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Single-use disposable duodenoscopes (SDD) have been developed to mitigate infectious risks related to reusable duodenoscopes. The aim of this study is to compare the safety and efficacy of the two available SDDs in the United States.We conducted a comparative study of 2 SDD in consecutive ERCP procedures performed by expert endoscopists from 9 academic centers. Performance ratings, procedure details, and adverse events were collected.A total of 201 patients were included: 129 patients underwent ERCP with Exalt (mean age 63, Males- 66 (51%), 72 with aScope Duodeno (mean age 65, males=30 (42%). A majority of endoscopists had performed2000 ERCPs in both groups (71% Exalt, 93% aScope Duodeno). Technical success was 92% in both groups (n=119 Exalt-group, n=66 aScope-Duodeno-group). The procedural complexity for the ERCP cases performed were: Grade 1: 35 cases (18%), Grade 2: 83 cases (41%), Grade 3: 65 cases (32%), and Grade 4: 18 cases (9%). Thirteen patients (10%) from the Exalt group and 16 patients (22%) from the aScope Duodeno group required conversion to a reusable duodenoscope. On a scale of 1 to 5, Exalt and aScope Duodeno, respectively, were rated: 2.31 versus 2.60 for location and visualization quality, 1.38 versus 1.57 for maneuverability based on papillary orientation, 1.48 versus 1.15 for suction/air control, and 2.31 versus 2.34 for elevator efficiency. None of the adverse events were related to the SDDs.The 2 SDDs were comparable. Further ongoing enhancements to these devices will improve maneuverability and clinical effectiveness.

Backgrounds Endoscopic ultrasound (EUS)-guided placement of lumen-apposing metal stents (LAMSs) has gained popularity for the treatment of pancreatic walled-off necrosis (WON). We compared the 20-mm and 15-mm LAMSs for the treatment of symptomatic WON in terms of clinical success and adverse events. Methods We conducted a retrospective, case-matched study of 306 adults at 22 tertiary centers from 04/2014 to 10/2018. A total of 102 patients with symptomatic WON who underwent drainage with 20-mm LAMS (cases) and 204 patients who underwent drainage with 15-mm LAMS (controls) were matched by age, sex, and drainage approach. Conditional logistic regression analysis was performed to compare clinical success (resolution of WON on follow-up imaging without reintervention) and adverse events (according to American Society for Gastrointestinal Endoscopy criteria). Results Clinical success was achieved in 92.2 % of patients with 20-mm LAMS and 91.7 % of patients with 15-mm LAMS (odds ratio 0.92; P = 0.91). Patients with 20-mm LAMS underwent fewer direct endoscopic necrosectomy (DEN) sessions (mean 1.3 vs. 2.1; P Conclusions The 20-mm LAMS showed comparable clinical success and safety profile to the 15-mm LAMS, with the need for fewer DEN sessions for WON resolution.

Background: Spinal cord injury (SCI) results in significant loss in pulmonary function secondary to respiratory muscle paralysis. Retention of secretions and atelectasis and, recurrent respiratory tract infections may also impact pulmonary function. Objective: To determine whether usage of lower thoracic spinal cord stimulation (SCS) to restore cough may improve spontaneous pulmonary function in individuals with chronic SCI. Design/Methods: 10 tetraplegics utilized SCS system on a regular daily basis. Spontaneous inspiratory capacity (IC), maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) were measured at baseline prior to usage of the device and repeated every 4–5 weeks over a 20-week period. Maximum airway pressure generation (P) during SCS (40 V, 50 Hz, 0.2 ms) at total lung capacity (TLC) with subject maximal expiratory effort, at the same timepoints were determined, as well. Results: Following daily use of SCS, mean IC improved from 1636 ± 229 to 1932 ± 239 ml (127 ± 8% of baseline values) after 20 weeks (P

Many applications involve a censored dependent variable, an endogenous independent variable, or both. Chernozhukov, Fernández-Val, and Kowalski (2015, Journal of Econometrics 186: 201–221) introduced a censored quantile instrumental-variable (CQIV) estimator for use in those applications. The estimator has been applied by Kowalski (2016, Journal of Business & Economic Statistics 34: 107–117), among others. In this article, we introduce a command, cqiv, that simplifies application of the CQIV estimator in Stata. We summarize the CQIV estimator and algorithm, describe the use of cqiv, and provide empirical examples.

