Case report: Association between PTEN-gene variant and an aggressive case of multiple dAVFs.

Introduction: Mutations of the phosphatase and tensin homolog (PTEN) gene have been associated with a spectrum of disorders called PTEN hamartoma tumor syndrome, which predisposes the individual to develop various types of tumors and vascular anomalies. Its phenotypic spectrum includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome, autism spectrum disorders (ASD), some sporadic cancers, Lhermitte-Duclos disease (LDD), and various types of associated vascular anomalies. Clinical presentation: A previously healthy 27-year-old woman was experiencing visual scintillating scotomas and mild chronic headaches for the past 2 years. The initial computed tomographic (CT) and magnetic resonance imaging (MRI) scans did not reveal any abnormalities, but the possibility of pseudotumor cerebri was considered. Furthermore, a cerebral angiogram showed a posterior fossa dural arteriovenous fistula (dAVF), which was initially treated through embolization. However, in spite of proper treatment, this patient experienced multiple recurrent dAVFs in different locations, requiring multiple embolizations and surgeries. Despite exhibiting altered cerebral perfusion and hemodynamics, the patient did not display any significant symptoms until she experienced a sudden stroke resulting from deep venous thrombosis, which was not associated with any medical procedures or medication use. A comprehensive analysis was performed due to the aggressive nature of the dAVFs. Surprisingly, exome sequencing of a blood sample revealed a PTEN gene variant in chromosome 10, indicative of Cowden syndrome. However, no tumors or other vascular lesions were detected in other systems that would constitute Cowden syndrome. Conclusion: The rapid formation of multiple and complex dAVFs, coupled with not meeting the criteria for any other PTEN-related syndrome, unequivocally leads to the presentation of a novel phenotype of the PTEN germline variant.

Cytomegalovirus infection in intensive care unit patients with hematological malignancies: Characteristics and clinical outcomes.

BACKGROUND: Cytomegalovirus (CMV) infection is associated with poor outcome in ICU patients. However, data on immunocompromised patients are scarce. This study aims to describe characteristics and outcomes of critically ill hematological patients and CMV infection. CMV disease characteristics and relationship between CMV viral load, CMV disease, coinfections by other pathogens and outcomes are described. METHODS: Retrospective single center study (Jan 2010-Dec 2017). Adult patients, admitted to the ICU, having underlying hematological malignancy and CMV infection were included. Results are reported as median (interquartile) or n (%). Factors associated with hospital mortality or CMV disease were analysed using logistic regression. RESULTS: 178 patients were included (median age 55y [42-64], 69.1% male). Hospital mortality was 53% (n = 95). Median viral load was 2.7 Log [2.3-3.5]. CMV disease occurred in 44 (24.7%) patients. Coinfections concerned 159 patients (89.3%). After adjustment for confounders, need for vasopressors (OR 2.53; 95%CI 1.11-5.97) and viral load (OR 1.88 per Log; 95%CI 1.29-2.85) were associated with hospital mortality. However, neither CMV disease nor treatment were associated with outcomes. Allogeneic stem cell transplantation (OR 2.55; 95%CI 1.05-6.16), mechanical ventilation (OR 4.11; OR 1.77-10.54) and viral load (OR 1.77 per Log; 95%CI 1.23-2.61) were independently associated with CMV disease. Coinfections were not associated with CMV disease or hospital mortality. CONCLUSION: In critically-ill hematological patients, CMV viral load is independently associated with hospital mortality. Conversely, neither CMV disease nor treatment was associated with outcome suggesting viral load to be a surrogate for immune status rather than a cause of poor outcome.

Microsurgical Resection for Cavernous Malformation of the Uncus: 3D-Operative Video.

