Association of travel time, patient characteristics, and hospital quality with patient mobility for breast cancer surgery: A national population-based study.

BACKGROUND: This national study investigated hospital quality and patient factors associated with treatment location for breast cancer surgery. METHODS: By using linked administrative data sets from the English National Health Service, the authors identified all women diagnosed between January 2, 2016, and December 31, 2018, who underwent breast-conserving surgery (BCS) or a mastectomy with or without immediate breast reconstruction. The extent to which patients bypassed their nearest hospital was investigated using a geographic information system (ArcGIS). Conditional logistic regressions were used to estimate the impact of travel time, hospital quality, and patient characteristics. RESULTS: 22,622 Of 69,153 patients undergoing BCS, 22,622 (32.7%) bypassed their nearest hospital; and, of 23,536 patients undergoing mastectomy, 7179 (30.5%) bypassed their nearest hospital. Women who were younger, without comorbidities, or from rural areas were more likely to travel to more distant hospitals (p < .05). Patients undergoing BCS (odds ratio [OR], 1.85; 95% confidence interval [CI], 1.36-2.50) or mastectomy (OR, 1.52; 95% CI, 1.14-2.02) were more likely to be treated at specialist breast reconstruction centers despite not undergoing the procedure. Patients receiving mastectomy and immediate breast reconstruction were more likely to travel to hospitals employing surgeons who had a media reputation (OR, 2.41; 95% CI, 1.28-4.52). Patients undergoing BCS were less likely to travel to hospitals with shorter surgical waiting times (OR, 0.65; 95% CI, 0.46-0.92). The authors did not observe a significant impact for research activity, hospital quality rating, breast re-excision rates, or the status as a multidisciplinary cancer center. CONCLUSIONS: Patient choice policies may drive inequalities in the health care system without improving patient outcomes.

Genome-wide association analysis identifies a susceptibility locus for sporadic vestibular schwannoma at 9p21.

Vestibular schwannomas are benign nerve sheath tumours that arise on the vestibulocochlear nerves. Vestibular schwannomas are known to occur in the context of tumour predisposition syndromes NF2-related and LZTR1-related schwannomatosis. However, the majority of vestibular schwannomas present sporadically without identification of germline pathogenic variants. To identify novel genetic associations with risk of vestibular schwannoma development, we conducted a genome-wide association study in a cohort of 911 sporadic vestibular schwannoma cases collated from the neurofibromatosis type 2 genetic testing service in the north-west of England, UK and 5500 control samples from the UK Biobank resource. One risk locus reached genome-wide significance in our association analysis (9p21.3, rs1556516, P = 1.47 × 10-13, odds ratio = 0.67, allele frequency = 0.52). 9p21.3 is a genome-wide association study association hotspot, and a number of genes are localized to this region, notably CDKN2B-AS1 and CDKN2A/B, also referred to as the INK4 locus. Dysregulation of gene products within the INK4 locus have been associated with multiple pathologies and the genes in this region have been observed to directly impact the expression of one another. Recurrent associations of the INK4 locus with components of well-described oncogenic pathways provides compelling evidence that the 9p21.3 region is truly associated with risk of vestibular schwannoma tumorigenesis.

Modifiability of surgical timing in postinjury multiple organ failure patients.

