Emission lines due to ionizing radiation from a compact object in the remnant of Supernova 1987A.

The nearby Supernova 1987A was accompanied by a burst of neutrino emission, which indicates that a compact object (a neutron star or black hole) was formed in the explosion. There has been no direct observation of this compact object. In this work, we observe the supernova remnant with JWST spectroscopy, finding narrow infrared emission lines of argon and sulfur. The line emission is spatially unresolved and blueshifted in velocity relative to the supernova rest frame. We interpret the lines as gas illuminated by a source of ionizing photons located close to the center of the expanding ejecta. Photoionization models show that the line ratios are consistent with ionization by a cooling neutron star or a pulsar wind nebula. The velocity shift could be evidence for a neutron star natal kick.

Amygdalar activity measured using FDG-PET/CT at head and neck cancer staging independently predicts survival.

IMPORTANCE: The mechanisms underlying the association between chronic stress and higher mortality among individuals with cancer remain incompletely understood. OBJECTIVE: To test the hypotheses that among individuals with active head and neck cancer, that higher stress-associated neural activity (ie. metabolic amygdalar activity [AmygA]) at cancer staging associates with survival. DESIGN: Retrospective cohort study. SETTING: Academic Medical Center (Massachusetts General Hospital, Boston). PARTICIPANTS: 240 patients with head and neck cancer (HNCA) who underwent 18F-FDG-PET/CT imaging as part of initial cancer staging. MEASUREMENTS: 18F-FDG uptake in the amygdala was determined by placing circular regions of interest in the right and left amygdalae and measuring the mean tracer accumulation (i.e., standardized uptake value [SUV]) in each region of interest. Amygdalar uptake was corrected for background cerebral activity (mean temporal lobe SUV). RESULTS: Among individuals with HNCA (age 59±13 years; 30% female), 67 died over a median follow-up period of 3 years (IQR: 1.7-5.1). AmygA associated with heightened bone marrow activity, leukocytosis, and C-reactive protein (P<0.05 each). In adjusted and unadjusted analyses, AmygA associated with subsequent mortality (HR [95% CI]: 1.35, [1.07-1.70], P = 0.009); the association persisted in stratified subset analyses restricted to patients with advanced cancer stage (P<0.001). Individuals within the highest tertile of AmygA experienced a 2-fold higher mortality rate compared to others (P = 0.01). The median progression-free survival was 25 months in patients with higher AmygA (upper tertile) as compared with 36.5 months in other individuals (HR for progression or death [95%CI], 1.83 [1.24-2.68], P = 0.001). CONCLUSIONS AND RELEVANCE: AmygA, quantified on routine 18F-FDG-PET/CT images obtained at cancer staging, independently and robustly predicts mortality and cancer progression among patients with HNCA. Future studies should test whether strategies that attenuate AmygA (or its downstream biological consequences) may improve cancer survival.

Can Crude Oil Exploration Influence the Phytochemicals and Bioactivity of Medicinal Plants? A Case of Nigerian Vernonia amygdalina and Ocimum gratissimum.

The Nigerian Niger-Delta crude oil exploration often results in spills that affect indigenous medicinal plant biodiversity, likely changing the phytochemical profile of surviving species, their bioactivity or toxicity. In crude oil-rich Kokori and crude oil-free Abraka, classic examples of indigenous plants occupying the medicine-food interface include Vernonia amygdalina (VAL) and Ocimum gratissimum leaves (OGL). These plants are frequently utilised during pregnancy and in anaemia. To date, no scientific investigation has been reported on the potential changes to the phytochemical or bioactivity of the study plants. To discuss the similarities and dissimilarities in antisickling bioactivity and phytochemicals in VAL and OGL collected from Kokori (VAL-KK and OGL-KK) and Abraka (VAL-AB and OGL-AB), in silico, in vitro and comparative UPLC-QTOF-MS analysis was performed. Nine unique compounds were identified in OGL-KK, which have never been reported in the literature, while differences in antisickling potentials were observed in VAL-KK, OGL-KK and, VAL-AB, OGL-AB. Our findings show that VAL-AB and OGL-AB are richer and more diverse in phytochemicals and displayed a slightly higher antisickling activity than VAL-KK and OGL-KK. Ligand-based pharmacophore modelling was performed to understand the potential compounds better; this study may provide a basis for explaining the effect of crude oil spills on secondary metabolites and a reference for further research.

