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Dysregulated extracellular matrix (ECM) is a hallmark of adverse cardiac remodeling after myocardial infarction (MI). Previous work from our laboratory suggests that synthesis of the major ECM component hyaluronan (HA) may be beneficial for post-infarct healing. Here, we aimed to investigate the mechanisms of hyaluronan synthase 3 (HAS3) in cardiac healing after MI. Mice with genetic deletion of Has3 (Has3 KO) and wildtype mice (WT) underwent 45 min of ischemia with subsequent reperfusion (I/R), followed by monitoring of heart function and analysis of tissue remodeling for up to three weeks. Has3 KO mice exhibited impaired cardiac function as evidenced by a reduced ejection fraction. Accordingly, Has3 deficiency also resulted in an increased scar size. Cardiac fibroblast activation and CD68sup+/supmacrophage counts were similar between genotypes. However, we found a significant decrease in CD4 T cells in the hearts of Has3 KO mice seven days post-MI, in particular reduced numbers of CD4sup+/supCXCR3sup+/supTh1 and CD4sup+/supCD25sup+/supTreg cells. Furthermore, Has3 deficient cardiac T cells were less activated and more apoptotic as shown by decreased CD69sup+/supand increased annexin Vsup+/supcells, respectively. In vitro assays using activated splenic CD3 T cells demonstrated that Has3 deficiency resulted in reduced expression of the main HA receptor CD44 and diminished T cell proliferation. T cell transendothelial migration was similar between genotypes. Of note, analysis of peripheral blood from patients with ST-elevation myocardial infarction (STEMI) revealed that HAS3 is the predominant HAS isoenzyme also in human T cells. In conclusion, our data suggest that HAS3 is required for mounting a physiological T cell response after MI to support cardiac healing. Therefore, our study may serve as a foundation for the development of novel strategies targeting HA-matrix to preserve T cell function after MI.

Following the spread of the infection from the new SARS-CoV2 coronavirus in March 2020, several surgical societies have released their recommendations to manage the implications of the COVID-19 pandemic for the daily clinical practice. The recommendations on emergency surgery have fueled a debate among surgeons on an international level.We maintain that laparoscopic cholecystectomy remains the treatment of choice for acute cholecystitis, even in the COVID-19 era. Moreover, since laparoscopic cholecystectomy is not more likely to spread the COVID-19 infection than open cholecystectomy, it must be organized in such a way as to be carried out safely even in the present situation, to guarantee the patient with the best outcomes that minimally invasive surgery has shown to have.

Background: This study aims to provide guidance for the use of neoadjuvant and adjuvant systemic therapy in women with newly diagnosed stage II–IV epithelial ovary, fallopian tube, or primary peritoneal carcinoma. Methods: EMBASE, MEDLINE, and Cochrane Library were investigated for relevant systematic reviews and phase III trials. Articles focusing on consolidation and maintenance therapies were excluded. Results: For women with potentially resectable disease, primary cytoreductive surgery, followed by six to eight cycles of intravenous three-weekly paclitaxel and carboplatin is recommended. For those with a high-risk profile for primary cytoreductive surgery, neoadjuvant chemotherapy can be an option. Adjuvant chemotherapy with six cycles of dose-dense weekly paclitaxel plus three-weekly carboplatin can be considered for women of Japanese descent. In women with stage III or IV disease, the incorporation of bevacizumab concurrent with paclitaxel and carboplatin is not recommended for use as adjuvant therapy unless bevacizumab is continued as maintenance therapy. Intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel can be considered for stage III optimally debulked women who did not receive neoadjuvant chemotherapy. However, intraperitoneal administration of chemotherapy with bevacizumab should not be considered as an option for stage II–IV optimally debulked women. Discussion: The recommendations represent a current standard of care that is feasible to implement and valued by both clinicians and patients.

CD8+T cells are a major prognostic determinant in solid tumors, including colorectal cancer (CRC). However, understanding how the interplay between different immune cells impacts on clinical outcome is still in its infancy. Here, we describe that the interaction of tumor infiltrating neutrophils expressing high levels of CD15 with CD8+T effector memory cells (TEM) correlates with tumor progression. Mechanistically, stromal cell-derived factor-1 (CXCL12/SDF-1) promotes the retention of neutrophils within tumors, increasing the crosstalk with CD8+T cells. As a consequence of the contact-mediated interaction with neutrophils, CD8+T cells are skewed to produce high levels of GZMK, which in turn decreases E-cadherin on the intestinal epithelium and favors tumor progression. Overall, our results highlight the emergence of GZMKhighCD8+TEMin non-metastatic CRC tumors as a hallmark driven by the interaction with neutrophils, which could implement current patient stratification and be targeted by novel therapeutics.

GOALS AND BACKGROUND Using natural language processing to create a nonalcoholic fatty liver disease (NAFLD) cohort in primary care, we assessed advanced fibrosis risk with the Fibrosis-4 Index (FIB-4) and NAFLD Fibrosis Score (NFS) and evaluated risk score agreement. MATERIALS AND METHODS In this retrospective study of adults with radiographic evidence of hepatic steatosis, we calculated patient-level FIB-4 and NFS scores and categorized them by fibrosis risk. Risk category and risk score agreement was analyzed using weighted κ, Pearson correlation, and Bland-Altman analysis. A multinomial logistic regression model evaluated associations between clinical variables and discrepant FIB-4 and NFS results. RESULTS Of the 767 patient cohorts, 71% had a FIB-4 or NFS score in the indeterminate-risk or high-risk category for fibrosis. Risk categories disagreed in 43%, and scores would have resulted in different clinical decisions in 30% of the sample. The weighted κ statistic for risk category agreement was 0.41 [95% confidence interval (CI): 0.36-0.46] and the Pearson correlation coefficient for log FIB-4 and NFS was 0.66 (95% CI: 0.62-0.70). The multinomial logistic regression analysis identified black race (odds ratio=2.64, 95% CI: 1.84-3.78) and hemoglobin A1c (odds ratio=1.37, 95% CI: 1.23-1.52) with higher odds of having an NFS risk category exceeding FIB-4. CONCLUSIONS In a primary care NAFLD cohort, many patients had elevated FIB-4 and NFS risk scores and these risk categories were often in disagreement. The choice between FIB-4 and NFS for fibrosis risk assessment can impact clinical decision-making and may contribute to disparities of care.

Background During laparoscopy, the abdominal cavity is insufflated with carbon dioxide (CO2) that could become contaminated with viruses and surgical smoke. Medical staff is potentially exposed when this gas leaks into the operating room through the instruments and past trocar valves. No detailed studies currently exist that have quantified these leakage pathways. Therefore, the goal of this study was to quantify the gas leakages through trocars and instruments, during minimally invasive procedures. Methods A model of the surgical environment was created, consisting of a rigid container with an interface for airtight clamping of laparoscopic equipment such as trocars and surgical instruments. The model was insufflated to 15 mm Hg using a pressure generator and a pneumotachograph measured the equipment gas leak. A protocol of several use cases was designed to simulate the motions and forces the surgeon exerts on the trocar during surgery. Results Twenty-three individual trocars and twenty-six laparoscopic instruments were measured for leakage under the different conditions of the protocol. Trocar leakages varied between 0 L/min and more than 30 L/min, the instruments revealed a range of leakages between 0 L/min and 5.5 L/min. The results showed that leakage performance varied widely between trocars and instruments and that the performance and location of the valves influenced trocar leakage. Conclusions We propose trocar redesigns to overcome specific causes of gas leaks. Moreover, an international testing standard for CO2 leakage for all new trocars and instruments is needed so surgical teams can avoid this potential health hazard when selecting new equipment.

