Evaluation of Morphometric Measurements on Preoperative CT Angiograms to Determine Risk of Abdominal Donor Site Complications-A Retrospective Review of 174 Patients.

Introduction: Autologous breast reconstruction remains a popular surgical option following mastectomy; however, it is not without complications. Preoperative CT angiograms (CTAs) are often obtained for surgical planning, and morphometric data such as fat and muscle distribution can be measured. This study aimed to assess if CTA morphometric data predicts abdominal donor site complications in patients undergoing abdominally based autologous breast reconstruction. Methods: A retrospective cohort study was performed for patients who underwent abdominally based autologous breast reconstruction from 2013 to 2018. Along with population and operative characteristics, preoperative morphometric variables were assessed for the following: subcutaneous adipose tissue, visceral adipose tissue, skeletal muscle area and index, rectus and psoas cross-sectional area, and bone density. Statistical comparison to abdominal donor site complications was performed using logistic regression analysis for every 100-unit change. Results: A total of 174 patients were included in this study. Visceral adipose tissue was significantly associated with the development of infection (P = .005), epidermolysis (P = .031), and seroma (P = .04). Subcutaneous adipose tissue, skeletal muscle index, cross-sectional muscle area, and bone density were not associated with abdominal donor site complications. Obesity (P = .024), history of smoking (P = .049), and the number of perforators harvested (P = .035) significantly increased the likelihood of delayed abdominal healing. Conclusions: This study demonstrates that increased visceral adipose tissue, as measured by CTA, is significantly associated with an increased risk of abdominal donor site complications. CTA morphometric data and identifying high-risk patient characteristics can help guide preoperative counseling and better inform surgical risks.

Introduction : La reconstruction mammaire autologue reste une option chirurgicale appréciée après une mastectomie. Toutefois, elle ne va pas sans complications. Des angio-TDM préopératoires sont souvent effectués dans le cadre de la planification chirurgicale et les données morphométriques (comme la répartition du tissu adipeux et musculaire) peuvent être mesurées. Cette étude a eu pour but d'évaluer si les données morphométriques de la TDM prédisent les complications abdominales au site donneur chez les patientes subissant une reconstruction mammaire autologue à partir de tissus abdominaux. Méthodes : Une étude de cohorte rétrospective a été effectuée avec des patients ayant subi une reconstruction mammaire autologue à base abdominale entre 2013 et 2018. Parallèlement aux caractéristiques opératoires et de la population, les variables morphométriques préopératoires suivantes ont été évaluées : tissu adipeux sous-cutané, tissu adipeux viscéral, surface de muscle squelettique et surface transversale index, du grand droit et du psoas, densité osseuse. Une comparaison statistique aux complications du site donneur abdominal a été réalisée au moyen d'une analyse de régression logistique pour chaque changement de 100 unités. Résultats: Cent-soixante-quatorze patientes ont été incluses dans l'étude. Le tissu adipeux viscéral a été associé de manière significative avec le développement d'une infection (P = 0005), d'une épidermolyse (P = 0031 et d'un sérome (P = 0,04). Le tissu adipeux sous-cutané, l'indice de muscle squelettique, la surface musculaire transversale et la densité osseuse n'ont pas été associées à des complications abdominales du site donneur. L'obésité (P = 0024), les antécédents de tabagisme (P = 0049) et le nombre de perforantes collectées (P = 0035) ont significativement augmenté la probabilité du retard de guérison abdominales. Conclusions: Cette étude démontre que l'augmentation de tissu adipeux viscéral, mesurée par angio-TDM, est significativement associée à une augmentation du risque de complications abdominales au site donneur. Les données morphométriques de l'angio-TDM et l'identification des caractéristiques des patients à risque élevé peuvent aider à orienter les conseils préopératoires et à mieux renseigner sur les risques chirurgicaux.

Adherence to Clinical Practice Guidelines for Treatment of Bell's Palsy.

