Acute intravascular haemolysis associated with scrub typhus.

Scrub typhus, a prevalent tropical infection, may sometimes manifest with unusual complications. Here, we present the case of a young man who was admitted to our facility with a fever for the past 3 days and passage of dark-coloured urine since that morning. On investigation, we identified intravascular haemolytic anaemia. Through meticulous examination, a black necrotic lesion (eschar) was discovered on his right buttock, a pathognomonic sign of scrub typhus infection. Treatment was initiated with oral doxycycline 100 mg two times a day. Subsequently, diagnosis of scrub typhus was confirmed through positive results from scrub typhus IgM via ELISA and PCR analysis from the eschar tissue. The patient responded well to oral doxycycline and his symptoms resolved within the next few days. This case highlights severe intravascular haemolysis associated with scrub typhus infection.

Extranodal diffuse large B-cell lymphoma involving the uterine cervix.

This is a case of primary diffuse large B-cell lymphoma involving the uterine cervix which presented with irregular vaginal bleeding. The diagnosis was confirmed following multiple cervical biopsies. Treatment with a combination of immunotherapy, chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP)) and radiotherapy produced a good response.

The enigma of sickle cell hepatopathy: Pathophysiology, clinical manifestations and therapy.

Sickle cell disease (SCD) is one of the most common genetic disorders in the world predominantly affecting economically disadvantaged populations. There is a notable discrepancy between the growing adult SCD population and available diagnostic and therapeutic interventions for SCD. Sickle cell hepatopathy (SCH) is an all-inclusive term to describe the acute and chronic liver manifestations of SCD. The pathophysiology of SCH follows no defined pattern or sequence that poses challenges to clinicians and researchers alike. Evidence is lacking for this underreported disease at various levels from diagnostic to therapeutic options. This paper reviews the basic pathophysiology, clinical features, biochemical and radiological findings of various SCH manifestations and outlines the management of each condition. Old and new therapy options in SCD including hydroxyurea, red blood cell exchange transfusion, ursodeoxycholic acid, voxelotor, l-glutamine and crizanlizumab have been reviewed to investigate the role of these options in treating SCH. The role of liver transplant, haematopoietic stem cell transplant and gene therapy in SCH patients have been reviewed.

Preventing adverse events during paediatric cancer treatment: protocol for a multi-site hybrid randomised controlled trial of catheter lock solutions (the CLOCK trial).

INTRODUCTION: Central venous access devices (CVADs) are commonly used for the treatment of paediatric cancer patients. Catheter locking is a routine intervention that prevents CVAD-associated adverse events, such as infection, occlusion and thrombosis. While laboratory and clinical data are promising, tetra-EDTA (T-EDTA) has yet to be rigorously evaluated or introduced in cancer care as a catheter lock. METHODS AND ANALYSIS: This is a protocol for a two-arm, superiority type 1 hybrid effectiveness-implementation randomised controlled trial conducted at seven hospitals across Australia and New Zealand. Randomisation will be in a 3:2 ratio between the saline (heparinised saline and normal saline) and T-EDTA groups, with randomly varied blocks of size 10 or 20 and stratification by (1) healthcare facility; (2) CVAD type and (3) duration of dwell since insertion. Within the saline group, there will be a random allocation between normal and heparin saline. Participants can be re-recruited and randomised on insertion of a new CVAD. Primary outcome for effectiveness will be a composite of CVAD-associated bloodstream infections (CABSI), CVAD-associated thrombosis or CVAD occlusion during CVAD dwell or at removal. Secondary outcomes will include CABSI, CVAD-associated-thrombosis, CVAD failure, incidental asymptomatic CVAD-associated-thrombosis, other adverse events, health-related quality of life, healthcare costs and mortality. To achieve 90% power (alpha=0.05) for the primary outcome, data from 720 recruitments are required. A mixed-methods approach will be employed to explore implementation contexts from the perspective of clinicians and healthcare purchasers. ETHICS AND DISSEMINATION: Ethics approval has been provided by Children's Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC) (HREC/22/QCHQ/81744) and the University of Queensland HREC (2022/HE000196) with subsequent governance approval at all sites. Informed consent is required from the substitute decision-maker or legal guardian prior to participation. In addition, consent may also be obtained from mature minors, depending on the legislative requirements of the study site. The primary trial and substudies will be written by the investigators and published in peer-reviewed journals. The findings will also be disseminated through local health and clinical trial networks by investigators and presented at conferences. TRIAL REGISTRATION NUMBER: ACTRN12622000499785.

