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.

Clinical Outcomes and Determinants of Survival in Patients with Hematologic Malignancies Admitted to Intensive Care Units with Critical Illness.

Outcomes of patients with hematologic malignancies requiring ICU care for critical illness are suboptimal and represent a major unmet need in this population. We present data from a dedicated haematology oncology setting including 63 patients with a median age of 60 years admitted to the ICU for critical illness with organ dysfunction. The most common underlying diagnosis was multiple myeloma (30%) followed by acute myeloid leukemia (25%). Chemotherapy had been initiated for 90.7% patients before ICU admission. The most common indication for ICU care was respiratory failure (36.5%) and shock (17.5%) patients. Evidence of sepsis was present in 44 (69%) patients. After shifting to ICU, 32 (50%) patients required inotropic support and 18 (28%) required invasive mechanical ventilation. After a median of 5 days of ICU stay, 43.1% patients had died, most commonly due to multiorgan dysfunction. Risk of mortality was higher with involvement of more than two major organs (p = .001), underlying AML (p = .001), need for mechanical ventilation (p = .001) and high inotrope usage (p = .004). Neutropenia was not associated with mortality. Our study indicates high rates of short term mortality and defines prognostic factors which can be used to prognosticate patients and establish goals of care. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-024-01757-3.

The effect of a pushing technique with normal saline on peripheral intravenous catheter placement success in paediatric haematology and oncology: A randomized controlled trial.

PURPOSE: The aim of the present study is to determine the effect of the pushing technique with saline on the success of peripheral IV catheter placement in a paediatric haematology and oncology sample. METHODS: The randomized controlled trial was conducted among 60 paediatric haematology and oncology patients aged between 0 and 17. The participants were randomly assigned to two peripheral intravenous catheter placement groups (intervention group, n:30, control group, n:30). Each patient was evaluated with the Difficult Intravenous Access (DIVA) score before being included in the study. Each patient was assessed using the Personal Information Form for Children and Catheter Registration Form. RESULTS: The average age of the children was 86.4 months (SD = 60.0); 36.7% were female. The pushing technique with saline significantly increased the success of placing a peripheral IV catheter on the first attempt in the intervention group compared to the control group (F = 42.391, p = 0.000). The number of attempts during peripheral IV catheter placement significantly decreased in the intervention group compared with the control group (t = -5.676, p = 0.000). Complications were less in the intervention group compared with the control group (χ2 = 24.438, p = 0.000). The procedure time was significantly shorter in the intervention group compared with the control group (t = -4.026, p = 0.000). CONCLUSION: The pushing technique with saline is an effective method to increase the first attempt success rate, decrease the number of attempts, reduce the procedure time, and reduce the complications during peripheral intravenous catheter placement procedures in paediatric haematology and oncology patients with difficult intravenous access. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov (NCT05685290 & date of first recruitment: January 3, 2023) https://clinicaltrials.gov/ct2/show/NCT05685290.

Systemic loxoscelism leading to autoimmune haemolytic anaemia in a healthy young adult.

The brown recluse spider (Loxosceles reclusa) is endemic to the southcentral Midwest and the Southern United States. A bite from a brown recluse spider may result in symptoms that range from local skin necrosis to systemic complications such as acute haemolytic anaemia, disseminated intravascular coagulopathy, rhabdomyolysis and death. Although rare, systemic loxoscelism is a clinical diagnosis of exclusion that should be considered in a patient with acute autoimmune haemolytic anaemia. We describe a case of a young man with autoimmune haemolytic anaemia secondary to systemic loxoscelism successfully treated with intravenous immunoglobulin and steroids.

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.

Assessing the impacts of trace element contamination on the physiology and health of seabirds breeding along the western and southern coasts of Portugal.

