Pressurised intraperitoneal aerosol chemotherapy: rationale, evidence, and potential indications.

Pressurised intraperitoneal aerosol chemotherapy (PIPAC) was introduced as a new treatment for patients with peritoneal metastases in November, 2011. Reports of its feasibility, tolerance, and efficacy have encouraged centres worldwide to adopt PIPAC as a novel drug delivery technique. In this Review, we detail the technique and rationale of PIPAC and critically assess its evidence and potential indications. A systematic search was done to identify all relevant literature on PIPAC published between Jan 1, 2011, and Jan 31, 2019. A total of 106 articles or reports on PIPAC were identified, and 45 clinical studies on 1810 PIPAC procedures in 838 patients were included for analysis. Repeated PIPAC delivery was feasible in 64% of patients with few intraoperative and postoperative surgical complications (3% for each in prospective studies). Adverse events (Common Terminology Criteria for Adverse Events greater than grade 2) occurred after 12-15% of procedures, and commonly included bowel obstruction, bleeding, and abdominal pain. Repeated PIPAC did not have a negative effect on quality of life. Using PIPAC, an objective clinical response of 62-88% was reported for patients with ovarian cancer (median survival of 11-14 months), 50-91% for gastric cancer (median survival of 8-15 months), 71-86% for colorectal cancer (median survival of 16 months), and 67-75% (median survival of 27 months) for peritoneal mesothelioma. From our findings, PIPAC has been shown to be feasible and safe. Data on objective response and quality of life were encouraging. Therefore, PIPAC can be considered as a treatment option for refractory, isolated peritoneal metastasis of various origins. However, its use in further indications needs to be validated by prospective studies

Oxaliplatin use in pressurized intraperitoneal aerosol chemotherapy (PIPAC) is safe and effective: A multicenter study.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new drug delivery method used in patients with peritoneal cancer (PC) of primary or secondary origin. Intraperitoneal use of oxaliplatin raises concerns about toxicity, especially abdominal pain. The objective of this study was to assess the tolerance of PIPAC with oxaliplatin (PIPAC-Ox) in a large cohort of patients and to identify the risk factors for high grade toxicity, discontinuation of treatment and impaired survival. This retrospective cohort study included all consecutive patients treated with PIPAC-Ox (92 mg/m <sup>2</sup> ) in five centers specialized in the treatment of PC. The procedure was repeated every 6 weeks. Outcomes of interest were Common Terminology Criteria for Adverse Events (CTCAE), symptoms and survival (Kaplan-Meier). Univariate risk factors were included in a multinominal regression model to control for bias. Overall, 251 PIPAC-Ox treatments were performed in 101 patients (45 female) having unresectable PC of various origins: 66 colorectal, 15 gastric, 5 ovarian, 3 mesothelioma, 2 pseudomyxoma, 10 other malignancies (biliary, pancreatic, endocrine) respectively. The median PCI was 19 (IQR: 10-28). Postoperative abdominal pain was present in 23 patients. Out of the 9 patients with grade 3 abdominal pain, only 3 needed a change of PIPAC drug. CTCAE 4.0 toxicity grade 4 or higher was encountered in 16(15.9%) patients. The patients had a mean of 2.5 procedures/patient (SD = 1.5). 50 subjects presented with symptom improvement. Oxaliplatin-based PIPAC appears to be a safe treatment that offers good symptom control and promising survival for patients with advanced peritoneal disease

Long-term follow-up after traditional versus modified perineal approach in the management of female epispadias

