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A modular approach to underexplored, unsymmetrical [1]benzothieno[3,2-b][1]benzothiophene (BTBT) scaffolds delivers a library of BTBT materials from readily available coupling partners by combining a transition-metal free Pummerer CH–CH-type cross-coupling and a Newman–Kwart reaction. This effective approach to unsymmetrical BTBT materials has allowed their properties to be studied. In particular, tuning the functional groups on the BTBT scaffold allows the solid-state assembly and molecular orbital energy levels to be modulated. Investigation of the charge transport properties of BTBT-containing small-molecule:polymer blends revealed the importance of molecular ordering during phase segregation and matching the highest occupied molecular orbital energy level with that of the semiconducting polymer binder, polyindacenodithiophene-benzothiadiazole (PIDTBT). The hole mobilities extracted from transistors fabricated using blends of PIDTBT with phenyl or methoxy functionalized unsymmetrical BTBTs were double those measured for devices fabricated using pristine PIDTBT. This study underscores the value of the synthetic methodology in providing a platform from which to study structure–property relationships in an underrepresented family of unsymmetrical BTBT molecular semiconductors., A modular approach to underexplored, unsymmetrical [1]benzothieno[3,2-b][1]benzothiophene (BTBT) scaffolds, combining a transition-metal free Pummerer CH–CH-type cross-coupling and a Newman–Kwart reaction, delivers a library of BTBT materials.

Background and Aims Laterally spreading lesions (LSLs) in the duodenum are conventionally treated by EMR. Recurrence is commonly encountered and can be difficult to treat safely due to the unique anatomic characteristics of the duodenum. Auxiliary techniques designed to prevent recurrence have not been described. Methods We sought to evaluate the effectiveness of thermal ablation of the defect margin after EMR (EMR-T) in reducing recurrence at first surveillance endoscopy (SE1, scheduled at 6 months) in a single tertiary referral center. All duodenal LSLs ≥10 mm referred for EMR were eligible. After successful EMR, thermal ablation was performed using snare-tip soft coagulation around the entire circumference of the resection defect. The primary outcome was the frequency of recurrence at SE1. A previous, well-characterized, prospective cohort of duodenal LSLs ≥10 mm treated by conventional EMR was the comparator. Results Over 43 months up to October 2019, 54 LSLs underwent EMR-T. One hundred twenty-five LSLs underwent conventional EMR in the comparator group. Patient and lesion characteristics were similar between the groups. Recurrence was significantly lower in the EMR-T group compared with the conventional EMR group (1 of 49 [2.3%] vs 19 of 108 [17.6%]; P = .01). No difference in technical success, EMR-related adverse outcomes, or referral to surgery were identified between the groups. Conclusions EMR-T significantly reduces the frequency of recurrence for duodenal LSLs. This technique is safe in the duodenum and has the potential to significantly improve the effectiveness of duodenal EMR. (Clinical trial registration number: NCT02306603.)

Elevated levels of circulating cobalt ions have been linked with a wide range of systemic complications including neurological, endocrine, and cardiovascular symptoms. Case reports of patients with elevated blood cobalt ions have described significant cardiovascular complications including cardiomyopathy. However, correlation between the actual level of circulating cobalt and extent of cardiovascular injury has not previously been performed. This review examines evidence from the literature for a link between elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties and cardiomyopathy. Correlation between low, moderate, and high blood cobalt with cardiovascular complications has been considered. Elevated blood cobalt at levels over 250 µg/l have been shown to be a risk factor for developing systemic complications and published case reports document cardiomyopathy, cardiac transplantation, and death in patients with severely elevated blood cobalt ions. However, it is not clear that there is a hard cut-off value and cardiac dysfunction may occur at lower levels. Clinical and laboratory research has found conflicting evidence of cobalt-induced cardiomyopathy in patients with MoM hips. Further work needs to be done to clarify the link between severely elevated blood cobalt ions and cardiomyopathy. Cite this article: Bone Joint Res 2021;10(6):340–347.

Background and Purpose: The DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) randomized clinical trial demonstrated the efficacy of endovascular therapy in treating ischemic stroke 6 to 16 hours after onset, resulting in better functional outcomes than standard medical therapy alone. The objective of this secondary analysis is to analyze the effect of late-window endovascular treatment of ischemic stroke on quality of life (QoL) outcomes. Methods: Patients (n=182) who presented between 6 and 16 hours after they were last known to be well with acute anterior circulation ischemic stroke were randomized to endovascular thrombectomy plus standard medical therapy or standard medical therapy alone and followed-up through 90 days poststroke. QoL at day 90 was assessed with the QoL in Neurological Disorders measurement tool. Results: Of the 146 subjects alive at day 90, 136 (95%) filled out QoL in Neurological Disorders short forms. Patients treated with endovascular therapy had better QoL scores in each domain: mobility, social participation, cognitive function, and depression ( P 2 =0.82), a moderate proportion in social participation (Rs 2 =0.62), and a low proportion in cognition (Rs 2 =0.31) and depression (Rs 2 =0.19). Conclusions: Patients treated with endovascular therapy 6 to 16 hours after stroke have better QoL than patients treated with medical therapy alone, including better mobility, more social participation, superior cognition, and less depression. The modified Rankin Scale fails to capture patients’ outcomes in cognition and depression, which should therefore be assessed with dedicated QoL tools. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02586415.

Background and Aims Although sporadic duodenal and/or ampullary adenomas (DAs) are uncommon, they are increasingly diagnosed during upper endoscopy. These patients have a 3- to 7-fold increased risk of colonic neoplasia compared with the normal population. It is unknown, however, whether they also have an increased risk of additional small-bowel (SB) polyps. Our aim was to establish the prevalence of SB polyps in patients with DA. Methods In a single-center, prospective study, we used video capsule endoscopy (VCE) to investigate the prevalence of SB polyps in patients with a DA compared with patients undergoing VCE for obscure GI bleeding or iron deficiency anemia. Results Over 25 months, 201 patients were enrolled in the study; the mean age was 65 years and 47% were male. There were 101 control patients and 100 cases of DA cases (mean size, 30 mm (range, 10-80 mm)). We did not identify any SB polyps in either group. Colonic polyps were found more frequently in the DA group compared with controls (61% versus 37%, respectively (P =.002)). Advanced colonic adenoma (high-grade dysplasia, >10 mm, villous histology) were found in 18% of the DA group and 5% of the control group (P =.018). Conclusion Our data suggest that patients with a DA are not at risk for additional SB polyps and hence do not support screening with VCE. However, colonoscopy is mandatory due to the significantly higher risk of colonic polyps including advanced adenomas. (Clinical trial registration number: NCT02470416.)