BACKGROUND: Bell's palsy is the most common cause of acute facial nerve paresis and paralysis with devastating disability yet high rate of spontaneous recovery. Patients who do not fully recover have functional disability that may require reconstructive surgery. The Clinical Practice Guideline: Bell's Palsy recommends treatment with high-dose steroids as it shows a higher likelihood of complete recovery. However, guideline adherence rates are inconsistent and unstudied. OBJECTIVE: To identify the frequency at which hospital-based clinicians at the University of Wisconsin-Madison follow recommended clinical guidelines and prescribe high-dose steroid medication. METHODS: Charts were reviewed from a single hospital (University Hospital) to evaluate Bell's palsy guideline adherence. All hospital-based encounters from 2008 through 2018 with primary diagnosis of Bell's palsy (ICD-9 351.0 and ICD-10 G51.0) were identified. Encounters were excluded if they had a diagnosis of Bell's palsy within 1 year prior (n=250) and did not have a medication list available (n=353). We examined patient demographics, common comorbidities, and any radiology and lab orders. RESULTS: We identified 565 patients with a primary diagnosis of Bell's palsy with available medication lists; 77.70% received the recommended treatment. The patients' median age was 47 (interquartile range 34-59), 52.16% were male, and 82.46% were treated by emergency medicine clinicians. Other treating clinicians were hospital-based primary care, otolaryngology and plastic surgery, and others. Multivariate analysis showed that treating clinician specialty was the only significant positive predictor. CONCLUSIONS: A significant portion of clinicians followed treatment guidelines for Bell's palsy. Further and larger research is needed to better identify points of intervention to improve guideline adherence.

The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression.

Neoplastic pancreatic epithelial cells are believed to die through caspase 8-dependent apoptotic cell death, and chemotherapy is thought to promote tumour apoptosis. Conversely, cancer cells often disrupt apoptosis to survive. Another type of programmed cell death is necroptosis (programmed necrosis), but its role in pancreatic ductal adenocarcinoma (PDA) is unclear. There are many potential inducers of necroptosis in PDA, including ligation of tumour necrosis factor receptor 1 (TNFR1), CD95, TNF-related apoptosis-inducing ligand (TRAIL) receptors, Toll-like receptors, reactive oxygen species, and chemotherapeutic drugs. Here we report that the principal components of the necrosome, receptor-interacting protein (RIP)1 and RIP3, are highly expressed in PDA and are further upregulated by the chemotherapy drug gemcitabine. Blockade of the necrosome in vitro promoted cancer cell proliferation and induced an aggressive oncogenic phenotype. By contrast, in vivo deletion of RIP3 or inhibition of RIP1 protected against oncogenic progression in mice and was associated with the development of a highly immunogenic myeloid and T cell infiltrate. The immune-suppressive tumour microenvironment associated with intact RIP1/RIP3 signalling depended in part on necroptosis-induced expression of the chemokine attractant CXCL1, and CXCL1 blockade protected against PDA. Moreover, cytoplasmic SAP130 (a subunit of the histone deacetylase complex) was expressed in PDA in a RIP1/RIP3-dependent manner, and Mincle--its cognate receptor--was upregulated in tumour-infiltrating myeloid cells. Ligation of Mincle by SAP130 promoted oncogenesis, whereas deletion of Mincle protected against oncogenesis and phenocopied the immunogenic reprogramming of the tumour microenvironment that was induced by RIP3 deletion. Cellular depletion suggested that whereas inhibitory macrophages promote tumorigenesis in PDA, they lose their immune-suppressive effects when RIP3 or Mincle is deleted. Accordingly, T cells, which are not protective against PDA progression in mice with intact RIP3 or Mincle signalling, are reprogrammed into indispensable mediators of anti-tumour immunity in the absence of RIP3 or Mincle. Our work describes parallel networks of necroptosis-induced CXCL1 and Mincle signalling that promote macrophage-induced adaptive immune suppression and thereby enable PDA progression.

Radiation Therapy Induces Macrophages to Suppress T-Cell Responses Against Pancreatic Tumors in Mice.

BACKGROUND & AIMS: The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcomes compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of preinvasive foci. METHODS: We investigated the effects of radiation therapy in p48(Cre);LSL-Kras(G12D) (KC) and p48(Cre);LSLKras(G12D);LSL-Trp53(R172H) (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony-stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2 to 12 Gy and analyzed by flow cytometry. RESULTS: Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from radiation treated invasive and preinvasive pancreatic tumors had an immune-suppressive, M2-like phenotype compared with control mice. Pancreata from mice exposed to radiation had fewer CD8(+) T cells than controls, and greater numbers of CD4(+) T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. A neutralizing antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. CONCLUSIONS: Radiation treatment causes macrophages murine PDA to acquire an immune-suppressive phenotype and disabled T-cell-mediated anti-tumor responses. MCSF blockade negates this effect, allowing radiation to have increased efficacy in slowing tumor growth.