We use administrative data from the Internal Revenue Service to examine long-term impacts of childhood Medicaid eligibility expansions on outcomes in adulthood at each age from 19 to 28. Greater Medicaid eligibility increases college enrolment and decreases fertility, especially through age 21. Starting at age 23, females have higher contemporaneous wage income, although male increases are imprecise. Together, both genders have lower mortality. These adults collect less from the earned income tax credit and pay more in taxes. Cumulatively from ages 19 to 28, at a 3% discount rate, the federal government recoups 58 cents of each dollar of its “investment” in childhood Medicaid.

High-frequency spinal cord stimulation (HF-SCS) applied at the T2 spinal level results in physiologic activation of the inspiratory muscles in C2 spinal-sectioned dogs. Although the bulbo-spinal fibers were cut, they likely survived the duration of acute experiments, and inspiratory muscle activation may have involved stimulation of these fibers. In two anesthetized, C2 paralyzed, intubated, and mechanically ventilated dogs, HF-SCS (300 Hz) was applied at the T2 level. The effectiveness of HF-SCS in generating inspired volume (V) and negative airway pressures (P) was evaluated over a period of 5 days during which time the bulbo-spinal fibers would have degenerated. Because the effectiveness of HF-SCS may be adversely affected by deterioration of these fibers and/or the condition of the animal, low-frequency (50 Hz) SCS (LF-SCS) was also performed and served as a control. All vital signs, oxygen saturation, and end-tidal Pco2 remained stable over the 5-day period. V and P also remained stable over the study period. For example, mean V and P were 771 ± 25 ml and 64 ± 1 cmH2O with HF-SCS (3 mA) during the initial and 674 ± 59 ml and 63 ± 5 cmH2O on the final day. Comparable values during LF-SCS (8 mA) were 467 ± 12 ml and 48 ± 1 cmH2O during the initial and 397 ± 20 ml and 42 ± 2 cmH2O on the final day. Because V and P in response to HF-SCS remained stable over a 5-day period following which the bulbo-spinal fibers would have degenerated, the mechanism of HF-SCS does not depend upon the viability of these tracts. HF-SCS therefore may be a useful method to restore ventilation in chronic ventilator dependent tetraplegics. NEW & NOTEWORTHY This study indicates that the respiratory responses to high-frequency spinal cord stimulation applied at the T2 level results in activation of the inspiratory motoneuron pools via interneuronal circuits and/or the inspiratory motoneurons directly and does not depend upon activation of long descending inspiratory bulbo-spinal fibers. This method therefore, may provide an alternative method to restore ventilation in ventilator dependent spinal cord injured patients.

Background Multiple studies have examined the use of lumen-apposing metal stents (LAMSs) for the drainage of peripancreatic fluid collections. Data on the use of LAMSs for postoperative fluid collections (POFCs) are scarce. POFCs may lead to severe complications without appropriate treatment. We aimed to study the outcomes (technical success, clinical success, rate/severity of adverse events, length of stay, recurrence) of the use of LAMSs for the drainage of POFCs. Methods This international, multicenter, retrospective study involved 19 centers between January 2012 and October 2017. The primary outcome was clinical success. Secondary outcomes included technical success and rate/severity of adverse events using the ASGE lexicon. Results A total of 62 patients were included during the study period. The most common etiology of the POFCs was distal pancreatectomy (46.8 %). The mean (standard deviation) diameter was 84.5 mm (30.7 mm). The most common indication for drainage was infection (48.4 %) and transgastric drainage was the most common approach (82.3 %). Technical success was achieved in 60/62 patients (96.8 %) and clinical success in 57/62 patients (91.9 %) during a median (interquartile range) follow-up of 231 days (90 – 300 days). Percutaneous drainage was needed in 8.1 % of patients. Adverse events occurred intraoperatively in 1/62 patients (1.6 %) and postoperatively in 7/62 (11.3 %). There was no procedure-related mortality. Conclusion This is the largest study on the use of LAMSs for POFCs. It suggests good clinical efficacy and safety of this approach. The use of LAMSs in the management of POFCs is a feasible alternative to percutaneous and surgical drainage.