Pediatric Groin Surgeries: A Comparison of Analgesic Effects of Caudal Block and Inguinal Field Block Using Plain Bupivacaine.

Introduction: There is a paucity of studies in the West African sub-region which have compared both the intraoperative and postoperative analgesic effects of caudal block and inguinal field block using plain bupivacaine in groin surgeries in children. The study aimed to compare the duration of analgesia and complications of caudal block and inguinal field block in pediatric groin surgeries. Patients and Methods: This was a prospective, double-blind randomized study conducted at a tertiary health institution in North Central, Nigeria, over a period of 6 months. A total of 74 children scheduled for day case groin surgeries for inguinal hernia, hydrocoele and palpable undescended testis were recruited into the study. The effectiveness of the analgesic effect was assessed by measuring serum cortisol levels before surgery (i.e. baseline at 8am), 5minutes after caudal block or inguinal field block, and 1-hour after surgery. Post-operative pain was determined using FLACC score (Face, Legs, Activity, Crying and Consolability) every 15 minutes till 6 hours after surgery when the patients were discharged home and the caregivers measured the patients' pain scores using the FLACC score every 1 hour to a maximum duration of 10 hours after surgery. Data obtained from the study was entered into the study proforma and analysed using IBM SPSS version 21.0. The P value was considered statistically significant at <0.05. Results: A total of 74 patients were recruited for this study, with 68 males (91.9%) and 6 females (8.1%). The children's age range was 6 months to 7 years, with a mean age of 3.35 ± 1.90 years. The mean basal serum cortisol levels of the caudal block group and inguinal block group were 11.15 ± 5.38 µg/dL and 10.79 ± 4.92µg/d respectively (p-value = 0.767). Five minutes after caudal block, the mean serum cortisol level was 10.50 ± 5.39µg/dL while inguinal field block was 10.63 ± 4.68µg/dL (p-value = 0.288). The mean serum cortisol level obtained one hour after each procedure was 9.34 ± 4.05 µg/dL for the caudal block group and 10.00 ± 3.56 µg/dL in the inguinal field block group with p-value = 0.275.Using the FLACC score, the mean duration of analgesia in caudal block group was 372.00 ± 71.55 minutes and was inguinal field block group was 387.43 ± 62.65 minutes with a p-value = 0.116. There was no anaesthetic technique related complications that was recorded in both caudal block group and inguinal group during the study period. Conclusion: This study demonstrated that caudal block and inguinal field block using plain bupivacaine provided comparable duration of analgesia in paediatric groin surgeries. Therefore, caudal block or inguinal field block using plain bupivacaine should be recommended for both intraoperative and postoperative analgesia in elective paediatric groin surgeries.

Artificial intelligence and machine learning algorithms for early detection of skin cancer in community and primary care settings: a systematic review.

Skin cancers occur commonly worldwide. The prognosis and disease burden are highly dependent on the cancer type and disease stage at diagnosis. We systematically reviewed studies on artificial intelligence and machine learning (AI/ML) algorithms that aim to facilitate the early diagnosis of skin cancers, focusing on their application in primary and community care settings. We searched MEDLINE, Embase, Scopus, and Web of Science (from Jan 1, 2000, to Aug 9, 2021) for all studies providing evidence on applying AI/ML algorithms to the early diagnosis of skin cancer, including all study designs and languages. The primary outcome was diagnostic accuracy of the algorithms for skin cancers. The secondary outcomes included an overview of AI/ML methods, evaluation approaches, cost-effectiveness, and acceptability to patients and clinicians. We identified 14 224 studies. Only two studies used data from clinical settings with a low prevalence of skin cancers. We reported data from all 272 studies that could be relevant in primary care. The primary outcomes showed reasonable mean diagnostic accuracy for melanoma (89·5% [range 59·7-100%]), squamous cell carcinoma (85·3% [71·0-97·8%]), and basal cell carcinoma (87·6% [70·0-99·7%]). The secondary outcomes showed a heterogeneity of AI/ML methods and study designs, with high amounts of incomplete reporting (eg, patient demographics and methods of data collection). Few studies used data on populations with a low prevalence of skin cancers to train and test their algorithms; therefore, the widespread adoption into community and primary care practice cannot currently be recommended until efficacy in these populations is shown. We did not identify any health economic, patient, or clinician acceptability data for any of the included studies. We propose a methodological checklist for use in the development of new AI/ML algorithms to detect skin cancer, to facilitate their design, evaluation, and implementation.

