Cadaveric dissection and clinical experience with 20 consecutive tunneled pedicled superficial temporal artery perforator (STAP) flaps for ear reconstruction

Introduction: Reconstruction of anterior ear defects is poorly described, but using "like" tissue provides the optimal reconstruction. We present a cadaveric dissection and our experience with the pedicled superficial temporal artery perforator (STAP) flap for reconstruction of partial ear defects. Materials and Methods: Two cadavers were dissected bilaterally (n = 4) following injection of latex and barium sulfate. A retrospective review of 20 consecutive patients undergoing reconstruction with the STAP flap from 2009 to 2012 was performed. Twenty patients underwent reconstruction of anterior ear defects following resection for non-melanoma skin malignancies using a tunneled pedicled STAP flap (scapha: 5, triangular fossa: 2, scapha and triangular fossa: 13). Results: Two perforators were identified in all dissections with one perforator at the level of the tragus, and the second perforator within 1 cm cephalad to the tragus. Thirteen patients underwent reconstruction following basal cell carcinoma excision and seven patients were reconstructed following excision of squamous cell carcinoma. There were no flap losses, but four flaps (20%) developed congestion at the tip of the flap that resolved without need for flap delay, leeching, or vasodilators. No patients developed complications with the donor site, and no patients underwent revisions. With a mean follow-up of 27.3 months (range: 19–38 months), all patients were pleased with their aesthetic outcomes and alive without recurrent disease. Conclusion: The STAP flap is a pedicled perforator flap providing local "like" tissue that can be utilized for resurfacing of defects involving the anterior upper external ear with minimal donor site morbidity.6 page(s

Datasheet2_Convolutional neural network (CNN)-enabled electrocardiogram (ECG) analysis: a comparison between standard twelve-lead and single-lead setups.pdf

BackgroundArtificial intelligence (AI) has shown promise in the early detection of various cardiac conditions from a standard 12-lead electrocardiogram (ECG). However, the ability of AI to identify abnormalities from single-lead recordings across a range of pathological conditions remains to be systematically investigated. This study aims to assess the performance of a convolutional neural network (CNN) using a single-lead (D1) rather than a standard 12-lead setup for accurate identification of ECG abnormalities.MethodsWe designed and trained a lightweight CNN to identify 20 different cardiac abnormalities on ECGs, using data from the PTB-XL dataset. With a relatively simple architecture, the network was designed to accommodate different combinations of leads as input (ResultsThe CNN based on single-lead ECG (D1) outperformed the one based on the standard 12-lead framework [with an average percentage difference of the area under the curve (AUC) of −8.7%]. Notably, for certain diagnostic classes, there was no difference in the diagnostic AUC between the single-lead and the standard 12-lead setups. When a second lead was detected in the CNN in addition to D1, the AUC gap was further reduced to an average percentage difference of −2.8% compared with that of the standard 12-lead setup.ConclusionsA relatively lightweight CNN can predict different classes of cardiac abnormalities from D1 alone and the standard 12-lead ECG. Considering the growing availability of wearable devices capable of recording a D1-like single-lead ECG, we discuss how our findings contribute to the foundation of a large-scale screening of cardiac abnormalities.</p

Datasheet1_Convolutional neural network (CNN)-enabled electrocardiogram (ECG) analysis: a comparison between standard twelve-lead and single-lead setups.pdf

BackgroundArtificial intelligence (AI) has shown promise in the early detection of various cardiac conditions from a standard 12-lead electrocardiogram (ECG). However, the ability of AI to identify abnormalities from single-lead recordings across a range of pathological conditions remains to be systematically investigated. This study aims to assess the performance of a convolutional neural network (CNN) using a single-lead (D1) rather than a standard 12-lead setup for accurate identification of ECG abnormalities.MethodsWe designed and trained a lightweight CNN to identify 20 different cardiac abnormalities on ECGs, using data from the PTB-XL dataset. With a relatively simple architecture, the network was designed to accommodate different combinations of leads as input (ResultsThe CNN based on single-lead ECG (D1) outperformed the one based on the standard 12-lead framework [with an average percentage difference of the area under the curve (AUC) of −8.7%]. Notably, for certain diagnostic classes, there was no difference in the diagnostic AUC between the single-lead and the standard 12-lead setups. When a second lead was detected in the CNN in addition to D1, the AUC gap was further reduced to an average percentage difference of −2.8% compared with that of the standard 12-lead setup.ConclusionsA relatively lightweight CNN can predict different classes of cardiac abnormalities from D1 alone and the standard 12-lead ECG. Considering the growing availability of wearable devices capable of recording a D1-like single-lead ECG, we discuss how our findings contribute to the foundation of a large-scale screening of cardiac abnormalities.</p

Platinum-induced mitochondrial DNA mutations confer lower sensitivity to paclitaxel by impairing tubulin cytoskeletal organization

Development of chemoresistance is a cogent clinical issue in oncology, whereby combination of anticancer drugs is usually preferred also to enhance efficacy. Paclitaxel (PTX), combined with carboplatin, represents the standard first-line chemotherapy for different types of cancers. We here depict a double-edge role of mitochondrial DNA (mtDNA) mutations induced in cancer cells after treatment with platinum. MtDNA mutations were positively selected by PTX, and they determined a decrease in the mitochondrial respiratory function, as well as in proliferative and tumorigenic potential, in terms of migratory and invasive capacity. Moreover, cells bearing mtDNA mutations lacked filamentous tubulin, the main target of PTX, and failed to reorient the Golgi body upon appropriate stimuli. We also show that the bioenergetic and cytoskeletal phenotype were transferred along with mtDNA mutations in transmitochondrial hybrids, and that this also conferred PTX resistance to recipient cells. Overall, our data show that platinum-induced deleterious mtDNA mutations confer resistance to PTX, and confirm what we previously reported in an ovarian cancer patient treated with carboplatin and PTX who developed a quiescent yet resistant tumor mass harboring mtDNA mutations