BACKGROUND: Postinjury multiple organ failure (MOF) is the leading cause of late trauma deaths, with primarily non-modifiable risk factors. Timing of surgery as a potentially modifiable risk factor is frequently proposed, but has not been quantified. We aimed to compare mortality, hospital length of stay (LOS), and ICU LOS between MOF patients who had surgery that preceded MOF with modifiable timings versus those with non-modifiable timings. METHODS: Retrospective analysis of an ongoing 17-year prospective cohort study of ICU polytrauma patients at-risk of MOF. Among MOF patients (Denver score>3), we identified patients who had surgery that preceded MOF, determined whether the timing of these operation(s) were modifiable(M) or non-modifiable (non-M), and evaluated the change in physiological parameters as a result of surgery. RESULTS: Of 716 polytrauma patients at-risk of MOF, 205/716 (29%) developed MOF, and 161/205 (79%) had surgery during their ICU admission. Of the surgical MOF patients, 147/161 (91%) had one or more operation(s) that preceded MOF, and 65/161 (40%) of them had operation(s) with modifiable timings. There were no differences in age (mean (SD) 52 (19) vs 53 (21)years), injury severity score (median (IQR) 34 (26-41)vs34 (25-44)), admission physiological and resuscitation parameters, between M and non-M-patients. M patients had longer ICU LOS (median (IQR) 18 (12-28)versus 11 (8-16)days, p < 0.0001) than non-M-patients, without difference in mortality (14%vs16%, p = 0.7347), or hospital LOS (median (IQR) 32 (18-52)vs27 (17-47)days, p = 0.3418). M-patients had less fluids and transfusions intraoperatively. Surgery did not compromise patient physiology. CONCLUSION: Operations preceding MOF are common in polytrauma and seem to be safe in maintaining physiology. The margin for improvement from optimizing surgical timing is modest, contrary to historical assumptions.

Post-streptococcal small-vessel vasculitis in a 16-month-old with associated intussusception and hypertension: Henoch Schönlein purpura?

Henoch Schönlein purpura (HSP), also known as IgA vasculitis, is a systemic small-vessel vasculitis typically occurring in children 3-15 years of age, with peak incidence at 4-6 years. It is characterized by a constellation of symptoms including palpable purpura, arthralgias or arthritis, abdominal pain including intussusception, and renal involvement. We report a patient with these clinical findings whose IgA immunofluorescence was negative but with a presumptive diagnosis of HSP at 16 months of age, significantly younger than the classic population. This condition rarely affects this age group, and we highlight the importance of considering vasculitis in children of all ages, as a failure to diagnose could lead to insufficient long-term monitoring, particularly regarding renal function.

Dysplastic Hips Have Decreased Iliofemoral Ligament Thickness on Coronal Sequences in Magnetic Resonance Imaging: A Matched Cohort Analysis.

PURPOSE: To characterize hip capsule thickness on advanced imaging in patients with and without hip dysplasia and to also evaluate differences in capsular thickness between borderline and true dysplastic patients. METHODS: Patients evaluated by the senior author for concerns of hip pathology from June 2020 to June 2021 were queried and images reviewed to determine dysplasia status by lateral center edge angle (LCEA) ≤ 25 degrees. A group of non-dysplastic patients was identified and matched for age, sex, and body mass index (BMI). Hip capsular thickness was quantified using MRI. A sub-analysis was conducted to compare true dysplastic patients (LCEA < 20°) to borderline dysplastic patients (LCEAs between 20 - 25°). Analysis included independent samples t-tests, Chi-square tests, and multivariable regression. RESULTS: Eighty total patients were included, with a mean age of 31.8 ± 11.7 years, a mean BMI of 26.6 ± 6.5 points, and 70% (56) female patients. Dysplastic patients had a mean LCEA of 19.8 ± 4.3 degrees. Dysplastic individuals had decreased capsular thickness compared to their non-dysplastic controls (2.75 ± 0.96 vs 3.52 ± 1.22 mm, p = 0.003). Multivariable regression showed decreased capsular thickness associated with decreased LCEAs (ß = 2.804, R = 0.432, p<0.001) and dysplasia (ß = -0.709, R2 = 0.056, p = 0.004). Results of a sub-analysis of the dysplastic group examining differences between accepted definitions of borderline dysplasia and true dysplasia showed no significant differences in capsular thickness between the two groups (p = 0.379). CONCLUSIONS: Patients with hip dysplasia were found to have thinner iliofemoral ligaments in the coronal plane on magnetic resonance imaging on magnetic resonance imaging. Further investigation is needed to evaluate any potential implications with hip instability given the thinner hip capsule demonstrated in this study.