Background The spread of the SARS-CoV2 virus, which causes COVID-19 disease, profoundly impacted the surgical community. Recommendations have been published to manage patients needing surgery during the COVID-19 pandemic. This survey, under the aegis of the Italian Society of Endoscopic Surgery, aims to analyze how Italian surgeons have changed their practice during the pandemic. Methods The authors designed an online survey that was circulated for completion to the Italian departments of general surgery registered in the Italian Ministry of Health database in December 2020. Questions were divided into three sections: hospital organization, screening policies, and safety profile of the surgical operation. The investigation periods were divided into the Italian pandemic phases I (March–May 2020), II (June–September 2020), and III (October–December 2020). Results Of 447 invited departments, 226 answered the survey. Most hospitals were treating both COVID-19-positive and -negative patients. The reduction in effective beds dedicated to surgical activity was significant, affecting 59% of the responding units. 12.4% of the respondents in phase I, 2.6% in phase II, and 7.7% in phase III reported that their surgical unit had been closed. 51.4%, 23.5%, and 47.8% of the respondents had at least one colleague reassigned to non-surgical COVID-19 activities during the three phases. There has been a reduction in elective (> 200 procedures: 2.1%, 20.6% and 9.9% in the three phases, respectively) and emergency ( Conclusion This survey offers three faithful snapshots of how the surgical community has reacted to the COVID-19 pandemic during its three phases. The significant reduction in surgical activity indicates that better health policies and more evidence-based guidelines are needed to make up for lost time and surgery not performed during the pandemic.

Totally minimally invasive Ivor-Lewis esophagectomy (TMIIL) is associated to lower rate of post-operative complication, decreases length of hospital stay and improves quality of life compared to open approach. Nevertheless, adaptation of TMIIL still proceeds at slow pace, mainly due to the difficulty to perform the intra-thoracic anastomosis and heterogeneity of surgical techniques. We present our experience with TMIIL utilizing a stapled side-to-side anastomosis. We retrospectively evaluated 36 patients who underwent a planned TMIIL from January 2017 to September 2020. Esophagogastric anastomoses were performed using a 3-cm linear-stapled side-to-side technique. General features, operative techniques, pathology data and short-term outcomes were analyzed. The median operative time was 365 min (ranging from 240 to 480 min) with a median blood loss of 100 ml (50–1000 ml). The median overall length of stay was 13 (7–64) days and in-hospital mortality rate was 2.8%. Two patients (5.6%) had an anastomotic leak, without need for operative intervention and another patient developed an anastomotic stricture, resolved with a single endoscopic dilation. Chylothorax occurred in three patients; two of these required a surgical intervention. Pulmonary complications occurred in six patients (16.7%). Based on Comprehensive Complications Index (CCI), median values of complications were 27.9 (ranging from 20.9 to 100). The results of our study suggest that TMIIL with a 3-cm linear-stapled anastomosis seems to be safe and effective, with low rates of post-operative anastomotic leak and stricture.

Background While laparoscopic approach for right hemicolectomy (LRH) is considered appropriate for the surgical treatment of both malignant and benign diseases of right colon, there is still debate about how to perform the ileo-colic anastomosis. The ColonDxItalianGroup (CoDIG) was designed as a cohort, observational, prospective, multi-center national study with the aims of evaluating the surgeons’ attitude regarding the intracorporeal (ICA) or extra-corporeal (ECA) anastomotic technique and the related surgical outcomes. Methods One hundred and twenty-five Surgical Units experienced in colorectal and advanced laparoscopic surgery were invited and 85 of them joined the study. Each center was asked not to change its surgical habits. Data about demographic characteristics, surgical technique and postoperative outcomes were collected through the official SICE website database. One thousand two hundred and twenty-five patients were enrolled between March 2018 and September 2018. Results ICA was performed in 70.4% of cases, ECA in 29.6%. Isoperistaltic anastomosis was completed in 85.6%, stapled in 87.9%. Hand-sewn enterotomy closure was adopted in 86%. Postoperative complications were reported in 35.4% for ICA and 50.7% for ECA; no significant difference was found according to patients’ characteristics and technologies used. Median hospital stay was significantly shorter for ICA (7.3 vs. 9 POD). Postoperative pain in patients not prescribed opioids was significantly lower in ICA group. Conclusions In our survey, a side-to-side isoperistaltic stapled ICA with hand-sewn enterotomy closure is the most frequently adopted technique to perform ileo-colic anastomosis after any indications for elective LRH. According to literature, our study confirmed better short-term outcomes for ICA, with reduction of hospital stay and postoperative pain. Trial registration Clinical trial (Identifier: NCT03934151).

Umbilical Cord Blood (UCB) transplant (UCBT) is a curative procedure for patients with hematologic malignancies and genetic disorders and expands access for non-Caucasian patients unable to find a fully matched unrelated donor. In 2011, the Food and Drug Administration (FDA) required that unrelated UCBT use either licensed UCB or unlicensed UCB via an Investigational New Drug (IND). The National Marrow Donor Program® (NMDP) manages an IND under which 2456 patients (1499 adults and 957 children (564 malignant disease and 393 non-malignant disease) received single or double UCBT between October 2011 and December, 2016. Median age was 31 years (

International literature reports an increase of the incidence of psychological disorders because of the COVID-19 pandemic. Especially young people and people with pre-existing psychological disorders are troubled by the pandemic. Objective of this study is the extent of psychological symptoms, the functioning and the treatment success of rehabilitation inpatients who participated in a medical and psychiatric rehabilitation in the year before the COVID-19 pandemic and those who participated during the COVID-19 phase.The data of N=1,715 rehabilitation inpatients who completed the rehabilitation before the lockdown in 2019 and N=707 rehabilitation inpatients who began in 2020 after the lockdown of the clinic due to the pandemic (during the COVID-19 phase) from March to Mai 2020 are compared in reference to their sample characteristics and their results in patient reported outcomes.There are no significant differences between the two observed time periods in reference to the sociodemographic characteristics of the rehabilitation inpatients. At the beginning of the rehabilitation there was no significant difference in the scale somatization. There was a significantly higher score in the scales' anxiety and depression during the COVID-19 phase, but only to the extent of a small effect. The results of the scales of activity and participation (ICF 3 F AT) as well as functionality (WHODAS 2.0) do not differ in the time periods at the beginning of the rehabilitation. However, rehabilitation inpatients with low socioeconomic status (rehabilitation allowance or disability pension) have critical scores in some scales. The rehabilitation success is comparable to the one before the COVID-19 pandemic and falls within the range of medium to high effect sizes.The study shows - with respect to its limitations - low or no significant differences in reference to the sociodemographic data and the symptomatic load at the beginning of the rehabilitation. The effect sizes are comparable with the time frame bevor the COVID-19 pandemic. The results of international studies, which reported a considerable increase in psychological stress of the population cannot directly be transferred to the Austrian rehabilitation clientele.In der internationalen Literatur werden Steigerungen der Inzidenzraten psychischer Erkrankungen durch die COVID-19-Pandemie berichtet. Junge Menschen und Menschen mit psychischen Vorerkrankungen sind besonders durch die Pandemie belastet. Gegenstand dieser Studie sind das Ausmaß psychischer Symptombelastung, die Funktionsfähigkeit und der Behandlungserfolg bei Rehabilitanden der medizinisch-psychiatrischen Rehabilitation im Jahr vor Beginn der COVID-19-Pandemie und während der COVID-19-Phase.Die Daten von N=1715 Rehabilitanden mit Reha-Abschluss vor dem ersten Lockdown und von N=707 Rehabilitanden mit Reha-Beginn nach der Corona-bedingten Schließung der Klinik von März bis Mai 2020 aus den Jahren 2019 und 2020 werden hinsichtlich der Stichprobencharakteristik sowie der Ergebnisse in den Patient-reported Outcomes (Beginn und Ende der Rehabilitation) verglichen.Zwischen den beiden Beobachtungszeiträumen zeigen sich keine bedeutsamen Unterschiede in der soziodemografischen Charakteristik der Rehabilitanden. Bei Reha-Beginn zeigt sich in der Skala Somatisierung kein signifikanter Unterschied, in den Skalen Ängstlichkeit und Depressivität zeigt sich während der COVID-19-Phase ein signifikant höherer Wert, allerdings im Ausmaß eines sehr kleinen Effekts. In den Skalen zu Aktivitäten und Teilhabe (ICF 3 F AT) sowie bei der Funktionsfähigkeit (WHODAS 2.0) unterscheiden sich die Werte der Vergleichszeiträume bei Reha-Beginn nicht. Rehabilitanden mit niedrigerem sozioökonomischem Status (Reha-Geld oder Invaliditäts-/Berufsunfähigkeitspension) weisen hingegen in einigen Skalen kritischere Werte auf. Der Reha-Erfolg ist vergleichbar mit dem Zeitraum vor der COVID-19-Pandemie und liegt im Bereich von mittleren bis hohen Effektgrößen.Die Studie zeigt – unter Berücksichtigung der Limitationen – geringe oder gar keine signifikanten Unterschiede in den soziodemografischen Daten und in der Symptombelastung bei Reha-Beginn und die Effektgrößen sind vergleichbar mit dem Zeitraum vor der COVID-19-Pandemie. Die Ergebnisse internationaler Studien, dass es zu einem deutlichen Anstieg psychischer Belastungen während der COVID-19-Pandemie in der Bevölkerung gekommen ist, können nicht direkt auf die österreichische Reha-Klientel übertragen werden.

