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41.

Background

Controversy exists whether low-dose vitamin K supplementation can improve anticoagulation control in patients with unstable anticoagulation under warfarin. In a single- centre randomized, double-blind, placebo-controlled study, we evaluated the effectiveness of 200 μg/day of vitamin K1 in patients with unstable control under warfarin.

Methods

Effectiveness of Vitamin K1 supplementation was primarily assessed by the percentage (%) of Time-in-Therapeutic-Range (TTR) and secondarily by the standard deviation (SD) of the patient’s INR values; the proportion of out-of-range INRs; and the number of dose changes on warfarin. Their change scores were obtained by subtracting the mean value in the 6 months pre-randomization from the mean value in the 6 months post-randomization. Multivariable linear-regressions identified factors associated with anticoagulation instability.

Results

Fifty out of 54 patients were analyzed (intervention: n = 26; placebo: n = 24). Most indications (87%) for anticoagulation were venous thromboembolism (VTE). The intervention was associated with a greater reduction in the change scores for the SD of INRs between the pre and post-randomization periods compared with placebo. The mean change score was -0.259 ± 0.307 with the intervention and -0.046 ± 0.345 with placebo (p = 0.026). There was no effect on the change scores of the (%) TTR (p = 0.98), the number of INRs out-of-range (p = 0.58) and the number of dose changes (p = 0.604). Factors independently associated with increased variability in the SD of INRs were increased alcoholic drinks/week (p = 0.017), dosing errors (p = 0.0009) and missed INR appointments (p = 0.035).

Conclusion

Vitamin K1 supplementation reduces the SD of INRs as an indicator of the variability in anticoagulation control in patients treated with warfarin for VTE.  相似文献   
42.
Bone remodeling is reduced in hypoparathyroidism, resulting in increased areal bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) and abnormal skeletal indices by transiliac bone biopsy. We have now studied skeletal microstructure by high-resolution peripheral quantitative computed tomography (HR-pQCT) through 4 years of treatment with recombinant human PTH(1–84) (rhPTH[1–84]) in 33 patients with hypoparathyroidism (19 with postsurgical disease, 14 idiopathic). We calculated Z-scores for our cohort compared with previously published normative values. We report results at baseline and 1, 2, and 4 years of continuous therapy with rhPTH(1–84). The majority of patients (62%) took rhPTH(1–84) 100 μg every other day for the majority of the 4 years. At 48 months, areal bone density increased at the lumbar spine (+4.9% ± 0.9%) and femoral neck (+2.4% ± 0.9%), with declines at the total hip (−2.3% ± 0.8%) and ultradistal radius (−2.1% ± 0.7%) (p < .05 for all). By HR-pQCT, at the radius site, very similar to the ultradistal DXA site, total volumetric BMD declined from baseline but remained above normative values at 48 months (Z-score + 0.56). Cortical volumetric BMD was lower than normative controls at baseline at the radius and tibia (Z-scores −1.28 and − 1.69, respectively) and further declined at 48 months (−2.13 and − 2.56, respectively). Cortical porosity was higher than normative controls at baseline at the tibia (Z-score + 0.72) and increased through 48 months of therapy at both sites (Z-scores +1.80 and + 1.40, respectively). Failure load declined from baseline at both the radius and tibia, although remained higher than normative controls at 48 months (Z-scores +1.71 and + 1.17, respectively). This is the first report of noninvasive high-resolution imaging in a cohort of hypoparathyroid patients treated with any PTH therapy for this length of time. The results give insights into the effects of long-term rhPTH(1–84) in hypoparathyroidism. © 2020 American Society for Bone and Mineral Research.  相似文献   
43.

Introduction

An ideal ligature should tighten readily and remain tight. Ligature failure can be a critical complication of invasive procedures in human and veterinary surgical practice. Previous studies have tested various knots but not the constrictor knot.

Methods

A new test bench was employed to compare six ligatures using four suture materials. As tension in a ligature is not readily measured, the study employed a surrogate measurement: the force required to slide a ligature along a rod. Benchmark values tested each suture material wrapped around the rod to establish the ratio between this force and the ligature tension for each material. Each ligature was tested first during tightening and then again afterwards. The benchmark ratios were employed to calculate the tensions to evaluate which ligature and which suture material retained tension best.

Results

The model provided consistent linear relationships between the tension in the suture and the force required to pull the ligature along the rod. The constrictor knot retained tension in the ligature best (55–107% better than the next best ligature). Among the suture materials, polydioxanone had the greatest ability to retain the tension in a ligature and polyglactin the least.