The efficacy and safety of cardio-protective therapy in patients with 5-FU (Fluorouracil)-associated coronary vasospasm.

BACKGROUND: Coronary vasospasm is a known side effect of 5-FU (fluorouracil) therapy. Beyond switching to non-5FU-based chemotherapy, there are no established treatments for 5-FU associated coronary vasospam. Our objective was to assess the safety and efficacy of re-challenge with 5-FU after pre-treatment with calcium channel blockers (CCBs) and long-acting nitrates among patients 5-FU associated coronary vasospasm. METHODS: We conducted a retrospective study of patients with 5-FU coronary vasospasm at a single academic center. By protocol, those referred to cardio-oncology received pre-treatment with either combination [nitrates and CCBs] or single-agent therapy [nitrates or CCBs]) prior to re-challenge with 5-FU. Our primary outcome was overall survival. Other important outcomes included progression-free survival and safety. RESULTS: Among 6,606 patients who received 5-FU from January 2001 to Dec 2020, 115 (1.74%) developed coronary vasospasm. Of these 115 patients, 81 patients continued 5-FU therapy, while 34 stopped. Of the 81 who continued, 78 were referred to cardio-oncology and prescribed CCBs and/or nitrates prior to subsequent 5-FU, while the remaining 3 continued 5-FU without cardiac pre-treatment. Of the 78, 56.4% (44/78) received both nitrates and CCBs, 19.2% (15/78) received CCBs alone, and 24.4% (19/78) received nitrates alone. When compared to patients who stopped 5-FU, those who continued 5-FU after pre-treatment (single or combination therapy) had a decreased risk of death (HR 0.42, P = 0.005 [95% CI 0.23-0.77]) and a trend towards decreased cancer progression (HR 0.60, P = 0.08 [95% CI 0.34-1.06]). No patient in the pre-treatment group had a myocardial infarct after re-challenge; however, chest pain (without myocardial infarction) recurred in 19.2% (15/78) among those who received cardiac pre-treatment vs. 66.7% (2/3) among those who did not (P = 0.048). There was no difference in efficacy or the recurrence of vasospasm among patients who received pre-treatment with a single agent (nitrates or CCBs) or combination therapy (14.7% (5/34) vs. 25.0% (11/44), P = 0.26). CONCLUSION: Re-challenge after pre-treatment with CCBs and nitrates guided by a cardio-oncology service was safe and allowed continued 5-FU therapy.

Idiopathic Intracranial Hypertension is Associated with a Higher Burden of Visible Cerebral Perivascular Spaces: The Glymphatic Connection.

BACKGROUND AND PURPOSE: Research suggests a connection between idiopathic intracranial hypertension and the cerebral glymphatic system. We hypothesized that visible dilated perivascular spaces, possible glymphatic pathways, would be more prevalent in patients with idiopathic intracranial hypertension. This prevalence could provide a biomarker and add evidence to the glymphatic connection in the pathogenesis of idiopathic intracranial hypertension. MATERIALS AND METHODS: We evaluated 36 adult (older than 21 years of age) patients with idiopathic intracranial hypertension and 19 controls, 21-69 years of age, who underwent a standardized MR imaging protocol that included high-resolution precontrast T2- and T1-weighted images. All patients had complete neuro-ophthalmic examinations for papilledema. The number of visible perivascular spaces was evaluated using a comprehensive 4-point qualitative rating scale, which graded the number of visible perivascular spaces in the centrum semiovale and basal ganglia; a 2-point scale was used for the midbrain. Readers were blinded to patient diagnoses. Continuous variables were compared using a Student t test. RESULTS: The mean number of visible perivascular spaces overall was greater in the idiopathic intracranial hypertension group than in controls (4.5 [SD, 1.9] versus 2.9 [SD, 1.9], respectively; P = .004). This finding was significant for centrum semiovale idiopathic intracranial hypertension (2.3 [SD, 1.4] versus controls, 1.3 [SD, 1.1], P = .003) and basal ganglia idiopathic intracranial hypertension (1.7 [SD, 0.6] versus controls, 1.2 [SD, 0.7], P = .009). There was no significant difference in midbrain idiopathic intracranial hypertension (0.5 [SD, 0.5] versus controls, 0.4 [SD, 0.5], P = .47). CONCLUSIONS: Idiopathic intracranial hypertension is associated with an increased number of visible intracranial perivascular spaces. This finding provides insight into the pathophysiology of idiopathic intracranial hypertension, suggesting a possible relationship between idiopathic intracranial hypertension and glymphatic dysfunction and providing another useful biomarker for the disease.