In the midst of the SARS-CoV-2 pandemic, the US Association of American Medical Colleges (AAMC) required residency programme transition from in-person to virtual interviews for all applicants. The new virtual format upended a system that has relied on programmes and applicants balancing the likelihood of acceptance with the financial and time demands of cross-country travel. In this commentary, we address the history of residency interviewing in the USA and the emerging changes that are taking place in light of virtual interviews. We discuss the advantages of the new online format, including the reduced cost for applicants and programmes, as well as the decreased carbon footprint. We also discuss the inequities of virtual interviewing, involving a national maldistribution of interviews to only the top-tier candidates. We share previously unpublished data on the number of virtual interviews accepted by Stanford's 2020 residency applicants, compared with those conducted in person in 2019. We find Stanford applicants in all fields accepted more interviews: from a mean of 8 in 2019 to 14 in 2020, a change of 160% on average. Despite this, only half of Stanford 2020 applicants interviewing in the virtual format thought they had accepted more interviews than they would have in person. We comment on how transitions to online interviewing may be affecting medical schools and applicants disproportionately. Ultimately, we highlight the need and offer ideas for additional regulation on behalf of the AAMC to ensure a more equitable distribution of interview opportunities.

INTRODUCTION Endoscopic mucosal resection (EMR) is an effective therapy for naive large nonpedunculated colorectal polyps (N-LNPCPs). The best approach for the treatment of previously attempted LNPCPs (PA-LNPCPs) is undetermined. METHODS EMR performance for PA-LNPCPs was evaluated in a prospective observational cohort of LNPCPs ≥20 mm. Efficacy was measured by technical success (removal of all visible polypoid tissue during index EMR) and recurrence at first surveillance colonoscopy (SC1). Safety was assessed by clinically significant intraprocedural bleeding, deep mural injury types III-V, clinically significant post-EMR bleeding, and delayed perforation. RESULTS From January 2012 to October 2019, 158 PA-LNPCPs and 1,134 N-LNPCPs underwent EMR. Median PA-LNPCP size was 30 mm (interquartile range 25-46 mm). Technical success was 93.0% and increased to 95.6% after adjusting for 2-stage EMR. Cold-forceps avulsion with adjuvant snare-tip soft coagulation (CAST) was required for nonlifting polypoid tissue in 73 (46.2%). Median time to SC1 was 6 months (interquartile range 5-7 months). Recurrence occurred in 9 (7.8%). No recurrence was identified among 65 PA-LNPCPs which underwent margin thermal ablation at SC1 vs 9 (18.0%; P < 0.001) which did not. There were significant differences in resection duration (35 vs 25 minutes; P < 0.001), technical success (93.0% vs 96.6%; P = 0.026), and use of CAST (46.2% vs 7.6%; P < 0.001), between PA-LNPCPs and N-LNPCPs. When adjusting for 2-stage EMR, no difference in technical success was identified (95.6% vs 97.8%; P = 0.100). No differences in adverse events or recurrence were identified. DISCUSSION EMR, using auxillary techniques where necessary, can achieve high technical success and low recurrence frequencies for PA-LNPCPs.

ObjectiveLarge (≥20 mm) sessile serrated lesions (L-SSL) are premalignant lesions that require endoscopic removal. Endoscopic mucosal resection (EMR) is the existing standard of care but carries some risk of adverse events including clinically significant post-EMR bleeding and deep mural injury (DMI). The respective risk-effectiveness ratio of piecemeal cold snare polypectomy (p-CSP) in L-SSL management is not fully known.DesignConsecutive patients referred for L-SSL management were treated by p-CSP from April 2016 to January 2020 or by conventional EMR in the preceding period between July 2008 and March 2016 at four Australian tertiary centres. Surveillance colonoscopies were conducted at 6 months (SC1) and 18 months (SC2). Outcomes on technical success, adverse events and recurrence were documented prospectively and then compared retrospectively between the subsequent time periods.ResultsA total of 562 L-SSL in 474 patients were evaluated of which 156 L-SSL in 121 patients were treated by p-CSP and 406 L-SSL in 353 patients by EMR. Technical success was equal in both periods (100.0% (n=156) vs 99.0% (n=402)). No adverse events occurred in p-CSP, whereas delayed bleeding and DMI were encountered in 5.1% (n=18) and 3.4% (n=12) of L-SSL treated by EMR, respectively. Recurrence rates following p-CSP were similar to EMR at 4.3% (n=4) versus 4.6% (n=14) and 2.0% (n=1) versus 1.2% (n=3) for surveillance colonoscopy (SC)1 and SC2, respectively.ConclusionsIn a historical comparison on the endoscopic management of L-SSL, p-CSP is technically equally efficacious to EMR but virtually eliminates the risk of delayed bleeding and perforation. p-CSP should therefore be considered as the new standard of care for L-SSL treatment.

Background Osteosarcoma (OSA) in dogs is an aggressive bone tumor with frequent chemotherapy failure and translational relevance for human health. Hypothesis/objectives We hypothesized that dogs with OSA could be treated safely by ex vivo activated T-cells that were generated by autologous cancer vaccination and supported by interleukin-2 (IL-2) treatment with survival more than twice that reported for amputation alone. Animals Osteosarcoma-bearing dogs (n = 14) were enrolled in a single-arm prospective trial after complete staging before amputation. Four healthy dogs also were treated in a safety study. Methods Autologous cancer cell vaccinations were administered intradermally and dogs underwent leukapheresis. Mononuclear cell products were stimulated ex vivo with a T-cell-activating agent. Activated product was transfused and 5 SC IL-2 injections were administered q48h. Dogs were monitored for metastasis by thoracic radiography every 3 months. Results Autologous cancer cell vaccine and activated cellular therapy (ACT) products were successfully generated. Toxicity was minimal after premedicants were instituted before ACT. With premedication, all toxicities were grade I/II. Median disease-free interval for all dogs was 213 days. One dog developed cutaneous metastasis but then experienced spontaneous complete remission. Median survival time for all dogs was 415 days. Five dogs survived >730 days. Conclusions and clinical importance This immunotherapy protocol without cytotoxic chemotherapy is safe and tolerable. Compared to historical amputation reports, survival was notably prolonged in this group of patients. Additional prospective studies are warranted to elucidate active immunologic mechanisms and further improve disease response and survival.

Background The IDEAL (Idea, Development, Evaluation, Assessment, Long‐term study) framework is a scheme of investigation for innovative surgical therapeutic interventions. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a procedure based on laparoscopy to deliver intraperitoneal chemotherapy for peritoneal metastases, introduced in 2011. The aim of this article was to review literature on PIPAC and assess whether development of the technique has followed the IDEAL framework. Methods A search of MEDLINE and Embase was carried out to identify scientific reports on PIPAC published between January 2000 and February 2019. The studies were categorized according to the IDEAL stages. Results Eighty‐six original research papers on PIPAC were identified. There were 23 stage 0, 18 stage 1, 25 stage 2a and six stage 2b studies. Protocol papers for stage 1, 2b and 3 studies, and trial registrations for stage 2a studies, were also identified. The number of centres publishing reports and the number of publications has increased each year. Overall, there has been progression through the IDEAL stages; however, about 60 per cent of clinical reports published in 2018 were stage 1 Idea‐type studies. Conclusion Since its introduction, studies investigating PIPAC have progressed in line with the IDEAL framework. However, the majority of studies reported recently were stage 0 and 1 studies., This review assesses whether the introduction of pressurized intraperitoneal aerosol chemotherapy has followed the IDEAL (Innovation, Development, Evaluation, Assessment, Long‐term use) framework, and whether the problems with surgical innovation have been addressed. Pipac and review