Cavernous malformations (CMs) are rare and often oligosymptomatic vascular lesions. The main symptoms include seizure and focal neurologic deficits.1-3 Depending on the symptomatology, location, size, and risk factors for bleeding, like the presence of a developmental venous anomaly, CMs can be highly morbid. Thus surgical resection may be considered. Deep-seated and eloquent CMs, like those in the uncus, can be challenging.4,5 In Video 1, we present a 23-year-old male adult who developed focal seizures (i.e., oral automatisms) after an episode of sudden intense headache 1 year ago. His neurologic examination was unremarkable. The patient consented to the procedure and publication of his image. Nevertheless, his magnetic resonance images showed an uncal 2-cm Zabramski type I CM. We exposed the insula and its limen through a right pterional craniotomy and transsylvian corridor. During the video, we discuss the surgical nuances to access and resect this CM lesion en bloc while preserving important vascular structures and white matter tracts. Postoperative neuroimaging demonstrated total resection. In postoperative day 1, the patient had 1 episode of generalized seizure and evolved with contralateral hemiparesis. The patient had a good recovery and was discharged on postoperative day 21. At the 6-month follow-up, the patient had no new epileptic events and presented complete weakness improvement. Through this minimally invasive and well-known surgical corridor, we preserve the mesial and lateral portion of the temporal lobe, reducing the risk of lesions to the Meyer loop and limbic association area.

Deep Learing for Sparse Domain Kalman Filtering with Applications on ECG Denoising and Motility Estimation.

OBJECTIVE: The reconstruction of an input based on a sparse combination of signals, known as sparse coding, has found widespread use in signal processing. In this work, the combination of sparse coding with Kalman filtering is explored and its potential is shown on two use-cases. METHODS: This work extends the Iterative Shrinkage and Thresholding Algorithm with a Kalman filter in the sparse domain. The resulting method may be implemented as a deep unfolded neural network and may be applied to any signal which has a sparse representation and a known or assumed relation between consecutive measurements. This method is evaluated on the use cases of noise reduction in the electrocardiogram (ECG) and the estimation of object motility. RESULTS: For ECG denoising, the proposed method achieved an improvement in Signal-to-Noise ratio of 18.6dB, which is comparable to state-of-the-art. In motility estimation, a correlation of 0.84 with ground truth simulations was found. CONCLUSION: The proposed method was shown to have advantages over sparse coding and Kalman filtering alone. Due to the low complexity and high generalizability of the proposed method, the implementation of context-specific knowledge or an extension to other applications can be readily made. SIGNIFICANCE: The presented Kalman-ISTA algorithm is a resource-efficient method combining the promise of both sparse coding and Kalman filtering, making it well-suited for various applications.

The effect of iron therapy on oxidative stress and intestinal microbiota in inflammatory bowel diseases: A review on the conundrum.

One in five patients with Inflammatory Bowel Disease (IBD) suffers from anemia, most frequently caused by iron deficiency. Anemia and iron deficiency are associated with worse disease outcomes, reduced quality of life, decreased economic participation, and increased healthcare costs. International guidelines and consensus-based recommendations have emphasized the importance of treating anemia and iron deficiency. In this review, we draw attention to the rarely discussed effects of iron deficiency and iron therapy on the redox status, the intestinal microbiota, and the potential interplay between them, focusing on the clinical implications for patients with IBD. Current data are scarce, inconsistent, and do not provide definitive answers. Nevertheless, it is imperative to rule out infections and discern iron deficiency anemia from other types of anemia to prevent untargeted oral or intravenous iron supplementation and potential side effects, including oxidative stress. Further research is necessary to establish the clinical significance of changes in the redox status and the intestinal microbiota following iron supplementation.

Pilot implementation of MiLES: a web-based intervention targeted at managers with the aim of enhancing the successful return to work of employees with cancer.

