Long-term Survival Among Patients With De Novo Human Epidermal Growth Receptor 2-Positive Metastatic Breast Cancer in Manitoba.

OBJECTIVES: Although metastatic breast cancer (MBC) is considered incurable, human epidermal growth receptor 2 (HER2)-directed therapy has improved outcomes significantly, with some patients experiencing durable responses to treatment. The aim of this study was to identify potential predictors of long-term survival (LTS) among patients with de novo HER2-positive MBC who received HER2-directed treatment. METHODS: Eligible patients from 2008 to 2018 were identified using the Manitoba Cancer Registry. LTS was defined as survival ≥5 years from the time of diagnosis. Univariate logistic regression models were performed to assess variables of clinical interest and the odds of LTS. Overall survival (OS) was defined as the time from diagnosis of MBC to death of any cause. OS was estimated using the Kaplan-Meier method with log-rank comparative analyses as a univariate analysis. A Cox proportional hazards model was used for OS estimates in a univariate analysis. RESULTS: A total of 62 patients were diagnosed with de novo HER2-positive MBC and received HER2-directed therapy. Eighteen (29%) achieved LTS. The median OS of the whole cohort was 50.2 months (95% CI: 28.6-not reached). Radiographic response to first-line treatment was associated with LTS; complete and partial responses were both associated with higher odds of LTS (odds ratio: 28.33 [95% CI: 2.47-4006.71, P = 0.0043] and odds ratio: 7.80 [95% CI: 0.7317-1072.00, P = 0.0972], respectively). The best radiographic response was associated with improved OS. CONCLUSIONS: Radiographic response to first-line HER2-directed therapy is a predictor for LTS in patients with de novo HER2-positive MBC. Larger studies are needed to identify patients who can safely discontinue HER2-targeted therapy.

Postoperative neurological symptoms following arthroscopic shoulder surgery with interscalene block: an exploratory secondary analysis of pooled randomized controlled trial data.

OBJECTIVE: Postoperative neurological symptoms (PONS) are recognized complications of regional anesthesia and orthopedic surgery. We aimed to better characterize prevalence and potential risk factors in a homogeneous population of randomized, controlled trial participants. METHODS: Data were pooled from two randomized controlled trials of analgesia after interscalene block with perineural or intravenous adjuvants (NCT02426736, NCT03270033). Participants were at least 18 years of age and undergoing arthroscopic shoulder surgery at a single ambulatory surgical center. PONS were assessed by telephone follow-up at 14 days and 6 months postoperatively, and defined as patient report of numbness, weakness, or tingling in the surgical limb, alone or in combination, and regardless of severity or etiology. RESULTS: At 14 days, PONS occurred in 83 of 477 patients (17.4%). Among these 83 patients, 10 (12.0%) continued to have symptoms a half-year after surgery. In exploratory univariate analyses, no patient, surgical or anesthetic characteristics were significantly associated with 14-day PONS except for lower postoperative day 1 Quality of Recovery-15 questionnaire total score (OR 0.97 (95% CI, 0.96 to 0.99), p<0.01). This result was driven largely by the emotional domain question scores (OR 0.90 95% CI 0.85 to 0.96, p<0.001). Report of all three of numbness, weakness and tingling at 14 days vs other 14-day symptom combinations was associated with persistent PONS at 6 months (OR 11.5 95% CI 2.2 to 61.8, p<0.01). CONCLUSION: PONS are common after arthroscopic shoulder surgery performed with single injection ultrasound-guided interscalene blocks. No definitive mitigating risk factors were identified.

Emergency airway management in a tertiary trauma centre (AIRMAN): a one-year prospective longitudinal study.

PURPOSE: Emergency airway management can be associated with a range of complications including long-term neurologic injury and death. We studied the first-pass success rate with emergency airway management in a tertiary care trauma centre. Secondary outcomes were to identify factors associated with first-pass success and factors associated with adverse events peri-intubation. METHODS: We performed a single-centre, prospective, observational study of patients ≥ 17 yr old who were intubated in the emergency department (ED), surgical intensive care unit (SICU), medical intensive care unit (MICU), and inpatient wards at our institution. Ethics approval was obtained from the local research ethics board. RESULTS: In a seven-month period, there were 416 emergency intubations and a first-pass success rate of 73.1%. The first-pass success rates were 57.5% on the ward, 66.1% in the intensive care units (ICUs) and 84.3% in the ED. Equipment also varied by location; videolaryngoscopy use was 65.1% in the ED and only 10.6% on wards. A multivariate regression model using the least absolute shrinkage and selection algorithm (LASSO) showed that the odds ratios for factors associated with two or more intubation attempts were location (wards, 1.23; MICU, 1.24; SICU, 1.19; reference group, ED), physiologic instability (1.19), an anatomically difficult airway (1.05), hypoxemia (1.98), lack of neuromuscular blocker use (2.28), and intubator inexperience (1.41). CONCLUSIONS: First-pass success rates varied widely between locations within the hospital and were less than those published from similar institutions, except for the ED. We are revamping ICU protocols to improve the first-pass success rate.