The Incidence, Risk Factors, and Outcomes With 5-Fluorouracil-Associated Coronary Vasospasm.

BACKGROUND: Coronary vasospasm is a recognized side effect of 5-FU (fluorouracil). There are limited and conflicting data on the incidence, risk factors and prognostic effect of 5-FU associated vasospasm. OBJECTIVES: To assess the incidence, risk factors and prognostic implications of 5-FU coronary vasospasm among patients receiving 5-FU regimens at a single tertiary care center. METHODS: We conducted a retrospective analysis of all patients who received 5-FU at a single academic center from January 2009 to July 2019. Vasospasm was defined as the occurrence of a typical chest pain syndrome in the presence of 5-FU. The presence of associated electrocardiogram (ECG) changes and/or elevated biomarkers was used to further confirm the diagnosis. Patients with vasospasm were compared to patients treated with 5-FU without vasospasm in a 1:2 ratio. Data regarding demographics, medical history, and follow-up were collected by manual chart review. RESULTS: From approximately 4019 individual patients who received 5-FU from 2009 to 2019 at a single center, 87 (2.16%) developed vasospasm. Patients who developed vasospasm were younger (58±13 vs. 64±13 years, P = 0.001), and were less likely to have any cardiovascular risk factors (70.1% vs. 84.5%, P = 0.007). Patients with vasospasm and patients without vasospasm were otherwise similar in terms of types of cancer, stage of cancer, sex, and race. There was no significant difference in progression-free survival, overall mortality or cancer specific mortality between patients who developed vasospasm versus those who did not. CONCLUSION: In a large, single-center report of 5-FU associated vasospasm, patients who developed vasospasm were younger, had lower rates of traditional cardiovascular risk factors and had no significant difference in progression-free or overall survival compared to those who did not develop vasospasm.

Electrocardiographic features of immune checkpoint inhibitor associated myocarditis.

BACKGROUND: Myocarditis is a highly morbid complication of immune checkpoint inhibitor (ICI) use that remains inadequately characterized. The QRS duration and the QTc interval are standardized electrocardiographic measures that are prolonged in other cardiac conditions; however, there are no data on their utility in ICI myocarditis. METHODS: From an international registry, ECG parameters were compared between 140 myocarditis cases and 179 controls across multiple time points (pre-ICI, on ICI prior to myocarditis, and at the time of myocarditis). The association between ECG values and major adverse cardiac events (MACE) was also tested. RESULTS: Both the QRS duration and QTc interval were similar between cases and controls prior to myocarditis. When compared with controls on an ICI (93±19 ms) or to baseline prior to myocarditis (97±19 ms), the QRS duration prolonged with myocarditis (110±22 ms, p<0.001 and p=0.009, respectively). In contrast, the QTc interval at the time of myocarditis (435±39 ms) was not increased compared with pre-myocarditis baseline (422±27 ms, p=0.42). A prolonged QRS duration conferred an increased risk of subsequent MACE (HR 3.28, 95% CI 1.98 to 5.62, p<0.001). After adjustment, each 10 ms increase in the QRS duration conferred a 1.3-fold increase in the odds of MACE (95% CI 1.07 to 1.61, p=0.011). Conversely, there was no association between the QTc interval and MACE among men (HR 1.33, 95% CI 0.70 to 2.53, p=0.38) or women (HR 1.48, 95% CI 0.61 to 3.58, p=0.39). CONCLUSIONS: The QRS duration is increased in ICI myocarditis and is associated with increased MACE risk. Use of this widely available ECG parameter may aid in ICI myocarditis diagnosis and risk-stratification.

Minimally invasive organ-preserving approaches in the management of mesh erosion after laparoscopic ventral mesh rectopexy.