Extranodal diffuse large B-cell lymphoma presenting with extensive organ involvement.

Extranodal involvement in diffuse large B-cell lymphoma (DLBCL) is defined as disease outside of the lymph nodes and occurs in up to one-third of patients, though multiorgan extranodal involvement is rare. Here, we describe a case of a patient presenting with widely metastatic lesions, including involvement of the lung, parotid gland, breast, pancreas, femur and multiple soft tissue masses, with initial concern for primary breast malignancy. Breast pathology and imaging were consistent with triple-expressor, double-hit stage IV high-grade B-cell lymphoma with extensive extranodal involvement. Extranodal involvement is a poor prognostic factor associated with high rates of treatment failure, and novel therapies targeting CD19 are currently being studied for relapsed and refractory DLBCL. Extranodal disease is a complex entity that can involve virtually any organ system and should be considered for new presentations of malignancy.

Phase II study in children and adults under 40 years with newly diagnosed Langerhans cell histiocytosis: protocol for an LCH-19-MSMFB clinical trial in Japan.

INTRODUCTION: Although the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and LCH-associated neurodegenerative diseases, remain to be resolved. Based on previous reports that patients with high-risk multisystem LCH show elevated levels of inflammatory molecules, we hypothesised that dexamethasone would more effectively suppress LCH-associated inflammation, especially in the central nervous system (CNS). We further hypothesised that intrathecal chemotherapy would effectively reduce CNS complications. We administer zoledronate to patients with multifocal bone LCH based on an efficacy report from a small case series. METHODS AND ANALYSIS: This phase II study (labelled the LCH-19-MSMFB study) is designed to evaluate the significance of introducing dexamethasone and intrathecal chemotherapy for multisystem disease and zoledronate for multifocal bone disease in previously untreated, newly diagnosed children, adolescents (under 20 years) and adults under 40 years. The primary endpoint is the 3-year event-free survival rate by risk group of under 20 years and the 3-year event-free survival rate of 20 years and over. ETHICS AND DISSEMINATION: This study was approved by the Central Review Board of the National Hospital Organisation Nagoya Medical Centre (Nagoya, Japan) on 21 January 2022 and was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp/en-latest-detail/jRCTs041210027). Written informed consent will be obtained from all patients and/or their guardians. TRIAL REGISTRATION NUMBER: jRCTs041210027.

Welfare and stress assessment of tourism carriage horses under real working conditions in Sicily.

Animal welfare has become an increasingly important concern regarding equids working as carriage animals. In the present study, the changes in the markers of stress and inflammatory responses as a result of the work performed by tourism carriage horses under real working conditions in Sicily (Italy) were investigated. Twenty-two Standardbreds performed a normal working day in the carriage tourism business during the months of May, June and July 2022, consisting of one day of work for each month. Blood samples were collected in the stables at rest before the tour route (Pre; 07.00 AM) and within 10 min after the end of the workday (Post; 05.00 PM). Haematological parameters, serum concentration of cortisol, total proteins together with the globulin fractions were investigated before and after the carriage work. Environmental temperature, relative humidity and temperature humidity index (THI) were also assessed. The direct erythrocyte indices increased after work compared to rest condition (P < 0.05). The values of cortisol, total proteins and globulins were not affected by carriage work (P > 0.05), while, higher cortisol, total proteins, α1- and α2-globulins values were observed in July compared to May and June (P < 0.05). These changes are probably due to the increase in THI values which showed mild stress in June and high stress in July. This study suggests that the tourism carriage horses herein investigated have adapted to their work activity, however, avoiding working horses during the hottest hours of the day in the summer months is advocated.

Atypical haemolytic uremic syndrome in a patient with severe Babesiosis.

Babesiosis is a tick-borne parasitic infection that can result in various haematological complications. This case report discusses a patient with severe Babesiosis complicated by an unorthodox presentation of Babesiosis-associated haemolytic uremic syndrome. Discussed here is the patient's clinical course and the management strategies employed, with an emphasis on early recognition and treatment of renal failure in the context of severe Babesiosis. Haematologic manifestations of Babesia are common and the severity of disease is dependent on parasite load. While treatment options such as red blood cell exchange have been proposed for severe cases, their impact on clinical outcomes is limited and they may not be readily available in resource-limited settings. Traditional management using antimicrobials has been proposed but there is limited discussion about managing unique presentations such as renal failure in Babesiosis. Hence, understanding the pathophysiology, early recognition and aggressive treatment strategies can optimise clinical outcomes and reduce mortality.

