Objective To evaluate the use of prospective screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol ...treatment.Design National prospective cohort study.Setting 15 medical centres in different regions of Taiwan, from July 2009 to August 2014.Participants 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants’ peripheral blood was used to assess the presence of HLA-B*58:01. Main outcome measures Incidence of allopurinol induced SCARs with and without screening.Results Participants who tested positive for HLA-B*58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test).Conclusions Prospective screening of the HLA-B*58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.
Nickel cobaltite (NiCo2O4) aerogels, synthesized with a chloride‐based epoxide‐driven sol–gel process, exhibit ultrahigh specific capacitances (1400 F g−1; see figure), excellent reversibility, and ...outstanding cycle stability, at a relatively high mass loading of 0.4 mg cm−2.
Diffuse alveolar damage (DAD) is the pathological hallmark of acute respiratory distress syndrome (ARDS), however, the presence of DAD in the clinical criteria of ARDS patients by Berlin definition ...is little known. This study is designed to investigate the role of DAD in ARDS patients who underwent open lung biopsy.
We retrospectively reviewed all ARDS patients who met the Berlin definition and underwent open lung biopsy from January 1999 to January 2014 in a referred medical center. DAD is characterized by hyaline membrane formation, lung edema, inflammation, hemorrhage and alveolar epithelial cell injury. Clinical data including baseline characteristics, severity of ARDS, clinical and pathological diagnoses, and survival outcomes were analyzed.
A total of 1838 patients with ARDS were identified and open lung biopsies were performed on 101 patients (5.5 %) during the study period. Of these 101 patients, the severity of ARDS on diagnosis was mild of 16.8 %, moderate of 56.5 % and severe of 26.7 %. The hospital mortality rate was not significant difference between the three groups (64.7 % vs 61.4 % vs 55.6 %, p = 0.81). Of the 101 clinical ARDS patients with open lung biopsies, 56.4 % (57/101) patients had DAD according to biopsy results. The proportion of DAD were 76.5 % (13/17) in mild, 56.1 % (32/57) in moderate and 44.4 % (12/27) in severe ARDS and there is no significant difference between the three groups (p = 0.113). Pathological findings of DAD patients had a higher hospital mortality rate than non-DAD patients (71.9 % vs 45.5 %, p = 0.007). Pathological findings of DAD (odds ratio: 3.554, 95 % CI, 1.385-9.12; p = 0.008) and Sequential Organ Failure Assessment score on the biopsy day (odds ratio: 1.424, 95 % CI, 1.187-1.707; p<0.001) were significantly and independently associated with hospital mortality. The baseline demographics and clinical characteristics were not significantly different between DAD and non-DAD patients.
The correlation of pathological findings of DAD and ARDS diagnosed by Berlin definition is modest. A pathological finding of DAD in ARDS patients is associated with hospital mortality and there are no clinical characteristics that could identify DAD patients before open lung biopsy.
Patients with sepsis frequently require mechanical ventilation (MV) to survive. However, MV has been shown to induce the production of proinflammatory cytokines, causing ventilator-induced lung ...injury (VILI). It has been demonstrated that hypoxia-inducible factor (HIF)-1α plays a crucial role in inducing both apoptotic and inflammatory processes. Low-molecular-weight heparin (LMWH) has been shown to have anti-inflammatory activities. However, the effects of HIF-1α and LMWH on sepsis-related acute lung injury (ALI) have not been fully delineated. We hypothesized that LMWH would reduce lung injury, production of free radicals and epithelial apoptosis through the HIF-1α pathway. Male C57BL/6 mice were exposed to 6-mL/kg or 30-mL/kg MV for 5 h. Enoxaparin, 4 mg/kg, was administered subcutaneously 30 min before MV. We observed that MV with endotoxemia induced microvascular permeability; interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2 and vascular endothelial growth factor protein production; neutrophil infiltration; oxidative loads; HIF-1α mRNA activation; HIF-1α expression; bronchial epithelial apoptosis; and decreased respiratory function in mice (
< 0.05). Endotoxin-induced augmentation of VILI and epithelial apoptosis were reduced in the HIF-1α-deficient mice and in the wild-type mice following enoxaparin administration (
< 0.05). Our data suggest that enoxaparin reduces endotoxin-augmented MV-induced ALI, partially by inhibiting the HIF-1α pathway.
A nanolaser is a key component for on-chip optical communications and computing systems. Here, we report on the low-threshold, continuous-wave operation of a subdiffraction nanolaser based on surface ...plasmon amplification by stimulated emission of radiation. The plasmonic nanocavity is formed between an atomically smooth epitaxial silver film and a single optically pumped nanorod consisting of an epitaxial gallium nitride shell and an indium gallium nitride core acting as gain medium. The atomic smoothness of the metallic film is crucial for reducing the modal volume and plasmonic losses. Bimodal lasing with similar pumping thresholds was experimentally observed, and polarization properties of the two modes were used to unambiguously identify them with theoretically predicted modes. The all-epitaxial approach opens a scalable platform for low-loss, active nanoplasmonics.
