Stereotactic Magnetic Resonance-Guided Daily Adaptive SABR (SMART) for Localised Non-Metastatic Pancreatic Cancer: First Reported Clinical Outcomes From the UK.

AIMS: Prognosis of locally advanced pancreatic cancer (LAPC) remains poor with limited therapeutic options. Radiation therapy in pancreatic cancer has been restricted by the disease's proximity to radiosensitive organs at risk (OAR). However, stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) has demonstrated promise in delivering ablative doses safely. We sought to report clinical outcomes from a UK-based Compassionate Access Programme that provided access to SMART to patients with LAPC. MATERIALS AND METHODS: This was a registry retrospective study conducted at a single centre with access to SMART. Patients with LAPC were treated with prescription dose of 40 Gy in 5 fractions. The planning objective was that 98% of PTV received ≥95% of the prescribed dose, prioritising duodenal, stomach and bowel UK SABR consortium constraints. Daily online adaptation was performed using magnetic resonance guidance and on-table re-optimisation. 0-3 months and > 3-month post-treatment-related toxicities, local progression-free survival, metastatic-free survival and overall survival were evaluated. RESULTS: 55 patients were treated with SMART at our institution from 2020 to 2022. Median follow-up from date of diagnosis was 17 months (range 5-37 months). Median age was 69.87% of patients underwent induction chemotherapy. 71% of patients reported 0-1 grade acute toxicity only. No grade >3 acute toxicity was reported. 5 patients (9%) reported a grade 3 toxicity (fatigue, nausea, abdominal pain, duodenal stricture). No grade >3 toxicity after 3 months was reported. 6 (10%) of patients had grade 3 toxicity (fatigue, nausea, abdominal pain, duodenal haemorrhage). Median local PFS post diagnosis was 17 months (95% CI 15.3-18.7). Median OS post diagnosis was 19 months (95% CI 15.9-22.1). One-year local control post SMART was 65%. CONCLUSION: This is the first UK-reported experience of MR-guided daily adaptive pancreatic SABR. SMART shows promise in delivering ablative doses with acceptable toxicity rates and good clinical outcomes.

Implementation of 26 Gy in five fractions over 1 week adjuvant radiotherapy for breast cancer: Prospective report of acute skin toxicity and consideration of resource implications.

PURPOSE: In March 2020, a 1-week adjuvant breast radiotherapy schedule, 26 Gy in 5 fractions, was adopted to reduce the risk of COVID19 for staff and patients. This study quantifies acute toxicity rates and the effect on linac capacity. MATERIALS AND METHODS: This is a report of consecutive patients receiving ultrafractionated breast radiotherapy ( ± sequential boost) Mar-Aug 2020. Virtual consultations assessed acute skin toxicity during treatment and weeks 1, 2, 3 and 4 post treatment using CTCAE V5 scoring criteria. The number of linac minutes saved was estimated accounting for boost and DIBH use. RESULTS: In total, 128/135 (95%) patients, including 31/33 boost patients, completed at least 3/5 assessments. 0/128 (0%) reported moist desquamation not confined to skin folds or minor bleeding (Grade 3), 41/128 (32%) reported brisk erythema, moist desquamation confined to skin folds or breast swelling (Grade 2), 62/128 (48%) reported faint erythema or dry desquamation (Grade 1) as their worst skin toxicity, with the remaining 20% reporting no skin toxicity. The highest prevalence of grade 2 toxicity occurred week 1 following treatment (20%), reducing to 3% by week 4. There was no difference in toxicity between those who received a boost versus not (p = 1.00). Delivering this schedule to 135 patients over six months saved 21,300 linac minutes and 1485 hospital visits compared to a 3-week schedule. CONCLUSION: Rapidly implementing ultrahypofractionated breast radiotherapy is feasible and acute toxicity rates are acceptable even when followed by boost.

Effectiveness of the DROP training for military behavioral health providers targeting therapeutic alliance and premature dropout.

