The influence of diagnosis on outcomes after reverse shoulder arthroplasty (RSA) is not completely understood. The purpose of this study was to compare clinical outcomes of different pathologies.
A ...total of 699 RSAs were performed for the following diagnoses: (1) rotator cuff tear arthropathy (RCA), (2) massive cuff tear (MCT) with osteoarthritis (OA), (3) MCT without OA, (4) OA, (5) acute proximal humeral fracture, (6) malunion, (7) nonunion, and (8) inflammatory arthropathy. All patients had minimum 2-year clinical follow-up (mean, 47 months; range, 24-155 months). Range of motion, Simple Shoulder Test scores, American Shoulder and Elbow Surgeons scores, visual analog scale scores for function, and health-related quality-of-life measures were obtained preoperatively and postoperatively.
The RCA, MCT-with-OA, MCT-without-OA, and OA groups all exhibited significant improvements in all outcome scores and in all planes of motion from preoperatively until a minimum of 2 years postoperatively. The malunion, nonunion, and inflammatory arthropathy groups showed improvements in American Shoulder and Elbow Surgeons scores, Simple Shoulder Test scores, forward flexion, and abduction. The average changes for all other outcomes and planes of motions were also positive but did not reach statistical significance. After adjustment for age and compared with RCA, female patients with malunion had significantly poorer forward flexion (P < .05), those with OA had significantly better abduction (P < .05), and those with fractures had significantly worse patient satisfaction (P < .05). Among male patients, those with MCTs without OA had significantly worse satisfaction (P < .05).
RSA reliably provides improvement regardless of preoperative diagnosis. Although subtle differences exist between male and female patients, improvements in clinical outcome scores were apparent after RSA.
A major hurdle in the study of rare tumors is a lack of existing preclinical models. Neuroendocrine prostate cancer is an uncommon and aggressive histologic variant of prostate cancer that may arise ...de novo or as a mechanism of treatment resistance in patients with pre-existing castration-resistant prostate cancer. There are few available models to study neuroendocrine prostate cancer. Here, we report the generation and characterization of tumor organoids derived from needle biopsies of metastatic lesions from four patients. We demonstrate genomic, transcriptomic, and epigenomic concordance between organoids and their corresponding patient tumors. We utilize these organoids to understand the biologic role of the epigenetic modifier EZH2 in driving molecular programs associated with neuroendocrine prostate cancer progression. High-throughput organoid drug screening nominated single agents and drug combinations suggesting repurposing opportunities. This proof of principle study represents a strategy for the study of rare cancer phenotypes.
Abstract Blood loss at the site of a wound in mammals is curtailed by the rapid formation of a hemostatic plug, i.e., a self-assembled network of the protein, fibrin that locally transforms liquid ...blood into a gelled clot. Here, we report an amphiphilic biopolymer that exhibits a similar ability to rapidly gel blood; moreover, the self-assembly underlying the gelation readily allows for reversibility back into the liquid state via introduction of a sugar-based supramolecule. The biopolymer is a hydrophobically modified (hm) derivative of the polysaccharide, chitosan. When hm-chitosan is contacted with heparinized human blood, it rapidly transforms the liquid into an elastic gel. In contrast, the native chitosan (without hydrophobes) does not gel blood. Gelation occurs because the hydrophobes on hm-chitosan insert into the membranes of blood cells and thereby connect the cells into a sample-spanning network. Gelation is reversed by the addition of α-cyclodextrin, a supramolecule having an inner hydrophobic pocket: polymer hydrophobes unbind from blood cells and embed within the cyclodextrins, thereby disrupting the cell network. We believe that hm-chitosan has the potential to serve as an effective, yet low-cost hemostatic dressing for use by trauma centers and the military. Preliminary tests with small and large animal injury models show its increased efficacy at achieving hemostasis – e.g., a 90% reduction in bleeding time over controls for femoral vein transections in a rat model.
Background
The utility of sodium‐glucose cotransporter 2 inhibitors (SGLT2i) has not been reported in insulin‐treated diabetic dogs.
Hypothesis
Canagliflozin, a PO‐administered SGLT2i, decreases ...interstitial glucose concentration (IG) in insulin‐treated diabetic dogs.