BACKGROUND: MiLES is a web-based intervention targeted at managers with the aim of enhancing the successful return to work (RTW) of employees with cancer. The purpose of this study was to identify barriers to and facilitators of implementing MiLES in organizations, from a manager's perspective. MATERIAL AND METHODS: MiLES was implemented as a pilot in four organizations for six weeks. Sixteen managers were included, of which fourteen were interviewed regarding their perceived barriers to and facilitators of implementation of MiLES in their organization. Interviews were recorded, transcribed verbatim and analyzed with content analysis. RESULTS: The managers experienced barriers to and facilitators of implementation related to: (1) implementation responsibilities, (2) the intervention's content, and (3) organizational characteristics. Regarding implementation responsibilities, management board approval and an organizational infrastructure with distinct described implementation responsibilities were perceived as facilitators. Regarding the intervention's content, its accessibility, user-friendliness and completeness were perceived as facilitators. If the content did not meet the manager's specific needs, this was perceived as a barrier. Regarding organizational characteristics, several intangible (e.g., added value of MiLES within different organizations) and tangible (e.g., integration into absenteeism registration) organizational characteristics were perceived as facilitators. The absence of a quiet place to use MiLES was perceived as barrier. CONCLUSION: Implementation of MiLES in organizations may benefit from an infrastructure within the organization that defines responsibilities regarding intervention delivery to managers of employees with cancer. Such an infrastructure should be aligned to existing organizational structures. As per interviewed managers, MiLES has added value in diverse organizations.

Lymphocele following lymph node dissection in cervical and endometrial cancer: A systematic review and meta-analysis.

OBJECTIVES: The purpose of this systematic review and meta-analysis was to evaluate the proportion and risk factors of lymphoceles and symptomatic lymphoceles after PLND in early-stage cervical and early-stage high or high-intermediate risk endometrial cancer. METHODS: Studies reporting on the proportion of lymphocele after PLND were conducted in PubMed, Embase and Cochrane Library. Retrieved studies were screened on title/abstract and full text by two reviewers independently. Quality assessment was conducted using the Newcastle Ottowa Scale and the Cochrane risk-of-bias tool. Proportion of lymphocele and possible risk factors were pooled through random-effects meta-analyses. RESULTS: From the 233 studies retrieved, 24 studies were included. The pooled proportion of lymphocele was 14% and of symptomatic lymphocele was 3%. Routinely performing diagnostics was associated with a significantly higher proportion of lymphocele compared to diagnostics performed on indication (21% versus 4%, p < 0.01). Laparotomic surgical approach led to a significantly higher proportion of lymphoceles than laparoscopic surgical approach (18% versus 7%, p = 0.05). The proportion of lymphocele was significantly higher when >15% of the study population underwent additional paraaortic lymph node dissection (PAOLND) opposed to <15% (15% versus 3%, p < 0.01). A mean number of lymph nodes dissected of <21 resulted in a significantly higher pooled proportion of lymphoceles opposed to when the mean number was 21 or higher (19% versus 5%, p = 0.02). Other risk factors analysed were BMI, lymph node metastasis, adjuvant radiotherapy and follow up. There was no sufficient data to detect significant risk factors for the development of symptomatic lymphoceles. CONCLUSION: The pooled proportion of lymphocele was 14% of which symptomatic lymphoceles occurred in 3%. Significant risk factors for the total proportion of lymphoceles were laparotomic approach, decreased number of lymph nodes dissected and additional PAOLND.

Differences in in-hospital outcomes and healthcare utilization for laparoscopic versus open approach for emergency inguinal hernia repair: a nationwide analysis.

PURPOSE: There has been a growing debate of whether laparoscopic or open surgical techniques are superior for inguinal hernia repair. For incarcerated and strangulated inguinal hernias, the laparoscopic approach remains controversial. This study aims to be the first nationwide analysis to compare clinical and healthcare utilization outcomes between laparoscopic and open inguinal hernia repair in an emergency setting. METHODS: A retrospective analysis of the National Inpatient Sample was performed. All patients who underwent laparoscopic inguinal hernia repair (LIHR) and open inguinal hernia repair (OIHR) between October 2015 and December 2019 were included. The primary outcome was mortality, and secondary outcomes include post-operative complications, ICU admission, length of stay (LOS), and total admission cost. Two approaches were compared using univariate and multivariate logistic and linear regression. RESULTS: Between the years 2015 and 2019, 17,205 patients were included. Among these, 213 patients underwent LIHR and 16,992 underwent OIHR. No difference was observed between laparoscopic and open repair for mortality (odds ratio [OR] 0.80, 95% CI [0.25, 2.61], p = 0.714). Additionally, there was no significant difference between groups for post-operative ICU admission (OR 1.11, 95% CI [0.74, 1.67], p = 0.614), post-operative complications (OR 1.09, 95% CI [0.76, 1.56], p = 0.647), LOS (mean difference [MD]: -0.02 days, 95% CI [- 0.56, 0.52], p = 0.934), or total admission cost (MD: $3,028.29, 95% CI [$- 110.94, $6167.53], p = 0.059). CONCLUSION: Laparoscopic inguinal hernia repair is comparable to the open inguinal hernia repair with respect to low rates of morbidity, mortality as well as healthcare resource utilization.

