Search Results (124)

Objectives: A percutaneous native kidney biopsy remains the gold standard for diagnosing glomerular, tubulointerstitial and vascular kidney diseases. Although generally safe, it may cause major haemorrhagic complications. Using the French national registry, Kaczmarek et al. developed a simplified bleeding risk score (anaemia, female sex, heart failure, acute kidney injury; range: 0–5), achieving an AUC of 0.755 in native biopsies. We aimed to externally validate this score in a Romanian cohort and to assess whether additional clinically relevant predictors could improve discrimination for major bleeding. Methods: We conducted a retrospective cohort study of all consecutive adults undergoing an ultrasound-guided percutaneous native kidney biopsy at a tertiary nephrology centre in Romania between January 2008 and December 2024. The primary outcome was a composite major bleeding event: clinically significant haematoma or haemorrhage, blood transfusion, angiographic intervention or nephrectomy. The Kaczmarek score was validated using a receiver operating characteristic (ROC) analysis. Candidate predictors were assessed by multivariable logistic regression, and a simplified score was derived from the regression coefficients. Results: Among 3081 patients, 162 (5.3%) experienced major bleeding. The Kaczmarek score showed modest discrimination (AUC: 0.624, 95% CI: 0.585–0.663). In the multivariable analysis (n = 2506 complete cases), anaemia, heart failure, solid neoplasm and fibrinogen were independently associated with major bleeding. An eight-component score (anaemia, heart failure, solid neoplasm, and fibrinogen < 511 mg/dL; female sex, hypertension, liver disease, and eGFR < 30 mL/min/1.73 m²) achieved an AUC of 0.676 (95% CI: 0.631–0.717), outperforming the Kaczmarek score. Conclusions: The French score performed only modestly in our cohort. Adding comorbidities, kidney function and haemostatic parameters, particularly fibrinogen, improved the risk discrimination. Full article

Severe anaemia remains a major public health challenge, disproportionately affecting children and women of reproductive age in sub-Saharan Africa. In high-burden settings, the aetiology of severe anaemia is multifactorial, encompassing nutritional deficiencies, infections, and host genetic factors. Beyond its direct clinical consequences, severe anaemia is also associated with increased susceptibility to invasive bacterial infections, particularly those caused by enteric pathogens such as non-typhoidal Salmonella and Escherichia coli. In this review, we present an integrated framework linking severe anaemia and invasive bacterial infection through three interconnected biological pathways, collectively termed the gut–iron–immune axis: gut microbial dysbiosis and impaired intestinal barrier integrity; disrupted iron homeostasis; and impaired immune function. We examine context-specific modifiers in endemic settings, including iron deficiency, malnutrition, malaria, sickle cell disease, and environmental enteric dysfunction. We also discuss how management of severe anaemia, including blood transfusion and iron supplementation, reshapes the gut microbiome, with direct implications for microbial translocation, invasive bacterial infection, and clinical outcomes. Finally, we identify key knowledge gaps and research priorities to guide safer and more effective prevention and management of severe anaemia in high-burden settings. Full article

