Acute Cholecystitis Is a Common Complication after Allogeneic Stem Cell Transplantation and Is Associated with the Use of Total Parenteral Nutrition

AbstractThe incidence and risk factors for acute cholecystitis after allogeneic hematopoietic stem cell transplantation (HSCT) are not well defined. Of 644 consecutive adult transplants performed at our institution between 2001 and 2011, acute cholecystitis occurred in the first year of transplant in 32 patients (5.0%). We conducted 2 retrospective case-control studies of this population to determine risk factors for cholecystitis after HSCT and to evaluate the performance of different methods of imaging to diagnosis cholecystitis in patients undergoing HSCT compared with non-HSCT patients. In the HSCT population, development of cholecystitis was associated with an increased 1-year overall mortality rate (62.5% versus 19.8%, P < .001). The risk of developing cholecystitis was higher in patients who received total parenteral nutrition (TPN) (adjusted odds ratio, 3.41; P = .009). There was a trend toward more equivocal abdominal ultrasound findings in HSCT recipients with acute cholecystitis compared with nontransplant patients (50.0% versus 30.6%, P = .06). However, hepatobiliary iminodiacetic acid (HIDA) scans were definitively positive for acute cholecystitis in most patients in both populations (80.0% of HSCT recipients versus 77.4% of control subjects, P = .82). In conclusion, acute cholecystitis is a common early complication of HSCT, the risk is increased in patients who receive TPN, and it is associated with high 1-year mortality. In HSCT recipients with findings suggestive of acute cholecystitis, especially those receiving TPN, early use of HIDA scan may be considered over ultrasound

Supplementary File for Capturing wheat phenotypes at the genome level

Supplementary S1: Yield and related traits in bread wheat. Table S1: Examples of genomic regions, candidate and cloned genes for yield and related traits in bread wheat. Supplementary S2: Drought tolerance. Table S2: Examples of genomic regions and candidate genes for drought tolerance. Supplementary S3: Heat tolerance. Table S3. Examples of genomic regions and candidate genes for heat tolerance. Supplementary S4: salinity tolerance in bread wheat. Table S4. Examples of genomic regions and candidate genes for salinity tolerance in bread wheat. Supplementary S5: Frost tolerance. Supplementary S6: Disease resistance. Table S5. Examples of genomic regions, candidate and cloned genes mapped for disease resistance in wheat species. Supplementary S7 insect and mite resistance. Table S6. Examples of genomic regions and candidate genes mapped for insect and mite resistance. Supplementary S8: Quality traits. Table S7. Examples of genomic regions, candidate and cloned genes for quality traits.Recent technological advances in next-generation sequencing (NGS) technologies have dramatically reduced the cost of DNA sequencing, allowing species with large and complex genomes to be sequenced. Although bread wheat (Triticum aestivum L.) is one of the world’s most important food crops, efficient exploitation of molecular marker-assisted breeding approaches has lagged behind that achieved in other crop species, due to its large polyploid genome. However, an international public–private effort spanning 9 years reported over 65% draft genome of bread wheat in 2014, and finally, after more than a decade culminated in the release of a gold-standard, fully annotated reference wheat-genome assembly in 2018. Shortly thereafter, in 2020, the genome of assemblies of additional 15 global wheat accessions was released. As a result, wheat has now entered into the pan-genomic era, where basic resources can be efficiently exploited. Wheat genotyping with a few hundred markers has been replaced by genotyping arrays, capable of characterizing hundreds of wheat lines, using thousands of markers, providing fast, relatively inexpensive, and reliable data for exploitation in wheat breeding. These advances have opened up new opportunities for marker-assisted selection (MAS) and genomic selection (GS) in wheat. Herein, we review the advances and perspectives in wheat genetics and genomics, with a focus on key traits, including grain yield, yield-related traits, end-use quality, and resistance to biotic and abiotic stresses. We also focus on reported candidate genes cloned and linked to traits of interest. Furthermore, we report on the improvement in the aforementioned quantitative traits, through the use of (i) clustered regularly interspaced short-palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated gene-editing and (ii) positional cloning methods, and of genomic selection. Finally, we examine the utilization of genomics for the next-generation wheat breeding, providing a practical example of using in silico bioinformatics tools that are based on the wheat reference-genome sequence.Peer reviewe

Multicenter study of the validity and reliability of subjective global assessment in the hemodialysis population.