RéSUMé: OBJECTIF: La prise en charge d'urgence des voies aériennes peut être associée à une multitude de complications, y compris des lésions neurologiques à long terme et la mort. Nous avons étudié le taux de réussite à la première tentative lors de la prise en charge d'urgence des voies aériennes dans un centre de traumatologie tertiaire. Les critères d'évaluation secondaires étaient l'identification des facteurs associés à la réussite de la première tentative et des facteurs associés aux événements indésirables péri-intubation. MéTHODE: Nous avons réalisé une étude observationnelle prospective monocentrique sur des patients âgés de 17 ans ou plus qui avaient été intubés à l'urgence, à l'unité de soins intensifs chirurgicaux (USIC), à l'unité de soins intensifs médicaux (USIM) et aux étages dans notre établissement. L'approbation a été obtenue du comité d'éthique de la recherche local. RéSULTATS: Au cours d'une période de sept mois, il y a eu 416 intubations d'urgence et un taux de réussite à la première tentative de 73,1 %. Les taux de réussite à la première tentative étaient de 57,5 % aux étages, de 66,1 % dans les unités de soins intensifs (USI) et de 84,3 % à l'urgence. Le matériel variait également selon l'emplacement; l'utilisation de la vidéolaryngoscopie était de 65,1 % à l'urgence et de seulement 10,6 % aux étages. Un modèle de régression multivariée utilisant l'algorithme LASSO (Least Absolute Shrinkage and Selection Algorithm) a montré que les rapports de cotes pour les facteurs associés à deux tentatives d'intubation ou plus étaient l'emplacement (étages, 1,23; USIM, 1,24; USIC, 1,19; groupe de référence, urgence), l'instabilité physiologique (1,19), des voies aériennes présentant des complications anatomiques (1,05), l'hypoxémie (1,98), la non-utilisation de bloqueurs neuromusculaires (2,28) et l'inexpérience de la personne pratiquant l'intubation (1,41). CONCLUSION: Les taux de réussite à la première tentative variaient considérablement d'un emplacement à l'autre au sein de l'hôpital et étaient inférieurs à ceux publiés par des établissements comparables, à l'exception du service des urgences. Nous retravaillons les protocoles des soins intensifs afin d'améliorer le taux de réussite à la première tentative.

A prospective observational study comparing outcomes before and after the introduction of an intubation protocol during the COVID-19 pandemic.

OBJECTIVE: Orotracheal intubation is a life-saving procedure commonly performed in the Intensive Care unit and Emergency Department as a part of emergency airway management. Prior to the COVID-19 pandemic, our center undertook a prospective observational study to characterize emergency intubation performed in the emergency department and critical care settings at Manitoba's largest tertiary hospital. During this study, a natural experiment emerged when a standardized "COVID-Protected Rapid Sequence Intubation Protocol" was implemented in response to the pandemic. The resultant study aimed to answer the question; in adult ED patients undergoing emergent intubation by EM and CCM teams, does the use of a "COVID-Protected Rapid Sequence Intubation Protocol" impact first-pass success or other intubation-related outcomes? METHODS: A single-center prospective quasi-experimental before and after study was conducted. Data were prospectively collected on consecutive emergent intubations. The primary outcome was the difference in first-pass success rates. Secondary outcomes included best Modified Cormack-Lehane view, hypoxemia, hypotension, esophageal intubation, cannot intubate cannot oxygenate scenarios, CPR post intubation, vasopressors required post intubation, Intensive Care Unit (ICU) mortality, ICU length of stay (LOS), and mechanical ventilation days. RESULTS: Data were collected on 630 patients, 416 in the pre-protocol period and 214 in the post-protocol period. First-pass success rates in the pre-protocol period were found to be 73.1% (n = 304). Following the introduction of the protocol, first-pass success rates increased to 82.2% (n = 176, p = 0.0105). There was a statistically significant difference in Modified Cormack-Lehane view favoring the protocol (p = 0.0191). Esophageal intubation rates were found to be 5.1% pre-protocol introduction versus 0.5% following the introduction of the protocol (p = 0.0172). CONCLUSION: A "COVID-Protected Protocol" implemented by Emergency Medicine and Critical Care teams in response to the COVID-19 pandemic was associated with increased first-pass success rates and decreases in adverse events.