Background: Alcohol use disorder (AUD) is generally regarded as a relative contraindication to pancreas transplantation. Yet the effect of documented AUD before transplantation on long-term results after pancreas transplantation is still poorly understood. Therefore, we used a large real-world electronic health records database to compare the three-year outcomes among pancreas transplant recipients who had and who had not had documented AUD before transplantation. Methods: We carried out a retrospective cohort study involving propensity score matching using the TriNetX US Collaborative Network. Each adult patient who had a documented case of alcohol use disorder (ICD-10-CM codes F10.1/F10.2) before transplantation was paired one to one with a patient who did not have such a disorder, matching them on demographic characteristics, comorbidities, transplant-related factors, medications, body mass index, and glycated hemoglobin. The outcomes were evaluated from one day after transplantation up to three years later and comprised all-cause mortality, emergency visits, transplant complications, cachexia, severe protein–calorie malnutrition, pain, vitamin deficiencies, iron deficiency anaemia, diarrhea, and adult failure to thrive. Results: Out of 14,367 eligible recipients, propensity score matching resulted in 439 patients in each group. Pretransplant AUD was linked to a significantly higher rate of all-cause mortality (15.1% compared with 8.5%; risk ratio [RR] 1.78, 95% CI 1.22–2.60; hazard ratio [HR] 1.86, 95% CI 1.25–2.78; p = 0.002). Cachexia affected 5.2% rather than 2.5% (RR 2.09, 95% CI 1.03–4.24; HR 2.16, 95% CI 1.06–4.44; p = 0.036), while diarrhea occurred in 39.6% compared with 28.2% (RR 1.40, 95% CI 1.16–1.69; HR 1.54, 95% CI 1.22–1.94; p < 0.001). There were no significant differences in the case of emergency visits (49.0% versus 44.6%; p = 0.199), transplant complications (11.1% versus 14.4%; p = 0.163), severe protein–calorie malnutrition (12.1% versus 8.9%; p = 0.123), pain (59.0% versus 54.7%; p = 0.195), vitamin deficiencies (31.4% versus 29.4%; p = 0.509), iron deficiency anemia (21.2% versus 21.9%; p = 0.805), or adult failure to thrive (7.3% versus 4.3%; p = 0.061). Conclusions: The presence of a history of alcohol use disorder (AUD) before transplantation was found to be independently linked to a higher three-year mortality rate, as well as the occurrence of cachexia and diarrhea after pancreas transplantation, but it was not associated with an increased number of coded transplant complications or most of the other adverse outcomes following the procedure. These results indicate that pancreas transplant recipients with a history of AUD should have enhanced monitoring in the areas of nutrition, the gastrointestinal system, and addiction. Full article

Whipple disease is a rare systemic infection caused by Tropheryma whipplei that often presents with nonspecific gastrointestinal symptoms and may mimic other disorders. We report the case of a 75-year-old woman with type 2 diabetes mellitus who presented with chronic diarrhoea and a 15 kg unintentional weight loss over 6 months despite preserved appetite. Laboratory investigations revealed iron-deficiency anaemia, hypoproteinaemia, mild inflammatory and liver function abnormalities, and peripheral eosinophilia. Extensive infectious, autoimmune, and gastrointestinal investigations were unrevealing. Abdominal computed tomography demonstrated mesenteric lymphadenopathy, raising suspicion for lymphoma. Histopathological examination of duodenal biopsies revealed numerous foamy macrophages containing periodic acid–Schiff-positive, diastase-resistant granular material, consistent with Whipple disease. Ziehl–Neelsen staining additionally demonstrated acid-fast bacilli, and subsequent investigations confirmed concomitant Mycobacterium szulgai infection. The significance of this finding remains uncertain, as it may represent either true coinfection or incidental colonisation. A potential explanation is that T. whipplei-induced macrophage dysfunction creates a permissive intracellular niche for nontuberculous mycobacteria, although supporting evidence is lacking. Following antimicrobial therapy, the patient experienced marked clinical improvement with resolution of symptoms and an 8 kg weight gain. This case highlights the diagnostic challenges of Whipple disease and the need to consider concomitant mycobacterial infection when acid-fast organisms are identified. Full article

Postoperative complications following colorectal surgery—including anastomotic leak (AL), surgical site infection (SSI), perioperative haemorrhage and colovesical fistula—represent major causes of patient morbidity and mortality, prolonged hospitalisation, and healthcare expenditure. This review summarises contemporary evidence across two key domains of complication management—prevention and diagnosis—applied to four major complications (AL, SSI, perioperative haemorrhage, and colovesical fistula), drawn from a comprehensive literature review of recent randomised controlled trials, systematic reviews, meta-analyses, and prospective cohort studies. Preventive strategies discussed include optimisation of surgical techniques (minimally invasive and robotic approaches, indocyanine green perfusion assessment, self-expanding metal stent bridge-to-surgery, and negative pressure wound therapy), modification of patient factors where possible (obesity, anaemia, malnutrition, and immunosuppression), and system-level interventions including Enhanced Recovery After Surgery (ERAS) protocols, perioperative beta-blockade, prehabilitation, and structured quality improvement bundles. Diagnostic strategies have evolved to incorporate biomarker surveillance (CRP and procalcitonin), drain fluid pH analysis, CT imaging (including angiography), endoscopy, and novel digital health tools including wearable monitoring and mobile health applications. Reducing the risk of postoperative complications should involve a multidisciplinary, protocolised approach combining intraoperative technique optimisation with structured perioperative care bundles and close post-discharge surveillance, and centralisation to specialist colorectal surgical units. Full article