Similar Efficacy and Lower Cost Associated With Ceftazidime Compared to Tobramycin Coupled With Vancomycin in Antibiotic Spacers in the Treatment of Periprosthetic Joint Infection.

BACKGROUND: Vancomycin and tobramycin have traditionally been used in antibiotic spacers. In 2020, our institution replaced tobramycin with ceftazidime. We hypothesized that the use of ceftazidime/vancomycin (CV) in antibiotic spacers would not lead to an increase in treatment failure compared to tobramycin/vancomycin (TV). METHODS: From 2014 to 2022, we identified 243 patients who underwent a stage I revision for periprosthetic joint infection. The primary outcome was a recurrent infection requiring antibiotic spacer exchange. We were adequately powered to detect a 10% difference in recurrent infection. Patients who had a prior failed stage I or two-stage revision for infection, acute kidney injury prior to surgery, or end-stage renal disease were excluded. Given no other changes to our spacer constructs, we estimated cost differences attributable to the antibiotic change. Chi-square and t-tests were used to compare the two groups. Multivariable logistic regressions were utilized for the outcomes. RESULTS: The combination of TV was used in 127 patients; CV was used in 116 patients. Within one year of stage I, 9.8% of the TV group had a recurrence of infection versus 7.8% of the CV group (P = .60). By final follow-up, results were similar (12.6 versus 8.6%, respectively, P = .32). Adjusting for potential risk factors did not alter the results. Cost savings for ceftazidime versus tobramycin are estimated to be $68,550 per one hundred patients treated. CONCLUSIONS: Replacing tobramycin with ceftazidime in antibiotic spacers yielded similar periprosthetic joint infection eradication success at a lower cost. While larger studies are warranted to confirm these efficacy and cost-saving results, our data justifies the continued investigation and use of ceftazidime as an alternative to tobramycin in antibiotic spacers.

Efficacy of virtual surgical planning and a three-dimensional-printed, patient-specific reduction system to facilitate alignment of diaphyseal tibial fractures stabilized by minimally invasive plate osteosynthesis in dogs: A prospective clinical study.

OBJECTIVE: To evaluate the efficacy of a three-dimensional (3D)-printed, patient-specific reduction system for aligning diaphyseal tibial fractures stabilized using minimally invasive plate osteosynthesis (MIPO). STUDY DESIGN: Prospective clinical trial. SAMPLE POPULATION: Fifteen client owned dogs. METHODS: Virtual 3D models of both pelvic limbs were created. Pin guides were designed to conform to the proximal and distal tibia. A reduction bridge was designed to align the pin guides based on the guides' spatial location. Guides were 3D printed, sterilized, and applied, in conjunction with transient application of a circular fixator, to facilitate indirect fracture realignment before plate application. Alignment of the stabilized tibiae was assessed using postoperative computed tomography scans. RESULTS: Mean duration required for virtual planning was 2.5 h and a mean of 50.7 h elapsed between presentation and surgery. Guide placement was accurate with minor median discrepancies in translation and frontal, sagittal, and axial plane positioning of 2.9 mm, 3.6°, 2.7°, and 6.8°, respectively. Application of the reduction system restored mean tibial length and frontal, sagittal, and axial alignment within 1.7 mm, 1.9°, 1.7°, and 4.5°, respectively, of the contralateral tibia. CONCLUSION: Design and fabrication of a 3D-printed, patient-specific fracture reduction system is feasible in a relevant clinical timeline. Intraoperative pin-guide placement was reasonably accurate with minor discrepancies compared to the virtual plan. Custom 3D-printed reduction system application facilitated near-anatomic or acceptable fracture reduction in all dogs. CLINICAL SIGNIFICANCE: Virtual planning and fabrication of a 3D-printing patient-specific fracture reduction system is practical and facilitated acceptable, if not near-anatomic, fracture alignment during MIPO.

