Serial ultrasonography is reliable for the diagnosis of deep venous thrombosis in symptomatic patients, but the low prevalence of thrombosis in this group renders the approach costly and inconvenient ...to patients. We studied the clinical validity of the combination of a pretest clinical probability score and a D-dimer test in the initial evaluation of patients suspected of deep venous thrombosis.
Patients with a normal D-dimer concentration (<500 fibrin equivalent units FEU microg/L) and a non-high probability score (<3) had no further testing. Patients with a normal D-dimer concentration and a high probability score (> or =3) underwent one ultrasonogram. Serial ultrasonography was performed in patients with an abnormal D-dimer concentration. Patients were followed for 3 months. A total of 812 patients were evaluable for efficacy. Only 1 of 176 patients (0.6%; 95% CI, 0.02% to 3.1%) with a normal D-dimer concentration and a non-high probability score developed thrombosis during follow-up. A normal D-dimer concentration and a high probability score were found in 39 patients; 3 of them (7.7%; 95% CI, 1.6% to 20.9%) had thrombosis at presentation, and one (2.8%; 95% CI, 0.07% to 14. 5%) developed pulmonary embolism during follow-up. In 306 of 597 patients (51.3%) with an abnormal D-dimer concentration, thrombosis was detected by serial ultrasonography. Six patients (2.1%; 95% CI, 0.8% to 4. 4%) developed thrombosis during follow-up. No deaths due to thromboembolism occurred during follow-up. The total need for ultrasonography was reduced by 29%.
The combination of a non-high pretest clinical probability score and a normal D-dimer concentration is a safe strategy to rule out deep venous thrombosis and to withhold anticoagulation.
Previous research has shown clinical effectiveness of dermal substitution; however, in burn wounds, only limited effect has been shown. A problem in burn wounds is the reduced take of the autograft, ...when the substitute and graft are applied in one procedure. Recently, application of topical negative pressure (TNP) was shown to improve graft take. The aim of this study was to investigate if application of a dermal substitute in combination with TNP improves scar quality after burns. In a four‐armed multicenter randomized controlled trial, a split‐skin graft with or without a dermal substitute and with or without TNP was compared in patients with deep dermal or full‐thickness burns requiring skin transplantation. Graft take and rate of wound epithelialization were evaluated. Three and 12 months postoperatively, scar parameters were measured. The results of 86 patients showed that graft take and epithelialization did not reveal significant differences. Significantly fewer wounds in the TNP group showed postoperative contamination, compared to other groups. Highest elasticity was measured in scars treated with the substitute and TNP, which was significantly better compared to scars treated with the substitute alone. Concluding, this randomized controlled trial shows the effectiveness of dermal substitution combined with TNP in burns, based on extensive wound and scar measurements.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Prime editing is a versatile genome-editing technique that shows great promise for the generation and repair of patient mutations. However, some genomic sites are difficult to edit and optimal design ...of prime-editing tools remains elusive. Here we present a fluorescent prime editing and enrichment reporter (fluoPEER), which can be tailored to any genomic target site. This system rapidly and faithfully ranks the efficiency of prime edit guide RNAs (pegRNAs) combined with any prime editor variant. We apply fluoPEER to instruct correction of pathogenic variants in patient cells and find that plasmid editing enriches for genomic editing up to 3-fold compared to conventional enrichment strategies. DNA repair and cell cycle-related genes are enriched in the transcriptome of edited cells. Stalling cells in the G1/S boundary increases prime editing efficiency up to 30%. Together, our results show that fluoPEER can be employed for rapid and efficient correction of patient cells, selection of gene-edited cells, and elucidation of cellular mechanisms needed for successful prime editing.
The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed ...to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR).
This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests.
The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38–50) mm and 68 (IQR 58–85) mm, respectively. Mortality was 1.3% (95% CI 0.7–2.4) after eIAA repair and 25.5% (95% CI 18.0–34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively).
In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
The transanal endoscopic operation (TEO) has proved to be an effective alternative to conventional surgery for the treatment of rectal lesions. The TEO procedure offers reduced morbidity, ...faster recovery and equivalent oncologic outcome. Currently, two instrument sets are available: one with three-dimensional (Wolf) and one with two-dimensional (Storz) optic capacities. The three-dimensional (3D) instrument set is considered the golden standard. Although the advantages of TEO are imposing, the procedure with the 3D armamentarium has certain technical and financial drawbacks. This study therefore aimed to compare results for the TEO 2D alternative with recently published results for 3D TEO.
