Rising prevalence of chronic cardiometabolic conditions may be partly driven by shifts in dietary patterns. Nutrient profiling systems (NPSs) aim to guide healthier food choices through labeling and consumer-facing technologies but vary in accessibility and how well they distinguish food healthfulness. The primary objective was to compare a web-enabled, ratio-based NPS, Nutrient Consume Score (NCS), and its underlying nutrient ratios with 4 other leading NPSs, Nutri-Score, Health Star Rating, NOVA Classification, and Food Compass 2.0, by examining associations with obesity and blood pressure. Secondary objectives included assessing associations with cardiometabolic biomarkers and identifying food categories contributing most to each score. Cross-sectional study of NHANES 2015-2016 data from 9971 adults aged ≥20 y were analyzed. Dietary intake was assessed using a single 24-h dietary recall (day 1), and NPS scores were calculated. Multivariable regression models adjusted for sociodemographic and health factors examined associations with obesity, blood pressure, and cardiometabolic biomarkers. Compositional analysis evaluated food categories driving scores. Higher NCS was associated with lower BMI [β = -0.64 kg/m2 per 10-unit increase; 95% confidence interval (CI): -0.86, -0.41; P < 0.0001], waist circumference (β = -1.63 cm; 95% CI: -2.23, -1.02; P < 0.0001), systolic blood pressure (β = -1.01 mm Hg; 95% CI: -1.67, -0.35; P < 0.0051), and diastolic blood pressure (β = -0.56 mm Hg; 95% CI: -0.90, -0.23; P < 0.0026), with effect sizes comparable with other NPSs. Calorie-to-weight, sodium-to-potassium, and saturated-to-unsaturated fat ratios were associated with weight outcomes, whereas sodium-to-potassium and carbohydrate-to-fiber ratios were associated with blood pressure outcomes. The NCS was associated with weight and blood pressure in this cross-sectional analysis, with effect estimates comparable in magnitude with other commonly used NPSs. These findings support the potential utility of a ratio-based, web-enabled NPS for assessing diet quality in relation to cardiometabolic risk factors.
Bombay phenotype is a rare blood group where individuals produce an anti-H antibody, which agglutinates with antigens on red blood cells from common blood groups. The presence of this antibody has significant implications for the management of pregnancy in these individuals, with both maternal and fetal considerations. Few descriptions of pregnancy with this condition exist in published literature. Described here is the case of a woman who was found to have the Bombay phenotype during her first pregnancy. The multidisciplinary input, logistical considerations and planning for possible complications that were required are described. Despite the onset of pre-term labour, she avoided the need for blood transfusion, and there were no adverse fetal effects. This case highlights the unique challenges that pregnancy poses in this condition.
Patients with multiple myeloma (MM) who experience early relapse (ER) within 24 months of autologous stem cell transplantation (ASCT) have inferior overall survival and represent a functionally high-risk (HR) subgroup. To investigate immune features of functionally HR MM, we performed immunohistochemistry (IHC) of the bone marrow and high-dimensional flow cytometry-based phenotyping of peripheral blood to evaluate the T-cell compartment of patients with MM at day 100 after ASCT. An initial IHC-based analysis of a cohort of patients with MM (n = 110) with long-term follow-up implicated CD3+PD-1+ T cells as a marker of functionally HR disease independent of maintenance therapy or cytogenetics, suggesting a role for activated T cells as a biomarker of disease biology. Next, to further refine the immunophenotype associated with ER, we conducted flow cytometry of peripheral blood samples from Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0702 trial participants with ER (n = 45) or long-term remission (LR; n = 51), defined as no relapse for >4 years of follow-up. Unsupervised clustering followed by multivariate logistic regression identified the differential expression of HLA-DR, granzyme B, CTLA4, CD27, TIGIT, and CD38 within discrete T-cell subsets, distinguishing ER from LR patients. After variable reduction and validation, CD38 expression by CD8+Eomes+ effector memory T cells emerged as the most predictive feature segregating ER from LR patients, with an area under the curve (AUC) of 86%. This immunophenotype was corroborated in a separate standard-of-care cohort (n = 18). Thus, flow cytometric analysis of peripheral blood at day 100 after ASCT identified a CD8+CD38+ T-cell subpopulation as a key feature of immunologically HR MM.