Role of burn severity and posttraumatic stress symptoms in the co-occurrence of itch and neuropathic pain after burns: A longitudinal study.

Itch and pain are common after burns. Neuropathic mechanisms may underlie both modalities but remain not well-understood. This study aims to prospectively document neuropathic pain symptoms and to identify potential itch symptom profiles that differ regarding duration and co-occurrence with neuropathic pain which may inform underlying pathophysiological mechanisms and respond to different treatments. Adult burn survivors (n = 192) self-reported itch and neuropathic pain at 2 weeks post-discharge, 3, 6, 12, and 18 months post-burn. Based on the presence of itch and pain symptoms over time, participants were allocated to one itch profile: transient itch/pain, chronic itch, or chronic itch & pain. Profiles were compared on itch intensity over time using General Linear Modeling. Age, gender, burn severity, posttraumatic stress (PTS) symptoms and baseline itch intensity were examined as potential predictors of the profiles in a Multi-nominal regression analysis. Neuropathic pain occurred in 54% after discharge which decreased to 24% 18 months later. Itch intensity was highest in the chronic itch & pain profile. Compared to the transient itch profile, the chronic itch & pain profile was associated with higher burn severity and more PTS symptoms. Compared to the chronic itch profile, the chronic itch & pain profile was associated with more PTS symptoms. Findings suggest that biological and psycho-dermatological processes underlie both chronic neuropathic pain and itch processes in burn scars. Further research should elucidate the mechanisms underlying the different itch profiles, with specific focus on skin innervation and psychological factors.

Guidelines of the French Society of ENT (SFORL): Drug-induced sleep endoscopy in adult obstructive sleep apnea syndrome.

OBJECTIVES: To determine the indications, anesthesiological and surgical procedure and interest of drug-induced sleep endoscopy in the treatment of adult obstructive sleep apnea syndrome. DESIGN: A redactional committee of 17 experts was set up. Conflicts of interest were disclosed and followed up throughout the process of drawing up the guidelines. The work received no funding from any firm dealing in health products (drugs or devices). The GRADE (Grading of Recommendations Assessment, Development and Evaluation) method was applied to assess the quality of the data on which the guidelines were founded. It was stressed that strong recommendations should not be made on the basis of poor-quality or insufficient data. METHODS: The committee studied 29 questions on 5 topics: indications and contraindications, anesthetic technique, surgical technique, interpretation and reporting of results, and management guided by results. RESULTS: Expert review and application of the GRADE method led to 30 guidelines: 10 with high level of evidence (Grade 1+ or 1-), 19 with low level (GRADE 2+ or 2-) and 1 expert opinion. CONCLUSION: Experts fully agreed on the strong guidelines formalizing the indications and modalities of drug-induced sleep endoscopy for adult obstructive sleep apnea syndrome.

Mycoplasma pneumoniae Compared to Streptococcus pneumoniae Avoids Induction of Proinflammatory Epithelial Cell Responses despite Robustly Inducing TLR2 Signaling.