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Background COVID-19 pandemic presented an unexpected challenge for the surgical community in general and Minimally Invasive Surgery (MIS) specialists in particular. This document aims to summarize recent evidence and experts’ opinion and formulate recommendations to guide the surgical community on how to best organize the recovery plan for surgical activity across different sub-specialities after the COVID-19 pandemic. Methods Recommendations were developed through a Delphi process for establishment of expert consensus. Domain topics were formulated and subsequently subdivided into questions pertinent to different surgical specialities following the COVID-19 crisis. Sixty-five experts from 24 countries, representing the entire EAES board, were invited. Fifty clinicians and six engineers accepted the invitation and drafted statements based on specific key questions. Anonymous voting on the statements was performed until consensus was achieved, defined by at least 70% agreement. Results A total of 92 consensus statements were formulated with regard to safe resumption of surgery across eight domains, addressing general surgery, upper GI, lower GI, bariatrics, endocrine, HPB, abdominal wall and technology/research. The statements addressed elective and emergency services across all subspecialties with specific attention to the role of MIS during the recovery plan. Eighty-four of the statements were approved during the first round of Delphi voting (91.3%) and another 8 during the following round after substantial modification, resulting in a 100% consensus. Conclusion The recommendations formulated by the EAES board establish a framework for resumption of surgery following COVID-19 pandemic with particular focus on the role of MIS across surgical specialities. The statements have the potential for wide application in the clinical setting, education activities and research work across different healthcare systems.

Purpose: To retrospectively review our experience on 84 patients with squamous cell anal canal cancer (SCAC) within 12 months after combined treatment with intensity-modulated RT (IMRT), in terms of acute and early-late toxicity, overall treatment time and interruptions, colostomy-free survival (CFS), and tumor response. Methods: Acute gastrointestinal (GI), genitourinary (GU), and cutaneous (CU) toxicities were assessed according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03. Early-late toxicity was scored using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity scoring system. Tumor response was evaluated with response evaluation criteria in solid tumors (RECIST) v1.1. Results: Acute toxicity for 84 subjects (100%): severe (≥ G3) GI and skin toxicity was observed in 4 (5%) and 19 patients (23%), respectively. Early-late toxicity for 73 subjects (87%): severe (≥ G3) GI and vulvo-vaginal toxicity was observed in 2 (3%) and 2 (3%) patients, respectively. No acute or early-late severe GU toxicity was reported. A treatment interruption occurred in 65 patients (77%). CFS was 96% (95% CI 89–99) at 6 months and 92% (95% CI 83–96) at 12 months. At 6 months complete response (CR), partial response (PR) and progressive disease (PD) was observed in 70 (83%), 3 (4%), and 7 patients (8%), respectively. At 12 months, CR was observed in 60 patients (81%); eleven patients (15%) experienced PD. Conclusion: Our study showed an excellent clinical result and very low acute toxicity rates, confirming the IMRT as standard of care for curative treatment of anal cancer patients. The current trial was registered with the number IEO N87/11

Background: Indocyanine green fluorescence vision is an upcoming technology in surgery. It can be used in three ways: angiographic and biliary tree visualization and lymphatic spreading studies. The present paper shows the most outstanding results from an health technology assessment study design, conducted on fluorescence-guided compared with standard vision surgery. Methods: A health technology assessment approach was implemented to investigate the economic, social, ethical, and organizational implications related to the adoption of the innovative fluorescence-guided view, with a focus on minimally invasive approach. With the support of a multidisciplinary team, qualitative and quantitative data were collected, by means of literature evidence, validated questionnaires and self-reported interviews, considering the dimensions resulting from the EUnetHTA Core Model. Results: From a systematic search of literature, we retrieved the following studies: 6 on hepatic, 1 on pancreatic, 4 on biliary, 2 on bariatric, 4 on endocrine, 2 on thoracic, 11 on colorectal, 7 on urology, 11 on gynecology, 2 on gastric surgery. Fluorescence guide has shown advantages on the length of hospitalization particularly in colorectal surgery, with a reduction of the rate of leakages and re-do anastomoses, in spite of a slight increase in operating time, and is confirmed to be a safe, efficacious, and sustainable vision technology. Clinical applications are still presenting a low evidence in the literature. Conclusion: The present paper, under the patronage of Italian Society of Endoscopic Surgery, based on an HTA approach, sustains the use of fluorescence-guided vision in minimally invasive surgery, in the fields of general, gynecologic, urologic, and thoracic surgery, as an efficient and economically sustainable technology.

Background: In the past three decades, different High Energy Devices (HED) have been introduced in surgical practice to improve the efficiency of surgical procedures. HED allow vessel sealing, coagulation and transection as well as an efficient tissue dissection. This survey was designed to verify the current status on the adoption of HED in Italy. Methods: A survey was conducted across Italian general surgery units. The questionnaire was composed of three sections (general information, elective surgery, emergency surgery) including 44 questions. Only one member per each surgery unit was allowed to complete the questionnaire. For elective procedures, the survey included questions on thyroid surgery, lower and upper GI surgery, proctologic surgery, adrenal gland surgery, pancreatic and hepatobiliary surgery, cholecystectomy, abdominal wall surgery and breast surgery. Appendectomy, cholecystectomy for acute cholecystitis and bowel obstruction due to adhesions were considered for emergency surgery. The list of alternatives for every single question included a percentage category as follows: “ < 25%, 25–50%, 51–75% or > 75%”, both for open and minimally-invasive surgery. Results: A total of 113 surgical units completed the questionnaire. The reported use of HED was high both in open and minimally-invasive upper and lower GI surgery. Similarly, HED were widely used in minimally-invasive pancreatic and adrenal surgery. The use of HED was wider in minimally-invasive hepatic and biliary tree surgery compared to open surgery, whereas the majority of the respondents reported the use of any type of HED in less than 25% of elective cholecystectomies. HED were only rarely employed also in the majority of emergency open and laparoscopic procedures, including cholecystectomy, appendectomy, and adhesiolysis. Similarly, very few respondents declared to use HED in abdominal wall surgery and proctology. The distribution of the most used type of HED varied among the different surgical interventions. US HED were mostly used in thyroid, upper GI, and adrenal surgery. A relevant use of H-US/RF devices was reported in lower GI, pancreatic, hepatobiliary and breast surgery. RF HED were the preferred choice in proctology. Conclusion: HED are extensively used in minimally-invasive elective surgery involving the upper and lower GI tract, liver, pancreas and adrenal gland. Nowadays, reasons for choosing a specific HED in clinical practice rely on several aspects, including surgeon’s preference, economic features, and specific drawbacks of the energy employed.