Hypoxia is associated with neoplastic tissue, protecting cancer cells from death by irradiation and chemotherapy. Identification of hypoxic volume of tumors could optimize patient selection for hypoxia-directed medical, immunological, and radiation therapies. Clostridium novyi-NT (CNV-NT) is an oncolytic bacterium derived from attenuated wild-type Clostridium novyi spores, which germinates exclusively in the anaerobic core of tumors with low-oxygen content. The hypothesis was that 64Cu-ATSM would localize to regions of hypoxia, and that greater hypoxic volume would result in greater germination of Clostridium novyi-NT (CNV-NT). Tumor-bearing companion dogs were recruited to a veterinary clinical trial. Dogs received a CT scan, 18F-FDG PET scan (74 MBq) and 64Cu-ATSM PET scan (74 MBq). Scan regions of interest were defined as the highest 20% of counts/voxel for each PET scan, and regions with voxels overlapping between the two scans. Maximum standardized uptake value (MaxSUV) and threshold volume were calculated. Direct oximetry was performed in select tumors. Tumor types evaluated included nerve sheath tumor (10), apocrine carcinoma (1), melanoma (3) and oral sarcoma (6). MaxSUVATSM ranged from 0.3-6.6. Measured oxygen tension ranged from 0.05-89.9 mmHg. Inverse of MaxSUVATSM had a linear relationship with oxygen tension (R2 = 0.53, P = 0.0048). Hypoxia8 mmHg was associated with an SUVATSM1.0. Hypoxic volume ranged from 0 to 100% of gross tumor volume (GTV) and MaxSUVATSM was positively correlated with hypoxic volume (R = 0.674; P = 0.0001), but not GTV (P = 0.182). Tumor hypoxic volume was heterogeneous in location and distribution. 64Cu-ATSM-avid regions were associated with differential CT attenuation. Hypoxic volume did not predict CNV-NT germination. 64Cu-ATSM PET scanning predicts hypoxia patterns within spontaneously occurring tumors of dogs as measured by direct oxymetry. Total tumor volume does not accurately predict degree or proportion of tumor hypoxia.

Background and Aims Clinically significant post-EMR bleeding (CSPEB) is the most-frequent serious adverse event after EMR of large laterally spreading colonic lesions (LSLs). There is no proven prophylactic therapy, and it remains a significant drawback of EMR. We aimed to systematically describe and evaluate the features of the post-EMR mucosal defect (PED) and their relationship to CSPEB. Methods A prospective study of LSLs referred for EMR at a tertiary center was performed. PEDs without visible features were recorded as bland blue. Nonbland blue (NBB) PED features included size, number, and herniation of submucosal vessels and presence of submucosal hemorrhage, fibrosis, fat, and exposed muscle. NBB PEDs were analyzed for association with CSPEB, defined as bleeding occurring after completion of the procedure necessitating readmission or reintervention. Results From April 2012 to May 2017, 501 lesions in 501 patients were eligible for analysis. The frequency of CSPEB was 30 of 501 (6.0%). More than or equal to 3 visible vessels was a significant predictor of CSPEB (P = .016). None of the following showed a significant correlation with CSPEB: presence of visible vessels, their diameter, herniation, or other nonvascular PED features. Submucosal vessels were more common in the left-sided colon segment (88.6% vs 78.3%, P = .004) and were significantly larger (20.8% vs 12.1% ≥1 mm, P = .037), more numerous (median 4 vessels [interquartile range, 2-7] vs 2 vessels [interquartile range, 1-4], P Conclusions More than or equal to 3 visible vessels within the PED may be predictive for CSPEB and may define a target group for real-time prophylactic intervention. No other endoscopically visible features of the PEDs were predictive of CSPEB. (Clinical trial registration number: NCT03117400 .)

Introduction: The goal of this study is to explore the impact of reperfusion and collateral status on infarct growth in the early and late time windows.Materials and Methods: Seventy patients from the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) with baseline, 24-h, and late follow-up scans were evaluated. Scans were taken with DWI or CTP at time of enrollment (Baseline), with DWI or CT 24-h after enrollment (24-h), and with DWI or CT 5 days after enrollment (Late). Early infarct growth (between baseline and 24-h scans) and late infarct growth (between 24-h and late scans) was assessed for each patient. The impact of collateral and reperfusion status on infarct growth was assessed in univariate and multivariate regression.Results: The median early infarct growth was 30.3 ml (IQR 16.4–74.5) and the median late infarct growth was 6.7 ml (IQR −3.5–21.6) in the overall sample. Patients with poor collaterals showed greater early infarct growth (Median 58.5 ml; IQR 18.6–125.6) compared to patients with good collaterals (Median 28.4 ml; IQR 15.8–49.3, unadjusted p = 0.04, adjusted p = 0.06) but showed no difference in late infarct growth. In contrast, patients who reperfused showed no reduction in early infarct growth but showed reduced late infarct growth (Median 1.9 ml; IQR −6.1–8.5) compared to patients without reperfusion (Median 11.2 ml; IQR −1.1–27.2, unadjusted p < 0.01, adjusted p = 0.04).Discussion: In the DEFUSE 3 population, poor collaterals predict early infarct growth and absence of reperfusion predicts late infarct growth. These results highlight the need for timely reperfusion therapy, particularly in patients with poor collaterals and indicate that the 24-h timepoint is too early to assess the full impact of reperfusion therapy on infarct growth.Clinical Trial Registration:http://www.clinicaltrials.gov, Unique identifier [NCT02586415].

* Abbreviations: CI — : confidence interval COVID-19 — : coronavirus disease 2019 PCR — : polymerase chain reaction SARS-CoV-2 — : severe acute respiratory syndrome coronavirus 2 Abbott BinaxNOW (a bedside lateral flow immunoassay intended for the qualitative detection of nucleocapsid protein antigen) is widely available under US Food and Drug Administration emergency use authorization for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in symptomatic patients within 7 days of symptom onset. Its diagnostic performance in symptomatic children has not been evaluated. Cross-sectional study of symptomatic children ≤20 years presenting for care to 1 of 2 primary care practices in December 2020, during which time coronavirus disease 2019 (COVID-19) rates were … Address correspondence to Nader Shaikh, MD, MPH, University of Pittsburgh Medical Center, Children’s Hospital of Pittsburgh, 1 Children’s Hospital Dr, 4401 Penn Ave, Pittsburgh, PA 15224. E-mail: nader.shaikh{at}chp.edu

Objective: Ultrasound-guided peripheral intravenous (USPIV) catheters are being placed in emergency department (ED) patients with increasing frequency. USPIV catheters have been shown to improve the success rates of cannulation. It is unknown what the long-term effect of USPIV placement will be on fistula creation in chronic kidney disease (CKD) patients considering these ultrasound-guided peripheral lines often target the same deeper vessels used for fistulas. This study aimed to survey whether emergency medicine programs place restrictions on USPIV placement in patients with CKD stages 3–5. Methods: This was a survey study encompassing all 110 emergency ultrasound fellowship directors in the United States at the time the survey was conducted. Data was collected on an anonymous and voluntary basis. The primary outcome was the number of programs with restrictions on USPIV placement in patients with CKD stage 3 or greater. Results: Of the 56 programs that responded, 21% reported having policies limiting which patients were appropriate for USPIV. Despite this, only one program reported placing restrictions on USPIV in CKD stage 3 or greater ( p Conclusions: Emergency departments do not have or follow restrictions placed on USPIV placement in patients with CKD stage 3 or greater. The use of these veins in the ED may result in thrombosis as well as inflammation and permanent scarring which could negatively impact the ability to utilize those vessels for fistula creation. Future studies are needed to further characterize the impact of USPIV on fistula creation.

