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.

Oro-Naso-Sino-Orbital-Cutaneous Fistula From Prolonged Cocaine Use.

Presentation We present the case of a 48-year-old man with nasal cellulitis and subsequent oro-naso-sino-orbital-cutaneous fistula from prolonged cocaine use. Diagnosis Initial laboratory investigations reported a raised white cell count (WBC) and C-Reactive Protein (CRP) and subsequently a positive atypical anti-neutrophil cytoplasm antibodies (ANCA) and positive anti-proteinase (PR3). Perihilar lung nodularity on chest imaging raised the possibility of a systemic autoimmune response. His urinalysis was positive for cocaine. Treatment He was commenced on Augmentin, Amphotericin B and Prednisolone. An obturator was created to manage the oro-nasal fistula. A subsequent naso-cutaneous defect was re-approximated. Daily nasal saline douche and abstinence of cocaine were recommended. Discussion Cocaine use in the community is rising and poses a challenge to multiple facets of our health care system.

Process evaluation of a cluster-randomised controlled trial of multi-component weight management programme in adults with intellectual disabilities and obesity.

BACKGROUND: Providing effective weight management to adults with intellectual disabilities is necessary to challenge the high rates of obesity. The aim of this process evaluation was to explore the feasibility of conducting a full-scale clinical trial of the TAKE 5 multi-component weight management programme. METHODS: The study was a 12-month pilot cluster-randomised controlled trial. Adults with intellectual disabilities and obesity were randomised to either TAKE 5, which included an energy deficit diet (EDD) or Waist Winners Too, based on health education principles. A mixed-methods process evaluation was conducted focussing on the reach, recruitment, fidelity, implementation, dose (delivered/received) and context. RESULTS: The study successfully recruited adults with intellectual disabilities. Both weight management programmes were delivered with high fidelity and implemented as intended. Only one weight management programme, TAKE 5, demonstrated potential efficacy in reducing body weight and body composition. The effectiveness was largely attributed to the EDD and social support from carers. CONCLUSIONS: The extensive process evaluation illustrated that a full-scale trial of a multi-component programme including an EDD is feasible and an acceptable approach to weight management for adults with intellectual disabilities and obesity.

Low rates of vaccination in listed kidney transplant candidates.

Despite clear consensus and strong recommendations, vaccination rates of kidney transplant (KT) recipients have remained below targets. As vaccination is most effective if it is given prior to transplantation and the initiation of immunosuppression, patients should ideally have their vaccination status assessed and optimized in the pre-transplant period. We performed a retrospective chart review to characterize vaccination rates and factors associated with gaps in vaccination in a single-center population of waitlisted patients being evaluated for kidney transplantation. We evaluated 362 KT patients. Three-quarters were receiving dialysis at the time of evaluation. Immunization rates were low with 35.9% of patients having completed vaccination for Pneumococcus, 55% for influenza, 6.9% for zoster, and 2.5% for tetanus. On multivariable analysis, patients who received other vaccines, including influenza, tetanus, or zoster vaccine (odds ratio [OR] 10.55, 95% confidence interval [CI] 5.65-19.71) were more likely to receive pneumococcal vaccine. Blacks (OR 0.24, 95% CI 0.12-0.47) were less likely to receive pneumococcal vaccine compared to whites. Patients on dialysis, and those active on the waiting list were more likely to receive pneumococcal vaccine than other groups (OR 2.81, 95% CI 1.44-5.51, and OR 1.84, 95% CI 1.08-3.14, respectively). We found that the overall immunization rate against common vaccine-preventable infections was low among patients evaluated for kidney transplantation. A significant gap remains between recommendations and vaccine uptake in clinical practice among this high-risk population.

A study of genotyping for management of human papillomavirus-positive, cytology-negative cervical screening results.