Background In robotic right hemicolectomy for cancer, appropriate lymphadenectomy is essential. Visualization of draining lymph nodes and blood flow with near-infrared (NIR) fluorescence DaVinci® imaging system is a recent development. We present the technique of robotic right colectomy with complete mesocolic excision (CME) and D3 lymphadenectomy using Indocyanine Green (ICG) endoscopic submucosal injection to intraoperatively identify tumour lymphatic basin. Methods The day before surgery, in patients scheduled for robotic right colectomy an endoscopic submucosal injection of 3 mg of ICG solution around the tumor is realized. Robotic right hemicolectomy is performed with suprapubic trocars layout and "bottom to up dissection", realizing a CME with central vessel ligation and D3 lymphadenectomy. Site of primary tumor and lymphatic basin are visible with the FireflyTM camera modality. Results From July 2016 to July 2020, 85 patients received a robotic right colectomy with CME and D3 lymphadenectomy. In 50 patients, ICG submucosal injection was performed: visualisation of the site of primary tumour and of LN in the D3 area was possible in all cases; in 17/50 patients (34%), LN out from anatomical lymphatic basin were identified. No side effects were observed. Conclusions In this series, submucosal ICG injection showed to be feasible and safe. The accuracy in identification of D3 lymphatic basin was high, thus permitting an image-guided radical lymphadenectomy. Fluorescent technology represents an interesting innovation to ameliorate surgery of colon cancer.

IMPORTANCE: The benefit of endovascular thrombectomy (EVT) for acute ischemic stroke is highly time-dependent, and it is challenging to expedite treatment for patients in remote areas. OBJECTIVE: To determine whether deployment of a flying intervention team, compared with patient interhospital transfer, is associated with a shorter time to endovascular thrombectomy and improved clinical outcomes for patients with acute ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS: This was a nonrandomized controlled intervention study comparing 2 systems of care in alternating weeks. The study was conducted in a nonurban region in Germany including 13 primary telemedicine-assisted stroke centers within a telestroke network. A total of 157 patients with acute ischemic stroke for whom decision to pursue thrombectomy had been made and deployment of flying intervention team or patient interhospital transfer was initiated were enrolled between February 1, 2018, and October 24, 2019. The date of final follow-up was January 31, 2020. EXPOSURES: Deployment of a flying intervention team for EVT in a primary stroke center vs patient interhospital transfer for EVT to a referral center. MAIN OUTCOMES AND MEASURES: The primary outcome was time delay from decision to pursue thrombectomy to start of the procedure in minutes. Secondary outcomes included functional outcome after 3 months, determined by the distribution of the modified Rankin Scale score (a disability score ranging from 0 [no deficit] to 6 [death]). RESULTS: Among the 157 patients included (median [IQR] age, 75 [66-80] y; 80 [51%] women), 72 received flying team care and 85 were transferred. EVT was performed in 60 patients (83%) in the flying team group vs 57 (67%) in the transfer group. Median (IQR) time from decision to pursue EVT to start of the procedure was 58 (51-71) minutes in the flying team group and 148 (124-177) minutes in the transfer group (difference, 90 minutes [95% CI, 75-103]; P

Background To systematically review neoadjuvant and adjuvant therapy options for women with newly diagnosed stage II-IV ovarian cancer. Methods Phase III trials were searched using MEDLINE, EMBASE, and Cochrane Library. Maintenance therapies were excluded. Results Thirty-three trials were included. For women with high-risk profiles that would contraindicate upfront cytoreductive surgery, neoadjuvant chemotherapy can be an option. In the post-surgical adjuvant setting, the three-weekly regimen consisting of paclitaxel and carboplatin remains the standard of care. Docetaxel may be offered to those who are unable to tolerate paclitaxel. Intraperitoneal cisplatin and paclitaxel increased OS for stage III optimally debulked women (GOG 172). The intraperitoneal regimens in GOG 252 offered no survival benefit and some harms in terms of toxicity and quality of life. Conclusions There is no evidence to support adding a third agent to the standard carboplatin and paclitaxel. Results of the iPocc study will clarify the role of intraperitoneal chemotherapy.

Tumor testing utility in Lynch syndrome (LS) diagnosis is established.Analyze the differences between tumor testing efficiency in rectal (RC) and colon cancer (CC).We performed immunohistochemistry (IHC) for MisMatch Repair (MMR) proteins (IHC-MMR) and MicroSatellite Instability analysis (MSI) on 482 unselected primary tumors: 320 CCs and 162 RCs. Samples had proficient-IHC, deficient-IHC or borderline-IHC ("patchy" expression). MSI-H borderline-IHC tumors were considered as likely MMR-deficient. Germline testing was offered to MMR-deficient patients without BRAF mutation or MLH1 promoter hypermetilation (MLH1-Hy).We identified 51/482 (10.6%) MMR-defective tumors. Multivariable analysis demonstrated a significant correlation between tumor testing results with histotype, lymph-node involvement and tumor location. In particular, RC showed a lower MMR-deficiency rate than CC (p0.0001). Interestingly, MLH1 loss was detected in 0% RCs and 76.1% CCs, with 80% of them showing BRAF mutation/MLH1-Hy. A germline variant was detected in 12 out of 18 patients (mutation detection rate of 66.7%).Tumor testing results showed molecular differences between CCs and RCs, in terms of MMR proteins expression, and presence of BRAF mutation/MLH1-Hy. MSH6 variants were the most frequent ones (50%). Although young age at diagnosis was associated with mutation detection (p = 0.045), 33.3% of LS patients were50 years.

REVIEW QUESTION/OBJECTIVE The objective of this review is to synthesize the best available evidence on the effectiveness of the application of extracellular matrix products as dressings or in topical form as treatment for venous, arterial and mixed leg ulcers, compared to compression therapy alone, any type of dressings and topical agents, or placebos in adults over 18 years in any care setting.