Background and study aims Stent migration is a common complication of fully-covered self-expanding metal stents (FCSEMS), but the rate of clinically relevant migration as defined by stent migration followed by reintervention via endoscopy for stent replacement is unknown. The goal of this study is to gain insight into the total migration rate and clinically relevant migration rate of different types of FCSEMS placed within benign and malignant strictures with specific attention paid to stent manufacturer, diameter, and length. Patients and methods Multicenter retrospective analysis of endoscopic data from patients with FCSEMS placed within benign or malignant strictures. FCSEMS used included a variety of sizes and manufacturers. Results A total of 369 patients were included, 161 of whom had benign strictures and 208 of whom had malignant strictures. The total migration rate and clinically relevant migration rate in benign strictures were 30 % and 17 %, respectively. For benign strictures, Wallflex stents had a clinically relevant migration rate of 15 %, compared to Endomaxx stents with 19 %, and Evolution stents with 25 % (P = 0.52). The total migration rate and clinically relevant migration rates in malignant strictures were 23 % and 14 %, respectively. Evolution stents had a significantly higher clinically relevant migration rate (29 %) than the Wallflex stents (7 %) and the endomaxx stents (12 %), P = 0.003. Conclusion This study is the largest to investigate migration rates for FCSEMS in benign and malignant strictures. Clinically relevant migration is a relatively common occurrence with all stent types studied and better anti-migration features are needed.

Previous analyses of recordings of alpha motoneuron discharges from branches of the intercostal and abdominal nerves in anesthetized cats under neuromuscular blockade demonstrated modulation with the cardiac cycle. This modulation was interpreted as evidence that thoracic somatosensory afferents, most likely muscle spindles, provide a signal to the CNS that could contribute to cardiac interoception. Here, two aspects of these observations have been extended. First, new measurements of thoracic and abdominal EMG activity in spontaneously breathing dogs show that a very similar modulation exists in these rather different circumstances. Second, further analysis of the cat recordings shows that cardiac modulation of the discharges of bulbospinal neurons that transmit the expiratory drive to thoracic motoneurons is weak and of an inappropriate time-course to be a contributor to the effect seen in the motoneurons.

Background and Objectives: Endoscopic drainage/debridement of symptomatic walled off necrosis (WON) using lumen-apposing metal stents (LAMS) is both safe and effective. While endoscopic management of WON is the standard approach to treatment, the ideal concomitant medical therapy remains unclear. The purpose of this study was to further elucidate the effect of proton pump inhibitor (PPIs) therapy on the technical and clinical success of endoscopic treatment of WON. Methods: Two hundred and seventy-two patients in 8 centers with WON managed by endoscopic drainage using LAMS were evaluated. Patients were followed for at least 6 months following treatment. The patients were divided into two groups: Those that used PPIs continuously during the therapy and those not on PPIs continuously during the interval of therapy. Outcomes included but were not limited to technical success, clinical success, number of procedures performed, and adverse events. Results: From 2013 to 2016, 272 patients underwent WON drainage with successful transmural LAMS placement. The two groups were split evenly into PPI users and non-PPI users, and matched in regards to demographics, etiology of pancreatitis, WON size, and location. There was no difference in the technical success between the two groups (100% vs. 98.8%, P = 1), or in clinical success rates (78.7% vs. 77.9%). There was a significant difference in the required number of direct endoscopic necrosectomies to achieve clinical success in the PPI vs. non-PPI group (3.2 vs. 4.6 respectively, P < 0.01). There were significantly more cases of stent occlusion in the non-PPI group vs. PPI group (9.5% vs. 20.1% P = 0.012), but all other documented adverse events were not significantly different. Conclusion: Discontinuing PPIs during endoscopic drainage and necrosectomy of symptomatic WON appears to reduce the number of endoscopic procedures required to achieve resolution. Continuous PPI results in higher rates of early stent occlusion.

OBJECTIVE: To compare the safety and effectiveness of wire (WE) vs. disc (DE) electrodes to restore cough in subjects with spinal cord injury (SCI). DESIGN: Clinical trials assessing the effectiveness and clinical outcomes associated with two electrode systems to activate the expiratory muscles. SETTING: Inpatient hospital setting for DE or WE electrode insertion; outpatient evaluation of cough efficacy and instructions for home use. PARTICIPANTS: Twenty-nine subjects with SCI; 17 participants with DE and 12 with WE implants. INTERVENTION: Surgical implantation of WE or DE to restore cough. Daily application of spinal cord stimulation (SCS) at home. MAIN OUTCOME MEASURE(S): Airway pressure (P) and peak airflow (F) generation achieved with SCS; clinical parameters including ease in raising secretions, incidence of acute respiratory tract infections (RTI) and side effects. RESULTS: P and F achieved with DE and WE were not significantly different. For example, at total lung capacity (TLC) with participant effort, P was 128 ± 12 cmH(2)O and 118 ± 14 cmH(2)O, with DE and WE, respectively. The degree of difficulty in raising secretions improved markedly in both groups. The incidence of RTI per year fell from 1.3 ± 0.3 and 1.3 ± 0.5–0.3 ± 0.1 and 0.1 ± 0.1 for DE and WE groups, respectively (P

