Thrombocytopenia is common in dogs and has a wide range of underlying causes, including vector-borne infectious diseases, the relative frequency of which may vary geographically. This retrospective cross-sectional study aimed to characterise the causes and clinicopathological features of thrombocytopenia in a hospital-based cohort of dogs evaluated at a mixed primary and referral veterinary hospital in Barcelona, Spain, and to identify differences across diagnostic categories, particularly those associated with primary immune thrombocytopenia (pITP). Medical records of dogs diagnosed with thrombocytopenia between 2021 and 2023 were reviewed. Of 612 dogs identified, 266 met the inclusion criteria. Neoplasia was the most common diagnosis (31.6%), followed by infectious diseases (24.4%), inflammatory or immune-mediated disorders (16.2%), miscellaneous conditions (15.4%) and primary immune thrombocytopenia (12.4%). Vector-borne diseases accounted for 10.9% of cases, mainly leishmaniosis and babesiosis. Dogs with neoplasia were older than those in other groups. Clinical bleeding was recorded in 42.5% of dogs and was most frequent in primary immune thrombocytopenia (78.8%). Fever was more common in infectious diseases, particularly non-vector-borne diseases. Albumin concentration was higher in primary immune thrombocytopenia than in infectious disease groups, whereas globulin concentration was higher in vector-borne diseases. Dogs with primary immune thrombocytopenia had lower platelet counts than all other groups. In this hospital-based cohort, neoplasia was the most common diagnostic category among dogs with thrombocytopenia, whereas vector-borne diseases were of intermediate frequency compared with reports from other European hospital-based cohorts. Distinct clinicopathological patterns, particularly severe thrombocytopenia and cutaneous haemorrhage, may help clinicians differentiate pITP from other causes of thrombocytopenia.

Fever of unknown origin (FUO) poses significant challenges for clinicians due to the myriad of possible etiologies, exhaustive evaluation requirements, diagnostic delays, patient and family frustration, and prolonged hospital stays. Defined as a fever lasting more than three weeks without a diagnosis despite one week of inpatient evaluation, this clinical phenomenon could result from infectious, autoimmune, neoplastic, or miscellaneous etiologies. We report the case of an elderly woman with FUO who was diagnosed with oncocytic carcinoma of thyroid origin on cervical lymph node biopsy. Interestingly, the biopsy was taken from a cervical node that was detected incidentally on neuroimaging. Oncocytic thyroid cancers, also known as Hürthle cell carcinomas, are differentiated but aggressive thyroid neoplasia. These rare tumors often present as thyroid nodules, detected incidentally during imaging or as palpable thyroid swellings. This case report highlights the clinical and diagnostic challenges in patients with FUO and reports an exceedingly rare presentation of oncocytic thyroid cancer as FUO. Additionally, it emphasizes the diagnostic utility of imaging and the need to follow even subtle diagnostic clues when evaluating patients with FUO.

We aimed to evaluate the diagnostic process and etiological spectrum of inflammation of unknown origin (IUO) and fever of unknown origin (FUO). Retrospectively, 8821 patients were evaluated between 2010 and 2024. 168 patients with IUO and 88 with FUO were included in the study. The demographic, clinical, and laboratory characteristics and diagnostic spectra of the IUO and FUO groups were compared. The diagnostic contribution, sensitivity, specificity, and positive and negative predictive values of computed tomography and 18F-FDG PET/CT were calculated. The median age (59 vs 46.7 years; P < .001) and the proportion of males (57.1% vs 40.9%; P = .014) were higher in the IUO. The most common symptom in all patients was arthralgia (78.5%). Weight loss and sore throat were more common in the FUO (P = .012 and P = .004, respectively). c-reactive protein and erythrocyte sedimentation rate levels were similar in both groups. Noninfectious inflammatory diseases (NIID) were the most common cause (31%), followed by neoplasms (18%), infections (11%), and miscellaneous diseases (7%). Infections were significantly more prevalent in the FUO (19.3% vs 6%, P < .001), whereas neoplasms were more commonly observed in the IUO (20.8% vs 12.5%, P = .099). In NIID, vasculitis occurred more frequently in the IUO, whereas adult-onset Still's disease was more prevalent in the FUO (P < .001). 18F-FDG PET/CT contributed 52.1% of cases, with 85% sensitivity and 17% specificity. Infections were common in FUO, whereas patients with IUO were older at presentation, more likely to be male, and had a higher frequency of neoplasms. Among NIIDs, vasculitis was predominant in the IUO, while adult-onset Still's disease was more prominent in the FUO.

