Patient and surgeon preferences for early ileostomy closure following restorative proctectomy for rectal cancer: why aren't we doing it?

BACKGROUND: Early ileostomy closure (EIC), ≤ 2 weeks from creation, is a relatively new practice. Multiple studies have demonstrated that this approach is safe, feasible, and cost-effective. Despite the demonstrated benefits, this is neither routine practice, nor has it been studied, in North America. This study aimed to assess patient and surgeon perspectives about EIC. METHODS: A mixed-methods, cross-sectional study of patients and surgeons was performed. Rectal cancer survivors from a single institution who underwent restorative proctectomy with diverting loop ileostomy and subsequent closure within the last 5 years were contacted. North American surgeons with high rectal cancer volumes (> 20 cases/year) were included. Surveys (patients) and semi-structured interviews (surgeons) were conducted. Analysis employed descriptive statistics and thematic analysis, respectively. RESULTS: Forty-eight patients were surveyed (mean age 65.1 ± 11.8 years; 54.2% male). Stoma closure occurred after a median of 7.7 months (IQR 4.8-10.9) and 50.0% (24) found it "difficult" or "very difficult" to live with their stoma. Patients considered improvement in quality of life and quicker return to normal function the most important advantages of EIC, whereas the idea of two operations in two weeks being too taxing on the body was deemed the biggest disadvantage. Most patients (35, 72.9%) would have opted for EIC. Surgeon interviews (15) revealed 4 overarching themes: (1) there are many benefits to EIC; (2) specific patient characteristics would make EIC an appropriate option; (3) many barriers to implementing EIC exist; and (4) many logistical hurdles need to be addressed for successful implementation. Most surgeons (12, 80.0%) would "definitely want to participate" in a North American randomized-controlled trial (RCT) on EIC for rectal cancer patients. CONCLUSIONS: Implementing EIC poses many logistical challenges. Both patients and surgeons are interested in further exploring EIC and believe it warrants a North American RCT to motivate a change in practice.

A Randomized, Dose-Finding, Proof-of-Concept Study of Berberine Ursodeoxycholate in Patients With Primary Sclerosing Cholangitis.

INTRODUCTION: Primary sclerosing cholangitis (PSC) is a fibroinflammatory disease of the bile ducts leading to cirrhosis and hepatic decompensation. There are no approved pharmaceutical therapies for PSC. Berberine ursodeoxycholate (HTD1801) is an ionic salt of berberine and ursodeoxycholic acid with pleiotropic mechanisms of action. METHODS: An 18-week proof-of-concept study was conducted to assess the safety and efficacy of HTD1801 in PSC. This study had three 6-week periods: (i) a placebo-controlled period, (ii) a treatment extension period, and (iii) a randomized treatment withdrawal period. The primary end point was change from baseline in alkaline phosphatase (ALP) at week 6. RESULTS: Fifty-five patients were randomized and treated; 35 (64%) had inflammatory bowel disease and 22 (40%) had previously received ursodeoxycholic acid. Patients were initially randomized to placebo (n = 16), HTD1801 500 mg BID (n = 15), or HTD1801 1000 mg BID (n = 24). At baseline, mean (range) ALP values were 414 U/L (138-1,048), 397 U/L (237-773), and 335 U/L (122-882) for the placebo, HTD1801 500 mg BID, and HTD1801 1,000 mg BID groups, respectively. At week 6, a significant decrease in ALP was observed with HTD1801 (least square mean; HTD1801 500 mg BID = -53 U/L, P = 0.016; HTD1801 1000 mg BID = -37 U/L, P = 0.019) compared with placebo (98 U/L). ALP reductions were sustained through week 18 in those who remained on therapy, whereas ALP increased in those who crossed over to placebo during period 3. HTD1801 was generally well tolerated; 4 patients experienced serious adverse events, none attributed to HTD1801. DISCUSSION: HTD1801 is associated with significant improvement in ALP and warrants further study as a treatment for PSC.

Home to Stay: A randomized controlled trial protocol to assess use of a mobile app to reduce readmissions following colorectal surgery.