A man in his early 50s with no significant prior renal history was admitted with acute kidney injury and sepsis secondary to right lower limb cellulitis, requiring prompt multidisciplinary management and further evaluation of the underlying etiology. Initial treatment included hemodialysis, following which the patient developed polyarticular septic arthritis (PASA), a rare condition. Examination revealed significant swelling and tenderness in multiple joints, and microbiological analysis confirmed a Staphylococcus aureus infection. Hemodialysis precipitated the bloodstream infection, as blood cultures were negative before hemodialysis but positive for Staphylococcus aureus post-dialysis. The patient underwent multiple joint washouts and was treated with intravenous vancomycin and linezolid. The patient's renal function normalized after treatment, and his symptoms resolved without recurrence. This case highlights the potential for PASA in an immunocompetent individual after a single hemodialysis session, emphasizing the role of catheter-related bloodstream infection (CRBSI) in its pathogenesis and underscoring the importance of timely diagnosis and treatment to prevent severe outcomes. Such presentations underscore the importance of heightened clinical vigilance, as delayed recognition can result in significant morbidity.
Spinal surgery, particularly spinal decompression and fusion surgery, commonly encounters intraoperative bleeding. Deep bleeding in the narrow operative area (e.g. bone marrow cavity and venous plexus) is a significant challenge for achieving accurate hemostasis with traditional strategies, posing a life-threatening risk. Herein, a novel dual-form hemostatic material (CMC-Gelatin, CG) composed of carboxymethyl cellulose (CMC) and gelatin is developed for non-compressible hemostasis in spinal surgery. For minor bleeding, CG in powder form reduces blood loss by 69.06% within a mouse bleeding model, demonstrating hemostatic efficacy comparable to that of the commercial Surgicel® powder, while exhibiting superior cytocompatibility. Notably, CG powder rapidly forms an injectable gel upon mixing with saline, making it suitable for severe bleeding in a confined space during spinal surgery. Specifically, in a pig paraspinal microvenous hemorrhage model, CG gel exhibits excellent hemostatic performance, reducing blood loss by 78.44% compared with the untreated group. Importantly, CG demonstrated a comparable hemostasis time and reduced blood loss in vivo compared to the commercial Surgiflo®. The designed CG materials exhibit outstanding hemostatic properties in deep, narrow areas, making them a promising hemostatic material in spinal surgery.
This study aimed to identify and validate potential endoplasmic reticulum stress-related biomarkers of focal segmental glomerulosclerosis(FSGS). Five microarray datasets were downloaded from the GEO database. The endoplasmic reticulum stress-related genes were extracted from GeneCards database. GSE104948, GSE129973, and GSE121233 datasets were used to identify DEGs by limma R package. WGCNA was performed to obtain hub gene modules. We intersected the DEGs, genes from hub module of WGCNA, and ERSRGs. GO and KEGG pathway enrichment analyses were performed. LASSO, SVM-RFE, and RF algorithms were used to screen characteristic genes. Further, GSE108109 and GSE104066 were used as validated datasets. Box plots, ROC curves, and AUC were created to identify potential biomarkers. A novel nomogram model was constructed using potential biomarkers. Immunohistochemistry validated the expression of the potential biomarkers, and correlation analysis was used to assess the correlation between the integrated optical density(IOD) value of GADD45A and the levels of 24-hour urinary protein, eGFR, and blood urea nitrogen. Intersecting DEGs, the brown module genes, and ERSRGs, we identified 15 hub ERSRGs of FSGS. AGO2, CCND1, GADD45A, TRAM2, and PTPN1 genes were screened by using Lasso, SVM-RFE, and RF. Further, CCND1, GADD45A, and TRAM2 were validated as significant in training and validation datasets. A nomogram based on CCND1, GADD45A, and TRAM2 expression was constructed. The calibration curves, decision analysis curve, and clinical impact curve showed that the nomogram had good consistency and clinical practical benefit. The expression of GADD45A is higher in FSGS than controls in immunohistochemical(IHC) results(P < 0.0001). The integrated optical density value of GADD45A shows a strong correlation with 24-hour urinary protein(r 2 = 0.8459,P < 0.0001), eGFR(r 2 = -0.8233,P < 0.0001), and blood urea nitrogen(r 2 = 0.8695,P < 0.0001). GADD45A may be a potential biomarker associated with endoplasmic reticulum stress in FSGS.With its potential applicability spanning both biomarker identification and therapeutic intervention, GADD45A offers a compelling avenue for improving FSGS detection and clinical management in subsequent investigations.