Background Splenomegaly, or enlargement of the spleen, is a clinical sign rather than a standalone diagnosis, often indicating underlying systemic disease. In children, it may present due to a broad spectrum of conditions ranging from infections to hematologic, metabolic, or neoplastic disorders. The present study aimed to identify the etiological spectrum of splenomegaly among children admitted to the pediatric ward of a tertiary care hospital. The present study also sought to analyze the clinical profile, associated systemic findings, grading patterns, and assess treatment response and outcomes, thereby identifying region-specific trends that may guide early diagnosis and management strategies. Despite earlier studies addressing pediatric splenomegaly in different Indian populations, data from this coastal Andhra Pradesh region remain limited. Variations in endemic infection patterns, hematologic disorders, and socioeconomic determinants necessitate region-specific analysis to strengthen clinical decision-making and improve early detection strategies. Methods This prospective observational study included 115 children aged 0-15 years with clinically palpable splenomegaly who were admitted to the pediatric ward over a 12-month period. A detailed history and thorough physical examination were performed for all participants, and relevant investigations were conducted to determine the underlying etiology. The degree of splenic enlargement was assessed and graded using Hackett's classification as well as conventional clinical criteria. The etiology of splenomegaly was identified, and clinical outcomes, including response to medical treatment, need for surgical intervention, recurrence, and mortality, were documented systematically. Results In this study of 115 children with splenomegaly, a male preponderance was observed with 73 (63.4%) males and 42 (36.6%) females. The highest incidence occurred in children under six years of age. According to Hackett's classification, Grade III splenomegaly was the most common, seen in 51 (44.3%) patients. The most frequent presenting symptom was fever, reported in 80 (70%) children, while the most common clinical sign was pallor, observed in 58 (50.4%) patients. Infections were the leading cause of splenomegaly, accounting for 64 (55.7%) cases, followed by hematological disorders in 44 (38%) children, with storage and miscellaneous causes being less common. Regarding outcomes, the majority of children, 98 (85.2%), responded well to medical management. Splenectomy was required in five (4.3%) cases, mainly for refractory hematological disorders. Recurrence occurred in 10 (8.7%) patients, and mortality was low at two (1.7%), highlighting an overall favorable prognosis with timely diagnosis and appropriate therapy. Conclusion In the present study, splenomegaly in children was most commonly caused by infectious diseases, with malaria, enteric fever, and tuberculosis being the leading contributors. A male predominance was observed, and the majority of cases presented with moderate splenomegaly (Grade III). These findings underscore the importance of early recognition, prompt diagnosis, and timely management of underlying infections to prevent complications and improve outcomes in pediatric patients presenting with splenomegaly.

Abstract.