The effective management of women with human papillomavirus (HPV)-positive, cytology-negative results is critical to the introduction of HPV testing into cervical screening. HPV typing has been recommended for colposcopy triage, but it is not clear which combinations of high-risk HPV types provide clinically useful information. This study included 18,810 women with Hybrid Capture 2 (HC2)-positive, cytology-negative results and who were age ≥30 years from Kaiser Permanente Northern California. The median follow-up was 475 days (interquartile range [IQR], 0 to 1,077 days; maximum, 2,217 days). The baseline specimens from 482 cases of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) and 3,517 random HC2-positive noncases were genotyped using 2 PCR-based methods. Using the case-control sampling fractions, the 3-year cumulative risks of CIN3+ were calculated for each individual high-risk HPV type. The 3-year cumulative risk of CIN3+ among all women with HC2-positive, cytology-negative results was 4.6%. HPV16 status conferred the greatest type-specific risk stratification; women with HC2-positive/HPV16-positive results had a 10.6% risk of CIN3+, while women with HC-2 positive/HPV16-negative results had a much lower risk of 2.4%. The next most informative HPV types and their risks in HPV-positive women were HPV33 (5.9%) and HPV18 (5.9%). With regard to the etiologic fraction, 20 of 71 cases of cervical adenocarcinoma in situ (AIS) and adenocarcinoma in the cohort were positive for HPV18. HPV16 genotyping provides risk stratification useful for guiding clinical management; the risk among HPV16-positive women clearly exceeds the U.S. consensus risk threshold for immediate colposcopy referral. HPV18 is of particular interest because of its association with difficult-to-detect glandular lesions. There is a less clear clinical value of distinguishing the other high-risk HPV types.

Comparing the effectiveness of a multi-component weight loss intervention in adults with and without intellectual disabilities.

BACKGROUND: The prevalence of obesity in adults with intellectual disabilities (ID) is rising, although the evidence base for its treatment in this population group is minimal. Weight management interventions that are accessible to adults with ID will reduce the inequalities that they frequently experience in health services. This short report compared the effectiveness of weight management in those with and without ID who completed nine sessions of a multi-component weight management programme. METHODS: TAKE 5 is a 16-week multi-component weight management intervention for adults with ID and obesity [body mass index (BMI) ≥30 kg m(-2) ]. This intervention is an adaption of the weight management programme provided by the Glasgow & Clyde Weight Management Service (GCWMS) for adults without ID and obesity (National Health Service based). Fifty-two participants of the TAKE 5 programme were individually matched by baseline characteristics (sex, age and BMI) with two participants without ID of the GCWMS programme. Comparisons in terms of weight and BMI change and rate of weight loss were made for those who attended all nine sessions. RESULTS: There were no significant differences between the groups in the amount of weight loss (median: -3.6 versus -3.8 kg, respectively, P = 0.4), change in BMI (median: -1.5 versus -1.4 kg m(-2) , P = 0.9), success of achieving 5% weight loss (41.3% versus 36.8%, P = 0.9) and rate of weight loss across the 16-week intervention. CONCLUSIONS: A multi-component weight loss intervention can be equally effective for adults with and without ID and obesity.

Connectivity of stormwater ponds impacts Odonata abundance and species richness.

Context: The successful dispersal of an animal depends, partly, on landscape connectivity. Urbanization poses risks to dispersal activities by increasing hostile land cover types. Objectives: We investigated how connectivity of urban ponds impacted Odonata communities (dragonflies and damselflies), an order of semi-aquatic insects that actively disperse. Methods: We sampled 41 constructed stormwater ponds and 8 natural ponds in a metropolitan area. The effect of connectivity and the quantity of available adjacent habitats was tested at different scales for dragonflies (900 m) and damselflies (300 m), determined by a literature analysis, to account for differences in suborder dispersal capabilities. Results: Lower levels of connectivity and fewer nearest neighbours negatively impacted abundance, species richness, and composition of dragonflies (p values < 0.01, R2 = 0.18-0.70). Adult dragonfly abundance had a stronger positive relationship with connectivity than species richness. In particular, the abundance of adult dragonfly Leucorrhinia frigida, found almost exclusively at natural ponds, had a positive relationship with connectivity. Connectivity and the number of nearest neighbours had no significant impact on damselflies apart from a slight negative relationship between connectivity and species richness (p value = 0.02, R2 = 0.11). Natural ponds had significantly higher levels of connectivity when compared to stormwater ponds. Conclusions: Our results suggest that dragonflies are positively affected by increased connectivity in an urban landscape, with no benefit of connectivity to damselflies at the scale measured. We recommend intentional planning of urban stormwater pond networks, where individual ponds can act as stepping stones, incorporated with strategic inclusion of beneficial land cover types. Supplementary Information: The online version contains supplementary material available at 10.1007/s10980-024-01817-z.

Pregnancy in Patients with the Fontan Operation.

Improved survival rates for patients with a Fontan circulation has allowed more women with this complex cardiac physiology to contemplate pregnancy. However, pregnancy in women with a Fontan circulation is associated with a high risk of adverse maternal and fetal outcomes, high rates of miscarriage and preterm delivery. Factors associated with a successful pregnancy outcome are: younger age, normal body weight, absence of significant functional limitation, no Fontan-related complications, and well-functioning single ventricle physiology. Appropriate care with timely preconception counselling and regular, frequent clinical reviews by a multidisciplinary team based at a tertiary centre, improves the chance of a successful pregnancy. Empowerment of patients with education on their specific congenital cardiac condition and its projected trajectory, helps them make informed choices regarding their health, reproductive choices and assists them to achieve their life goals.

