DLG1 functions upstream of SDCCAG3 and IFT20 to control ciliary targeting of polycystin-2.

Polarized vesicular trafficking directs specific receptors and ion channels to cilia, but the underlying mechanisms are poorly understood. Here we describe a role for DLG1, a core component of the Scribble polarity complex, in regulating ciliary protein trafficking in kidney epithelial cells. Conditional knockout of Dlg1 in mouse kidney causes ciliary elongation and cystogenesis, and cell-based proximity labeling proteomics and fluorescence microscopy show alterations in the ciliary proteome upon loss of DLG1. Specifically, the retromer-associated protein SDCCAG3, IFT20, and polycystin-2 (PC2) are reduced in the cilia of DLG1-deficient cells compared to control cells. This phenotype is recapitulated in vivo and rescuable by re-expression of wild-type DLG1, but not a Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)-associated DLG1 variant, p.T489R. Finally, biochemical approaches and Alpha Fold modelling suggest that SDCCAG3 and IFT20 form a complex that associates, at least indirectly, with DLG1. Our work identifies a key role for DLG1 in regulating ciliary protein composition and suggests that ciliary dysfunction of the p.T489R DLG1 variant may contribute to CAKUT.

The impact of normothermic machine perfusion and acuity circles on waitlist time, mortality, and cost in liver transplantation: A multicenter experience.

Ex situ normothermic machine perfusion (NMP) helps increase the use of extended criteria donor livers. However, the impact of an NMP program on waitlist times and mortality has not been evaluated. Adult patients listed for liver transplant (LT) at 2 academic centers from January 1, 2015, to September 1, 2023, were included (n=2773) to allow all patients ≥6 months follow-up from listing. Routine NMP was implemented on October 14, 2022. Waitlist outcomes were compared from pre-NMP pre-acuity circles (n=1460), pre-NMP with acuity circles (n=842), and with NMP (n=381). Median waitlist time was 79 days (IQR: 20-232 d) at baseline, 49 days (7-182) with acuity circles, and 14 days (5-56) with NMP ( p <0.001). The rate of transplant-per-100-person-years improved from 61-per-100-person-years to 99-per-100-person-years with acuity circles and 194-per-100-person-years with NMP ( p <0.001). Crude mortality without transplant decreased from 18.3% (n=268/1460) to 13.3% (n=112/843), to 6.3% (n=24/381) ( p <0.001) with NMP. The incidence of mortality without LT was 15-per-100-person-years before acuity circles, 19-per-100 with acuity circles, and 9-per-100-person-years after NMP ( p <0.001). Median Model for End-Stage Liver Disease at LT was lowest with NMP, but Model for End-Stage Liver Disease at listing was highest in this era ( p <0.0001). The median donor risk index of transplanted livers at baseline was 1.54 (1.27-1.82), 1.66 (1.42-2.16) with acuity circles, and 2.06 (1.63-2.46) with NMP ( p <0.001). Six-month post-LT survival was not different between eras ( p =0.322). The total cost of health care while waitlisted was lowest in the NMP era ($53,683 vs. $32,687 vs. $23,688, p <0.001); cost-per-day did not differ between eras ( p =0.152). The implementation of a routine NMP program was associated with reduced waitlist time and mortality without compromising short-term survival after liver transplant despite increased use of riskier grafts. Routine NMP use enables better waitlist management with reduced health care costs.

The bioequivalence study design recommendations for immediate-release solid oral dosage forms in the international pharmaceutical regulators programme participating regulators and organisations: differences and commonalities.