AIM: Patients undergoing colorectal surgery face high rates of emergency room visits and readmission to hospital. These unplanned hospital visits lead to both increased patient anxiety and health care costs. The aim of this study is to evaluate the use of mobile application to support patients undergoing colorectal surgery following discharge from hospital. METHOD: This study is a randomized controlled trial in which the control group will receive standard follow-up care following discharge after surgery and the intervention group will receive standard follow-up care in addition to the mobile application. The primary outcome is the proportion of patients with unplanned hospital visits within 30 days of discharge. The secondary outcomes are patient-reported outcomes on validated scales evaluating their quality of recovery following discharge. A sample size of 670 subjects is planned. For the primary outcome, the control and intervention groups will be compared using a generalized linear model to account for clustering of patients within centres. For the secondary outcomes, the overall scores on the Quality of Recovery 15 and Patient Activation Measure will be analysed using a linear regression model. RESULTS: It is expected that the results of this study will show that the mobile app will lead to significant improvements in unplanned hospital visits as well as improved quality of recovery for patients. CONCLUSION: If the trial is successful, the mobile app can be easily adopted more widely into clinical practice to support patients at home following surgery.

Obeticholic acid is associated with improvements in AST-to-platelet ratio index and GLOBE score in patients with primary biliary cholangitis.

BACKGROUND & AIMS: Biochemical markers, including GLOBE score and aspartate aminotransferase-to-platelet ratio index (APRI), are used to stratify risk in patients with primary biliary cholangitis (PBC). This study aimed to evaluate the effects of obeticholic acid (OCA) on categorical shifts in GLOBE score, APRI, and both combined, based on data from POISE, a phase III placebo-controlled trial in patients with PBC who had an incomplete response or were intolerant to ursodeoxycholic acid. METHODS: In a post hoc analysis, baseline and Month 12 data from POISE were used to calculate the APRI and GLOBE score. Patients were stratified into 3 risk groups based on a combination of APRI (0.54) and GLOBE (0.3 or age-specific) thresholds. RESULTS: The analysis included 215 patients (47 low risk; 79 moderate risk; 89 high risk). Using the combined GLOBE score (threshold of 0.3) and APRI thresholds, there was improvement in ≥1 risk stage in 37% and 35% of patients in the OCA 5-10 mg and 10 mg groups, respectively, vs. 12% in the placebo group (both p <0.05). Progression occurred in 10% and 0% in the 5-10 mg and 10 mg groups vs. 37% in the placebo group. Results with GLOBE age-specific thresholds were similar. CONCLUSIONS: Based on change in APRI and GLOBE score at 12 months, OCA treatment is associated with reduction in the predicted risk of liver-related complications in patients with PBC. LAY SUMMARY: Primary biliary cholangitis (PBC) is a chronic disease affecting the liver. People who suffer from PBC are at risk of serious long-term complications. Information from certain blood tests can be used to estimate the likelihood of experiencing long-term complications. The results of this study showed that based on blood test results, people taking obeticholic acid, with or without ursodeoxycholic acid, for PBC were predicted to have a better outcome than those taking placebo. CLINICAL TRIALS REGISTRATION: NCT01473524.

Impact of Facilitation of Early Mobilization on Postoperative Pulmonary Outcomes After Colorectal Surgery: A Randomized Controlled Trial.

OBJECTIVE: To estimate the extent to which staff-directed facilitation of early mobilization impacts recovery of pulmonary function and 30-day postoperative pulmonary complications (PPCs) after colorectal surgery. SUMMARY BACKGROUND DATA: Early mobilization after surgery is believed to improve pulmonary function and prevent PPCs; however, adherence is low. The value of allocating resources (eg, staff time) to increase early mobilization is unknown. METHODS: This study involved the analysis of a priori secondary outcomes of a pragmatic, observer-blind, randomized trial. Consecutive patients undergoing colorectal surgery were randomized 1:1 to usual care (preoperative education) or facilitated mobilization (staff dedicated to assist transfers and walking during hospital stay). Forced vital capacity, forced expiratory volume in 1 second (FEV1), and peak cough flow were measured preoperatively and at 1, 2, 3 days and 4 weeks after surgery. PPCs were defined according to the European Perioperative Clinical Outcome Taskforce. RESULTS: Ninety-nine patients (57% male, 80% laparoscopic, median age 63, and predicted FEV1 97%) were included in the intention-to-treat analysis (usual care 49, facilitated mobilization 50). There was no between-group difference in recovery of forced vital capacity [adjusted difference in slopes 0.002 L/d (95% CI -0.01 to 0.01)], FEV1 [-0.002 L/d (-0.01 to 0.01)] or peak cough flow [-0.002 L/min/d (-0.02 to 0.02)]. Thirty-day PPCs were also not different between groups [adjusted odds ratio 0.67 (0.23-1.99)]. CONCLUSIONS: In this randomized controlled trial, staff-directed facilitation of early mobilization did not improve postoperative pulmonary function or reduce PPCs within an enhanced recovery pathway for colorectal surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02131844.

