High intra-abdominal pressure during hyperthermic intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery (CRS) for peritoneal surface malignancies.

OBJECTIVE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) represent a mainstay of treatment for peritoneal malignancies. There is evidence that HIPEC using high intra-abdominal pressure (IAP) results in increased tissue penetration, although its safety profile remains relatively unknown. We thus aim to evaluate differences in intra- and post-operative outcomes in patients undergoing CRS-HIPEC with different levels of IAP. METHODS: This pilot prospective cohort study was conducted from January 2020 to February 2021 with patients undergoing CRS-HIPEC. Low IAP during HIPEC was defined as <18 mmHg and high IAP as ≥18 mmHg. Data was collected on patient and tumor characteristics, intra-operative clinical and biochemical parameters, and immediate post-operative outcomes. RESULTS: 40 patients underwent CRS-HIPEC (n low = 20, n high = 20). Median IAP in the low and high IAP groups were 12.0 and 19.0 mmHg respectively. During HIPEC, both groups experienced increase in heart rate, central venous pressure, end tidal CO2, temperature, and serum glucose, with decrease in mean arterial pressure and base excess. There were no significant differences in hemodynamics between the 2 groups. Mild electrolyte derangements and a decrease in hemoglobin were noted in the high IAP group but were of small magnitude. Post-operatively, high IAP did not result in increased rate of complications, time to full feeds, ICU or total hospital stay. CONCLUSIONS: High IAP in HIPEC is well tolerated and did not result in additional adverse events.

Introduction of Group Electronic Monitoring of Hand Hygiene on Inpatient Units: A Multicenter Cluster Randomized Quality Improvement Study.

BACKGROUND: The current approach to measuring hand hygiene (HH) relies on human auditors who capture <1% of HH opportunities and rapidly become recognized by staff, resulting in inflation in performance. Group electronic monitoring is a validated method of measuring HH adherence, but data demonstrating the clinical impact of this technology are lacking. METHODS: A stepped-wedge cluster randomized quality improvement study was performed on 26 inpatient medical and surgical units across 5 acute care hospitals in Ontario, Canada. The intervention involved daily HH reporting as measured by group electronic monitoring to guide unit-led improvement strategies. The primary outcome was monthly HH adherence (percentage) between baseline and intervention. Secondary outcomes included transmission of antibiotic-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and other healthcare-associated infections. RESULTS: After adjusting for the correlation within inpatient units and hospitals, there was a significant overall improvement in HH adherence associated with the intervention (incidence rate ratio [IRR], 1.73 [95% confidence interval {CI}, 1.47-1.99]; P < .0001). Monthly HH adherence relative to the intervention increased from 29% (1 395 450/4 544 144) to 37% (598 035/1 536 643) within 1 month, followed by consecutive incremental increases up to 53% (804 108/1 515 537) by 10 months (P < .0001). There was a trend toward reduced healthcare-associated transmission of MRSA (IRR, 0.74 [95% CI, .53-1.04]; P = .08). CONCLUSIONS: The introduction of a system for group electronic monitoring led to rapid, significant improvements in HH performance within a 2-year period. This method offers significant advantages over direct observation for measurement and improvement of HH.

Prevention of gallbladder hypomotility via FATP2 inhibition protects from lithogenic diet-induced cholelithiasis.

Gallstone disease is a widespread disorder costing billions for annual treatment in the United States. The primary mechanisms underlying gallstone formation are biliary cholesterol supersaturation and gallbladder hypomotility. The relative contribution of these two processes has been difficult to dissect, as experimental lithogenic diets cause both bile supersaturation and alterations in gallbladder motility. Importantly, there is no mechanistic explanation for obesity as a major risk factor for cholelithiasis. We discovered that lithogenic diets induce ectopic triacylglycerol (TAG) accumulation, a major feature of obesity and a known muscle contraction impairing condition. We hypothesized that prevention of TAG accumulation in gallbladder walls may prevent gallbladder contractile dysfunction without impacting biliary cholesterol saturation. We utilized adeno-associated virus-mediated knock down of the long-chain fatty acid transporter 2 (FATP2; Slc27A2), which is highly expressed by gallbladder epithelial cells, to downregulate lithogenic diet-associated TAG accumulation. FATP2-knockdown significantly reduced gallbladder TAG, but did not affect key bile composition parameters. Importantly, measurements with force displacement transducers showed that contractile strength in FATP2-knockdown gallbladders was significantly greater than in control gallbladders following lithogenic diet administration, and the magnitude of this effect was sufficient to prevent the formation of gallstones. FATP2-driven fatty acid uptake and the subsequent TAG accumulation in gallbladder tissue plays a pivotal role in cholelithiasis, and prevention of this process can protect from gallstone formation, even in the context of supersaturated bile cholesterol levels, thus pointing to new treatment approaches and targets.