Objective To compare the effectiveness of wire versus disc electrodes to activate the inspiratory muscles via high frequency spinal cord stimulation. Design Animal study. Setting Research laboratory. Animals Dogs (n = 5) Interventions In separate trials, spinal cord stimulation (SCS) was applied via disc (DE) and two parallel wire electrodes (WE) on the ventral epidural space at the T2-T3 spinal region. Main Outcome Measure(s) Airway pressure (P) and inspired volume (V) generation following stimulation with DE and WE were compared. Given our previous success with (DE), outcome variables with this electrode were used as our gold standard to which all comparisons were made. Results Two configurations of WE using monopolar stimulation (MS) resulted in P and V that were similar to those generated with MS with DE. For example, MS with parallel WE connected together to function as a common cathode (Y-connection) and a 2-channel system (separate cathodes with a remote ground), resulted in P that were 91 ± 6 and 92 ± 4%, respectively, of those achieved with DE (NS for both). Bipolar stimulation with parallel WE using a Y-connection and with a 2-channel system, resulted in P that were 96 ± 4 and 94 ± 4%, of the P achieved with DE (NS for both). Conclusion(s) These results suggest that specific configurations of WE, which can be placed via minimally invasive techniques, provide comparable activation of the inspiratory muscles compared to DE and may be a useful technique to restore ventilatory support in persons with spinal cord injury.

BackgroundSystemic autoimmune rheumatic disease (SARD) patients may be at risk for disease flare and prolonged symptom duration after COVID-19, perhaps related to DMARD disruption and immune activation.ObjectivesTo describe DMARD disruption and identify differences in SARD activity among patients with and without prolonged COVID-19 symptom duration.MethodsWe identified all SARD patients with confirmed COVID-19 at the Mass General Brigham healthcare system in Boston, USA; prospective recruitment is ongoing. Surveys were used to collect demographics, clinical characteristics, DMARD disruption, COVID-19 course, and SARD disease activity before and after COVID-19. The survey included validated instruments measuring disease activity, pain, fatigue, functional status, and respiratory quality of life. Prolonged symptom duration was defined as COVID-19 symptoms lasting ≥28 days. We compared differences in patient-reported measures between those with and without prolonged symptoms.ResultsWe analyzed survey responses from 174 COVID-19 survivors with SARDs (mean age 52±16 years, 81% female, 80% White). The most common SARDs were RA (40%) and SLE (14%). Fifty-one percent of the 127 respondents on any DMARD reported a disruption to their regimen at COVID-19 onset (Figure 1). Among individual DMARDs, 56-77% were reported to have any change, except for hydroxychloroquine (23%) and rituximab (46%). SARD flare after COVID-19 was reported by 41% of respondents (Table 1). Patient global assessment of SARD activity was worse after COVID-19 (mean 7.6±2.3 before vs. 6.6±2.9 after COVID-19, pTable 1.Acute COVID-19 course, SARD flare/activity, and patient-reported outcomes among COVID-19 survivors with SARDs.All COVID-19 survivors with SARDs (n=174)Prolonged symptom duration ≥28 days (n=78)No prolonged symptom duration/(n=96)p-value (prolonged vs. not)Acute COVID-19 courseCOVID-19 symptom duration, days, median [IQR]14 [9, 29]46 [30, 65]11 [7, 14]Initial symptom count, median [IQR]6 [3, 8]7 [6, 9]4 [2, 7]Hospitalized, n (%)38 (22)22 (28)16 (17)0.001SARD flare/activitySelf-reported SARD flare after COVID-19, n (%)71 (41)38 (49)33 (34)0.15Disease activity by RAPID3, median [IQR]9 [4, 14]11.2 [6, 16]7 [3, 13]0.0067RAPID3 categorical score, n (%)0.13Remission (0)11 (7)4 (5)7 (7)Near remission (0.3-1.0)23 (14)5 (7)18 (19)Low severity (1.3-2.0)26 (15)10 (14)16 (17)Moderate severity (2.3-4.0)55 (33)27 (36)28 (29)High severity (4.3-10.0)54 (32)28 (38)26 (27)Patient-reported outcomesPain by SF-MPQ, median [IQR]2 [1, 2]2 [1, 2]1 [0, 2]0.0008Fatigue by FSI, median [IQR]53 [27, 84]66 [31, 91.5]43 [26, 76]0.031mHAQ, median [IQR]0.125 [0, 0.38]0.25 [0, 0.75]0.125 [0, 0.38]0.11Respiratory quality of life by SGRQ, global [IQR]15 [4, 29]16 [4, 36]10 [4, 26]0.49RAPID3, Routine Assessment of Patient Index Data 3; SF-MPQ, Short-form McGill Pain Questionnaire; FSI, Fatigue Symptom Inventory; mHAQ, modified Health Assessment Questionnaire; SGRQ, Saint George’s Respiratory Questionnaire.Figure 1.Frequency of baseline DMARD use and proportion with any disruption at COVID-19 onset.ConclusionDMARD disruption, SARD flare, and prolonged symptoms were common in this prospective study of COVID-19 survivors with SARDs. Those with prolonged COVID-19 symptom duration, defined as ≥28 days, had higher SARD activity, more pain, and more fatigue compared to those without prolonged symptoms. These findings suggest that post-acute sequelae of COVID-19 may have a large impact on underlying SARD activity and quality of life.Disclosure of InterestsMichael Di Iorio: None declared, Claire Cook: None declared, Kathleen Vanni: None declared, Naomi Patel Consultant of: Receives consulting fees from FVC Health unrelated to this work., Kristin D’Silva: None declared, Xiaoqing Fu: None declared, Jiaqi Wang: None declared, Lauren Prisco: None declared, Emily Kowalski: None declared, Alessandra Zaccardelli: None declared, Lily Martin: None declared, Grace Qian: None declared, Tiffany Hsu: None declared, Zachary Wallace Consultant of: Receives consulting fees from Viela Bio, Zenas BioPharma, and MedPace unrelated to this work., Grant/research support from: Receives research support from Bristol-Myers Squibb and Principia/Sanofi., Jeffrey Sparks Consultant of: Receives consultant fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer unrelated to this work., Grant/research support from: Receives research support from Bristol Myers Squibb.