ObjectiveSubjective Global Assessment (SGA) is a nutrition assessment tool recommended by the 2000 NKF K/DOQI Nutrition Guidelines. However, the validity and reliability of this tool have not been established in hemodialysis (HD) patients. The purpose of this observational study was to determine the reliability and validity of SGA in the HD population. Renal dietitians (RD) were recruited to perform SGA (7-point scale version) and collect data on demographics, clinical status, biochemistries, dietary intake, and quality of life (Medical Outcomes Short Form-36) on 3 HD patients at baseline and 6 months later.DesignThe 54 participating RDs were trained to perform SGA and collect data via a website created for this study. Interrater reliability for SGA was tested in a subset of 76 patients, via an SGA performed by a second RD at baseline, while intrarater reliability was assessed by the original RD repeating the SGA at 1 month. Data collection occurred at HD facilities in the United States (109 patients), Canada (35 patients), and New Zealand (9 patients).ResultsOf the 153 patients, 46% were female, 64% were Caucasian, 6% were Hispanic, 21% were African American, and 6% were Asian. The primary etiologies were hypertension (33%), type 2 diabetes mellitus (DM) (27%), type 1 DM (10%), and glomerular nephritis (10%); 59% had cardiovascular disease. The mean age, body mass index (BMI), serum albumin, and duration on HD were 64 +/- 14 years (mean +/- SD), 28 +/- 7 kg/m(2), 3.7 +/- 0.4 mg/dL, and 41 +/- 34 months, respectively. SGA scores were well nourished (7)-30%; mildly malnourished (MN 6)-41%; moderately MN 5-21%, 4-7%, and 3-2%; and severely MN (2 and 1)-0%. SGA training via the Internet achieved fair interrater reliability (weighted Kappa = 0.5, Spearman's Rho = 0.7) and substantial intrarater reliability (weighted Kappa = 0.7, Spearman's Rho = 0.8) (P &lt; .001). Validity was demonstrated through statistically significant differences in mean BMI and serum albumin across the 5 categories of SGA (7-28 +/- 7, 6-29 +/- 7, 5-28 +/- 8, 4-21 +/- 4, 3-24 +/- 2, P &lt; .05; and 7-3.8 +/- 0.3, 6-3.8 +/- 0.4, 5-37 +/- 0.05, 4-3.4 +/- 0.07, 3-2.9 +/- 1.2, P &lt; .001, respectively). Nutritional status varied by age (P &lt; .05), but not ethnicity or nationality.ConclusionWe conclude that the 7-point scale SGA is a reliable and valid tool for nutritional assessment in adults on HD

Statistical assessment of normal mitral annular geometry using automated three-dimensional echocardiographic analysis.

BACKGROUND: The basis of mitral annuloplasty ring design has progressed from qualitative surgical intuition to experimental and theoretical analysis of annular geometry with quantitative imaging techniques. In this work, we present an automated three-dimensional (3D) echocardiographic image analysis method that can be used to statistically assess variability in normal mitral annular geometry to support advancement in annuloplasty ring design. METHODS: Three-dimensional patient-specific models of the mitral annulus were automatically generated from 3D echocardiographic images acquired from subjects with normal mitral valve structure and function. Geometric annular measurements including annular circumference, annular height, septolateral diameter, intercommissural width, and the annular height to intercommissural width ratio were automatically calculated. A mean 3D annular contour was computed, and principal component analysis was used to evaluate variability in normal annular shape. RESULTS: The following mean ± standard deviations were obtained from 3D echocardiographic image analysis: annular circumference, 107.0 ± 14.6 mm; annular height, 7.6 ± 2.8 mm; septolateral diameter, 28.5 ± 3.7 mm; intercommissural width, 33.0 ± 5.3 mm; and annular height to intercommissural width ratio, 22.7% ± 6.9%. Principal component analysis indicated that shape variability was primarily related to overall annular size, with more subtle variation in the skewness and height of the anterior annular peak, independent of annular diameter. CONCLUSIONS: Patient-specific 3D echocardiographic-based modeling of the human mitral valve enables statistical analysis of physiologically normal mitral annular geometry. The tool can potentially lead to the development of a new generation of annuloplasty rings that restore the diseased mitral valve annulus back to a truly normal geometry

Three-dimensional ultrasound-derived physical mitral valve modeling.

