Improved outcomes of large B-cell lymphoma patients treated with CD19 CAR T in the UK over time.

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 'standard-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.

Outcome and feasibility of radiotherapy bridging in large B-cell lymphoma patients receiving CD19 CAR T in the UK.

Radiotherapy (RT) has potential synergistic effects with chimeric antigen receptor (CAR) T but is not widely used as bridging therapy due to logistical challenges and lack of standardised protocols. We analysed RT bridging in a multicentre national cohort of large B-cell lymphoma patients approved for 3L axicabtagene ciloleucel or tisagenlecleucel across 12 UK centres. Of 763 approved patients, 722 were leukapheresed, 717 had data available on bridging therapy. 169/717 (24%) received RT bridging, 129 as single modality and 40 as combined modality treatment (CMT). Of 169 patients, 65.7% had advanced stage, 36.9% bulky disease, 86.5% elevated LDH, 41.7% international prognostic index (IPI) ≥3 and 15.2% double/triple hit at the time of approval. Use of RT bridging varied from 11% to 32% between centres and increased over time. Vein-to-vein time and infusion rate did not differ between bridging modalities. RT-bridged patients had favourable outcomes with 1-year progression-free survival (PFS) of 56% for single modality and 47% for CMT (1-year PFS 43% for systemic bridging). This is the largest cohort of LBCL patients receiving RT bridging prior to CAR T reported to date. Our results show that RT bridging can be safely and effectively used even in advanced stage and high-risk disease, with low dropout rates and excellent outcomes.

One hundred questions of importance to the conservation of global biological diversity.

We identified 100 scientific questions that, if answered, would have the greatest impact on conservation practice and policy. Representatives from 21 international organizations, regional sections and working groups of the Society for Conservation Biology, and 12 academics, from all continents except Antarctica, compiled 2291 questions of relevance to conservation of biological diversity worldwide. The questions were gathered from 761 individuals through workshops, email requests, and discussions. Voting by email to short-list questions, followed by a 2-day workshop, was used to derive the final list of 100 questions. Most of the final questions were derived through a process of modification and combination as the workshop progressed. The questions are divided into 12 sections: ecosystem functions and services, climate change, technological change, protected areas, ecosystem management and restoration, terrestrial ecosystems, marine ecosystems, freshwater ecosystems, species management, organizational systems and processes, societal context and change, and impacts of conservation interventions. We anticipate that these questions will help identify new directions for researchers and assist funders in directing funds.

Lemierre's syndrome presenting with peritonsillar abscess and VIth cranial nerve palsy.

Lemierre's syndrome is characterized by acute oropharyngeal infection complicated by internal jugular venous thrombosis secondary to septic thrombophlebitis, and metastatic abscesses. We report a case of Lemierre's syndrome in an 18-year-old Caucasian woman presenting with a peritonsillar abscess and ipsilateral VIth cranial nerve palsy.

Determination of the structure of dextran by 13C-nuclear magnetic resonance spectroscopy.

The 13C-n.m.r. spectra have been recorded for a series of dextrans whose structures, in terms of degree and type of branching, had previously been determined by methylation analysis. The spectra established that all observable linkages in these dextrans are alpha-linked. Correlation of the spectra with methylation data indicated that the 75-85-p.p.m. spectral region is diagnostic for establishing the presence of alpha-D-(1 leads to 2)-, alpha-D-(1 leads to 3)-, or alpha-D-(1 leads to 4)-linkages. Each chemical shift has been found to be temperature-dependent (deltadelta/deltaT) when referenced to either the deuterium lock or an external standard (tetramethylsilane). All carbohydrate deltadelta values are positive, and range from 0.01 to 0.03 p.p.m./degrees C. These values are considerably larger than analogous deltadelta/deltaT values previously observed for smaller molecules. Larger than average deltadelta/deltaT values are associated with the non-anomeric, sugar-linking carbon atoms.

Phosphorus-31 nuclear magnetic resonance spectroscopy of extracellular, yeast O-phosphonohexoglycans.

P nuclear magnetic resonance spectra of a number of purified yeast O-phosphonohexoglycans were recorded. The data therefrom were correlated with established chemicals aspects of individual and collective polymer structures, permitting (a) conclusions to be drawn regarding the chemical environment of the phosphate groups of these polymers, and (b) assignment of anormeric configurations to the hexosyl phosphate residues.

Methylation and acetolysis of extracellular D-mannans from yeast.

