OBJECTIVES:Limited data exist comparing robotic and open approaches to pancreaticoduodenectomy (PD). We performed a multicenter comparison of perioperative outcomes of robotic PD (RPD) and open PD ...(OPD).
METHODS:Perioperative data for patients who underwent postlearning curve PD at 8 centers (8/2011–1/2015) were assessed. Univariate analyses of clinicopathologic and treatment factors were performed, and multivariable models were constructed to determine associations of operative approach (RPD or OPD) with perioperative outcomes.
RESULTS:Of the 1028 patients, 211 (20.5%) underwent RPD (4.7% conversions) and 817 (79.5%) underwent OPD. As compared with OPD, RPD patients had higher body mass index, rates of prior abdominal surgery, and softer pancreatic remnants, whereas OPD patients had a higher percentage of pancreatic ductal adenocarcinoma cases, and greater proportion of nondilated (<3 mm) pancreatic ducts. On multivariable analysis, as compared with OPD, RPD was associated with longer operative times mean difference = 75.4 minutes, 95% confidence interval (CI) 17.5–133.3, P = 0.01, reduced blood loss (mean difference = −181 mL, 95% CI −355–(−7.7), P = 0.04) and reductions in major complications (odds ratio = 0.64, 95% CI 0.47–0.85, P = 0.003). No associations were demonstrated between operative approach and 90-day mortality, clinically relevant postoperative pancreatic fistula and wound infection, length of stay, or 90-day readmission. In the subset of 522 (51%) pancreatic ductal adenocarcinomas, operative approach was not a significant independent predictor of margin status or suboptimal lymphadenectomy (<12 lymph nodes harvested).
CONCLUSIONS:Postlearning curve RPD can be performed with similar perioperative outcomes achieved with OPD. Further studies of cost, quality of life, and long-term oncologic outcomes are needed.
Background & Aims Little is known about in utero exposure to and postnatal clearance of anti–tumor necrosis factor (anti-TNF) agents in neonates. We investigated the concentrations of adalimumab and ...infliximab in umbilical cord blood of newborns and rates of clearance after birth, and how these correlated with drug concentrations in mothers at birth and risk of infection during the first year of life. Methods We performed a prospective study of 80 pregnant women with inflammatory bowel diseases at tertiary hospitals in Denmark, Australia, and New Zealand from March 2012 through November 2014: 36 received adalimumab and 44 received infliximab; 39 received concomitant thiopurines during pregnancy. Data were collected from medical records on disease activity and treatment before, during, and after pregnancy. Concentrations of anti-TNF agents were measured in blood samples from women at delivery and in umbilical cords, and in infants for every 3 months until the drug was no longer detected. Results The time from last exposure to anti-TNF agent during pregnancy correlated inversely with the concentration of the drugs in the umbilical cord (adalimumab: r = -0.64, P = .0003; infliximab: r = -0.77, P < .0001) and in mothers at time of birth (adalimumab, r = -0.80; infliximab, r = -0.80; P < .0001 for both). The median ratio of infant:mother drug concentration at birth was 1.21 for adalimumab (95% confidence interval CI, 0.94–1.49) and 1.97 for infliximab (95% CI, 1.50–2.43). The mean time to drug clearance in infants was 4.0 months for adalimumab (95% CI, 2.9–5.0) and 7.3 months for infliximab (95% CI, 6.2–8.3; P < .0001). Drugs were not detected in infants after 12 months of age. Bacterial infections developed in 4 infants (5%) and viral infections developed in 16 (20%), all with benign courses. The relative risk for infection was 2.7 in infants whose mothers received the combination of an anti-TNF agent and thiopurine, compared with anti-TNF monotherapy (95% CI, 1.09–6.78; P = .02). Conclusions In a prospective study of infants born to mothers who received anti-TNF agents during pregnancy, we detected the drugs until 12 months of age. There was an inverse correlation between the time from last exposure during pregnancy and drug concentration in the umbilical cord. Infliximab was cleared more slowly than adalimumab from the infants. The combination of an anti-TNF agent and thiopurine therapy during pregnancy increased the relative risk for infant infections almost 3-fold compared with anti-TNF monotherapy. Live vaccines therefore should be avoided for up to 1 year unless drug clearance is documented, and pregnant women should be educated on the risks of anti-TNF use.