Epilepsy is an ancient disease, which has fascinated and frightened scientists and laymen alike. Before the working knowledge of the central nervous system, seizures were shrouded in mystery. In antiquity, this disease was accredited to gods and demonic possession, causing those with epilepsy to be feared and isolated. Epilepsy patients continued to face discrimination through the mid-20th century. This discrimination ranged from lack of access to health insurance, jobs, and marriage equality to forced sterilizations. Despite the strides that have been made, there are still many misconceptions globally regarding epilepsy. Studies show that patients with epilepsy in communities that understand the pathology and cause of seizures are generally more successful in social and educational environments. While there has been progress, there is more work which needs to be done to educate people across the globe about the pathology of epilepsy.

The Ionospheric Data Assimilation Four-Dimensional (IDA4D) technique has been coupled to Sami3, which is another model of the ionosphere (SAMI3). In this application, ground-based and space-based GPS total electron content (TEC) data have been assimilated into SAMI3, while in-situ electron densities, autoscaled ionosonde NmF2, and reference GPS stations have been used for validation. IDA4D/SAMI3 shows that night-time ionospheric localized enhancements (NILE) are formed following geomagnetic storms in November 2003 and August 2018. The NILE phenomenon appears as a moderate, longitudinally extended enhancement of NmF2 at 30°-40°N MLAT, occurring in the late evening (20-24 LT) following much larger enhancements of the equatorial anomaly crests in the main phase of the storms. The NILE appears to be caused by upward and northward plasma transport around the dusk terminator, which is consistent with eastward polarization electric fields. Independent validation confirms the presence of the NILE, and indicates that IDA4D is effective in correcting random errors and systematic biases in SAMI3. In all cases, biases and root-mean-square errors are reduced by the data assimilation, typically by a factor of 2 or more. During the most severe part of the November 2003 storm, the uncorrected ionospheric error on a GPS 3D position at 1LSU (Louisiana) is estimated to exceed 34 m. The IDA4D/SAMI3 specification is effective in correcting this down to 10 m.

Background & Aims Although perforation is the most feared adverse event associated with endoscopic mucosal resection (EMR), limited data exists concerning its management. Therefore, we sought to evaluate the short- and long-term outcomes of intra-procedural deep mural injury (DMI) in an international multi-center observational cohort of large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs). Methods Consecutive patients who underwent EMR for a LNPCP ≥20 mm were evaluated. Significant DMI (S-DMI) was defined as Sydney DMI Classification type III (muscularis propria injury, target sign) or type IV/V (perforation without or with contamination, respectively). The primary outcome was successful S-DMI defect closure. Secondary outcomes included technical success (removal of all visible polypoid tissue during index EMR), surgical referral and recurrence at first surveillance colonscopy (SC1). Results Between July 2008 to May 2020, 3717 LNPCPs underwent EMR. Median lesion size was 35mm (interquartile range (IQR) 25 to 45mm). Significant DMI was identified in 101 cases (2.7%), with successful defect closure in 98 (97.0%) using a median of 4 through-the-scope clips (TTSCs; IQR 3 to 6 TTSCs). Three (3.0%) patients underwent S-DMI-related urgent surgery. Technical success was achieved in 94 (93.1%) patients, with 46 (45.5%) admitted to hospital (median duration 1 day; IQR 1 to 2 days). Comparing LNPCPs with and without S-DMI, no differences in technical success (94 (93.1%) vs 3316 (91.7%); P = .62) or SC1 recurrence (12 (20.0%) vs 363 (13.6%); P = .15) were identified. Conclusions Significant DMI is readily managed endoscopically and does not appear to affect technical success or recurrence.

Background Glioblastoma (GBM) treatment requires access to complex medical services, and the Patient Protection and Affordable Care Act (ACA) sought to expand access to health care, including complex oncologic care. Whether the implementation of the ACA was subsequently associated with changes in 1-year survival in GBM is not known. Methods A retrospective cohort study was performed using the Surveillance, Epidemiology, and End Results (SEER) database. We identified patients with the primary diagnosis of GBM between 2008 and 2016. A multivariable-adjusted Cox proportional hazards model was developed using patient and clinical characteristics to determine the main outcome: the 1-year cumulative probability of death by state expansion status. Results A total of 25 784 patients and 14 355 deaths at 1 year were identified and included in the analysis, 49.7% were older than 65 at diagnosis. Overall 1-year cumulative probability of death for GBM patients in non-expansion versus expansion states did not significantly worsen over the 2 time periods (2008–2010: hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.04–1.19; 2014–2016: HR 1.18, 95% CI 1.09–1.27). In GBM patients younger than age 65 at diagnosis, there was a nonsignificant trend toward the poorer 1-year cumulative probability of death in non-expansion versus expansion states (2008–2010: HR 1.09, 95% CI 0.97–1.22; 2014–2016: HR 1.23, 95% CI 1.09–1.40). Conclusions No differences were found over time in survival for GBM patients in expansion versus non-expansion states. Further study may reveal whether GBM patients diagnosed younger than age 65 in expansion states experienced improvements in 1-year survival.

Background "Readability" of consent forms is vital to the informed consent process. The average human hospital consent form is written at a 10th grade reading level, whereas the average American adult reads at an 8th grade level. Limited information currently exists regarding the readability of veterinary general medical or clinical research consent forms. Hypothesis/objectives The goal of this study was to assess the readability of veterinary clinical trial consent forms from a group of veterinary referral centers recently involved in a working group focused on veterinary clinical trial review and consent. We hypothesized that consent forms would not be optimized for client comprehension and would be written above the National Institutes of Health-recommended 6th grade reading level. Animals None. Methods This was a prospective study assessing a convenience sample of veterinary clinical trial consent forms. Readability was assessed using 3 methods: the Flesch-Kincaid (F-K) Grade Level, Flesch Reading Ease Score (FRES), and the Readability Test Tool (RTT). Results were reported as mean (±SD) and compared across specialties. Results Fifty-three consent forms were evaluated. Mean FRES was 37.5 ± 6.0 (target 60 or higher). Mean F-K Grade Level was 13.0 ± 1.2 and mean RTT grade level was 12.75 ± 1.1 (target 6.0 or lower). There was substantial agreement between F-K and RTT grade level scores (intraclass correlation coefficient 0.8). Conclusions and clinical importance No form evaluated met current health literacy recommendations for readability. A simple and readily available F-K Microsoft-based approach for evaluating grade level was in substantial agreement with other methods, suggesting that this approach might be sufficient for use by clinicians and administrators drafting forms for future studies.