AbstractPremature discontinuation from behavioral health treatment is a major problem reducing effectiveness of care in military populations. A training was developed and delivered to 622 behavioral health providers across 15 sites within the Army behavioral healthcare system. The training taught two techniques to foster treatment engagement: (1) Progress Informed Treatment, consisting of reviewing symptom assessments and outcome measures, and (2) assessment and discussion of the treatment alliance via a paper survey given near the end of each session. Eighty-five percent of providers indicated the training was useful and 89% of providers incorporated a technique into their practice. Dropout before the fourth session was significantly reduced in the six months following training, from 72.5% to 67.1% in Service Members (SM; X2(1, N=9127) = 39.58, p < .001). In both the pre and post-training periods, providers working at the Master's level, SM aged 17 or 46 or older, and clients receiving a mood, PTSD, anxiety, adjustment, substance or childhood/adolescent psychiatric diagnosis experienced significantly less dropout, while SM aged 18-21 had significantly more dropout. This training is a feasible and available option to increase treatment engagement and improve treatment outcomes for service members.

Proton pump inhibitors and histamine-2 receptor antagonists on the risk of pancreatic cancer: a systematic review and meta-analysis.

BACKGROUND: Proton pump inhibitors (PPI) and histamine-2 receptor antagonists (H2RA) have been widely used for multiple purposes. Recent studies have suggested an association between these medications and the risk of pancreatic cancer. However, the results have been inconclusive. AIM: We, therefore, conducted a study to assess the risk of developing pancreatic cancer in patients who used PPI and H2RA. DESIGN: A systematic review and meta-analysis. METHODS: A literature search was performed using MEDLINE and EMBASE databases from inception through February 2019. Studies that reported risk ratio comparing the risk of pancreatic cancer in patients who received PPI or H2RA versus those who did not receive treatments were included. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effect generic inverse variance method. Sensitivity analysis, excluding one study at a time, was performed. RESULTS: After screening abstracts from the searching methods, seven studies (six case-control studies and one cohort study) were included in the analysis with total 546 199 participants. Compared to patients who did not take medications, the pooled RR of developing pancreatic cancer in patients receiving PPI and H2RA were 1.73 (95% CI: 1.16-2.57) and 1.26 (95% CI: 1.02-1.57), respectively. However, the sensitivity analysis of PPI changed the pooled RR to 1.87 (95% CI: 1.00-3.51) after a study was dropped out. Likewise, H2RA sensitivity analysis also resulted in non-significant pooled RR. CONCLUSIONS: This meta-analysis did not find the strong evidence for the associations between the use of PPI and H2RA and pancreatic cancer.

Bilateral versus unilateral botulinum toxin injections for chronic anal fissure: a randomised trial.

BACKGROUND: Botulinum toxin injected into the internal anal sphincter is used in the treatment of chronic anal fissure but there is no standardised technique for its administration. This randomised single centre trial compares bilateral (either side of fissure) to unilateral injection. METHODS: Participants were randomised to receive bilateral (50 + 50 units) or unilateral (100 units) Dysport® injections into the internal anal sphincter in an outpatient setting. Injection-related pain assessed by visual analogue scale was the primary outcome measure. Secondary outcomes were healing rate, fissure pain, incontinence, and global health scores. RESULTS: Between October 2008 and April 2012, 100 patients with chronic anal fissure were randomised to receive bilateral or unilateral injections. Injection-related pain was comparable in both groups. There was no difference in healing rate. Initially, there was greater improvement in fissure pain in the bilateral group but at 1 year the unilateral group showed greater improvement. Cleveland Clinic Incontinence score was lower in the unilateral group in the early post-treatment period and global health assessment (EuroQol EQ-VAS) was higher in the unilateral group at 1 year. CONCLUSIONS: Injection-related pain was similar in bilateral and unilateral injection groups. Unilateral injection was as effective as bilateral injections in healing and improving fissure pain without any deterioration in continence.

A transvaginal approach to rectovaginal fistulae for the colorectal surgeon: technical notes and case series.

Rectovaginal fistulae (RVF) are not uncommonly seen by the colorectal surgeon and gynaecologist, often debilitating for patients and typically managed with multiple operative procedures, achieving control rather than cure. Transvaginal repair is the least common surgical approach but has clear advantages and equivalent healing rates to other approaches. Here, we describe a simple, safe and effective flapless transvaginal technique for the repair of primary and recurrent low- and mid-level RVF of varying aetiology. We report 15 cases of RVF (nine recurrent) treated by this technique at a single UK centre. The healing rate was 67%. There were no major complications. Median follow-up was 48 months.

Acute Hemolysis with Renal Failure due to Clostridium Bacteremia in a Patient with AML.