The clinical spectrum of HbSC sickle cell disease-not a benign condition.

Sickle cell disease (SCD) includes a group of heterogenous disorders that result in significant morbidities. HbSS is the most common type of SCD and HbSC is the second most common type of SCD. The prevalence of HbSC disease in the United States and United Kingdom is ~1 in 7174 births and 1 in 6174 births respectively. Despite its frequency, however, HbSC disease has been insufficiently studied and was historically categorized as a more 'mild' form of SCD. We conducted this study of HbSC disease as part of the NHLBI funded Sickle Cell Disease Implementation Consortium (SCDIC). The SCDIC registry included 2282 individuals with SCD, ages 15-45 years of whom 502 (22%) had HbSC disease. Compared with people with sickle cell anaemia (SCA), the study found that people with HbSC disease had a higher frequency of splenomegaly (n (%) = 169 (33.7) vs. 392 (22.1)) and retinopathy (n (%) = 116 (23.1) vs. 189 (10.6)). A Many people with HbSC also had avascular necrosis (n (%) = 112 (22.3)), pulmonary embolism (n (%) = 43 (8.6)) and acute chest syndrome (n (%) = 228 (45.4)) demonstrating significant disease severity. HbSC disease is more clinically severe than was previously recognized and deserves additional evaluation and targeted treatments.

Chronic myeloid leukaemia with soft tissue mass formed by mature granulocytes.

Extramedullary lesions in patients with chronic myeloid leukaemia (CML) suggest progression to the blast phase because such lesions generally consist of immature granulocytes. We here report a case of an extramedullary mass formed by mature granulocytes during the chronic phase of CML. A 60-year-old woman who had discontinued treatment for CML with dasatinib of her own accord several years ago presented to our hospital with a complaint of right thigh pain. She had a mass on her right leg, which was located on her right thigh and was elastic, soft and fist-sized. Blood tests and the bone marrow findings were compatible with the chronic phase of CML, and a CT-guided needle biopsy showed an infiltrate containing numerous mature neutrophils and foam cells. The mass disappeared with dasatinib alone, without antibacterial agents or drainage.Although the detailed pathogenesis of mass formation with mature granulocytes in the chronic phase of CML has not been elucidated, the clinical course of the current case highlights the importance of prompt biopsy, pathological examination and the early initiation of appropriate treatment.

Massive arterial and venous thrombosis from smouldering multiple myeloma: further evidence for monoclonal gammopathy of thrombotic significance.

A man in his 40s presented to the emergency department after 2 weeks of abdominal pain and bloating. Radiological investigations revealed multiple unusual sites of thrombosis, including large thrombi in his portal and mesenteric veins, and a left ventricular thrombus with resultant embolic infarcts to his spleen, kidneys, coronary arteries and brain. Standard causes of underlying thrombophilia were excluded. A serum protein electrophoresis and serum-free light chains, with subsequent bone marrow biopsy, lead to the diagnosis of smouldering multiple myeloma (sMM), albeit an unusual presentation with severe clinical sequelae. Although sMM is known to be associated with an increased risk of venous thromboembolism, it is not recognised to cause thrombosis in both venous and arterial vascular beds simultaneously. Physicians encountering patients with multiple thrombi in unusual vascular beds without clear aetiology should consider an underlying monoclonal gammopathy in their list of differentials.

The causality between gut microbiota and non-Hodgkin lymphoma: a two-sample bidirectional Mendelian randomization study.

Background: Studies have indicated an association between gut microbiota (GM) and non-Hodgkin lymphoma (NHL). However, the causality between GM and NHL remains unclear. This study aims to investigate the causality between GM and NHL using Mendelian randomization (MR). Methods: Data on GM is sourced from the MiBioGen consortium, while data on NHL and its subtypes is sourced from the FinnGen consortium R10 version. Inverse variance weighted (IVW) was employed for the primary MR analysis method, with methods such as Bayesian weighted Mendelian randomisation (BWMR) as an adjunct. Sensitivity analyses were conducted using Cochran's Q test, MR-Egger regression, MR-PRESSO, and the "Leave-one-out" method. Results: The MR results showed that there is a causality between 27 GMs and NHL. Among them, 20 were negatively associated (OR < 1), and 7 were positively associated (OR > 1) with the corresponding diseases. All 27 MR results passed sensitivity tests, and there was no reverse causal association. Conclusion: By demonstrating a causal link between GM and NHL, this research offers novel ideas to prevent, monitor, and cure NHL later.