Mycoplasma pneumoniae and Streptococcus pneumoniae are the most common bacterial causes of pneumonia in children. The clinical characteristics of pneumonia differ significantly between the two bacteria. We aimed to elucidate the differences in pathogenesis between M. pneumoniae and S. pneumoniae by characterizing the respiratory epithelial cell immune response to both pathogens. Using primary human bronchial epithelial cells in air-liquid interface cultures, we observed lower production of the proinflammatory cytokines interleukin-6 (IL-6) and IL-8 in response to M. pneumoniae than to S. pneumoniae. In contrast to the differences in proinflammatory cytokine production, Toll-like receptor 2 (TLR2)-mediated signaling in response to M. pneumoniae was stronger than to S. pneumoniae. This difference largely depended on TLR1 and not TLR6. We found that M. pneumoniae, but not S. pneumoniae, also induced signaling of TLR10, a coreceptor of TLR2 that has inhibitory properties. M. pneumoniae-induced TLR10 signaling on airway epithelial cells was partially responsible for low IL-8 production, as blocking TLR10 by specific antibodies increased cytokine production. M. pneumoniae maintained Th2-associated cytokine production by epithelial cells, which concurs with the known association of M. pneumoniae infection with asthma. M. pneumoniae left IL-33 levels unchanged, whereas S. pneumoniae downregulated IL-33 production both under homeostatic and Th2-promoting conditions. By directly comparing M. pneumoniae and S. pneumoniae, we demonstrate that M. pneumoniae avoids induction of proinflammatory cytokine response despite its ability to induce robust TLR2 signaling. Our new findings suggest that this apparent paradox may be partially explained by M. pneumoniae-induced signaling of TLR2/TLR10.

p21-activated kinase 4 controls the aggregation of α-synuclein by reducing the monomeric and aggregated forms of α-synuclein: involvement of the E3 ubiquitin ligase NEDD4-1.

Aggregation of misfolded alpha-synuclein (α-synuclein) is a central player in the pathogenesis of neurodegenerative diseases. Therefore, the regulatory mechanism underlying α-synuclein aggregation has been intensively studied in Parkinson's disease (PD) but remains poorly understood. Here, we report p21-activated kinase 4 (PAK4) as a key regulator of α-synuclein aggregation. Immunohistochemical analysis of human PD brain tissues revealed an inverse correlation between PAK4 activity and α-synuclein aggregation. To investigate their causal relationship, we performed loss-of-function and gain-of-function studies using conditional PAK4 depletion in nigral dopaminergic neurons and the introduction of lentivirus expressing a constitutively active form of PAK4 (caPAK4; PAK4S445N/S474E), respectively. For therapeutic relevance in the latter setup, we injected lentivirus into the striatum following the development of motor impairment and analyzed the effects 6 weeks later. In the loss-of-function study, Cre-driven PAK4 depletion in dopaminergic neurons enhanced α-synuclein aggregation, intracytoplasmic Lewy body-like inclusions and Lewy-like neurites, and reduced dopamine levels in PAK4DAT-CreER mice compared to controls. Conversely, caPAK4 reduced α-synuclein aggregation, as assessed by a marked decrease in both proteinase K-resistant and Triton X100-insoluble forms of α-synuclein in the AAV-α-synuclein-induced PD model. Mechanistically, PAK4 specifically interacted with the NEDD4-1 E3 ligase, whose pharmacological inhibition and knockdown suppressed the PAK4-mediated downregulation of α-synuclein. Collectively, these results provide new insights into the pathogenesis of PD and suggest PAK4-based gene therapy as a potential disease-modifying therapy in PD.

Adjuvant Use of PlasmaJet Device During Cytoreductive Surgery for Advanced-Stage Ovarian Cancer: Results of the PlaComOv-study, a Randomized Controlled Trial in The Netherlands.