We present a case of acute hemolytic anemia, renal failure, and Clostridium perfringens bacteremia in a patient with acute myelogenous leukemia. The high fatality of C. perfringens bacteremia requires that clinicians recognize and rapidly treat patients at risk for this infection. Although other hemolytic processes are in the differential diagnosis of these events, the presence of high fever, chills, and rapidly positive blood cultures may help narrow the diagnosis. Most cases of C. perfringens bacteremia have a concomitant coinfection, which makes broad spectrum empiric therapy essential. There is a high mortality rate of C. perfringens infections associated with leukemia.

Medial frontal GABA is lower in older schizophrenia: a MEGA-PRESS with macromolecule suppression study.

Gamma-butyric acid (GABA) dysfunction has been implicated in the pathophysiology of schizophrenia and its cognitive deficits. Proton magnetic resonance spectroscopy (MRS) was used to test the hypothesis that older participants with schizophrenia have lower anterior cingulate GABA levels compared with older control participants. One-hundred forty-five participants completed this study. For detection of GABA, spectra were acquired from the medial frontal/anterior cingulate cortex using a macromolecule-suppressed MEGA-PRESS sequence. Patients were evaluated for psychopathology and all participants completed neuropsychological tests of working memory, processing speed and functional capacity. GABA levels were significantly lower in the older participants with schizophrenia (n=31) compared with the older control (n=37) group (P=0.003) but not between the younger control (n=40) and schizophrenia (n=29) groups (P=0.994). Age strongly predicted GABA levels in the schizophrenia group accounting for 42% of the variance, but the effect of age was less in the control group accounting for 5.7% of the variance. GABA levels were specifically related to working memory but not processing speed performance, functional capacity, or positive or negative symptom severity. This is the largest MRS study of GABA in schizophrenia and the first to examine GABA without macromolecule contamination, a potentially significant issue in previous studies. GABA levels more rapidly declined with advancing age in the schizophrenia compared with the control group. Interventions targeted at halting the decline or increasing GABA levels may improve functional outcomes and quality of life as patients with schizophrenia age.

Persistent and Unusual Respiratory Findings after Prolonged Glutaraldehyde Exposure.

Glutaraldehyde is commonly used in endoscopy labs to clean and disinfect instruments. It can cause direct irritation of the skin and the upper and lower airways. Health care workers are also at risk for the development of irritant-induced or sensitizer-induced occupational asthma when exposed to this chemical. Herein, we report on a patient who had frequent exposures to glutaraldehyde over one year while working in an endoscopy lab and developed chronic upper and lower respiratory tract symptoms. Multiple spirometric tests during her evaluation revealed variable results including restrictive pattern with a response to bronchodilators, obstructive pattern with a paradoxic bronchoconstrictive response to bronchodilators, and obstructive pattern with a partial response to bronchodilators. These results indicate that the distribution of inflammation and bronchial responsiveness can vary in a single patient with glutaraldehyde-induced occupational asthma. Therefore, the evaluation may be more difficult than might be expected in patients with occupational asthma, and some patients will need multiple pulmonary function tests to characterize their airway disease.

Leflunomide-induced interstitial lung disease (a systematic review).

BACKGROUND: Leflunomide, a disease modifying anti-rheumatic drug in use since 1998, causes interstitial lung disease (ILD) and other pulmonary complications. METHODS: We undertook a systematic review of literature of PubMed (March 2013) to identify the published literature pertaining to pulmonary toxicity associated with leflunomide. RESULTS: We identified 41 relevant articles detailing four population studies and case reports/series on an additional 42 patients. Available data were reviewed and summarized. CONCLUSIONS: Leflunomide can cause ILD. Most of these patients present within three months of starting leflunomide with acute symptoms for a week or less. Bilateral ground glass opacities and diffuse alveolar damage are the most common radiologic and histopathologic findings, respectively. Patients with pre-existing ILD are particularly at risk for this complication, and leflunomide should be avoided in this population. Activated charcoal and cholestyramine significantly decrease the half-life of the drug because of its enterohepatic circulation and should be considered in cases with acute toxicity.

Persistent respiratory symptoms following prolonged capsaicin exposure.

Capsaicin causes direct irritation of the eyes, mucous membranes, and respiratory tract. It is used in self-defense, in crowd control, and as a less lethal weapon in police work. Controlled trials suggest that capsaicin has minimal serious acute effects. Herein, we report a woman who had a 20-minute exposure to capsaicin during a jail riot. She subsequently developed episodic dyspnea and cough, and increased sensitivity to scents, perfumes, and cigarette smoke. She has not had wheezes on physical examination or abnormal pulmonary function tests. Her response to inhaled steroids and long-acting beta-agonists has been incomplete. She appears to have developed airway sensory hyperreactivity syndrome after the inhalation of capsaicin, which likely injured sensory nerves and/or caused persistent neurogenic inflammation.