AIM: This is a systematic approach for minimally invasive methods in the management of mesh erosion after laparoscopic ventral mesh rectopexy. METHODS: All patients managed with organ-preserving techniques for mesh erosion were identified from a prospective database and clinical records were reviewed. Each patient was contacted via telephone and a structured questionnaire was applied. A Likert score was used to assess patient symptoms and overall satisfaction with management. One or more of the following techniques were used: (i) transanal or transvaginal trimming/excision of exposed mesh and sutures, with or without using transanal endoscopic micro surgery or transanal minimally invasive surgery; (ii) laparoscopic pelvic assessment and detachment of mesh from the sacral promontory. RESULTS: Eleven patients were managed for mesh erosion with organ-preserving techniques. All were women with a median age of 60 years [interquartile range (IQR) 53.5-68.5]. Vaginal, rectal, perineal erosion and recto-vaginal fistulation occurred in five, four, one and one patient respectively. Vaginal erosions presented at a median of 51 months (IQR 36-56) after index laparoscopic ventral mesh rectopexy compared to 17.5 months (IQR 14.5-27.25) for the rectal erosions. Median follow-up time was 24 months (IQR 19-49). Four of the meshes (36%) were removed completely whereas seven (63%) were partially removed. Vaginal erosions required a median of two procedures to achieve resolution as opposed to five for rectal. Out of 11 patients, eight were satisfied with the outcome of their management, whereas two were not and one remained ambivalent. CONCLUSION: An organ-sparing minimally invasive approach is feasible in managing mesh erosions but requires multiple procedures and months to complete.

Non-invasive beam profile monitor for medical accelerators.

A beam profile monitor based on a supersonic gas-curtain is currently under development for transverse profile diagnostics of electron and proton beams in the High Luminosity LHC. This monitor uses a thin supersonic gas curtain that crosses the primary beam to be characterized under an angle of 45 degrees. The fluorescence caused by the interaction between the beam and gas-curtain is detected using a specially designed imaging system to determine the 2D transverse profile of the primary beam. Another prototype monitor based on beam induced ionization is installed at The Cockcroft Institute. This paper presents the design features of both the monitors, the gas-jet curtain formation and various experimental tests, including profile measurements of an electron beam, using helium, nitrogen and neon as gases. Such a non-invasive online beam profile monitor would be highly desirable also for medical LINAC's and storage rings as it can characterize the beam without stopping machine operation. The paper discusses opportunities for simplifying the monitor design for integration into a medical accelerator and expected monitor performance.

Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis.

BACKGROUND: There is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving standard chemotherapy. There are no data on the use of GLS in ICI myocarditis. OBJECTIVES: This study sought to evaluate the role of GLS and assess its association with cardiac events among patients with ICI myocarditis. METHODS: This study retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI myocarditis (cases, n = 101) to that from patients receiving an ICI who did not develop myocarditis (control subjects, n = 92). Where available, GLS was also measured pre-ICI in both groups. Major adverse cardiac events (MACE) were defined as a composite of cardiogenic shock, arrest, complete heart block, and cardiac death. RESULTS: Cases and control subjects were similar in age, sex, and cancer type. At presentation with myocarditis, 61 cases (60%) had a normal ejection fraction (EF). Pre-ICI, GLS was similar between cases and control subjects (20.3 ± 2.6% vs. 20.6 ± 2.0%; p = 0.60). There was no change in GLS among control subjects on an ICI without myocarditis (pre-ICI vs. on ICI, 20.6 ± 2.0% vs. 20.5 ± 1.9%; p = 0.41); in contrast, among cases, GLS decreased to 14.1 ± 2.8% (p < 0.001). The GLS at presentation with myocarditis was lower among cases presenting with either a reduced (12.3 ± 2.7%) or preserved EF (15.3 ± 2.0%; p < 0.001). Over a median follow-up of 162 days, 51 (51%) experienced MACE. The risk of MACE was higher with a lower GLS among patients with either a reduced or preserved EF. After adjustment for EF, each percent reduction in GLS was associated with a 1.5-fold increase in MACE among patients with a reduced EF (hazard ratio: 1.5; 95% confidence interval: 1.2 to 1.8) and a 4.4-fold increase with a preserved EF (hazard ratio: 4.4; 95% confidence interval: 2.4 to 7.8). CONCLUSIONS: GLS decreases with ICI myocarditis and, compared with control subjects, was lower among cases presenting with either a preserved or reduced EF. Lower GLS was strongly associated with MACE in ICI myocarditis presenting with either a preserved or reduced EF.

Dermoscopy for melanoma detection and triage in primary care: a systematic review.