Animals
Five insulin‐treated diabetic dogs.
Methods
Uncontrolled open label longitudinal study. Canagliflozin (2‐4 mg/kg/day PO) was added to an unchanged insulin dose for 7 days. Fractional excretion of glucose was calculated by dividing the product of urine glucose and serum creatinine concentrations by the product of serum glucose and urine creatinine concentrations. Hypoglycemia was defined as IG <60 mg/dL.
Results
Median IG in 2869 measurements obtained while dogs were treated with insulin and canagliflozin was 87 mg/dL (range, 40‐500 mg/dL) and was significantly lower than median IG in 1426 measurements obtained while dogs were treated with insulin alone (212 mg/dL; range, 41‐500 mg/dL; P < .001). Median fractional excretion of glucose when dogs were treated with insulin and canagliflozin was 1.1% (range, 0.9%‐2.0%), significantly higher than when dogs were treated with insulin alone (0.3%; range, 0.01%‐1.0%; P = .04). The frequency of hypoglycemia was higher in dogs treated with insulin and canagliflozin (544 of 2869 IG measurements, 19%) compared with the frequency of hypoglycemia in dogs treated with insulin alone (52 of 1426 IG measurements, 4%; P < .001).
Conclusions and Clinical Importance
Canagliflozin may have a role in improving glycemic control in insulin‐treated diabetic dogs, but the dose of insulin should be decreased when adding canagliflozin to insulin treatment.
Most patients with chronic lymphocytic leukemia (CLL) are diagnosed with early-stage disease and managed with active surveillance. The individual course of patients with early-stage CLL is ...heterogeneous, and their probability of needing treatment is hardly anticipated at diagnosis. We aimed at developing an international prognostic score to predict time to first treatment (TTFT) in patients with CLL with early, asymptomatic disease (International Prognostic Score for Early-stage CLL IPS-E). Individual patient data from 11 international cohorts of patients with early-stage CLL (n = 4933) were analyzed to build and validate the prognostic score. Three covariates were consistently and independently correlated with TTFT: unmutated immunoglobulin heavy variable gene (IGHV), absolute lymphocyte count higher than 15 × 109/L, and presence of palpable lymph nodes. The IPS-E was the sum of the covariates (1 point each), and separated low-risk (score 0), intermediate-risk (score 1), and high-risk (score 2-3) patients showing a distinct TTFT. The score accuracy was validated in 9 cohorts staged by the Binet system and 1 cohort staged by the Rai system. The C-index was 0.74 in the training series and 0.70 in the aggregate of validation series. By meta-analysis of the training and validation cohorts, the 5-year cumulative risk for treatment start was 8.4%, 28.4%, and 61.2% among low-risk, intermediate-risk, and high-risk patients, respectively. The IPS-E is a simple and robust prognostic model that predicts the likelihood of treatment requirement in patients with early-stage CLL. The IPS-E can be useful in clinical management and in the design of early intervention clinical trials.
•IPS-E is a simple and robust prognostic model for early-stage CLL.•IPS-E can be helpful in patients' counseling and design of clinical trials.
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Abstract
We present a four-step group-finding algorithm for the Gas in Galaxy Groups (G3) initiative, a spin-off of the
z
∼ 0 REsolved Spectroscopy Of a Local VolumE (RESOLVE) and Environmental ...COntext (ECO) surveys. In preparation for future comparisons to intermediate redshift (e.g., the LADUMA survey), we design the group finder to adapt to incomplete, shallow, or nonuniform data. We use mock catalogs to optimize the group finder’s performance. Compared to friends-of-friends (with false-pair splitting), the G3 algorithm offers improved completeness and halo-mass recovery with minimal loss of purity. Combining it with the volume-limited H
i
census data for RESOLVE and ECO, we examine the H
i
content of galaxy groups as a function of group halo mass. Group-integrated H
i
mass
M
H I,grp
rises monotonically over halo masses
M
halo
∼ 10
11
–10
14.5
M
⊙
, pivoting in slope at
M
halo
∼ 10
11.4
M
⊙
, the gas-richness threshold scale. We present the first measurement of the scatter in this relation, which has a median of ∼0.3 dex and is asymmetric toward lower
M
H I,grp
. We discuss interesting tensions with theoretical predictions and prior measurements of the
M
H I,grp
–
M
halo
relation. In an appendix, we release RESOLVE DR4 and ECO DR3, including updates to survey redshifts, photometry, and group catalogs, as well as a major expansion of the ECO H
i
inventory with value-added data products.