Using coherent X-ray ptychography to probe medium-range order.

Characterization of microscopic structural order and in particular medium range order (MRO) in amorphous materials is challenging. A new technique is demonstrated that allows analysis of MRO using X-rays. Diffraction data were collected from a sample consisting of densely packed polystyrene-latex micro-spheres. Ptychography is used to reconstruct the sample transmission function and fluctuation microscopy applied to characterize structural order producing a detailed `fluctuation map' allowing analysis of the sample at two distinct length scales. Independent verification is provided via X-ray diffractometry. Simulations of dense random packing of spheres have also been used to explore the origin of the structural order measured.

Use and safety of conducted electronic devices: what is known?

Conductive electronic devices (CED), such as Taser and stun guns, are sold worldwide for use by security services, although they have also been used for self-defence and even for torture. CED are promoted as non-lethal weapons which can potentially save lives. However, there are multiple reports of deaths temporally associated with CED use. These weapons have definite physiological effects in normal volunteers, especially when accompanied by exertion. Medical examiners often report that deaths followed physical encounters which included the use of CED were due to natural causes, excited delirium and/or drug intoxication. These cases present complex situations in which multiple factors potentially contribute to the death, including electric shocks which cause neuromuscular incapacitation, severe pain and anxiety. Public health officials, physicians and hospital personnel need to be aware that individuals controlled with CED are at increased risk of death. We need better recording of incidents worldwide to understand the extent and outcomes of CED use.

Nanoscale Fresnel coherent diffraction imaging tomography using ptychography.

We demonstrate Fresnel Coherent Diffractive Imaging (FCDI) tomography in the X-ray regime. The method uses an incident X-ray illumination with known curvature in combination with ptychography to overcome existing problems in diffraction imaging. The resulting tomographic reconstruction represents a 3D map of the specimen's complex refractive index at nano-scale resolution. We use this technique to image a lithographically fabricated glass capillary, in which features down to 70nm are clearly resolved.

Simultaneous X-ray fluorescence and ptychographic microscopy of Cyclotella meneghiniana.

Scanning X-ray fluorescence microscopy (XFM) is a particularly useful method for studying the spatial distribution of trace metals in biological samples. Here we demonstrate the utility of combining coherent diffractive imaging (CDI) with XFM for imaging biological samples to simultaneously produce high-resolution and high-contrast transmission images and quantitative elemental maps. The reconstructed transmission function yields morphological details which contextualise the elemental maps. We report enhancement of the spatial resolution in both the transmission and fluorescence images beyond that of the X-ray optics. The freshwater diatom Cyclotella meneghiniana was imaged to demonstrate the benefits of combining these techniques that have complementary contrast mechanisms.

Acute respiratory symptoms following massive carbon black exposure.

BACKGROUND: Chronic carbon black exposure in the work environment can cause both respiratory symptoms and changes in lung function. There is limited information on the respiratory effects of acute exposure to carbon black. METHODS: Case report and literature review. RESULTS: A 44-year-old man had intense exposure to carbon black when his crane ran into a truck with a trailer filled with carbon black. One week after this exposure he developed shortness of breath and cough with sputum production. These symptoms persisted and increased in intensity. Physical examination revealed expiratory wheezes when in the supine position. Pulmonary function tests revealed a mild obstructive ventilatory defect with a reduced FEV(1)/FVC ratio. The patient responded to treatment with fluticasone and salmeterol with a reduction in symptoms and improvement in his spirometry to a normal range. CONCLUSIONS: Acute exposure to carbon black can cause respiratory symptoms and an obstructive ventilatory defect. This presentation suggests a small airway disease which improved over time with inhaled steroids and long-acting beta-agonists. Patients with intense carbon black exposure following industrial accidents will need frequent evaluation to manage any related respiratory tract injury.

The soft x-ray instrument for materials studies at the linac coherent light source x-ray free-electron laser.

The soft x-ray materials science instrument is the second operational beamline at the linac coherent light source x-ray free electron laser. The instrument operates with a photon energy range of 480-2000 eV and features a grating monochromator as well as bendable refocusing mirrors. A broad range of experimental stations may be installed to study diverse scientific topics such as: ultrafast chemistry, surface science, highly correlated electron systems, matter under extreme conditions, and laboratory astrophysics. Preliminary commissioning results are presented including the first soft x-ray single-shot energy spectrum from a free electron laser.