Human hepatocellular carcinomas (HCCs) expressing the biliary/hepatic progenitor cell marker keratin 19 (K19) have been linked with a poor prognosis and exhibit an increase in platelet-derived growth factor receptor α (PDGFRα) and laminin beta 1 (LAMB1) expression. PDGFRα has been reported to induce de novo synthesis of LAMB1 protein in a Sjogren syndrome antigen B (La/SSB)-dependent manner in a murine metastasis model. However, the role of this cascade in human HCC remains unclear. This study focused on the functional role of the PDGFRα-La/SSB-LAMB1 pathway and its molecular link to K19 expression in human HCC. In surgical HCC specimens from a cohort of 136 patients, PDGFRα expression correlated with K19 expression, microvascular invasion and metastatic spread. In addition, PDGFRα expression in pre-operative needle biopsy specimens predicted poor overall survival during a 5-year follow-up period. Consecutive histological staining demonstrated that the signaling components of the PDGFRα-La/SSB-LAMB1 pathway were strongly expressed at the invasive front. K19-positive HCC cells displayed high levels of α2β1 integrin (ITG) receptor, both in vitro and in vivo. In vitro activation of PDGFRα signaling triggered the translocation of nuclear La/SSB into the cytoplasm, enhanced the protein synthesis of LAMB1 by activating its internal ribosome entry site, which in turn led to increased secretion of laminin-111. This effect was abrogated by the PDGFRα-specific inhibitor crenolanib. Importantly LAMB1 stimulated ITG-dependent focal adhesion kinase/Src proto-oncogene non-receptor tyrosine kinase signaling. It also promoted the ITG-specific downstream target Rho-associated coiled-coil containing protein kinase 2, induced K19 expression in an autocrine manner, invadopodia formation and cell invasion. Finally, we showed that the knockdown of LAMB1 or K19 in subcutaneous xenograft mouse models resulted in significant loss of cells invading the surrounding stromal tissue and reduced HepG2 colonization into lung and liver after tail vein injection. The PDGFRα-LAMB1 pathway supports tumor progression at the invasive front of human HCC through K19 expression.Oncogene advance online publication, 7 August 2017; doi:10.1038/onc.2017.260. ispartof: Oncogene vol:36 issue:47 pages:6605-6616 ispartof: location:England status: published

Neonatal diabetes is frequently part of a complex syndrome with extrapancreatic features: 18 genes causing syndromic neonatal diabetes have been identified to date. There are still patients with neonatal diabetes who have novel genetic syndromes. We performed exome sequencing in a patient and his unrelated, unaffected parents to identify the genetic etiology of a syndrome characterized by neonatal diabetes, sensorineural deafness, and congenital cataracts. Further testing was performed in 311 patients with diabetes diagnosed before 1 year of age in whom all known genetic causes had been excluded. We identified 5 patients, including the initial case, with three heterozygous missense mutations in WFS1 (4/5 confirmed de novo). They had diabetes diagnosed before 12 months (2 before 6 months) (5/5), sensorineural deafness diagnosed soon after birth (5/5), congenital cataracts (4/5), and hypotonia (4/5). In vitro studies showed that these WFS1 mutations are functionally different from the known recessive Wolfram syndrome–causing mutations, as they tend to aggregate and induce robust endoplasmic reticulum stress. Our results establish specific dominant WFS1 mutations as a cause of a novel syndrome including neonatal/infancy-onset diabetes, congenital cataracts, and sensorineural deafness. This syndrome has a discrete pathophysiology and differs genetically and clinically from recessive Wolfram syndrome.

Background and aims Fatigue is a common symptom of primary biliary cirrhosis (PBC), and is associated with an impaired quality of life. Study question No studies have assessed the use of modafinil in fatigue related to PBC in a controlled manner. Study design, measures, and outcomes A randomized, double-blind, placebo-controlled study was conducted to determine the safety and efficacy of modafinil for the treatment of fatigue in PBC. Forty patients were randomized to modafinil (n = 20) or placebo (n = 20) for 12 weeks. A verbal report of fatigue for at least 6 months was required for enrollment. Modafinil was administered at 100 mg by mouth once daily; a change by 50 mg every 2 weeks (maximum: 200 mg once daily) was allowed, depending on the subject's response to treatment. The primary outcome was defined as a ≥50% improvement in fatigue severity [quantified by the Fisk Fatigue Impact Scale (FFIS)] after 12 weeks of treatment, compared with baseline values. Results Thirty-three PBC patients completed the study. After 12 weeks of therapy, only 5 patients had a ≥50% reduction in FFIS scores: 3 patients (17.6%) in the modafinil arm and 2 (12.5%) in the placebo arm (P = 1.00). Change in median FFIS score was not statistically different between patients in the 2 treatment groups (P = 0.36). Modafinil was associated with minimal adverse events (headaches, diarrhea, and rash). Conclusions In patients with PBC who have fatigue, treatment with modafinil for 12 weeks was safe and fairly well tolerated; however, it did not result in beneficial effects on fatigue compared with patients treated with placebo (CONSORT Table 1). ClinicalTrials.gov identifier NCT00943176.

Primary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver disease in which emerging data suggest that oral antibiotics may offer therapeutic effects. We enrolled patients with PSC in a 12-week, open-label pilot study to investigate the efficacy and safety of 550 mg of oral rifaximin twice daily. The primary end point was serum alkaline phosphatase (ALK) at 12 weeks. Secondary end points included (1) serum bilirubin, gamma-glutamyl transpeptidase, and Mayo PSC risk score; (2) fatigue impact scale, chronic liver disease questionnaire, and short form health survey (SF-36) scores; and (3) adverse effects (AEs). Analyses were performed with nonparametric tests. Sixteen patients were enrolled, among whom the median age was 40 years; 13 (81%) were male, 13 had inflammatory bowel disease, and baseline ALK was 342 IU/mL (interquartile range, 275-520 IU/mL). After 12 weeks of treatment, there were no significant changes in ALK (median increase of 0.9% to 345 IU/mL; P = 0.47) or any of the secondary biochemical end points (all P > 0.05). Similarly, there were no significant changes in fatigue impact scale, chronic liver disease questionnaire, or SF-36 scores (all P > 0.05). Three patients withdrew from the study due to AEs; 4 others reported mild AEs but completed the study. In conclusion, although some antibiotics may have promise in treating PSC, oral rifaximin, based on the results herein, seems inefficacious for this indication. Future studies are needed to understand how the antimicrobial spectra and other properties of antibiotics might determine their utility in treating PSC.

BACKGROUND: Many residency programs have struggled to meaningfully meet the ACGME quality improvement (QI) requirements. Similarly, our residents were receiving limited QI education, and their longitudinal projects were ineffective. AIM: Create an integrated didactic and experiential learning environment that equips residents to become leaders of QI. SETTING AND PARTICIPANTS: Internal medicine (IM) residency program of 45 residents in a large community hospital. PROGRAM DESCRIPTION: This curriculum included eight content areas. Games, real-life application, and project celebrations cultivated engagement. Sessions occurred during residents’ 2-week outpatient rotations. Project development was standardized. PROGRAM EVALUATION: The QI Knowledge Application Tool-Revised (QIKAT-R) and separate surveys were used before and after the curriculum’s implementation to evaluate resident QI knowledge and confidence, respectively. We also tracked QI scholarship and faculty engagement. Mean QIKAT-R scores improved significantly from 7.0 (SD 2.9) at baseline to 16.6 (SD 4.7) post-curriculum (n = 37 pairs, p = 0.043). Residents’ adverse event reporting increased from 44% (19/43) at baseline to 90% (28/31) post-curriculum. Seven presentations were accepted for local, regional, and national conferences, compared with one presentation the preceding year. DISCUSSION: A QI curriculum can be successfully integrated in a “4 + 2” program. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-019-05059-7) contains supplementary material, which is available to authorized users.