Exosomes are nanovesicles secreted by many cells, including cancer cells. Extensive research has been carried out to validate potential applications of exosomes and to evaluate their efficiency in a wide range of diseases, including cancer. The current knowledge on the origin, biogenesis and composition of exosomes is described. This review then focuses on the use of exosomes in cancer diagnostics and therapeutics.

Carriers used to solubilize taxane chemotherapy drugs cause severe hypersensitivity. Nanoparticle formulations can provide improved dissolution and bioavailability of taxanes. Thus, a nanoparticulate, excipient-free formulation of paclitaxel (CTI52010) was evaluated in tumour-bearing dogs with intravenous and subcutaneous delivery. Tumour-bearing dogs were treated with intravenous CTI52010 using a modified rapid dose escalation scheme. Subcutaneous administration was then planned for a small cohort of dogs for comparison. For both groups, serial blood samples were collected after first dosing for pharmacokinetic analysis by LCMSMS. Tumour response was measured using RECIST criteria. Toxicity was recorded using VCOG-CTCAEv1.1. Fifteen dogs were treated with intravenous delivery at increasing dosages (80-136 mg/m2 ), with one objective response in the urethral component of a prostatic carcinoma (probable transitional cell carcinoma) and four dogs with durable stable disease (two carcinomas, two sarcomas). Pharmacokinetic data indicate a rapid initial clearing of the drug from serum followed by an extended elimination half-life, similar to normal dogs and suggesting reticuloendothelial clearance. Parameters and toxicity were highly variable and a maximally tolerated dosage could not be reliably confirmed. Three dogs were treated with subcutaneous delivery and no drug was detected in circulation, resulting in termination of the study. This novel formulation of paclitaxel is well tolerated in dogs and no unique toxicity or hypersensitivity was noted. The preliminary responses suggest biologic activity. The lack of systemic absorption after subcutaneous administration suggests a possible role for intratumoural anticancer therapy.

Background The SMSA (size, morphology, site, access) polyp scoring system is a method of stratifying the difficulty of polypectomy through assessment of four domains. The aim of this study was to evaluate the ability of SMSA to predict critical outcomes of endoscopic mucosal resection (EMR). Methods We retrospectively applied SMSA to a prospectively collected multicenter database of large colonic laterally spreading lesions (LSLs) ≥ 20 mm referred for EMR. Standard inject-and-resect EMR procedures were performed. The primary end points were correlation of SMSA level with technical success, adverse events, and endoscopic recurrence. Results 2675 lesions in 2675 patients (52.6 % male) underwent EMR. Failed single-session EMR occurred in 124 LSLs (4.6 %) and was predicted by the SMSA score (P Conclusion SMSA is a simple, readily applicable, clinical score that identifies a subgroup of patients who are at increased risk of failed EMR, adverse events, and adenoma recurrence at surveillance colonoscopy. This information may be useful for improving informed consent, planning endoscopy lists, and developing quality control measures for practitioners of EMR, with potential implications for EMR benchmarking and training.

Background: The prognosis of patients with peritoneal metastases is poor. Treatment options are limited because systemically delivered chemotherapy is not usually effective in this type of disease. Pressurised intraperitoneal aerosolised chemotherapy (PIPAC) is a recently developed alternative technology for delivering intraperitoneal chemotherapy, potentially enhancing treatment efficacy. Here, we assess the feasibility of pressurised intraperitoneal aerosolised virotherapy (PIPAV) to deliver a different class of anticancer agents, oncolytic adenoviruses, in vitro and in vivo. Methods: Adenoviral vectors expressing reporter genes green fluorescence protein (Ad5.GFP) or firefly luciferase (Ad5.Luc) were subject to pressurised aerosolisation. The ability of the virus to survive PIPAV was assessed in vitro and in vivo by monitoring reporter gene activity. Wistar rats subjected to PIPAV were assessed for any adverse procedure related events. Results: In vitro transduction assays demonstrated that Ad5 retained viability following pressurised aerosolisation and could transduce permissive cells equally effectively as non-aerosolised control vector. PIPAV was well tolerated in rats, although minimal transduction was observed following intraperitoneal administration. Conclusions: PIPAV appears viable and well tolerated, though in vivo efficacy requires further optimisation.

Introduction Cold snare polypectomy (CSP) is safe and effective for the removal of small adenomas (≤10 mm); however, reported incomplete resection rates (IRRs) vary. The optimal CSP technique, where a wide margin of normal tissue is resected around the target lesion, and snare design have both been hypothesized to reduce the IRR after CSP. We sought to investigate the efficacy of a thin-wire versus thick-wire diameter snare on IRR, using the standardized CSP technique. Methods This was an international multicenter parallel design randomized trial with 17 endoscopists of varying experience (NCT02581254). Patients were randomized in a 1:1 ratio to the use of a thin-wire (0.30 mm) or thick-wire (0.47 mm) snare for CSP of small (≤10 mm) colorectal polyps. The primary end point was the IRR as determined by the histologic assessment of the defect margin after polypectomy. Results Over 52 months to January 2020, 1,393 patients were eligible. A total of 660 patients with polyps (57.4% male) were randomized to a thin-wire (n = 339) or thick-wire (n = 321) snare. The overall IRR of the cohort was 1.5%. There was no significant difference in the IRR between the thin- and thick-wire arms; relative risk-0.41, 95% CI (0.11-1.56), P = 0.21. No significant differences were observed in the rate of adverse events. Discussion In this multicenter randomized trial, CSP is safe and effective with very low rates of incomplete resection independent of the diameter of the snare wire used. This suggests that the optimal operator technique is more important than the snare design alone in minimizing residual adenoma after CSP.

The ability of optical evaluation to diagnose submucosal invasive cancer (SMIC) prior to endoscopic resection of large (≥20 mm) nonpedunculated colorectal polyps (LNPCPs) is critical to inform therapeutic decisions. Prior studies suggest that it is insufficiently accurate to detect SMIC. It is unknown whether lesion morphology influences optical evaluation performance.LNPCPs ≥20 mm referred for endoscopic resection within a prospective, multicenter, observational cohort were evaluated. Optical evaluation was performed prior to endoscopic resection with the optical prediction of SMIC based on established features (Kudo V pit pattern, depressed morphology, rigidity/fixation, ulceration). Optical evaluation performance outcomes were calculated. Outcomes were reported by dominant morphology: nodular (Paris 0-Is/0-IIa+Is) vs flat (Paris 0-IIa/0-IIb) morphology.From July 2013 to July 2019, 1583 LNPCPs (median size 35 [interquartile range, 25-50] mm; 855 flat, 728 nodular) were assessed. SMIC was identified in 146 (9.2%; 95% confidence interval [CI], 7.9%-10.8%). Overall sensitivity and specificity were 67.1% (95% CI, 59.2%-74.2%) and 95.1% (95% CI, 93.9%-96.1%), respectively. The overall SMIC miss rate was 3.0% (95% CI, 2.3%-4.0%). Significant differences in sensitivity (90.9% vs 52.7%), specificity (96.3% vs 93.7%), and SMIC miss rate (0.6% vs 5.9%) between flat and nodular LNPCPs were identified (all P.027). Multiple logistic regression identified size ≥40 mm (odds ratio [OR], 2.0; 95% CI, 1.0-3.8), rectosigmoid location (OR, 2.0; 95% CI, 1.1-3.7), and nodular morphology (OR, 7.2; 95% CI, 2.8-18.9) as predictors of missed SMIC (all P.039).Optical evaluation performance is dependent on lesion morphology. In the absence of features suggestive of SMIC, flat lesions can be presumed benign and be managed accordingly.

