Early Prophylactic Gastrectomy for the Management of Gastric Adenomatous Proximal Polyposis Syndrome (GAPPS).

Background: Gastric adenomatous proximal polyposis syndrome (GAPPS) is a recently described, rare, autosomal dominant condition characterized by the extensive involvement of the proximal stomach with hundreds of heterogeneous fundic gland polyps with antral and duodenal sparing. GAPPS is caused by a point mutation of the APC gene promoter 1B and is associated with a risk of malignant transformation, distant metastasis, and death. There are no surveillance, screening, or treatment guidelines for managing GAPPS. The few reported cases have been variably managed with endoscopic surveillance or prophylactic gastrectomy. However, there is no consensus on the optimal management approach. Summary: In this case series, we review the relevant literature on GAPPS and present two siblings who underwent early prophylactic total gastrectomies with good outcomes. Conclusion: Due to the poor correlation between the endoscopic findings on sampled polyps and the risk of harboring invasive gastric cancer, patients with GAPPS should be strongly considered for early prophylactic total gastrectomies in the absence of prohibitive comorbidities.

Comparative safety profile of chloral hydrate versus other sedatives for procedural sedation in hospitalized infants.

BACKGROUND: Given the limited available evidence on chloral hydrate safety in neonatal populations and the discrepancy in chloral hydrate acceptance between the US and other countries, we sought to clarify the safety profile of chloral hydrate compared to other sedatives in hospitalized infants. METHODS: We included all infants <120 days of life who underwent a minor procedure and were administered chloral hydrate, clonidine, clonazepam, dexmedetomidine, diazepam, ketamine, lorazepam, midazolam, propofol, or pentobarbital on the day of the procedure. We characterized the distribution of infant characteristics and evaluated the relationship between drug administration and any adverse event. We performed propensity score matching, regression adjustment (RA), and inverse probability weighting (IPW) to ensure comparison of similar infants and to account for confounding by indication and residual bias. Results were assessed for robustness to analytical technique by reanalyzing the main outcomes with multivariate logistic regression, a doubly robust IPW with RA model, and a doubly robust augmented IPW model with bias-correction. RESULTS: Of 650 infants, 497 (76%) received chloral hydrate, 79 (12%) received midazolam, 54 (8%) received lorazepam, and 15 (2%) received pentobarbital. Adverse events occurred in 41 (6%) infants. Using propensity score matching, chloral hydrate was associated with a decreased risk of an adverse event compared to other sedatives, risk difference (95% confidence interval) of -12.79 (-18.61, -6.98), p <  0.001. All other statistical methods resulted in similar findings. CONCLUSION: Administration of chloral hydrate to hospitalized infants undergoing minor procedures is associated with a lower risk for adverse events compared to other sedatives.

Intranasal midazolam and fentanyl for procedural sedation and analgesia in infants in the neonatal intensive care unit.

BACKGROUND: The intranasal route is a minimally invasive method for rapidly delivering midazolam and fentanyl to provide short-term analgesia and sedation in infants. However, intranasal use of midazolam and fentanyl is not labeled for infants and safety data are sparse. The objective of this study is to evaluate the safety of intranasal midazolam and intranasal fentanyl in infants admitted to the Neonatal Intensive Care Unit (NICU). METHODS: We retrospectively identified all infants receiving intranasal midazolam or fentanyl in the NICU from 2009 to 2015. We recorded indication for use and vital signs and determined the proportion of infants experiencing the following adverse events: death within 24 hours, hypotension, bradycardia, worsening respiratory status, and chest wall rigidity. Vital signs 4 hours before and after each dose were compared using the Wilcoxon signed-rank test. RESULTS: We identified 17 infants (gestational ages 23- 41 weeks) receiving 25 intranasal doses. None of the infants died or developed hypotension, bradycardia, or chest wall rigidity. Intranasal delivery was most commonly used for sedation during magnetic resonance imaging studies. Other indications include analgesia or sedation for retinopathy of prematurity surgery, intubation, and peripherally inserted central catheter placement. One infant receiving intranasal midazolam experienced worsening respiratory status. Vital signs before and after dosing were not significantly different. CONCLUSIONS: Intranasal midazolam and fentanyl use in term and preterm infants appeared safe and well-tolerated in this small cohort of infants. Larger, prospective studies evaluating the safety and efficacy of intranasal midazolam and fentanyl use in infants are warranted.