Knowledge and thresholds for palliative care and surgery among healthcare providers caring for adults with serious illness.

Introduction: Timely palliative care and surgical interventions improve symptoms, health-related quality of life (HRQoL), and reduce medical cost for seriously ill adults at end of life (EOL). However, there is still poor delivery and underutilization of these palliative services. We hypothesize that the sub-optimal delivery is due to limited understanding among healthcare providers. Methods: A nationwide cross-sectional online survey was conducted among primary and tertiary healthcare providers. The survey assessed challenges faced, palliative education, confidence in managing palliative patients, and knowledge on palliative surgery. Overall palliative care awareness and knowledge was assessed using a 6-point score. Likelihood of considering various palliative interventions at EOL was also determined using a threshold score (higher score = higher threshold). Results: There were 145 healthcare providers who completed the survey (81.9% response rate); majority reported significant challenges in providing various aspects of palliative care: 57% (n = 82) in the provision of emotional support. Sixty-nine percent (n = 97) in managing social issues, and 71% (n = 103) in managing family expectations. Most expressed inadequate palliative care training in both under-graduate and post-graduate training and lack confidence in managing EOL issues. Up to 57% had misconceptions regarding potential benefits, morbidity and mortality after palliative surgery. In general, most providers had high thresholds for Intensive Care Unit admissions and palliative surgery, and were more likely to recommend endoscopic or interventional radiology procedures at EOL. Conclusion: Healthcare providers in Singapore have poor knowledge and misconceptions about palliative care and surgery. Improving awareness and education among those caring for seriously ill adults is essential.

A Systematic Review and Meta-Analysis of Mapping Biopsy for Primary Extramammary Paget's Disease in Reducing Recurrence Following Surgical Excision.

Objective: To examine the association between the performance of mapping biopsies and surgical outcomes postexcision of extramammary Paget's disease (EMPD). Background: Primary EMPD is a rare entity associated with poorly defined surgical margins and difficult-to-access sites of lesions. Surgical resection with clear margins remains the preferred management method. The use of mapping biopsies might be beneficial, particularly in lowering disease recurrence. Methods: Available literature was reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology before a fixed-effect meta-analysis was performed to identify the presence of a correlation between performing mapping biopsies and positive margins on permanent sections as well as disease-free survival. Additional study results not included in the quantitative assessment were qualitatively assessed and reported. Results: A total of 12 studies were shortlisted for final analysis. 294 patients who underwent mapping biopsies and 48 patients who did not undergo mapping biopsies were included in the assessment. Forest plot analysis revealed a pooled rate ratio of 0.50 (95% CI, 0.32-0.77) in the prevalence of positive margins in patients with mapping biopsies performed as compared to patients without. The pooled rate ratio of the prevalence of disease-free survival in patients with mapping biopsies performed as compared to patients without was 1.38 (95% CI, 1.03-1.84). Qualitative assessment of the remaining selected studies revealed equivocal results. Conclusions: Mapping biopsies are able to improve EMPD surgical excision outcomes but given the rarity of the disease and heterogeneity of mapping biopsy procedures, further confirmation with randomized controlled trials or a larger patient pool is necessary.

A systematic review on quality of life (QoL) of patients with peritoneal metastasis (PM) who underwent pressurized intraperitoneal aerosol chemotherapy (PIPAC).