Impact of centralization of prostate cancer services on the choice of radical treatment.

OBJECTIVE: To assess the impact of centralization of prostate cancer surgery and radiotherapy services on the choice of prostate cancer treatment. PATIENTS AND METHODS: This national population-based study used linked cancer registry data and administrative hospital-level data for all 16 621 patients who were diagnosed between 1 January 2017 and 31 December 2018 with intermediate-risk prostate cancer and who underwent radical prostatectomy (RP) or radical radiation therapy (RT) in the English National Health Service (NHS). Travel times by car to treating centres were estimated using a geographic information system. We used logistic regression to assess the impact of the relative proximity of alternative treatment options on the type of treatment received, with adjustment for patient characteristics. RESULTS: Of the 78 NHS hospitals that provide RT or RP for prostate cancer, 41% provide both, 36% provide RT and 23% provide RP. Compared to patients who had both treatment options available at their nearest centre where overall 57% of patients received RT and 43% RP, patients were less likely to receive RT if their nearest centre offered RP only and the extra travel time to a hospital providing RT was >15 min (52% of patients received RT and 48% RP%, odds ratio [OR] 0.70 (0.58-0.85); P < 0.001). Conversely, patients were more likely to receive RT if their nearest centre offered RT and the extra travel time to a hospital providing RP was >15 min (63% of patients received RT and 37% RP, OR 1.23 (1.08-1.40); P < 0.001). There was a negligible impact on the type of treatment received if centres providing alternative treatment options were ≤15-min travel time from each other. CONCLUSION: The relative proximity of prostate cancer treatment options to a patient's residence is an independent predictor for the type of radical treatment received. Centralization policies for prostate cancer should not focus on one treatment modality but should consider all treatments to avoid a negative impact on treatment choice.

No bilingual advantage in children's attentional disengagement: Congruency and sequential congruency effects in a large sample of monolingual and bilingual children.

According to recent accounts, bilingualism in childhood confers an advantage in a specific domain of executive functioning termed attentional disengagement. The current study tested this hypothesis in 492 children (245 boys; Mage = 10.98 years) from Canada, China, and Lebanon by testing for an association between language status and measures of attentional disengagement. Across the entire sample, monolinguals responded more quickly and accurately than bilinguals on a measure of attentional disengagement but differed in age, socioeconomic status, and general cognitive ability. Differences between monolinguals and bilinguals disappeared when the influence of these confounding variables was controlled using a matched samples analysis (ns = 105). Bayesian analyses further confirmed that the evidence was more likely under the null hypothesis than under the alternative hypothesis. In sum, there was little evidence of an association between language status and attentional disengagement in children.

Rapid ossification of a giant post-operative occipital pseudomeningocele following posterior fossa surgery.

Pseudomeningocele formation following posterior fossa surgery is a well-recognised complication, occurring in up to 33% of operated cases in some series. Ossification of a cranial pseudomeningocele is, however, an exceptionally rare event with only three prior reported cases. We present the unique case of a paediatric patient who developed rapid ossification of a giant occipital pseudomeningocele following posterior fossa surgery. An 8-year-old female patient underwent a midline posterior fossa craniotomy for resection of an exophytic brainstem low-grade glioma. Post-surgery, the patient developed pan-ventricular hydrocephalus and a large occipital pseudomeningocele, which initially increased in size despite a successful endoscopic third ventriculostomy (ETV) being performed. At approximately 3 months post-surgery, reduction of the pseudomeningocele was observed with associated prominent ossification of the pseudomeningocele wall on computed tomography (CT) imaging. Surgical excision was subsequently undertaken, and intra-operatively, a large ossified pseudomeningocele was found. Follow-up MRI 1 month later demonstrated almost complete resolution of the pseudomeningocele with an associated reduction in the degree of pan-ventricular ventriculomegaly. This case highlights that ossification of even giant pseudomeningoceles can occur over a time period of just a few months and clinicians should consider ossification whenever a change in size or consistency of a post-operative pseudomeningocele is encountered.

