Aliment Pharmacol Ther 31, 415–423
Summary
Background Long‐term results after downstaging hepatocellular carcinoma (HCC) prior to liver transplantation (LT) remain unknown.
Aims To investigate ...dropouts and post‐transplant outcome among patients with downstaged HCC by transarterial chemo‐lipiodolization (TACL).
Methods Between 2000 and 2007, 386 patients with HCC initially exceeding Milan criteria underwent TACL for tumour downstaging and were consecutively enrolled.
Results Overall, 160 (41.5%) patients achieved successful downstaging of HCC to within Milan criteria. During the follow‐up, 82 eventually dropped off the waiting list for LT, with estimated dropout rates at 1, 2 and 5 years of 46.7%, 70.2%, and 87.2%, respectively. The overall post‐transplant survival rates at 1, 2 and 5 years were 89.2%, 70.3% and 54.6% and the corresponding rates for recurrence‐free survival were 74.7%, 71.8% and 66.3% respectively. Multivariate analysis indentified alpha‐fetoprotein (AFP) levels ≥100 ng/mL at LT (P = 0.003), maximum tumour size ≥7 cm (P = 0.002) and the lack of complete necrosis by TACL (P = 0.048) as independent predictors of HCC recurrence after LT. Patients with none of these risk factors had an excellent post‐transplant outcome, with an 87.5% probability of recurrence‐free survival up to 6 years.
Conclusions These long‐term results may contribute to the database for optimizing management of LT candidates with downstaged HCC. Based on our data, patients with a maximum tumour size <7 cm who achieve complete necrosis together with AFP levels <100 ng/mL at LT may be the best candidates for LT following downstaging using TACL.
Equine recurrent uveitis (ERU) is a painful and debilitating autoimmune disease and represents the only spontaneous model of human recurrent uveitis (RU). Despite the efficacy of existing treatments, ...RU remains a leading cause of visual handicap in horses and humans. Cytokines, which utilize Janus kinase 2 (Jak2) for signaling, drive the inflammatory processes in ERU that promote blindness. Notably, suppressor of cytokine signaling 1 (SOCS1), which naturally limits the activation of Jak2 through binding interactions, is often deficient in autoimmune disease patients. Significantly, we previously showed that topical administration of a SOCS1 peptide mimic (SOCS1-KIR) mitigated induced rodent uveitis. In this pilot study, we test the potential to translate the therapeutic efficacy observed in experimental rodent uveitis to equine patient disease. Through bioinformatics and peptide binding assays we demonstrate putative binding of the SOCS1-KIR peptide to equine Jak2. We also show that topical, or intravitreal injection of SOCS1-KIR was well tolerated within the equine eye through physical and ophthalmic examinations. Finally, we show that topical SOCS1-KIR administration was associated with significant clinical ERU improvement. Together, these results provide a scientific rationale, and supporting experimental evidence for the therapeutic use of a SOCS1 mimetic peptide in RU.
We report a unique case of a 12-year-old girl with unilateral proptosis form orbital extension of an extensive bilateral cephalhematoma. Loss of vision in the left eye due to severe proptosis was ...reversed by prompt aspiration and tarsorrhaphy.
To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant ...data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium.
We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis.
In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethnoracial groups, some interethnic differences were found in the effects of risk factors on cognition.
This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethnoracial differences that warrant attention in the development of prevention strategies.
Background: Sevoflurane is a widely used inhalation anesthetic, but there are no studies on its effect on the wound‐healing process. This study was undertaken to evaluate the effect of exposure time ...to sevoflurane on wound healing.
Method: Male Sprague–Dawley rats were used. Two circular full‐thickness skin defects 8 mm in diameter were made on the dorsum of the rats. The animals were divided into six groups according to exposed gas type and time: S1 (sevoflurane, 1 h), S4 (sevoflurane, 4 h), S8 (sevoflurane, 8 h), O1 (oxygen, 1 h), O4 (oxygen, 4 h), and O8 (oxygen, 8 h). The surface area of the wounds was measured 0, 1, 3, and 7 days after surgery. Separately, the mean blood pressures (MBP) and arterial oxygen pressures (PaO2) were monitored during the sevoflurane exposure. Collagen type I production and transforming growth factor‐β1 (TGF‐β1) and basic fibroblast growth factor (bFGF) expression on the wound surface were analyzed. Routine histological analysis was also performed.