RéSUMé: OBJECTIFS: L'intubation orotrachéale est une procédure de sauvetage couramment réalisée dans l'unité de soins intensifs et le service des urgences dans le cadre de la gestion des voies aériennes d'urgence. Avant la pandémie de COVID-19, notre centre a entrepris une étude prospective d'observation pour caractériser l'intubation d'urgence effectuée dans le service des urgences et les établissements de soins intensifs du plus grand hôpital tertiaire du Manitoba. Au cours de cette étude, une expérience naturelle est apparue lorsqu'un " protocole d'intubation à séquence rapide protégé contre le COVID " standardisé a été mis en œuvre en réponse à la pandémie. L'étude qui en a résulté visait à répondre à la question suivante : chez les patients adultes des urgences soumis à une intubation urgente par les équipes de médecine d'urgence et de médecine de soins critiques, l'utilisation d'un " protocole d'intubation à séquence rapide protégé par COVID " a-t-elle un impact sur la réussite du premier passage ou sur d'autres résultats liés à l'intubation ? MéTHODE: Une étude prospective quasi-expérimentale avant et après a été menée dans un seul centre. Les données ont été recueillies prospectivement sur des intubations émergentes consécutives. Le résultat principal était la différence entre les taux de réussite au premier passage. Les résultats secondaires comprenaient la meilleure vue de Cormack­Lehane modifiée, l'hypoxémie, l'hypotension, l'intubation œsophagienne, les scénarios d'impossibilité d'intubation et d'oxygénation, la réanimation cardio-pulmonaire après l'intubation, les vasopresseurs nécessaires après l'intubation, la mortalité en unité de soins intensifs (USI), la durée de séjour en USI et les jours de ventilation mécanique. RéSULTATS: Des données ont été recueillies sur 630 patients, 416 dans la période pré-protocole et 214 dans la période post-protocole. Les taux de réussite au premier passage dans la période pré-protocole se sont avérés être de 73,1 % (n = 304). Suite à l'introduction du protocole, les taux de réussite au premier passage ont augmenté à 82,2 % (n = 176, p = 0,0105). Il y avait une différence statistiquement significative dans la vue Cormack­Lehane modifiée en faveur du protocole (p = 0,0191). Les taux d'intubation œsophagienne se sont avérés être de 5,1 % avant l'introduction du protocole contre 0,5 % après l'introduction du protocole (p = 0,0172). CONCLUSION: Un « protocole protégé contre la COVID ¼ mis en œuvre par les équipes de médecine d'urgence et de médecine de soins critiques en réponse à la pandémie de COVID-19 a été associé à une augmentation des taux de réussite du premier passage et à une diminution des événements indésirables.

Chronic kidney damage pathology score for systematic assessment of the non-neoplastic kidney tissue and prediction of post-operative renal function outcomes.

To establish a systematic histological assessment of non-neoplastic kidney (NNK) tissue at the time of nephrectomy to evaluate a patient's risk of developing post-operative renal dysfunction, a combined prospective pathologic assessment of the NNK and a retrospective clinical chart review was conducted. A blinded nephropathologist performed standardized assessment of glomerular sclerosis, tubulointerstitial fibrosis, arteriosclerosis, and hyaline arteriolosclerosis. Combined these formulated the chronic kidney damage pathology score (CKDPS). Multivariate logistic regression models were developed to assess the effect of CKDPS and other clinical factors on renal function up to 24 months following nephrectomy (partial or radical). 156 patients were included in the analysis with a median age of 60 years. 70% patients underwent radical nephrectomy. A history of hypertension and/or diabetes was present in 55.8% and 22.1%, respectively. Higher CKDPS (particularly glomerular global sclerosis and arteriosclerosis scores), radical nephrectomy, and reduced baseline estimated glomerular filtration rate (eGFR) were associated with worsening post-operative renal function outcomes. The systematic assessment of non-neoplastic kidney tissue at the time of renal surgery can help identify patients at risk of post-operative renal dysfunction. CKDPS represents a standardized and prognostically relevant histologic reporting system for non-neoplastic kidney tissue.