IMPORTANCE: Optimal use of whole-exome sequencing (WES) in the pediatric setting requires an understanding of who should be considered for testing and when it should be performed to maximize clinical ...utility and cost-effectiveness. OBJECTIVES: To investigate the impact of WES in sequencing-naive children suspected of having a monogenic disorder and evaluate its cost-effectiveness if WES had been available at different time points in their diagnostic trajectory. DESIGN, SETTING, AND PARTICIPANTS: This prospective study was part of the Melbourne Genomics Health Alliance demonstration project. At the ambulatory outpatient clinics of the Victorian Clinical Genetics Services at the Royal Children’s Hospital, Melbourne, Australia, children older than 2 years suspected of having a monogenic disorder were prospectively recruited from May 1 through November 30, 2015, by clinical geneticists after referral from general and subspecialist pediatricians. All children had nondiagnostic microarrays and no prior single-gene or panel sequencing. EXPOSURES: All children underwent singleton WES with targeted phenotype-driven analysis. MAIN OUTCOMES AND MEASURES: The study examined the clinical utility of a molecular diagnosis and the cost-effectiveness of alternative diagnostic trajectories, depending on timing of WES. RESULTS: Of 61 children originally assessed, 44 (21 48% male and 23 52% female) aged 2 to 18 years (mean age at initial presentation, 28 months; range, 0-121 months) were recruited, and a diagnosis was achieved in 23 (52%) by singleton WES. The diagnoses were unexpected in 8 of 23 (35%), and clinical management was altered in 6 of 23 (26%). The mean duration of the diagnostic odyssey was 6 years, with each child having a mean of 19 tests and 4 clinical genetics and 4 nongenetics specialist consultations, and 26 (59%) underwent a procedure while under general anesthetic for diagnostic purposes. Economic analyses of the diagnostic trajectory identified that WES performed at initial tertiary presentation resulted in an incremental cost savings of A$9020 (US$6838) per additional diagnosis (95% CI, A$4304-A$15 404 US$3263-US$11 678) compared with the standard diagnostic pathway. Even if WES were performed at the first genetics appointment, there would be an incremental cost savings of A$5461 (US$4140) (95% CI, A$1433-A$10 557 US$1086- US$8004) per additional diagnosis compared with the standard diagnostic pathway. CONCLUSIONS AND RELEVANCE: Singleton WES in children with suspected monogenic conditions has high diagnostic yield, and cost-effectiveness is maximized by early application in the diagnostic pathway. Pediatricians should consider early referral of children with undiagnosed syndromes to clinical geneticists.
A significant fraction of fine-needle aspirates obtained from thyroid nodules are read as indeterminate. A new molecular test accurately predicts whether a cytologically indeterminate nodule is ...benign 93% of the time, permitting a conservative approach to management.
Thyroid nodules are common and are usually benign.
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However, 5 to 15% prove to be malignant; accordingly, identification of a nodule 1 cm or larger in diameter often prompts a diagnostic evaluation.
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,
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The cornerstone of thyroid-nodule evaluation is fine-needle aspiration,
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which enables the assessment of cellular morphologic features that could not be identified by means of clinical assessment or imaging. Preoperative, ultrasonographically guided fine-needle aspiration has been shown to accurately classify 62 to 85% of thyroid nodules as benign, thereby avoiding diagnostic surgery.
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However, 15 to 30% of aspirations yield indeterminate cytologic findings,
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which include three subtypes: “atypia (or . . .
Mortality in pulmonary sarcoidosis is highly variable and a reliable prognostic algorithm for disease staging and for guiding management decisions is needed. The objective of this study is to derive ...and test a staging system for determining prognosis in pulmonary sarcoidosis.
We identified the prognostic value of high-resolution computed tomography (HRCT) patterns and pulmonary function tests, including the composite physiological index (CPI) in patients with pulmonary sarcoidosis. We integrated prognostic physiological and HRCT variables to form a clinical staging algorithm predictive of mortality in a test cohort. The staging system was externally validated in a separate cohort by the same methods of discrimination used in the primary analysis and tested for clinical applicability by four test observers.
The test cohort included 251 patients with pulmonary sarcoidosis in the study referred to the Sarcoidosis clinic at the Royal Brompton Hospital, UK, between Jan 1, 2000, and June 30, 2010. The CPI was the strongest predictor of mortality (HR 1·04, 95% CI 1·02-1·06, p<0·0001) in the test cohort. An optimal CPI threshold of 40 units was identified (HR 4·24, 2·84-6·33, p<0·0001). The CPI40, main pulmonary artery diameter to ascending aorta diameter ratio (MPAD/AAD), and an extent of fibrosis threshold of 20% were combined to form a staging algorithm. When assessed in the validation cohort (n=252), this staging system was strikingly more predictive of mortality than any individual variable alone (HR 5·89, 2·68-10·08, p<0·0001). The staging system was successfully applied to the test and validation cohorts combined, by two radiologists and two physicians.
A clear prognostic separation of patients with pulmonary sarcoidosis is provided by a simple staging system integrating the CPI and two HRCT variables.