Background: Fever of unknown origin (FUO) in children remains a diagnostic challenge due to heterogeneous etiologies. This study investigated the etiological distribution, long-term outcomes of undefined cases, and laboratory predictors that differentiate infectious from non-infectious etiologies. Methods: We retrospectively evaluated 87 children (1 month-18 years) hospitalized with fever > 38.3 °C for ≥7 days with no detectable source (2018-2024). Patients were categorized into five groups: infectious, inflammatory, neoplastic, miscellaneous, and undefined. Comparisons between these groups were performed in terms of age, laboratory values, and duration of fever using the Kruskal-Wallis test and one-way ANOVA. Demographic, clinical, laboratory, and follow-up data were compared. ROC analysis and binary logistic regression identified predictors of non-infectious etiologies. Results: Infectious diseases (42.5%) and inflammatory disorders (19.5%) were the most common causes, while 17.2% of cases remained undefined. The median age was 60 months. Rash (31%) and fatigue (27.5%) were the most common complaints on admission. The undefined group showed complete spontaneous resolution during a median 63-month follow-up, with no recurrence or new diagnoses, except for one patient. Miscellaneous etiologies accounted for 14.9% of cases, and more than half of these were newly diagnosed primary immunodeficiencies. C-reactive protein and ferritin levels were significantly higher in the inflammatory disease group compared to the groups with unknown and infectious etiologies. In the binary logistic regression analysis, longer fever duration combined with elevated ferritin level was a combined predictor of non-infectious causes (AUC = 0.718). Conclusions: Infectious and inflammatory conditions predominate in pediatric FUO, yet a subset of cases resolve spontaneously and follow a benign course. The combination of fever duration and ferritin count may aid early differentiation of non-infectious etiologies, supporting more focused diagnostic approaches. Given the notable proportion of primary immune deficiencies, especially in populations with high consanguinity, early immunologic screening should be incorporated into FUO evaluation protocols.

Background: The minimized pan-coronavirus (CoV) vaccine-1 developed by our laboratory contained pDNA sequences of feline coronavirus serotype-1 (FCoV1) and SARS-CoV2 (SCoV2) spike B-cell epitopes plus FCoV/SCoV2-conserved, CoV-specific polymerase cytotoxic T-lymphocyte (CTL) epitopes formulated in lipid nanoparticle (LNP). Only FCoV2 infects feline cell lines needed for developing native challenge inoculum that causes feline infectious peritonitis (FIP). Hence, Pilot Study 1 evaluated the therapeutic efficacy and safety of the pan-CoV vaccine-1 in feline immunodeficiency virus (FIV)-infected cats, with or without FCoV1 coinfection. Pilot Study 2 evaluated the cross-protective effect of pan-CoV vaccines in specific-pathogen-free (SPF) cats against intranasal challenge with FIP virus serotype 2 (FIPV2). Methods: In Study 1, we vaccinated two FIV-infected cats (one negative and another positive for FCoV1 coinfection) intramuscularly twice with CTL epitopes-LNP vaccine and later twice with pan-CoV vaccine-1. Controls included two unvaccinated FIV-infected cats with or without FCoV1 coinfection. Study 2 assessed the sequential vaccinations of three pan-CoV vaccines in four SPF cats. The first two vaccinations were with pan-CoV vaccine-2, followed by pan-CoV vaccine-3 (twice), and lastly with pan-CoV vaccine-1 (once). Three SPF controls included two cats immunized with LNP and one lacking any immunization. Pan-CoV vaccine-2 contained pDNAs with modified FCoV1/SCoV2 B-cell epitopes plus CTL epitopes in LNP. Pan-CoV vaccine-3 contained only pDNAs with FCoV1 B-cell epitopes plus CTL epitopes in LNP. Results: Study 1 demonstrated no adverse effect with 25 μg and 50 μg CTL epitopes-LNP vaccine and 50 μg pan-CoV vaccine-1. However, 100 μg pan-CoV vaccine-1 caused fever 24 h later, which was resolved by a single Meloxicam treatment. Both vaccinees developed cross-FCoV2 neutralizing antibodies (XNAbs), immunoblot binding antibodies (bAbs) to FCoV1 receptor-binding domain (RBD), and T-cell responses to FCoV1 RBD, whereas one vaccinee also developed bAbs to SCoV2 RBD. Study 2 demonstrated no adverse effects after each vaccination. Three vaccinees developed low-titer XNAbs and bAbs to FCoV2 spike-2 by the fourth vaccination. Upon challenge, all cats developed FCoV2 NAbs and bAbs to FCoV2 nucleocapsid and RBD. High vaccine-induced T-cell responses to FCoV1 RBD and T-cell mitogen responses declined with an increase in responses to FCoV2 RBD at three weeks post-challenge. Two of the three controls died from FIP, whereas one vaccinee, with the lowest vaccine-induced immunity, died from skin vasculitis lesions and detection of FIPV2 infection by semi-nested RT-snPCR in feces. Conclusions: In Pilot Study 1, the pan-CoV vaccine-LNP dose of 50 μg had no adverse effects, but adverse effects were observed at 100 μg dose. In Pilot Study 2, the FCoV1-based B-cell vaccine(s) induced low levels of XNAbs against FIPV2 and delayed challenge infection against high-dose FIPV2. The high-dose FIPV2 infections in the vaccinated and control cats started to clear, by single housing at 23-26 weeks post-challenge, whereas two cats in Pilot Study 1 cleared natural FCoV1 transmission by 26 weeks post-infection.