Objective: Dog ear infections can have a variety of multifactorial causes, some of which are regarded as zoonotic. Thus, the present study was aimed at understanding the microbial causes, clinical evaluation, molecular analysis and associated risk factors of ear infections in dogs for their management. Methods: A total of 167 dogs were screened for ear infections based on history and clinical signs. An auricular swab was collected and processed with standard methods. Head tilting to the afflicted side, ear pain when palpated, pawing at the ear and purulent discharges from the ear canal were typical clinical symptoms. Results: A total of 13.77% of dogs were positive for ear infection, and among these, 13.17% showed unilateral right-sided ear infections. Dogs with pendulous ears (56.52%), Labrador breeds (34.78%), males (56.52%), dogs older than 4 years (52.17%), and during the monsoon season (65.21%) had higher rates of ear infections among the total dogs screened (n = 167) for aural infections. Anaemia, leukocytosis, neutrophilia, and elevated levels of total protein, cholesterol, BUN, and AST were observed in dogs with ear infections. Cytological analyses showed the presence of yeast cells and bacteria, along with hyperkeratosis and degenerated neutrophils. Mammaliicoccus sciuri, Bacillus cereus, Klebsiella aerogenes, Pseudomonas aeruginosa, and Malassezia spp. were the organisms isolated. Bacterial isolates showed high sensitivity to gentamicin for the otitis treatment. Clinical Significance: This study highlights the need for preventive measures to curb the spread of potentially zoonotic pathogens such as Bacillus cereus and Klebsiella aerogenes, which can pose significant threats to both human and animal health. Full article

Background/Objectives: Oral iron supplementation is widely used to treat iron deficiency but frequently causes gastro-intestinal side effects that limit treatment adherence. Unabsorbed luminal iron has been proposed to influence intestinal microbial communities, yet the effects of different oral iron doses on the human gut microbiome remain insufficiently characterized. Methods: In this randomized open-label study, 30 healthy premenopausal women with iron deficiency without anaemia received either low-dose oral iron supplementation (6 mg twice daily) administered under fasting conditions or standard-dose iron supplementation (100 mg once daily) taken with a meal for four weeks. Stool samples were collected before and after treatment and analyzed using 16S rRNA sequencing to evaluate microbiome composition. Results: Baseline characteristics, including age, body mass index, hemoglobin concentration and serum ferritin, were comparable between groups. After four weeks of treatment, distinct alterations in gut microbiome composition were observed between the low-dose and standard-dose groups. The genera Colidextribacter and GCA-900066575 decreased in the low-dose group but increased in the standard-dose group, whereas Oscillospira showed the opposite pattern. Gastrointestinal adverse events were reported by 87% of participants receiving standard-dose iron supplementation compared with 7% receiving low-dose iron supplementation (p < 0.0001). Conclusions: Oral iron supplementation induces dose-dependent changes in the intestinal microbiome and higher doses are associated with substantially increased gastrointestinal intolerance. These findings suggest that lower iron doses may reduce microbiome disruption and improve treatment tolerability. Full article