Effect of two different pre-operative exercise training regimens before colorectal surgery on functional capacity: A randomised controlled trial.

BACKGROUND: Multimodal prehabilitation, including exercise training, nutritional therapy and anxiety reduction, has been shown to attenuate functional decline associated with surgery. Due to the growing interest in functional status as a targeted surgical outcome, a better understanding of the optimal prescription of exercise is critical. OBJECTIVE: The objective is to compare peri-operative functional trajectory in response to two different exercise training protocols within a 4-week, supervised, multimodal prehabilitation programme. DESIGN: This was a single blinded, single centre, randomised controlled study. Participants performed four assessments: at baseline, after prehabilitation (just before surgery), and at 1 and 2 months after surgery. PATIENTS: Adult patients scheduled for elective resection of nonmetastatic colorectal cancer were included provided there were no absolute contraindications to exercise nor poor language comprehension. INTERVENTION: Patients followed either high-intensity interval training (HIIT), or moderate intensity continuous training (MICT), as part of a 4-week multimodal prehabilitation programme. Both groups followed the same supervised resistance training, nutritional therapy and anxiety reduction interventions. All patients followed standardised peri-operative management. MAIN OUTCOME MEASURE: Changes in oxygen consumption at anaerobic threshold, measured with sequential cardio-pulmonary exercise testing, were assessed and compared between groups. RESULTS: Forty two patients were included in the primary analysis (HIIT n = 21 vs. MICT n = 21), with mean ±â€ŠSD age 64.5 ±â€Š11.2 years and 62% were men. At 2 months after surgery, 13/21 (62%) in HIIT and 11/21 (52%) in MICT attended the study visits. Both protocols significantly enhanced pre-operative functional capacity, with no difference between groups: mean (95% confidence interval) oxygen consumption at anaerobic threshold 1.97 (0.75 to 3.19) ml kg min in HIIT vs. 1.71 (0.56 to 2.85) in MICT, P = 0.753. At 2 months after surgery, the HIIT group showed a higher improvement in physical fitness: 2.36 (0.378 to 4.34) ml kg min, P = 0.021. No adverse events occurred during the intervention. CONCLUSION: Both MICT and HIIT enhanced pre-operative functional capacity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03361150.

Reduction and stabilization of bilirubin with obeticholic acid treatment in patients with primary biliary cholangitis.

BACKGROUND & AIMS: Total bilirubin is a predictor of survival in primary biliary cholangitis, with the main elevated component being direct bilirubin. The purpose of this post hoc analysis was to assess the efficacy and safety of obeticholic acid across quartiles of varying baseline levels of direct bilirubin in the phase 3, randomized, placebo-controlled Primary Biliary Cholangitis Obeticholic Acid International Study of Efficacy. METHODS: This analysis assessed patients on the basis of their baseline direct bilirubin level (divided by quartile). Biochemistry and safety outcomes were evaluated within each quartile over time. RESULTS: In the quartile with the highest baseline direct bilirubin (>5.47 µmol/L), there was a significant reduction in both direct and total bilirubin at Month 12 compared with placebo. Least squares mean (standard error) change from baseline in direct bilirubin at Month 12 was 4.17 (1.42) µmol/L for placebo, -3.48 (1.63) µmol/L for obeticholic acid 5-10 mg and -3.66 (1.51) µmol/L for obeticholic acid 10 mg (P < .0001, obeticholic acid vs placebo); the corresponding values for total bilirubin at Month 12 were 4.38 (1.55) µmol/L for placebo, -4.53 (1.83) µmol/L for obeticholic acid 5-10 mg and -5.06 (1.64) µmol/L for obeticholic acid 10 mg (P < .0001, obeticholic acid vs placebo). CONCLUSIONS: Obeticholic acid treatment was associated with significant reductions in total and direct bilirubin, particularly in patients with high baseline direct bilirubin. Because raised direct bilirubin levels, even within the normal range, are predictive of survival in primary biliary cholangitis, these results suggest substantial benefits of obeticholic acid in at-risk patients.