Background and Aims The endoscopic management of large nonpedunculated colorectal polyps involving the ileocecal valve (ICV-LNPCPs) remains challenging because of its unique anatomic features, with long-term outcomes inferior to LNPCPs not involving the ICV. We sought to evaluate the impact of technical innovations and advances in the EMR of ICV-LNPCPs. Methods The performance of EMR for ICV-LNPCPs was retrospectively evaluated in a prospective observational cohort of LNPCPs ≥20 mm. Efficacy was measured by clinical success (removal of all polypoid tissue during index EMR and avoidance of surgery) and recurrence at first surveillance colonoscopy. Accounting for the adoption of technical innovations, comparisons were made between an historical cohort (September 2008 to April 2016) and contemporary cohort (May 2016 to October 2020). Safety was evaluated by documenting the frequencies of intraprocedural bleeding, delayed bleeding, deep mural injury, and delayed perforation. Results Between September 2008 to October 2020, 142 ICV-LNPCPs were referred for EMR. Median ICV-LNPCP size was 35 mm (interquartile range, 25-50 mm). When comparing the contemporary (n = 66) and historical cohorts (n = 76) of ICV-LNPCPs, there were significant differences in clinical success (93.9% vs 77.6%, P = .006) and recurrence (4.6% vs 21.0%, P = .019). Conclusions With technical advances, ICV-LNPCPs can be effectively and safely managed by EMR, independent of lesion complexity. Most patients experience excellent outcomes and avoid surgery.

Background and study aims Large series suggest endoscopic mucosal resection is safe and effective for the removal of large (≥ 10 mm) sessile serrated polyps (SSPs), but it exposes the patient to the risks of electrocautery, including delayed bleeding. We examined the feasibility and safety of piecemeal cold snare polypectomy (pCSP) for the resection of large SSPs. Methods Sequential large SSPs (10 – 35 mm) without endoscopic evidence of dysplasia referred over 12 months to a tertiary endoscopy center were considered for pCSP. A thin-wire snare was used in all cases. Submucosal injection was not performed. High definition imaging of the defect margin was used to ensure the absence of residual serrated tissue. Adverse events were assessed at 2 weeks and surveillance was planned for between 6 and 12 months. Results 41 SSPs were completely removed by pCSP in 34 patients. The median SSP size was 15 mm (interquartile range [IQR] 14.5 – 20 mm; range 10 – 35 mm). The median procedure duration was 4.5 minutes (IQR 1.4 – 6.3 minutes). There was no evidence of perforation or significant intraprocedural bleeding. At 2-week follow-up, there were no significant adverse events, including delayed bleeding and post polypectomy syndrome. First follow-up has been undertaken for 15 /41 lesions at a median of 6 months with no evidence of recurrence. Conclusions There is potential for pCSP to become the standard of care for non-dysplastic large SSPs. This could reduce the burden of removing SSPs on patients and healthcare systems, particularly by avoidance of delayed bleeding.

Background Transitional cell carcinoma is the most common bladder cancer of dogs. Cisplatin combined with piroxicam provides superior response rates, but unacceptable rates of nephrotoxicity. Tavocept is a chemoprotectant that has mitigated cisplatin toxicity and decreased the required infusion/diuresis volume in clinical trials in humans. Hypothesis/Objectives We hypothesized that Tavocept would decrease diuresis volume and time and facilitate safe administration of a cisplatin/piroxicam protocol to dogs with bladder cancer. Secondary objectives were to compare response rate and survival times to an historical comparator group treated without Tavocept. Animals Fourteen client-owned dogs were prospectively enrolled. Methods Tumor volume was measured by computed tomography at days 0, 42, and 84. Dogs received combination Tavocept/cisplatin with a shortened diuresis protocol. A total of 4 doses was planned, with concurrent administration of piroxicam. Serial biochemical analyses were evaluated for azotemia. Results A 90-minute infusion/diuresis time was used for all dogs. Three dogs (21%) had concurrent increases in serum creatinine (>2.0 mg/dL) and BUN (>42 mg/dL) concentrations; 2 of these dogs were isosthenuric. This frequency of nephrotoxicity is significantly less (P = 0.0406) than that of an historical control group treated without Tavocept. Overall response rate was 27%. Median survival time was comparable to historical controls (253 vs. 246 days). Conclusions and Clinical Importance Tavocept decreased the required diuresis time with cisplatin from > 6 hours to 90 minutes, while also decreasing occurrence of azotemia. Survival time was comparable, but the response rate was inferior to an historical comparator group. Further evaluation in other tumors susceptible to platinum agents is warranted.

© 2017 Elsevier Ltd Background On Aug 14, 2014, the US Food and Drug Administration approved the antiangiogenesis drug bevacizumab for women with advanced cervical cancer on the basis of improved overall survival (OS) after the second interim analysis (in 2012) of 271 deaths in the Gynecologic Oncology Group (GOG) 240 trial. In this study, we report the prespecified final analysis of the primary objectives, OS and adverse events. Methods In this randomised, controlled, open-label, phase 3 trial, we recruited patients with metastatic, persistent, or recurrent cervical carcinoma from 81 centres in the USA, Canada, and Spain. Inclusion criteria included a GOG performance status score of 0 or 1; adequate renal, hepatic, and bone marrow function; adequately anticoagulated thromboembolism; a urine protein to creatinine ratio of less than 1; and measurable disease. Patients who had received chemotherapy for recurrence and those with non-healing wounds or active bleeding conditions were ineligible. We randomly allocated patients 1:1:1:1 (blocking used; block size of four) to intravenous chemotherapy of either cisplatin (50 mg/m2on day 1 or 2) plus paclitaxel (135 mg/m2or 175 mg/m2on day 1) or topotecan (0·75 mg/m2on days 1–3) plus paclitaxel (175 mg/m2on day 1) with or without intravenous bevacizumab (15 mg/kg on day 1) in 21 day cycles until disease progression, unacceptable toxic effects, voluntary withdrawal by the patient, or complete response. We stratified randomisation by GOG performance status (0 vs 1), previous radiosensitising platinum-based chemotherapy, and disease status (recurrent or persistent vs metastatic). We gave treatment open label. Primary outcomes were OS (analysed in the intention-to-treat population) and adverse events (analysed in all patients who received treatment and submitted adverse event information), assessed at the second interim and final analysis by the masked Data and Safety Monitoring Board. The cutoff for final analysis was 450 patients with 346 deaths. This trial is registered with ClinicalTrials.gov, number NCT00803062. Findings Between April 6, 2009, and Jan 3, 2012, we enrolled 452 patients (225 [50%] in the two chemotherapy-alone groups and 227 [50%] in the two chemotherapy plus bevacizumab groups). By March 7, 2014, 348 deaths had occurred, meeting the prespecified cutoff for final analysis. The chemotherapy plus bevacizumab groups continued to show significant improvement in OS compared with the chemotherapy-alone groups: 16·8 months in the chemotherapy plus bevacizumab groups versus 13·3 months in the chemotherapy-alone groups (hazard ratio 0·77 [95% CI 0·62–0·95]; p=0·007). Final OS among patients not receiving previous pelvic radiotherapy was 24·5 months versus 16·8 months (0·64 [0·37–1·10]; p=0·11). Postprogression OS was not significantly different between the chemotherapy plus bevacizumab groups (8·4 months) and chemotherapy-alone groups (7·1 months; 0·83 [0·66–1·05]; p=0·06). Fistula (any grade) occurred in 32 (15%) of 220 patients in the chemotherapy plus bevacizumab groups (all previously irradiated) versus three (1%) of 220 in the chemotherapy-alone groups (all previously irradiated). Grade 3 fistula developed in 13 (6%) versus one (

