Bone marrow manifestations in multicentric Castleman disease

This study aimed to document the morphological and immunophenotypic features, and describe the diagnostic features of bone marrow (BM) involvement in human herpes virus 8 Multicentric Castleman disease (HHV8‐MCD). BM trephine biopsy (BMTB) specimens from 28 patients were revisited. Samples were evaluated for expression of CD3, CD20, CD138, CD68R, glycophorin C, CD42b, HHV8‐latency‐associated nuclear antigen (LANA1), Epstein–Barr virus‐encoded small RNA and light chains. Presence of significant numbers of HHV8‐LANA1⁺ lymphoid/plasmacytic cells, noted in 10/28 cases, was indicative of BM involvement and was associated with low CD4 and CD8 counts in peripheral blood. The characteristic morphological appearance of MCD seen in lymph nodes is a rare finding in BMTB. 4/5 cases with lymphoid aggregates were involved by MCD, whereas 6/23 cases without lymphoid aggregates were involved by MCD (P = 0·023). 9/18 cases with hypercellular marrow were involved by MCD, whilst only 1/8 cases with normo/hypocellular marrow showed involvement by MCD (P = 0·070). While 9/21 cases with increased marrow reticulin were involved by MCD, none of the cases with no increase in reticulin were involved by MCD (P = 0·080). Reactive plasmacytosis is a frequent finding. We conclude that bone marrow is involved in a significant proportion of patients with MCD (36%), and involvement can be identified by HHV8‐LANA1 immunohistochemistry.     

Preparedness of emergency departments in northwest England for managing chemical incidents: a structured interview survey

Background

Ocular injuries are common in survivors of terror incidents that involve the use of explosive materials. These explosives are commonly of a High Explosive type (HE) and may be fashioned into improvised explosive devices (IED) that incorporate additional materials to maximise trauma and injuries. Serial IED explosions have occurred in commuter trains in several cities including London and Madrid but data on ocular injuries is limited. We report the ocular injuries of the survivors of a series of IED explosions in crowded commuter trains.

Methods

28 patients (56 eyes, 28 male, ages ranging from 22 to 52 years (mean 35.27 years) were screened in the triage area or the Intensive Care Unit (ICU). Testing included bedside visual acuity testing, torchlight examination of the anterior segment and dilated (or if necessary, undilated) fundus examination. Selected patients underwent B-scan examination, magnetic resonance imaging of the brain, orbits and the optic nerves or visual evoked potential assessment. The injuries, investigations and procedures were entered into the patient's case sheet as well as into a standardised format suggested by the Indian eye injury registry (IER).

Results

16 of 28 patients (57.1%) had ocular injuries whereas 12 (42.8%) were found to be normal. Injuries were seen unilaterally in 10 patients and bilaterally in six yielding a total of 22 injured eyes. The common injuries were periorbital haemorrhages (09 eyes, 40%); first or second degree burns to the upper or lower lids (seen in 07 eyes, 31.8 %) and corneal injuries (seen in 08 eyes, 36.3%). Open globe injuries were seen in two eyes of two patients (09%). One patient (4.5%) had a traumatic optic neuropathy.

Conclusion

Ophthalmologists and traumatologists should be aware of these patterns of ocular injuries. Protocols need to include the screening of large numbers of patients in a short time, diagnostic tests (B scan, visual evoked potential (VEP) etc) and early surgery preferably at the initial triage itself as most of the serious injuries in our studies had been missed or not treated at an initial assessment.     

Investigation into cases of hepatitis of unknown aetiology among young children,Scotland, 1 January 2022 to 12 April 2022

On 31 March 2022, Public Health Scotland was alerted to five children aged 3–5 years admitted to hospital with severe hepatitis of unknown aetiology. Retrospective investigation identified eight additional cases aged 10 years and younger since 1 January 2022. Two pairs of cases have epidemiological links. Common viral hepatitis causes were excluded in those with available results. Five children were adenovirus PCR-positive. Other childhood viruses, including SARS-CoV-2, have been isolated. Investigations are ongoing, with new cases still presenting.     