Detection of novel duplication variant in ADAMTS13 gene using chromosomal microarray analysis.

We present a case of a child with congenital thrombotic thrombocytopenic purpura found to have a compound heterozygous variant in the ADAMTS13 gene with a novel variant resulting in a large duplication of exons 9-11 of ADAMTS13 This variant was identified through additional molecular testing via a chromosomal microarray analysis. To our knowledge, this assay had not previously been utilised to identify an ADAMTS13 variant and the additional testing was possible through the involvement of a genetic counsellor.

Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression in myelodysplastic neoplasms (MPO-MDS-Valid): protocol for a multicentre diagnostic accuracy study.

INTRODUCTION: Many patients referred for suspicion of myelodysplastic neoplasm (MDS) are subjected to unnecessary discomfort from bone marrow aspiration, due to the low disease prevalence in this population. Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression could rule out MDS with sensitivity and negative predictive value estimates close to 100%, ultimately obviating the need for bone marrow aspiration in up to 35% of patients. However, the generalisability of these findings is uncertain due to the limited sample size, the enrolment of patients at a single study site, and the reliability issues associated with laboratory-developed tests and varying levels of operator experience. This study aims to validate the accuracy attributes of peripheral blood neutrophil myeloperoxidase expression quantified by flow cytometric analysis in an independent multicentre sample. METHODS AND ANALYSIS: The MPO-MDS-Valid project is a cross-sectional diagnostic accuracy study comparing an index test to a reference standard. Consecutive adult patients referred for suspicion of MDS are being recruited at seven university hospitals and one cancer centre in France. At each site, flow cytometric analysis of peripheral blood samples is performed by operators who are blinded to the reference diagnosis. A central adjudication committee whose members are unaware of the index test results will determine the reference diagnosis of MDS, based on cytomorphological evaluation of bone marrow performed in duplicate by experienced hematopathologists. The target sample size is 400 patients and the anticipated study recruitment completion date is 31 December 2025. ETHICS AND DISSEMINATION: An institutional review board (Comité de Protection des Personnes Nord-Ouest III, Caen, France) approved the protocol, prior to the start of the study. Participants are recruited using an opt-out approach. Efforts will be made to publish the primary results within 6 months after study completion. TRIAL REGISTRATION NUMBER: NCT05175469.

Severe non-hepatic hyperammonaemic encephalopathy in an immunocompromised adolescent with enterocolitis.

Non-hepatic causes of hyperammonaemia are uncommon relative to hepatic aetiologies. An adolescent female was admitted to the hospital with a diagnosis of very severe aplastic anaemia. During her treatment with immunosuppressive therapy, she developed neutropenic enterocolitis, pseudomonal bacteraemia and hyperammonaemia. A combination of intermittent haemodialysis and high-volume continuous veno-venous haemodiafiltration (CVVHDF) was required to manage the hyperammonaemia. Despite a thorough investigation, there were no hepatic, metabolic or genetic aetiologies identified that explained the hyperammonaemia. The hyperammonaemia resolved only after the surgical resection of her inflamed colon, following which she was successfully weaned off from the renal support. This is a novel case report of hyperammonaemia of non-hepatic origin secondary to widespread inflammation of the colon requiring surgical resection in an immunocompromised patient. This case also highlights the role of high-volume CVVHDF in augmenting haemodialysis in the management of severe refractory hyperammonaemia.

Physiological stress responses in horses participating in novice endurance rides.