BackgroundRA has been associated with poor COVID-19 outcomes, but few studies have investigated outcomes in RA features such as interstitial lung disease.ObjectivesTo assess COVID-19 outcomes in patients with RA overall, and those with and without ILD, compared to general population comparators.MethodsA multicenter, retrospective cohort study was conducted at Mayo Clinic (19 hospitals and affiliated outpatient centers in 4 states) and Mass General Brigham (14 hospitals and affiliated outpatient centers in New England). Consecutive patients with RA meeting ACR/EULAR criteria and a positive COVID-19 test from March 1, 2020 through June 6, 2021 were matched 1:5 on age, sex, race, and COVID-19 test date with general population comparators without RA. RA features assessed included: RA-ILD per Bongartz criteria [1], duration, rheumatoid factor (RF), cyclic citrullinated peptide antibody (CCP), bone erosions, and treatments. The primary outcome was a composite of hospitalization or death following COVID-19 diagnosis. We used multivariable Cox regression to investigate the association of RA, and features such as ILD, with COVID-19 outcomes compared to matched comparators.ResultsWe analyzed 582 patients with RA and 2892 comparators without RA, all with COVID-19. Mean age was 62 years, 51% were female, and 79% were White. Mean RA duration was 11 years, 67% were seropositive (52% RF+ and 54% CCP+), 27% had bone erosions, 28% were on steroids, and 79% were on DMARDs. 50/582 (9%) patients with RA had ILD.The COVID-19 hospitalization or death rate for RA patients was higher than comparators (3.0 per 1,000 days [95% CI 2.5-3.6] vs. 1.9 per 1,000 days [95% CI 1.7-2.1], respectively). Overall, RA patients had a 53% higher risk of hospitalization or death than comparators after adjustment (95% CI 1.20-1.94).Among those with RA-ILD, the hospitalization or death rate was significantly higher than comparators (10.9 [95% CI 6.7-15.2] vs. 2.5 per 1,000 days [1.8-3.2], respectively). RA-ILD was associated with nearly 3-fold higher risk for hospitalization or death than comparators (multivariable HR 2.84 [95% CI 1.64-4.91], Table 1). There was a significant interaction between RA/comparator status and presence/absence of ILD for risk of severe COVID-19 (pTable 1.Frequencies, proportions, and hazard ratios for COVID-19 outcomes, comparing all RA patients, and subgroups with or without RA-ILD, to matched comparators.COVID-19 OutcomesAll RA Patients (n=582)RA-ILD (n=50)RA Patients without ILD (n=532)Comparators (n=2,892)Hospitalization, n (%)121 (21)24 (48)97 (18)402 (14)Unadjusted HR (95% CI)1.58 (1.27, 1.96)2.65 (1.71, 4.09)1.43 (1.12, 1.82)Ref.Adjusted* HR (95% CI)1.45 (1.14, 1.83)2.35 (1.38, 4.00)1.31 (1.00, 1.70)Ref.Death, n (%)26 (4)9 (18)17 (3)63 (2)Unadjusted HR (95% CI)1.72 (0.98, 3.01)5.88 (2.07, 16.71)1.13 (0.56, 2.29)Ref.Adjusted* HR (95% CI)1.24 (0.66, 2.32)13.94 (4.30, 45.18)0.75 (0.35, 1.63)Ref.Hospitalization or death, n (%)126 (22)25 (50)101 (19)419 (14)Unadjusted HR (95% CI)1.66 (1.33, 2.07)3.01 (1.93, 4.70)1.47 (1.14, 1.89)Ref.Adjusted* HR (95% CI)1.53 (1.20, 1.94)2.84 (1.64, 4.91)1.34 (1.02, 1.77)Ref.*Adjusted for age, sex, race, and smokingFigure 1.Multivariable hazard ratios for the composite outcome of hospitalization or death from COVID-19, comparing all RA and subgroups by serostatus, bone erosions, and ILD to matched comparators without RA.ConclusionWe confirmed that RA was associated with severe COVID-19 outcomes compared to the general population. We found evidence that ILD may be an effect modifier for the relationship between RA and severe COVID-19 outcomes, but RA subgroups defined by serostatus and bone erosions had similarly elevated risk. These findings suggest that ILD or its treatment may be a major contributor to severe COVID-19 outcomes in RA.References[1]Bongartz, T, et al, Arthritis Rheum. 2010 Jun;62(6):1583-91.Disclosure of InterestsNone declared