Characterizing Deficit Accumulation Among Gulf War Era Veterans.

BACKGROUND: Veterans of the first Gulf War (1990-1991) are reaching middle and older adulthood in differing degrees of health and biological age. Many Gulf War veterans report myriad negative symptoms classified as Gulf War illness (GWI), a chronic multi-symptom illness. OBJECTIVES: To describe and analyze deficit accumulation, among veterans with Severe GWI (SGWI+) and those without Severe GWI (SGWI-), to assess the association between a medically unexplained illness and aging. DESIGN: This study uses a retrospective cohort design with quasi-longitudinal data. SETTING: The recruitment sample included 10,042 Gulf War era veterans across all four US Census regions. PARTICIPANTS: The analytic sample included 1,054 participants of the GWECB for whom SGWI case status could be determined and who had valid responses for at least 90% of the deficits included in the deficit accumulation index. MEASUREMENTS: Chronic health conditions were retroactively reported, including year of diagnosis, enabling us to create a longitudinal measure of deficit accumulation. This deficit accumulation index (DAI) ranged from 0-1 for each respondent in each year between 1991-2013. We compare veterans with SGWI+ to those with SGWI- using the CDC case definition. RESULTS: Most veterans in our sample could expect to spend more years with moderate or substantial deficits than without deficits. SGWI+ was associated with spending more years with substantial deficits than those with SGWI-. Veterans in middle age (age 35-65) experienced more years with substantial deficits than younger veterans. Individuals with SGWI+ had 13 times the hazard of accumulating substantial deficits than those without. CONCLUSIONS: This study demonstrated that veterans with SGWI+, even those in midlife, experienced aging as measured by accumulating deficits. Practitioners should consider patients with multi-symptom illnesses as at risk of accelerated aging, tailoring treatments to address patients' holistic needs.

Carers' perspectives of a weight loss intervention for adults with intellectual disabilities and obesity: a qualitative study.

BACKGROUND: To date, no studies have explored the role of carers in supporting adults with intellectual disabilities (ID) and obesity during a weight loss intervention. The present study explored perceptions of carers supporting adults with ID, as they participated in a 6-month multi-component weight loss intervention (TAKE 5). METHODS: Semi-structured interviews were used to explore the experiences of 24 carers. The transcripts were analysed qualitatively using thematic analysis. RESULTS: Three themes emerged from the analysis: carers' perceptions of participants' health; barriers and facilitators to weight loss; and carers' perceptions of the weight loss intervention. Data analysis showed similarities between the experiences reported by the carers who supported participants who lost weight and participants who did not. Lack of sufficient support from people from the internal and external environment of individuals with ID and poor communication among carers, were identified as being barriers to change. The need for accessible resources tailored to aid weight loss among adults with ID was also highlighted. CONCLUSION: This study identified specific facilitators and barriers experienced by carers during the process of supporting obese adults with ID to lose weight. Future research could utilise these findings to inform appropriate and effective weight management interventions for individuals with ID.

Self-reported gastrointestinal disorders among veterans with gulf war illness with and without posttraumatic stress disorder.

BACKGROUND: Gulf War Illness (GWI) is a chronic, multi-symptom disorder affecting 25%-32% of Gulf War veterans. Veterans with GWI disproportionately suffer from gastrointestinal (GI) disorders. Given the increasing evidence supporting a gut-brain axis, we explore the relationship between post-traumatic stress disorder (PTSD), GWI, and self-reported GI disorders among GW veterans. METHODS: Veterans from the Gulf War Era Cohort and Biorepository responded to a mail-based survey (N = 1058). They were stratified by GWI (Centers for Disease Control definition) and PTSD status. This yielded three groups: GWI-, GWI+/PTSD-, and GWI+/PTSD+. Multivariable logistic regression adjusting for demographic and military characteristics examined associations between GWI/PTSD groups and GI disorders. Results were expressed as adjusted odds ratios (aOR) with 95% confidence intervals (95% CI). KEY RESULTS: The most frequently reported GI disorders were irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), and colon polyps (CP). The GWI+/PTSD+ group had a higher odds of these disorders than the GWI+/PTSD- group (aORIBS  = 3.12, 95% CI: 1.93-5.05; aORGERD  = 2.04, 95% CI: 1.44-2.90; aORCP  = 1.85, 95% CI: 1.23-2.80), which had a higher odds of these disorders than the GWI- group (aORIBS  = 4.38, 95% CI: 1.55-12.36; aORGERD  = 2.51 95% CI: 1.63-3.87; aORCP  = 2.57, 95% CI: 1.53-4.32). CONCLUSIONS & INFERENCES: GW veterans with GWI and PTSD have significantly higher odds of specific self-reported GI disorders than the other groups. Given the known bidirectional influences of the gut and brain, these veterans may benefit from a holistic healthcare approach that considers biopsychosocial contributors to the assessment and management of disease.