Minimally invasive plate osteosynthesis of femoral fractures with 3D-printed bone models and custom surgical guides: A cadaveric study in dogs.

OBJECTIVE: Assess the accuracy and efficiency of reduction provided by application of plates precontoured to 3-dimensional (3D)-printed femoral bone models using a custom fracture reduction system (FRS) or intramedullary pin (IMP) to facilitate femoral minimally invasive plate osteosynthesis (MIPO) in dogs. STUDY DESIGN: Experimental cadaveric study. SAMPLE POPULATION: Seven dog cadavers. METHODS: Virtual 3D femoral models were created using computed tomographic images. Simulated, virtual mid-diaphyseal femoral fractures were created and reduced. Reduced femoral models were 3D-printed and a plate was contoured. Custom drill guides for plate screw placement were designed and 3D-printed for the FRS. Mid-diaphyseal simulated comminuted fractures were created in cadavers, and fractures were aligned using FRS or IMP and stabilized with the precontoured plates. Number of fluoroscopic images acquired per procedure and surgical duration were recorded. Computed tomographic scans were repeated to assess femoral length and alignment. RESULTS: Compared to the preoperative virtual plan, median change in femoral length and frontal, sagittal, and axial alignment was less than 3 mm, 2°, 3°, and 3° postoperatively, respectively, in both reduction groups. There was no difference in length or alignment between reduction groups (P > .05). During FRS, fewer fluoroscopic images were taken (P = .001), however, surgical duration was longer than IMP procedures (P = .011). CONCLUSION: Femoral alignment was accurate when using plates precontoured to 3D printed models, regardless of reduction method. CLINICAL SIGNIFICANCE: Accurate plate contouring using anatomically accurate models may improve fracture reduction accuracy during MIPO applications. Custom surgical guides may reduce fluoroscopy use associated with MIPO.

Delayed diagnosis of DRESS syndrome in a patient with skin of color.

We describe a particularly severe case of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome with hemodynamic instability, erythroderma, profound eosinophilia, and severe organ dysfunction. We attribute the severity in part to a delay in diagnosis due to patient's skin of color, as the erythroderma was not noticed until a dermatologist was consulted. This case highlights how even severe skin disease can present less conspicuously in patients with darker skin types. We outline several strategies that can help clinicians to recognize DRESS and other skin disease phenotypes in patients of color, thereby avoiding delays in diagnosis as seen in this case.

Successful radical surgical resection of a giant neurofibroma.

Large neurofibromas often cause significant patient morbidity and present a unique challenge to dermatologists and surgeons. Radical resection offers the lowest rate of recurrence but is not often pursued due to the high risk of intraoperative hemorrhage and difficulty in repairing large defects. Subtotal resection and debulking are more frequently performed, leading to higher rates of recurrence. This case highlights a particularly large neurofibroma and demonstrates how surgical techniques like preoperative embolization and advancement flaps can improve outcomes in the radical resection of large neurofibromas.

Health service planning to assess the expected impact of centralising specialist cancer services on travel times, equity, and outcomes: a national population-based modelling study.