Canadian Guidelines for Controlled Pediatric Donation After Circulatory Determination of Death-Summary Report

OBJECTIVES: Create trustworthy, rigorous, national clinical practice guidelines for the practice of pediatric donation after circulatory determination of death in Canada. METHODS: We followed a process of clinical practice guideline development based on World Health Organization and Canadian Medical Association methods. This included application of Grading of Recommendations Assessment, Development, and Evaluation methodology. Questions requiring recommendations were generated based on 1) 2006 Canadian donation after circulatory determination of death guidelines (not pediatric specific), 2) a multidisciplinary symposium of national and international pediatric donation after circulatory determination of death leaders, and 3) a scoping review of the pediatric donation after circulatory determination of death literature. Input from these sources drove drafting of actionable questions and Good Practice Statements, as defined by the Grading of Recommendations Assessment, Development, and Evaluation group. We performed additional literature reviews for all actionable questions. Evidence was assessed for quality using Grading of Recommendations Assessment, Development, and Evaluation and then formulated into evidence profiles that informed recommendations through the evidence-to-decision framework. Recommendations were revised through consensus among members of seven topic-specific working groups and finalized during meetings of working group leads and the planning committee. External review was provided by pediatric, critical care, and critical care nursing professional societies and patient partners. RESULTS: We generated 63 Good Practice Statements and seven Grading of Recommendations Assessment, Development, and Evaluation recommendations covering 1) ethics, consent, and withdrawal of life-sustaining therapy, 2) eligibility, 3) withdrawal of life-sustaining therapy practices, 4) ante and postmortem interventions, 5) death determination, 6) neonatal pediatric donation after circulatory determination of death, 7) cardiac and innovative pediatric donation after circulatory determination of death, and 8) implementation. For brevity, 48 Good Practice Statement and truncated justification are included in this summary report. The remaining recommendations, detailed methodology, full Grading of Recommendations Assessment, Development, and Evaluation tables, and expanded justifications are available in the full text report. CONCLUSIONS: This process showed that rigorous, transparent clinical practice guideline development is possible in the domain of pediatric deceased donation. Application of these recommendations will increase access to pediatric donation after circulatory determination of death across Canada and may serve as a model for future clinical practice guideline development in deceased donation

Risk factors for group B streptococcal disease in neonates of mothers with negative antenatal testing.

OBJECTIVE: The aim of this study was to identify risk factors for early-onset group B Streptococcus (EOGBS) disease in neonates of mothers with negative antenatal screening. STUDY DESIGN: We performed a retrospective cohort study of neonates born to mothers with negative antenatal GBS screening between 2002 and 2012. Our primary outcome was EOGBS infection. We used multivariable logistic regression to assess factors associated with EOGBS. RESULTS: EOGBS was confirmed in 492 of the 179 818 neonates that met the study inclusion criteria. Risk factors for EOGBS included black race (reference: white, odds ratio (OR) =1.81 (95% confidence interval: 1.43, 2.31)), maternal age <18 years (reference: >35 years, OR=2.63 (1.54, 4.51)) and maternal age 18 to 35 years (reference: >35 years, OR=1.94 (1.30, 2.88)). CONCLUSION: Maternal age <18 years and black race were the strongest predictors of EOGBS. Further research investigating contributors to the discordance between screening results and neonatal outcomes in these populations is needed.

Is it necessary to perform week three dosimetric analysis in low-dose-rate brachytherapy for prostate cancer when day 0 dosimetry is done? A quality assurance assessment.