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has recently emerged as a palliative alternative for patients with unresectable peritoneal metastasis (PM). Quality of life (QoL) has increasingly been used as an endpoint to evaluate treatment outcomes. This review aims to identify evidence on how PIPAC would impact the QoL of PM patients. Content: A systematic review was performed on articles identified from Medline, EMBASE, PsycInfo, and Web of Sciences. A meta-analysis was conducted on further selected studies. ACROBAT-NRSI was attempted to assess the risk of bias (RoB). Summary: Nine studies using the EORTC QLQ-C30 questionnaire to assess QoL after repeated PIPAC cycles were identified. Majority was found to be moderately biased and a great extent of heterogeneity was observed. Four studies on PM from either gastric cancer (GC) or epithelial ovarian cancer (EOC) were included for meta-analysis. In 31 GC patients and 104 EOC patients, QoL remained stable in 13/14 and 11/14 EORTC QLQ-C30 scales. PIPAC was inferior to cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in global QoL and functioning but superior in symptom reduction. Outlook: PIPAC is a well-tolerated option for most GC and EOC patients with irresectable PM. Future trials are warranted to confirm the findings.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal sarcomatosis-A systematic review and meta-analysis.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) play an important role in the treatment of various peritoneal surface malignancies, but its efficacy in peritoneal sarcomatosis (PS) remains unknown. Hence, we performed a systematic review and meta-analysis to investigate outcomes of CRS-HIPEC in PS, in accordance with PRISMA guidelines. 16 studies with a total of 320 patients were included in the meta-analysis. Pooled mean length of hospital stay after CRS-HIPEC was 16.0 days (95% CI: 12.2-19.8) and rate of serious complications was 17.4% (95% CI: 9.8-26.3). The median DFS was 12.0 months (95% CI: 8.0-16.0) and the 5-year DFS was 21.8% (95% CI: 13.2-31.7). Overall pooled median OS was 29.3 months (95% CI: 23.8-34.8), with a 5-year OS of 35.3% (95% CI: 26.3-44.8). Subgroup analysis showed that patients with CC-0 cytoreduction had a higher median OS of 34.6 months (95% CI: 23.2-45.9). Median OS for patients with a primary tumour histology of leiomyosarcoma and liposarcoma was 33.5 months (95% CI: 15.9-51.1) and 39.1 months (95% CI: 20.8-57.5) respectively. The site of recurrence was locoregional in 57.3% (95% CI: 38.9-74.8), distant in 17.3% (95% CI: 3.9-35.6), and both in 17.4% (95% CI: 5.8-32.2). In conclusion, our results suggest that CRS-HIPEC may improve outcomes in a select group of PS patients.

Prospective Comparison of the Performance of MRI Versus CT in the Detection and Evaluation of Peritoneal Surface Malignancies.

Background: The performance of MRI versus CT in the detection and evaluation of peritoneal surface malignancies (PSM) remains unclear in the current literature. Our study is the first prospective study in an Asian center comparing the two imaging modalities, validated against intra-operative findings. Methods: A total of 36 patients with PSM eligible for CRS-HIPEC underwent both MRI and CT scans up to 6 weeks before the operation. The scans were assessed for the presence and distribution of PSM and scored using the peritoneal cancer index (PCI), which were compared against PCI determined at surgery. Results: Both MRI and CT were 100% sensitive and specific in detecting the overall presence of PSM. Across all peritoneal regions, the sensitivity and specificity for PSM detection was 49.1% and 93.0% for MRI, compared to 47.8% and 95.1% for CT (p = 0.76). MRI was more sensitive than CT for small bowel disease, although the difference did not reach statistical significance. Comparing PCI on imaging with intra-operative PCI, the mean difference was found to be −3.4 ± 5.4 (p < 0.01) for MRI, and −3.9 ± 4.1 (p < 0.01) for CT. The correlation between imaging and intra-operative PCI was poor, with a concordance coefficient of 0.76 and 0.79 for MRI and CT, respectively. Within individual peritoneal regions, there was also poor agreement between imaging and intra-operative PCI for both modalities, other than in regions 1 and 3. Conclusion: MRI and CT are comparable in the detection and evaluation of PSM. While sensitive in the overall detection of PSM, they are likely to underestimate the true disease burden.

Safety, effectiveness and sustainability of a laboratory intervention to de-adopt culture of midstream urine samples among hospitalized patients.

