Semaglutide treatment for PRevention Of Toxicity in high-dosE Chemotherapy with autologous haematopoietic stem-cell Transplantation (PROTECT): study protocol for a randomised, double-blind, placebo-controlled, investigator-initiated study.

INTRODUCTION: Cancer treatment with high-dose chemotherapy damages the mucosal barrier of the gastrointestinal (GI) tract and is associated with severe toxicity involving mucositis, severe inflammation and organ dysfunction. Currently, there is no effective prophylaxis against this. Glucagon-like peptide 1 (GLP-1), a well-known regulator of blood glucose, has been suggested in mouse studies to possess trophic effects on gut epithelial cells as well as anti-inflammatory properties. In line with this, endogenous GLP-1 levels have been shown to be inversely correlated with toxicities after haematopoietic stem cell transplantation (HSCT) and treatment with a GLP-1 receptor agonist (GLP-1RA) was shown to limit chemotherapy-induced mucositis in rodents. This present study investigates the effects of the GLP-1RA semaglutide on GI mucositis severity score in patients with lymphoma undergoing high-dose chemotherapy followed by autologous (auto) HSCT. METHODS AND ANALYSIS: This is a randomised, double-blind, placebo-controlled, two-centre investigator-initiated clinical study. Forty adult patients with malignant lymphoma referred for auto-HSCT will be randomised in a 1:1 manner to receive either semaglutide or placebo once-weekly for 8 weeks. This includes a run-in period of 3-4 weeks with semaglutide 0.25 mg prior to high-dose chemotherapy treatment followed by a period of 4-5 weeks with semaglutide 0.5 mg including the 1 week of high-dose chemotherapy treatment. Clinical assessment of endpoint measurements and safety will be performed weekly during treatment and in a follow-up period of 10 weeks. The primary endpoint is GI mucositis severity (mean severity grade (0-II) during week 1-4 after auto-HSCT). Secondary endpoints include C-reactive protein increment, quality of life and safety. Fever, bacteraemia, antibiotic use, weight loss, morphine consumption, duration of hospitalisation, use of parenteral nutrition, change in muscle mass and clinical and laboratory evidence of organ toxicities will also be assessed. ETHICS AND DISSEMINATION: The study complies with Danish and European Union legislation and is approved by the Danish Medicines Agency, the Danish National Medical Research Ethics Committee (EU CT #2022-502139-20-00) and the Danish Data Protection Agency. The study is monitored by the Capital Region of Denmark's good clinical practice unit. All results, positive, negative and inconclusive, will be disseminated at national and international scientific meetings and in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT06449625.

Gangrene and osteomyelitis of the toe in a previously healthy patient due to undiagnosed essential thrombocythemia.

We report a case of gangrene and osteomyelitis of the toe in a young, previously healthy male with undiagnosed essential thrombocythemia (ET). The patient experienced persistent right fifth toe pain, discolouration and ulceration for 3-4 months, unresponsive to antibiotics. Despite multiple normal X-rays, 2 months later, MRI revealed osteomyelitis. On inpatient admission, testing revealed thrombocytosis and abnormal blood flow to right fourth and fifth toes without thrombus, consistent with vasospasm. This ultimately resulted in ischemia, gangrene and osteomyelitis of the toe, necessitating amputation. The patient was subsequently treated with hydroxyurea for ET. This unusual presentation underscores the importance of a broad differential in cases when conventional treatments fail to yield improvement.

The effect of Vachellia eriolaba leaf meal inclusion on growth performance, blood parameters and methane gas emission in lambs fed diets containing ammoniated maize stover.

The study evaluated the effect of Vachellia erioloba leaf meal in diets containing ammoniated maize stove on growth performance, methane emission and heath of growing lambs. Thirty-two female lambs were allocated to the following four dietary treatments: total mixed ration (TMR, control), 20% inclusion of untreated maize stover (UMS), 20% inclusion of ammoniated maize stover (AMS), and combined inclusion of 10% ammoniated maize stover and 10% Vachellia erioloba leaves (AMSVL). Each treatment was replicated 8 times and a lamb in an individual pen was regarded as an experimental unit in a completely randomized design. Feed intake was higher (P < 0.05) in lambs fed the AMS and AMSVL diets compared to those fed UMS. Final body weights were higher in lambs fed the AMS and AMSVL diets. Both average daily gain (ADG) and feed convention ratio (FCR) were not affected by diet. In comparison with the AMS and AMSVL diets, the lambs fed the UMS diet had the highest (P < 0.05) methane emission. Overall, lambs fed the control diets had the lowest (P < 0.05) methane gas emission. Blood hematological values were affected by diet with the AMSVL fed lambs having the highest (P < 0.05) mean platelet volume (MPV) and procalcitonin (PCT) values. Furthermore, total albumin, amylase and total bilirubin were the highest (P < 0.05) in lambs fed on the AMSVL diet. Lambs fed on AMS diet had the highest (P < 0.05) serum urea levels. It can be concluded that combined inclusion of ammoniated maize stover and Vachellia leaves improved feed value and lamb performance when compared to the individual inclusion of both UMS and AMS.