The Canadian Partnership Against Cancer Rectal Cancer Project: Protocol for a Pan-Canadian, Multidisciplinary Quality Improvement Initiative to Optimize the Quality of Rectal Cancer Care.

BACKGROUND: Over the last 2 decades, the use of multimodal strategies, including total mesorectal excision (TME) surgery, preoperative chemotherapy, multidisciplinary case conference, pelvic magnetic resonance imaging, and pathologic assessment using Quirke method, has led to significant improvements in oncologic outcomes for patients with rectal cancer. Although the literature supports claims on the effectiveness of these multimodal strategies, the uptake of these multimodal strategies varies considerably among centers, suggesting that the best evidence is not always implemented into clinical practice. OBJECTIVE: This study aims to perform a quality improvement initiative to (1) identify existing gaps in care for these multimodal strategies and (2) implement knowledge translation (KT) interventions to close these gaps to optimize quality of care for patients with rectal cancer across high-volume centers in Canada. METHODS: Process indicators for the selected multimodal strategies to optimize rectal cancer care will be selected and prospectively collected for all patients with stages 1 to 3 rectal cancer undergoing TME surgery. KT interventions, including audit and feedback, opinion leaders, and community of practice, will be implemented to increase the uptake of these clinical strategies. RESULTS: The uptake of the process indicators over time and the effect of the uptake of the process indicators on short- and long-term oncologic outcomes will be evaluated for each multimodal strategy. CONCLUSIONS: This quality improvement initiative will identify existing gaps in care for the selected multimodal strategies and implement KT interventions to close these gaps. The results of this study will inform further efforts to optimize rectal cancer care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15535.

Long-Term Obeticholic Acid Therapy Improves Histological Endpoints in Patients With Primary Biliary Cholangitis.

BACKGROUND & AIMS: Primary biliary cholangitis (PBC) is an autoimmune disease characterized by bile duct destruction that can progress to cirrhosis. A liver biopsy substudy was conducted in the PBC obeticholic acid (OCA) International Study of Efficacy (POISE) to determine the long-term effects of OCA on liver damage and fibrosis in patients with PBC. POISE is a phase 3, double-blind, placebo-controlled, randomized trial with a 5-year open-label extension that evaluated 5 to 10 mg OCA daily in patients who were intolerant or unresponsive to ursodeoxycholic acid. METHODS: Liver biopsy specimens were collected from 17 patients at time of enrollment in the double-blind phase and after 3 years of OCA treatment. Histologic evaluations were performed by 2 pathologists in a blinded, randomized fashion to determine the effects of OCA on fibrosis and other histologic parameters. Collagen morphometry assessments were performed by automated second harmonic generation and 2-photon excitation microscopy to observe quantitative measures of fibrosis. RESULTS: From the time of enrollment until 3 years of treatment, most patients had improvements or stabilization in fibrosis (71%), bile duct loss (76%), ductopenia (82%), ductular reaction (82%), interface hepatitis (100%), and lobular hepatitis (94%). Over the 3-year period, we found significant reductions in collagen area ratio (median, -2.1; first quartile, -4.6, third quartile, -0.3; P = .013), collagen fiber density (median, -0.8; first quartile, -2.5; third quartile, 0; P = .021), collagen reticulation index (median, -0.1; first quartile, -0.3; third quartile, 0; P = .008), and fibrosis composite score (median, -1.0; first quartile, -2.5; third quartile, -0.5; P = .002). CONCLUSIONS: A subanalysis of data from the POISE study showed that long-term OCA treatment in patients with PBC is associated with improvements or stabilization of disease features, including ductular injury, fibrosis, and collagen morphometry features (ClinicalTrials.gov no: NCT01473524 and EudraCT no: 2011-004728-36).

The impact of improved functional capacity before surgery on postoperative complications: a study in colorectal cancer.