Background: Non-cardiac comorbidities (NCCs) are highly prevalent among patients hospitalized for acute heart failure (HF). However, data from sub-Saharan Africa (SSA) on their distribution across HF phenotypes and association with in-hospital outcomes remain limited. Methods: We prospectively enrolled adults hospitalized with acute HF at a tertiary centre in South Africa between February and November 2023. Ten NCCs were assessed and patients were categorized according to comorbidity burden. The primary outcomes were all-cause in-hospital mortality and length of stay. Multivariable regression and sensitivity analyses were performed to identify predictors of outcomes. Results: Of the 406 patients (mean age 54.9 ± 15.8 years; 51% women), HF with reduced ejection fraction (HFrEF) accounted for 63%, HF with mildly reduced ejection fraction (HFmrEF) for 15%, and HF with preserved ejection fraction (HFpEF) for 21%. The most common NCCs were diabetes (47%), chronic kidney disease (CKD) (46%), obesity (45%), and anaemia (33%). Two-thirds had ≥2 NCCs. The median hospital stay was 8 days (IQR: 5–12) and in-hospital mortality was 3.4% (p > 0.05 across NCC groups). Higher heart rate predicted longer hospitalization, while renin angiotensin system inhibitor (RASi) therapy was associated with shorter stay. Lower Kansas City Cardiomyopathy Questionnaire (KCCQ) score (adjusted odds ratio [aOR] 1.009; 95% confidence interval [CI]: 1.003–1.015) and higher log-transformed NT-proBNP were independently associated with increased in-hospital mortality (aOR 1.85; 95% CI: 1.07–3.50; p = 0.026). Total comorbidity burden was not independently associated with length of stay or in-hospital mortality. Conclusions: Non-cardiac comorbidities are common in acute HF in SSA, and functional status and clinical markers were the strongest predictors of length of stay and in-hospital mortality. Full article

Congenital dyserythropoietic anaemia type-I (CDA-I) is a rare autosomal recessive disease characterised by ineffective erythropoiesis, haemolysis and non-haematological developmental abnormalities. Its treatment is multifactorial, including the management of anaemia, iron overload and prevention of osteoporosis. The only treatment specific to CDA-I is subcutaneous interferon alpha (IFNα) 2A. This study presents the first summary of all published cases of CDA-I patients (n = 33) treated with IFNα and categorises their outcome. We also present new unpublished cases (n = 7). Overall, we find that IFNα administration causes a statistically significant mean increase in haemoglobin of 30.7 g/L (p < 0.001). However, we note that previous studies do not assess the impact of IFNα therapy on providing symptomatic benefit to patients with CDA-I, or the weight of side effects on their quality of life. We collaborate directly with patients through the organisation Congenital Anaemia Network to establish patient preferences regarding IFNα treatment. We propose a classification framework for the use of IFNα in CDA-I that includes patient-reported outcome measures in addition to grading response according to changes in Hb levels. We believe that the use of this framework will aid standardisation in measuring response to therapy, improve clinical practice and assist in future research. Full article

Background/Objectives: Vitamin B12 (B12) is essential for the provision of methyl groups for numerous essential pathways. Infant B12 deficiency (B12D) can lead to severe, even irreversible neurological abnormalities. Maternal B12 status in pregnancy and during the breastfeeding period correlates significantly with the child’s B12 status. B12D is a target disease in some newborn screening (NBS) programs. This study investigates whether infants that were clinically symptomatic and diagnosed with B12D in their first year of life could be retrospectively detected by the Austrian NBS algorithm. Methods: Data from infants with clinically diagnosed B12D in their first year of life between 2012 and 2022 were retrospectively collected in Austria (B12-related NBS implemented in 2018) and Switzerland (B12-related NBS not implemented). NBS data were retrospectively analysed, and clinical information was collected by a survey. Correlations between clinical symptoms, NBS data, biochemical parameters at diagnosis, maternal medical history and B12 status were analysed. Results: Four/forty-eight cases were retrospectively detected by the first-tier NBS parameters. From two children material for second-tier testing was available and B12D was confirmed by elevated total homocysteine (tHcy), resulting in a detection rate between 4.3 and 9.3%. The numbers of neurological and haematological symptoms correlated with low B12 and elevated levels of tHcy and methylmalonic acid. Although the detection rate of symptomatic B12D by NBS was low, fewer infants with symptomatic B12D were observed in the period after implementation of B12-related NBS (Austria). A history of B12D-relevant maternal disease such as pernicious anaemia was reported in 12 cases. Conclusions: B12D causes severe clinical symptoms in infants. NBS has a very limited retrospective detection rate of infants with severe B12D but seems to correlate with a reduction in cases due to not yet precisely quantified mechanisms. The workup triggered by NBS recalls is costly and often challenging for families. Maternal B12D increases the risk of infant B12D but also of other pregnancy-related health risks. To increase the efficacy of the prevention of infant B12D, to promote a healthy pregnancy and breastfeeding period, and to reduce the frequency of NBS recalls, pregnant women should be screened for B12D to be counselled and treated. Full article

