Background
Human intestinal organoids (HIOs), when transplanted into immunocompromised mice (tHIOs), demonstrate significant growth and maturation. While both male and female mice are reported to be ...viable hosts for these experiments, a direct comparison of sex-related differences in tHIO structure and development has not been performed.
Aims
We sought to identify host sex-related differences in tHIO engraftment, morphology, and epithelial and mesenchymal development.
Methods
HIOs were generated in vitro and transplanted beneath the kidney capsule of NSG male and female mice. tHIOs were harvested at 8–9 weeks. Anthropometric measurements were captured. tHIOs were divided in half and histology or RT-qPCR performed. Morphology was evaluated and epithelial architecture graded on a scale of 1 (absence of crypts/villi) to 4 (elongated crypt-villus axis). RT-qPCR and immunofluorescence microscopy were performed for epithelial and mesenchymal differentiation markers.
Results
Host survival and tHIO engraftment were equivalent in male and female hosts. tHIO weight and length were also equivalent between groups. The number of lumens per tHIOs from male and female hosts was similar, but the mean lumen circumference was larger for tHIOs from male hosts. tHIOs from male hosts were more likely to demonstrate higher grades of epithelial development. However, both groups showed similar differentiation into secretory and absorptive epithelial lineages. Markers for intestinal identity, mesenchymal development, and brush border enzymes were also expressed similarly between groups.
Conclusions
While male host sex was associated with larger tHIO lumen size and mucosal maturation, tHIOs from both groups had similar engraftment, growth, and epithelial and mesenchymal cytodifferentiation.
Bronchopulmonary sequestration (BPS) has long been identified in patients with congenital diaphragmatic hernia (CDH), however the reported incidence in the literature varies widely and is not based ...on large series.
Version 4 of the Congenital Diaphragmatic Hernia Study Group (CDHSG) included questions specifically identifying BPS-associated cases. The data were prospectively collected between 2015 and 2020. Clinical characteristics and outcomes for CDH+BPS patients were compared to patients without BPS using univariate and multiple regression analyses.
Out of 2118 total patients, 72 had a pulmonary sequestration (3.4%). The amount of CDH+BPS with high-risk (CDHSG type C and D) defects was significantly greater than those without BPS (68.0% vs 49.3%, respectively; p = 0.001). The need for ECLS (35/72, 48.6%) and overall mortality (21/72, 29.2%) was significantly higher in CDH+BPS. When corrected for hernia size, cardiac and chromosomal anomalies, the need for ECLS (OR 2.2, p = 0.004) and mortality (OR 2.0, p = 0.015) was significantly greater in CDH+BPS.
This is the largest series to look at the incidence of BPS in children with CDH. They are associated with larger defect sizes, a greater need for ECLS and higher mortality than those patients without BPS.
Patients with acute leukemia refractory to induction or reinduction chemotherapy have poor prognoses if they do not undergo hematopoietic stem-cell transplantation (HSCT). However, HSCT when a ...patient is not in complete remission (CR) is of uncertain benefit. We hypothesized that pretransplantation variables may define subgroups that have a better prognosis.
Overall, 2,255 patients who underwent transplantation for acute leukemia in relapse or with primary induction failure after myeloablative conditioning regimen between 1995 and 2004 were reported to the Center for International Blood and Marrow Transplant Research. The median follow-up of survivors was 61 months. We performed multivariate analysis of pretransplantation variables and developed a predictive scoring system for survival.
The 3-year overall survival (OS) rates were 19% for acute myeloid leukemia (AML) and 16% for acute lymphoblastic leukemia (ALL). For AML, five adverse pretransplantation variables significantly influenced survival: first CR duration less than 6 months, circulating blasts, donor other than HLA-identical sibling, Karnofsky or Lansky score less than 90, and poor-risk cytogenetics. For ALL, survival was worse with the following: first refractory or second or greater relapse, > or = 25% marrow blasts, cytomegalovirus-seropositive donor, and age of 10 years or older. Patients with AML who had a predictive score of 0 had 42% OS at 3 years, whereas OS was 6% for a score > or = 3. Patients with ALL who had a score of 0 or 1 had 46% 3-year OS but only 10% OS rate for a score > or = 3.
Pretransplantation variables delineate subgroups with different outcomes. HSCT during relapse can achieve long-term survival in selected patients with acute leukemia.