Auditing the Representation of Female Versus Male Athletes in Sports Science and Sports Medicine Research: Evidence-Based Performance Supplements

Although sports nutrition guidelines promote evidence-based practice, it is unclear whether women have been adequately included in the underpinning research. In view of the high usage rates of performance supplements by female athletes, we conducted a standardised audit of the literature supporting evidence-based products: β-alanine, caffeine, creatine, glycerol, nitrate/beetroot juice and sodium bicarbonate. Within 1826 studies totalling 34,889 participants, just 23% of participants were women, although 34% of studies included at least one woman. Across different supplements, 0–8% of studies investigated women exclusively, while fewer (0–2%) were specifically designed to compare sex-based responses. The annual publication of female-specific studies was ~8 times fewer than those investigating exclusively male cohorts. Interestingly, 15% of the female participants were classified as international/world-class athletes, compared with 7% of men. Most studies investigated performance outcomes but displayed poorer representation of women (16% of participants), whereas health-focussed studies had the greatest proportion of female participants (35%). Only 14% of studies including women attempted to define menstrual status, with only three studies (~0.5%) implementing best practice methodologies to assess menstrual status. New research should target the efficacy of performance supplements in female athletes, and future sports nutrition recommendations should specifically consider how well female athletes have contributed to the evidence-base.     

Working the edges of Posthuman disability studies: theorising with disabled young people with life‐limiting impairments

This paper is built upon an assumption: that social theory can be generated through a meaningful engagement with a co‐researcher group of disabled young people. Our co‐researchers are theoretical provocateurs and theorists in their own right who, through their activism and writing, are challenging us to reconsider the meaning of life, death and disability. Their work on our funded Economic and Social Research Council (ESRC) project has enabled us to consider the promise and potential of humanist and posthuman epistemologies, theories, methodologies, interventions and activisms. The paper introduces the research, the authors of this paper (academics and co‐researchers) and then explores three layers of analysis that work the edges of posthuman thinking; sovereign and assembled selves; affects and desires; mourning and affirmation. We conclude by asserting that as a research team we are engaging with a DisHuman approach to theory and activism: one that blends the pragmatics of humanism with posthuman possibilities.     

UK consensus statement on the use of plerixafor to facilitate autologous peripheral blood stem cell collection to support high‐dose chemoradiotherapy for patients with malignancy

Plerixafor is a CXC chemokine receptor (CXCR4) antagonist that mobilizes stem cells in the peripheral blood. It is indicated (in combination with granulocyte‐colony stimulating factor [G‐CSF]) to enhance the harvest of adequate quantities of cluster differentiation (CD) 34+ cells for autologous transplantation in patients with lymphoma or multiple myeloma whose cells mobilize poorly. Strategies for use include delayed re‐mobilization after a failed mobilization attempt with G‐CSF, and rescue or pre‐emptive mobilization in patients in whom mobilization with G‐CSF is likely to fail. Pre‐emptive use has the advantage that it avoids the need to re‐schedule the transplant procedure, with its attendant inconvenience, quality‐of‐life issues for the patient and cost of additional admissions to the transplant unit. UK experience from 2 major centers suggests that pre‐emptive plerixafor is associated with an incremental drug cost of less than £2000 when averaged over all patients undergoing peripheral blood stem cell (PBSC) transplant. A CD34+ cell count of <15 µl^?1 at the time of recovery after chemomobilization or after four days of G‐CSF treatment, or an apheresis yield of <1 × 10⁶ CD34+ cells/kg on the first day of apheresis, could be used to predict the need for pre‐emptive plerixafor.     