Background Engraftment syndrome (ES) is a common complication of autologous hematopoietic cell transplantation (HCT). The difference in incidence of ES between melphalan formulations has not been widely reported throughout the literature and would allow for a more comprehensive understanding of the advantages and disadvantages of both melphalan formulations. Patients and methods This retrospective, single-center, observational study evaluated 83 adult multiple myeloma and immunoglobulin light chain amyloidosis patients who received either propylene glycol-containing (PG) or propylene glycol-free (PG-free) melphalan 140 mg/m2 as single-agent conditioning chemotherapy for autologous HCT from May 31, 2015 to May 31, 2019. The primary outcome was to assess the incidence of ES, as defined using the Maiolino criteria, with both melphalan formulations. Secondary outcomes included an analysis of potential risk factors for the development of ES, as well as an evaluation of overall length of stay (LOS). Results The incidence of ES for PG and PG-free melphalan did not differ significantly, 14/39 (35.9%) and 12/44 (27.3%) (P = 0.4), respectively. No potential risk factors for ES were identified on multivariate logistic regression analysis. A statistically significant difference in number of days to engraftment was identified for PG and PG-free melphalan, 15.56 vs. 13.82 days (P = 0.01), respectively; although, this did not translate to a decrease in LOS, 19.9 vs. 18.59 days (P = 0.14). Conclusions The incidence of ES did not differ significantly between melphalan formulations. Future research is needed to determine whether the faster time to engraftment seen with PG-free melphalan may translate to a decrease in LOS.

Background To compare fully covered bi-flanged metal stents (BFMS) and lumen-apposing metal stents (LAMS) for endoscopic ultrasound (EUS)-guided drainage/debridement of pancreatic walled-off necrosis (WON). Methods Patients with WON managed by EUS-guided therapy were divided into those who underwent: 1) drainage using BFMS; and 2) drainage using LAMS and scheduled direct endoscopic necrosectomy (DEN). Clinical success (resolution of the WON), technical success (successful stent placement), and adverse events (AEs) were evaluated. Results 387 patients underwent WON endoscopic drainage, 205 using BFMS and 182 using LAMS. The clinical success in the BFMS or LAMS groups were similar (197 [96.1%] vs. 174 [95.6%]; P=0.81). Median number of procedures required for WON resolution was significantly lower in BFMS compared to LAMS (2 vs. 3, P