Effects of In Ovo Administration of Freeze-Dried Royal Jelly on Hatchability, Blood Parameters, and Organ Weights of Day-Old Chicks.

Royal jelly renowned for its robust nutritional, functional, and biological properties, is a pivotal product derived from honeybees. The purpose of this investigation was to assess the theory that in ovo injection of freeze-dried royal jelly (FDRJ) solutions at varying concentrations can influence the hatchability, blood properties and hatching characteristics of day-old chicks. A total of 480 eggs (54.81 ± 0.187 g) were allocated into four experimental groups: negative control (NC), without injection, positive control (PC), administered with regular saline, a low FDRJ dose group (9 mg/egg), and a high FDRJ dose group (18 mg/egg). The in ovo injections were administered on Day 18 of incubation, and the experiment was subsequently continued until the incubation period concluded at 21 days. Results revealed that the lower FDRJ dose (9 mg/egg) significantly improved hatchability percentages compared to other treatments. Conversely, the higher FDRJ dose (18 mg/egg) and control groups (NC and PC) resulted in significantly higher chick yield percentages than the lower FDRJ and PC groups. The NC group showed the supreme yolk sac (YS) percentage, whereas the yolk-free body mass (YFBM) percentages displayed an inverse trend. Furthermore, the in ovo FDRJ injection did not affect haematological values or the relative organ weight of day-old chicks. In conclusion, in ovo FDRJ injection demonstrated beneficial effects on hatchability and chick weight, as evidenced by the studied parameters.

Thiamine-responsive megaloblastic anaemia in a young adult with acute pancytopenia.

Thiamine-responsive megaloblastic anaemia (TRMA) is a rare autosomal recessive disorder characterised by the clinical triad of megaloblastic anaemia, sensorineural hearing loss and diabetes mellitus (DM) in young patients. We present a case of a young man with type 1 DM who presented with pancytopenia of unclear aetiology, initially attributed to a COVID-19 infection. After obtaining a bone marrow biopsy and pursuing genetic testing, two pathogenic variants of the SLC19A2 gene consistent with TRMA were discovered in this patient. Treatment with 100 mg of thiamine oral supplementation daily led to the complete resolution of his pancytopenia. It is important to consider a genetic cause of pancytopenia in a young person. Early recognition and diagnosis of TRMA can be life-altering given early treatment can reduce insulin requirements and resolve anaemia.

Rare presentation and unconventional treatment of Rosai-Dorfman disease.

Rosai-Dorfman disease (RDD) is a rare myeloproliferative disorder involving histiocytes, with an incidence of 1:200 000 and approximately 100 new cases diagnosed annually in the USA. The condition presents a diverse range of clinical manifestations, and early recognition and treatment generally result in a favourable prognosis. However, diagnosing RDD poses challenges due to its rarity. The clinical management of RDD lacks a consensus, further complicating its diagnostic and therapeutic approach. We present a case of a man in his late 50s with RDD who experienced worsening cytopenias, including severe neutropenia and respiratory distress, despite an initial positive response to steroids, rituximab and lenalidomide. Genetic testing revealed mutations in POLE, KRAS (G13C), NDE1 and EZH2, suggesting potential new therapeutic targets. Sirolimus was initiated and led to complete radiological remission of the disease. This case adds strength to the growing evidence supporting the efficacy of sirolimus in refractory RDD cases.

Synchronous presentation of recurrent intracranial solitary fibrous tumour and chronic myeloid leukaemia: a diagnostic challenge.

Solitary fibrous tumours (SFTs) and chronic myeloid leukaemia (CML) are both uncommon neoplasms with distinct chromosomal aberrations and clinical presentations. Here, we present a case of a male in his late 50s with a history of intracranial SFT who presented 8 years after subtotal resection and adjuvant radiotherapy with splenic infarcts, a white blood cell of 83 000 cells/mL, and liver masses. He was treated with dasatinib for CML and temozolomide/bevacizumab for SFT. This case emphasises the benefits of broad differential diagnoses that include multiple concurrent disease processes when confronted with unusual presentations. It highlights the need for interdisciplinary efforts and personalised approaches when managing patients with multiple primary malignancies.