BackgroundDiarrhoeal diseases are a major contributor to morbidity and mortality in humanitarian crises. Handwashing with soap may reduce diarrhoea by up to 47%, however, the circumstances associated with displacement make it challenging for crisis-affected populations to be able to wash their hands with soap. The Supertowel is an alternative hand-cleaning product, proven to be as efficacious as handwashing with soap. The Supertowel is a micro-fibre towel with an anti-microbial treatment. When dipped in water it is capable of removing and killing pathogens from hands. This study aims to assess whether the Supertowel could be an acceptable and feasible product for crisis-affected populations.MethodsThe study took place in an Eritrean refugee camp located in Tigray state in Ethiopia. We used a mix of qualitative methods to understand use and acceptability, including baseline observations (n = 13), behaviour trials involving interviews at three time points (n = 19) and focus group discussions (n = 3). We thematically analysed data from interviews and discussions.ResultsParticipants indicated that the Supertowel was convenient, easy to use and saved them water and money. All households participating in the behaviour trials had at least one Supertowel in use at the end of the trials (follow-up visit two). In discussions participants reported that the Supertowel was more desirable than comparable hand cleaning products. In interviews, trial participants explained that the product enabled them to clean their hands at times when they might not normally bother. The research also identified some issues with the smell of the Supertowel and its intuitive use.ConclusionsThe Supertowel was found to be an acceptable and useful hand-cleaning product that could complement soap use in crisis contexts. This pilot study also identified areas of future research including the need to compare different distribution models for the Supertowel (distribution in hygiene kits compared to distribution with an accompanying communication package) and to evaluate its use at scale over a longer time period.

Evaluation of photobiomodulation therapy (PBMT) in the treatment of pressure ulcers in adults and the elderly. Systematic review, based on the recommendations of the handbook, proposed by Cochrane. The search was carried out in databases, records of randomized clinical trials, list of references cited in the selected articles, as well as a manual search in meetings and specialized journals. A total of 1342 studies were identified, 18 were preselected and 5 were included in this review. Clinical heterogeneity of the participants was observed, in addition to variation in the laser parameters and predominance of studies of low methodological quality. PBMT with the use of laser (658 nm; 4 J cm-2 ;50 mw) showed complete wound healing (P < 0.001) when compared to lasers (990 nm and 808 nm). However, there was no statistically significant difference in relation to time to complete wound healing and in area reduction compared to standard care. PBMT in the infrared wavelength showed efficacy in the healing of the pressure ulcer, similar to the standard care presented in the different studies. PBMT (658 nm) was effective in promoting healing when compared to standard care. Laser can be a therapy of choice in the treatment of pressure ulcers, since no evidence has been found to refute its clinical application.

OBJECTIVE To evaluate the effectiveness of hyaluronic acid in the healing of partial thickness burns. METHOD Systematic review of randomized controlled trials on the use of hyaluronic acid for the topical treatment of skin burns, based on recommendations of the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS Two randomized controlled trials that analyzed 143 patients with partial thickness burns and/or deep partial thickness burns were selected. They compared the application of hyaluronic acid 0.2% associated to silver sulfadiazine 1% 5g/cm2 versus silver sulfadiazine 1% 5g/cm2 alone for the outcome of complete healing. CONCLUSION This review emphasizes the need for new well-designed randomized controlled trials to establish the therapeutic relevance of hyaluronic acid with respect to the healing of burns of partial thickness or deep partial thickness. Resumen OBJETIVO Evaluar la efectividad del ácido hialurónico en la cicatrización de quemaduras de espesor parcial. MÉTODO Revisión sistemática de ensayos clínicos randomizados acerca de la utilización de ácido hialurónico en el tratamiento tópico de quemaduras de piel, basada en las recomendaciones del Cochrane Handbook for Systematic Reviews of Interventions. RESULTADOS Fueron recuperados de los ensayos clínicos randomizados que analizaron 143 pacientes portadores de quemaduras de espesor parcial y/o espesor parcial profundo, comparando la aplicación de Ácido Hialurónico al 0,2%, asociado con la Sulfadiazina de Plata al 1% 5g/cm2, versus Sulfadiazina de Plata al 1% 5g/cm2 aislada, para el resultado de una cicatrización completa. CONCLUSIÓN Esta revisión subraya la necesidad de nuevos ensayos clínicos randomizados bien planteados para el establecimiento de la relevancia terapéutica del ácido hialurónico en lo que se refiere a la cicatrización de quemaduras de espesor parcial o espesor parcial profundo. Resumo OBJETIVO Avaliar a efetividade do ácido hialurônico na cicatrização de queimaduras de espessura parcial. MÉTODO Revisão sistemática de ensaios clínicos randomizados sobre a utilização de ácido hialurônico no tratamento tópico de queimaduras de pele, baseada nas recomendações do Cochrane Handbook for Systematic Reviews of Interventions. RESULTADOS Foram recuperados dois ensaios clínicos randomizados que analisaram 143 pacientes portadores de queimaduras de espessura parcial e/ou espessura parcial profunda, comparando a aplicação de Ácido Hialurônico 0,2% associado à Sulfadiazina de Prata 1% 5g/cm2, versus Sulfadiazina de Prata 1% 5g/cm2 isolada, para o desfecho cicatrização completa. CONCLUSÃO Esta revisão enfatiza a necessidade de novos ensaios clínicos randomizados bem delineados para estabelecimento da relevância terapêutica do ácido hialurônico no que tange à cicatrização de queimaduras de espessura parcial ou espessura parcial profunda.

Background Robotic complete mesocolic excision (CME) has recently emerged as promising technique to enhance oncologic results in hemicolectomy for cancer. The potential near-infrared (NIR) fluorescence with indocyanine-green (ICG) dye for lymphatic mapping is under investigation and few small case-series are reported. Methods ICG solution was endoscopically injected the day before surgery in patients undergoing robotic right colectomy with CME using the Da Vinci Xi® system and the bottom to up technique. During surgery the ICG was excited by light in the near-infrared (NIR) spectrum of the Firefly™ system, of the Da Vinci Xi® system for image comparison in standard white light and NIR, and real-time visualization of the lymphatic drainage. Results Twenty patients affected by right colon cancer underwent robotic right colectomy with the bottom to up technique. No cases converted to open surgery were observed. During surgery, a fluorescent mapping of draining lymph nodes, was visualized in all the 20 patients. In seven patients (35%), lymph nodes outside the standard lymphatic basin were identified and removed. Conclusions The association of robotic right colectomy with the bottom to up technique and ICG-guided lymphadenectomy is a feasible and safe procedure. ICG lymphatic mapping may help to perform a correct CME, although the independent impact of these procedures on oncologic outcome deserves further investigations.

Fluorescent imaging with indocyanine green (ICG) is an emerging technology that is gaining acceptance for being a valid tool in surgeons' decision making. ICG binds to plasma lipoproteins if injected intravenously and, when excited by near-infrared light, provides anatomic information about organs vascularization and tissues perfusion. If injected in tissues, it migrates in the lymphatic system, therefore enabling the identification of lymphatic draining pathways of different organs. In this paper we address specific applications of ICG fluorescence in robotic general surgery.

During the past decade, the concept of complete mesocolic excision (CME) has emerged as a possible strategy to minimize recurrence for right colon cancers. The purpose of this study was to compare robotic versus laparoscopic CME in performing right colectomy for cancer. Pertinent data of all patients who underwent robotic or laparoscopic right colectomy with CME using a Pfannenstiel incision and intracorporeal anastomosis performed between October 2005 and November 2015 were entered in a prospectively maintained database. A total of 202 patients underwent robotic (n = 101) or laparoscopic (n = 101) right colectomy within the study period. Patient characteristics were equivalent between groups. The robotic group showed a statistically significant reduction in conversion rate (0% vs. 6.9%, p = 0.01) but a longer operative time (279 min vs. 236 min, p

Variations in cord blood manufacturing and administration are common, and the optimal practice is not known. We compared processing and banking practices at 16 public cord blood banks (CBB) in the United States and assessed transplantation outcomes on 530 single umbilical cord blood (UCB) myeloablative transplantations for hematologic malignancies facilitated by these banks. UCB banking practices were separated into 3 mutually exclusive groups based on whether processing was automated or manual, units were plasma and red blood cell reduced, or buffy coat production method or plasma reduced. Compared with the automated processing system for units, the day 28 neutrophil recovery was significantly lower after transplantation of units that were manually processed and plasma reduced (red cell replete) (odds ratio, .19; P = .001) or plasma and red cell reduced (odds ratio, .54; P = .05). Day 100 survival did not differ by CBB. However, day 100 survival was better with units that were thawed with the dextran-albumin wash method compared with the "no wash" or "dilution only" techniques (odds ratio, 1.82; P = .04). In conclusion, CBB processing has no significant effect on early (day 100) survival despite differences in kinetics of neutrophil recovery.