Analgesic duration of interscalene block after outpatient arthroscopic shoulder surgery with intravenous dexamethasone, intravenous dexmedetomidine, or their combination: a randomized-controlled trial.

PURPOSE: Both intravenous dexamethasone and dexmedetomidine prolong the analgesic duration of interscalene blocks (ISB) after arthroscopic shoulder surgery. This study compared their relative effectiveness and the benefit of their use in combination. METHODS: This single-centre, double-blinded, parallel three-group superiority trial randomized 198 adult patients undergoing ambulatory arthroscopic shoulder surgery. Patients received preoperative ISB with 30 mL 0.5% bupivacaine and 50 µg dexmedetomidine or 4 mg dexamethasone or both of these agents as intravenous adjuncts. The primary outcome was analgesic block duration. Secondary outcomes included the quality of recovery 15 score (range: 0-150) on day 1 and postoperative neurologic symptoms in the surgical arm. RESULTS: Block durations (n = 195) with dexamethasone (median [range], 24.5 [2.0-339.5] hr) and both adjuncts (24.0 [1.5-157.0] hr) were prolonged compared with dexmedetomidine (16.0 [1.5-154.0] hr). When analyzed by linear regression after an unplanned log transformation because of right-skewed data, the corresponding prolongations of block duration were 59% (95% confidence interval [CI], 28 to 97) and 46% (95% CI, 18 to 80), respectively (both P < 0.001). The combined adjuncts were not superior to dexamethasone alone (-8%; 95% CI, -26 to 14; P = 0.42). Median [IQR] quality of recovery 15 scores (n = 197) were significantly different only between dexamethasone (126 [79-149]) and dexmedetomidine (118.5 [41-150], P = 0.004), but by an amount less than the 8-point minimum clinically important difference. CONCLUSION: Dexamethasone is superior to dexmedetomidine as an intravenous adjunct for prolongation of bupivacaine-based ISB analgesic duration. There was no additional benefit to using both adjuncts in combination. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03270033); registered 1 September 2017.

RéSUMé: OBJECTIF: La dexaméthasone et la dexmédétomidine intraveineuses prolongent toutes deux la durée analgésique des blocs interscaléniques (BIS) après une chirurgie arthroscopique de l'épaule. Cette étude a comparé leur efficacité relative et les avantages d'une utilisation des deux agents en combinaison. MéTHODE: Cette étude de supériorité monocentrique en trois groupes parallèles à double insu a randomisé 198 patients adultes subissant une chirurgie arthroscopique de l'épaule en ambulatoire. Les patients ont reçu un BIS préopératoire composé de 30 mL de bupivacaïne 0,5 % avec 50 µg de dexmédétomidine, 4 mg de dexaméthasone, ou la combinaison de ces deux agents comme adjuvants intraveineux. Le critère d'évaluation principal était la durée analgésique du bloc. Les critères d'évaluation secondaires comprenaient le score de qualité de récupération (QoR) 15 (plage : 0-150) au jour 1 et les symptômes neurologiques postopératoires dans le bras opéré. RéSULTATS: Les durées des blocs (n = 195) avec la dexaméthasone (médiane [plage], 24,5 [2,0-339,5] heures) et la combinaison des deux adjuvants (24,0 [1,5-157,0] heures) ont été prolongées par rapport à la dexmédétomidine (16,0 [1,5-154,0] heures). Lorsqu'elles ont été analysées par régression linéaire après une transformation logarithmique non planifiée en raison de données biaisées vers la droite, les prolongations correspondantes de la durée du bloc étaient de 59 % (intervalle de confiance [IC] 95 %, 28 à 97) et de 46 % (IC 95 %, 18 à 80), respectivement (les deux P < 0,001). La combinaison des adjuvants n'était pas supérieure à la dexaméthasone seule (-8 %; IC 95 %, -26 à 14; P = 0,42). Les scores médians [ÉIQ] de qualité de récupération 15 (n = 197) n'étaient significativement différents qu'entre la dexaméthasone (126 [79-149]) et la dexmédétomidine (118,5 [41-150], P = 0,004), mais la différence observée était inférieure à la différence minimale de 8 points nécessaire pour être considérée cliniquement importante. CONCLUSION: La dexaméthasone est supérieure à la dexmédétomidine en tant qu'adjuvant intraveineux pour prolonger la durée analgésique d'un BIS à base de bupivacaïne. Aucun avantage supplémentaire n'a été observé lors de l'utilisation combinée des deux adjuvants. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT03270033); enregistrée le 1er septembre 2017.