Serotonin Syndrome Following Methylene Blue Administration for Vasoplegic Syndrome.

Methylene blue (MB) has been used for additional blood pressure support in patients who develop severe, refractory vasoplegia; however, MB can induce serotonin syndrome, especially when used in conjunction with other serotonergic agents. We describe a case of serotonin syndrome in a patient who received MB for vasoplegic syndrome after left ventricular assist device implantation and discuss its presentation and management.

Dectin-1 Regulates Hepatic Fibrosis and Hepatocarcinogenesis by Suppressing TLR4 Signaling Pathways.

Dectin-1 is a C-type lectin receptor critical in anti-fungal immunity, but Dectin-1 has not been linked to regulation of sterile inflammation or oncogenesis. We found that Dectin-1 expression is upregulated in hepatic fibrosis and liver cancer. However, Dectin-1 deletion exacerbates liver fibro-inflammatory disease and accelerates hepatocarcinogenesis. Mechanistically, we found that Dectin-1 protects against chronic liver disease by suppressing TLR4 signaling in hepatic inflammatory and stellate cells. Accordingly, Dectin-1(-/-) mice exhibited augmented cytokine production and reduced survival in lipopolysaccharide (LPS)-mediated sepsis, whereas Dectin-1 activation was protective. We showed that Dectin-1 inhibits TLR4 signaling by mitigating TLR4 and CD14 expression, which are regulated by Dectin-1-dependent macrophage colony stimulating factor (M-CSF) expression. Our study suggests that Dectin-1 is an attractive target for experimental therapeutics in hepatic fibrosis and neoplastic transformation. More broadly, our work deciphers critical cross-talk between pattern recognition receptors and implicates a role for Dectin-1 in suppression of sterile inflammation, inflammation-induced oncogenesis, and LPS-mediated sepsis.

Outcomes of subtalar arthroereisis for the planovalgus foot.

Chronic pain and gait disturbance are possible complications of subtalar arthroereisis. Despite literature indicating a considerably high rate of such complications, subtalar arthroereisis continues to be commonly performed for children with pes planus. The goals of this study are to identify common presenting features and an approach to the treatment of foot pain after subtalar arthroereisis. This case report includes six feet in which subtalar implants were used to treat flatfoot deformities in children. After failing conservative management for chronic postoperative pain, all patients had their implants removed resulting in relief of pain. The expedited removal of subtalar implants in cases of chronic foot pain after arthroereisis is encouraged. The authors do not recommend the use of subtalar arthroereisis in pes planus given its potential complications and literature review indicating a paucity of cases with improved function and activity level as a result of the procedure.

The effect of HDL mimetic peptide 4F on PON1.

Several lines of evidence indicate that serum paraoxonase 1 (PON1) acts as an important guardian against cellular damage from oxidized lipids in plasma membrane, in low-density lipoprotein (LDL), against bacterial endotoxin and against toxic agents such as pesticide residues including organophosphates. In circulation, the high-density lipoprotein (HDL)-associated PON1 has the ability to prevent the formation of proinflammatory oxidized phospholipids. These oxidized phospholipids negatively regulate the activities of the HDL-associated PON1 and several other anti-inflammatory factors in HDL. During the acute phase response in rabbits, mice, and humans, there appears to be an increase in the formation of these oxidized lipids that results in the inhibition of the HDL-associated PON1 and an association of acute phase proteins with HDL that renders HDL proinflammatory. Low serum HDL is a risk factor for atherosclerosis and attempts are directed toward therapies to improve the quality and the relative concentrations of LDL and HDL. Apolipoprotein A-I (apoA-I) has been shown to reduce atherosclerotic lesions in laboratory animals. ApoA-I, however, is a large protein and needs to be administered parenterally, and it is costly. We have developed apoA-I mimetic peptides that are much smaller than apoA-I, and much more effective in removing the oxidized phospholipids and other oxidized lipids. These mimetic peptides improve LDL and HDL composition and function and reduce lesion formation in animal models of atherogenesis. Following is a brief description of some of the HDL mimetic peptides that can improve HDL and the effect of the peptide on PON1 activity.