The purpose of this study was to report on the clinical outcomes of patients undergoing revision reverse shoulder arthroplasty (RSA) by the cement-within-cement technique, as well as to identify ...whether surgical technique can affect subsequent humeral loosening.
In 98 patients, cemented humeral components that were revised to RSA using the cement-within-cement technique were identified and included in this study. We compared 8 patients in whom humeral stem loosening developed with 90 patients whose stem remained fixed. Preoperative and postoperative radiographs of each patient were downloaded in DICOM (Digital Imaging and Communications in Medicine) format and analyzed in Mimics. The total area of the cement mantle (in square millimeters) and of the stem (in square millimeters), as visualized on 2-dimensional plain films, was measured in each subject on both preoperative and postoperative radiographs. Outcomes at a minimum of 2 years of follow-up were analyzed.
Clinical outcomes were available in 57 patients, with a mean follow-up period of 54 months (range, 21-156 months). Patients demonstrated significantly improved functional outcome scores and shoulder range of motion. In the group without loosening, the mean increase in the cement mantle area was 4380 ± 12701 mm2 (P < .0001). In the group with loosening, the mean increase in the cement mantle area was only 811 ± 4014 mm2 (P = .484).
Use of the cement-within-cement technique for fixation of the humeral component in revision RSA is effective in improving functional outcome scores and shoulder range of motion. Furthermore, these findings suggest that efforts to maximize the cement volume during reimplantation may lessen the chance of humeral stem loosening requiring additional revision.
There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we ...present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.
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•Comprehensive molecular analysis of 333 primary prostate carcinomas•Seven subtypes defined by ETS fusions or mutations in SPOP, FOXA1, and IDH1•Substantial epigenetic heterogeneity, including a hypermethylated IDH1 mutant subset•Presumed actionable lesions in the PI3K, MAPK, and DNA repair pathways
Molecular analysis of 333 primary prostate carcinomas reveals substantial heterogeneity and major subtypes among patients, as well as potentially actionable lesions valuable for clinical management of the disease.
In the Systolic Blood Pressure Intervention Trial (SPRINT), adults at high risk for cardiovascular disease who received intensive systolic blood-pressure control (target, <120 mm Hg) had ...significantly lower rates of death and cardiovascular disease events than did those who received standard control (target, <140 mm Hg). On the basis of these data, we wanted to determine the lifetime health benefits and health care costs associated with intensive control versus standard control.
We used a microsimulation model to apply SPRINT treatment effects and health care costs from national sources to a hypothetical cohort of SPRINT-eligible adults. The model projected lifetime costs of treatment and monitoring in patients with hypertension, cardiovascular disease events and subsequent treatment costs, treatment-related risks of serious adverse events and subsequent costs, and quality-adjusted life-years (QALYs) for intensive control versus standard control of systolic blood pressure.
We determined that the mean number of QALYs would be 0.27 higher among patients who received intensive control than among those who received standard control and would cost approximately $47,000 more per QALY gained if there were a reduction in adherence and treatment effects after 5 years; the cost would be approximately $28,000 more per QALY gained if the treatment effects persisted for the remaining lifetime of the patient. Most simulation results indicated that intensive treatment would be cost-effective (51 to 79% below the willingness-to-pay threshold of $50,000 per QALY and 76 to 93% below the threshold of $100,000 per QALY), regardless of whether treatment effects were reduced after 5 years or persisted for the remaining lifetime.
In this simulation study, intensive systolic blood-pressure control prevented cardiovascular disease events and prolonged life and did so at levels below common willingness-to-pay thresholds per QALY, regardless of whether benefits were reduced after 5 years or persisted for the patient's remaining lifetime. (Funded by the National Heart, Lung, and Blood Institute and others; SPRINT ClinicalTrials.gov number, NCT01206062 .).
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