An in-vacuum x-ray diffraction microscope for use in the 0.7-2.9 keV range.

A dedicated in-vacuum coherent x-ray diffraction microscope was installed at the 2-ID-B beamline of the Advanced Photon Source for use with 0.7-2.9 keV x-rays. The instrument can accommodate three common implementations of diffractive imaging; plane wave illumination; defocused-probe (Fresnel diffractive imaging) and scanning (ptychography) using either a pinhole, focused or defocused probe. The microscope design includes active feedback to limit motion of the optics with respect to the sample. Upper bounds on the relative optics-to-sample displacement have been measured to be 5.8 nm(v) and 4.4 nm(h) rms/h using capacitance micrometry and 27 nm/h using x-ray point projection imaging. The stability of the measurement platform and in-vacuum operation allows for long exposure times, high signal-to-noise and large dynamic range two-dimensional intensity measurements to be acquired. Finally, we illustrate the microscope's stability with a recent experimental result.

Factors affecting chronic obstructive pulmonary disease early rehospitalization.

The Centers for Medicare and Medicaid Services has identified early rehospitalization of patients with chronic obstructive pulmonary disease (COPD) exacerbations as a performance measure for hospital care. We retrospectively reviewed patients with COPD who were admitted to University Medical Center, Lubbock, Texas, USA, between October 2010 and March 2011. There were 81 COPD patients with 103 hospitalizations. The mean age was 73.9 years. Pulmonary function tests using the Global initiative for chronic Obstructive Lung Disease criteria had been done in 36 patients (44.4%) and revealed 1 mild (2.8%), 7 moderate (19.4%), 20 severe (55.6%), and 8 very severe (22.2%) cases. Only 38.4% of the patients had prior influenza vaccine. Most patients were treated with antibiotics (81.8%) and corticosteroids (87.9%). The mean length of stay was 4.9 days, and 4 patients died. Most of the patients were discharged home (63.6%) with a median follow-up interval of 14 days. Thirty-two percent did not have long-acting bronchodilators and/or inhaled corticosteroids prescribed on discharge. There were 14 early rehospitalizations within 30 days. Logistic regression analysis indicated that a history of coronary artery disease (odds ratio (OR) 6.4, 95% confidence interval (CI) 1.1-37.4) and unilateral pulmonary infiltrates (OR 12.8, 95% CI 1.9-86.4) significantly increased the early rehospitalization rates. Acute exacerbations of COPD in patients with a history of ischemic heart disease or unilateral pulmonary infiltrates are at increased risk for early readmission. These risk factors should be identified during hospitalization; early follow-up or other interventions may reduce readmissions. Influenza vaccine, maintenance bronchodilators and/or inhaled corticosteroids, and pulmonary function tests were underused, and these standards of care should be provided to improve care.

Barium proctography vs magnetic resonance proctography for pelvic floor disorders: a comparative study.

AIM: Accurate and reliable imaging of pelvic floor dynamics is important for tailoring treatment in pelvic floor disorders; however, two imaging modalities are available. Barium proctography (BaP) is widely used, but involves a significant radiation dose. Magnetic resonance (MR) proctography allows visualization of all pelvic midline structures but patients are supine. This project investigates whether there are measurable differences between BaP and MR proctography. Patient preference for the tests was also investigated. METHODS: Consecutive patients referred for BaP were invited to participate (National Research Ethics Service approved). Participants underwent BaP in Poole and MR proctography in Dorchester. Proctograms were reported by a consultant radiologist with pelvic floor subspecialization. RESULTS: A total of 71 patients were recruited. Both tests were carried out on 42 patients. Complete rectal emptying was observed in 29% (12/42) on BaP and in 2% (1/42) on MR proctography. Anismus was reported in 29% (12/42) on BaP and 43% (18/42) on MR proctography. MR proctography missed 31% (11/35) of rectal intussusception detected on BaP. In 10 of these cases no rectal evacuation was achieved during MR proctography. The measure of agreement between grade of rectal intussusception was fair (κ=0.260) although MR proctography tended to underestimate the grade. Rectoceles were extremely common but clinically relevant differences in size were evident. Patients reported that they found MR proctography less embarrassing but harder to empty their bowel. CONCLUSIONS: The results demonstrate that MR proctography under-reports pelvic floor abnormalities especially where there has been poor rectal evacuation.