Background
Interposition vein grafts (IVG) and vascular bridge flaps (VBF) have been exploited as vascular conduit in challenging head and neck reconstructions.
Methods
A retrospective review was ...conducted on 6025 flaps. The effect of patients' characteristics and length of IVG on flap compromise and loss were analyzed. Comparison between IVG and VBF was performed.
Results
The flap compromise and loss rates for the overall group were 8.2% and 3.2%, respectively. An IVG was used in 309 free flaps. The average length of the vein grafts was 6.9 ± 4.2 cm. An unplanned return to the operation room occurred in 32 cases (10.4%) and failure of the flap in 12 patients (3.9%). Binary logistic regression found a significant association between flap compromise and loss rates and length of IVG, hypertension, prior radiation, and neck dissection. In the multiple regression model, length of IVG and prior radiation significantly influenced the outcomes. Thirty‐nine patients underwent reconstruction with a long IVG (>10 cm). Twenty‐six patients underwent surgical reconstruction with radial forearm flap as a VBF. The rate of flap compromise was higher in the group with a long IVG (P = .01).
Conclusions
In head and neck free flap reconstruction, the length of IVGs and history of radiotherapy are associated with flap compromise and loss. In case of long distance between the pedicle and the recipient site, the use of a VBF bridge should be considered as a safe alternative.
Aging and frailty are associated with a high risk of lean mass (LM) loss, which leads to physical disability and can be effectively alleviated by protein supplementation (PS) and muscle strengthening ...exercise (MSE). In this study, the associations between LM gain and PS + MSE efficacy (measured using physical outcomes) in elderly patients with a high risk of sarcopenia or frailty were identified. A comprehensive search of online databases was performed to identify randomized controlled trials (RCTs) reporting the efficacy of PS + MSE in elderly patients with sarcopenia or frailty. The included RCTs were analyzed using meta-analysis and risk of bias assessment. We finally included 19 RCTs in this meta-analysis with a median (range/total) Physiotherapy Evidence Database score of 7/10 (5-9/10). The PS + MSE group exhibited significant improvements in the whole-body LM (standard mean difference (SMD) = 0.66;
< 0.00001), appendicular LM (SMD = 0.35;
< 0.00001), leg strength (SMD = 0.65;
< 0.00001), and walking capability (SMD = 0.33;
= 0.0006). Meta-regression analyses showed that changes in appendicular LM were significantly associated with the effect sizes of leg strength (β = 0.08;
= 0.003) and walking capability (β = 0.17;
= 0.04), respectively. Our findings suggest that LM gain after PS + MSE significantly contributes to the efficacy of the intervention in terms of muscle strength and physical mobility in elderly patients with a high risk of sarcopenia or frailty.
Background
This study evaluated the long‐term clinical outcomes among different vascularized lymph node transfers (VLNT) used at our institution.
Methods
Between July 2010 and July 2016, all patients ...with International Society of Lymphology (ISL) stages II‐III who underwent VLNT were evaluated. Demographic and clinical data (limb circumference, infectious episodes, lymphoscintigraphic studies) were recorded pre‐operatively. Clinical outcomes, complications, and additional excisional procedures were analyzed post‐operatively. At least 2‐year follow‐up was required for inclusion.
Results
Overall, 83 patients (Stage II:47, Stage III:36) met the inclusion criterion. Mean follow‐up was 32.8 months (range, 24‐49). Lymph node flaps used were groin (n = 13), supraclavicular (n = 25), gastroepiploic (n = 42), ileocecal (n = 2), and appendicular (n = 1). Total mean circumference reduction rate was 29.1% (Stage II) and 17.9% (Stage III) (P < 0.05). A paired t‐test showed that VLNT significantly decreased the number of infections (P < 0.05). Three patients reported no improvement of the symptoms. Major complications included one flap loss and one donor site hematoma. After the period of follow‐up, 18 patients (21.7%) underwent additional excisional procedures.
Conclusion
VLNT is a promising technique used for the treatment of lymphedema and appears to be more effective in moderate stages (Stage II). Patients with advanced stage lymphedema (Stage III) may benefit from additional excisional procedures.
Abstract
Pulmonary fibrosis (PF) is a major public health problem with limited therapeutic options. There is a clear need to identify novel mediators of PF to develop effective therapeutics. Here we ...show that an ER protein disulfide isomerase, thioredoxin domain containing 5 (TXNDC5), is highly upregulated in the lung tissues from both patients with idiopathic pulmonary fibrosis and a mouse model of bleomycin (BLM)-induced PF. Global deletion of
Txndc5
markedly reduces the extent of PF and preserves lung function in mice following BLM treatment. Mechanistic investigations demonstrate that TXNDC5 promotes fibrogenesis by enhancing TGFβ1 signaling through direct binding with and stabilization of TGFBR1 in lung fibroblasts. Moreover, TGFβ1 stimulation is shown to upregulate TXNDC5 via ER stress/ATF6-dependent transcriptional control in lung fibroblasts. Inducing fibroblast-specific deletion of
Txndc5
mitigates the progression of BLM-induced PF and lung function deterioration. Targeting TXNDC5, therefore, could be a novel therapeutic approach against PF.
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