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Summary: The success of CD19 Chimeric antigen receptor (CAR) T‐cell therapy in large B‐cell lymphoma (LBCL) has been partially offset by toxicity and logistical challenges, which off‐the‐shelf agents like CD20xCD3 bispecific antibodies might potentially overcome. However, when using CAR T outcomes as the ʽstandard‐of‐care comparator̕ for relapsed/refractory (r/r) LBCL, a potential learning curve with implementing a novel, complex therapy like CAR T needs to be considered. To address this, we analysed 726 UK patients intended to be treated with CD19 CAR T for r/r LBCL and compared outcomes between the first year of the national CAR T programme (Era 1; 2019) and the more recent treatment era (Era 2; 2020–2022). We identified significant improvements for Era 2 versus Era 1 in dropout rate (17% vs. 27%, p = 0.001), progression‐free survival (1‐year PFS 50% vs. 32%, p < 0.001) and overall survival (1‐year OS 60% vs. 40%, p < 0.001). We also observed increased use of bridging therapy, improvement in bridging outcomes, more tocilizumab/corticosteroid use, reduced high‐grade cytokine release syndrome (4% vs. 9%, p = 0.01) and intensive care unit admissions (20% vs. 32%, p = 0.001). Our results demonstrate significant improvement in CAR T outcomes over time, highlighting the importance of using up‐to‐date clinical data when comparing CAR T against new treatment options for r/r LBCL. [ABSTRACT FROM AUTHOR]

BACKGROUND: Echocardiographic screening can detect asymptomatic cases of rheumatic heart disease (RHD), facilitating access to treatment. Barriers to implementation of echocardiographic screening include the requirement for expensive equipment and expert practitioners. We aimed to evaluate the diagnostic accuracy of an abbreviated echocardiographic screening protocol (single parasternal-long-axis view with a sweep of the heart) performed by briefly trained, nonexpert practitioners using handheld ultrasound devices. METHODS: Participants aged 5 to 20 years in Timor-Leste and the Northern Territory of Australia had 2 echocardiograms: one performed by an expert echocardiographer using a GE Vivid I or Vivid Q portable ultrasound device (reference test), and one performed by a nonexpert practitioner using a GE Vscan handheld ultrasound device (index test). The accuracy of the index test, compared with the reference test, for identifying cases with definite or borderline RHD was determined. RESULTS: There were 3111 enrolled participants; 2573 had both an index test and reference test. Median age was 12 years (interquartile range, 10-15); 58.2% were female. Proportion with definite or borderline RHD was 5.52% (95% CI, 4.70-6.47); proportion with definite RHD was 3.23% (95% CI, 2.61-3.98). Compared with the reference test, sensitivity of the index test for definite or borderline RHD was 70.4% (95% CI, 62.2-77.8), specificity was 78.1% (95% CI, 76.4-79.8). CONCLUSIONS: Nonexpert practitioners can be trained to perform single parasternal-long-axis view with a sweep of the heart echocardiography. However, the specificity and sensitivity are inadequate for echocardiographic screening. Improved training for nonexpert practitioners should be investigated. [ABSTRACT FROM AUTHOR]

Objectives: Using echocardiographic screening, to estimate the prevalence of rheumatic heart disease (RHD) in a remote Northern Territory town.Design: Prospective, cross-sectional echocardiographic screening study; results compared with data from the NT rheumatic heart disease register.Setting, Participants: People aged 5-20 years living in Maningrida, West Arnhem Land (population, 2610, including 2366 Indigenous Australians), March 2018 and November 2018.Intervention: Echocardiographic screening for RHD by an expert cardiologist or cardiac sonographer.Main Outcome Measures: Definite or borderline RHD, based on World Heart Federation criteria; history of acute rheumatic fever (ARF), based on Australian guidelines for diagnosing ARF.Results: The screening participation rate was 72%. The median age of the 613 participants was 11 years (interquartile range, 8-14 years); 298 (49%) were girls or women, and 592 (97%) were Aboriginal Australians. Definite RHD was detected in 32 screened participants (5.2%), including 20 not previously diagnosed with RHD; in five new cases, RHD was classified as severe, and three of the participants involved required cardiac surgery. Borderline RHD was diagnosed in 17 participants (2.8%). According to NT RHD register data at the end of the study period, 88 of 849 people in Maningrida and the surrounding homelands aged 5-20 years (10%) were receiving secondary prophylaxis following diagnoses of definite RHD or definite or probable ARF.Conclusion: Passive case finding for ARF and RHD is inadequate in some remote Australian communities with a very high burden of RHD, placing children and young people with undetected RHD at great risk of poor health outcomes. Active case finding by regular echocardiographic screening is required in such areas. [ABSTRACT FROM AUTHOR]