Background: Poor functional capacity (FC) is an independent predictor of postoperative morbidity. However, there is still a lack of evidence as to whether enhancing FC before surgery has a protective effect on postoperative complications. The purpose of this study was to determine whether an improvement in preoperative FC impacted positively on surgical morbidity. Methods: This was a secondary analysis of a cohort of patients who underwent colorectal resection for cancer under Enhanced Recovery After Surgery care. FC was assessed with the 6-min walk test, which measures the distance walked in 6 min (6MWD), at 4 weeks before surgery and again the day before. The study population was classified into two groups depending on whether participants achieved a significant improvement in FC preoperatively (defined as a preoperative 6MWD change ≥19 meters) or not (6MWD change <19 meters). The primary outcome measure was 30-d postoperative complications, assessed with the Comprehensive Complication Index (CCI). The association between improved preoperative FC and severe postoperative complication was evaluated using multivariable logistic regression. Results: A total of 179 eligible adults were studied: 80 (44.7%) improved in 6MWD by ≥19 m preoperatively, and 99 (55.3%) did not. Subjects whose FC increased had lower CCI (0 [0-8.7] versus 8.7 [0-22.6], p = .022). Furthermore, they were less likely to have a severe complication (adjusted OR 0.28 (95% CI 0.11-0.74), p = .010), and to have an ED visit. Conclusion: Improved preoperative FC was independently associated with a lower risk of severe postoperative complications. Further investigation is required to establish a causative relationship conclusively.

A Multicenter Matched Comparison of Transanal and Robotic Total Mesorectal Excision for Mid and Low-rectal Adenocarcinoma.

OBJECTIVE: To compare the quality of surgical resection of transanal total mesorectal excision (TA-TME) and robotic total mesorectal excision (R-TME). BACKGROUND: Both TA-TME and R-TME have been advocated to improve the quality of surgery for rectal cancer below 10 cm from the anal verge, but there are little data comparing TA-TME and R-TME. METHODS: Data of patients undergoing TA-TME or R-TME for rectal cancer below 10 cm from the anal verge and a sphincter-saving procedure from 5 high-volume rectal cancer referral centers between 2011 and 2017 were obtained. Coarsened exact matching was used to create balanced cohorts of TA-TME and R-TME. The main outcome was the incidence of poor-quality surgical resection, defined as a composite measure including incomplete quality of TME, or positive circumferential resection margin (CRM) or distal resection margin (DRM). RESULTS: Out of a total of 730 patients (277 TA-TME, 453 R-TME), matched groups of 226 TA-TME and 370 R-TME patients were created. These groups were well-balanced. The mean tumor height from the anal verge was 5.6 cm (SD 2.5), and 70% received preoperative radiotherapy. The incidence of poor-quality resection was similar in both groups (TA-TME 6.9% vs R-TME 6.8%; P = 0.954). There were no differences in TME specimen quality (complete or near-complete TA-TME 99.1% vs R-TME 99.2%; P = 0.923) and CRM (5.6% vs 6.0%; P = 0.839). DRM involvement may be higher after TA-TME (1.8% vs 0.3%; P = 0.051). CONCLUSIONS: High-quality TME for patients with rectal adenocarcinoma of the mid and low rectum can be equally achieved by transanal or robotic approaches in skilled hands, but attention should be paid to the distal margin.

