases [4.5%]), lung cancer (23 cases [3.9%]), colorectal cancer (19 cases [3.3%]), acute coronary syndrome (18 cases [3.1%]), breast cancer (18 cases [3.1%]), and stroke (15 cases [2.6%]). Errors occurred most frequently in the testing phase (failure to order, report, and follow-up laboratory results) (44%), followed by clinician assessment errors (failure to consider and overweighing competing diagnosis) (32%), history taking (10%), physical examination (10%), and referral or consultation errors and delays (3%). CONCLUSIONS: Physicians readily recalled multiple cases of diagnostic errors and were willing to share their experiences. Using a new taxonomy tool and aggregating cases by diagnosis and error type revealed patterns of diagnostic failures that suggested areas for improvement. Systematic solicitation and analysis of such errors can identify potential preventive strategies.