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.

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.

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.

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.

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.

How we do it: patient participation in cochlear implant selection.

. Involving patients and parents in the choice of their cochlear implant encourages an active role in the process and facilitates 'bonding' and 'ownership' of the device. . The most frequent reasons given by patients for selecting a device included cochlear implant comfort and appearance. . We describe the Implant Programme based at the Royal National Throat, Nose and Ear Hospital, London, and also examine patient satisfaction with the scheme.

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.

Characterisation of bacterial cultures enriched on the chlorophenoxyalkanoic acid herbicides 4-(2,4-dichlorophenoxy) butyric acid and 4-(4-chloro-2-methylphenoxy) butyric acid.

The aim of this study was to enrich and characterise bacterial consortia from soils around a herbicide production plant through their capability to degrade the herbicides 4-(2,4-dichlorophenoxy) butyric acid (2,4-DB) and 4-(4-chloro-2-methylphenoxy) butyric acid (MCPB). Partial 16S rRNA gene sequencing revealed members of the genera Stenotrophomonas, Brevundimonas, Pseudomonas, and Ochrobactrum in the 2,4-DB- and MCPB-degrading communities. The degradation of 2,4-DB and MCPB was facilitated by the combined activities of the community members. Some of the members were able to utilise other herbicides from the family of chlorophenoxyalkanoic acids. During degradation of 2,4-DB and MCPB, phenol intermediates were detected, indicating ether cleavage of the side chain as the initial step responsible for the breakdown. This was also verified using an indicator medium. Repeated attempts to amplify putatively conserved tfd genes by PCR indicated the absence of tfd genes among the consortia members. First step cleavage of the chlorophenoxybutyric acid herbicides is by ether cleavage in bacteria and is encoded by divergent or different tfd gene types. The isolation of mixed cultures capable of degrading 2,4-DB and MCPB will aid future investigations to determine both the metabolic route for dissimilation and the fate of these herbicides in natural environments.

Tie-overs under pressure.

Dressings tied over skin grafts reduce the size of dead space, prevent haematoma formation, and immobilize the grafts [McCarthy, Plastic Surgery, 1990]. Their mechanism of action was thought to include the application of pressure to the bed and stabilization of the graft and dressing. A quantitative analysis of the pressure exerted by these dressings has never been reported [Wolf at al., Ann Plast Surg 40 (1998) 149]. This study measures the pressure exerted by tie-over dressings at the graft-bed interface and finds that no significant pressure is exerted.

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.

Characterization of (R/S)-mecoprop [2-(2-methyl-4-chlorophenoxy) propionic acid]-degrading Alcaligenes sp.CS1 and Ralstonia sp. CS2 isolated from agricultural soils.

The herbicide mecoprop [2-(2-methyl-4-chlorophenoxy) propionic acid] is widely applied to corn fields in order to control broad-leaved weeds. However, it is often detected in groundwater where it can be a persistent contaminant. Two mecoprop-degrading bacterial strains were isolated from agricultural soils through their capability to degrade (R/S)-mecoprop rapidly. 16S rDNA sequencing of the isolates demonstrated that one was closely related to the genera Alcaligenes sp. (designated CS1) and the other to Ralstonia sp. (designated CS2). Additionally, these isolates demonstrated ability to grow on other related herbicides, including 2,4-D (2,4-dichlorophenoxyacetic acid), MCPA [4-chloro-2-methyl phenoxy acetic acid] and (R/S)-2,4-DP [2-(2,4-dichlorophenoxy)propionic acid] as sole carbon sources. tfdABC gene-specific probes derived from the 2,4-D-degrading Variovorax paradoxus TV1 were used in hybridization analyses to establish whether tfd-like genes are present in mecoprop-degrading bacteria. Hybridization analysis demonstrated that both Alcaligenes sp. CS1 and Ralstonia sp. CS2 harboured tfdA, tfdB and tfdC genes on plasmids that have approximately > 60% sequence similarity to the tfdA, tfdB and tfdC genes of V. paradoxus. It is therefore likely that tfd-like genes may be involved in the degradation of mecoprop, and we are currently investigating this further.

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.

Reducing sleep disruptions in young children: evaluation of therapist-guided and written information approaches: a brief report.

Regular night waking of young children is one of the most common problems encountered by parents. This study compared a standardized night waking programme that involved organized bedtime routines, procedures for settling the child and for the handling of crying, calling out and getting out of bed, with a group which received written information only and a waiting list control group. The children receiving the standard programme and those receiving written information only showed significant improvement over children in the waiting list group. This result supports the use of written parent instructions with or without therapist support.

A simple systems model for community programs.

A simple model for general application to the planning and evaluation of community programs is presented. It is based on a systems approach and consists of seven procedural steps: overview, need assessment, goal-setting, resource organization, action, reviews, and outcome statements. Feedback information is used to correct and improve system performance. Two examples of the model in use are given to illustrate both its application and its generality. These concern the management of individual patients in a community-oriented psychiatric ward program and the organization of a comprehensive community development project. The feature common to these applications is the ability of the model to reduce complex endeavors to a few manageable steps, with no loss of comprehensiveness.