The implicit didactic information embedded in the theoretical part of math schoolbooks is one of the keys for successful learning mathematics, but mostly reserved for sighted students. Thus, the methodology for analyzing this theoretical part of selected math schoolbooks is developed for extracting this implicit didactic information, which will be made accessible. Combined with the blind students' teaching methods in classrooms, a dialog-based assistant concept is suggested for covering core didactics for teaching the blind.

Introduction Right-sided colon cancer has a worse prognosis than left-sided colon cancer. Complete mesocolic excision (CME) with central vessels ligation (CVL) reduces local recurrence, but is technically demanding, particularly with a laparoscopic approach. Aim of this study is to describe a new robotic approach to right colectomy with CME and CVL and to report oncologic safety and short term outcomes. Methods Twenty consecutive patients were included. All patients had a right colon adenocarcinoma and underwent right colectomy with a suprapubic approach. Surgery was realized with the Da Vinci Xi ® system and all trocars were placed along a horizontal line 3–6 cm above the pubis. CME with CVL was realized in all the patients. Data analysed were: duration of surgery, conversions to open surgery, intraoperative and postoperative complication by Clavien Dindo classification, margins of resections, length of specimen and number of lymph nodes retrieved. Results Patients median age was 69 years, median body mass index was 27 kg/m 2 . Median operative time was 249 min, blood loss was negligible, no conversions to open or laparoscopic surgery occurred. Median hospital stay was six days; two postoperative grade IIIa Clavien–Dindo complications occurred, no 30-days postoperative death was registered. Resection margins were negative in all patients; median tumour diameter was 3.6 cm, median specimen length was 40 cm, median number of harvested lymph nodes was 40. Conclusions Robotic right colectomy with CME using a suprapubic approach is a feasible and safe technique that allows for an extended lymphadenectomy and provides high quality surgical specimens.

Background: Studies on the association between traffic noise and cardiovascular diseases have rarely considered air pollution as a covariate in the analyses. Isolated systolic hypertension has not yet been in the focus of epidemiological noise research. Methods: The association between traffic noise (road and rail) and the prevalence of hypertension was assessed in two study populations with a total of 4,166 participants 25–74 years of age. Traffic noise (weighted day–night average noise level; LDN) at the facade of the dwellings was derived from noise maps. Annual average PM2.5 mass concentrations at residential addresses were estimated by land-use regression. Hypertension was assessed by blood pressure readings, self-reported doctor-diagnosed hypertension, and antihypertensive drug intake. Results: In the Greater Augsburg, Germany, study population, traffic noise and air pollution were not associated with hypertension. In the City of Augsburg population (n = 1,893), where the exposure assessment was more detailed, the adjusted odds ratio (OR) for a 10-dB(A) increase in noise was 1.16 (95% CI: 1.00, 1.35), and 1.11 (95% CI: 0.94, 1.30) after additional adjustment for PM2.5. The adjusted OR for a 1-μg/m3 increase in PM2.5 was 1.15 (95% CI: 1.02, 1.30), and 1.11 (95% CI: 0.98, 1.27) after additional adjustment for noise. For isolated systolic hypertension, the fully adjusted OR for noise was 1.43 (95% CI: 1.10, 1.86) and for PM2.5 was 1.08 (95% CI: 0.87, 1.34). Conclusions: Traffic noise and PM2.5 were both associated with a higher prevalence of hypertension. Mutually adjusted associations with hypertension were positive but no longer statistically significant. Citation: Babisch W, Wolf K, Petz M, Heinrich J, Cyrys J, Peters A. 2014. Associations between traffic noise, particulate air pollution, hypertension, and isolated systolic hypertension in adults: the KORA Study. Environ Health Perspect 122:492–498; http://dx.doi.org/10.1289/ehp.1306981

Neurofibroma is a benign tumour composed from Schwann cells. Localization in sinus maxillea is very rare. Authors presenting case which was treatment in Maxillo-Facial Surgery Clinic in Wrocław.

Visual design, learning sciences, and nanotechnology may be strange bedfellows; yet, as this paper highlights, peer interaction between a designer and a scientist is an effective method for helping scientists acquire visual design skills. We describe our findings from observing twelve sessions at the Design Help Desk, a tutoring center at the University of Washington. At each session, a scientist (who is expert in his own domain but a novice in design) consulted a designer (who is expert in design but a novice in science) in order to receive advice and guidance on how to improve a scientific visualization. At the Design Help Desk, this pairing consistently produced a momentary disequilibrium in the scientist's thought process: a disequilibrium that led to agency (where the scientist gained ownership of his/her own learning) and conceptual change in the scientist's understanding of visual design. Scientists who visited the Design Help Desk were satisfied with their experience, and their published work demonstrated an improved ability to visually communicate research findings-a skill critical to the advancement of science. To our knowledge, the Design Help Desk is a unique effort to educate scientists in visual design; we are not aware of any other design-advice/tutoring centers at public or private universities in the United States or abroad.

Avoidance of corticosteroids could be beneficial after pediatric liver transplantation (LTx). To test this hypothesis, we performed a randomized prospective study to compare immunosuppression with tacrolimus (TAC) and steroids versus TAC and basiliximab (BAS) after pediatric LTx. Seventy-two patients were recruited, 36 receiving TAC and steroids and 36 TAC and BAS. The primary endpoint was the occurrence of the first rejection episode. Secondary endpoints were the cumulative incidence and severity of rejection, patient and graft survival, and incidence of adverse events. Overall 1-year patient and graft survival rates were 91.4% and 85.5% in the steroid group, and 88.6% and 80% in the BAS group (p = NS). Patients free from rejection were 87.7% in the BAS group and 67.7% in the steroid group (p = 0.036). The use of BAS was associated with a 63.6% reduction in incidence of acute rejection episodes. Overall incidence of infection was 72.3% in the steroid group and 50% in the BAS group (p = 0.035). We conclude that the combination of TAC with BAS is an alternative to TAC and steroid immunosuppression in pediatric LTx, which allows for a significant reduction in the incidence of acute rejection and infectious complications.

Hematopoietic cell transplantation (HCT) using CCR5-Δ32/Δ32 stem cells from an adult donor has resulted in the only known cure of human immunodeficiency virus (HIV) infection. However, it is not feasible to repeat this procedure except rarely because of the low incidence of the CCR5-Δ32 allele, the availability of only a small number of potential donors for most patients, and the need for a very close human leukocyte antigen (HLA) match between adult donors and recipients. In contrast, cord blood (CB) transplantations require significantly less stringent HLA matching. Therefore, our hypothesis is that cure of HIV infections by HCT can be accomplished much more readily using umbilical CB stem cells obtained from a modestly sized inventory of cryopreserved CCR5-Δ32/Δ32 CB units. To test this hypothesis, we developed a screening program for CB units and are developing an inventory of CCR5-Δ32/Δ32 cryopreserved units available for HCT. Three hundred such units are projected to provide for white pediatric patients a 73.6% probability of finding an adequately HLA matched unit with a cell dose of ≥2.5 × 107 total nucleated cells (TNCs)/kg and a 27.9% probability for white adults. With a cell dose of ≥1 × 107 TNCs/kg, the corresponding projected probabilities are 85.6% and 82.1%. The projected probabilities are lower for ethnic minorities. Impetus for using CB HCT was provided by a transplantation of an adult with acute myelogenous leukemia who was not HIV infected. The HCT was performed with a CCR5-Δ32/Δ32 CB unit, and posttransplantation in vitro studies indicated that the patient's peripheral blood mononuclear cells were resistant to HIV infection.

