The topic of this monograph is liver cancer associated with chronic HCV infection. We start with some background information on chronic HCV infection and its long‐term sequelae, one of which is liver ...cancer. The rest of the article is concerned with liver cancer or hepatocellular carcinoma (HCC). Epidemiology, risk factors, treatment and outcomes are discussed. We focus on those aspects that are of specific interest in people with haemophilia: studies performed in haemophilia populations, the use of invasive diagnostic and therapeutic tools and the outcome of liver transplantation. Throughout the paper, recommendations are given on surveillance for and diagnosis of HCC and on the practical aspects of invasive procedures. These recommendations are based on professional guidelines, other published evidence and the authors’ experience. In general, diagnostic and therapeutic options are the same in persons with and without haemophilia.
The outcomes of total knee arthroplasty (TKA) and total hip arthroplasty (THA) in patients with haemophilia have not been compared with other patient populations. The aim of this study was to compare ...the results of joint replacement therapy in patients with and without haemophilia retrospectively. This is a controlled retrospective cohort study. The complications and long‐term results of 21 TKAs and 6 THAs performed in 22 haemophilia patients were compared with those of 42 TKAs and 12 THAs in patients without bleeding disorders. Patients were matched for type of arthroplasty, gender, year of surgery and age. Blood loss, infection rate, revision, implant survival and function as judged by the patient were recorded. Haemarthrosis occurred in 14 (52%) of the 27 arthroplasties performed in the haemophilia patients, while four bleedings were recorded in the 54 arthroplasties in the control group (7%, P < 0.001). All bleeds occurred in TKAs. In the patient group, two infections (7%, both in TKAs) occurred compared to seven (13%, 6/7 in TKAs) in the control group (NS). In the haemophilia patients, all but one (96%) arthroplasties were still in situ at the end of follow‐up, vs. 44 (81%, NS) in the control group. For TKAs, survival was 20/21 vs. 34/42 respectively (P = 0.25). Subjective function was good in 22/27 (81%; 76% in TKAs) arthroplasties in haemophilia patients, vs. 40/54 (74%; 71% in TKAs) in controls. Haemophilia patients experienced significantly more haemarthroses, but no more infections and they have an excellent implant survival compared with non‐haemophilia controls.
Purpose
Activation of tubular epithelial cells by transforming growth factor-beta (TGF-β) plays an important role in the pathogenesis of renal tubulointerstitial fibrosis. We developed a renally ...accumulating conjugate of a TGF-β type-I receptor kinase inhibitor (TKI) and evaluated its efficacy
in vitro
and
in vivo
.
Methods
TKI was conjugated to the protein Lysozyme (LZM) via a platinum-based linker. TKI-LZM was evaluated in human tubular cells (HK-2) for its anti-fibrotic activity. Plasma, kidney and urine drug levels after a single intravenous dose of TKI-LZM in rats were determined by HPLC or immunodetection. Anti-fibrotic effects of TKI-LZM were examined in the unilateral ureteral obstruction (UUO) model.
Results
TKI-LZM conjugate was successfully synthesized at an 1:1 drug/carrier ratio, and inhibited TGF-β1-induced procollagen-1α1 gene expression in HK-2 cells.
In vivo
, TKI-LZM accumulated rapidly in tubular cells and provided a local depot for 3 days. Interestingly, a single dose of TKI-LZM inhibited the activation of tubular cells and fibroblasts in UUO rats and reduced renal inflammation. In contrast, free TKI at an equimolar (low) dosage exhibited little effects.
Conclusions
Inhibition of TGF-beta signaling by local drug delivery is a promising antifibrotic strategy, and demonstrated the important role of tubular activation in renal fibrosis.
Neuromuscular disorders are characterised by muscle weakness that limits upper extremity mobility, but can be alleviated with dynamic arm support devices. Current research highlights the importance ...and difficulties of evidence-based recommendations for device development. We aim to provide research recommendations primarily concerning upper extremity body functions, and secondarily activity and participation, environmental and personal factors.
Evidence was synthesised from literature, ongoing studies, and expert opinions and tabulated within a framework based on a combination of the International Classification of Functioning, Disability and Health (ICF) model and contextual constructs.
Current literature mostly investigated the motor capacity of muscle function, joint mobility, and upper body functionality, and a few studies also addressed the impact on activity and participation. In addition, experts considered knowledge on device utilisation in the daily environment and characterising the beneficiaries better as important. Knowledge gaps showed that ICF model components and contextual constructs should be better integrated and more actively included in future research.
It is recommended to, first, integrate multiple ICF model components and contextual constructs within one study design. Second, include the influence of environmental and personal factors when developing and deploying a device. Third, include short-term and long-term measurements to monitor adaptations over time. Finally, include user satisfaction as guidance to evaluate the device effectiveness.
IMPLICATIONS ON REHABILITATION
Synthesized evidence will support future research and development of dynamic arm supports.