BACKGROUND: Centralisation of specialist cancer services is occurring in many countries, often without evaluating the potential impact before implementation. We developed a health service planning model that can estimate the expected impacts of different centralisation scenarios on travel time, equity in access to services, patient outcomes, and hospital workload, using rectal cancer surgery as an example. METHODS: For this population-based modelling study, we used routinely collected individual patient-level data from the National Cancer Registration and Analysis Service (NCRAS) and linked to the NHS Hospital Episode Statistics (HES) database for 11 888 patients who had been diagnosed with rectal cancer between April 1, 2016, and Dec 31, 2018, and who subsequently underwent a major rectal cancer resection in 163 National Health Service (NHS) hospitals providing rectal cancer surgery in England. Five centralisation scenarios were considered: closure of lower-volume centres (scenario A); closure of non-comprehensive cancer centres (scenario B); closure of centres with a net loss of patients to other centres (scenario C); closure of centres meeting all three criteria in scenarios A, B, and C (scenario D); and closure of centres with high readmission rates (scenario E). We used conditional logistic regression to predict probabilities of affected patients moving to each of the remaining centres and the expected changes in travel time, multilevel logistic regression to predict 30-day emergency readmission rates, and linear regression to analyse associations between the expected extra travel time for patients whose centre is closed and five patient characteristics, including age, sex, socioeconomic deprivation, comorbidity, and rurality of the patients' residential areas (rural, urban [non-London], or London). We also quantified additional workload, defined as the number of extra patients reallocated to remaining centres. FINDINGS: Of the 11 888 patients, 4130 (34·7%) were women, 5249 (44·2%) were aged 70 years and older, and 5005 (42·1%) had at least one comorbidity. Scenario A resulted in closures of 43 (26%) of the 163 rectal cancer surgery centres, affecting 1599 (13·5%) patients; scenario B resulted in closures of 112 (69%) centres, affecting 7029 (59·1%) patients; scenario C resulted in closures of 56 (34%) centres, affecting 3142 (26·4%) patients; scenario D resulted in closures of 24 (15%) centres, affecting 874 (7·4%) patients; and scenario E resulted in closures of 16 (10%) centres, affecting 1000 (8·4%) patients. For each scenario, there was at least a two-times increase in predicted travel time for re-allocated patients with a mean increase in travel time of 23 min; however, the extra travel time did not disproportionately affect vulnerable patient groups. All scenarios resulted in significant reductions in 30-day readmission rates (range 4-48%). Three hospitals in scenario A, 41 hospitals in in scenario B, 13 hospitals in scenario C, no hospitals in scenario D, and two hospitals in scenario E had to manage at least 20 extra patients annually. INTERPRETATION: This health service planning model can be used to to guide complex decisions about the closure of centres and inform mitigation strategies. The approach could be applied across different country or regional health-care systems for patients with cancer and other complex health conditons. FUNDING: National Institute for Health Research.

Quantitative Magnetic Resonance-Derived Biomarkers as Predictors of Function and Histotype in Adenohypophyseal Tumours.

INTRODUCTION: Magnetic resonance imaging (MRI) is the main modality to diagnose adenohypophyseal tumours, while biochemical assessment of pituitary hormones allows for their functional classification. In this retrospective exploratory cohort study, we investigated if quantitative differences in tumour MR signal intensity (SI) could be utilized to predict the function and histotype. METHODS: Clinically acquired pretreatment MRI images were retrospectively analysed in 67 clinically non-functioning gonadotropinomas (NFG), 38 somatotropinomas, and 16 medically treated giant macroprolactinomas. Mean T1- and T2-weighted SI values were determined for each tumour and normalized against either centrum semiovale white matter or CSF to derive relative T1W and T2W SI values and the relative tumour T2/T1 SI ratio. Inter-group differences in quantitative MR parameters were compared, and the power of each parameter to discriminate tumour type and subtype was assessed using the area under the receiver operator characteristic curve (AUROC). In resected somatotropinomas, the relationship between tumour granulation status, relative MR SI values, and biochemical data was also compared. RESULTS: Compared to somatotropinomas, NFG and macroprolactinomas displayed higher relative T2W SI (p < 0.001) and higher relative tumour T2/T1 SI ratio values (p < 0.001, ANOVA). Compared to intermediate/densely granulated tumours, sparsely granulated somatotropinomas were larger (p = 0.006, Mann-Whitney U test), had higher relative T2W SI (p ≤ 0.005), and higher relative tumour T2/T1 SI ratios (p ≤ 0.001, 2-tailed t test). Relative tumour T2W SI values and relative tumour T2/T1 ratio values demonstrated good discriminatory power in differentiating NFG from somatotropinoma (AUROC = 0.87-0.94) and predicting somatotropinoma subtypes (AUROC = 0.87-0.95). CONCLUSION: Quantitative SI-based MR parameters derived using clinical acquisition MRI protocols may help non-invasively discriminate the functional status of adenohypophyseal tumours and the histological subtype of somatotropinomas.