Consequences of deregulated protein N-glycosylation on cancer pathogenesis are poorly understood. TUSC3 is a gene with a putative function in N-glycosylation, located on the short arm of chromosome 8. This is a chromosomal region of frequent genetic loss in ovarian cancer. We established recently that the expression of TUSC3 is epigenetically decreased in epithelial ovarian cancer compared to benign controls and provides prognostic information on patient survival. Therefore, we analyzed the consequences of silenced TUSC3 expression on proliferation, invasion and migration of ovarian cell lines. In addition, we performed subcellular fractionation, co-immunofluorescence and co-immunoprecipitation experiments to establish the molecular localization of TUSC3 in ovarian cancer cells. We demonstrated that TUSC3 is localized in the endoplasmic reticulum as a subunit of the oligosaccharyltransferase complex and is capable of modulation of glycosylation patterning of ovarian cancer cells. Most importantly, silencing of TUSC3 enhances proliferation and migration of ovarian cancer cells in vitro. Our observations suggest a role for N-glycosylating events in ovarian cancer pathogenesis in general, and identify TUSC3 as a tumor suppressor gene in ovarian cancer in particular.

Highly multiplexed assays, such as microarrays, can benefit arbovirus surveillance by allowing researchers to screen for hundreds of targets at once. We evaluated amplification strategies and the practicality of a portable DNA microarray platform to analyze virus-infected mosquitoes. The prototype microarray design used here targeted the nonstructural protein 5, ribosomal RNA, and cytochrome b genes for the detection of flaviviruses, mosquitoes, and bloodmeals, respectively. We identified 13 of 14 flaviviruses from virus inoculated mosquitoes and cultured cells. Additionally, we differentiated between four mosquito genera and eight whole blood samples. The microarray platform was field evaluated in Thailand and successfully identified flaviviruses (Culex flavivirus, dengue-3, and Japanese encephalitis viruses), differentiated between mosquito genera (Aedes, Armigeres, Culex, and Mansonia), and detected mammalian bloodmeals (human and dog). We showed that the microarray platform and amplification strategies described here can be used to discern specific information on a wide variety of viruses and their vectors.

K(ATP) channels regulate insulin secretion from pancreatic beta-cells. Loss- and gain-of-function mutations in the genes encoding the Kir6.2 and SUR1 subunits of this channel cause hyperinsulinism of infancy and neonatal diabetes, respectively. We report two novel mutations in the gating loop of Kir6.2 which cause neonatal diabetes with developmental delay (T293N) and hyperinsulinism (T294M). These mutations increase (T293N) or decrease (T294M) whole-cell K(ATP) currents, accounting for the different clinical phenotypes. The T293N mutation increases the intrinsic channel open probability (Po((0))), thereby indirectly decreasing channel inhibition by ATP and increasing whole-cell currents. T294M channels exhibit a dramatically reduced Po((0)) in the homozygous but not in the pseudo-heterozygous state. Unlike wild-type channels, hetT294M channels were activated by MgADP in the absence but not in the presence of MgATP; however, they are activated by MgGDP in both the absence and presence of MgGTP. These mutations demonstrate the importance of the gating loop of Kir channels in regulating Po((0)) and further suggest that Mg-nucleotide interaction with SUR1 may reduce ATP inhibition at Kir6.2.

Splenic flexure mobilization is a challenging surgical procedure, but is it necessary to safely perform left colon and rectal resections. This paper is a technical focus detailing the four ways to mobilize splenic flexure in robotic surgery. The medial approach involves an extensive dissection of the medial plane separating descending mesocolon form Toldt fascia; the sovramesocolic approach starts with gastrocolic ligament section; the lateral approach starts with coloparietal detachment and the "one inch-one inch" approach starts with section of transverse mesocolon.

In conclusion, our case highlights the unusual presentation of tropical pyomyositis in a temperate environment. It is important to consider this diagnosis in immunocompromised hosts, even in those with vague complaints such as muscle pain or erythema. The patient's immunocompromised state as well as the rarity of tropical pyomyositis outside of a tropical country led to a late diagnosis. Tropical pyomyositis is a potentially life threatening disease, but if recognized and treated early, the prognosis is good.

The laparoscopic approach for treatment of rectal cancer has been proven feasible and oncologically safe, and is able to offer better short-term outcomes than traditional open procedures, mainly in terms of reduced length of hospital stay and time to return to working activity. In spite of this, the laparoscopic technique is usually practised only in high-volume experienced centres, mainly because it requires a prolonged and demanding learning curve. It has been estimated that over 50 operations are required for an experienced colorectal surgeon to achieve proficiency with this technique. Robotic surgery enables the surgeon to perform minimally invasive operations with better vision and more intuitive and precise control of the operating instruments, thus promising to overcome some of the technical difficulties associated with standard laparoscopy. It has high-definition three-dimensional vision, it translates the surgeon's hand movements into precise movements of the instruments inside the patient, the camera is held and moved by the first surgeon, and a fourth robotic arm is available as a fixed retractor. The aim of this review is to summarise the current data on clinical and oncologic outcomes of robot-assisted surgery in rectal cancer, focusing on short- and long-term results, and providing original data from the authors' centre.

To report on the development of the Profile of Visual Functioning as a framework for information exchange between schools and medical specialists involved in the education or care of children with impaired vision due to brain damage.The role of vision loss in a child's functioning can be in part assessed by medical services, but in order to meet the needs of early intervention and education, numerous activities and tasks need to be observed during therapies, early intervention activities, and at local and special schools.Information on vision loss can be gathered effectively and shared between medicine and education using well-structured lists of the most important functions, the Profile of Visual Functioning. We describe a common type of list of vision-related functions and activities.Cooperation between education and medicine requires development of a common language and agreements on how the large amount of information is collected. A basic list of measurements and observations covers functions of most children and thus gives a firm structure to the information exchange.Lists of functions to be examined and activities to be observed, if used by all stakeholders, may improve the quality of assessments for early intervention and special education. At the same time, schools and hospitals need to jointly arrange further education so that the names of activities start to make sense to doctors and the medical terms to teachers.

A novel NAT2 tagSNP (rs1495741) and a 2-SNP genotype (rs1041983 and rs1801280) have been recently shown to accurately predict the NAT2 acetylator phenotypes in populations of exclusive or predominant European/White ancestry. We confirmed the accuracy of the tagSNP approach in White Brazilians, but not in Brown or Black Brazilians, sub-Saharan Mozambicans, and Guarani Amerindians. The combined rs1041983 and rs1801280 genotypes provided considerably better prediction of the NAT2 phenotype in Guarani, but no consistent improvement in Brown or Black Brazilians and Mozambicans. Best predictions of the NAT2 phenotype in Mozambicans using NAT2 SNP pairs were obtained with rs1801280 and rs1799930, but the accuracy of the estimates remained inadequate for clinical use or for investigations in this sub-Saharan group or in Brazilians with considerable African ancestry. In conclusion, the rs1495741 tagSNP cannot be applied to predict the NAT2 acetylation phenotype in Guarani and African-derived populations, whereas 2-SNP genotypes may accurately predict NAT2 phenotypes in Guarani, but not in Africans.