Summary
Background
Long‐term oral nucleos(t)ide analogue (NUC) therapy in hepatitis B virus (HBV)‐related compensated cirrhotics prevents clinical decompensation but not hepatocellular carcinoma ...(HCC) development.
Aims
To define the clinical features and outcomes of HCC in long‐term NUC‐treated HBV patients.
Methods
All HCCs developing between 2005 and 2016 in NUC‐treated HBV patients under surveillance were studied, excluding those that occurred within the first 6 months of therapy. Clinical features of HCC, alpha faetoprotein (AFP) patterns and patients' outcome were studied.
Results
Seventy‐six HCC patients were included. Median age was 67 (40‐83) years, 84% males, 96% Caucasian, 95% HBeAg‐negative, 96% with undetectable HBV DNA, 83% with normal ALT levels, and 92% with compensated cirrhosis. Median serum AFP levels were 4 (1‐3615) ng/mL (>7 ng/mL in 36%). HCC was monofocal in 78%, had a median diameter of 20 (6‐57) mm and was in its early stage in 92% which allowed potentially curative treatments in 78% (39% ablation, 28% surgical resection, 11% liver transplantation). Overall, a complete response was obtained in 61 (80%) patients: in 40 after a first‐line treatment, in 3 after the second–line treatment, in 2 after the third‐line treatment, while 16 underwent liver transplantation (8 as second line). During 45 (7‐144) months after HCC diagnosis, 19 patients died, 84% from HCC progression. The median time to recurrence was 20.2 (3‐53) months, and the cumulative 5‐year liver‐related survival was 74%.
Conclusions
HCCs developing in patients under long‐term NUC treatment were single, small tumours, amenable to curative therapies able to confer excellent 5‐year survival rates.
Genetic experiments established that p63 is crucial for the development and maintenance of pluri-stratified epithelia and KLF4 for the barrier function of the skin. KLF4 is one of the factors that ...reprogram differentiated cells to iPS. We investigated the relationship between p63 and KLF4 using RNA interference, overexpression, chromatin immunoprecipitation and transient transfections with reporter constructs. We find that p63 directly represses KLF4 in normal keratinocytes (KCs) by binding to upstream promoter sites. Unlike p63, KLF4 levels are high in the upper layers of human skin and increase upon differentiation of KCs in vitro. In HaCaT KCs, which harbor two mutant alleles of p53, inactivation of p63 and of mutant p53 leads to KLF4 repression. p63 and p53 mutants are bound to sites in the KLF4 core promoter. Importantly, expression of the H179Y and R282Q p53 mutants in primary KCs is sufficient to activate endogenous KLF4. Finally, immunohistochemical analysis of tissue arrays confirms increased coexpression of KLF4 and mutant p53 in squamous cell carcinomas. Our data indicate that suppression of KLF4 is part of the growth-promoting strategy of p63 in the lower layers of normal epidermis, and that tumor-predisposing p53 mutations hijack p63 to a different location on the promoter, turning it into an activator of this reprogramming factor.
Objective
Conversion total hip arthroplasty (CTHA) through a direct anterior approach (DAA) in supine position.
Indications
Failed osteosynthesis of proximal femoral fractures or failed conservative ...hip surgery, with hardware in situ.
Contraindications
Decayed general conditions, infection (peri-implant or systemic infection), need for greater trochanter reconstruction, severe proximal femur deformity.
Surgical technique
Supine position. Mark DAA and expected limited incisions for hardware removal (HR) with the help of a C-arm. Use guidewire and extraction devices for HR. Perform a DAA with particular attention to a wide release of the femur.
Postoperative management
Full progressive weight-bearing starting on day 1, depending on bone quality. Discharge with crutches following patient walking capability. Precautions for 6 weeks.
Results
In all, 27 conversion THAs through a DAA. Mean age at the time of surgery 59.8 (range 18–81) years. Mean body mass index was 23.5 (range 17–31.6). Reasons of previous surgery failures were avascular necrosis of the femoral head, posttraumatic arthritis and nonunion with or without hardware migration. Mean surgical time was 125.8 min (range 58–190 min, standard deviation SD 38.2 min). Mean follow-up time was 6.9 years (range 2–15, SD 5.03 years). Mean pre-Harris Hip Score (mHHs) was 24.4 (range 19–36, SD 5.4), while the mean post-mHHS was 90.3 (range 89–91, SD 0.95). Two patients required postoperative osteosynthesis for periprosthetic fractures due to falls. Overall complication rate was 10%.
Low frequency pulsed electromagnetic field (PEMF) has proven to be effective in the modulation of bone and cartilage tissue functional responsiveness, but its effect on tendon tissue and tendon cells ...(TCs) is still underinvestigated. PEMF treatment (1.5 mT, 75 Hz) was assessed on primary TCs, harvested from semitendinosus and gracilis tendons of eight patients, under different experimental conditions (4, 8, 12 h). Quantitative PCR analyses were conducted to identify the possible effect of PEMF on tendon-specific gene transcription (scleraxis, SCX and type I collagen, COL1A1); the release of pro- and anti-inflammatory cytokines and of vascular endothelial growth factor (VEGF) was also assessed. Our findings show that PEMF exposure is not cytotoxic and is able to stimulate TCs’ proliferation. The increase of SCX and COL1A1 in PEMF-treated cells was positively correlated to the treatment length. The release of anti-inflammatory cytokines in TCs treated with PEMF for 8 and 12 h was significantly higher in comparison with untreated cells, while the production of pro-inflammatory cytokines was not affected. A dramatically higher increase of VEGF-A mRNA transcription and of its related protein was observed after PEMF exposure. Our data demonstrated that PEMF positively influence, in a dose-dependent manner, the proliferation, tendon-specific marker expression, and release of anti-inflammatory cytokines and angiogenic factor in a healthy human TCs culture model.