OBJECTIVE: To assess the safety, sustainability, and effectiveness of a laboratory intervention to reduce processing of midstream urine (MSU) cultures. DESIGN: Prospective observational cohort. SETTING: Medical and surgical inpatients in a tertiary-care hospital. PARTICIPANTS: The study included 1,678 adult inpatients with an order for MSU culture. METHODS: From 2013 to 2019, ordered MSU cultures were not processed unless the laboratory was called. Patients were interviewed on days 0 and 4; from 2017 to 2019, day-30 follow-up was added. Primary outcome was serious adverse events due to not processing MSU cultures. Secondary outcomes were nonserious adverse events due to not processing MSU cultures, rates of MSU cultures submitted, proportion of MSU cultures processed, proportion of patients prescribed urinary tract infection (UTI)-directed antibiotics, and laboratory workload. RESULTS: Among 912 and 459 patients followed to days 4 and 30, respectively, no serious adverse events attributable to not processing MSU cultures were identified. However, 6 patients (0.66%) had prolonged urinary symptoms potentially associated with not processing MSU cultures. We estimated that 4 patients missed having empiric antibiotics stopped in response to negative MSU cultures, and 99 antibiotic courses for asymptomatic bacteriuria (ASB) and 8 antibiotic-associated adverse events were avoided. The rate of submitted MSU samples and proportion of patients receiving empiric UTI-directed antibiotics did not change. The proportion of MSU cultures processed declined from 59% to 49% (P < .0001), and total laboratory workload was reduced by 185 hours. CONCLUSIONS: De-adopting the processing of MSU cultures from medical and surgical inpatient units is safe and sustainable, and it reduces antibiotic prescriptions for ASB at a cost of prolonged urinary symptoms in a small proportion of patients.

The Complex Maze of the Informed Consent Process: Helping to Improve Comprehension in Clinical Trial Participants with Alzheimer's Disease.

We intend for this article to provide a foundation toward the creation of a more patient-centric approach to the informed consent process. Our overall objectives are to promote ethical clinical research standards and procedures toward enhanced supportive systems for clinical trial participants. We provide a suggested format which multidisciplinary clinical trial researchers can adapt for their own clinical trial setting.

Interethnic differences in neuroimaging markers and cognition in Asians, a population-based study.

We examined interethnic differences in the prevalence of neuroimaging markers of cerebrovascular and neurodegenerative disease in 3 major Asian ethnicities (Chinese, Malays, and Indians), as well as their role in cognitive impairment. 3T MRI brain scans were acquired from 792 subjects (mean age: 70.0 ± 6.5years, 52.1% women) in the multi-ethnic Epidemiology of Dementia In Singapore study. Markers of cerebrovascular disease and neurodegeneration were identified. Cognitive performance was evaluated using Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and a neuropsychological assessment. Compared to Chinese, Malays had a higher burden of intracranial stenosis (OR: 2.28. 95%CI: 1.23-4.20) and cortical atrophy (ß: -0.60. 95%CI: -0.78, -0.41), while Indians had a higher burden of subcortical atrophy (ß: -0.23. 95%CI: -0.40, -0.06). Moreover, Malay and Indian ethnicities were likely to be cognitively impaired (OR for Malays: 3.79. 95%CI: 2.29-6.26; OR for Indians: 2.87. 95%CI: 1.74-4.74) and showed worse performance in global cognition (ß for Malays: -0.51. 95%CI: -0.66, -0.37; and Indians: -0.32. 95%CI: -0.47, -0.17). A higher burden of cerebrovascular and neurodegenerative markers were found in Malays and Indians when compared to Chinese. Further research is required to fully elucidate the factors and pathways that contribute to these observed differences.

Feasibility and Acceptability of a Web-Based Dietary Intervention with Text Messages for Colorectal Cancer: A Randomized Pilot Trial.

