Dermatofibrosarcoma protuberans: A 10-year experience

SummaryBackgroundProviding soft-tissue coverage after wide excision of dermatofibrosarcoma protuberans (DFSP) is always challenging; according to the literature, a skin graft is often chosen as the first option. However, possible suboptimal functional and cosmetic results have been noted.Aims and objectivesWe present our 10-year experience using pedicled or free flaps for reconstruction after a wide excision of DFSP to provide adequate soft-tissue augmentation and enhanced esthetic results.Materials and methodsThis was a retrospective study comprising 14 DFSP patients who were treated between February 2003 and December 2013. All patients underwent a wide excision with a 3-cm safe margin with immediate reconstruction, and a negative deep margin confirmed with a frozen section. The reconstruction method included nine pedicled perforator flaps and five free perforator flaps. All patients received adjuvant radiotherapy after surgery.ResultsThe peak incidence that occurred in this series was the highest in patients younger than 30 years. None of the 14 patients exhibited recurrence, and the mean follow-up time was 30 months. Half of the patients exhibited DFSP distributed over the trunk; the patients in the series were predominantly male. A total of 13 flaps were successful except for one pedicled flap that failed from venous congestion; we used it in a salvage procedure by using full-thickness skin graft for coverage.ConclusionA wide excision with a 3-cm margin of safety with immediate reconstruction is a reliable method for DFSP resection. Initiating adjuvant radiotherapy might reduce the chance of local recurrence. To minimize the complications of skin graft, pedicled, or free flaps provide superior functional outcome, soft-tissue augmentation, and esthetic results

Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

<p>Abstract</p> <p>Background</p> <p>Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE). Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE.</p> <p>Methods</p> <p>We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7) rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry.</p> <p>Results</p> <p>Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats.</p> <p>Conclusion</p> <p>These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.</p

Mutations in the PKM2 exon-10 region are associated with reduced allostery and increased nuclear translocation.

PKM2 is a key metabolic enzyme central to glucose metabolism and energy expenditure. Multiple stimuli regulate PKM2's activity through allosteric modulation and post-translational modifications. Furthermore, PKM2 can partner with KDM8, an oncogenic demethylase and enter the nucleus to serve as a HIF1α co-activator. Yet, the mechanistic basis of the exon-10 region in allosteric regulation and nuclear translocation remains unclear. Here, we determined the crystal structures and kinetic coupling constants of exon-10 tumor-related mutants (H391Y and R399E), showing altered structural plasticity and reduced allostery. Immunoprecipitation analysis revealed increased interaction with KDM8 for H391Y, R399E, and G415R. We also found a higher degree of HIF1α-mediated transactivation activity, particularly in the presence of KDM8. Furthermore, overexpression of PKM2 mutants significantly elevated cell growth and migration. Together, PKM2 exon-10 mutations lead to structure-allostery alterations and increased nuclear functions mediated by KDM8 in breast cancer cells. Targeting the PKM2-KDM8 complex may provide a potential therapeutic intervention

Overweight worsens apoptosis, neuroinflammation and blood-brain barrier damage after hypoxic ischemia in neonatal brain through JNK hyperactivation