However, patients from more deprived areas had inferior overall survival and access to post-CAR T therapies, underscoring healthcare inequalities in these patients. B Background: b CAR T-cell therapy has revolutionised treatment of relapsed/refractory (r/r) large B-cell lymphoma (LBCL), but it is unclear whether access and clinical benefit is equal for ethnic minorities and deprived communities. CAR T treatment access and outcomes in patients with large B-cell lymphoma according to ethnicity and socioeconomic deprivation. [Extracted from the article]

Dimethylsulfoniopropionate (DMSP) is a biogenic compound that could be involved in metal detoxification in both the host and endosymbionts of symbiotic corals. Acropora aspera , a common reef-building coral of the Great Barrier Reef, was exposed to zinc doses from 10 to 1000 μg/L over 96 h, with zinc being a low-toxic trace metal commonly used in the shipping industry. Over time, significantly lower DMSP concentrations relative to the control were found in both the host and symbionts in the highest zinc treatment where zinc uptake by both partners of the symbiosis was the highest. This clearly indicates that DMSP was consumed or stopped being produced under high and extended zinc exposure. This drop in DMSP was first observed in the host tissue, suggesting that the coral host was the first to respond to metal contamination. Such decrease in DMSP concentrations could influence the long-term health of corals under zinc exposure. [ABSTRACT FROM AUTHOR]

Coral skeletons record historical trace metal levels in the environment, however, the use of coral skeletal records for biomonitoring studies mostly fail to consider the influence of metal regulation by the living components of coral and subsequent incorporation into the skeleton. This study presents Exaiptasia pallida as a representative of the living components of coral and shows metal partitioning between the tissue and zooxanthellae after chronic exposure to Zn. A strong tendency for preferential accumulation in the zooxanthellae occurred after 32 days exposure and Zn concentrations in tissue and zooxanthellae were 123.3 ± 0.7 mg kg −1 and 294.9 ± 8.5 respectively. This study shows zooxanthellae density plays an important role in controlling Zn loading in whole anemones and must be considered when investigating metal uptake and loading in zooxanthellate organisms. Further studies that investigate links between aragonite deposition rates and zooxanthellae density and incorporation pathways of metals into skeleton are warranted. [ABSTRACT FROM AUTHOR]

Then article presents a case study on a pregnant alpaca hembra with urogenital leiomyosarcoma. A vaginoscopy was conducted that reveled a multinodular mass which was poorly visualized due to the marked hemorrhage of an unidentified source. The article discusses the clinical symptoms in leiomyosarcoma, tube cystotomy and antibiotic therapy in pregnant alpacas with life threatening disease.

Background: Lifestyle has been shown to significantly effect breast cancer incidence evident in the increased risk associated with obesity, diabetes, cigarettes and alcohol. The aim of this meta-analysis was to investigate the effect of two traditionally "beneficial" lifestyle choices: physical activity and weight loss. Specifically, we aimed to investigate the effect of the timing, intensity and duration of exercise on breast cancer incidence in women classified as either normal risk or increased risk. Finally, we aimed to investigate the effect of weight loss on breast cancer incidence. Method: Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar. Databases were searched using subject headings, keyword searches and text word searches wherever possible using the search terms "Exercise" OR "weight loss" AND "breast cancer" OR "breast carcinoma" OR "breast neoplasm". Inclusion criteria required a confirmed diagnosis of breast cancer, reporting of an odds ratio or data to calculate an odds ratio (and 95% confidence interval) and the use of an internal control group as the comparator. Exercise was catagorised as "high intensity" if it was vigorous exercise likely to cause sweating (ie. Running, competitive sport) while lower impact activities such as walking and golf were categorized as "low intensity". The effect of the timing on breast cancer incidence was quantified across three time periods: adolescence, adulthood and post menopause. Collated data was assessed for heterogeneity and a pooled odds ratio calculated. Results: 111 studies were identified in the literature search of which 76 were included in the meta-analysis. Overall, both exercise and weight loss were associated with a significantly reduced risk of breast cancer in women (OR 0.77, 95% CI 0.72-0.81 and OR 0.74, 95% CI 0.60-0.93 respectively). Heterogeneity was high (I²=77.12) and publication bias was significant (p < 0.001). Subgrouping by menopausal status at diagnosis of breast cancer found an increased reduction in the incidence of postmenopausal breast cancer when compared with premenopausal breast cancer and exercise (OR 0.68, 95% CI 0.60-0.78 and OR 0.81, 95% CI 0.71-0.92 respectively). The protection offered by exercise was not effected by the intensity of the exercise evident in a pooled odds ratio of 0.78 (95%CI 0.70-0.86) for low intensity exercise and 0.77 (95%CI 0.69-0.85) for high intensity. A similar consistency in the level of protection was present in regards to the timing of the physical activity with regular exercise during adolescence, adulthood and post menopause associated with odds ratios of 0.79 (95% CI 0.72-0.88), 0.84 (95% CI 0.77-0.92) and 0.82 (95% CI 0.75-0.89) respectively. In regards to the subpopulation at an increased risk of breast cancer, exercise significantly reduced the incidence of breast cancer in overweight individuals (OR 0.80, 95% CI 0.68-0.94) however the reduced risk in women with a positive family history did not reach statistical significance (OR 0.78, 95% CI 0.60-1.00). Conclusion: Breast cancer incidence is significantly reduced by both physical exercise and weight loss, especially in the postmenopausal population. Intensity, timing and nature of the exercise did not significantly alter the protective effect. [ABSTRACT FROM AUTHOR]