Bioequivalence (BE) studies are considered the standard for demonstrating that the performance of a generic drug product in the human body is sufficiently similar to that of its comparator product. The objective of this article is to describe the recommendations from participating Bioequivalence Working Group for Generics (BEWGG) members of the International Pharmaceutical Regulators Programme (IPRP) regarding the conduct and acceptance criteria for BE studies of immediate release solid oral dosage forms. A survey was conducted among BEWGG members regarding their BE recommendations and requirements related to study subjects, study design, sample size, single or multiple dose administration, study conditions (fasting or fed), analyte to be measured, selection of product strength, drug content, handling of endogenous substances, BE acceptance criteria, and additional design aspects. All members prefer conducting single dose cross-over designed studies in healthy subjects with a minimum of 12 subjects and utilizing the parent drug data to assess BE. However, differences emerged among the members when the drug's pharmacokinetics and pharmacodynamics become more complex, such that the study design (e.g., fasting versus fed conditions) and BE acceptance criteria (e.g., highly variable drugs, narrow therapeutic index drugs) may be affected. The survey results and discussions were shared with the ICH M13 Expert Working Group (EWG) and played an important role in identifying and analyzing gaps during the harmonization process. The draft ICH M13A guideline developed by the M13 EWG was endorsed by ICH on 20 December 2022, under Step 2.

Oxygenated versus non-oxygenated flush out during deceased donor liver procurement: The first proof-of-concept study in humans.

BACKGROUND: Liver transplantation is used for treating end-stage liver disease, fulminant hepatitis, and oncological malignancies and organ shortage is a major limiting factor worldwide. The use of grafts based on extended donor criteria have become internationally accepted. Oxygenated machine perfusion technologies are the most recent advances in organ transplantation; however, it is only applied after a period of cold ischemia. Due to its high cost, we aimed to use a novel device, OxyFlush®, based on oxygenation of the preservation solution, applied during liver procurement targeting the maintenance of ATP during static cold storage (SCS). METHODS: Twenty patients were randomly assigned to the OxyFlush or control group based on a 1:1 ratio. In the OxyFlush group, the perfusion solution was oxygenated with OxyFlush® device while the control group received a non-oxygenated solution. Liver and the common bile duct (CBD) biopsies were obtained at three different time points. The first was at the beginning of the procedure, the second during organ preparation, and the third after total liver reperfusion. Biopsies were analyzed, and adenosine triphosphate (ATP) levels and histological scores of the liver parenchyma and CBD were assessed. Postoperative laboratory tests were performed. RESULTS: OxyFlush® was able to maintain ATP levels during SCS and improved the damage caused by the lack of oxygen in the CBD. However, OxyFlush® did not affect laboratory test results and histological findings of the parenchyma. CONCLUSION: We present a novel low-cost device that is feasible and could represent a valuable tool in organ preservation during SCS.

Liver transplantation for intrahepatic cholangiocarcinoma: who, when and how.

PURPOSE OF REVIEW: Using transplant oncology principles, selected patients with intrahepatic cholangiocarcinoma (iCCA) may achieve long-term survival after liver transplantation. Strategies for identifying and managing these patients are discussed in this review. RECENT FINDINGS: Unlike initial reports, several modern series have reported positive outcomes after liver transplantation for iCCA. The main challenges are in identifying the appropriate candidates and graft scarcity. Tumor burden and response to neoadjuvant therapies have been successfully used to identify favorable biology in unresectable cases. New molecular biomarkers will probably predict this response in the future. Also, new technologies and better strategies have been used to increase graft availability for these patients without affecting the liver waitlist. SUMMARY: Liver transplantation for the management of patients with unresectable iCCA is currently a reality under strict research protocols. Who is a candidate for transplantation, when to use neoadjuvant and locoregional therapies, and how to increase graft availability are the main topics of this review.

Low-dose aspirin confers protection against acute cellular allograft rejection after primary liver transplantation.