Methylation-fragmentation analyses were conducted on a series of extra-cellular, yeast alpha-D-linked mannans representing six different structural types. D-Mannans of low degree of branching were produced by Hansenula capsulata strains and by species related to H. holstii, The former consisted primarily of (1 leads to 2)- and (1 leads to 6)-linked D-mannosyl residues; the latter, of (1 leads to 2)- and (1 leads to 3)-linked D-mannosyl residues. Although the remaining structural types were highly branched, each gave distinct methylation-patterns indicative of (1 leads to 6)-linked backbones to which are appended non-(1 leads to 6)-linked side-chains. Acetolysis studies were correlated with the methylation analyses, and the correlation demonstrated that each branched polymer possesses side chains of heterogeneous length.

Assessment and management of acute poisoning by petroleum products.

Petroleum products are highly complex chemical mixtures consisting predominantly of hydrocarbons. Their composition varies with source and intended use of the product. Virtually all are blended products that come into contact with man in a wide range of circumstances. Their toxicity for man is generally low and the use of additives rarely affects the toxicity of the final product. Because products are blended to meet performance, and not chemical specifications, their composition varies significantly. Management of toxicity benefits from simplified guidelines that consider the product by its type. Management in most cases is symptomatic, but the doctor needs to be aware of the potential for development of sequelae such as aspiration pneumonia and central nervous system (CNS) depression. Local and systemic effects of exposure to hydrocarbons are reviewed, as are immediate assessment and recommended management of acute exposure to petroleum products. Because of the large scope of this subject, this paper limits itself to acute toxicity of petroleum products encountered inthe public domain. It does not address topics such as chronic toxicity, solvent abuse, petrochemicals, or pesticides.

Glomus jugulare tumour presenting with isolated accessory nerve palsy.

Glomus tumours of the skull base are rare, and most frequently present with symptoms of hearing loss and tinnitus. Diagnosis is often delayed due to the slow growth of the tumour. We describe the previously unreported occurrence of a glomus tumour presenting with a unilateral accessory nerve palsy.

Medical evaluations in cases of suspected child sexual abuse: referrals and perceptions.

AIMS: To explore referrals to medical evaluations and children's and primary carers' experiences of those evaluations in Auckland. METHODS: Semi-structured interviews were conducted with children and young people who had made clear disclosures of sexual abuse, their primary carers and the social workers involved. RESULTS: More than 90% of children alleging penetration or attempted penetration were referred for a medical evaluation, but less than two thirds of children alleging oral genital or digital contact abuse were referred. Although the majority perceived the medical practitioners positively, many also commented on the distressing nature of the examinations, the photographs of children's genitalia and lack of preparation for those examinations. CONCLUSIONS: The findings highlight the need for improved preparation of children and their primary carers for medical evaluations. Ongoing discussion between referring agents and medical practitioners is desirable to ensure protocols are updated and adhered to.

Self-recording in training girls to increase work and evoke staff praise in an institution for offenders.

Self-recording procedures were used by four adolescent girls to increase work and comments (cues) that evoked staff praise during vocational training sessions in a maximum-security institution for offenders. The girls were selected on the basis of their not responding to a staff-directed token program. The self-recording procedures were directed by a therapist who saw the girls outside the vocational training sessions. According to a multiple-baseline design, self-recording of work was introduced sequentially to each of the two or three settings the girls attended each day. A few days after work had increased, self-recording of cues was introduced. Tokens were delivered by the therapist for work and cues recorded by the girls. Work and cues increased following self-recording for three of the girls and increased cues evoked higher rates of staff praise. Girl and staff behaviors were maintained during short follow-up periods when tokens were not given for the girls' records. The procedures failed to effect desirable changes with a fourth girl's work and self-recording of work was terminated without introducing cueing.

Assessment of clinical improvement and quality of life before and after tonsillectomy.

OBJECTIVE: To assess clinical improvement and quality of life measures in patients who had undergone tonsillectomy for recurrent acute and chronic tonsillitis between March 2004 and March 2005. METHOD: A retrospective survey of all adults and children who had undergone tonsillectomy for recurrent acute and chronic tonsillitis. Patients were asked to compare their symptoms for the 12-month period before and after tonsillectomy. RESULTS: A review of 100 patients revealed that, following tonsillectomy: their days off work (or school) due to sore throat reduced by 95.3 per cent (from a mean of 27.6 to 1.3 days; confidence intervals 89.7 and 99.6 per cent); their visits to their general practitioner due to sore throat reduced by 95.6 per cent (from a mean of 7.9 to 0.4 visits; confidence intervals 93.8 and 95.1 per cent); and more than 90 per cent reported improved feelings of well-being, general health and energy. CONCLUSION: We conclude that tonsillectomy is of benefit for patients with recurrent acute and chronic tonsillitis. Tonsillectomy significantly reduced general practitioner attendances and resulted in an improved feeling of health and well-being.