Health assessment of nesting loggerhead sea turtles (Caretta caretta) in one of their largest rookeries (central eastern Florida coast, USA).

Reproduction is a physiologically demanding process for sea turtles. Health indicators, including morphometric indices and blood analytes, provide insight into overall health, physiology and organ function for breeding sea turtles as a way to assess population-level effects. The Archie Carr National Wildlife Refuge (ACNWR) on Florida's central eastern coast is critical nesting habitat for loggerhead sea turtles (Caretta caretta), but health variables from this location have not been documented. Objectives of the study were to (1) assess morphometrics and blood analyte data (including haematology, plasma biochemistry, protein electrophoresis, ß-hydroxybutyrate, trace nutrients, vitamins and fatty acid profiles) from loggerheads nesting on or near the beaches of the ACNWR, (2) investigate correlations of body condition index (BCI) with blood analytes and (3) analyse temporal trends in morphometric and blood analyte data throughout the nesting season. Morphometric and/or blood analyte data are reported for 57 nesting loggerheads encountered between 2016 and 2019. Plasma copper and iron positively correlated with BCI. Mass tended to decline across nesting season, whereas BCI did not. Many blood analytes significantly increased or decreased across nesting season, reflecting the catabolic state and haemodynamic variations of nesting turtles. Twenty-three of 34 fatty acids declined across nesting season, which demonstrates the physiological demands of nesting turtles for vitellogenesis and reproductive activities, thus suggesting potential utility of fatty acids for the assessment of foraging status and phases of reproduction. The findings herein are relevant for future spatiotemporal and interspecies comparisons, investigating stressor effects and understanding the physiological demands in nesting sea turtles. This information provides comparative data for individual animals in rescue or managed care settings and for assessment of conservation strategies.

CNS prophylaxis in large B-cell lymphomas: A balance with three pans.

Given the significant limitations of available literature, central nervous system (CNS) prophylaxis in large B-cell lymphomas remains debatable. Wilson and colleagues provide cautious recommendations, on a case-by-case basis, useful to guide discussion with individual patient. In daily practice, CNS relapse risk, prophylaxis safety and prognosis of CNS recurrence must be considered. Commentary on: Wilson et al. Central nervous system prophylaxis in large B-cell lymphoma: A British Society for Haematology Good Practice Paper. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19686.

Cytokine profiles, blood parasite load and clinical features of visceral leishmaniasis in West Pokot County, Kenya.

Visceral leishmaniasis (VL) is a severe infectious disease caused by protozoan parasites of the Leishmania donovani complex. Blood cytokine concentrations in VL patients can inform us about underlying immunopathogenesis and may serve as a biomarker for treatment effectiveness. However, cytokine levels have not yet been studied in VL patients from Kenya, where case load is high. This study measured the serum cytokine profile, blood parasite load and clinical and haematological features of VL patients from West Pokot County, Kenya, over the course of treatment with sodium stibogluconate and paromomycin (SSG-PM). VL patients recruited at the hospital presented with splenomegaly and weight loss, and frequently had pancytopenia and anaemia. Median Leishmania parasite load in blood, determined with real-time polymerase chain reaction, was 2.6 × 104 parasite equivalents mL−1. Compared to endemic healthy controls, serum interferon gamma (IFN-γ), interleukin 5 (IL-5), IL-6, IL-10, IL-12p70, IL-17A and IL-27 were significantly elevated in untreated VL patients. Severe VL was associated with higher IL-10 and lower IFN-γ levels. After 17 daily injections with SSG-PM, disease symptoms disappeared, leukocyte and thrombocyte counts significantly increased, and blood parasite load decreased to undetectable levels in all VL patients. There was a significant decrease in IL-10 and IL-6, whereas IL-17A levels increased; the remaining cytokines showed no significant concentration change during treatment. In conclusion, the results suggest that SSG-PM treatment of VL patients from West Pokot was effective. Moreover, both inflammatory and regulatory immune responses appeared to decrease during treatment, although the increase in IL-17A could reflect a partial continuation of immune activation.

Bortezomib-induced neuropathy in multiple myeloma manifesting as foot drop due to peroneal nerve palsy.

We present the case of a man in his 50s with multiple myeloma who developed foot drop after receiving bortezomib-dexamethasone combination chemotherapy. Diagnostic evaluations, including haematological parameters, nerve conduction studies and imaging, were performed to confirm the diagnosis and assess the extent of neuropathy. He was managed conservatively with analgesics and vitamin supplements, and bortezomib was temporarily withheld. The neuropathy gradually improved, and bortezomib was successfully reintroduced without recurrence of foot drop. Bortezomib-induced foot drop is a rare complication of bortezomib-based therapy in patients with multiple myeloma. Early recognition and intervention are crucial to minimise impact on quality of life. This case report emphasises the safe reintroduction of bortezomib post-neuropathy resolution, emphasising the importance of early recognition and multidisciplinary management.