Coherent optical control of the spin of a single hole in an InAs/GaAs quantum dot.

We demonstrate coherent optical control of a single hole spin confined to an InAs/GaAs quantum dot. A superposition of hole-spin states is created by fast (10-100 ps) dissociation of a spin-polarized electron-hole pair. Full control of the hole spin is achieved by combining coherent rotations about two axes: Larmor precession of the hole spin about an external Voigt geometry magnetic field, and rotation about the optical axis due to the geometric phase shift induced by a picosecond laser pulse resonant with the hole-trion transition.

Unexpected intraoperative hypotension in a chronic cocaine user.

It is not uncommon for patients to present for procedures under anaesthesia with a history of recent cocaine use. The acute effects of cocaine toxicity are well documented, but the pathophysiological changes caused by chronic use are complex and can result in unexpected cardiovascular responses and interactions with anaesthetic agents. In this case report, we describe an episode of hypotension under general anaesthesia, likely due to catecholamine depletion, an unusual but significant consequence of chronic cocaine use. It should be treated with intravenous fluids and direct-acting vasopressors such as phenylephrine or noradrenaline, as they are likely to be more effective than indirect acting agents. As the prevalence of cocaine use continues to increase, anaesthesia providers need to not only be familiar with the treatment of acute cocaine toxicity, but also to anticipate and manage the cardiovascular changes associated with chronic use of this drug.

An awareness and prevalence study of Irish cold-water athletes and external auditory canal exostoses.

OBJECTIVE: This study aimed to determine the awareness, otological symptoms and prevalence of external auditory canal exostoses in Irish cold-water athletes. METHOD: An online and in person cross-sectional survey was undertaken with Irish cold-water athletes to explore athletes' awareness, known prevalence of external auditory canal exostoses and attitudes towards preventive measures. RESULTS: Of the 926 participants surveyed, 67.5 per cent were aware of external auditory canal exostoses. Triathletes reported the lowest awareness (39.9 per cent) among water athletes. A total of 9.7 per cent (n = 90) had previously been diagnosed with external auditory canal exostoses and 46.7 per cent (n = 42) were non-surfers. Ear symptoms were reported in 76 per cent of athletes. Otoscopic examinations showed that 23.7 per cent had external auditory canal exostoses, 3.6 per cent of whom were aware of their diagnosis. CONCLUSION: The majority of Irish surfing athletes are aware of external auditory canal exostoses. There is less awareness with regard to Ireland's newly emerging sports such as open water swimming and triathlons. Over 90 per cent of athletes surveyed had no idea they had external auditory canal exostoses, which highlights the need to increase public awareness.

Phonon-induced Rabi-frequency renormalization of optically driven single InGaAs/GaAs quantum dots.

We study optically driven Rabi rotations of a quantum dot exciton transition between 5 and 50 K, and for pulse areas of up to 14π. In a high driving field regime, the decay of the Rabi rotations is nonmonotonic, and the period decreases with pulse area and increases with temperature. By comparing the experiments to a weak-coupling model of the exciton-phonon interaction, we demonstrate that the observed renormalization of the Rabi frequency is induced by fluctuations in the bath of longitudinal acoustic phonons, an effect that is a phonon analogy of the Lamb shift.

Predictors of antidepressant use in the English population: analysis of the Adult Psychiatric Morbidity Survey.