Combined Janus kinase 1 (JAK1) and JAK2 inhibition therapy effectively reduces splenomegaly and symptom burden related to myelofibrosis but is associated with dose-dependent anemia and ...thrombocytopenia. In this open-label phase II study, we evaluated the efficacy and safety of three dose levels of INCB039110, a potent and selective oral JAK1 inhibitor, in patients with intermediate- or high-risk myelofibrosis and a platelet count ≥50×10
/L. Of 10, 45, and 32 patients enrolled in the 100 mg twice-daily, 200 mg twice-daily, and 600 mg once-daily cohorts, respectively, 50.0%, 64.4%, and 68.8% completed week 24. A ≥50% reduction in total symptom score was achieved by 35.7% and 28.6% of patients in the 200 mg twice-daily cohort and 32.3% and 35.5% in the 600 mg once-daily cohort at week 12 (primary end point) and 24, respectively. By contrast, two patients (20%) in the 100 mg twice-daily cohort had ≥50% total symptom score reduction at weeks 12 and 24. For the 200 mg twice-daily and 600 mg once-daily cohorts, the median spleen volume reductions at week 12 were 14.2% and 17.4%, respectively. Furthermore, 21/39 (53.8%) patients who required red blood cell transfusions during the 12 weeks preceding treatment initiation achieved a ≥50% reduction in the number of red blood cell units transfused during study weeks 1-24. Only one patient discontinued for grade 3 thrombocytopenia. Non-hematologic adverse events were largely grade 1 or 2; the most common was fatigue. Treatment with INCB039110 resulted in clinically meaningful symptom relief, modest spleen volume reduction, and limited myelosuppression.
There is a known association between Cornelia de Lange syndrome (CdLS) and congenital diaphragmatic hernia (CDH), with CDH being the cause of death in 5%–20% of CdLS cases. We aimed to identify and ...describe patients with CDLS and CDH. We hypothesized that CdLS would be associated with high-risk CDH and poor outcomes.
CDH Study Group patients from 1995 to 2019 were included. Those with CdLS were reviewed retrospectively. Rates of repair and outcomes were compared between patients with and without CdLS.
We identified 9,251 CDH patients. Of those, 21 had confirmed CdLS. CdLS patients had a lower birth weight (2.2±0.57 kg) than non-CdLS patients (2.9±0.64 kg) (p<0.001). 5-min Apgar scores were lower in CdLS patients (6, 4–7) than non-CdLS patients (7, 5–8) (p=0.014). Only 33% of CdLS patients underwent diaphragmatic repair compared to 84.2% of non-CdLS patients (p<0.001). Mortality was 76% for CdLS patients compared with 29% for non-CdLS patients (p<0.001). Of the 7 CdLS patients who underwent repair, 5 survived to hospital discharge.
Infants with CdLS and CDH have a poor prognosis. However, CdLS patients who undergo repair can survive to discharge; therefore, the concomitant diagnosis of CdLS and CDH is not necessarily a contraindication to repair. Early recognition of these anomalies can assist with counseling and prognostication.
Retrospective comparative study
III
•CDH patients with Cornelia de Lange syndrome have a low rate of operative repair.•CDH patients with Cornelia de Lange that are repaired can survive to discharge.•Careful screening for chromosomal abnormalities is critical in CDH patients.•Patients with possible Cornelia de Lange syndrome should be screened for CDH.
Background Surgical site infections (SSIs) are associated with substantial morbidity, mortality, and cost. Few studies have examined the causative pathogens, mortality, and economic burden among ...patients rehospitalized for SSIs. Methods From 2003 to 2007, 8302 patients were readmitted to 97 US hospitals with a culture-confirmed SSI. We analyzed the causative pathogens and their associations with in-hospital mortality, length of stay (LOS), and cost. Results The proportion of methicillin-resistant Staphylococcus aureus (MRSA) significantly increased among culture-positive SSI patients during the study period (16.1% to 20.6%, respectively, P < .0001). MRSA (compared with other) infections had higher raw mortality rates (1.4% vs 0.8%, respectively, P = .03), longer LOS (median, 6 vs 5 days, respectively, P < .0001), and higher hospital costs ($7036 vs $6134, respectively, P < .0001). The MRSA infection risk-adjusted attributable LOS increase was 0.93 days (95% confidence interval CI: 0.65-1.21; P < .0001), and cost increase was $1157 (95% CI: $641-$1644; P < .0001). Other significant independent risk factors increasing cost and LOS included illness severity, transfer from another health care facility, previous admission (<30 days), and other polymicrobial infections ( P < .05). Conclusion SSIs caused by MRSA increased significantly and were independently associated with economic burden. Admission illness severity, transfer from another health care setting, and recent hospitalization were associated with higher mortality, increased LOS, and cost.