Background: Varicose veins (VVs) are an overlying manifestation of chronic venous disease, commonly occurring in the lower extremities. While typically linked to primary venous insufficiency, they can occasionally be secondary to systemic disease, e.g., malignancies, by various mechanisms such as tumor compression, hypercoagulability, and paraneoplastic syndromes. Bilateral varicose veins, as a presenting symptom of gastric cancer, are extremely rare and poorly documented. Materials and Methods: A comprehensive literature search was conducted to identify reports and studies linking varicose veins and malignancies, with particular focus on gastric cancer. The search was performed using the PubMed, Scopus, and Web of Science databases covering the last 13 years. Results: Literature Review: A review of the literature in the past decade identified publications, mostly case reports, describing associations between varicose-like venous changes and malignancies such as gastric, pancreatic, hepatic, and small-bowel tumors. The predominant mechanisms reported were inferior vena cava obstruction, tumor-related thrombosis, and paraneoplastic migratory superficial thrombophlebitis (Trousseau’s syndrome). Only a few cases involved gastric cancer as the primary site, with venous changes often being the first clinical sign. There is limited experience with gastric cancer that presents alongside bilateral collateral or varicose veins initially. Apart from the various reports having malignancies and varicose veins we also describe the case of a 50-year-old man who had extended history of bilateral lower-limb varicose veins. Severe, unexplained anaemia without obvious bleeding was discovered during examination. A biopsy verified a gastric adenocarcinoma, while upper gastrointestinal endoscopy revealed an ulcerated mass on the stomach’s greater curvature. Peritoneal dissemination was discovered with additional staging. A palliative subtotal gastrectomy was carried out because of the patient’s ongoing anaemia and suspected chronic bleeding caused by the tumour. The venous symptoms preceded any gastrointestinal issues. Conclusions: Although uncommon, malignancy should be considered in the differential diagnosis for atypical or rapidly progressing bilateral varicose veins, especially when accompanied by systemic symptoms or lab results such as unexplained anemia. Increased suspicion may lead to earlier cancer detection in some patients. Full article

The intensity and prevalence of different gastrointestinal nematode species vary across regions worldwide. Oesophagostomum radiatum commonly shows a high occurrence in young cattle. O. radiatum causes anaemia, hypoproteinaemia, and immunopathological changes in the large intestine wall, impairing calves’ body weight gain. This study aimed to assess the impact of natural O. radiatum infection on haematological parameters and immune responses in 23 Nellore calves, considering sex-based differences. Assessments included Oesophagostomum egg count (EPG), worm count, packed cell volume (PCV), total plasma protein, histopathological and immunohistochemistry analyses. A large number of parasites attached to the colon mucosa were observed, along with massive nodule formation and haemorrhagic lesions, mainly within a 20–30 cm-long segment adjacent to the nodules. The maximum mean egg shedding was approximately 165 EPG for males and 173 EPG for female calves; however, males presented a significantly higher worm count (969 ± 200.5) than females (460 ± 99.5). There were significant positive correlations between the total O. radiatum worm count and O. radiatum EPG for both female and male calves. Significant negative correlations were observed between the total O. radiatum worm count and PCV in female calves. Our results demonstrated that natural O. radiatum infection in Nellore calves induced marked immunopathological alterations, including chronic inflammatory responses that impaired intestinal function. Sex-related differences suggested that female calves may develop more effective tissue responses. These findings emphasise the economic impact of subclinical infections and reinforce the importance of control strategies to minimise productivity losses in cattle. Full article

Background and Clinical Significance: Triosephosphate isomerase (TPI) deficiency is a rare autosomal recessive metabolic disorder caused by a pathogenic variant in the TPI1 gene. It is characterised by chronic haemolytic anaemia, progressive neuromuscular dysfunction, and reduced life expectancy. Patients typically present with symptoms in the first few months of life, including muscle weakness, ataxia, and recurrent respiratory infections. Diagnosis is confirmed by genetic testing, and management is generally symptomatic as no treatment is available. Case Presentation: We describe the case of an infant diagnosed with TPI deficiency in the context of haemolytic anaemia with progressive neurological deterioration and respiratory failure. Conclusions: This case illustrates the complexity of the disease and highlights the importance of early diagnosis and contributes to the limited literature by providing a detailed clinical description and highlighting the diagnostic challenges associated with this condition. Beyond its clinical relevance, this report emphasises the potential role of personalised medicine in the management of TPI deficiency. Early identification of specific genotypes may inform prognosis and guide individualised supportive strategies. As knowledge of the molecular underpinnings of TPI deficiency expands, opportunities may emerge for targeted therapeutic approaches tailored to patient-specific characteristics. Full article