Methods
All consecutive patients with benign or malignant pT1 or pT2 rectal lesions undergoing TEO were prospectively followed. All procedures were performed with the 2D armamentarium using standard endoscopic instruments, a rectoscope (diameter, 4 cm; working length, 7.5–15 cm), and 5-mm Ligasure and Ultracision. Operating times, complications, hospital stay, and oncologic outcome were gathered and compared with published data.
Results
Between 2004 and 2006, 31 patients with a median age of 75 years (range, 33–87 years) underwent 31 TEOs for a total of 36 rectal lesions (29 tubulovillous adenomas and 7 adenocarcinomas). The median distance of the lesion from the anal verge was 7.5 cm (range, 5–15 cm). The median lesion diameter was 2.3 cm (range, 0.5–5.0 cm). The locations of the lesions were as follows: 18 on the dorsal, 5 on the ventral, and 5 on the lateral rectal wall. The median operating time was 55 min (range, 25–165 min), compared with 105 min reported in the literature. All the lesions except one could be radically excised. No intraoperative complications occurred. Postoperative complications occurred for three patients, all due to hemorrhage. The median hospital stay was 3 days (range, 1–21 days). During a median follow-up period of 15 months (range, 1–35 months), two recurrences took place.
Conclusion
The study findings showed that for rectal tumors located up to 15 cm from the anal verge with a maximal diameter of 5 cm, TEO using standard laparoscopic instruments with a 2D view is feasible and provides results comparable with those associated with a 3D view and dedicated instruments. Furthermore, the 2D procedure can be performed with improved ergonomics due to movable monitors and is considerably less expensive.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Background Burn injuries may cause long term disability and work absence, and therefore result in high healthcare and productivity costs. Up to now, detailed information on return to work ...(RTW) and productivity costs after burns is lacking. Aims The aim of this study was to accurately assess RTW after burn injuries, to identify predictors of absenteeism and to calculate healthcare and productivity costs from a societal perspective. Methods A prospective cohort study was conducted in the burn centre of Rotterdam, the Netherlands, including all admitted working-age patients from 1 August 2011 until 31 July 2012. At 3, 12 and 24 months post-burn, patients were sent a questionnaire: including the Work and Medical Consumption questionnaire for the assessment of work absence and medical consumption and the EQ-5D-3L plus a cognitive dimension to assess post-burn and pre-burn quality of life (QOL). Costs analysis were from a societal perspective according the micro-costing method and the friction cost method was applied for the calculation of productivity loss. Univariate logistic regression was used to identify predictors of absenteeism at three months. Results A total of 104 patients were included in the study with a mean total body surface area (TBSA) burned of 8% (median 4%). 66 respondents were pre-employed, at 3 months 70% was back at work, at 12 months 92% and 8% had not returned to work at time of final follow-up at 24 months. Predictors of absenteeism at 3 months were: TBSA, length of stay, ICU-admission and surgery. Mean costs related to loss in productivity were €11.916 95% CI 8.930-14.902 and accounted for 30% of total costs in pre-employed respondents in the first two years. Conclusion This two year follow-up study demonstrates that burn injuries cause substantial and prolonged productivity loss amongst burn survivors with mixed burn severity. This absenteeism contributes to already high societal costs of burn injuries. Predictors of absenteeism found in this study were primarily fixed patient and treatment related factors, future studies should focus on modifiable factors, in order to improve RTW outcomes. Also, more attention in the rehabilitation trajectory is needed to optimally support RTW in burn survivors.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Summary
TIRC7 is a cell surface molecule which is expressed in T and B lymphocytes and negatively regulates their function. Anti‐TIRC7 specific monoclonal antibody (mAb) inhibited T cell memory ...response to recall antigens. Up‐regulation of TIRC7 on lymphocytes from joint tissue of patients with Rheumatoid Arthritis (RA) and mice with collagen induced arthritis (CIA) suggested TIRC7 as a novel target to promote anti‐inflammatory reaction. Anti‐TIRC7 mAb administration significantly inhibited the induction and progression of CIA and the anti‐collagen IgG1 and IgG2a antibody response. Combination therapy of anti‐TIRC7 mAb and soluble TNF‐α receptor demonstrated an increased inhibitory effect over the single compounds on CIA. The results demonstrate the therapeutic potential of TIRC7 targeting with mAb in diseases associated with exaggerated T and B cell responses.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Kidney transplant recipients (KTR) have impaired health-related quality of life (HRQoL) and suffer from intestinal dysbiosis. Increasing evidence shows that gut health and HRQoL are tightly ...related in the general population. Here, we investigate the association between the gut microbiome and HRQoL in KTR, using metagenomic sequencing data from fecal samples collected from 507 KTR. Multiple bacterial species are associated with lower HRQoL, many of which have previously been associated with adverse health conditions. Gut microbiome distance to the general population is highest among KTR with an impaired physical HRQoL (
R
= −0.20,
P
= 2.3 × 10
−65
) and mental HRQoL (
R
= −0.14,
P
= 1.3 × 10
−3
). Physical and mental HRQoL explain a significant part of variance in the gut microbiome (
R
2
= 0.58%, FDR = 5.43 × 10
−4
and
R
2
= 0.37%, FDR = 1.38 × 10
−3
, respectively). Additionally, multiple metabolic and neuroactive pathways (gut brain modules) are associated with lower HRQoL. While the observational design of our study does not allow us to analyze causality, we provide a comprehensive overview of the associations between the gut microbiome and HRQoL while controlling for confounders.