Study Design Controlled laboratory study, within-session design. Background Gait retraining has been proposed as an effective intervention to reduce impact loading in runners at risk of stress fractures. Interventions that can be easily implemented in the clinic are needed. Objective To assess the immediate effects of sound-intensity feedback related to impact during running on vertical impact peak, peak vertical instantaneous loading rate, and vertical average loading rate. Methods Fourteen healthy, college-aged runners who ran at least 9.7 km/wk participated (4 male, 10 female; mean ± SD age, 23.7 ± 2.0 years; height, 1.67 ± 0.08 m; mass, 60.9 ± 8.7 kg). A decibel meter provided real-time sound-intensity feedback of treadmill running via an iPad application. Participants were asked to reduce the sound intensity of running while receiving continuous feedback for 15 minutes, while running at their self-selected preferred speed. Baseline and follow-up ground reaction force data were collected during overground running at participants' self-selected preferred running speed. Results Dependent t tests indicated a statistically significant reduction in vertical impact peak (1.56 BW to 1.13 BW, P≤.001), vertical instantaneous loading rate (95.48 BW/s to 62.79 BW/s, P = .001), and vertical average loading rate (69.09 BW/s to 43.91 BW/s, P≤.001) after gait retraining, compared to baseline. Conclusion The results of the current study support the use of sound-intensity feedback during treadmill running to immediately reduce loading rate and impact force. The transfer of within-session reductions in impact peak and loading rates to overground running was demonstrated. Decreases in loading were of comparable magnitude to those observed in other gait retraining methods. J Orthop Sports Phys Ther 2017;47(8):565-569. Epub 6 Jul 2017. doi:10.2519/jospt.2017.7275.

A principal focus in GIS higher education has been with developing curricula or accommodating new technologies to reflect the needs of the developing discipline. Pedagogy has largely reflected traditional metaphors of acquisition and transfer in the context of formal education, and this extends to preparation of students for the workplace. In this paper, the authors explore the potential for communities of practice, and in particular virtual communities of practice as a complement to more formal GIS education to provide a route to more situated, participatory learning. In so doing, the emphasis towards creating a GIS professional community of practice offers both the recognition of the role of situated knowledge in developing professional GIS expertise, and provides an important bridge from higher education to the workplace.

Some of the more popular sporting activities for those living in rural areas include equestrian activities such as rodeo events and horseback riding. The lack of helmet use poses a concern for those who participate in these activities due to the risk of sustaining a traumatic brain injury (TBI) and ultimately having a negative effect on their future. A retrospective cohort study was conducted at a trauma center comparing the data on animal-riding patients and their use or lack of use of headgear and incidence of TBI. Of the patients identified, 16.2% sustained a head injury, ranking TBI fourth among all injuries sustained by the animal-riding population. Males were predominantly affected; however, females of pediatric age 5-17 years (54.5%) ranked high among the TBI population. Among all the patients identified with TBI, none of the patients were wearing a helmet and all sustained a head injury. The average injury severity score was 11, with hospital length of stay averaging less than 2 days and the overall mortality was 3.6%. Findings from the study should be considered for the purpose of implementing an age-specific educational program focused on head injury prevention and utilization of protective headgear. Current literature supports the use of protective headgear to reduce the risk of head injuries. Animal riders should be educated on the importance of using headgear as a preventive measure. Future studies are needed to indicate the effectiveness of injury prevention in regard to head injury severity and the use of protective headgear.

Familial and sporadic essential tremor (ET) cases differ in several respects. Whether they differ with respect to cerebellar pathologic changes has yet to be studied. We quantified a broad range of postmortem features (Purkinje cell (PC) counts, PC axonal torpedoes, a host of associated axonal changes, heterotopic PCs, and hairy basket ratings) in 60 ET cases and 30 controls. Familial ET was defined using both liberal criteria (n = 27) and conservative criteria (n = 20). When compared with controls, ET cases had lower PC counts, more torpedoes, more heterotopic PCs, a higher hairy basket rating, an increase in PC axonal collaterals, an increase in PC thickened axonal profiles, and an increase in PC axonal branching. Familial and sporadic ET had similar postmortem changes, with few exceptions, regardless of the definition criteria. The PC counts were marginally lower in familial than sporadic ET (respective p values = 0.059 [using liberal criteria] and 0.047 [using conservative criteria]). The PC thickened axonal profile count was marginally lower in familial ET than sporadic ET (respective p values = 0.037 [using liberal criteria] and 0.17 [using conservative criteria]), and the PC axonal branching count was marginally lower in familial than sporadic ET (respective p values = 0.045 [using liberal criteria] and 0.079 [using conservative criteria]). After correction for multiple comparisons, however, there were no significant differences. Overall, familial and sporadic ET cases share very similar cerebellar postmortem features. These data indicate that pathological changes in the cerebellum are a part of the pathophysiological cascade of events in both forms of ET.