OBJECTIVE: Most skin lesions first present in primary care, where distinguishing rare melanomas from benign lesions can be challenging. Dermoscopy improves diagnostic accuracy among specialists and is promoted for use by primary care physicians (PCPs). However, when used by untrained clinicians, accuracy may be no better than visual inspection. This study aimed to undertake a systematic review of literature reporting use of dermoscopy to triage suspicious skin lesions in primary care settings, and challenges for implementation. DESIGN: A systematic literature review and narrative synthesis. DATA SOURCES: We searched MEDLINE, Cochrane Central, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and SCOPUS bibliographic databases from 1 January 1990 to 31 December 2017, without language restrictions. INCLUSION CRITERIA: Studies including assessment of dermoscopy accuracy, acceptability to patients and PCPs, training requirements, and cost-effectiveness of dermoscopy modes in primary care, including trials, diagnostic accuracy and acceptability studies. RESULTS: 23 studies met the review criteria, representing 49 769 lesions and 3708 PCPs, all from high-income countries. There was a paucity of studies set truly in primary care and the outcomes measured were diverse. The heterogeneity therefore made meta-analysis unfeasible; the data were synthesised through narrative review. Dermoscopy, with appropriate training, was associated with improved diagnostic accuracy for melanoma and benign lesions, and reduced unnecessary excisions and referrals. Teledermoscopy-based referral systems improved triage accuracy. Only three studies examined cost-effectiveness; hence, there was insufficient evidence to draw conclusions. Costs, training and time requirements were considered important implementation barriers. Patient satisfaction was seldom assessed. Computer-aided dermoscopy and other technological advances have not yet been tested in primary care. CONCLUSIONS: Dermoscopy could help PCPs triage suspicious lesions for biopsy, urgent referral or reassurance. However, it will be important to establish further evidence on minimum training requirements to reach competence, as well as the cost-effectiveness and patient acceptability of implementing dermoscopy in primary care. TRIAL REGISTRATION NUMBER: CRD42018091395.

Two new phytoecdysteroids from Sphenocentrum jollyanum Pierre root.

The crude methanol extract of Sphenocentrum jollyanum root exhibited 98% and 80% antimicrobial activity against Aspergillus fumigatus Pinh and Vancomycin resistant enterococcus (VRE) at a concentration of 200 µg/mL, with IC50 11.45 and 12.95 µg/mL, respectively. The ethyl acetate fraction of methanol extract showed in-vitro antimicrobial activity against A. fumigatus Pinh at 83% with IC50 of <8 µg/mL. The phytochemical investigation of ethyl acetate fraction yielded six compounds, which were identified by their NMR, IR and MS spectral analyses as two new phytoecdysteroidal glycosides Sphenocentroside A (1), and Sphenocentroside B (2), and four known phytoecdysteroids: polypodoaurein (3), polypodine B (4), ecdysterone (5), and 20, 26-dihydroxyecdysone (6).

Cardiotoxicity of Immune Checkpoint Inhibitors.

PURPOSE OF REVIEW: Immunotherapies, particularly immune checkpoint inhibitors (ICI), are revolutionary cancer therapies being increasingly applied to a broader range of cancers. Our understanding of the mechanism, epidemiology, diagnosis, and treatment of cardiotoxicity related to immunotherapies remains limited. We aim to synthesize the limited current literature on cardiotoxicity of ICIs and to share our opinions on the diagnosis and treatment of this condition. RECENT FINDINGS: The incidence of ICI-associated myocarditis ranges from 0.1 to 1%. Patients with ICI-associated myocarditis often have a fulminant course with a case fatality rate of 25-50%. The diagnosis of this condition poses many challenges because independently a normal electrocardiogram, biomarkers, or a preserved left ventricular function do not rule out ICI-associated myocarditis. Endomyocardial biopsy should be pursued when clinical suspicion remains despite normal non-invasive tests. Data on optimal screening and surveillance tools are lacking. Cessation of ICIs, combined with high dose corticosteroids and other immunosuppressant approaches are the cornerstones of the treatment of ICI-associated myocarditis. This condition may recur when patients are re-challenged with these agents and the decision to resume ICIs should be made through a multidisciplinary discussion. Immunotherapies have changed the landscape of cancer treatment. Recognizing and managing cardiotoxicity related to ICIs is of critical importance. Our understanding of ICI-cardiotoxicity has improved, but large information gaps remain for further research. Due to the high case fatality rate, any type of cardiac symptoms or signs in a patient who has recently started an ICI should prompt consideration of ICI-cardiotoxicity.

Dermoscopy use in UK primary care: a survey of GPs with a special interest in dermatology.