BACKGROUND: Fever of unknown origin (FUO) remains a significant diagnostic challenge. Changes in patient populations and diagnostic technologies may shift the spectrum of underlying etiologies. This study aimed to examine recent FUO cases at a single tertiary center to identify changes in etiology compared with previous reports and between the pre- and post-COVID-19 pandemic periods, assess the diagnostic value of laboratory and imaging findings, and examine FUO characteristics in underrepresented subpopulations, including people living with HIV (human immunodefficiency virus), those on immunosuppressive therapy, and individuals with recurrent fever, with the goal of informing a center-specific diagnostic approach. METHODS: A retrospective analysis was performed on 100 patients hospitalized with FUO between 2017 and 2024, classified according to Durack and Street’s criteria. Subgroups included classical (n = 85), HIV-associated (n = 13), neutropenic (n = 1), and nosocomial FUO (n = 1). Clinical, laboratory, imaging, and biopsy findings were reviewed, and subgroup-specific analyses were conducted. RESULTS: Among 100 FUO patients (mean age 45.1 years; 52 males), recurrent fever was observed in 14 patients within the classical FUO group. The median fever duration at admission was 6 weeks. The average time to diagnosis was 14 days, and the mean hospital stay was 21 days. Final diagnoses were: collagen vascular diseases (CVD, 39%), infections (19%), malignancies (17%), miscellaneous (12%), and undiagnosed (13%). Vasculitis predominated among CVDs (25.6%), extrapulmonary tuberculosis (TB) among infections (36.8%), lymphomas among malignancies (52.9%) and, subacute thyroiditis among “miscellaneous” category (25%). In subgroup analysis, people living with HIV had no CVD, while no infections were found in recurrent fever cases. Among people living with HIV, infections (46%) and malignancies (38%) were most common. Immunosuppressed patients had diverse etiologies, including drug-induced pneumonitis and disease flares. CRP ≥140 mg/L, low hemoglobin, and anti-HIV positivity were independent predictors of malignancy; ferritin ≥875 µg/L was significantly associated (p = 0.01). PET-CT (Positron Emission Tomography – Computed Tomography) had the highest diagnostic yield, especially in infections and malignancies (p = 0.004). Microbiological studies were diagnostic in > 50% of infectious cases; autoantibodies aided diagnosis in ~50% of CVDs. During follow-up, 11 patients died, including 7 from the malignancy group. CONCLUSION: Our findings indicate a shift toward non-infectious inflammatory causes of FUO, with CVD surpassing infections. PET-CT and targeted biopsies are valuable diagnostic tools, particularly in suspected malignancies or infections. Subgroup-specific approaches are essential, especially in people living with HIV and immunosuppressed patients. Despite advances, a proportion of FUO cases remain undiagnosed, underscoring the need for stepwise, individualized diagnostic strategies. CLINICAL TRIAL NUMBER: Not applicable.