This study investigated the effect of low-dose aspirin in primary adult liver transplantation (LT) on acute cellular rejection (ACR) as well as arterial patency rates. The use of low-dose aspirin after LT is practiced by many transplant centers to minimize the risk of hepatic artery thrombosis (HAT), although solid recommendations do not exist. However, aspirin also possesses potent anti-inflammatory properties and might mitigate inflammatory processes after LT, such as rejection. Therefore, we hypothesized that the use of aspirin after LT has a protective effect against ACR. This is an international, multicenter cohort study of primary adult deceased donor LT. The study included 17 high-volume LT centers and covered the 3-year period from 2013 to 2015 to allow a minimum 5-year follow-up. In this cohort of 2365 patients, prophylactic antiplatelet therapy with low-dose aspirin was administered in 1436 recipients (61%). The 1-year rejection-free survival rate was 89% in the aspirin group versus 82% in the no-aspirin group (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.63-0.94; p = 0.01). The 1-year primary arterial patency rates were 99% in the aspirin group and 96% in the no-aspirin group with an HR of 0.23 (95% CI, 0.13-0.40; p < 0.001). Low-dose aspirin was associated with a lower risk of ACR and HAT after LT, especially in the first vulnerable year after transplantation. Therefore, low-dose aspirin use after primary LT should be evaluated to protect the liver graft from ACR and to maintain arterial patency.

Airborne bacterial and fungal concentrations and fungal diversity in bedrooms of infant twins under 1 year of age living in Porto.

Exposure to airborne microorganisms has been linked to the development of health detriments, particularly in children. Microbial pollution can constitute a relevant health concern indoors, where levels of airborne microorganisms may be specially increased. This work aimed to characterize the airborne bacterial levels, and fungal concentration and diversity to which twins are exposed in their bedrooms (n = 30) during the first year of life. Bacterial and fungal levels varied widely across the studied bedrooms, with 10% of the rooms presenting values exceeding the national limit for both indoor bacterial and fungal counts. Cladosporium was the predominant genera, but Penicillium, Aspergillus, Alternaria, Trichoderma and Chrysonilia were also identified in the samples collected. In addition, two toxicogenic species, A. flavus and T. viride, were identified at counts that exceeded the established limit (12 CFU/m3) in 3 and 7% of the bedrooms surveyed, respectively. Based on indoor-to-outdoor concentration ratios, outdoor air seemed to be the main contributor to the total load of fungi found indoors, while airborne bacteria appeared to be mainly linked to indoor sources. Higher indoor nitrogen dioxide levels were negatively correlated with indoor fungi concentrations, whereas particulate matter and volatile organic compounds concentrations were associated with an increase in fungal prevalence. In addition, rooms with small carpets or located near outdoor agriculture sources presented significantly greater total fungal concentrations. Multiple linear regression models showed that outdoor levels were the single significant predictor identified, explaining 38.6 and 53.6% of the Cladosporium sp. and total fungi counts, respectively. The results also suggest the existence of additional factors contributing to airborne biologicals load in infants' bedrooms that deserve further investigation. Findings stress the need for investigating the existence of declared interactive effects between chemical and biological air pollutants to accurately understand the health risk that the assessed levels can represent to infants.

A Survey of the Criteria Used for the Selection of Alternative Comparator Products by Participating Regulators and Organizations of the International Pharmaceutical Regulators Programme.

The safety and efficacy of a generic product are partly based on demonstrating bioequivalence to the innovator product; however, when the innovator product is no longer available as a comparator product, a survey conducted within the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Programme (IPRP) indicated that the criteria for selecting an alternative comparator product varies. For most members of the BEWGG, an existing marketed generic that was approved based on a comparison with the locally registered innovator product can be used, contingent on criteria that ranges from allowing any generic to be used, to allowing only specific criteria-defined generics to be used. Notwithstanding the acceptability of a generic as an alternative comparator, it is not always the preferred comparator for several jurisdictions. Some jurisdictions require the use of a locally sourced alternative innovator comparator (e.g., the same medicinal ingredient manufactured by a different company) or a foreign innovator comparator. Unlike the other members of the BEWGG, the European Union (EU) has no such options available, rather mechanisms are in place to allow manufacturers to develop a new comparator. The criteria described herein regarding the use of an alternative comparator product can also be applied to scenarios where a specific strength of a series of strengths or an innovative fixed dose combination are discontinued. The results of the survey demonstrate that while criteria for selecting alternative comparator products are not harmonized among the BEWGG participants, the common concern for all jurisdictions is to select a comparator product that meets the safety and efficacy standards of the original innovator product.