Coastal seabirds serve as sentinels of ecosystem health due to their vulnerability to contamination from human activities. However, our understanding on how contaminant burdens affect the physiological and health condition of seabirds is still scarce, raising the uncertainty on the species' vulnerability vs tolerance to environmental contamination. Here, we quantified 15 Trace Elements (TE) in the blood of gull (yellow-legged gull Larus michahellis and Audouin's gull Ichthyaetus audouinii) and shearwater (Cory's shearwater Calonectris borealis) adults, breeding in five colonies along the Portuguese coastline. Additionally, stable isotopes of carbon (δ13C) and nitrogen (δ15N) were quantified to elucidate foraging habitat and trophic ecology of adults, to identify potential patterns of TE contamination among colonies. We used immuno-haematological parameters as response variables to assess the influence of TE concentrations, stable isotope values, and breeding colony on adults' physiological and health condition. Remarkably, we found blood mercury (Hg) and lead (Pb) concentrations to exceed reported toxicity thresholds in 25% and 13% of individuals, respectively, raising ecotoxicological concerns for these populations. The breeding colony was the primary factor explaining variation in five out of six models, underlining the influence of inherent species needs on immuno-haematological parameters. Model selection indicated a negative relationship between erythrocyte sedimentation rate and both Hg and selenium (Se) concentrations, but a positive relationship with δ13C. The number of immature erythrocyte counts was positively related to Hg and Se, particularly in yellow-legged gulls from one colony, highlighting the colony-site context's influence on haematological parameters. Further research is needed to determine whether essential TE concentrations, particularly copper (Cu) and Se, are falling outside the normal range for seabirds or meet species-specific requirements. Continuous monitoring of non-essential TE concentrations like aluminium (Al), Hg, and Pb, is crucial due to their potential hazardous concentrations, as observed in our study colonies.

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.

Validation of the HemoCue Hb 801 portable haemoglobin analyser for fish blood.

Haemoglobin concentration ([Hb]) assessment in fish blood has become a routine parameter to measure the health and welfare status of the animals. The original method (haemoglobincyanide method, best known as the Drabkin method) for measuring Hb in human and animals is not well suited for work outside of a laboratory setting. It is relatively time consuming, contains hazardous cyanide elements, and requires specific laboratory material. As an alternative to the Drabkin method, portable analysers have been developed for human blood, but they need to be first validated for fish blood before being used in experiments. In this study, the performance of the new HemoCue Hb 801 portable haemoglobin analyser was compared to the validated Drabkin method to determine [Hb] in three fish species. Hb readings between the two methods were not different for any of the species tested (rainbow trout, Onchorynchus mykiss, Atlantic wolffish, Anarhichas lupus, and Nile tilapia, Oreochromis niloticus). Therefore, this new portable device can be readily used to measure Hb in fish blood. Unlike the previous model from HemoCue, the Hb 201+, this device does not need an incubation time or a correction factor, representing a major gain of time and precision.

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.

[18F]-florbetaben PET/CT is sensitive for cardiac AL amyloidosis.

Often differential diagnosis between AL and ATTR amyloidosis is difficult. Concerning ATTR, sensitive diagnostic tool, as diphosphonate scintigraphy, was validated, instead of no imaging approach is as accurate in AL. Cardiac ultrasound and circulating biomarkers may raise the clinical suspicion but biopsy remains the only option for diagnosis. We aimed to explore the sensitivity of 18F-Florbetaben PET respect to blood tests or periumbilical fat (POF), cardiac, bone marrow (BM) or other tissues biopsies in a cohort of 33 patients.

Hyperbaric oxygen treatment in bilateral orchiopexy and post-circumcision haematoma in a thrombocytopenic patient with Noonan syndrome.

Hyperbaric oxygen treatment (HBOT) can be utilised for necrotising soft tissue infections, clostridial myonecrosis (gas gangrene), crush injuries, acute traumatic ischaemia, delayed wound healing, and compromised skin grafts. Our case was a 17-month-old male patient with Noonan syndrome, idiopathic thrombocytopenic purpura, and bilateral undescended testicles. Haematoma and oedema developed in the scrotum and penis the day after bilateral orchiopexy and circumcision. Ischaemic appearances were observed on the penile and scrotal skin on the second postoperative day. Enoxaparin sodium and fresh frozen plasma were started on the recommendation of haematology. Hyperbaric oxygen treatment was initiated considering the possibility of tissue necrosis. We observed rapid healing within five days. We present this case to emphasise that HBOT may be considered as an additional treatment option in patients with similar conditions. To our knowledge, no similar cases have been reported in the literature.