OBJECTIVES: The rate of antidepressant use in the United Kingdom has outpaced diagnostic increases in the prevalence of depression. Research has suggested that personal and socioeconomic risk factors may be contributing to antidepressant use. To date, few studies have addressed these possible contributions. Thus, this study aimed to assess the relative strength of personal, socioeconomic and trauma-related risk factors in predicting antidepressant use. METHODS: Data were derived from the Adult Psychiatric Morbidity Survey (n=7403), a nationally representative household sample of adults residing in England in 2007. A multivariate binary logistic regression model was developed to assess the associations between personal, socioeconomic and trauma-related risk factors and current antidepressant use. RESULTS: The strongest predictor of current antidepressant use was meeting the criteria for an ICD-10 depressive episode [odds ratio (OR)=9.04]. Other significant predictors of antidepressant use in this analysis included English as first language (OR=3.45), female gender (OR=1.98), unemployment (OR=1.82) and childhood sexual abuse (OR=1.53). CONCLUSIONS: Several personal, socioeconomic and trauma-related factors significantly contributed to antidepressant use in the multivariate model specified. These findings aid our understanding of the broader context of antidepressant use in the United Kingdom.

Differences in the localization and morphology of chromosomes in the human nucleus.

Using fluorescence in situ hybridization we show striking differences in nuclear position, chromosome morphology, and interactions with nuclear substructure for human chromosomes 18 and 19. Human chromosome 19 is shown to adopt a more internal position in the nucleus than chromosome 18 and to be more extensively associated with the nuclear matrix. The more peripheral localization of chromosome 18 is established early in the cell cycle and is maintained thereafter. We show that the preferential localization of chromosomes 18 and 19 in the nucleus is reflected in the orientation of translocation chromosomes in the nucleus. Lastly, we show that the inhibition of transcription can have gross, but reversible, effects on chromosome architecture. Our data demonstrate that the distribution of genomic sequences between chromosomes has implications for nuclear structure and we discuss our findings in relation to a model of the human nucleus that is functionally compartmentalized.

A versatile computational pipeline for bacterial genome annotation improvement and comparative analysis, with Brucella as a use case.

We present a bacterial genome computational analysis pipeline, called GenVar. The pipeline, based on the program GeneWise, is designed to analyze an annotated genome and automatically identify missed gene calls and sequence variants such as genes with disrupted reading frames (split genes) and those with insertions and deletions (indels). For a given genome to be analyzed, GenVar relies on a database containing closely related genomes (such as other species or strains) as well as a few additional reference genomes. GenVar also helps identify gene disruptions probably caused by sequencing errors. We exemplify GenVar's capabilities by presenting results from the analysis of four Brucella genomes. Brucella is an important human pathogen and zoonotic agent. The analysis revealed hundreds of missed gene calls, new split genes and indels, several of which are species specific and hence provide valuable clues to the understanding of the genome basis of Brucella pathogenicity and host specificity.

PATRIC: the VBI PathoSystems Resource Integration Center.

The PathoSystems Resource Integration Center (PATRIC) is one of eight Bioinformatics Resource Centers (BRCs) funded by the National Institute of Allergy and Infection Diseases (NIAID) to create a data and analysis resource for selected NIAID priority pathogens, specifically proteobacteria of the genera Brucella, Rickettsia and Coxiella, and corona-, calici- and lyssaviruses and viruses associated with hepatitis A and E. The goal of the project is to provide a comprehensive bioinformatics resource for these pathogens, including consistently annotated genome, proteome and metabolic pathway data to facilitate research into counter-measures, including drugs, vaccines and diagnostics. The project's curation strategy has three prongs: 'breadth first' beginning with whole-genome and proteome curation using standardized protocols, a 'targeted' approach addressing the specific needs of researchers and an integrative strategy to leverage high-throughput experimental data (e.g. microarrays, proteomics) and literature. The PATRIC infrastructure consists of a relational database, analytical pipelines and a website which supports browsing, querying, data visualization and the ability to download raw and curated data in standard formats. At present, the site warehouses complete sequences for 17 bacterial and 332 viral genomes. The PATRIC website (https://patric.vbi.vt.edu) will continually grow with the addition of data, analysis and functionality over the course of the project.

Development of an auxotrophic, live-attenuated Brucella suis vaccine strain capable of expressing multimeric GnRH.

Feral swine cost around $1.5 billion each year in agricultural, environmental, and personal property damages. They are also the most widespread carriers of the zoonotic disease brucellosis, which threatens both livestock bio-security and public health. Currently, there is no approved vaccine against brucellosis in pigs. This is a preliminary report on the development of a live-attenuated B. suis vaccine that could be employed to deliver heterologous antigens to control swine populations. An attenuated vaccine strain provided significant protection against B. suis challenge in mice. Leucine auxotrophy in the vaccine strain allowed the over-expression of heterologous antigens without the use of antibiotic resistant markers. Vaccinated mice showed the development of antibodies against expressed antigen. Further evaluation is required to assess its ability to cause infertility using the mouse model prior to further testing for use as a tool for feral swine population and disease control.