Blastic plasmacytoid dendritic cell neoplasm: a rare external ear lesion presenting with leukaemia.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive haematological malignancy, typically characterised by cutaneous lesions and bone marrow involvement. We present a unique case of a woman in her 70s, initially seen for a spontaneous swelling on her left external ear resembling a haematoma, which recurred after initial treatment, triggering further evaluation.Diagnostic challenges arose as the patient displayed positive markers for Myeloperoxidase (MPO) (p-ANCA), suggesting vasculitis. Dermatology considered various differential diagnoses, but imaging and tests ruled out significant pathology. Steroid treatment led to improvement, but coincided with a surge in white cell count (WCC), prompting an urgent haematological review.Subsequent investigations, including a punch biopsy of the external ear and a bone marrow biopsy revealed BPDCN concurrent with chronic myelomonocytic leukaemia. This case highlights the challenging diagnostic journey, emphasising the need for multidisciplinary collaboration and the potential for unique BPDCN presentations, expanding our understanding of this malignancy.

Metastatic gastric adenocarcinoma discovered in the bone marrow.

Gastric cancer primarily metastasizes to the peritoneum, liver and lungs, with bone marrow involvement being a rare occurrence, found in less than 1% of cases. Disseminated carcinomatosis of the bone marrow (DCBM) is characterised by widespread infiltration of cancer cells into the bone marrow, leading to haematological disorders such as disseminated intravascular coagulation and thrombocytopenia. We present a unique case of a man in his late 50s with acute thrombocytopenia as the initial symptom, subsequently diagnosed with gastric cancer on bone marrow examination. Despite receiving chemotherapy, the patient's condition deteriorated rapidly, emphasising the challenging management and poor prognosis associated with DCBM. This case underscores the need for improved diagnostic strategies and therapeutic approaches to enhance patient outcomes in DCBM associated with gastric cancer.

Investigating the impact of multidisciplinary prehabilitation on deconditioning in patients eligible for haematopoietic allogenic stem cell transplantation: protocol for a feasibility trial.

BACKGROUND: Assessing multidisciplinary prehabilitation strategies becomes crucial to pre-emptively counter the physical, psychological and social negative impacts experienced during an allogenic haematopoietic stem cell transplant (allo-HSCT) among acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients. Current evidence is restricted to studies during induction chemotherapy, omitting rehabilitation interventions and predominantly using exercise-only approaches without a multidisciplinary framework. The aim of this study is to investigate the feasibility, safety and preliminary efficacy of multidisciplinary prehabilitation in adults offered allo-HSCT. METHODS AND ANALYSIS: This 8-week single-group pre-post feasibility study aims to pilot a multidisciplinary prehabilitation intervention for participants undergoing allo-HSCT, with a focus on feasibility and safety. Participants, aged 18 or older, diagnosed with AML or MDS, and offered allo-HSCT, will be recruited between June 2023 and July 2024. The multidisciplinary prehabilitation intervention, conducted by the cancer allied health team at the Royal Adelaide Hospital, includes exercise physiology, physiotherapy, dietetics, social work, occupational therapy and psychology interventions. Consistent with a multidisciplinary treatment approach, each component is tailored to address different aspects of patient care, and adherence calculations will assess patient engagement and compliance. In addition, participants will continue to receive usual care from cancer allied health staff. The primary outcome of the study is to assess the feasibility of a multidisciplinary prehabilitation intervention by evaluating intervention uptake, retention, adherence, acceptability and safety. Secondary outcomes are leg strength, upper-body strength, aerobic fitness, falls risk, anthropometry, nutritional status, quality of life, anxiety, depression, self-efficacy for coping with cancer and distress. ETHICS AND DISSEMINATION: Ethics approval for this study has been provided by the Central Adelaide Local Health Network (HREC 2022/HRE00284). Recruitment for the study commenced in June 2023 and will continue until July 2024. The methods have been designed and are reported according to the SPIRIT and CONSORT-pilot study checklist. TRIAL REGISTRATION NUMBER: The Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623000052639.

Tumour-directed radiotherapy as a successful bridge to curative chemotherapy in early stage Hodgkin's lymphoma-associated vanishing bile duct syndrome.