<p>Abstract</p> <p>Background</p> <p>Apoptosis, neuroinflammation and blood-brain barrier (BBB) damage affect the susceptibility of the developing brain to hypoxic-ischemic (HI) insults. c-Jun N-terminal kinase (JNK) is an important mediator of insulin resistance in obesity. We hypothesized that neonatal overweight aggravates HI brain damage through JNK hyperactivation-mediated upregulation of neuronal apoptosis, neuroinflammation and BBB leakage in rat pups.</p> <p>Methods</p> <p>Overweight (OF) pups were established by reducing the litter size to 6, and control (NF) pups by keeping the litter size at 12 from postnatal (P) day 1 before HI on P7. Immunohistochemistry and immunoblotting were used to determine the TUNEL-(+) cells and BBB damage, cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP), and phospho-JNK and phospho-Bim_ELlevels. Immunofluorescence was performed to determine the cellular distribution of phospho-JNK.</p> <p>Results</p> <p>Compared with NF pups, OF pups had a significantly heavier body-weight and greater fat deposition on P7. Compared with the NF-HI group, the OF-HI group showed significant increases of TUNEL-(+) cells, cleaved levels of caspase-3 and PARP, and ED1-(+) activated microglia and BBB damage in the cortex 24 hours post-HI. Immunofluorescence of the OF-HI pups showed that activated-caspase 3 expression was found mainly in NeuN-(+) neurons and RECA1-(+) vascular endothelial cells 24 hours post-HI. The OF-HI group also had prolonged escape latency in the Morris water maze test and greater brain-volume loss compared with the NF-HI group when assessed at adulthood. Phospho-JNK and phospho-Bim_ELlevels were higher in OF-HI pups than in NF-HI pups immediately post-HI. JNK activation in OF-HI pups was mainly expressed in neurons, microglia and vascular endothelial cells. Inhibiting JNK activity by AS601245 caused more attenuation of cleaved caspase-3 and PARP, a greater reduction of microglial activation and BBB damage post-HI, and significantly reduced brain damage in OF-HI than in NF-HI pups.</p> <p>Conclusions</p> <p>Neonatal overweight increased HI-induced neuronal apoptosis, microglial activation and BBB damage, and aggravated HI brain damage in rat pups through JNK hyperactivation.</p

Evaluation of Intrarenal Blood Flow by Doppler Ultrasonography Immediately after Extracorporeal Shock Wave Lithotripsy on Hydronephrotic Kidney

Extracorporeal shock wave lithotripsy (ESWL) is an effective and relatively noninvasive mode of treatment for urinary calculi. The aim of this study was to test whether therapeutic ESWL induces changes in renal parenchymatous blood flow and to evaluate shock wave side effects on the renal parenchyma. A total of 45 patients who underwent ESWL for ureteropelvic stone between January 2002 and July 2003 were included in this prospective study. Color Doppler sonography before and 30 minutes after ESWL showed no significant morphologic change. Resistive index (RI) was used to estimate renovascular resistance. The RI significantly increased in obstructed hydronephrotic kidneys. However, no significant change was observed in both treated and untreated kidneys before and after treatment. Hydronephrotic kidneys do not have a higher risk of post-ESWL renovascular resistance interference. The measurement of changes in RI with Doppler ultrasonography may provide useful information for clinical diagnosis of renal tubulointerstitial and vascular damage

Pleural Effusion after Percutaneous Radiofrequency Ablation for Hepatic Malignancies

AbstractBackground and AimsRadiofrequency ablation (RFA) can play an important role in the treatment of primary or metastatic liver tumors. Currently, percutaneous RFA is generally regarded as a safe, effective, and minimally invasive procedure. This study aimed to evaluate the presence and course of pleural effusion after monopolar RFA.MethodsFrom October 2008 to July 2013, a total of 54 patients (28 male and 26 female, mean age 65.2) treated with monopolar RFA were included in our study. 47 patients were diagnosed with hepatocellular carcinoma, 4 patients with hepatic metastasis, and 3 patients had other diagnoses. There were a total of 115 sessions of treatment and 199 liver tumors to be treated (1.73 ± 1.02 tumors treated per session). The tumor size ranged from 0.8 cm to 5.0 cm (mean 2.31 cm, standard deviation 1.04 cm). Thereafter, a follow-up ultrasound was performed within 24 hours subsequent to ablation to evaluate the presence of pleural effusion. The degree of pleural effusion was assessed by chest X-ray.ResultsFifteen (13.0%) treatment sessions in 14 patients showed right-sided pleural effusion after ablations. One patient had a large amount of effusion, while other patients manifested a minimal to small amount of effusion. There were 5 patients that experienced delayed resolution of pleural effusion; one patient (0.87%) had a minimal amount of pleural effusion even after one month. Overall, there was no pneumothorax, or periprocedural morality. Age, gender, tumor numbers, tumor sizes, and complete ablation of target tumors were similar among groups presenting with or without pleural effusion. Tumor locations associated with S78 segments abutting the diaphragm or right lobe of the liver were not associated with development of pleural effusion. Only the duration of ablation time had a marginal trend toward significance (p = 0.051).ConclusionsThe transient appearance of right-sided pleural effusion after percutaneous RFA for hepatic malignancies was not infrequent. However, refractory pleural effusion was rare