Nucleotide-binding site leucine-rich repeat resistance genes (NLRs) allow plants to detect microbial effectors. We hypothesized that NLR expression patterns could reflect organ-specific differences ...in effector challenge and tested this by carrying out a meta-analysis of expression data for 1,235 NLRs from nine plant species. We found stable NLR root/shoot expression ratios within species, suggesting organ-specific hardwiring of NLR expression patterns in anticipation of distinct challenges. Most monocot and dicot plant species preferentially expressed NLRs in roots. In contrast, Brassicaceae species, including oilseed rape (Brassica napus) and the model plant Arabidopsis (Arabidopsis thaliana), were unique in showing NLR expression skewed toward the shoot across multiple phylogenetically distinct groups of NLRs. The Brassicaceae are also outliers in the sense that they have lost the common symbiosis signaling pathway, which enables intracellular infection by root symbionts. While it is unclear if these two events are related, the NLR expression shift identified here suggests that the Brassicaceae may have evolved unique pattern-recognition receptors and antimicrobial root metabolites to substitute for NLR protection. Such innovations in root protection could potentially be exploited in crop rotation schemes or for enhancing root defense systems of non-Brassicaceae crops.
•We evaluated 1,330,095 Enterobacterales urine isolates from US facilities (2018-2020)•Isolates had high rates of resistance to drugs used for urinary tract infections•Geographic variations in ...antibiotic resistance were observed•The East South Central region had the highest rates of antibiotic resistance•In most regions, drug resistance levels exceeded the thresholds for empiric therapy
Antimicrobial resistance (AMR) can complicate effective management of urinary tract infections. We conducted a retrospective study of AMR in Enterobacterales urine isolates from ambulatory and hospitalized adult patients from 2018-2020 (BD Insights Research Database) to evaluate regional differences in isolates with an extended-spectrum beta-lactamase–producing phenotype and those not susceptible to beta-lactams, fluoroquinolone (FQ), nitrofurantoin (NFT), trimethoprim/sulfamethoxazole (TMP/SMX), or multiple antibiotic classes (≥ 2 or ≥ 3). Our analyses included 349,741 Enterobacterales urine isolates from 321 inpatient facilities and 980,354 isolates from 338 ambulatory care facilities. In multivariable analyses, the highest rate of resistance was to beta-lactams (60.8% and 55.8% for inpatient and ambulatory settings, respectively), followed by FQ (27.5%), NFT (27.0%), and TMP/SMX (25.4%) for inpatients and by TMP/SMX (22.4%), FQ (21.6%), and NFT (21.6%) for ambulatory patients. Isolates with an extended-spectrum beta-lactamase–producing phenotype (13.2% and 8.6% for inpatient and ambulatory settings, respectively) and multidrug resistance (inpatient and ambulatory rates of 23.4% and 17.7% for ≥ 2 drugs; 9.9% and 6.4% for ≥ 3 drugs) were also prevalent. Statistically significant differences by geographic region (P ≤ 0.005) were observed for AMR classes in both inpatient and ambulatory settings, but the rates remained above the thresholds recommended for empiric urinary tract infection therapy across most regions.
Purpose
The purpose of this bibliometric and systematic literature review is to survey and evaluate key study’s in tacit knowledge (TK). Through analysing and synthesizing based on the antecedents, ...decisions, outcomes-theories, context and methods (ADO-TCM) framework, this paper highlights research gaps and avenues for future research. It is important to recognize the antecedents, results and theories in the available literature as it offers enough evidence for encouraging the significance of TK.
Design/methodology/approach
This research paper follows a bibliometric analysis and systematic approach in identifying, analyzing and synthesizing pertinent literature in TK. A total of 59 research studies were carefully and systematically reviewed with the help of NVivo12 and excel software to code and analyse.
Findings
With the help of bibliometric analysis and framework-based systematic review, this research paper offers a retrospective view of the TCM framework in the amalgamation with ADO framework, bibliometric analysis and important themes of TK research.
Originality/value
This paper is different from existing reviews as the authors have to combine bibliometric analysis and framework-based systematic review approach to provide a more robust encapsulation of TK research. To the best of the knowledge, the present research is one of the first systematic reviews based on a framework relating to TK.
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