Q2e1–497.e5Objective Isolated female epispadias (IFE) is a rare congenital anomaly. The defect extends to the bladder neck, which is usually incompetent. The traditional surgical approach includes urethral and genital reconstruction in the first year, followed by bladder neck reconstruction (Young-Dees-Leadbetter cervicoplasty (YDL)) at the age of social continence. An alternative single-stage technique includes urethral, bladder neck and clitoris repair by a perineal approach. The aim of the present study was to describe long-term follow-up of patients who underwent the traditional vs alternative approach. Materials and methods A retrospective review was performed of all female epispadias cases managed between 2000 and 2013. The YDL procedure (Group 1) vs single-stage perineal approach (Group 2) cases were followed and compared. Collected variables included: patients' demographics, age at diagnosis and surgery, presence of associated anomalies, clinical presentation, presence of vesicoureteral reflux (VUR), and pre-operative and postoperative continence. Results A total of 12 cases of female epispadias were managed and followed between 2000 and 2013. No major complications occurred in either group. Urinary continence evaluated in seven children showed that none (0/3) and 4/7 (57%) were continent following the initial procedure in Group 1 and Group 2, respectively. All patients in Group 1 failed to achieve continence and required re-intervention. Conclusions Female epispadias could be successfully repaired using a single-stage modified perineal approach that achieved good continence with volitional voiding, good cosmetic results and compared favorably with the ones repaired with the YDL technique. The additional step of performing bladder neck tailoring to achieve a funneling configuration seemed to be useful in improving continence

Deep CNN-LSTM With Self-Attention Model for Human Activity Recognition Using Wearable Sensor

Human Activity Recognition (HAR) systems are devised for continuously observing human behavior - primarily in the fields of environmental compatibility, sports injury detection, senior care, rehabilitation, entertainment, and the surveillance in intelligent home settings. Inertial sensors, e.g., accelerometers, linear acceleration, and gyroscopes are frequently employed for this purpose, which are now compacted into smart devices, e.g., smartphones. Since the use of smartphones is so widespread now-a-days, activity data acquisition for the HAR systems is a pressing need. In this article, we have conducted the smartphone sensor-based raw data collection, namely H-Activity , using an Android-OS-based application for accelerometer, gyroscope, and linear acceleration. Furthermore, a hybrid deep learning model is proposed, coupling convolutional neural network and long-short term memory network (CNN-LSTM), empowered by the self-attention algorithm to enhance the predictive capabilities of the system. In addition to our collected dataset ( H-Activity ), the model has been evaluated with some benchmark datasets, e.g., MHEALTH, and UCI-HAR to demonstrate the comparative performance of our model. When compared to other models, the proposed model has an accuracy of 99.93% using our collected H-Activity data, and 98.76% and 93.11% using data from MHEALTH and UCI-HAR databases respectively, indicating its efficacy in recognizing human activity recognition. We hope that our developed model could be applicable in the clinical settings and collected data could be useful for further research.publishedVersio

Urinary Properdin and sC5b-9 Are Independently Associated With Increased Risk for Graft Failure in Renal Transplant Recipients

The pathophysiology of late kidney-allograft failure remains complex and poorly understood. Activation of filtered or locally produced complement may contribute to the progression of renal failure through tubular C5b-9 formation. This study aimed to determine urinary properdin and sC5b-9 excretion and assess their association with long-term outcome in renal transplant recipients (RTR). Methods: We measured urinary properdin and soluble C5b-9 in a well-defined cross-sectional cohort of RTR. Urinary specimens were taken from a morning urine portion, and properdin and sC5b-9 were measured using an enzyme-linked-immunosorbent assay (ELISA). Cox proportional hazard regression analyses were used to investigate prospective associations with death-censored graft failure. Results: We included 639 stable RTR at a median [interquartile range] 5.3 (1.8-12.2) years after transplantation. Urinary properdin and sC5b-9 excretion were detectable in 161 (27%) and 102 (17%) RTR, respectively, with a median properdin level of 27.6 (8.6-68.1) ng/mL and a median sC5b-9 level of 5.1 (2.8-12.8) ng/mL. In multivariable-adjusted Cox regression analyses, including adjustment for proteinuria, urinary properdin (HR, 1.12; 95% CI 1.02-1.28; P = 0.008) and sC5b-9 excretion (HR, 1.34; 95% CI 1.10-1.63; P = 0.003) were associated with an increased risk of graft failure. If both urinary properdin and sC5b-9 were detectable, the risk of graft failure was further increased (HR, 3.12; 95% CI 1.69-5.77; P < 0.001). Conclusions: Our findings point toward a potential role for urinary complement activation in the pathogenesis of chronic allograft failure. Urinary properdin and sC5b-9 might be useful biomarkers for complement activation and chronic kidney allograft deterioration, suggesting a potential role for an alternative pathway blockade in RTR