Cerebral venous thrombosis (CVT) is an uncommon cerebrovascular condition with highly variable clinical presentations and a wide spectrum of underlying causes. Iron deficiency anemia (IDA) has been increasingly recognized as a significant predisposing factor for CVT. We describe the case of a 45-year-old woman who presented with a gradually intensifying headache, followed by acute onset of left facial palsy and left-sided weakness. Laboratory tests demonstrated microcytic, hypochromic anemia, consistent with IDA. Computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance venography (MRV) revealed thrombosis of the right transverse sinus, accompanied by venous infarction and intracranial hemorrhage. An extensive workup showed no evidence of hereditary thrombophilia or autoimmune disease. Subsequent evaluation identified a uterine fibroid causing chronic menorrhagia, which was considered the primary source of her IDA. Anticoagulation therapy was started with low-molecular-weight heparin (LMWH) and later transitioned to apixaban. She also received iron supplementation and blood transfusion. Her neurological deficits gradually improved, with no progression of the intracranial hemorrhage and no new thrombotic events. Follow-up imaging showed substantial resolution of venous edema and mass effect; however, MRV continued to demonstrate persistent occlusion of the right transverse sinus. Anticoagulation was stopped four months after disease onset, and no recurrence occurred during subsequent follow-up. This case underscores several key clinical considerations. First, IDA resulting from chronic gynecologic blood loss should be recognized as a modifiable risk factor for CVT. Second, anticoagulation can be used safely in patients with hemorrhagic CVT, even in the presence of severe anemia. Third, good clinical and radiologic outcomes are possible despite incomplete venous recanalization. Collectively, these observations suggest that restoration of overall cerebral venous hemodynamics, rather than recanalization by itself, may be crucial for recovery from CVT.
Norrin, secreted by retinal Müller cells, activates canonical Wnt signaling via Frizzled-4 and co-receptors. Loss-of-function mutations abolish intraretinal capillary formation in mice. In humans, mutations in NDP, which encodes norrin, cause Norrie disease, characterized by retinal hypovascularization and congenital blindness, and X-linked familial exudative vitreoretinopathy (FEVR), resembling retinopathy of prematurity (ROP). We evaluated adeno-associated viral (AAV) vectors expressing norrin as gene therapy for Norrie disease, FEVR, and ROP. AAV2-7m8 and AAV-ShH10 were tested in juvenile wild-type and norrin-deficient (Ndp KO) mice via intravitreal injection at postnatal day 7, with some mice subjected to oxygen-induced retinopathy (OIR). AAV2-7m8 transduced Müller glia, while AAV-ShH10 targeted retinal ganglion cells. Both vectors fully restored intraretinal capillary growth in Ndp KO mice, normalizing vessel density and plexus organization, preserving the blood-retinal barrier, and rescuing visual function. In OIR, scAAV2-7m8-huNorrin reduced vaso-obliteration and neovascular tuft formation, increasing deep plexus coverage, and suppressed Vegfa164 and Ang-2 upregulation. The findings demonstrate that AAV-mediated norrin delivery efficiently targets retinal glia and neurons, restores vascular structure and function, stabilizes the blood-retinal barrier, and mitigates OIR-induced pathological angiogenesis, supporting its potential as a therapeutic strategy for Norrie-related retinopathies and ROP.
Solid organ transplant (SOT) recipients undergoing total joint arthroplasty (TJA) may face elevated perioperative risk because of chronic immunosuppression, medical comorbidity, and organ-specific physiologic considerations. Although intravenous tranexamic acid (TXA) is widely used during TJA to reduce perioperative blood loss, evidence regarding outcomes among SOT recipients receiving TXA remains limited. A retrospective review was performed of 29,240 consecutive primary TJA patients who all received intraoperative intravenous TXA between June 2011 and March 2025. Patients undergoing unicompartmental knee arthroplasty, hemiarthroplasty, TJA for fracture, bilateral procedures, revision procedures, or those with less than 90 days of postoperative follow-up were excluded. SOT history was identified using diagnosis and procedural codes and verified by manual review. Outcomes included 90-day deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI), operative time, and hospital length of stay (LOS). Sixty-six patients with verified SOT were identified. The most common transplant types were kidney (59%), liver (24%), and heart (9%). One SOT patient experienced a 90-day VTE event compared with 95 control patients (1.5% versus 0.3%, P = 0.20). There were no PEs or MIs in the SOT cohort, compared with PE and MI rates of 0.2% and 0.01% in controls, respectively (P > 0.05 for both). Operative times were similar between groups (100.8 versus 108.5 min, P = 0.11), while LOS was significantly longer among SOT recipients (86.2 versus 43.8 h, P < 0.001). In this retrospective cohort of primary TJA patients who all received intraoperative intravenous TXA, SOT recipients had low observed rates of VTE, PE, and MI. Because all patients received TXA and the SOT cohort was small, these findings should be interpreted as comparative observational safety data rather than evidence that TXA independently increases or does not increase thromboembolic risk in this population.