BACKGROUND: Melanoma accounts for 90% of skin cancer mortality and typically presents in primary care, where it can be challenging to distinguish from benign lesions. Dermoscopy is a tool for skin visualization that is routinely used for melanoma diagnosis in secondary care. However, the role of dermoscopy in primary care remains unclear. OBJECTIVES: To determine views on, and use of, dermoscopy by dermatology-interested general practitioners (GPs). METHODS: An online questionnaire was emailed to the UK Primary Care Dermatology Society members in February 2018, and responses collected over the following 4 weeks. RESULTS: A total of 205 responses were analysed. Most respondents were GPs (94%), aged over 50 (53%), had a postgraduate dermatological qualification (67%) and used dermoscopy regularly when reviewing pigmented skin lesions (97%). Dermoscopy use was commoner amongst GPs who had worked longer in primary care and had experience of secondary care dermatology. Most had undertaken training in dermoscopy (91%), although one-fifth (20%) had not updated their training in over 5 years. Most of those who had received only 1 day of face-to-face training reported feeling confident using a dermatoscope. Few respondents (11%) reported access to teledermatology or teledermoscopy for urgent or routine referrals. CONCLUSIONS: UK GPs with a special interest in dermatology are routinely using dermoscopy in the primary care setting. More research is needed to establish optimal approaches to training and updating GP dermoscopy skills. When dermoscopy has been shown to be safe, effective, acceptable and cost-effective in this setting, more GPs may also be able to gain and maintain the skills to implement dermoscopy into routine primary care. Technological advances, including incorporation of artificial intelligence (AI) and algorithms to guide GPs, could also contribute to widening use of dermoscopy among GPs.

Influenza vaccination and myocarditis among patients receiving immune checkpoint inhibitors.

BACKGROUND: Influenza vaccination (FV) is recommended for patients with cancer. Recent data suggested that the administration of the FV was associated with an increase in immune-related adverse events (irAEs) among patients on immune checkpoint inhibitors (ICIs). Myocarditis is an uncommon but serious complication of ICIs and may also result from infection with influenza. There are no data testing the relationship between FV and the development of myocarditis on ICIs. METHODS: Patients on ICIs who developed myocarditis (n = 101) (cases) were compared to ICI-treated patients (n = 201) without myocarditis (controls). A patient was defined as having the FV if they were administered the FV from 6 months prior to start of ICI to anytime during ICI therapy. Alternate thresholds for FV status were also tested. The primary comparison of interest was the rate of FV between cases and controls. Patients with myocarditis were followed for major adverse cardiac events (MACE), defined as the composite of cardiogenic shock, cardiac arrest, hemodynamically significant complete heart block and cardiovascular death. RESULTS: The FV was administered to 25% of the myocarditis cases compared to 40% of the non-myocarditis ICI-treated controls (p = 0.01). Similar findings of lower rates of FV administration were noted among myocarditis cases when alternate thresholds were tested. Among the myocarditis cases, those who were vaccinated had 3-fold lower troponin levels when compared to unvaccinated cases (FV vs. No FV: 0.12 [0.02, 0.47] vs. 0.40 [0.11, 1.26] ng/ml, p = 0.02). Within myocarditis cases, those administered the FV also had a lower rate of other irAEs when compared to unvaccinated cases (36 vs. 55% p = 0.10) including lower rates of pneumonitis (12 vs. 36%, p = 0.03). During follow-up (175 [IQR 89, 363] days), 47% of myocarditis cases experienced a MACE. Myocarditis cases who received the FV were at a lower risk of cumulative MACE when compared to unvaccinated cases (24 vs. 59%, p = 0.002). CONCLUSION: The rate of FV among ICI-related myocarditis cases was lower than controls on ICIs who did not develop myocarditis. In those who developed myocarditis related to an ICI, there was less myocardial injury and a lower risk of MACE among those who were administered the FV.

Positive reinforcement targeting abstinence in substance misuse (PRAISe): Study protocol for a Cluster RCT & process evaluation of contingency management.