OBJECTIVE: Standard surgical treatment of advanced-stage ovarian carcinoma with electrosurgery cannot always result in complete cytoreductive surgery (CRS), especially when many small metastases are found on the mesentery and intestinal surface. We investigated whether adjuvant use of a neutral argon plasma device can help increase the complete cytoreduction rate. PATIENTS AND METHODS: 327 patients with FIGO stage IIIB-IV epithelial ovarian cancer (EOC) who underwent primary or interval CRS were randomized to either surgery with neutral argon plasma (PlasmaJet) (intervention) or without PlasmaJet (control group). The primary outcome was the percentage of complete CRS. The secondary outcomes were duration of surgery, blood loss, number of bowel resections and colostomies, hospitalization, 30-day morbidity, and quality of life (QoL). RESULTS: Complete CRS was achieved in 119 patients (75.8%) in the intervention group and 115 patients (67.6%) in the control group (risk difference (RD) 8.2%, 95% confidence interval (CI) -0.021 to 0.181; P = 0.131). In a per-protocol analysis excluding patients with unresectable disease, complete CRS was obtained in 85.6% in the intervention group and 71.5% in the control group (RD 14.1%, 95% CI 0.042 to 0.235; P = 0.005). Patient-reported QoL at 6 months after surgery differed between groups in favor of PlasmaJet surgery (95% CI 0.455-8.350; P = 0.029). Other secondary outcomes did not differ significantly. CONCLUSIONS: Adjuvant use of PlasmaJet during CRS for advanced-stage ovarian cancer resulted in a significantly higher proportion of complete CRS in patients with resectable disease and higher QoL at 6 months after surgery. (Funded by ZonMw, Trial Register NL62035.078.17.) TRIAL REGISTRATION: Approved by the Medical Ethics Review Board of the Erasmus University Medical Center Rotterdam, the Netherlands, NL62035.078.17 on 20-11-2017. Recruitment started on 30-1-2018.

Disease activity in inflammatory bowel disease patients is associated with increased liver fat content and liver fibrosis during follow-up.

PURPOSE: Liver steatosis is a frequently reported condition in patients with inflammatory bowel disease (IBD). Different factors, both metabolic and IBD-associated, are believed to contribute to the pathogenesis. The aim of our study was to calculate the prevalence of liver steatosis and fibrosis in IBD patients and to evaluate which factors influence changes in steatosis and fibrosis during follow-up. METHODS: From June 2017 to February 2018, demographic and biochemical data was collected at baseline and after 6-12 months. Measured by transient elastography (FibroScan), liver steatosis was defined as Controlled Attenuation Parameter (CAP) ≥248 and fibrosis as liver stiffness value (Emed) ≥7.3 kPa. IBD disease activity was defined as C-reactive protein (CRP) ≥10 mg/l and/or fecal calprotectin (FCP) ≥150 µg/g. Univariate and multivariate regression analysis was performed; a p-value of ≤0.05 was considered significant. RESULTS: Eighty-two out of 112 patients were seen for follow-up; 56% were male. The mean age was 43 ± 16.0 years, and mean BMI was 25.1 ± 4.7 kg/m2. The prevalence of liver steatosis was 40% and of fibrosis was 20%. At baseline, 26 patients (32%) had an active episode of IBD. Using a multivariate analysis, disease activity at baseline was associated with an increase in liver steatosis (B = 37, 95% CI 4.31-69.35, p = 0.027) and liver fibrosis (B = 1.2, 95% CI 0.27-2.14, p = 0.016) during follow-up. CONCLUSIONS: This study confirms the relatively high prevalence of liver steatosis and fibrosis in IBD patients. We demonstrate that active IBD at baseline is associated with both an increase in liver steatosis and fibrosis during follow-up.

Development of a plain-language guide for discussing breast cancer genetic counseling and testing with patients with limited health literacy.

PURPOSE: Due to limited health literacy and resulting ineffective communication between healthcare professionals and patients, not all eligible patients are offered breast cancer genetic counseling and testing. We aimed to develop a plain-language guide to increase effective communication about genetic counseling and testing with breast cancer patients with limited health literacy. METHODS: Together with oncological healthcare professionals, we drafted a list of jargon words frequently used during (breast) cancer genetic counseling. In a focus group interview with breast cancer counselees with limited health literacy, who had received genetic counseling before, we reformulated these words in plain language. Low-literate individuals, who are not familiar with breast cancer care or genetic counseling, reflected on the draft of the guide. Completeness, acceptability, and perceived usability were tested in an online questionnaire among healthcare professionals. RESULTS: The result is a plain-language guide for genetic counseling and testing with 33 frequently used jargon words and a reformulation of these words in plain language. Acceptability and perceived usefulness of the guide among healthcare professionals (n = 58) were high. CONCLUSION: The plain-language guide provides opportunities to facilitate communication about genetic counseling and testing with patients with limited health literacy and could enhance opportunities for patients to make informed decisions to participate in genetic testing. As the intention from healthcare professionals to use the plain-language guide is high, implementation of the guide in a real-life setting seems promising.