PURPOSE: To determine whether computed tomography/magnetic resonance imaging-based day 0 (d0) dosimetry is a meaningful predictor of day 21 (d21) dosimetry in low-dose-rate brachytherapy for localized prostate cancer. METHODS AND MATERIALS: The study population consisted of 277 men with localized (T1-2 N0 M0), low-/intermediate-risk prostate cancer treated with low-dose-rate brachytherapy. Computed tomography/magnetic resonance imaging fusion was used for postimplant dosimetry at d0 and d21. Logistic regression was used to construct receiver operating characteristic curves for achieving each constraint at d21, based on d0 D90 and V100, and Youden's index was used to evaluate cutpoints. Freedom from biochemical failure (FBCF) was estimated with the Kaplan-Meier method. RESULTS: The median d0 D90 increased from 133 to 150 Gy at d21, and median d0 V100 increased from 87% to 91%. For achieving the D90 constraint at d21, the optimal cut-point for d0 D90 was 135 Gy, with 84% of these patients maintaining a d21 D90 > 145 Gy. For achieving the D90 constraint at d21, the optimal cut-point for d0 V100 was 87%, with 83% of these patients maintained a d21 V100 > 90%. There was no improvement in FBCF in patients with a d0 D90 > 135 Gy or D90 > 145 Gy. Similarly, there was no improvement in FBCF in patients with a d0 V100 > 87% or V100 > 90%. CONCLUSIONS: Meeting dosimetric constraints on d0 does not obviate d21 dosimetric analysis. Constraints used for dose prescriptions on d0 are not the ideal predictors of d21 dosimetry.

Diabetes and youth resources for school nurses: an update from the National Diabetes Education Program.

In response to the challenge of diabetes in youth, the National Diabetes Education Program (NDEP) has developed free, evidence-based education materials and online resources for school nurses, parents, and children living with or at risk for diabetes. This article highlights some of NDEP's resources and identifies ways for school nurses to use them with students and their families.

Bioethics consultation practices and procedures: a survey of a large Canadian community of practice.

The literature fails to reflect general agreement over the nature of the services and procedures provided by bioethicists, and the training and core competencies this work requires. If bioethicists are to define their activities in a consistent way, it makes sense to look for common ground in shared communities of practice. We report results of a survey of the services and procedures among bioethicists affiliated with the University of Toronto Joint Centre for Bioethics (JCB). This is the largest group of bioethicists working in healthcare organizations in Canada. The results suggest there are many common services and procedures of JCB bioethicists. This survey can serve as a baseline for further exploration of the work of JCB bioethicists. Common practices exist with respect to the domains of practice, individual reporting relationships, service availability within business hours and the education and training of the bioethicist.

C-reactive protein as a marker of complicated diverticulitis in patients on anti-inflammatory medications.

BACKGROUND: Diverticulitis is a common indication for surgical emergency room admission, often leading to abdominal computed tomography (CT) scanning for both diagnosis and staging. C-reactive protein (CRP) has been identified as a useful biomarker of inflammation. Aspirin and corticosteroids are known to down-regulate CRP production. In this study, we evaluated the usefulness of CRP as a biomarker for complicated diverticulitis and specifically in patients on anti-inflammatory medications: aspirin and corticosteroids. METHODS: We analyzed the medical records of patients diagnosed at one medical center during a two-year period, with left-sided diverticulitis, according to clinical data and CT scan. Disease severity was assessed by the Hinchey score using the radiological findings detected by CT. RESULTS: A total of 295 patients were included in the study. Two hundred and forty-three (82 %) were classified with uncomplicated (Hinchey 1a) and 52 (18 %) with complicated disease (Hinchey > 1a). Mean CRP levels were 133.5 and 63.5 mg/ml for those with complicated and uncomplicated disease, respectively (p < 0.001), and 139 and 60 mg/ml, respectively (p < 0.001) in the subgroup of patients taking aspirin (n = 61). For 14 patients on corticosteroid treatment, the difference in mean CRP levels for complicated and uncomplicated disease was not statistically significant. CRP > 90 mg/ml had 88 % sensitivity and 75 % specificity for complicated disease. CONCLUSIONS: The CRP level distinguished between complicated and uncomplicated disease among left-sided diverticulitis patients including those taking aspirin, but not among those on corticosteroid treatment.

Factors Affecting Perceptual Threshold in Argus II Retinal Prosthesis Subjects.