PURPOSE: Advances in mitral valve repair and adoption have been partly attributed to improvements in echocardiographic imaging technology. To educate and guide repair surgery further, we have developed a methodology for fast production of physical models of the valve using novel three-dimensional (3D) echocardiographic imaging software in combination with stereolithographic printing. DESCRIPTION: Quantitative virtual mitral valve shape models were developed from 3D transesophageal echocardiographic images using software based on semiautomated image segmentation and continuous medial representation algorithms. These quantitative virtual shape models were then used as input to a commercially available stereolithographic printer to generate a physical model of the each valve at end systole and end diastole. EVALUATION: Physical models of normal and diseased valves (ischemic mitral regurgitation and myxomatous degeneration) were constructed. There was good correspondence between the virtual shape models and physical models. CONCLUSIONS: It was feasible to create a physical model of mitral valve geometry under normal, ischemic, and myxomatous valve conditions using 3D printing of 3D echocardiographic data. Printed valves have the potential to guide surgical therapy for mitral valve disease

Lisocabtagene maraleucel (liso-cel) for treatment of second-line (2L) transplant noneligible (TNE) relapsed/refractory (R/R) aggressive large B-cell non-Hodgkin lymphoma (NHL): Updated results from the PILOT study.

Background: Patients (pts) with aggressive large B-cell NHL who are R/R after first-line immunochemotherapy and not eligible for high-dose chemotherapy and HSCT have a poor prognosis and no established standard of care. The ongoing, open-label phase 2 PILOT study is the first to assess the safety and efficacy of liso-cel, an investigational, CD19-directed, defined composition, 4-1BB CAR T cell product infused at equal target doses of CD8+ and CD4+ CAR+ T cells, as 2L therapy in TNE pts (NCT03483103). Methods: Eligible pts had aggressive R/R diffuse large B-cell lymphoma NOS (de novo or transformed follicular lymphoma [FL]), high-grade B-cell lymphoma, or FL grade 3B with 1 line of prior therapy containing an anthracycline and anti-CD20 agent. Pts were deemed TNE by meeting ≥1 criteria: age ≥70 y, ECOG PS 2, or impaired organ function (DLCO ≤60% [but SaO2 ≥92% and CTCAE ≤1 dyspnea], LVEF ≥40% to \u3c 50%, creatinine clearance \u3e 30 to \u3c 60 mL/min, or AST/ALT \u3e 2 to ≤5 × ULN). Liso-cel (100 × 106 CAR+ T cells) was administered 2–7 days after lymphodepletion (LD) with fludarabine/cyclophosphamide. The primary endpoint is ORR; key secondary endpoints are AEs and CR rate. Results: At data cutoff, 25 pts had LD followed by liso-cel infusion. Pt characteristics are summarized in the Table. Overall, 48% (n = 12) had high tumor burden and 48% were primary refractory. 18/25 (72%) pts had grade ≥3 treatment-emergent AEs, 40% of which were cytopenias. No grade 5 AEs occurred within the first 30 days after liso-cel. Five pts (20%) had cytokine release syndrome (CRS) and 3 (12%) had neurological events (NEs). No grade 3/4 CRS was observed; 2 pts (8%) had grade 3/4 NEs. Five pts (20%) received tocilizumab and/or dexamethasone for CRS/NEs. At a median follow-up of 3.5 mo, the ORR was 80% (95% CI, 59–93; n = 20); 48% of pts (n = 12) achieved CR. Conclusions: These interim data suggest that elderly and/or comorbid pts with R/R aggressive large B-cell NHL, who are not eligible for high-dose chemotherapy and HSCT, can receive 2L liso-cel with similar safety and efficacy to 3L+ pts as previously reported (Abramson, ASH 2019 #241). Updated data with longer follow-up will be presented. Clinical trial information: NCT03483103

Three-dimensional ultrasound-derived physical mitral valve modeling.

PurposeAdvances in mitral valve repair and adoption have been partly attributed to improvements in echocardiographic imaging technology. To educate and guide repair surgery further, we have developed a methodology for fast production of physical models of the valve using novel three-dimensional (3D) echocardiographic imaging software in combination with stereolithographic printing.DescriptionQuantitative virtual mitral valve shape models were developed from 3D transesophageal echocardiographic images using software based on semiautomated image segmentation and continuous medial representation algorithms. These quantitative virtual shape models were then used as input to a commercially available stereolithographic printer to generate a physical model of the each valve at end systole and end diastole.EvaluationPhysical models of normal and diseased valves (ischemic mitral regurgitation and myxomatous degeneration) were constructed. There was good correspondence between the virtual shape models and physical models.ConclusionsIt was feasible to create a physical model of mitral valve geometry under normal, ischemic, and myxomatous valve conditions using 3D printing of 3D echocardiographic data. Printed valves have the potential to guide surgical therapy for mitral valve disease