Burn survivors are frequently faced with disfiguring scars. Various techniques exist to improve scar appearance, such as laser treatment and dermabrasion. Next to that, surgical reconstruction, such ...as scar excision is an option. This randomized controlled trial investigates whether a larger burn scar can be excised using a skin-stretching device for wound closure, thereby optimizing use of adjacent healthy skin. This technique may allow scar excision in a one-step procedure instead of two or more steps, which is necessary for serial excision and tissue expansion.
Two arms were compared: scar excision and closure by skin stretch and scar excision without additional techniques. The primary outcome measure was scar surface area reduction. In addition, complications were registered.
Fifteen patients were randomized for skin stretch and 15 patients were randomized for scar excision only. In the skin stretch group, 10 of 15 scars were completely excised compared with three of 15 in the scar excision-only group (p = 0.025). In the skin stretch group, a significantly larger reduction in scar area was achieved: 95 ± 11 percent of the scar was excised versus 78 ± 17 percent in the scar excision-only group (p = 0.003). One patient in the skin stretch group and three patients in the scar excision-only group experienced partial wound dehiscence (p = 0.598).
In burn scar reconstructions, a significantly larger reduction in scar area can be achieved using a skin-stretching device compared with scar excision with no additional techniques, without an increased risk of complications. It was shown that skin stretching is of added value for scars that cannot be excised in a one-step procedure.
Guillain–Barré syndrome (GBS) is a post-infectious disease in which the human peripheral nervous system is affected after infection by specific pathogenic bacteria, including
Campylobacter jejuni
. ...GBS is suggested to be provoked by molecular mimicry between sialylated lipooligosaccharide (LOS) structures on the cell envelope of these bacteria and ganglioside epitopes on the human peripheral nerves, resulting in autoimmune-driven nerve destruction. Earlier, the
C. jejuni
sialyltransferase (Cst-II) was found to be linked to GBS and demonstrated to be involved in the biosynthesis of the ganglioside-like LOS structures. Apart from a role in pathogenicity, we report here that Cst-II-generated ganglioside-like LOS structures confer efficient bacteriophage resistance in
C. jejuni
. By bioinformatic analysis, it is revealed that the presence of sialyltransferases in
C. jejuni
and other potential GBS-related pathogens correlated significantly with the apparent degeneration of an alternative anti-virus system: type II
C
lusters of
R
egularly
I
nterspaced
S
hort
P
alindromic
R
epeat and
as
sociated genes (CRISPR-Cas). Molecular analysis of the
C. jejuni
CRISPR-Cas system confirmed the bioinformatic investigation. CRISPR degeneration and mutations in the
cas
genes
cas2
,
cas1
and
csn1
were found to correlate with Cst-II sialyltransferase presence (
p
< 0.0001). Remarkably, type II CRISPR-Cas systems are mainly found in mammalian pathogens. To study the potential involvement of this system in pathogenicity, we inactivated the type II CRISPR-Cas marker gene
csn1
, which effectively reduced virulence in primarily
cst
-II-positive
C. jejuni
isolates. Our findings indicate a novel link between viral defence, virulence and GBS in a pathogenic bacterium.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
PDF