PURPOSE: The Argus II epiretinal prosthesis has been developed to provide partial restoration of vision to subjects blinded from outer retinal degenerative disease. Participants were surgically implanted with the system in the United States and Europe in a single arm, prospective, multicenter clinical trial. The purpose of this investigation was to determine which factors affect electrical thresholds in order to inform surgical placement of the device. METHODS: Electrode-retina and electrode-fovea distances were determined using SD-OCT and fundus photography, respectively. Perceptual threshold to electrical stimulation of electrodes was measured using custom developed software, in which current amplitude was varied until the threshold was found. Full field stimulus light threshold was measured using the Espion D-FST test. Relationships between electrical threshold and these three explanatory variables (electrode-retina distance, electrode-fovea distance, and monocular light threshold) were quantified using regression. RESULTS: Regression analysis showed a significant correlation between electrical threshold and electrode-retina distance (R2 = 0.50, P = 0.0002; n = 703 electrodes). 90.3% of electrodes in contact with the macula (n = 207) elicited percepts at charge densities less than 1 mC/cm2/phase. These threshold data also correlated well with ganglion cell density profile (P = 0.03). A weaker, but still significant, inverse correlation was found between light threshold and electrical threshold (R2 < 0.52, P = 0.01). Multivariate modeling indicated that electrode-retina distance and light threshold are highly predictive of electrode threshold (R2 = 0.87; P < 0.0005). CONCLUSIONS: Taken together, these results suggest that while light threshold should be used to inform patient selection, macular contact of the array is paramount. TRANSLATIONAL RELEVANCE: Reported Argus II clinical study results are in good agreement with prior in vitro and in vivo studies, and support the development of higher-density systems that employ smaller diameter electrodes. (clinicaltrials.gov identifier: NCT00407602).

How young is too young to be a living donor?

Assessing people in adolescence and early adulthood who wish to become living organ donors (LDs) provides unique challenges. In several Canadian provinces, 16-year-old can legally consent to living organ donation. While the World Health Organization states that adolescence corresponds roughly to the ages of 10-19 years, parts of the brain associated with judgment continue to develop into the mid-20s. Therefore, it is legally possible for some young people to donate organs before their capacity to judge the benefits and risks of surgery has fully matured. Potential young living donors (YLDs) may be financially and/or psychologically dependent on their recipients (e.g. parents), which can make it difficult to determine if the YLD's donation is voluntary. This paper suggests ways to manage three ethical challenges in the use of young people as LDs: (1) determining the YLD's ability to appreciate the consequences of living organ donation, (2) determining whether the YLD's donation is voluntary and (3) evaluating the unique risks and benefits to the YLD. We conclude that there are compelling ethical reasons to offer the opportunity of living donation to selected young people. A thorough and fair evaluation process can address social, emotional and developmental issues associated with YLDs.

Mulga snake (Pseudechis australis) envenoming: a spectrum of myotoxicity, anticoagulant coagulopathy, haemolysis and the role of early antivenom therapy - Australian Snakebite Project (ASP-19).

CONTEXT: Mulga snakes (Pseudechis australis) are venomous snakes with a wide distribution in Australia. Objective. The objective of this study was to describe mulga snake envenoming and the response of envenoming to antivenom therapy. MATERIALS AND METHODS: Definite mulga bites, based on expert identification or venom-specific enzyme immunoassay, were recruited from the Australian Snakebite Project. Demographics, information about the bite, clinical effects, laboratory investigations and antivenom treatment are recorded for all patients. Blood samples are collected to measure the serum venom concentrations pre- and post-antivenom therapy using enzyme immunoassay. RESULTS: There were 17 patients with definite mulga snake bites. The median age was 37 years (6-70 years); 16 were male and six were snake handlers. Thirteen patients had systemic envenoming with non-specific systemic symptoms (11), anticoagulant coagulopathy (10), myotoxicity (7) and haemolysis (6). Antivenom was given to ten patients; the median dose was one vial (range, one-three vials). Three patients had systemic hypersensitivity reactions post-antivenom. Antivenom reversed the coagulopathy in all cases. Antivenom appeared to prevent myotoxicity in three patients with high venom concentrations, given antivenom within 2 h of the bite. Median peak venom concentration in 12 envenomed patients with samples was 29 ng/mL (range, 0.6-624 ng/mL). There was a good correlation between venom concentrations and the area under the curve of the creatine kinase for patients receiving antivenom after 2 h. Higher venom concentrations were also associated with coagulopathy and haemolysis. Venom was not detected after antivenom administration except in one patient who had a venom concentration of 8.3 ng/ml after one vial of antivenom, but immediate reversal of the coagulopathy. DISCUSSION: Mulga snake envenoming is characterised by myotoxicity, anticoagulant coagulopathy and haemolysis, and has a spectrum of toxicity that is venom dose dependant. This study supports a dose of one vial of antivenom, given as soon as a systemic envenoming is identified, rather than waiting for the development of myotoxicity.