Effect of dexamethasone dose and route on the duration of interscalene brachial plexus block for outpatient arthroscopic shoulder surgery: a randomized controlled trial.

PURPOSE: Dexamethasone prolongs the duration of interscalene block, but the benefits of higher doses and perineural vs intravenous administration remain unclear. METHODS: This factorial design, double-blinded trial randomized 280 adult patients undergoing ambulatory arthroscopic shoulder surgery at a single centre in a 1:1:1:1 ratio. Patients received ultrasound-guided interscalene block with 30 mL 0.5% bupivacaine and 4 mg or 8 mg dexamethasone by either the perineural or intravenous route. The primary outcome (block duration measured as the time of first pain at the surgical site) and secondary outcomes (adverse effects, postoperative neurologic symptoms) were assessed by telephone. In this superiority trial, the predetermined minimum clinically important difference for comparisons between doses and routes was 3.0 hr. RESULTS: The perineural route significantly prolonged the mean block duration by 2.0 hr (95% confidence interval [CI], 0.4 to 3.5 hr; P = 0.01), but 8 mg of dexamethasone did not significantly prolong the mean block duration compared with 4 mg (1.3 hr; 95% CI, -0.3 to 2.9 hr, P = 0.10), and there was no significant statistical interaction (P = 0.51). The mean (95% CI) block durations, in hours, were 24.0 (22.9 to 25.1), 24.8 (23.2 to 26.3), 25.4 (23.8 to 27.0), and 27.2 (25.2 to 29.3) for intravenous doses of 4 and 8 mg and perineural doses of 4 and 8 mg, respectively. There were no marked differences in side effects between groups. At 14 postoperative days, 57 (20.4%) patients reported neurologic symptoms, including dyspnea and hoarseness. At six months postoperatively, only six (2.1%) patients had residual symptoms, with four (1.4%) patients' symptoms unlikely related to interscalene block. CONCLUSION: Compared with the intravenous route, perineural dexamethasone prolongs the mean interscalene block duration by a small amount that may or may not be clinically significant, regardless of dose. However, the difference in mean block durations between 8 mg and 4 mg of dexamethasone is highly unlikely to be clinically important, regardless of the administration route. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02426736). Registered 14 April 2015.

Correction: Dignity and Distress towards the End of Life across Four Non-Cancer Populations.

[This corrects the article DOI: 10.1371/journal.pone.0147607.].

Prevalence of Parastomal Hernia and Factors Associated With Its Development.

PURPOSE: The purpose of this study was to identify risk factors for development of a parastomal hernia (PH). DESIGN: Cross-sectional survey. SETTING AND SUBJECTS: The target population comprised 2854 persons receiving services from the Manitoba Ostomy Program. Seven hundred sixty-four responses were received, yielding a response rate of 29.3%. Respondents average age was 70 years (SD = 12.8); 425 (55.6%) had a colostomy, 236 (30.8%) had an ileostomy, 63 (8.2%) had a urostomy, and 40 (5.2%) indicated other types of stomas or fistula. INSTRUMENTS: A questionnaire was developed by the authors that collected the following data: demographics, relevant medical history, personal and lifestyle factors, surgery-related factors, pre- and postoperative care factors, and information about the presence of a PH and physical and lifestyle effects related to a PH. Devices to enable respondents to measure the size of their stoma and abdominal girth were included in the survey package. The survey tool took approximately 30 to 45 minutes to complete. METHODS: An informational pamphlet and introductory letter were mailed 2 weeks before the survey was mailed. This was followed by a reminder letter. Bivariate analyses were completed in order to identify potential associations between all variables and a diagnosis of a PH; multivariate analysis was then completed to determine which factors were associated with an increased likelihood of a PH. RESULTS: Significant univariate associations were found between a diagnosis of a PH and diverticulitis, cirrhosis, benign prostatic enlargement, previous diagnosis of hernia, a smoking history, type of ostomy, stoma size, and continuous variables age and abdominal girth. Multiple regression analysis indicated that patients who underwent stoma surgery for cancer had larger stomas (1.5 to >3 in), and a colostomy were more likely to develop a PH. CONCLUSIONS: The results of this study indicate that PHs are prevalent. Additional research is needed to determine more effective intervention for preventing and managing a PH.