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.

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.

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.

Erythroblastosis Transformation-Specific Regulated Gene 1 (ERG) Immunohistochemistry in the Diagnosis of Acute Myeloid Leukemia.

INTRODUCTION: The erythroblastosis transformation-specific regulated gene 1 (ERG) is a transcription factor that can be used as an immunohistochemical (IHC) marker in the diagnosis and prognostication of malignancy. ERG was initially used in prostate cancer; however, it is a useful marker in extramedullary myeloid disease. Patients with acute myeloid leukemia (AML), dry bone marrow aspirate, and CD34, CD117-negative blast cells can be in a diagnostic dilemma. This audit aimed to (a) validate ERG IHC in bone marrow trephine samples, (b) quantify ERG IHC positivity in an AML cohort, and correlate concordance with CD34 and CD117 IHC, when available, and (c) to see whether ERG is a useful adjunct in the diagnosis of cases of AML. METHODS: A retrospective audit was completed of all new and relapsed cases of AML over one year at a single center. For inclusion, patients needed a trephine specimen at presentation, and all had a hematoxylin and eosin(H&E) specimen, ERG IHC, and at least one or both of CD34 and CD117 IHC. Four pathologists independently assessed the stains quantitatively and qualitatively in comparison to the morphology seen on the H&E sample. The kappa value was used to assess agreement. RESULTS: Seventeen patients with AML met the inclusion criteria. All specimens had H&E, CD34, and ERG stains; 9/17 (53%) had CD117 IHC. ERG demonstrated high concordance with blast cells on H&E morphology, with a high agreement among pathologists. Qualitatively, pathologists recognized that ERG spared lymphoid nodules; however, it also stained granulocytes at various maturation stages. CONCLUSION: ERG is a sensitive marker for the diagnosis of AML. ERG can help visualize blast cells that have been confirmed by ancillary tests. More research into the utility of ERG in AML diagnostics is recommended.

Pulmonary venous thrombosis in a healthy pregnancy.

We describe an unusual case of bilateral pulmonary venous thrombosis in a pregnant woman in her mid 30s, who presented at 34 weeks of gestation with symptoms of sudden onset chest pain, shortness of breath and near syncope attacks. The patient was treated with enoxaparin and made an excellent clinical and hemodynamic recovery.

Carfilzomib, lenalidomide, dexamethasone (KRD) in BTKi relapsed or refractory mantle cell lymphoma: A phase II study from Fondazione Italiana Linfomi.

Mantle cell lymphoma (MCL) is a rare lymphoproliferative neoplasm considered incurable, with a median survival of 3-5 years. In recent years, Bruton's tyrosine kinase inhibitors (BTKi) have been introduced, demonstrating high therapeutic activity. However, the prognosis for MCL patients failing ibrutinib therapy is particularly poor, with a survival expectation of a few months. In this phase II trial, we assessed the efficacy and safety of the carfilzomib-lenalidomide-dexamethasone (KRD) combination in MCL patients who were relapsed/refractory (R/R) or intolerant to BTKi and in need of treatment. The primary objective of the study was to evaluate the antitumor efficacy of the KRD combination in terms of 12-month overall survival (12-month OS). From September 2019 to December 2020, 16 patients were enrolled from 11 Italian centers. After a median follow-up of 2.37 months (95% CI 0.92-6.47), the 12-month OS was 13%. The rate of grade 3-4 adverse events (AEs) was 35%, and the overall response rate (ORR) was 19%. These results led to the premature termination of enrollment, as defined in the protocol stopping rules. The efficacy of the KRD combination in advanced-stage MCL patients who are R/R to BTKi is unsatisfactory and too toxic.