Soil-transmitted helminths (STHs) are parasitic nematodes that infect humans, particularly in tropical and subtropical regions, where they contribute substantially to neglected tropical diseases (NTDs). Among them, hookworms (Ancylostoma duodenale, Necator americanus and Ancylostoma ceylanicum) cause substantial morbidity, leading to anaemia, malnutrition, and developmental impairment. Despite the global impact of hookworm disease, genomic research on A. duodenale has lagged behind that of other hookworms, limiting comparative and molecular biological investigations. Here, we report the first chromosome-level reference genome of A. duodenale, assembled from a single adult specimen archived in ethanol at −20 °C for more than 27 years. Using third-generation sequencing (PacBio Revio, Menlo Park, CA, USA, Oxford Nanopore, Oxford, UK), Hi-C scaffolding, and advanced computational tools, we produced a high-quality 319 Mb genome, filling a critical gap in hookworm genomics. Comparative analyses with N. americanus and the related, free-living nematode Caenorhabditis elegans provided new insights into genome organisation, synteny, and specific adaptations. While A. duodenale exhibited strong chromosomal synteny with N. americanus, its limited synteny with C. elegans highlights its distinct parasitic adaptations. We identified 20,015 protein-coding genes, including conserved single-copy orthologues (SCOs) linked to host–pathogen interactions, immune evasion and essential biological processes. The first comprehensive secretome analysis of A. duodenale revealed a diverse repertoire of excretory/secretory (ES) proteins, including immunomodulatory candidates predicted to interact with host structural and immune-related proteins. This study advances hookworm genomics, establishes a basis for the sequencing of archival specimens, and provides fundamental insights into the molecular biology of A. duodenale. The genomic resource for this hookworm species creates new opportunities for diagnostic, therapeutic, and vaccine development within a One Health framework. It complements recent epidemiological work and aligns with the WHO NTD roadmap (2021–2030) and Sustainable Development Goal 3.3. Full article

Background: Idiopathic intracranial hypertension (IIH) is, by definition, of unknown cause. Davson’s equation indicates that the increased intracranial pressure (ICP) found in IIH could be due to an increase in the CSF formation rate (CSF_fr), the CSF outflow resistance (R_out) or the venous sinus pressure. Studies simultaneously measuring the ICP and sagittal sinus pressures in IIH suggest that there is either a reduction in the R_out and/or the CSF_fr. The latter suggests that the increased venous pressure can be the only variable causing this disease process. A study maintaining the ICP at zero showed a significantly elevated CSF_fr in this disease. The purpose of the current study is to define the most feasible explanation for these findings and to suggest a viable pathophysiology for IIH. Methods: A lumped parameter vascular model, originally developed to study normal pressure hydrocephalus, was extended to investigate IIH. The model used the simultaneously obtained ICP and sagittal sinus pressure measurements from five experiments published in the literature to estimate the CSF_fr and the capillary transmural pressure (TMP). The assumptions made during this study were those of a normal mean arterial pressure, a normal total R_out and a normal blood flow rate. Results: When the CSF formation rates were plotted against the estimated capillary transmural pressures, a straight line was returned, suggesting that the CSF_fr and capillary TMP are related. Conclusions: The novel findings of this study suggest that the CSF_fr in IIH varies with the capillary TMP. A reduced capillary TMP in IIH can moderate the ICP if there is net CSF absorption across the capillaries. This would require the blood–brain barrier (BBB) to be disrupted. The model suggests that drugs which stabilise the BBB may trigger IIH by blocking CSF absorption across the capillaries, increasing the apparent CSF formation rate back toward normal and increasing the ICP. Anaemia will promote IIH by increasing the cerebral blood flow, the capillary TMP and the CSF_fr. Full article