More a finger than a nose: The trigeminal motor and sensory innervation of the Schnauzenorgan in the elephant-nose Fish Gnathonemus petersii

The weakly electric fish Gnathonemus petersii uses its electric sense to actively probe the environment. Its highly mobile chin appendage, the Schnauzenorgan, is rich in electroreceptors. Physical measurements have demonstrated the importance of the position of the Schnauzenorgan in funneling the fish's self-generated electric field. The present study focuses on the trigeminal motor pathway that controls Schnauzenorgan movement and on its trigeminal sensory innervation and central representation. The nerves entering the Schnauzenorgan are very large and contain both motor and sensory trigeminal components as well as an electrosensory pathway. With the use of neurotracer techniques, labeled Schnauzenorgan motoneurons were found throughout the ventral main body of the trigeminal motor nucleus but not among the population of larger motoneurons in its rostrodorsal region. The Schnauzenorgan receives no motor or sensory innervation from the facial nerve. There are many anastomoses between the peripheral electrosensory and trigeminal nerves, but these senses remain separate in the sensory ganglia and in their first central relays. Schnauzenorgan trigeminal primary afferent projections extend throughout the descending trigeminal sensory nuclei, and a few fibers enter the facial lobe. Although no labeled neurons could be identified in the brain as the trigeminal mesencephalic root, some Schnauzenorgan trigeminal afferents terminated in the trigeminal motor nucleus, suggesting a monosynaptic, possibly proprioceptive, pathway. In this first step toward understanding multimodal central representation of the Schnauzenorgan, no direct interconnections were found between the trigeminal sensory and electromotor command system, or the electrosensory and trigeminal motor command. The pathways linking perception to action remain to be studied. J. Comp. Neurol. 523:769–789, 2015. © 2014 Wiley Periodicals, Inc.     

Reduced-intensity conditioning for allogeneic haematopoietic stem cell transplantation in relapsed and refractory Hodgkin lymphoma: impact of alemtuzumab and donor lymphocyte infusions on long-term outcomes

The introduction of reduced-intensity conditioning (RIC) has enabled the role of allogeneic transplantation to be re-evaluated in Hodgkin lymphoma (HL). While T-cell depletion reduces graft-versus-host disease (GvHD), it potentially abrogates graft-versus-tumour activity and increases infective complications. We compared the results in 67 sibling donor transplantations following RIC in multiply relapsed patients from two national phase II studies conditioned with fludarabine/melphalan. One used cyclosporine/alemtuzumab (MF-A, n = 31), the other used cyclosporine/methotrexate (MF, n = 36) as GvHD prophylaxis. There was a small excess of chemorefractory cases in the MF cohort (P = NS). MF-A resulted in significantly lower incidences of non-relapse mortality, acute and chronic GvHD, but no significant excess of relapse/progression. Post donor lymphocyte infusion (DLI) disease responses occurred in 8/14 (57%) and 6/11 (55%) patients in the MF-A and MF groups, respectively. Current progression-free survival (CPFS) was superior with MF-A (univariate analysis), with durable responses to DLI contributing to the favourable outcome (43% vs. 25%, P = 0.0356). Disease status at transplantation significantly influenced overall survival (P = 0.0038) and CPFS (P = 0.0014), retaining significance in multivariate analyses, which demonstrated a trend towards improved CPFS with T-cell depletion (P = 0.0939). These data suggest that alemtuzumab significantly reduced GvHD without resulting in a deleterious impact on survival outcomes following RIC in HL, and that durable responses to DLI may be more common following the inclusion of alemtuzumab in the conditioning protocol.     

Enhanced glucocorticoid receptor signaling in T cells impacts thymocyte apoptosis and adaptive immune responses

To study the effect of enhanced glucocorticoid signaling on T cells, we generated transgenic rats overexpressing a mutant glucocorticoid receptor with increased ligand affinity in the thymus. We found that this caused massive thymocyte apoptosis at physiological hormone levels, which could be reversed by adrenalectomy. Due to homeostatic proliferation, a considerable number of mature T lymphocytes accumulated in the periphery, responding normally to costimulation but exhibiting a perturbed T-cell repertoire. Furthermore, the transgenic rats showed increased resistance to experimental autoimmune encephalomyelitis, which manifests in a delayed onset and milder disease course, impaired leukocyte infiltration into the central nervous system and a distinct cytokine profile. In contrast, the ability of the transgenic rats to mount an allergic airway response to ovalbumin was not compromised, although isotype switching of antigen-specific immunoglobulins was altered. Collectively, our findings suggest that endogenous glucocorticoids impact T-cell development and favor the selection of Th2- over Th1-dominated adaptive immune responses.