Feasibility and safety of PIPAC combined with additional surgical procedures: PLUS study.

PIPAC (Pressurized IntraPeritoneal Aerosol Chemotherapy) is a minimally invasive approach relying on physical principles for improving intraperitoneal drug delivery, including optimizing the homogeneity of drug distribution through an aerosol. Feasibility and safety of the new approach are now consolidated and data on its effectiveness are continuously increasing. Although any surgical procedure associated with PIPAC had always been discouraged due to the high risk of complications, surgical practice is constantly changing: with growing expertise, more and more surgical teams associate PIPAC with surgery. PLUS study is part of the retrospective international cohort studies including 10 centers around the world (India, Italy, France, Germany, Belgium, Russia, Saudi Arabia, Switzerland) and 96 cases of combined approaches evaluated through a propensity score analysis. the procedures most frequently associated with PIPAC were not only adhesiolysis, omentectomy, adnexectomy, umbilical/inguinal hernia repairs, but also more demanding procedures such as intestinal resections, gastrectomy, splenectomy, bowel repair/stoma creation. Although the evidence is currently limited, PLUS study demonstrated that PIPAC associated with additional surgical procedures is linked to an increase of surgical time (p &lt; 0.001), length of stay (p &lt; 0.001) and medical complication rate (p &lt; 0.001); the most frequently reported medical complications were mild or moderate in severity, such as abdominal pain, nausea, ileus and hyperthermia. No difference in terms of surgical complications was registered; neither reoperation or postoperative deaths were reported. these results suggest that PIPAC can be safely combined in expert centers with additional surgeries. Widespread change of practice should be discouraged before the results of ongoing prospective studies are available

Current opinions and recommendations of paediatric healthcare professionals - The importance of tablets:Emerging orally disintegrating versus traditional tablets

The appropriate prescribing of paediatric dosage forms is paramount in providing the desired therapeutic effect alongside successful medication adherence with the paediatric population. Often it is the opinion of the healthcare practitioner that dictates which type of dosage form would be most appropriate for the paediatric patient, with liquids being both the most commonly available and most commonly used. Orally disintegrating tablets (ODTs) are an emerging dosage form which provide many benefits over traditional dosage forms for paediatric patients, such as rapid disintegration within the oral cavity, and the reduction in the risk of choking. However the opinion and professional use of healthcare practitioners regarding ODT's is not known. This study was designed to assess the opinions of several types of healthcare professionals (n = 41) regarding ODTs, using a survey across two hospital sites. Results reaffirmed the popularity of liquids for prescribing in paediatrics, with 58.0% of participants preferring this dosage form. ODTs emerged as the second most popular dosage form (30.0%), with healthcare practitioners indicating an increasing popularity amongst patients in the hospital setting, belief with 63.0% of practitioners agreeing that many liquid formulations could be substituted with a suitable ODT. The desired properties of an ideal ODT were also identified by healthcare practitioners preferring a small, fast disintegrating tablet (90.2% and 95.1% respectively), with the taste, disintegration time and flavour being the three most important attributes identified (29.5%, 28.7% and 21.7% respectively). This study provided a pragmatic approach in assessing healthcare professional's opinions on ODTs, highlighting the ideas and thoughts of practitioners who are on the frontline of paediatric prescribing and treatment and gave an indication to their preference for ODT properties