Result: Exposure duration to sevoflurane had no influence on MBP and PaO2. The reduction in wound size and collagen type I production was delayed in S8. The expression of TGF‐β1 and bFGF on the wound surface in S8 was significantly attenuated in S8. The histology of the S8 demonstrated a delayed healing status.
Conclusions: Prolonged exposure to sevoflurane might alter the inflammatory phase of the wound‐healing process by attenuation of growth factor expression such as TGF‐β1 and bFGF and subsequently by reduced collagen production.
The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since ...then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.
A prospective phase II study of neoadjuvant chemoradiotherapy (CRT) for resectable esophageal squamous cell carcinoma was conducted from May 1993 to March 1996. A total of 88 patients fitted the ...eligibility criteria and were treated with two courses of induction chemotherapy (cisplatin 60 mg/m2/day on day 1 and 5-fluorouracil (5-FU) 1000 mg/m2/day on days 2-6) with concurrent hyperfractionated radiotherapy (48 Gy/40 fractions/4 weeks) followed by esophagectomy or definitive CRT comprising 4 cycles of cisplatin/5-FU and hyperfractionated radiotherapy (additional 12 Gy) with intracavitary brachytherapy (9 Gy). Clinical response and downstaging were achieved in 83% and 42% of the patients, respectively. With a median follow-up of 77 months, median survival time was 18 months with a 5-year survival rate of 23%. The clinical responses to CRT and surgery were independent prognostic factors for overall survival. Among the intended surgery group (n = 52), 41 (79%) patients underwent surgery and 36 had a resection with a pathologic complete response rate of 43%. When compared with a matched historical control (n = 40), there was a significant survival benefit in the multimodality arm (p = 0.04). This multimodality therapy was feasible and its efficacy was promising, especially when surgical resection was performed. The therapeutic benefit of neoadjuvant CRT remains to be assessed in large well-designed randomized trials, one of which is ongoing at our institution.
Background and aims
This study explores the relationship between systolic blood pressure during the acute period of stroke and poor functional outcome in patients with lacunar stroke, emphasizing a ...possible time-dependent nature of the relationship.
Methods
Based on multicenter stroke registry data, patients with acute lacunar stroke were identified, and systolic blood pressure levels at eight time points (1, 2, 4, 8, 16, 24, 48, and 72 h) after stroke onset were extracted at the 15 participating centers in South Korea. Poor functional outcome was defined as a three-month modified Rankin Scale score of 2–6. Non-linear restricted cubic spline and linear models were used for assessing the relationship at each time point.
Results
A total of 97,349 systolic blood pressure measurements of 3,042 patients were analyzed. At 1 h and 4 h after stroke onset, the relationship between systolic blood pressure and poor outcome showed a non-linear association. The nadir was 155 mmHg at 1 h and 124 mmHg at 4 h. After this time period, a higher systolic blood pressure was associated with a poorer outcome. This linear relationship weakened over time after 12 h (coefficient values of the adjusted linear models: 0.0081 at 8 h, 0.0105 at 12 h, 0.0102 at 24 h, 0.0082 at 48 h, 0.0054 at 72 h).
Conclusions
Based on our cohort of large number of lacunar stroke patients, our findings suggest that systolic blood pressure levels may follow a time-dependent course in relation to prediction of outcome at three months. The findings may be valuable for hypothesis generation in association with clinical trial development for blood pressure control in acute stroke patients.
Fine-grained magnesium alloys reinforced by quasicrystalline particles were easily developed by thermomechanical processes for as-cast Mg-rich Mg–Zn–Y and Mg–Zn–Y–Zr alloys. The deformation behavior ...of the alloys at room and high temperatures was investigated and compared with that of commercial AZ31, AZ61 and AZ91 alloys. The yield strength of the Mg–Zn–Y alloys, increasing with an increase of the volume fraction of the quasicrystalline phase, is relatively high due to the strengthening effect of the quasicrystalline particles. At high temperatures, the level of flow stress of the Mg–Zn–Y alloys is lower than that of commercial magnesium alloys due to the softness of the eutectic region, but the alloys exhibit much higher elongation since the large number of quasicrystalline particles in the Mg–Zn–Y alloys can effectively prohibit microstructural evolution of the α-Mg matrix during deformation. Icosahedral particles in the alloy are also stable against coarsening during deformation near the melting temperature of the eutectic due to their low interfacial energy, thereby forming a stable quasicrystalline particle/matrix interface. The stability of both the quasicrystalline particles and the microstructure of the Mg–Zn–Y alloys provides a large elongation with no void opening at the interface between the quasicrystalline particle and the α-Mg matrix.
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