Bricker ileal conduit vs. Cutaneous ureterostomy after radical cystectomy for bladder cancer: a systematic review.

PURPOSE: A systematic review of the literature with available published literature to compare ileal conduit (IC) and cutaneous ureterostomy (CU) urinary diversions (UD) in terms of perioperative, functional, and oncological outcomes of high-risk elderly patients treated with radical cystectomy (RC). Protocol Registration: PROSPERO ID CRD42020168851. MATERIALS AND METHODS: A systematic review, according to the PRISMA Statement, was performed. Search through the Medline, Embase, Scopus, Scielo, Lilacs, and Cochrane Database until July 2020. RESULTS: The literature search yielded 2,883 citations and were selected eight studies, including 1096 patients. A total of 707 patients underwent IC and 389 CU. Surgical procedures and outcomes, complications, mortality, and quality of life were analyzed. CONCLUSIONS: CU seems to be a safe alternative for the elderly and more frail patients. It is associated with faster surgery, less blood loss, lower transfusion rates, a lower necessity of intensive care, and shorter hospital stay. According to most studies, complications are less frequent after CU, even though mortality rates are similar. Studies with long-term follow up are awaited.

The use of BCAA to decrease delayed-onset muscle soreness after a single bout of exercise: a systematic review and meta-analysis.

Branched-chain amino acids (BCAA) are used as a recovery method after exercise-induced muscle damage (EIMD). Although data suggest that BCAA may alleviate the delayed-onset muscle soreness (DOMS) evoked by EIMD, there is no consensus about the most effective supplementation protocol. To investigate the effects of BCAA on DOMS after a single exercise session that caused EIMD, a systematic review and meta-analysis were conducted on the effectiveness of BCAA supplementation to reduce DOMS symptoms in healthy subjects after a single session of EIMD. Randomized clinical trials (RCT) were searched in Medline, Cochrane Library, Science Direct, SciELO, LILACS, SciVerse Scopus, Springer Link journals, Wiley Online Library, and Scholar Google, until May 2021. Ten RCTs were included in the systematic review and nine in the meta-analysis. Seven studies demonstrated that BCAA reduced DOMS after 24 to 72 h. BCAA doses of up to 255 mg/kg/day, or in trained subjects, for mild to moderate EIMD, could blunt DOMS symptoms. However, high variability between studies due to training status, different doses, time of treatment, and severity of EIMD do not allow us to conclude whether BCAA supplementation is efficient in untrained subjects, applied acutely or during a period of pre to post days of EIMD, and at higher doses (> 255 mg/kg/day). The overall effects of BCAA on DOMS after a single session of exercise were considered useful for improving muscle recovery by reducing DOMS in trained subjects, at low doses, in mild to moderate EIMD, and should not be administered only after the EIMD protocol.

Indoor environmental quality in households of families with infant twins under 1 year of age living in Porto.

Exposure to air pollution in early years can exacerbate the risk of noncommunicable diseases throughout childhood and the entire life course. This study aimed to assess temperature, relative humidity (RH), carbon dioxide (CO2) and monoxide (CO), particulate matter (PM2.5, PM10), ultrafine particles, nitrogen dioxide (NO2), ozone (O3), formaldehyde, acetaldehyde and volatile organic compounds (VOC) levels in the two rooms where infant twins spend more time at home (30 dwellings, Northern Portugal). Findings showed that, in general, the worst indoor environmental quality (IEQ) settings were found in bedrooms. In fact, although most of the bedrooms surveyed presented adequate comfort conditions in terms of temperature and RH, several children are sleeping in a bedroom with improper ventilation and/or with a significant degree of air pollution. In particular, mean concentrations higher than recommended limits were found for CO2, PM2.5, PM10 and total VOC. Additionally, terpenes and decamethylcyclopentasiloxane were identified as main components of emissions from indoor sources. Overall, findings revealed that factors related to behaviors of the occupants, namely related to a conscientious use of cleaning products, tobacco and other consumer products (air-fresheners, incenses/candles and insecticides) and promotion of ventilation are essential for the improvement of air quality in households and for the promotion of children's health.