Phonon assisted electron emission from quasi-freestanding bilayer epitaxial graphene microstructures.

Electron emission from quasi-freestanding bilayer epitaxial graphene (QFEG) on a silicon carbide substrate is reported, demonstrating emission currents as high as 8.5µA, at ∼200 °C, under 0.3 Torr vacuum. Given the significantly low turn-on temperature of these QFEG devices, ∼150°C, the electron emission is explained by phonon-assisted electron emission, where the acoustic and optical phonons of QFEG causes carrier acceleration and emission. Devices of differing dimensions and shapes are fabricated via a simple and scalable fabrication procedure and tested. Variations in device morphology increase the density of dangling bonds, which can act as electron emission sites. Devices exhibit emission enhancement at increased temperatures, attributed to greater phonon densities. Devices exhibit emission under various test conditions, and a superior design and operating methodology are identified.

Management of relapsed cutaneous T-Cell lymphoma following allogeneic hematopoietic stem cell transplantation: Review with representative patient case.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with refractory cutaneous T-cell lymphoma (CTCL) through replacement of the bone marrow responsible for lymphoma cells and possibly induction of a graft-versus-lymphoma effect. However, allo-HSCT is not always curative; relapse of CTCL occurs in about half of patients post-transplant. Treatment of relapsed CTCL after allo-HSCT is challenging because post-transplant patients are at high risk of graft-versus-host disease, and this condition may be precipitated or exacerbated by standard CTCL therapies. The benefit of each potential therapy must therefore be weighed against its risk of graft versus host disease (GVHD). In this article, we review the management of relapsed CTCL after allo-HSCT. We begin with an exemplative patient whose relapsed Sezary syndrome was successfully treated without development of GVHD. We also report high-throughput T-cell receptor sequencing data obtained during the patient's disease relapse and remission. We then review general guidelines for management of relapsed CTCL and summarize all reported cases and outcomes of relapsed CTCL after transplant. We conclude by reviewing the current CTCL therapies and their risk of GVHD.

Equivalent outcomes in nasal symptoms following microscopic or endoscopic transsphenoidal surgery: results from multi-centre, prospective study.

BACKGROUND: T ranssphenoidal surgery (TSS) is the standard approach for resection of pituitary lesions. Historically, this has utilized the microscopic approach (mTSS); however, the past decade has seen widespread uptake of the endoscopic approach (eTSS). The purported benefits of this include improved visualization and illumination, resulting in improved surgical and endocrinological patient outcomes. It is also believed that eTSS results in fewer post-operative nasal symptoms compared to mTSS; however, few papers have directly compared these groups. OBJECTIVES: We sought to compare nasal symptoms after endoscopic uninostril (eTSS-uni), endoscopic binostril (eTSS-bi) and microscopic endoscopic transsphenoidal surgery (mTSS). METHODS: The General Nasal Patient Inventory (GNPI) was prospectively administered to 136 patients (71 non-functioning adenomas, 26 functioning adenomas, 39 other pathology) undergoing transsphenoidal surgery at multiple time points (pre-operatively; days 1, 3 and 7-14; months 1, 3 and 6 and 1 year post-operatively). All surgeries were performed by subspecialist pituitary surgeons in three subgroups - mTSS (25), eTSS-uni (74) and eTSS-bi (37). The total GNPI scores (0-135) and subscores for the 45 individual components were compared across three groups assessing for temporal and absolute changes. RESULTS: Irrespective of surgical approach used, GNPI scores were significantly higher on post-operative day 1 (p < 0.001) and day 3 (p ≤ 0.03) compared to pre-treatment baseline (mixed-effects model). By 1 month post-operatively, however, post-operative GNPI scores were no different from pre-treatment (p > 0.05, mixed-effects model). Whilst the eTSS-uni group demonstrated significantly lower GNPI scores at day 1 post-op compared to the mTSS group (p = 0.05) and eTSS-bi group (p < 0.001), there was no significant difference in post-operative scores between approaches beyond 1-2 weeks post-operatively. Similar results were obtained when the non-functioning tumour group was analysed separately. CONCLUSIONS: Transsphenoidal pituitary surgery is well tolerated. Post-operative nasal symptoms transiently worsen but ultimately improve compared to pre-operative baseline. Operative approach (microscopic, endoscopic uninostril or endoscopic binostril) only has a transient effect on severity of post-operative nasal symptoms.