Tabulated evidence stresses the importance of integrating ICF model components and contextual constructs to fill the knowledge gaps.
Presented knowledge gaps and proposed steps guide the set up of future studies on dynamic arm supports
The Rho kinase pathway plays an important role in dedifferentiation of epithelial cells and infiltration of inflammatory cells. For testing of the hypothesis that blockade of this cascade within the ...kidneys might be beneficial in the treatment of renal injury the Rho kinase inhibitor, Y27632 was coupled to lysozyme, a low molecular weight protein that is filtered through the glomerulus and is reabsorbed in proximal tubular cells. Pharmacokinetic studies with Y27632-lysozyme confirmed that the conjugate rapidly and extensively accumulated in the kidney. Treatment with Y27632-lysozyme substantially inhibited ischemia/reperfusion-induced tubular damage, indicated by reduced staining of the dedifferentiation markers kidney injury molecule 1 and vimentin, and increased E-cadherin relative to controls. Rho kinase activation was inhibited by Y27632-lysozyme within tubular cells and the interstitium. Y27632-lysozyme also inhibited inflammation and fibrogenesis, indicated by a reduction in gene expression of monocyte chemoattractant protein 1, procollagen Ialpha1, TGF-beta1, tissue inhibitor of metalloproteinase 1, and alpha-smooth muscle actin. Immunohistochemistry revealed reduced macrophage infiltration and decreased expression of alpha-smooth muscle actin, collagen I, collagen III, and fibronectin. In contrast, unconjugated Y27632 did not have these beneficial effects but instead caused systemic adverse effects, such as leukopenia. Neither treatment improved renal function in the bilateral ischemia/reperfusion model. In conclusion, the renally targeted Y27632-lysozyme conjugate strongly inhibits tubular damage, inflammation, and fibrogenesis induced by ischemia/reperfusion injury.
•First describing biomechanics after Lisfranc injury.•Lower speed, and lower flexion/extension in patients after Lisfranc injury.•Motion significantly correlated with patient reported outcome ...measures.•Stability, BMI and gait were factors most influencing outcome.
Lisfranc injuries involve any bony or ligamentous disruption of the tarsometatarsal joint. Outcome results after treatment are mainly evaluated using patient-reported outcome measures (PROM), physical examination and radiographic findings. Less is known about the kinematics during gait.
Nineteen patients (19 feet) treated for Lisfranc injury were recruited. Patients with conservative treatment and surgical treatment consisting of open reduction and internal fixation (ORIF) or primary arthrodesis were included. PROM, radiographic findings and gait analysis using the Oxford Foot Model (OFM) were analysed. Results were compared with twenty-one healthy subjects (31 feet). Multivariable logistic regression was used to determine factors influencing outcome.
Patients treated for Lisfranc injury had a significantly lower walking speed than healthy subjects (P<0.001). There was a significant difference between the two groups regarding the range of motion (ROM) in the sagittal plane (flexion-extension) in the midfoot during the push-off phase (p<0.001). The ROM in the sagittal plane was significantly correlated with the AOFAS midfoot score (r2=0.56, p=0.012), FADI (r2=0.47, p=0.043) and the SF-36-physical impairment score (r2=0.60, p=0.007) but not with radiographic parameters for quality of reduction. In a multivariable analysis, the best explanatory factors were ROM in the sagittal plane during the push-off phase (β=0.707, p=0.001), stability (β=0.423, p=0.028) and BMI (β=−0.727 p=<0.001). This prediction model explained 87% of patient satisfaction.
This study showed that patients treated for Lisfranc injury had significantly lower walking speed and significantly lower flexion/extension in the midfoot than healthy subjects. The ROM in these patients was significantly correlated with PROM, but not with radiographic quality of reduction. Most important satisfaction predictors were BMI, ROM in the sagittal plane during the push-off phase and fracture stability.
Considering the relationship between inflammation and thrombosis, patients with tuberculosis (TB) patients might be at high risk of venous thrombosis.
To evaluate the risk of venous thromboembolism ...in patients admitted to the Beatrixoord Tuberculosis Centre (BTBC), a tertiary centre for TB. We specifically explored which cofactors elevate the risk of venous thrombosis (VTE), and whether the timing of venous thrombotic events would justify extended primary prophylaxis.
retrospective cohort study.
We performed a retrospective chart review of all patients with TB discharged from BTBC between 2000 and 2010. We excluded patients who were already on therapeutic anticoagulation before their TB episode, below the age of 18 years and patients in which TB diagnosis was withdrawn. For evaluating the timing of venous thrombosis, we calculated the time between commencement of anti TB therapy and the VTE.
Of 750 included in the final analysis, 18 (2.4%) suffered a venous thrombotic event. 3 of these events were not related to classic risk factors or hospitalization. Most (13/18) VTE's occurred in the time window of two weeks before starting TB medication.