Perioperative blood transfusion in cancer patients undergoing laparoscopic colorectal resection: risk factors and impact on survival.

BACKGROUND: Perioperative blood transfusion has been associated with a poor prognosis in patients undergoing surgery for colorectal cancer. The aim of this study was to evaluate risk factors for blood transfusion and its impact on long-term outcome exclusively in patients undergoing laparoscopic surgery for curable colorectal cancer. METHODS: Data were retrieved from a prospectively collected database of patients who underwent laparoscopic surgery for curable colorectal cancer over a 6-year period. Long-term data were collected from our outpatient clinic and personal contact when necessary. RESULTS: Two hundred and one patients underwent laparoscopic surgery for curable colorectal cancer (stage I-III). Sixty-eight (33.8 %) received blood transfusions during or after surgery. These patients were typically older, had lower preoperative hemoglobin levels, had a more advanced cancer, had a higher Charlson score, had a higher rate of complications and had a higher conversion rate. Kaplan-Meier overall survival analysis was significantly worse in patients who received blood transfusions (P = 0.004). Decreased disease-free survival was also observed in transfused patients; however, this did not reach statistical significance (P = 0.21). A multivariate analysis revealed that transfusion was not an independent risk factor for decreased overall and disease-free survival. The Charlson score was the only independent risk factor for overall survival (OR = 2.1, P = 0.002). Independent factors affecting disease-free survival were stage of disease, Charlson score and, to a lesser degree, age and body mass index. CONCLUSIONS: Perioperative blood transfusion is associated with decreased long-term survival in patients undergoing laparoscopic resection for colorectal cancer. However, this association apparently reflects the poorer medical condition of patients requiring surgery and not a causative relationship.

Is Doppler ultrasonography essential for hemorrhoidal artery ligation?

BACKGROUND: Doppler ultrasonography enables accurate identification of the terminal branches of the superior rectal artery prior to hemorrhoidal artery ligation (HAL). However, since the positions of these branches have been found to be relatively constant, the question arises as to the necessity of ultrasonography for their identification. The aim of the current study was to examine the positions of all arteries identified and ligated during the HAL procedure. METHODS: We recorded the position of all arteries located and ligated in 135 consecutive patients who underwent the HAL procedure during the years 2003 to 2006. RESULTS: In all patients, 6-8 terminal arterial branches were located above the dentate line. In 102 (76 %) patients, terminal branches were located in all 6 of the odd-numbered clock positions around the anus (1, 3, 5, 7, 9, and 11 o'clock in the lithotomy position). If we had ligated arteries only at these odd-numbered clock positions, without using Doppler ultrasonography, we would have located all the arteries in 96 (71 %) of our patients. CONCLUSIONS: The number and location of arterial branches of the superior rectal artery are relatively constant. Nevertheless, if, Doppler ultrasonography had not been performed and, ligation in the HAL procedure had been at the odd-numbered clock positions only, then at least one artery would have been missed in 29 % of our patients.

Endovascular strategies for the management of aortic connective tissue disorders.