Background: The hyperinsulinaemia associated with type 2 diabetes and the known proliferative effects of insulin lead to the hypothesis that diabetes mellitus increases the risk of breast cancer. The aim of this meta-analysis was to collate and analyse all primary observational studies investigating the risk of breast cancer associated with diabetes. In addition, we aimed to complete sub group analyses by both type of diabetes and gender of study participants to further clarify the origin of any such association between the two. Method: Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar with additional cross checking of reference lists. Databases were searched using subject headings, keyword searches and text word searches wherever possible using the search terms 'diabetes' AND 'breast cancer' OR 'breast carcinoma' OR 'breast neoplasm'. Inclusion criteria required a confirmed diagnosis of both diabetes and breast cancer, reporting of an odds ratio or data to calculate an unadjusted odds ratio (and 95% confidence interval) and the use of an internal control group as the comparator. Collated data was assessed for heterogeneity and a pooled odds ratio calculated. Results: 34 studies were included in the meta-analysis with 31 studies investigating breast cancer in women and 5 studies investigating breast cancer in men. Overall, we found a significantly increased risk of breast cancer associated with diabetes in both women (OR 1.25, 95% CI 1.13-1.38) and men (OR 1.40, 95% CI 1.10-1.79). The pooled odds ratio was consistent across both case control studies (OR 1.25, 95% CI 1.06-1.46) and cohort studies (OR 1.26, 95% CI 1.09-1.45). Heterogeneity was significant (I² = 73.40, p < 0.001) and publication bias was present (p = 0.03). The 31 studies investigating breast cancer in women were sub grouped by type of diabetes with the association strengthened by a diagnosis of type 2 diabetes (OR 1.32, 95% CI 1.09-1.61) but nullified with gestational diabetes (OR 1.06, 95% CI 0.79-1.40). There were insufficient studies to calculate a pooled odds ratio of the risk of breast cancer associated with type 1 diabetes. Conclusion: Diabetes increases the risk of breast cancer in both women and men. This association is strengthened in women with type 2 diabetes and supports the hypothesis that diabetes is an independent risk factor for breast cancer. [ABSTRACT FROM AUTHOR]