Factors Associated With Histologic Response in Adult Patients With Nonalcoholic Steatohepatitis.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is a leading cause of liver transplantation, and many trials are underway to evaluate potential therapies. The farnesoid X receptor ligand obeticholic acid in the NASH treatment trial evaluated the effects of obeticholic acid vs placebo on histologic response (defined as decrease in nonalcoholic fatty liver disease activity score [NAS] by ≥2, with no worsening of fibrosis); 45% of patients had a histologic response to obeticholic acid (25 mg), and 21% had a response to placebo (P < .01). We performed a secondary analysis of data from this trial to identify clinical parameters associated with a histologic response. METHODS: We used a logistic regression model with a stepwise selection procedure to identify baseline and early on-treatment factors associated with a histologic response at 72 weeks. Baseline demographics, liver histology, medical history, concomitant medications, cardiometabolic parameters, and serum biochemistry, as well as the changes over the course of the trial (at weeks 12 and 24), were evaluated as potential predictors of a histologic response. The model was cross-validated by a jackknife method, and performance was evaluated with the area under the receiver operating characteristic curve. RESULTS: The logistic regression model found that obeticholic acid treatment, baseline NAS > 5, baseline triglyceride level ≤ 154 mg/dL, baseline international normalized ratio ≤ 1, baseline aspartate aminotransferase level ≤ 49 U/L, and a decrease in alanine aminotransferase level at week 24 by 17 U/L or more, to be significantly associated with histologic response (area under the receiver operating characteristic curve, 0.83; 95% confidence interval, 0.77-0.89; P < .0001). CONCLUSIONS: In a secondary analysis of data from a clinical trial of obeticholic acid in patients with NASH, we identified routine clinical and laboratory parameters during the first 24 weeks of treatment (such as baseline NAS, triglyceride levels, and a decrease in alanine aminotransferase level) to significantly associate with histologic markers of response.

Assessment of in vivo systemic toxicity and biodistribution of iron-doped silica nanoshells.

Silica nanoparticles are an emerging class of biomaterials which may be used as diagnostic and therapeutic tools for biomedical applications. In particular, hollow silica nanoshells are attractive due to their hollow core. Approximately 70% of a 500 nm nanoshell is hollow, therefore more particles can be administered on a mg/kg basis compared to solid nanoparticles. Additionally, their nanoporous shell permits influx/efflux of gases and small molecules. Since the size, shape, and composition of a nanoparticle can dramatically alter its toxicity and biodistribution, the toxicology of these nanomaterials was assessed. A single dose toxicity study was performed in vivo to assess the toxicity of 500 nm iron-doped silica nanoshells at clinically relevant doses of 10-20 mg/kg. This study showed that only a trace amount of silica was detected in the body 10 weeks post-administration. The hematology, biochemistry and pathological results show that the nanoshells exhibit no acute or chronic toxicity in mice.

Trauma care and referral patterns in Rwanda: implications for trauma system development.

BACKGROUND: Trauma remains a leading cause of death worldwide. The development of trauma systems in low-resource settings may be of benefit. The objective of this study was to describe operative procedures performed for trauma at a tertiary care facility in Kigali, Rwanda, and to evaluate geographical variations and referral patterns of trauma care. METHODS: We retrospectively reviewed all prospectively collected operative cases performed at the largest referral hospital in Rwanda, the Centre Hospitalier Universitaire de Kigali (CHUK), between June 1 and Dec. 1, 2011, for injury-related diagnoses. We used the Pearson χ² and Fisher exact tests to compare cases arising from within Kigali to those transferred from other provinces. Geospatial analyses were also performed to further elucidate transfer patterns. RESULTS: Over the 6-month study period, 2758 surgical interventions were performed at the CHUK. Of these, 653 (23.7%) were for trauma. Most patients resided outside of Kigali city, with 337 (58.0%) patients transferred from other provinces and 244 (42.0%) from within Kigali. Most trauma procedures were orthopedic (489 [84.2%]), although general surgery procedures represented a higher proportion of trauma surgeries in patients from other provinces than in patients from within Kigali (28 of 337 [8.3%] v. 10 of 244 [4.1%]). CONCLUSION: To our knowledge, this is the first study to highlight geographical variations in access to trauma care in a low-income country and the first description of trauma procedures at a referral centre in Rwanda. Future efforts should focus on maturing prehospital and interfacility transport systems, strengthening district hospitals and further supporting referral institutions.