There are approximately 256,000 heroin and other opiate users in England of whom 155,000 are in treatment for heroin (or opiate) addiction. The majority of people in treatment receive opiate substitution treatment (OST) (methadone and buprenorphine). However, OST suffers from high attrition and persistent heroin use even whilst in treatment. Contingency management (CM) is a psychological intervention based on the principles of operant conditioning. It is delivered as an adjunct to existing evidence based treatments to amplify patient benefit and involves the systematic application of positive reinforcement (financial or material incentives) to promote behaviours consistent with treatment goals. With an international evidence base for CM, NICE recommended that CM be implemented in UK drug treatment settings alongside OST to target attendance and the reduction of illicit drug use. While there was a growing evidence base for CM, there had been no examination of its delivery in UK NHS addiction services. The PRAISe trial evaluates the feasibility, acceptability, clinical and cost effectiveness of CM in UK addiction services. It is a cluster randomised controlled effectiveness trial of CM (praise and financial incentives) targeted at either abstinence from opiates or attendance at treatment sessions versus no CM among individuals receiving OST. The trial includes an economic evaluation which explores the relative costs and cost effectiveness of the two CM intervention strategies compared to TAU and an embedded process evaluation to identify contextual factors and causal mechanisms associated with variations in outcome. This study will inform UK drug treatment policy and practice. Trial registration ISRCTN 01591254.

Multicentre phase II trial of near-infrared imaging in elective colorectal surgery.

BACKGROUND: Decreasing anastomotic leak rates remain a major goal in colorectal surgery. Assessing intraoperative perfusion by indocyanine green (ICG) with near-infrared (NIR) visualization may assist in selection of intestinal transection level and subsequent anastomotic vascular sufficiency. This study examined the use of NIR-ICG imaging in colorectal surgery. METHODS: This was a prospective phase II study (NCT02459405) of non-selected patients undergoing any elective colorectal operation with anastomosis over a 3-year interval in three tertiary hospitals. A standard protocol was followed to assess NIR-ICG perfusion before and after anastomosis construction in comparison with standard operator visual assessment alone. RESULTS: Five hundred and four patients (median age 64 years, 279 men) having surgery for neoplastic (330) and benign (174) pathology were studied. Some 425 operations (85·3 per cent) were started laparoscopically, with a conversion rate of 5·9 per cent. In all, 220 patients (43·7 per cent) underwent high anterior resection or reversal of Hartmann's operation, and 90 (17·9 per cent) low anterior resection. ICG angiography was achieved in every patient, with a median interval of 29 s to visualization of the signal after injection. NIR-ICG assessment resulted in a change in the site of bowel division in 29 patients (5·8 per cent) with no subsequent leaks in these patients. Leak rates were 2·4 per cent overall (12 of 504), 2·6 per cent for colorectal anastomoses and 3 per cent for low anterior resection. When NIR-ICG imaging was used, the anastomotic leak rates were lower than those in the participating centres from over 1000 similar operations performed with identical technique but without NIR-ICG technology. CONCLUSION: Routine NIR-ICG assessment in patients undergoing elective colorectal surgery is feasible. NIR-ICG use may change intraoperative decisions, which may lead to a reduction in anastomotic leak rates.

Pregnancy after laparoscopic ventral mesh rectopexy: implications and outcomes.

AIM: Surgical management of rectal prolapse varies considerably. Most surgeons are reluctant to use ventral mesh rectopexy in young women until they have completed their family. The aim of the present study was to review outcomes of pregnancy following laparoscopic ventral mesh rectopexy from a tertiary referral centre over a 10-year period (2006-2016) and to review the impact on pelvic floor symptoms. METHOD: We undertook a retrospective review of a prospectively compiled database of patients who had undergone laparoscopic ventral rectopexy in a single centre over a 10-year period. Pelvic floor symptom scores (Vaizey for incontinence and Longo for obstructive defaecation) were collected at initial presentation (pre-intervention), post-intervention and after child birth. RESULTS: In all, 954 rectopexies were performed over this 10-year period. 225 (24%) patients were women and under 45 years of age (taken as an arbitrary cut-off for decreased likelihood of pregnancy). Eight (4%) of these patients became pregnant following rectopexy. The interval between rectopexy and delivery was 42 months (21-50). Six patients delivered live babies by elective lower segment caesarean section and two by spontaneous vaginal delivery. Six were first babies and two were second. No mesh related adverse outcome was reported. No difference in pelvic floor symptoms was demonstrated on comparison of post-rectopexy and post-delivery scores. CONCLUSION: This study provides the first description in the English language literature of safe delivery by elective lower segment caesarean section or spontaneous vaginal delivery following laparoscopic ventral mesh rectopexy. No adverse impact on pelvic floor related quality of life was detected.