Acute enterocolitis encompasses a broad spectrum of conditions affecting the small and large bowel, frequently presenting with nonspecific symptoms such as abdominal pain, diarrhea, fever, and vomiting. Given the clinical overlap among infectious, inflammatory, immune-mediated, vascular, and miscellaneous etiologies, imaging plays a pivotal role in refining the differential diagnosis, identifying complications, and guiding timely management. Computed tomography (CT), owing to its accessibility and rapid acquisition, remains the cornerstone of imaging evaluation in acute settings. CT enables detailed assessment of bowel wall morphology, disease distribution, vascular involvement, and extraintestinal manifestations. While ancillary imaging modalities have a role in select scenarios, this review emphasizes a CT-focused approach tailored for acute care. We present a comprehensive, pattern-based review of the CT imaging features across various forms of acute enterocolitis, highlighting diagnostic hallmarks, interpretive pitfalls, and clinically relevant mimics. The included cases were encountered by the radiologists in their day-to day practice and included based on their ability to highlight the majority representative features of each pathology. Through the integration of structured tables, illustrative cases, and diagnostic tips, this article aims to enhance the radiologist's ability to recognize key imaging signatures, avoid diagnostic errors, and contribute meaningfully to multidisciplinary patient care.

Turraeanthus (Meliaceae) is a genus of trees and shrubs that is widely distributed across tropical and subtropical regions of Africa. Ethnopharmacological studies of this genus suggest that T. africanus is the species most commonly used in traditional medicine to treat various diseases, including malaria, typhoid fever, stomach aches, intestinal worms, coughs and inflammatory and cardiovascular conditions. Previous chemical studies have identified approximately 86 distinct compounds (including 21 synthetic derivatives), with diterpenoids (40.69 %) representing the predominant chemotaxonomic markers in the Turraeanthus genus. Other reported classes of compounds include limonoids (2.32 %), protolimonoids (16.28 %), triterpenoids (3.48 %), sesquiterpenoids (4.65 %), steroids (8.14 %), epoxyquinols (8.14 %), alkaloids (5.81 %), coumarins (4.65 %) and miscellaneous compounds (5.84 %). Some of these isolates have exhibited various bioactivities, including antibacterial, antifungal, toxic, cytotoxic, antiplasmodial and antioxidant effects. This review compiles insights into the traditional uses and chemical and pharmacological aspects of the Turraeanthus genus from 1965 to May 2025. Additionally, it provides a database for UPLC/MS[n] studies, as well as evidence on the absorption and permeation properties of the isolated compounds from the genus. The data presented were gathered from scientific articles available in online libraries, including Google Scholar, PubMed, Elsevier and SciFinder. The aim of this work is to inspire further research into the rich chemical diversity of Turraeanthus and potentially contribute to the discovery of new therapeutic agents to improve human health.

Fever and inflammation of unknown origin (FUO/IUO) remain challenging clinical syndromes today, in which the internists play a central role in orchestrating the diagnostic process and interpreting key findings. FUO and IUO share similar diagnostic evaluations and overlapping etiologies, although the relative frequencies of their causes may differ. The established five-category classification includes infectious diseases (INF), non-infectious inflammatory diseases (NIID), malignancies (MAL), miscellaneous (MISC) and undiagnosed illnesses (UI). The relative distribution of these categories varies depending on the FUO diagnostic criteria applied, as well as geographical region and socioeconomic factors. Although infectious diseases were historically the predominant cause of FUO, in recent years there has been a shift toward UI and NIID, especially in high-income settings. IUO is typically associated with a lower likelihood of infections compared to FUO, while the most common causes are mainly NIID. Meticulous medical history and clinical examination, aimed at identifying potential diagnostic clues (PDCs), remain pivotal to FUO/IUO diagnostics. Modern technologies such as PET/CT and next-generation sequencing (NGS) have advanced the diagnostic workup of FUO/IUO. However, they should be employed selectively, guided by PDCs, and with consideration of their limitations and cost-effectiveness. Emerging techniques, including metagenomic NGS and cytokine-based assays (e.g. IL-1β/DNA complex detection), show promising results in distinguishing sterile from infectious inflammation. Despite advancements in diagnostics and considering that UI now represent a leading cause of FUO in the European region, there remains an urgent need to deepen our understanding of underlying disease mechanisms and to develop novel, pathophysiology-based diagnostic tools.