CONTEXTE: Les traumatismes demeurent l'une des principales causes de décès dans le monde. La mise au point de systèmes de traumatologie dans des milieux défavorisés pourrait toutefois contribuer à améliorer la situation. Notre étude avait pour objectif de décrire les interventions chirurgicales pratiquées sur les victimes de traumatismes dans un établissement de soins tertiaires de Kigali, au Rwanda, et d'évaluer les variations géographiques et les habitudes d'orientation des patients dans le domaine de la traumatologie. MÉTHODES: Nous avons évalué rétroactivement les données recueillies de façon prospective sur l'ensemble des interventions réalisées au plus grand centre hospitalier régional du Rwanda, le Centre hospitalier universitaire de Kigali (CHUK), du 1er juin au 1er décembre 2011 pour les diagnostics liés à des blessures. Nous avons eu recours au test χ² de Pearson et au test exact de Fisher pour comparer les cas issus de la province de Kigali à ceux provenant d'autres provinces. Nous avons en outre effectué des analyses géospatiales afin de mieux comprendre les habitudes d'orientation des patients. RÉSULTATS: Au cours des 6 mois de l'étude, 2758 interventions chirurgicales ont été pratiquées au CHUK, dont 653 (23,7 %) pour des traumatismes. La majorité des patients résidaient à l'extérieur de la capitale : 337 (58,0 %) d'entre eux avaient été transférés d'autres provinces, et 244 (42,0 %), d'ailleurs dans la province. Si la plupart des interventions chirurgicales étaient orthopédiques (489, soit 84,2 %), les patients d'autres provinces ont plus souvent subi des interventions générales que leurs compatriotes de la province de Kigali (28 sur 337, soit 8,3 %, par rapport à 10 sur 244, soit 4,1 %). CONCLUSION: À notre connaissance, il s'agit de la première étude mettant en lumière les variations géographiques de l'accès aux soins en traumatologie dans un pays à faible revenu et de la première description des interventions chirurgicales pratiquées sur des victimes de traumatismes dans un centre régional du Rwanda. Les travaux à venir devraient être axés sur le développement des systèmes de transport avant l'hospitalisation et entre les établissements, le renforcement des hôpitaux de district et l'augmentation du soutien aux centres régionaux.

Acute care surgery in Rwanda: Operative epidemiology and geographic variations in access to care.

BACKGROUND: Surgical management of emergent, life-threatening diseases is an important public health priority. The objectives of this study were to (1) describe acute care general surgery procedures performed at the largest referral hospital in Rwanda and (2) understand the geographic distribution of disease presentations and referral patterns. METHODS: We performed a retrospective review of prospectively collected acute care surgery cases performed at the Centre Hospitalier Universitaire de Kigali (CHUK) in Rwanda between June 1 and December 1, 2011. Using Pearson's χ(2) test and the Fisher exact test, we compared cases originating from within Kigali and transfers from other provinces. Geospatial analyses also were used to further describe transfer patterns. RESULTS: During the study period, 2,758 surgical interventions were performed, of which 25.6% (707/2,758) were general surgery operations. Of these, 45.4% (321/707) met the definition of acute care surgery. Only about one-third-32.3% (92/285)-of patients resided within Kigali, whereas about two-thirds-67.7% (193/285)-were transferred from other provinces. Most patients transferred from other provinces were younger than 18 years of age (40.4%; 78/193), and 83.0% (39/47) of patients older than 50 years of age originated from outside of Kigali. Specific operative indications and surgical procedures varied substantially between patients from Kigali and patients transferred from other provinces. CONCLUSION: Emergency surgical conditions remain important contributors to the global burden of disease, particularly in low- and middle-income countries. Geographic variations exist in terms of operative diagnoses and procedures, which implies a need for improved access to surgical care at the district level with defined transfer mechanisms to greater-level care facilities when needed.

Alkaline and ultrasonic dissolution of biological materials for trace silicon determination.

A simple method for trace elemental determination in biological tissue has been developed. Novel nanomaterials with biomedical applications necessitate the determination of the in vivo fate of the materials to understand their toxicological profile. Hollow iron-doped calcined silica nanoshells have been used as a model to demonstrate that potassium hydroxide and bath sonication at 50 °C can extract elements from alkaline-soluble nanomaterials. After alkali digestion, nitric acid is used to adjust the pH into a suitable range for analysis using techniques such as inductively coupled plasma optical emission spectrometry which require neutral or acidic analytes. In chicken liver phantoms injected with the nanoshells, 96% of the expected silicon concentration was detected. This value was in good agreement with the 94% detection efficiency of nanoshells dissolved in aqueous solution as a control for potential sample matrix interference. Nanoshell detection was further confirmed in a mouse 24 h after intravenous administration; the measured silica above baseline was 35 times greater or more than the standard deviations of the measurements. This method provides a simple and accurate means to quantify alkaline-soluble nanomaterials in biological tissue.