In the multivariate analysis, only Human Immunodeficiency Virus (HIV) infection was strongly associated with risk of VTE (adjusted Odds ratio 8.2 (95% confidence interval: 2.9-22.7)).
This high risk in HIV co-infected TB patients suggests that standard thrombo-prophylaxis should be routinely considered in this group. However, our findings might not be generalizable due to referral bias. Further prospective studies in unselected HIV co-infected TB patients are needed to corroborate our findings.
Essentials
Targeting of factor VIII values is a challenge during perioperative replacement therapy in hemophilia.
This study aims to identify the extent and predictors of factor VIII underdosing and ...overdosing.
Blood group O predicts underdosing and is associated with perioperative bleeding.
To increase quality of care and cost‐effectiveness of treatment, refining of dosing is obligatory.
Summary
Background
Perioperative administration of factor VIII (FVIII) concentrate in hemophilia A may result in both underdosing and overdosing, leading to respectively a risk of bleeding complications and unnecessary costs.
Objectives
This retrospective observational study aims to identify the extent and predictors of underdosing and overdosing in perioperative hemophilia A patients (FVIII levels < 0.05 IU mL−1).
Patients and Methods
One hundred nineteen patients undergoing 198 elective, minor, or major surgical procedures were included (median age 40 years, median body weight 75 kg). Perioperative management was evaluated by quantification of perioperative infusion of FVIII concentrate and achieved FVIII levels. Predictors of underdosing and (excessive) overdosing were analyzed by logistic regression analysis. Excessive overdosing was defined as upper target level plus ≥ 0.20 IU mL−1.
Results
Depending on postoperative day, 7–45% of achieved FVIII levels were under and 33–75% were above predefined target ranges as stated by national guidelines. A potential reduction of FVIII consumption of 44% would have been attained if FVIII levels had been maintained within target ranges. Blood group O and major surgery were predictive of underdosing (odds ratio OR 6.3, 95% confidence interval CI 2.7–14.9; OR 3.3, 95% CI 1.4–7.9). Blood group O patients had more bleeding complications in comparison to patients with blood group non‐O (OR 2.02, 95% CI 1.00–4.09). Patients with blood group non‐O were at higher risk of overdosing (OR 1.5, 95% CI 1.1–1.9). Additionally, patients treated with bolus infusions were at higher risk of excessive overdosing (OR 1.8, 95% CI 1.3–2.4).
Conclusion
Quality of care and cost‐effectiveness can be improved by refining of dosing strategies based on individual patient characteristics such as blood group and mode of infusion.
Essentials
The value of compression therapy in acute phase of deep vein thrombosis is still unclear.
Patients with deep vein thrombosis received acute compression hosiery, bandaging, or none.
Acute ...compression reduces irreversible skin signs related to post thrombotic syndrome.
Compression hosiery may be the preferred choice for the acute phase
Summary
Background
The effectiveness of compression therapy in the acute phase of deep vein thrombosis (DVT) is not yet determined.
Objectives
To investigate the impact of compression therapy in the acute phase of DVT on determinants of the Villalta score, health‐related quality of life (HRQOL), and costs.
Patients/Methods
Eight hundred and sixty‐five patients with proximal DVT (substudy of the IDEAL DVT study) received, immediately after DVT diagnosis, either no compression, multilayer bandaging, or hosiery. In the acute phase and 3 months after diagnosis, HRQOL was determined by use of the EQ‐5D, SF6D, and VEINES‐QoL intrinsic method (VEINES‐QoLint). At 3 months, signs and symptoms were assessed for the total and separate items of the Villalta score, and healthcare costs were calculated.
Results
The compression groups had lower overall objective Villalta scores than the no‐compression group (1.47 standard deviation (SD) 1.570 and 1.59 SD 1.64 versus 2.21 SD 2.15). The differences were mainly attributable to irreversible skin signs (induration, hyperpigmentation, and venectasia) and pain on calf compression. Subjective and total Villalta scores were similar across groups. Differences in HRQOL were only observed at 1 month; HRQOL was better for hosiery (EQ‐5D 0.86 SD 0.18; VEINES‐QoLint 0.66 SD 0.18) than for multilayer compression bandaging (EQ‐5D 0.81 SD 0.23; VEINES‐QoLint 0.62 SD 0.19). Mean healthcare costs per patient were €417.08 (€354.10 to €489.30) for bandaging, €114.25 (€92.50 to €198.43) for hosiery, and €105.86 (€34.63 to €199.30) for no compression.
Conclusions
Initial compression reduces irreversible skin signs, edema, and pain on calf compression. Multilayer bandaging is slightly more effective than hosiery, but has substantially higher costs, without a gain in HRQOL. From a patient and economic perspective, compression hosiery would be preferred when initial compression is applied. Trial registration: IDEAL DVT study ClinicalTrials.gov number, NCT01429714.
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