ObjectivesTo assess which osmolarity equation best predicts directly measured serum/plasma osmolality and whether its use could add value to routine blood test results through screening for ...dehydration in older people.DesignDiagnostic accuracy study.ParticipantsOlder people (≥65 years) in 5 cohorts: Dietary Strategies for Healthy Ageing in Europe (NU-AGE, living in the community), Dehydration Recognition In our Elders (DRIE, living in residential care), Fortes (admitted to acute medical care), Sjöstrand (emergency room) or Pfortmueller cohorts (hospitalised with liver cirrhosis).Reference standard for hydration statusDirectly measured serum/plasma osmolality: current dehydration (serum osmolality >300 mOsm/kg), impending/current dehydration (≥295 mOsm/kg).Index tests39 osmolarity equations calculated using serum indices from the same blood draw as directly measured osmolality.ResultsAcross 5 cohorts 595 older people were included, of whom 19% were dehydrated (directly measured osmolality >300 mOsm/kg). Of 39 osmolarity equations, 5 showed reasonable agreement with directly measured osmolality and 3 had good predictive accuracy in subgroups with diabetes and poor renal function. Two equations were characterised by narrower limits of agreement, low levels of differential bias and good diagnostic accuracy in receiver operating characteristic plots (areas under the curve >0.8). The best equation was osmolarity=1.86×(Na++ K+)+1.15×glucose+urea+14 (all measured in mmol/L). It appeared useful in people aged ≥65 years with and without diabetes, poor renal function, dehydration, in men and women, with a range of ages, health, cognitive and functional status.ConclusionsSome commonly used osmolarity equations work poorly, and should not be used. Given costs and prevalence of dehydration in older people we suggest use of the best formula by pathology laboratories using a cutpoint of 295 mOsm/L (sensitivity 85%, specificity 59%), to report dehydration risk opportunistically when serum glucose, urea and electrolytes are measured for other reasons in older adults.Trial registration numbers:DRIE: Research Register for Social Care, 122273; NU-AGE: ClinicalTrials.gov NCT01754012.
To further explore the effect of weighted arms on toddler's performance in problem solving (Arterberry et al., 2018, Infancy, 23(2), 173), the present study explored scale errors and categorization, ...two instances where infants appear to show more advanced knowledge than toddlers. Experiment 1 (N = 67) used a novel task for inducing scale errors among 24‐ to 29‐month‐olds. Results replicated rates of scale errors found in previous research that used different tasks. Experiment 2 used sequential touching (N = 31) and sorting measures (N = 23) to test categorization in 24‐month‐old children. In both measures, children showed categorization at the basic level when there was high contrast between the exemplars, but not at a basic level with low contrast or a subordinate level. In Experiments 1 and 2, half the participants were tested while wearing weighted wristbands. Weighting the arms did not affect error rates, in contrast to previous research showing that weights improved performance in search tasks. The findings are discussed in light of children's difficulty in integrating perception, cognition, and action.
To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis.
We used unpublished survival time data for 2,242 patients ...from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model.
The combined 10-year overall survival rate was 30% 95% confidence interval (CI), 28%-31% for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality.
BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.
Dirofilaria immitis is a filarial parasite of dogs that can cause serious or fatal cardiopulmonary disease. Three studies were conducted to evaluate the efficacy and safety of monthly treatment with ...moxidectin in a chewable tablet product in combination with sarolaner and pyrantel to prevent heartworm disease in dogs after experimental challenge and in a clinical field study in the USA.
In two laboratory studies, dogs (8 per group) that had been inoculated 30 days prior with 50 third-stage D. immitis larvae were randomized to treatment on Day 0 with placebo or combination product, at the minimum dose of 24 µg/kg moxidectin, 2 mg/kg sarolaner and 5 mg/kg pyrantel (as pamoate salt). Study 2 also included groups treated with tablets containing moxidectin-alone (24 µg/kg) or sarolaner-alone (2 mg/kg). Efficacy was evaluated ~ 5 months after inoculation by adult heartworm counts at necropsy. In the field study, 410 dogs ≥ 8 weeks-old from 23 USA veterinary clinics were treated for 11 months with either combination product at 24-48 µg/kg moxidectin, 2-4 mg/kg sarolaner and 5-10 mg/kg pyrantel (n = 272) or Heartgard® Plus (ivermectin/pyrantel) at the label recommended dose rate (n = 138). Efficacy was evaluated on Day 330 using antigen and microfilaria testing to assess adult heartworm infection.
In the laboratory studies, there were no heartworms recovered from any dog treated with the combination product or moxidectin alone and all dogs treated with placebo or sarolaner-alone were infected with 20-44 adult heartworms. In the field study, all dogs treated with the combination product tested negative for heartworm infection on Day 330, whereas two dogs treated with Heartgard® Plus tested positive. The Heartgard® Plus-treated dogs that tested heartworm positive were from the lower Mississippi River Valley region, where heartworm resistance has been confirmed to occur. The combination product was well tolerated in all studies.
In laboratory studies, no heartworms were recovered from dogs treated with a single dose of the novel combination product containing moxidectin, sarolaner and pyrantel. Additionally, in the field study no dog tested positive for adult heartworm infection when dosed with the combination product monthly for 11 months, while two dogs treated with Heartgard® Plus tested positive.
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