Introduction. We evaluate whether a combination of financial incentives and deposit contracts improves cessation rates among low- to moderate-income smokers. Methods. We randomly assigned 311 smokers covered by Medicaid at 12 health clinics in Connecticut to usual care or one of the three treatment arms. Each treatment arm received financial incentives for two months and either (i) nothing further (“incentives only”), (ii) the option to start a deposit contract with incentive earnings after the incentives ended (“commitment”), or (iii) the option to precommit any earned incentives into a deposit contract starting after the incentives ended (“precommitment”). Smoking cessation was confirmed biochemically at two, six, and twelve months. Results. At two, six, and twelve months after baseline, our estimated treatment effects on cessation are positive but imprecise, with confidence intervals containing effect sizes estimated by prior studies of financial incentives alone and deposit contracts alone. At two months, the odds ratio for quitting was 1.4 in the incentive-only condition (95% CI: 0.5 to 3.5), 2.0 for incentives followed by commitment (95% CI: 0.6 to 6.1), and 1.9 for incentives and precommitment (95% CI: 0.7 to 5.3). Conclusions. A combined incentive and deposit contract program for Medicaid enrollees, with incentives offering up to $300 for smoking cessation and use of support services, produced a positive but imprecisely estimated effect on biochemically verified cessation relative to usual care and with no detectable difference in cessation rates between the different treatment arms.

Decades of evidence reveal a complicated relationship between mammograms and mortality. Mammograms may detect deadly cancers early, but they may also lead to the diagnosis and potentially fatal treatment of cancers that would never progress to cause symptoms. I provide a brief history of the evidence on mammograms and mortality, focusing on evidence from clinical trials, and I discuss how this evidence informs mammography guidelines. I then explore the evolution of all-cause mortality relative to breast cancer mortality within an influential clinical trial. I conclude with some responses to the evolving evidence.

Porous protein crystals provide a template for binding and organizing guest macromolecules. Peroxidase, oxidase, and reductase enzymes immobilized in protein crystals retained activity in single-crystal and bulk assay formats. Several binding strategies, including metal affinity and physical entrapment, were employed to encourage enzyme adsorption into the protein crystals and to retain the enzymes for multiple recycles. Immobilized enzymes had lower activity compared to free enzyme in solution, in part due to diffusion limitations of substrate within the crystal pores. However, the immobilized enzymes were long-term stable and showed increased thermal tolerance. The potential applications of enzyme-laden crystals as sensing devices, delivery capsules, and microreactors motivate future development of this technology.

Childhood and adolescent obesity are epidemic in the United States. Because of this crisis, schools in our nation have been challenged to develop strategies to decrease the number of overweight and obese youth, with many states passing legislation requiring body mass index (BMI) monitoring by the school. This may be done as a screening or surveillance program depending on the state, with some states requiring notification to parents. As school nurses are often the only health professional in the school, they are typically the employee tasked with leading the BMI screening programs. School nurses, both in states requiring and in states without requirements for BMI screening programs, must be knowledgeable about evidence-based programs and strategies that have promise in reversing the obesity epidemic. Indeed, school nurses are in a position to be an active participant in the fight against the obesity and overweight crisis.

Background and Aims ERCP performed through previously placed enteral stents is an uncommon procedure without a significant amount of supporting literature and with a wide reported range of technical success. The purpose of this study was to evaluate and better define the technical feasibility and safety of performing ERCP through enteral stents in patients with combined malignant biliary and gastric outlet obstruction. Methods We conducted a multicenter, retrospective study on 71 patients with combined gastric outlet and biliary obstruction who underwent ERCP through a previously placed enteral stent at 2 tertiary care centers. Outcomes included but were not limited to technical success, clinical success, need for repeat ERCP, adverse events, and survival time. Results Overall technical success was achieved in 60 of 71 patients (85%), with technical success of 40 of 46 (87%) in type I obstructions (gastric outlet obstruction above the ampulla), 16 of 21 (76%) in type II obstructions (gastric outlet obstruction at the level of the ampulla), and 4 of 4 (100%) in type III obstructions (gastric outlet obstruction distal to the ampulla). In general, patients who achieved technical success also achieved clinical success. Adverse events occurred in 3 patients (3/71): 2 patients with acute cholangitis and 1 patient with perforation. Average survival time after the procedure was 4.6 months overall. Conclusions ERCP performed through enteral stents is safe, with a high technical and clinical success rate, but may be more technically challenging in the setting of type II obstructions. This procedure could be considered first line in the unique setting that a patient requires ERCP through a previously placed enteral stent for malignant gastric outlet and biliary obstruction.