Conclusions

The constrictor knot showed superior characteristics for use as a ligature, and should be introduced into teaching and clinical practice for human and veterinary surgery. The new test bench is recommended for future testing of ligatures as well as objective comparison of suture materials.  相似文献   
44.

Introduction

Stomas often have to be sited in emergencies by trainees who may have had little training in this. Emergency stomas and stomas where the site has not been marked preoperatively by a stoma therapist are more prone to complications. These complications may severely affect a patient’s quality of life. Advice in the literature on how to best site stomas is conflicting. We compared two easy anatomical methods of siting stomas to sites chosen by a stoma therapist and looked at how this site was affected by the patients’ body mass index (BMI).

Methods

Patients undergoing elective colorectal surgery were seen either pre or postoperatively. Each patient’s BMI was recorded and the positions of three different potential stoma positions (site G: the gold standard, marked by a stoma therapist; site S: marked using a pair of scissors against the umbilicus; site H: halfway between the umbilicus and anterior superior iliac spine) were compared.

Results

The two fixed anatomical methods described (method S and method H) both gave poor results. The most common reason for poor siting was the proximity of a skin crease. There was a statistically significant correlation between the patient’s BMI and the laterality of the gold standard site.

Conclusions

The two simple anatomical methods described here do not provide a shortcut to effective siting. A more effective method may be calculating the laterality of the site using the patient’s BMI, and then moving up/down to avoid a skin crease and improve the patient’s view for changing the bag. This deserves further study.  相似文献   
45.

INTRODUCTION

The Triathlon® (Stryker, Kalamazoo, MI, US) total knee replacement was designed to improve patient function and survivorship. The aim of this study was to determine whether the Triathlon® prosthesis produces better patient reported outcomes than a previous design by the same manufacturer, the Kinemax Plus.

METHODS

The outcome of 233 knees of patients with a mean age of 68 years (range: 40–80 years) who received the Kinemax Plus prosthesis were compared with the outcomes of 220 knees of patients with a mean age of 70 years (range: 42–90 years) who received the Triathlon® prosthesis. Data were collected via postal questionnaire prior to surgery as well as at 8–12 weeks and at 1 year following surgery. Validated questionnaires were used including the WOMAC® (Western Ontario and McMaster Universities) pain and function scales, the Knee injury and Osteoarthritis Outcome Score quality of life scale and the self-administered patient satisfaction scale.

RESULTS

This study found that patients who had the Triathlon® prosthesis had significantly better pain relief (p<0.0001), function (p=0.028), knee related quality of life (p<0.0001) and satisfaction (p=0.0003) at three months after surgery than those who received the Kinemax Plus prosthesis. In addition, knee related quality of life (p=0.002) and satisfaction (p=0.021) were significantly higher at one year after surgery in Triathlon® patients.