Neutrophils promote Alzheimer's disease-like pathology and cognitive decline via LFA-1 integrin

Inflammation is a pathological hallmark of Alzheimer's disease, and innate immune cells have been shown to contribute to disease pathogenesis. In two transgenic models of Alzheimer's disease (5xFAD and 3xTg-AD mice), neutrophils extravasated and were present in areas with amyloid-β (Aβ) deposits, where they released neutrophil extracellular traps (NETs) and IL-17. Aβ42 peptide triggered the LFA-1 integrin high-affinity state and rapid neutrophil adhesion to integrin ligands. In vivo, LFA-1 integrin controlled neutrophil extravasation into the CNS and intraparenchymal motility. In transgenic Alzheimer's disease models, neutrophil depletion or inhibition of neutrophil trafficking via LFA-1 blockade reduced Alzheimer's disease-like neuropathology and improved memory in mice already showing cognitive dysfunction. Temporary depletion of neutrophils for 1 month at early stages of disease led to sustained improvements in memory. Transgenic Alzheimer's disease model mice lacking LFA-1 were protected from cognitive decline and had reduced gliosis. In humans with Alzheimer's disease, neutrophils adhered to and spread inside brain venules and were present in the parenchyma, along with NETs. Our results demonstrate that neutrophils contribute to Alzheimer's disease pathogenesis and cognitive impairment and suggest that the inhibition of neutrophil trafficking may be beneficial in Alzheimer's disease

Secukinumab shows high efficacy irrespective of HLA-Cw6 status in patients with moderate-to-severe plaque-type psoriasis: SUPREME study

Background: Understanding genetic variations is important in predicting treatment response and forms the basis for identifying new pharmacogenetic and pharmacogenomic targets for psoriasis treatment. There are limited data on the efficacy of secukinumab in relation to genetic markers. Objectives: To evaluate the efficacy and safety of secukinumab 300 mg in HLA-Cw6-positive (Cw6-POS) and HLA-Cw6-negative (Cw6-NEG) patients with moderate-to-severe chronic plaque-type psoriasis. Methods: SUPREME was a 24-week, phase IIIb study with an extension period up to 72 weeks. Primary end point was Psoriasis Area Severity Index (PASI) 90 response rate after 16 weeks. Results: In total, 434 patients were recruited: 185 (42·6%) were Cw6-POS and 246 (56·7%) were Cw6-NEG (three not assessed). Mean ± SD age was 45·2 ± 13·2 years (Cw6-POS 42·7 ± 13·1; Cw6-NEG 47·2 ± 12·9). The baseline PASI score was comparable between the cohorts [Cw6-POS 20·7 ± 8·99; Cw6-NEG 21·5 ± 9·99 (P = 0·777)]. At week 16, PASI 90 was achieved in 80·4% of Cw6-POS and 79·7% of Cw6-NEG patients (difference 0·76; 95% confidence interval −7·04 to 8·23). No differences in absolute PASI at week 16 (Cw6-POS 1·36 ± 3·58; Cw6-NEG 1·18 ± 2·29) were observed. The overall safety profile of secukinumab was consistent with that previously reported. No statistically significant difference was detected in the rate of treatment-emergent adverse events [Cw6-POS 42·7%; Cw6-NEG 49·6% (P = 0·295)]. A high PASI 90 response was achieved with secukinumab with a fast reduction in absolute PASI. Conclusions: Determination of HLA-Cw6 status for secukinumab therapy is unnecessary, as it is highly effective regardless of HLA-Cw6 status

Secukinumab shows high efficacy irrespective of HLA-Cw6 status in patients with moderate-to-severe plaque-type psoriasis: SUPREME study

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Neutrophils promote Alzheimer's disease–like pathology and cognitive decline via LFA-1 integrin

Inflammation is a pathological hallmark of Alzheimer's disease, and innate immune cells have been shown to contribute to disease pathogenesis. In two transgenic models of Alzheimer's disease (5xFAD and 3xTg-AD mice), neutrophils extravasated and were present in areas with amyloid-β (Aβ) deposits, where they released neutrophil extracellular traps (NETs) and IL-17. Aβ42 peptide triggered the LFA-1 integrin high-affinity state and rapid neutrophil adhesion to integrin ligands. In vivo, LFA-1 integrin controlled neutrophil extravasation into the CNS and intraparenchymal motility. In transgenic Alzheimer's disease models, neutrophil depletion or inhibition of neutrophil trafficking via LFA-1 blockade reduced Alzheimer's disease-like neuropathology and improved memory in mice already showing cognitive dysfunction. Temporary depletion of neutrophils for 1 month at early stages of disease led to sustained improvements in memory. Transgenic Alzheimer's disease model mice lacking LFA-1 were protected from cognitive decline and had reduced gliosis. In humans with Alzheimer's disease, neutrophils adhered to and spread inside brain venules and were present in the parenchyma, along with NETs. Our results demonstrate that neutrophils contribute to Alzheimer's disease pathogenesis and cognitive impairment and suggest that the inhibition of neutrophil trafficking may be beneficial in Alzheimer's disease