European anurans are prey for a variety of predators, against which they have evolved a range of defense behaviors. We investigated defensive behaviors of three European anurans: the Common Toad (Bufo bufo), the Common Frog (Rana temporaria), and the Edible Frog (Pelophylax esculentus) during interactions with a predator (hedgehog) and a control stimulus (rabbit). We hypothesized that (H1) due to small capacity to flee quickly from a predator, B. bufo has evolved a more diverse repertoire of behavioral defenses than the ranids, R. temporaria and P. esculentus. We also hypothesized that (H2) B. bufo can minimize the secretion of metabolically costly poison through behavioral control. According to our predictions, the repertoire of defensive behaviors was more complex in B. bufo than in the ranids. Also, the number of threatening behaviors was higher in toads than in both frog species. Fleeing was the most common response employed by all tested anurans. We report a new anti-predator behavior in the Common T...

Being venomous should help a predator to maximize foraging gain, reduce handling time, and hoard food. Shrews are a good model for study of the relationship between venomousness and optimal foraging as they have to be highly efficient foragers (because of extremely high energy requirements) and comprise a few venomous species. We hypothesized that venom facilitates shrews to overpower large prey and enables hoarding of (mainly large) prey in a comatose state. We compared hunting and hoarding behaviors of the venomous Neomys fodiens and the nonvenomous Sorex araneus, which were allowed to forage on live prey differing in body size. As we predicted, small invertebrates were immediately consumed by both shrew species, whereas larger ones were immobilized and hoarded. Smaller S. araneus hoarded proportionally more food than larger N. fodiens. Although different ways of prey immobilization were expected (venomous paralyzing by N. fodiens and mechanical damage by S. araneus), both species seemed to use mechanical immobilization. However, N. fodiens required significantly less time than S. araneus to subdue prey of proportionally similar sizes and this difference grew with the increase in prey mass. Only N. fodiens was able to overpower and kill frogs (but not larger toads). We concluded that the relatively weak venom of N. fodiens is helpful in overpowering and hoarding mainly medium-sized prey. Thus, venomousness helps N. fodiens to optimize its foraging as it reduces prey handling time, enables it to gain larger energy portions, and facilitates food hoarding, which reduces foraging time.

Anuran toxins released from the skin glands are involved in defence against predators and microorganisms. Secretion from parotoid macroglands of bufonid toads is a rich source of bioactive compounds with the cytotoxic, cardiotoxic and hemolytic activity. Bufadienolides are considered the most toxic components of the toad poison, whereas the protein properties are largely unknown. In the present work, we analysed the cardio-, myo-, and neurotropic activity of extract and the selected proteins from Bufo bufo parotoids in in vitro physiological bioassays carried out on two standard model organisms: beetles and frogs. Our results demonstrate a strong cardioactivity of B. bufo gland extract. The toad poison stimulates (by 16%) the contractility of the insect heart and displays the cardioinhibitory effect on the frog heartbeat frequency (a 27% decrease), coupled with an irreversible cardiac arrest. The gland extract also exhibits significant myotropic properties (a 10% decrease in the muscle contraction force), whereas its neuroactivity remains low (a 4% decrease in the nerve conduction velocity). Among identified peptides present in the B. bufo parotoid extract are serine proteases, muscle creatine kinase, phospholipid hydroperoxide glutathione peroxidase, cytotoxic T-lymphocyte protein, etc. Some proteins contribute to the cardioinhibitory effect. Certain compounds display the paralytic (myo- and neurotropic) properties. As the toad gland extract exhibits a strong cardiotoxic activity, we conclude that the poison is a potent agent capable of slaying a predator. Our results also provide the guides for the use of toad poison-peptides in therapeutics and new drug development.

Immunocastraten worden minstens vier weken vóór de slacht gevaccineerd om berengeur effectief te reduceren en de vleeskwaliteit te verbeteren ten opzichte van intacte beren. Uit een onderzoek van ILVO en UGent (LANUPRO) blijkt dat het toepassen van de tweede injectie (op acht of zes weken vóór de slacht) echter niet helpt om de vleeskwaliteit verder te verbeteren. Het blijkt zelfs economisch minder voordelig te zijn voor de varkenshouder aangezien de vroeg-gevaccineerde immunocastraten een hogere voederconversie en lagere slachtkwaliteit hebben.