CONCLUSIONS

The findings suggest that return to function and reduction in pain may occur more quickly in patients with a Triathlon® prosthesis than in those with the Kinemax Plus.  相似文献   
46.
Both tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are accepted as first‐line treatments for chronic hepatitis B (CHB). However, there are few randomized studies comparing their efficacy. The primary aim of this study was to compare the efficacy of TDF and ETV using a network meta‐analysis of randomized trials. The secondary aim was to additionally include propensity‐matched cohort studies in a conventional meta‐analysis. We systematically searched PubMed, EMBASE, Cochrane Library and Web of Science for published English‐language randomized and propensity‐matched studies between 1/1/2000 and 4/2/2020. Outcomes included undetectable HBV DNA, ALT normalization and HBeAg seroconversion at 48 weeks. We excluded patients who had co‐infection or significant prior treatment with antivirals. 13 517 participants from 16 studies (11 RCTs, n = 2675; five propensity‐matched cohort studies, n = 10 842) were included. Virological response at 48 weeks was higher in patients receiving TDF compared to ETV using both the network meta‐analytic approach (OR 1.69, P < .001) and the conventional meta‐analysis including propensity‐matched cohort studies (OR 1.40, P < .001). On subgroup analysis, this difference was only significant in HBeAg‐positive patients (OR 1.81, P = .037). There was limited evidence to suggest a higher rate of ALT normalization with ETV (OR 0.74, P = .07). There was no difference in rates of HBeAg seroconversion between the two antivirals. TDF is more likely than ETV to induce virological response at 48 weeks in treatment‐naïve CHB patients. Future studies should focus on elucidating associations between early and sustained virological response with adverse patient outcomes including development of HCC or cirrhosis.  相似文献   
47.
To define an optimal regimen for mobilizing and collecting peripheral blood progenitor cells (PBPC) for use in allogeneic transplantation, we evaluated the kinetics of mobilization by filgrastim (recombinant met- human granulocyte colony-stimulating factor [r-metHuG-CSF]) in normal volunteers. Filgrastim was injected subcutaneously for up to 10 days at a dose of 3 (n = 10), 5 (n = 5), or 10 micrograms/kg/d (n = 15). A subset of volunteers from each dose cohort underwent a 7L leukapheresis on study day 6 (after 5 days of filgrastim). Granulocyte-macrophage colony-forming cell (GM-CFC) numbers in the blood were maximal after 5 days of filgrastim; a broader peak was evident for CD34+ cells between days 4 and 6. The 95% confidence intervals (CI) for mean number of PBPC per milliliter of blood in the three dose cohorts overlapped on each study day. However, on the peak day, CD34+ cells were significantly higher in the 10 micrograms/kg/d cohort than in a pool of the 3 and 5 micrograms/kg/d cohorts. Mobilization was not significantly influenced by volunteer age or sex. Leukapheresis products obtained at the 10 micrograms/kg/d dose level contained a median GM-CFC number of 93 x 10(4)/kg (range, 50 x 10(4)/kg to 172 x 10(4)/kg). Collections from volunteers receiving lower doses of filgrastim contained a median GM- CFC number of 36 x 10(4)/kg (range, 5 x 10(4)/kg to 204 x 10(4)/kg). The measurement of CD34+ cells per milliliter of blood on the day of leukapheresis predicted the total yield of PBPC in the leukapheresis product (r = .87, P < .0001). Assuming a minimum GM-CFC requirement of 50 x 10(4)/kg (based on our experience with autologous PBPC transplantation), all seven leukapheresis products obtained at the 10 micrograms/kg/d dose level were potentially sufficient for allogeneic transplantation purposes. We conclude that in normal donors, filgrastim 10 micrograms/kg/d for 5 days with a single leukapheresis on the following day is a highly effective regimen for PBPC mobilization and collection. Further studies are required to determine whether PBPC collected with this regimen reliably produce rapid and sustained engraftment in allogeneic recipients.  相似文献   
48.
Different types of gross chromosomal rearrangements (GCRs), including translocations, interstitial deletions, terminal deletions with de novo telomere additions, and chromosome fusions, are observed in many cancers. Multiple pathways, such as S-phase checkpoints, DNA replication, recombination, chromatin remodeling, and telomere maintenance that suppress GCRs have been identified. To experimentally expand our knowledge of other pathway(s) that suppress GCRs, we developed a generally applicable genome-wide screening method. In this screen, we identified 10 genes (ALO1, CDC50, CSM2, ELG1, ESC1, MMS4, RAD5, RAD18, TSA1, and UFO1) that encode proteins functioning in the suppression of GCRs. Moreover, the breakpoint junctions of GCRs from these GCR mutator mutants were determined with modified breakpoint-mapping methods. We also identified nine genes (AKR1, BFR1, HTZ1, IES6, NPL6, RPL13B, RPL27A, RPL35A, and SHU2) whose mutations generated growth defects with the pif1Delta mutation. In addition, we found that some of these mutations changed the telomere size.  相似文献   
49.
To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL- 3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c- kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL- 3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.  相似文献   
50.
We describe the development of a human bone marrow (BM) culture system which allows study of the interaction of stromal cell lines (SCL) and highly purified hematopoietic progenitor cells. Normal BM stromal cells were electroporated with a plasmid containing the simian virus 40 (SV40) large T antigen (SV40 T Ag) under the control of a synthetic metallothionein promoter (MT4); this construct is designated MT4 SV40 T Ag. SCL in which the rate of proliferation could be controlled by altering the zinc (Zn) concentration were characterized, demonstrating that the SCL were heterogeneous with respect to G-CSF and GM-CSF production. Suppression of SCL proliferation on removal of Zn made it possible to use these lines in coculture with purified CD34+ progenitor cells from umbilical cord blood. The ability to control proliferation of SCL has allowed us to maintain the survival and expansion of colony- forming cells in culture for up to 2 months. These lines have enabled us to test for stromal cell characteristics at a clonal level and provided us with a tool to analyze the events leading to lineage commitment and hematopoietic differentiation, as demonstrated by suppression of hematopoiesis by an antibody directed against the c-kit molecule.  相似文献   
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