Hodgkin's lymphoma (HL)-associated vanishing bile duct syndrome (VBDS) is a paraneoplastic phenomenon leading to cholestasis, end-stage liver failure and potentially death, due to cholestatic liver dysfunction typically precluding the commencement of curative intent chemotherapy. A female in her 20s presented with pruritus, jaundice and cholestatic hepatitis on laboratory tests, confirmed as VBDS on liver biopsy. CT of the chest demonstrated a mediastinal mass and widespread cervical lymphadenopathy. The patient received 30.6 Gy in 17 fractions to the involved sites of disease which led to a marked improvement in liver function, allowing curative intent chemotherapy to be initiated. The patient achieved complete metabolic response and at the most recent follow-up she had no signs of recurrent disease and near-normal liver function tests. This demonstrates that tumour-directed radiotherapy can be used as a potential bridge to curative chemotherapy in early stage HL-associated VBDS.

The power and perils of large language models in haematology.

Large language models (LLMs) are a transformative technology poised to fundamentally change multiple fields including haematology. Here, we review the history of large language model development, describe their current capabilities and identify opportunities in haematology poised to benefit from their judicious application. We conclude by suggesting a framework for the safe and ethical development of LLM-derived tools in a way that minimizes risk and maximizes clinical benefit for haematology physicians and patients.

Establishment of reference intervals of haematology and biochemistry analytes in ICR mice of different ages.

Outbred stocks of mice are widely used in pre-clinical research as these animals possess a diversified genetic background when compared with inbred strains of mice. It is crucial to assess particular alterations in the physiological and functional profiles of laboratory animals using haematological and biochemical indicators. These values can also differ between laboratories because they are influenced by many different factors. We aimed to provide normal values and reference intervals for selected haematology and biochemistry analytes of 570 ICR mice at three different ages: 6-8 weeks, 10-14 weeks and 6-9 months. Reference values were calculated by non-parametric methods. For comparisons between sexes, the independent-sample t-test and Mann-Whitney test were employed, and analysis of variance was used for age differences. The findings of the study revealed age-related declines in haemoglobin concentration, haematocrit, mean corpuscular volume and mean corpuscular haemoglobin concentrations. Mice aged 6-9 months had statistically higher platelet counts in their blood than mice of other ages. The white blood cell count had a significant age effect and progressively decreased with age. As mice get older, the percentage of neutrophils, monocytes and basophils increases, but the percentage of lymphocytes decreases. For the biochemical values, age-related significant differences in glucose, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and albumin concentrations were found. It was also found that creatinine concentrations were comparable across all age ranges. The values presented in the present work can be used as a reference to interpret clinical pathology data for other studies and to evaluate health status.

Importance of immunosuppression in haemophagocytic lymphohistiocytosis caused by miliary tuberculosis.

Haemophagocytic lymphohistiocytosis (HLH) is a syndrome with an abnormal activation of the immune system and is associated with a high mortality even with treatment. We present a case of a woman in her mid-50s who developed HLH triggered by miliary tuberculosis (TB) while receiving a tumour necrosis factor alpha inhibitor.The patient was admitted with a high fever and respiratory pain. Her condition deteriorated despite empirical treatment. Diagnosis of HLH was established based on clinical presentation, H-score and HLH-04 criteria. Concurrently, miliary TB was identified as the trigger. She was treated with anti-tuberculous therapy and HLH-directed treatment with dexamethasone, etoposide and anakinra. Initial improvement was observed, leading to the withholding of HLH-orientated treatment. However, several relapses occurred, necessitating prolonged HLH treatment.A literature review corroborated the importance of combined anti-tuberculous and immunosuppressive therapy for managing HLH. This case underscores the necessity of timely and comprehensive management of HLH-oriented treatment.

[Nurturing and growing a community of department heads: Act 2 in haematology]. / Faire vivre et grandir une communauté de chefs de service : acte 2 en hématologie.

In response to the French hospital system crisis and the challenges faced by the heads of departments, we have undertaken an initiative to create a community of heads of haematology departments willing to assist each other. Our inaugural seminar, held in January 2023, established the foundational "core" group of heads of department. Throughout 2023, this emerging community has prospered, offering sustained support to peers. In January 2024, we broadened our community to include other heads of departments, following a second seminar gathering 36 participants. During this event, we took the time to exchange thoughts and reflect on our missions. Building on the experience of guest speakers and employing methods of co-development and co-construction in plenary sessions, small-group workshops, and social gathering, we were able to discover and experience the collective intelligence, creativity, strength, and support stemming from such a group. This peer community of heads of departments stands as a powerful tool for management support, whereby personal experiences nourish and enrich the experience of others. We hope that our initiative will inspire heads of departments from other specialties so that, together, we can better work towards our missions as heads of departments and collaborate on rebuilding the hospital "from the bottom up".