Synthesis and surface functionalization of silica nanoparticles for nanomedicine.

There are a wide variety of silica nanoformulations being investigated for biomedical applications. Silica nanoparticles can be produced using a wide variety of synthetic techniques with precise control over their physical and chemical characteristics. Inorganic nanoformulations are often criticized or neglected for their poor tolerance; however, extensive studies into silica nanoparticle biodistributions and toxicology have shown that silica nanoparticles may be well tolerated, and in some case are excreted or are biodegradable. Robust synthetic techniques have allowed silica nanoparticles to be developed for applications such as biomedical imaging contrast agents, ablative therapy sensitizers, and drug delivery vehicles. This review explores the synthetic techniques used to create and modify an assortment of silica nanoformulations, as well as several of the diagnostic and therapeutic applications.

Hollow iron-silica nanoshells for enhanced high intensity focused ultrasound.

BACKGROUND: High intensity-focused ultrasound (HIFU) is an alterative ablative technique currently being investigated for local treatment of breast cancer and fibroadenomas. Current HIFU therapies require concurrent magnetic resonance imaging monitoring. Biodegradable 500 nm perfluoropentane-filled iron-silica nanoshells have been synthesized as a sensitizing agent for HIFU therapies, which aid both mechanical and thermal ablation of tissues. In low duty cycle high-intensity applications, rapid tissue damage occurs from mechanical rather than thermal effects, which can be monitored closely by ultrasound obviating the need for concurrent magnetic resonance imaging. MATERIALS AND METHODS: Iron-silica nanoshells were synthesized by a sol-gel method on polystyrene templates and calcined to yield hollow nanoshells. The nanoshells were filled with perfluoropentane and injected directly into excised human breast tumor, and intravenously (IV) into healthy rabbits and Py8119 tumor-bearing athymic nude mice. HIFU was applied at 1.1 MHz and 3.5 MPa at a 2% duty cycle to achieve mechanical ablation. RESULTS: Ex vivo in excised rabbit livers, the time to visually observable damage with HIFU was 20 s without nanoshells and only 2 s with nanoshells administered IV before sacrifice. Nanoshells administered IV into nude mice with xenograft tumors were activated in vivo by HIFU 24 h after administration. In this xenograft model, applied HIFU resulted in a 13.6 ± 6.1 mm(3) bubble cloud with the IV injected particles and no bubble cloud without particles. CONCLUSIONS: Iron-silica nanoshells can reduce the power and time to perform HIFU ablative therapy and can be monitored by ultrasound during low duty cycle operation.

Color Doppler ultrasound and gamma imaging of intratumorally injected 500 nm iron-silica nanoshells.

Perfluoropentane gas filled iron-silica nanoshells have been developed as stationary ultrasound contrast agents for marking tumors to guide surgical resection. It is critical to establish their long-term imaging efficacy, as well as biodistribution. This work shows that 500 nm Fe-SiO2 nanoshells can be imaged by color Doppler ultrasound over the course of 10 days in Py8119 tumor bearing mice. The 500 nm nonbiodegradable SiO2 and biodegradable Fe-SiO2 nanoshells were functionalized with diethylenetriamine pentaacetic acid (DTPA) ligand and radiolabeled with (111)In(3+) for biodistribution studies in nu/nu mice. The majority of radioactivity was detected in the liver and kidneys following intravenous (IV) administration of nanoshells to healthy animals. By contrast, after nanoshells were injected intratumorally, most of the radioactivity remained at the injection site; however, some nanoshells escaped into circulation and were distributed similarly as those given intravenously. For intratumoral delivery of nanoshells and IV delivery to healthy animals, little difference was seen between the biodistribution of SiO2 and biodegradable Fe-SiO2 nanoshells. However, when nanoshells were administered IV to tumor bearing mice, a significant increase was observed in liver accumulation of SiO2 nanoshells relative to biodegradable Fe-SiO2 nanoshells. Both SiO2 and Fe-SiO2 nanoshells accumulate passively in proportion to tumor mass, during intravenous delivery of nanoshells. This is the first report of the biodistribution following intratumoral injection of any biodegradable silica particle, as well as the first report demonstrating the utility of DTPA-(111)In labeling for studying silica nanoparticle biodistributions.