High mobility group A protein-2 as a tumor cancer diagnostic and prognostic marker: a systematic review and meta-analysis.

High mobility group A protein-2 (HMGA2) is an architectural transcription factor that binds to the A/T-rich DNA minor groove and is responsible for regulating transcriptional activity of multiple genes indirectly through chromatin change and assembling enhanceosome. HMGA2 is overexpressed in multiple tumor types, suggesting its involvement in cancer initiation and progression, thus, making it an ideal candidate for cancer diagnostic and prognostic. We performed a systematic review to examine the role of HMGA2 as a universal tumor cancer diagnostic and prognostic marker. We used Reporting Recommendations for Tumor Marker Prognostic Studies to systematically search OvidMedline, PubMed, and the Cochrane Library for English language studies, published between 1995 and June 2019. Meta-analysis provided pooled risk estimates and their 95% confidence intervals (CIs) for an association between overall survival and recurrence of cancers for studies with available estimates. We identified 42 eligible studies with a total of 5123 tumor samples in 15 types of cancer. The pooled percentage of HMGA2 gene expression in tumor samples was 65.14%. Meta-analysis showed that cancer patients with HMGA2 positive have significantly reduced survival, compared to patients without HMGA2 gene [pooled-hazard ratio (HR) = 1.85, 95% CI 1.48-2.22]. There was a positive association between cancer patients with HMGA2 overexpression and cancer recurrence though this association did not reach significance (pooled-HR = 1.44, 95% CI 0.80-2.07). Overexpression of HMGA2 was found in 15 types of cancer. There was an association between HMGA2 overexpression with reduced survival of cancer patients. HMGA2 is thus considered a promising universal tumor marker for prognostics.

Complex Geometric Structure of a Simple Solid-Liquid Interface: GaN(0001)-Ga.

The equilibrium atomic interface structure between Ga and GaN(0001) is shown to contain substrate surface vacancies followed by substrate-induced layering and preferential lateral ordering in the liquid. The uncovered presence of point defects, in the form of vacancies at both sides of the solid-liquid interface, is an important structural feature which governs the local physical properties. Our x-ray diffraction study reveals that the layering is very stable and persists up to a temperature of 1123 K and a nitrogen pressure of 32 bar. The Ga layer spacing agrees remarkably well with the Friedel oscillation period for this system.

[Preoperative risk and perioperative management of obese patients]. / Risque pré-opératoire et gestion péri-opératoire des patients obèses.

The obese patient is at an increased risk of perioperative complications. Most importantly, these include difficult access to the airways (intubation, difficult or impossible ventilation), and post-extubation respiratory distress secondary to the development of atelectasis or obstruction of the airways, sometimes associated with the use of morphine derivatives. The association of obstructive sleep apnea syndrome (OSA) with obesity is very common, and induces a high risk of peri- and postoperative complications. Preoperative OSA screening is crucial in the obese patient, as well as its specific management: use of continuous positive pre, per and postoperative pressure. For any obese patient, the implementation of protocols for mask ventilation and/or difficult intubation and the use of protective ventilation, morphine-sparing strategies and a semi-seated positioning throughout the care, is recommended, combined with close monitoring postoperatively. The dosage of anesthetic drugs should be based on the theoretical ideal weight and then titrated, rather than dosed to the total weight. Monitoring of neuromuscular blocking should be used where appropriate, as well as monitoring of the depth of anesthesia. The occurrence of intraoperative recall is indeed more frequent in the obese patient than in the non-obese patient. Appropriate prophylaxis against venous thromboembolic disease and early mobilization are recommended, as thromboembolic disease is increased in the obese patient. The use of non-invasive ventilation to prevent the occurrence of acute post-operative respiratory failure and for its treatment is particularly effective in obese patients. In case of admission to ICU, an individualized ventilatory management based on pathophysiology and careful monitoring should be initiated.