Introduction Colonoscopy prevents colorectal cancer via the detection and resection of premalignant polyps. This effect may be attenuated by variations in polypectomy, with multiple techniques available and a wide range of experience amongst endoscopists. We assessed current practice against the best available contemporary evidence. Methods An online survey was distributed to members of the gastroenterological and surgical societies of seven countries during July 2017. Images of colorectal polyps were presented and respondents requested to provide the polypectomy technique they would employ in their daily practice. Responses were compared to the evidence-based techniques in the 2017 ESGE Colorectal Polypectomy Guideline. Results In total, 707 endoscopists (627 physicians, 71 surgeons, 9 nurse endoscopists, median practice duration 18 years) completed the survey. Of these, 3.1 % selected hot biopsy forceps and 5.2 % hot snare polypectomy (without submucosal lifting) to remove a 3 mm ascending colon polyp. Only 43.3 % selected cold snare polypectomy (CSP) to remove an 8 mm ascending colon polyp. Surgical referral was selected by 16.7 % of respondents for a 45 mm transverse colon polyp without endoscopic evidence of submucosal invasive cancer (SMIC). Endoscopic resection was selected by 12.0 % for an 80 mm sigmoid polyp with imaging consistent with deep SMIC, and a further 26.4 % selected tertiary endoscopist referral, suggesting they had not appreciated that it was endoscopically unresectable. Conclusion CSP is underutilized for small polyp resection despite its favorable safety and efficacy. Benign polyps are commonly referred for surgery and overt SMIC is underappreciated using endoscopic imaging. Addressing these issues may reduce diathermy-related adverse events, surgery, and unnecessary colonoscopic procedures for patients and reduce rates of post-colonoscopy colorectal cancer.

Background Oral direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) became government subsidized in Australia in March 2016, bringing the interferon era to a close. The ideal monitoring schedule for patients receiving DAAs is unclear. Methods This study is a randomized controlled trial comparing standard with minimal monitoring in adults receiving sofosbuvir-based therapy for HCV genotypes 1 or 3. Exclusion criteria were cirrhosis or predicted poor adherence. Standard monitoring included blood tests and face-to-face clinic visits at treatment weeks 4 and 12 and 12 weeks after treatment completion. Minimal monitoring included a phone call at weeks 4 and 12 and one set of blood tests plus a clinic visit 12 weeks after treatment completion. The coprimary outcomes were as follows: (1) proportion of participants with sustained virological response; (2) staff time spent on patient support; and (3) patient satisfaction on a 10-point Likert scale. Results Thirty-six patients were randomized to standard monitoring and 38 to minimal monitoring. Sustained virological response at 12 weeks after the end of treatment was documented in 32 of 36 (89%) in the standard versus 37 of 38 (97%) in the minimal monitoring group. Staff time was nonsignificantly longer in the standard group (median 69 [interquartile range {IQR}, 54–80] versus 52 [IQR, 40–75] minutes). Patient satisfaction scores were not different (mean 9.8 of 10 standard versus 9.6 of 10 minimal group). There was no difference in adverse events or unplanned hospital visits; mean per-patient blood test costs were higher in the standard monitoring group ($432 versus $123, P, In this pilot, randomized, controlled trial including 74 patients treated for HCV with sofosbuvir-based regimens, a strategy of minimal monitoring led to an equal cure rate with less costs compared with standard monitoring.

There is a critical research need for efficient luminescent colloidal nanocrystals, free from cadmium and lead whose toxicity subjects them to usage restrictions, with applications from display devices to biology. Approaches to directly replace cadmium-based materials have mainly focused on indium phosphide-based nanocrystals, however these too are subject to concerns over toxicity. Few other alternatives have been found that can compete with the emission range and efficiency of Cd and Pb-based nanocrystals. Group III-nitride nanocrystals, and their alloys, offer the exciting potential to tune bandgap energies from the ultraviolet to the near infrared yet a robust route towards efficient luminescent nitride nanocrystals is lacking. Here, the synthesis of photoluminescent indium zinc nitride quantum dots exhibiting tunable emission through the visible to near infrared spectra region, with quantum yields of up to 30% is reported. Capping the nanocrystals with both a GaN and ZnS shell significantly increased air stability and emission quantum yields. A proof-of-principle indium zinc nitride nanocrystal light emitting diode is also demonstrated. This work overcomes the significant challenges that have prevented the full exploration of nitride-based semiconductor nanocrystal development, providing a new system for further exploration as a heavy-metal free alternative to current state-of-the-art materials.

Thoracic oesophageal diverticula are often associated with spastic motility disorders. Despite correction of the underlying motility disorder, in a subgroup of patients, symptoms persist, primarily regurgitation. Surgical diverticulectomy is then proposed; however, as the approach is thoracoscopic or via thoracotomy, it is associated with significant morbidity and cost. Descriptions of endoscopic techniques for the treatment of symptomatic midoesophageal diverticula are few. We propose the novel technique of diverticular myotomy (DM) to treat this disorder. In this case series, we describe two patients who successfully underwent DM with no adverse outcomes and excellent clinical results at 24-month follow-up.

Background and Aims Colorectal cancer (CRC) can be prevented through colonoscopic polypectomy, but this exposes patients to risks, including delayed post-polypectomy bleeding (DPPB). Endoscopists increasingly use clips prophylactically with the aim of preventing DPPB. However, clips are costly, and data to support their efficacy in this context are inconsistent. We performed a systematic review and meta-analysis of randomized controlled trials to assess the efficacy of prophylactic clipping for preventing DPPB. Methods We searched electronic databases and other relevant sources for randomized controlled trials assessing the efficacy of prophylactic clipping versus no clipping for the prevention of DPPB. Pooled relative risks were determined using a fixed-effects model. Subgroup analyses were also performed. Results A total of 2305 citations were initially screened. Seven randomized controlled trials satisfied all criteria for inclusion. The quality of included studies was generally low to moderate. A total of 2851 patients underwent 5405 polypectomies. Delayed post-polypectomy bleeding occurred at an overall pooled rate of 2.5%. No overall benefit of clipping for preventing DPPB was observed, with a pooled relative risk of 0.86 (95% confidence interval [CI], 0.55 to 1.36). No significant patient or polyp factors predicting DPPB were found through subgroup analyses. No publication bias was identified. Conclusions Randomized trials to date do not demonstrate a protective effect of prophylactic clipping for the prevention of DPPB, and therefore, the practice of routine prophylactic clipping appears unjustified. Additional high quality randomized trials are required to identify higher-risk groups that may benefit from prophylactic clipping.

Background and Purpose— The DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) demonstrated that endovascular thrombectomy in the 6- to 16-hour time window improves functional outcomes of patients with evidence of salvageable tissue on baseline computed tomography or magnetic resonance imaging. The purpose of this study is to assess the effect of endovascular therapy on length of hospital stay, home-time during the first 3 months poststroke, and living situation poststroke in DEFUSE 3. Methods— Duration of hospital stay and home-time (number of days during the 90-day poststroke period that the patient resides in their own home or in that of a relative) were compared between treatment groups using the Wilcoxon rank-sum test. Patient living situation was assessed at discharge, 30 days, and 90 days on an ordinal 4-point scale (home, acute rehabilitation unit, institutionalized care, or hospice/death) and differences between groups were analyzed using the Cochran-Armitage trend test. Results— Median length of hospital stay was 9.1 (interquartile range, 6.2–15.0) days in the medical group versus 6.5 (interquartile range, 3.7–9.3) days in the endovascular group ( P P P P P Conclusions— Endovascular thrombectomy resulted in reduced hospital stay, more home-time, and more desirable living situations in the 90 days after stroke. These results provide evidence that endovascular therapy in the delayed time window can improve quality of life for stroke patients and reduce healthcare costs. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.