Dignity and Distress towards the End of Life across Four Non-Cancer Populations.

OBJECTIVE: The purpose of this study was to identify four non-cancer populations that might benefit from a palliative approach; and describe and compare the prevalence and patterns of dignity related distress across these diverse clinical populations. DESIGN: A prospective, multi-site approach was used. SETTING: Outpatient clinics, inpatient facilities or personal care homes, located in Winnipeg, Manitoba and Edmonton, Alberta, Canada. PARTICIPANTS: Patients with advanced Amyotrophic Lateral Sclerosis (ALS), Chronic Obstructive Pulmonary Disease (COPD), End Stage Renal Disease (ESRD); and the institutionalized alert frail elderly. MAIN OUTCOME MEASURE: In addition to standardized measures of physical, psychological and spiritual aspects of patient experience, the Patient Dignity Inventory (PDI). RESULTS: Between February 2009 and December 2012, 404 participants were recruited (ALS, 101; COPD, 100; ESRD, 101; and frail elderly, 102). Depending on group designation, 35% to 58% died within one year of taking part in the study. While moderate to severe loss of sense of dignity did not differ significantly across the four study populations (4-11%), the number of PDI items reported as problematic was significantly different i.e. ALS 6.2 (5.2), COPD 5.6 (5.9), frail elderly 3.0 (4.4) and ESRD 2.3 (3.9) [p < .0001]. Each of the study populations also revealed unique and distinct patterns of physical, psychological and existential distress. CONCLUSION: People with ALS, COPD, ESRD and the frail elderly face unique challenges as they move towards the end of life. Knowing the intricacies of distress and how they differ across these groups broadens our understanding of end-of-life experience within non-cancer populations and how best to meet their palliative care needs.

Prevalence of Peripheral Eosinophilia at Diagnosis in Children With Inflammatory Bowel Disease.

BACKGROUND AND OBJECTIVE: Inflammatory bowel disease (IBD) encompasses 2 disorders of unknown etiology: Crohn disease (CD) and ulcerative colitis (UC). There has been a continuous search for markers for disease activity. Eosinophils are granulocytic leukocytes that are implicated in the pathogenesis of IBD. The aim of this study was to examine the prevalence and significance of peripheral eosinophilia (PE) at diagnosis in children with IBD. METHODS: A comprehensive chart review of all children with diagnosed as having IBD between January 2006 and August 2014 was performed. Patients with PE at diagnosis were compared with those without in relation to disease clinical activity and disease course. RESULTS: A total of 109 children (mean age 14.6 ± 2.77, range 4.5-17.9 years, 55 boys) with IBD (68 with CD and 41 with UC) who were studied for a mean duration of 2.82 ± 1.89 (range 0.1-9.2 years) were identified. At diagnosis, 44 (40.4%) children had PE, which was more prevalent in patients with UC compared with those with CD (61.3% vs 36.3%, P < 0.05). At diagnosis, PE was more common in patients with high eosinophilic count in colonic biopsy samples (P < 0.01) and was significantly associated with disease activity as indicated by Pediatric CD Activity Index for children with CD (P < 0.05), Pediatric UC Activity Index for children with UC (P < 0.01). CONCLUSIONS: PE is a common finding at diagnosis in children with IBD especially in those with UC. Patients with PE at diagnosis are more likely to present with higher clinical activity indices. PE is associated with more eosinophils in colonic biopsy samples.

Elevated urinary CXCL10-to-creatinine ratio is associated with subclinical and clinical rejection in pediatric renal transplantation.