A Survey of the Regulatory Requirements for the Waiver of In Vivo Bioequivalence Studies of Generic Products in Certain Dosage Forms by Participating Regulators and Organisations of the International Pharmaceutical Regulators Programme.

The requirements to waive in vivo bioequivalence studies for immediate release solid oral dosage forms based on the Biopharmaceutics Classifications System (BCS) are well known, and biowaivers[1] for other types of oral dosage forms based on pre-defined criteria may also be acceptable. Similarly, biowaivers for dosage forms such as injectable products may also be allowed if certain criteria are met. The current paper summarises the biowaiver requirements for oral solutions and suspensions, soft gelatin capsules and injectable products (intravenous injections, subcutaneous and intramuscular injections, emulsions for injection and micellar solutions for injection) among the participants of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Programme (IPRP). A review of the requirements indicated that there was a trend towards convergence when the dosage form became less complex; however, the most common approach used by each of the jurisdictions was a case-by-case approach given that most jurisdictions do not have well defined guidelines to support all possible scenarios. Even in the simplest case of intravenous solutions, the acceptability of qualitative changes in excipients differ between the IPRP members.  Notwithstanding the differences, the dissemination of the information is a first step towards regulatory convergence regarding biowaivers for certain dosage forms and should be useful for pharmaceutical companies currently developing generic medicinal products for IPRP jurisdictions.

Requirements for Additional Strength Biowaivers for Modified Release Solid Oral Dosage Forms in International Pharmaceutical Regulators Programme Participating Regulators and Organisations: Differences and Commonalities.

This article describes an overview of waivers of in vivo bioequivalence studies for additional strengths in the context of the registration of modified release generic products and is a follow-up to the recent publication for the immediate release solid oral dosage forms. The current paper is based on a survey among the participating members of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Program (IPRP) regarding this topic. Most jurisdictions consider the extrapolation of bioequivalence results obtained with one (most sensitive) strength of a product series as less straightforward for modified release products than for immediate release products. There is consensus that modified release products should demonstrate bioequivalence not only in the fasted state but also in the fed state, but differences exist regarding the necessity of additional multiple dose studies. Fundamental differences between jurisdictions are revealed regarding requirements on the quantitative composition of different strengths and the differentiation of single and multiple unit dosage forms. Differences in terms of in vitro dissolution requirements are obvious, though these are mostly related to possible additional comparative investigations rather than regarding the need for product-specific methods. As with the requirements for immediate release products, harmonization of the various regulations for modified release products is highly desirable to conduct the appropriate studies from a scientific point of view, thus ensuring therapeutic equivalence.

Association of subjective health symptoms with indoor air quality in European office buildings: The OFFICAIR project.

The aim of this study was to explore the association between the building-related occupants' reported health symptoms and the indoor pollutant concentrations in a sample of 148 office rooms, within the framework of the European OFFICAIR research project. A large field campaign was performed in 37 office buildings among eight countries, which included (a) 5-day air sampling of volatile organic compounds (VOCs), aldehydes, ozone, and NO2 (b) collection of information from 1299 participants regarding their personal characteristics and health perception at workplace using online questionnaires. Stepwise and multilevel logistic regressions were applied to investigate associations between health symptoms and pollutant concentrations considering personal characteristics as confounders. Occupants of offices with higher pollutant concentrations were more likely to report health symptoms. Among the studied VOCs, xylenes were associated with general (such as headache and tiredness) and skin symptoms, ethylbenzene with eye irritation and respiratory symptoms, a-pinene with respiratory and heart symptoms, d-limonene with general symptoms, and styrene with skin symptoms. Among aldehydes, formaldehyde was associated with respiratory and general symptoms, acrolein with respiratory symptoms, propionaldehyde with respiratory, general, and heart symptoms, and hexanal with general SBS. Ozone was associated with almost all symptom groups.