The feasibility and safety of training patients in opioid treatment to serve as peer recovery support service interventionists.

Background: The use of peer interventionists may be helpful in addressing problems associated with substance use disorders. However, implementation issues such as training, supervision, and the impact of delivering the intervention on the interventionists themselves require additional examination. This report describes the training methods and peer interventionist outcomes in a pilot study of a single-session Peer Recovery Support Services (PRSS) telephone intervention to facilitate enrollment in medication for opioid use disorder (MOUD) treatment. Methods: This was a secondary analysis of a pilot study testing a PRSS intervention in adults using illicit opioids who reported a recent non-fatal opioid overdose (N = 80, with 40 PRSS participants). Candidates recruited from MOUD treatment programs were trained to deliver the PRSS intervention. Assessments of adverse events, global health, and peer satisfaction were used to evaluate the effects of serving as an interventionist. Fidelity and proportion of cases enrolling in MOUD were calculated for each interventionist. Results: Four consented candidates were trained to deliver the PRSS intervention to thirty-six study participants (90% PRSS arm). All interventionists successfully maintained fidelity to the PRSS intervention and reported no negative effects. Interventionists experienced differential success in encouraging treatment enrollment ranging from 16%-60% of their cases. Conclusions: This pilot study demonstrates promise in utilizing peer interventionists to deliver a brief PRSS intervention with limited training and no reported negative effects on the interventionists themselves. Factors contributing to the differential success of the interventionists are unclear. Future research on the variable efficacy of peer interventionists is warranted to identify, quantify, and evaluate specific interactional elements associated with peer efficacy. Additionally, further evaluation of training, supervision practices, and the effects of serving as a PRSS interventionist, is needed. Trial Registration: Clinical Trials.gov http://www.clinicaltrials.gov; Identifier: NCT02922959.

Thermodynamic examination of pH and magnesium effect on U6 RNA internal loop.

U6 RNA contains a 1 × 2-nt internal loop that folds and unfold during spliceosomal assembly and activation. The 1 × 2 loop consists of a C67•A79 base pair that forms an additional hydrogen bond upon protonation, C67•A+79, and uracil (U80) that coordinates the catalytically essential magnesium ions. We designed a series of RNA and DNA constructs with a 1 × 2 loop sequence contained in the ISL, and its modifications, to measure the thermodynamic effects of protonation and magnesium binding using UV-visible thermal denaturation experiments. We show that the wild-type RNA construct gains 0.43 kcal/mol in 1 M KCl upon lowering the pH from 7.5 to 5.5; the presence of magnesium ions increases its stability by 2.17 kcal/mol at pH 7.5 over 1 M KCl. Modifications of the helix closing base pairs from C-G to U•G causes a loss in protonation-dependent stability and a decrease in stability in the presence of magnesium ions, especially in the C68U construct. A79G single-nucleotide bulge loop construct showed the largest gain in stability in the presence of magnesium ions. The DNA wild-type construct shows a smaller effect on stability upon lowering the pH and in the presence of magnesium ions, highlighting differences in RNA and DNA structures. A U6 RNA 1 × 2 loop sequence is rare in the databases examined.