During the last several decades, the endovascular management of patients with aortic connective tissue disorders (CTD) has greatly evolved. While open surgery remains the gold standard, endovascular strategies can play an important role in the overall management of arterial lesions. CTD result from mutations in specific genes responsible for maintaining and regulating tissue integrity. While each CTD has a unique phenotype, all patients are at an increased risk for the early onset of aortic aneurysms and dissections, leading to premature death if left untreated. In such patients, the interface between the device and arterial wall remains the primary concern, guiding the selection of appropriate landing zones and the means to ensure a circumferential seal excluding the aneurysm. In patients with aortic dissections, the goal of the endovascular treatment should achieve true lumen perfusion, favorable remodeling of the false lumen, and prevent aortic growth and rupture. While patients with proximal dissections should be treated with open surgery, distal dissections can be managed with a pure endovascular approach by placing the stent- graft proximal and distal to the entry sites of false lumen. Albeit less common than aortic lesions, aneurysms of the subclavian, vertebral, visceral, iliac, and internal iliac arteries may be present, underscoring the need to screen the entire vascular bed. Endovascular strategies may be implemented in each of these anatomical locations but may require a hybrid approach, involving both open and surgical techniques. Last, it must be stressed that both endovascular and open surgical repair represent treatments, not cures for these diseases. Therefore, every intervention must be strategized with the need for future reoperations.

Five-year follow-up of Doppler-guided hemorrhoidal artery ligation.

BACKGROUND: Doppler-guided hemorrhoidal artery ligation (DGHAL) was described as lower risk and a less painful alternative to hemorrhoidectomy. We report our experience and 5-year follow-up with this procedure. METHODS: Between May 2003 and December 2004, 100 patients with symptomatic Grade II or III hemorrhoids underwent ultrasound identification and ligation of 6-8 terminal branches of the superior rectal artery above the dentate line by a single surgeon using local, regional, or general anesthesia. There were 42 men and 58 women (mean age 42 years, median duration of symptoms 6/3 years). A 10-point visual analog scale was used for postoperative pain scoring. Surgical and functional outcome was assessed at 6 weeks and 3 and 12 months after surgery, with long-term follow-up by a telephone questionnaire at 5 years after the procedure. RESULTS: The mean operative time was 19 min. Local anal block combined with intravenous sedation (n = 93) or general or spinal (n = 7) anesthesia was used. Only 5 patients were hospitalized overnight. There was no urinary retention, bleeding, or mortality in the immediate postoperative period. The mean pain score decreased from 2.1 at 2 h postoperatively to 1.3 on the first postoperative day. All patients had complete functional recovery by the third postoperative day. Ninety-six patients completed 12 months of follow-up. Eighty-five of these patients (89%) remained asymptomatic at 12 months, though this number dropped to 67/92 (73%) at 5 years. CONCLUSIONS: Long-term follow-up confirms the effectiveness of the DGHAL procedure for treatment for Grade II hemorrhoids. The DGHAL procedure alone seems less effective for Grade III hemorrhoids.

Metastatic lymph node ratio (LNR) as a prognostic variable in colorectal cancer patients undergoing laparoscopic resection.

BACKGROUND: Lymph node ratio (LNR: the ratio of metastatic to total retrieved nodes) has shown prognostic significance in several tumors. Its role in patients with colorectal cancer submitted to laparoscopic resection is still not clearly defined. The aim of this study was to evaluate the impact of LNR on long-term outcome in patients undergoing curative laparoscopic resection. METHODS: Patients' data were retrieved from our prospective in-hospital collected data of patients that underwent laparoscopic surgery for curable colorectal cancer over a 6-year period. Long-term data were collected from our outpatient's clinic data and personal contact when necessary. RESULTS: Two hundred and five patients underwent laparoscopic resection for curable colorectal cancer in the study period. Sixty-five patients were node positive. Receiver operating characteristic (ROC) analysis selected 0.13 as the best LNR cutoff value in this group. Kaplan-Meier 5-year survival analysis revealed a significant decrease in overall and disease-free survival in patients with an LNR above 0.13. Long-term outcome of patients with an LNR below 0.13 was similar to node-negative stage II patients. CONCLUSIONS: The lymph node ratio is a valuable prognostic factor in node-positive colon cancer patients undergoing laparoscopic resection. Patients with an LNR below 0.13 have the same long-term outcome as stage II node-negative patients. The laparoscopic approach presents the same trends in terms of overall survival and disease-free survival as conventional open access when LNR is considered.