Horses participating in endurance events encounter enormous physical challenges. Heart rate (HR) and heart rate variability (HRV) have been reported before and after endurance rides, but these have not been determined during the rides. Moreover, the modulation in HRV and haematology in horses with different ride results (completed a course or disqualified due to irregular gait) have not been elucidated. Therefore, this study aimed to investigate changes in HR, HRV, and haematological parameters during novice endurance rides and to compare these parameters between horses that successfully completed the course (SC) or were disqualified for irregular gait (FTQ-GA). Beat-to-beat (RR) intervals of 16 healthy horses (aged 6-14 years) were recorded before and throughout the approximately 40 km endurance event. Blood samples were taken at the pre-ride inspection and after passing each veterinary inspection. HRV and haematology measures were determined from nine SC and seven FTQ-GA horses. Horses with different ride results demonstrated distinctive physiological stress responses. Increases in PCV, RBC, WBC and neutrophils after completing the ride were found only in SC horses, implying that they were ridden with greater effort than FTQ-GA horses. A reduction in HRV during warm-up, followed by a significant reduction during the first and second riding phases, was observed. HRV returned to baseline at the compulsory rest period of both phases. FTQ-GA horses experienced lower RR intervals, RR triangular index, modified deceleration capacity, very-low-frequency band, and parasympathetic nervous system index, coinciding with higher HR and sympathetic nervous system and stress indices than SC horses. These results indicated that endurance horses revealed a shift toward sympathetic activity during the ride. Lower parasympathetic activity in FTQ-GA horses suggests they were under more stress or discomfort than SC horses in novice endurance rides. These results have welfare implications, indicating the need for additional rest breaks in FTQ-GA horses.

Successful management of haemophagocytic lymphohistiocytosis in an adolescent with newly diagnosed HIV/AIDS and histoplasmosis.

Haemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening hyperinflammatory syndrome characterised by persistent fevers, cytopenia, hepatosplenomegaly and systemic inflammation. Secondary HLH can be triggered by various aetiologies including infections, malignancies and autoimmune conditions. We highlight the complexity of HLH diagnosis and management by describing a case of an adolescent Salvadoran immigrant with HLH, newly diagnosed HIV, Streptococcal bacteraemia and disseminated histoplasmosis. The patient presented with neurological and ocular findings along with persistent fevers and cytopenia. He was diagnosed with HLH and treated with anakinra in addition to receiving treatment for HIV, Streptococcal bacteraemia and histoplasmosis. The patient's HLH resolved without corticosteroids or chemotherapy, which are considered the mainstays for HLH treatment. This case underscores the need for the evaluation and management of multiple infections and individualised management in patients presenting with HLH to achieve favourable outcomes.

Dismantle and rebuild: the importance of preparedness and self-efficacy before, during and after allogeneic haematopoietic cell transplantation.

PURPOSE: The aim of this study was to explore patients' experiences of being prepared for allogenic haematopoietic cell transplantation and to explore their perceived self-efficacy and preparedness for self-care after allogenic haematopoietic cell transplantation. METHODS: Nine participants, who recently underwent allo-HCT, were interviewed regarding their views on preparedness, self-efficacy and self-care. The interviews were analysed using inductive qualitative content analysis. RESULTS: An overarching theme, Life is taken apart, then you have to know how to put the pieces together, and four sub-themes: Convert information into something understandable; Taking responsibility, maintaining and preparing for an uncertain time in life; Balancing vigilance with independence; and Reorientating in an altered body places new demands on self-care illustrate the dismantlement of life during treatment and how actions and approaches can build a new life. CONCLUSIONS: Both participants and healthcare professionals prioritised preparing for allo-HCT in the period before admission. However, during admission, preparation decreased and the time was not used for preparatory learning. This meant that participants were well prepared for the acute phase but unprepared for life after completion of treatment. Among the participants, self-efficacy was good. They sought information about taking care of their health before and in the aftermath of allo-HCT. IMPLICATIONS FOR CANCER SURVIVORS: This study provides insight into, and knowledge about, how patients prepare before, during and after treatment. This knowledge should primarily be directed towards healthcare professionals to be used for future patients who may need advice and support, as well as continued preparation for a life after transplantation.

Acute deep vein thrombosis with concurrent new diagnosis of AL-amyloid-induced factor X deficiency.

Acquired factor X (FX) deficiency is a rare but well-documented clinical feature of AL amyloidosis. Patients with FX deficiency can present with clinically significant bleeding diathesis due to the adsorption of circulating FX to amyloid fibrils. Here, we report an unusual case of a man in his 60s who presented with 6 months of intermittent bruising, labs demonstrating new FX deficiency, elevated free lambda light chains for underlying AL amyloidosis and concurrent new peroneal vein thrombosis. This is the first report of concurrent thrombotic complications in the setting of AL-amyloid-induced FX deficiency. We discuss the diagnostic and therapeutic conundrum of diagnosing AL amyloidosis with bruising as the leading clinical symptom and the management of acute deep vein thrombosis in the setting of FX deficiency.