Radiotherapy is an accepted bridging prior to CD19 CAR T in large B cell lymphoma (LBCL) and is sometimes used post CAR T for residual disease. However, consolidation (cRT) is not well established and there is no agreed standard for patient selection, timing, doses or techniques. Concern also exists regarding effect on circulating CAR T in responding patients. We initiated a prospective protocol for the use of RT with CAR T to: (1) standardize the selection of patients, (2) promote the use of RT consolidation post CAR T according to pre defined criteria, and (3) optimize the use of CAR T sparing RT in the consolidation setting. The eligibility criteria included LBCL patients approved for CD19 CAR T and no contraindication for RT. Patients were selected for pathway A (Bridging RT alone) if most sites of disease can be covered with RT. Pathway B (bridging systemic therapy ± cRT) was selected for rapidly progressing disease, wide-spread extranodal disease (e.g. liver, lung, bone, peritoneum) or LDH >2xULN. Baseline PET CT was reviewed and sites at high risk for local recurrence (≥5cm or SUVmax ≥15) were recorded. cRT post CAR T was given to high-risk lesions which on D28 PET CT showed a Deauville score (DS) 3-4 or 5 (but partial response). RT was planned 6-8 weeks post CAR T, with CAR T sparing technique. 28 patients were entered between Nov 2021 – Oct 2023, 10 in pathway A & 18 in pathway B. Median age was 55 years. 51.7% had stage 4 (20% vs. 68.4% in A vs. B). 44.8% had bulky disease, 24.1% ≥2 extranodal sites, and 48.2% high LDH. 1 patient in pathway A did not receive CAR T due to PD. RT dose was 20-36Gy (10-12#) in pathway A, all delivered with VMAT and with no gaps. Pathway B doses were 25-37.5Gy / 5-15# (23/26 sites treated with VMAT) and with no gaps. Planning modifications for early cRT post CAR T included: (1) contouring and dose-optimisation of blood vessels (BV) and blood-rich OARs (BR-OAR) to reduce doses to blood, and (2) measures to reduce beam-on time to account for the circulating nature of blood; hypofractionation (2.5 – 5 Gy/#, median = 3), limited beam angles (e.g. partial single arcs) avoiding BV and BR-OAR, and flattening filter free (FFF) beams. Overall response rate at 1 month was 86.2% (41.4% DS 1-3) and 48.2% at 6 months. With a median follow-up of 180 days, 9 patients progressed (4 in pathway A and 5 in pathway B) and 5 died, all due to disease progression. Data on local disease control, progression-free and overall survival will be provided at the meeting. Significant toxicity included 2 G3 ICANS but no CRS G≥ 3. No G≥3 toxicity reported after cRT. Implementing a comprehensive protocol of RT bridging and post CAR T RT consolidation with selection of patients based on pre-defined criteria was feasible. All patients but one completed treatment according to protocol. The disease control outcomes and the toxicity are promising, particularly in the RT consolidation setting. [ABSTRACT FROM AUTHOR]

Data on the impact of ethnic and socioeconomic factors on Chimeric antigen receptor (CAR) T-cell therapy (access and outcomes are limited, but key to understand whether results from the registration trials are generalizable to real-world patient populations. Here, we analysed ethnicity, socioeconomic deprivation and referral patterns in a cohort of 314 large B-cell lymphoma patients approved for third-line CD19 CAR-T across three large UK CAR-T centres. Patients from deprived areas had a lower infusion rate compared to low deprivation areas (73% vs. 86%, p = 0.04). CAR-T response rates, toxicities, progression-free survival or non-relapse mortality were similar with respect to ethnicity or deprivation. We did not find evidence of referral barriers according to ethnicity, but potential regional barriers for socioeconomically deprived patients in two of three centres. Intention-to-treat overall survival was significantly inferior in patients from deprived areas (1-year OS 44.5% vs. 58% for high vs. low deprivation; p = 0.02), likely reflecting general health disparities and higher drop-out rates in this group. Our data suggest similar outcomes of CD19 CAR-T-treated patients across a socioeconomically and ethnically heterogeneous real-world population. Results demonstrate broad access to CAR-T within the UK national delivery system, but the high drop-out rate and potential regional referral barriers for deprived communities should be further investigated., (© 2025 British Society for Haematology and John Wiley & Sons Ltd.)

Sinusoidal obstructive syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a potentially life-threatening complication following haemopoietic stem cell transplantation (HSCT). The availability of new drugs for malignant hematological conditions has allowed more patients to be eligible for allogeneic haematopoietic stem cell transplants, which has translated into a significant proportion of transplant patients having multiple risk factors for VOD/SOS. Based on these considerations, we undertook a dedicated weekly VOD/SOS ward round, aiming to facilitate early diagnosis of VOD/SOS and pre-emptively identify patients at risk, where a careful evaluation of differential diagnosis is essential. Herein, we present the results of our VOD/SOS ward round; between September 2020 and April 2022, 110 consecutive patients were evaluated in a focused VOD/SOS ward round. From the 110 patients, 108 had undergone HSCT and had at least one known risk factor for developing VOD/SOS. The median number of risk factors present in the VOD/SOS group and non-VOD/SOS group was five (range: three to six) and three (range: zero to seven), respectively. Late-onset VOD/SOS was diagnosed in 45% of our patients. The early identification of patients with multiple risk factors for VOD/SOS allowed an earlier diagnosis and the administration of defibrotide on the same day of diagnosis, which was two days earlier than our previous experience prior to the implementation of this protocol., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Avenoso, Kenyon, Mehra, Krishnamurthy, Kulasekararaj, Gandhi, Dazzi, Naresh Shah, Wood, Leung, Eaton, Anteh, Cuadrado, Correia de Farias, Bourlon, Dragoi, Hardefeldt, Pagliuca and Potter.)