Background and purpose
Head down tilt 15° (HDT15°), applied before recanalization, increases collateral flow and improves outcome in experimental ischemic stroke. For its simplicity and low cost, ...HDT15° holds considerable potential to be developed as an emergency treatment of acute stroke in the prehospital setting, where hemorrhagic stroke is the major mimic of ischemic stroke. In this study, we assessed safety of HDT15° in the acute phase of experimental intracerebral hemorrhage.
Methods
Intracerebral hemorrhage was produced by stereotaxic injection of collagenase in Wistar rats. A randomized noninferiority trial design was used to assign rats to HDT15° or flat position (n = 64). HDT15° was applied for 1 h during the time window of hematoma expansion. The primary outcome was hematoma volume at 24 h. Secondary outcomes were mass effect, mortality, and functional deficit in the main study and acute changes of intracranial pressure, hematoma growth, and cardiorespiratory parameters in separate sets of randomized animals (n = 32).
Results
HDT15° achieved the specified criteria of noninferiority for hematoma volume at 24 h. Mass effect, mortality, and functional deficit at 24 h showed no difference in the two groups. HDT15° induced a mild increase in intracranial pressure with respect to the pretreatment values (+2.91 ± 1.76 mmHg). HDT15° had a neutral effect on MRI‐based analysis of hematoma growth and cardiorespiratory parameters.
Conclusions
Application of HDT15° in the hyperacute phase of experimental intracerebral hemorrhage does not worsen early outcome. Further research is needed to implement HDT15° as an emergency collateral therapeutic for acute stroke.
Exploring safety of head down 15° (HDT15°) application in the acute phase of intracerebral hemorrhage is highly relevant for its translation into a collateral therapeutic for prehospital treatment of acute ischemic stroke. Application of head down tilt 15° for 1 h in a rat model of large supratentorial intracerebral hemorrhage does not worsen early outcome compared to flat position in terms of hematoma volume, hematoma growth, mass effect, mortality, and functional deficit at 24 h. Intracranial pressure was increased by a few millimeters of mercury (+2.91 ± 1.76 mmHg) after HDT15° application.
Abstract Objective Management of periodontal defects has always been a challenge in clinical periodontics. Recently mesenchymal stem cells (MSC) have been proposed for tissue regeneration in ...periodontal disease and repair of large bone defects. Bone regeneration has to be supported by a scaffold which has to be biocompatible, biodegradable, and able to support cell growth and differentiation. The aim of this study was to evaluate osteogenic differentiation of MSC seeded on a collagen scaffold. Design MSC were obtained from adult rat bone marrow, expanded and cultured in plastic dishes or seeded in a collagen scaffold (Gingistat® ). MSC were induced towards osteogenic differentiation using osteogenic supplements. Cell differentiation and calcium deposits were evaluated by immunoblotting, immunohistochemistry, histochemical techniques, enzymatic activity assay, and SEM–EDX analysis. Biomaterial in vitro degradation was evaluated by measuring mass reduction after incubation in culture medium. Results Rat MSC osteogenic differentiation was demonstrated by osteopontin and osteocalcin expression and an increase in alkaline phosphatase activity. MSC were distributed homogeneously in the collagen scaffold. Nodular aggregates and alizarin red stained calcium deposits were observed in MSC induced towards osteogenic differentiation cultured in dishes or seeded in the collagen scaffold. SEM–EDX analysis demonstrated that calcium co-localized with phosphorous. The biomaterial in vitro degraded in 4–5 weeks. Conclusions MSC from bone marrow differentiate towards osteogenic lineage, representing a suitable cell source for bone formation in periodontal regeneration. Gingistat® collagen scaffold supports MSC distribution and differentiation, but its short degradation time may be a limitation for a future application in bone tissue regeneration.
Summary
Background
Interferon lambda 3 (IFN‐λ3) polymorphisms are the strongest genetic predictor of outcome of hepatitis C virus infection and of response to Pegylated interferon (PegIFN)‐based ...therapy. Whether this holds true for hepatitis B virus (HBV) infection is matter of controversy.
Aim
To review the association between host genomics and spontaneous or interferon‐induced clearance of HBV with specific reference to the recently identified interleukin 28B gene now renamed IFN‐λ3.
Methods
A literature search was performed on MEDLINE, EMBASE and Web of Science for English articles and s using free text words and combinations of the following terms ‘IL28B’, ‘IFN lambda’, ‘genomics’, ‘hepatitis B virus’, ‘interferon’ ‘GWAS’, ‘treatment’, ‘SNPs’, ‘HLA’, ‘polymorphisms’.
Results
Genome‐wide association studies convincingly demonstrated an association between SNPs in the HLA locus and spontaneous resolution of HBV infection in subgroups of Asian patients, yet no information is available for Caucasians. The preliminary observations of an association between IFN‐λ3 SNP and virological and serological responses to IFN in both HBeAg‐positive and ‐negative patients could not be replicated by subsequent studies. Yet, majority of studies performed so far suffer several limitations in terms of sample size, selection of the patients, endpoints of therapy, treatment strategies and duration of follow‐up.
Conclusions
While host genetics is associated with an increased likelihood of spontaneous clearance of HBV among genotype B/C patients, the relationship between IFN‐λ3 polymorphisms and response to IFN has not been confirmed. Further studies in large cohorts of homogeneous patients are required, before this genetic test can be recommended in clinical practice.
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