BACKGROUND: Diet is associated with colorectal cancer survival. Yet, adherence to nutrition guidelines is low among colorectal cancer survivors. METHODS: We conducted a pilot trial among colorectal cancer survivors to evaluate a 12-week remote dietary intervention. Participants received print materials and were randomized (1:1) to intervention (website, text messages) or wait-list control. Primary outcomes included feasibility and acceptability. We also explored change in diet from 0 to 12 and 24 weeks and change from 0 to 12 weeks in anthropometry and circulating biomarkers (Trial Registration: NCT02965521). RESULTS: We randomized 50 colorectal cancer survivors (25 intervention, 25 control). Retention was 90% at 12 weeks and 84% at 24 weeks. Participants had a median age of 55 years and were 66% female, 70% non-Hispanic white, and 96% had a college degree. The intervention arm responded to a median 15 (71%) of 21 text messages that asked for a reply [interquartile range (IQR) = 8, 19] and visited the website a median of 13 (15%) days (IQR = 1, 33) of the 84 study days. CONCLUSIONS: We developed a Web-based dietary intervention for colorectal cancer survivors. Our pilot results suggest that colorectal cancer survivors may engage more with text messages than a study website. Research to improve tailoring of text messages, while maintaining scalability, is needed. IMPACT: Remote dietary interventions using text messages may be feasible for colorectal cancer survivors.See all articles in this CEBP Focus section, "Modernizing Population Science."

Power law relations in earthquakes from microscopic to macroscopic scales.

Understanding the physics of earthquakes is a crucial step towards improving the prediction accuracy of earthquakes. Scale invariance or fractal features are often reported in earthquakes, such as the size distribution of earthquakes, the spatial distribution of hypocenters, and the frequency of aftershocks. Here we assess whether other key parameters and quantities involved in earthquakes also conform to the power law. By analyzing a large amount of data collected from the laboratory experiments and field monitoring of earthquakes, we find that the crack density on the two sides of small scale fracture or large scale fault decreases with increasing distance following the power law, and the crack number-crack length distribution is also scale invariant like natural faults. Besides, the earthquake b-value is found to decrease with increasing stress in a power law in the brittle regime of the Earth's crust. The friction coefficient for dry fault and gouges or for partially saturated gouges decreases with the increasing effective normal stress in a power law. The stress dependency of b-value and friction coefficient is dictated by different mechanisms. Our findings will advance the understanding of earthquake physics, and will enable us to better model, predict and conduct hazard assessment of earthquakes.

Electro-oxidation of ascorbic acid by cobalt core-shell nanoparticles on a H-terminated Si(100) and by nanostructured cobalt-coated Si nanowire electrodes.

Determination of the concentration of ascorbic acid in a solution has attracted intense recent interest. Here we demonstrate the feasibility of electro-oxidation of ascorbic acid on spherical cobalt core-shell nanoparticles (10-50 nm dia.) prepared by electrochemical deposition on a H-terminated Si(100) substrate. Depth-profiling X-ray photoelectron spectroscopy reveals that these nanoparticles consist of a metallic cobalt core covered by a Co(OH)2 shell without any evidence of CoOx. Glancing-incidence X-ray diffraction studies further show that the metallic Co core consists of a mixture of hexagonal close packed and face centered cubic structures, the relative composition of which can be easily controlled by the deposition potential. We further demonstrate that when these Co nanoparticles are deposited on a high-surface-area electrode as provided by a Si nanowire template, the resulting nanostructured Co-coated Si nanowire electrode offers a promising high-performance sensor platform for ascorbic acid detection.

Normal distribution of palpebral fissure lengths in Canadian school age children.

BACKGROUND: Fetal alcohol syndrome (FAS) includes the facial dysmorphic feature of short palpebral fissures (PFs) and short PFs are a key physical marker for identifying children with FAS and some other rarer conditions. There is concern that normative data on PFs now available may not reflect all racial/ethnic groups and might be inaccurate in general. OBJECTIVES: To accomplish a large population based study that would accurately determine normative PF values across the full diversity of the Canadian school age population. METHODS: A normative sample of school age children was identified in Vancouver, British Columbia and Winnipeg, Manitoba to reflect the diversity of racial and national groups in Canada. The sample included students in grades 2, 4, 6, 8, and 10 from 17 schools in Vancouver and 31 schools in Winnipeg. Schools were selected based on racial diversity obtained from data from the 2001 Statistics Canada census. 1064 students in Vancouver and 1033 students in Winnipeg were photographed in a standardized way. Photographs were analyzed using a computerized method. RESULTS: Analysis demonstrated that PFs do grow with age and there is a slight but meaningful difference between boys and girls in each age group. It is possible to define Canadian standards without reference to racial or ethnic origin. CONCLUSION: Mean results with norms and standard deviations are presented in figures for clinical use and are clinically smaller than those found in the most commonly used reference book.