What do surgeons need to know about the mesopancreas.

BACKGROUND: Pancreatoduodenectomy is the only treatment with a promise of cure for patients with pancreatic head adenocarcinoma, and a negative resection margin is an important factor related to overall survival. Complete clearance of the medial margin with removal of the so-called mesopancreas may decrease the recurrence rate after pancreatic resection. Here, we present some important information about the mesopancreas, total mesopancreas excision, and technical aspects to achieve negative resection margins. The area named mesopancreas is defined as the tissue located between the head of the pancreas and the superior mesenteric vessels and the celiac axis and consists of the nerve plexus, lymphatic tissue, and connective tissue. The superior mesenteric and celiac arteries define the border of the mesopancreas. En bloc resection of anterior and posterior pancreatoduodenal nodes, hepatoduodenal nodes, along the superior mesenteric artery nodes, pyloric nodes, and nodes along the common hepatic artery is necessary. CONCLUSIONS: Improved knowledge of the surgical anatomy of the region and technical refinements of excision of the mesopancreas along with standardized pathological examination are important to increase and to determine radical resection of pancreatic head cancer.

Laparoscopic intragastric resection of gastric synovial sarcoma: report of the first ever case with video demonstration.

BACKGROUND: Synovial sarcoma (SS) is a rare soft tissue tumor. Among different anatomical locations where it can be found, gastric localization is a very uncommon one. Based on soft tissue sarcoma guidelines, complete tumor excision is considered the main treatment approach. Depending on size and localization of the tumor, both wedge and major gastric resections have been performed in the past for the treatment of this condition. CASE PRESENTATION: We present the case of a 43-year-old woman who underwent a laparoscopic intragastric excision of a gastric 10-mm SS located nearby the esophagogastric junction. Pathology examination confirmed the presence of a SS. The resected specimen confirmed margin-free excision of a monophasic spindle cell neoplasm invading the submucosa and presenting the rearrangement of SS18 gene at fluorescence in situ hybridization (FISH). No adjuvant treatment was offered, and 18 months after surgery, the patient was alive and disease free. CONCLUSIONS: This represents the first case reported in literature of a laparoscopic intragastric resection for a gastric SS. This approach allowed to obtain a full thickness radical tumor resection with the advantages of minimally invasive and organ preserving surgery.

First Long-term Oncologic Results of the ALPPS Procedure in a Large Cohort of Patients With Colorectal Liver Metastases.

OBJECTIVES: To analyze long-term oncological outcome along with prognostic risk factors in a large cohort of patients with colorectal liver metastases (CRLM) undergoing ALPPS. BACKGROUND: ALPPS is a two-stage hepatectomy variant that increases resection rates and R0 resection rates in patients with primarily unresectable CRLM as evidenced in a recent randomized controlled trial. Long-term oncologic results, however, are lacking. METHODS: Cases in- and outside the International ALPPS Registry were collected and completed by direct contacts to ALPPS centers to secure a comprehensive cohort. Overall, cancer-specific (CSS), and recurrence-free (RFS) survivals were analyzed along with independent risk factors using Cox-regression analysis. RESULTS: The cohort included 510 patients from 22 ALPPS centers over a 10-year period. Ninety-day mortality was 4.9% and median overall survival, CSS, and RFS were 39, 42, and 15 months, respectively. The median follow-up time was 38 months (95% confidence interval 32-43 months). Multivariate analysis identified tumor-characteristics (primary T4, right colon), biological features (K/N-RAS status), and response to chemotherapy (Response Evaluation Criteria in Solid Tumors) as independent predictors of CSS. Traditional factors such as size of metastases, uni versus bilobar involvement, and liver-first approach were not predictive. When hepatic recurrences after ALPPS was amenable to surgical/ablative treatment, median CSS was significantly superior compared to chemotherapy alone (56 vs 30 months, P < 0.001). CONCLUSIONS: This large cohort provides the first evidence that patients with primarily unresectable CRLM treated by ALPPS have not only low perioperative mortality, but achieve appealing long-term oncologic outcome especially those with favorable tumor biology and good response to chemotherapy.

ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study.

BACKGROUND: ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC). METHODS: The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis. RESULTS: One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p < 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC. CONCLUSION: ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.

Assessment of indoor air conditions in households of Portuguese families with newborn children. Implementation of the HEALS IAQ checklist.

Conducting epidemiological and risk assessment research that considers the exposome concept, as in the case of HEALS project, requires the acquisition of higher dimension data sets of an increased complexity. In this context, new methods that provide accurate and interpretable data summary on relevant environmental factors are of major importance. In this work, a questionnaire was developed to collect harmonized data on potential pollutant sources to air in the indoor environment where children spend an important part of their early life. The questionnaire was designed in a user friendly checklist format to be filled out at the maternity in ten European cities. This paper presents and discusses the rationale for the selection of the questionnaire contents and the results obtained from its application in the households of 309 HEALS-enrolled families with babies recently born in Porto, Portugal. The tool was very effective in providing data on the putative air pollution sources in homes, with special focus on the bedroom of the newborns. The data collected is part of a wider effort to build the databases and risk assessment models of the HEALS project. The results of the analysis of the collected data suggest that, for the population under study, the main concerns on early life exposures at home can be related to emissions from the use of household solid fuels, indoor tobacco, household cleaning products, fragranced consumer products (e.g. air fresheners, incense and candles), moisture-related pathologies and traffic-related outdoor pollution. Furthermore, it is anticipated that the tool can be a valuable means to empower citizens to actively participate in the control of their own exposures at home. Within this context, the application of the checklist will also allow local stakeholders to identify buildings presenting most evident IAQ problems for sampling or intervention as well as to guide them in preparing evidence-based educational/awareness campaigns to promote public health through creating healthy households.

Educational step-by-step surgical video about operative technique in robotic pancreaticoduodenectomy (RPD) at University of Illinois at Chicago (UIC): 17 steps standardized technique-Lessons learned since the first worldwide RPD performed in the year 2001.

BACKGROUND: RPD (Robotic pancreatoduodenectomy) was first performed by P. C. Giulianotti in 2001 (Arch Surg 138(7):777-784, 2003). Since then, the complexity and lack of technique standardization has slowed down its widespread utilization. RPD has been increasingly adopted worldwide and in few centres is the preferred apporached approach by certain surgeons. Some large retrospective series are available and data seem to indicate that RPD is safe/feasible, and a valid alternative to the classic open Whipple. Our group has recently described a standardized 17 steps approach to RPD (Giulianotti et al. Surg Endosc 32(10): 4329-4336, 2018). Herin, we present an educational step-by-step surgical video with short technical/operative description to visually exemplify the RPD 17 steps technique. METHODS: The current project has been approved by our local Institutional Review Board (IRB). We edited a step-by-step video guidance of our RPD standardized technique. The data/video images were collected from a retrospective analysis of a prospectively collected database (IRB approved). The narration and the images describe hands-on operative "tips and tricks" to facilitate the learning/teaching/evaluation process. RESULTS: Each of the 17 surgical steps is visually represented and explained to help the in-depth understanding of the relevant surgical anatomy and the specific operative technique. CONCLUSIONS: Educational videos descriptions like the one herein presented are a valid learning/teaching tool to implement standardized surgical approaches. Standardization is a crucial component of the learning curve. This approach can create more objective and reproducible data which might be more reliably assessed/compared across institutions and by different surgeons. Promising results are arising from several centers about RPD. However, RPD as gold standard-approach is still a matter of debate. Randomized-controlled studies (RCT) are required to better validate the precise role of RPD.