BACKGROUND: Subclinical and clinical T cell-mediated rejection (TCMR) has significant prognostic implications in pediatric renal transplantation. The goal of this study was to independently validate urinary CXCL10 as a noninvasive biomarker for detecting acute rejection in children and to extend these findings to subclinical rejection. METHODS: Urines (n = 140) from 51 patients with surveillance or indication biopsies were assayed for urinary CXCL10 using enzyme-linked immunosorbent assay and corrected with urinary creatinine. RESULTS: Median urinary CXCL10-to-creatinine (Cr) ratio (ng/mmol) was significantly elevated in subclinical TCMR (4.4 [2.6, 25.4], P < 0.001, n = 17); clinical TCMR (24.3 [11.2, 44.8], P < 0.001, n = 9); and antibody-mediated rejection (6.0 [3.3, 13.7], P = 0.002, n = 9) compared to noninflamed histology (1.4 [0.4, 4.2], normal and interstitial fibrosis and tubular atrophy, n = 52), and borderline tubulitis (3.3, [1.3, 4.9], n = 36). Elevated urinary CXCL10:Cr was independently associated with t scores (P < 0.001) and g scores (P = 0.006) on multivariate analysis. The area under receiver operating curve for subclinical and clinical TCMR was 0.81 (P = 0.045) and 0.88 (P = 0.019), respectively. This corresponded to a sensitivity-specificity of 0.59-0.67 and 0.77-0.60 for subclinical and clinical TCMR at cutoffs of 4.82 and 4.72 ng/mmol, respectively. CONCLUSION: This study demonstrates that urinary CXCL10:Cr corresponds with microvascular inflammation and is a sensitive and specific biomarker for subclinical and clinical TCMR in children. This may provide a noninvasive monitoring tool for posttransplant immune surveillance for pediatric renal transplant recipients.

Eliciting Personhood Within Clinical Practice: Effects on Patients, Families, and Health Care Providers.

CONTEXT: Failure to acknowledge personhood is often the cause of patient and family dissatisfaction. We developed the Patient Dignity Question (PDQ) as a simple means of inquiring about personhood: "What do I need to know about you as a person to give you the best care possible?" OBJECTIVES: This study aimed to evaluate the impact of the PDQ on patients and families, evaluate its influence on health care providers (HCPs), and determine if HCP characteristics mediate receptivity to PDQ-elicited information. METHODS: Palliative care patients or their family members were asked to respond to the PDQ. Responses were summarized, read to participants to ensure accuracy, and with permission, placed in their charts. Patient, family, and HCP responses to the PDQ were then elicited. RESULTS: A total of 126 participants (66 patients and 60 family members) responded to the PDQ; 99% indicated that the summaries were accurate, 97% permitted the summary to be placed in the chart, 93% felt that the information was important for HCPs to know, and 99% would recommend the PDQ for others. A total of 137 HCPs completed 293 evaluations of individual PDQs; 90% indicated that they learned something new from it, 64% that they were emotionally affected by it, 59% that it influenced their sense of empathy, and 44% that it influenced their care. HCP empathy, job satisfaction, having a meaningful life, and social support mediated responsiveness to PDQ-elicited information. CONCLUSION: The PDQ offers an effective way of eliciting personhood, enhancing patient, family, and HCP experience alike.

Differences in the gingival crevicular fluid composition between adults and adolescents undergoing orthodontic treatment.

OBJECTIVES: To investigate differences in the gingival crevicular fluid (GCF) composition between adolescent and adult patients undergoing orthodontic treatment with fixed appliances. MATERIALS AND METHODS: Ten adolescents (14.4 ± 1.43) and 10 adults (28.5 ± 7.83) with Class I malocclusions and minor upper incisor crowding were allocated to two different age groups. Brackets were bonded only in the upper arch over the 20-week period of the experiment. Samples of GCF were collected from the labial sides of the upper incisors (experimental sites) and lower incisors (control sites) of each subject at five time points. Aliquots from diluted GCF were screened for the presence of receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), interleukin-1 (IL-1), interleukin-1 receptor antagonist (IL-1RA), and metalloproteinase-9 (MMP-9) using a microarray technique. The values were statistically analyzed. RESULTS: In adults, the ratio of IL-1 to IL-1RA decreased significantly (P  =  .033) in experimental sites 3 weeks after appliance placement and first archwire activation. In adolescents, the ratio of RANKL to OPG peaked 6 weeks after the insertion of the first rectangular archwire. This ratio peak found in adolescents was a consequence of a decrease in the mean concentration of OPG. No significant changes over time were observed in the concentration of MMP-9. CONCLUSION: This study demonstrates age trends in the GCF levels of IL-1, IL-1RA, RANKL, and OPG that may be used to track differences in tissue response between adults and adolescents undergoing orthodontic treatment.