Eosinophilic colitis (EC) is a rare clinical entity. Advanced cases with severe inflammation may develop severe abdominal pain and distension, malabsorption, intestinal obstruction, and even GI hemorrhage. Once diagnosed early, EC responds to steroid therapy. We report the case of a 46-year-old male who presented with acute-onset left upper abdominal pain, enlargement of the right scrotal sac, and hemoperitoneum. A contrast-enhanced CT scan of the abdomen revealed an irregular hypoechoic lesion measuring approximately 6.5 × 4.8 cm, likely a transverse mesocolon hematoma in the epigastric region with hemoperitoneum and right-sided hematocele with persistent processus vaginalis. USG-guided ascitic tap yielded bloody aspirate. Ascitic fluid analysis showed sheets of eosinophils (60%) with a hemorrhagic background. CBC showed eosinophilia (38%). He underwent diagnostic laparoscopy and laparoscopic left hemicolectomy; histopathological examination of the resected colon revealed EC (transmural type). He was given oral corticosteroids for two weeks after discharge. EC is a rare condition. It may present acutely and give rise to potentially severe and fatal complications like hemorrhage and perforation. With early diagnosis and appropriate treatment, we may be able to avoid serious complications in such patients.
This study sought to examine the correlation between antiretinal antibodies (ARAs) and OCT manifestations in patients diagnosed with nonparaneoplastic autoimmune retinopathy (npAIR). A retrospective, observational case series. Fifty-five patients (92 eyes) diagnosed with probable or possible npAIR. Patients underwent comprehensive evaluation, including best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, fundus photography, autofluorescence, OCT scanning, and electroretinogram. Blood samples were analyzed for the presence of ARAs using Western Blot, including anti-recoverin (ARc), anti-α-enolase (AeNO), anti-carbonic anhydrase II (ACA), and anti-CRMP5 (AC5). Statistical analyses included the Kruskal-Wallis test (logarithm of the minimum angle of resolution BCVA) and 1-way analysis of variance (central retinal thickness [CRT]) for group comparisons. Diagnostic performance of key OCT features was assessed. Multimodal imaging, BCVA, and CRT of patients diagnosed with npAIR. Among the 55 npAIR patients, 52.7% were positive for a single tested antibody, while 25.5%, 14.5%, and 7.3% had two, three, or four of the tested antibodies, respectively. Central retinal thickness and BCVA were significantly worse in most ARA-positive groups versus controls. However, the AeNO(+) subgroup showed the best-preserved CRT and BCVA. The AeNO(+) eyes predominantly exhibited inner retinal (ganglion cell complex/retinal nerve fiber layer) thinning (66.7%). The ACA(+) and ARc(+) eyes showed patterns of diffuse outer retinal degeneration (50% and 75%, respectively). The AC5(+) eyes uniquely presented outer plexiform layer (OPL) "double-layer signs" (45.8%) and "retinitis pigmentosa-like" changes (25%). Analysis of diagnostic performance revealed that "inner retinal thinning" had moderate sensitivity (66.7%) for AeNO, while "OPL double-layer signs" showed perfect specificity (100%) for AC5 within our cohort. This study provides valuable insights into the correlation between ARA profiles and specific OCT patterns in npAIR patients. The findings advance our understanding of npAIR pathogenesis and highlight the potential of OCT imaging and ARA profiling in the diagnosis and management of this complex condition. The authors have no proprietary or commercial interest in any materials discussed in this article.
Obesity is associated with structural and functional cardiac remodeling; however, its quantitative imaging characteristics and the role of left ventricular trabeculation remain incompletely understood. This study aimed to characterize left ventricular trabeculation using multi-parametric cardiac magnetic resonance in patients with obesity, explore its association with subclinical cardiac dysfunction, and evaluate longitudinal changes following bariatric surgery. In this prospective single-center study, 30 patients with severe obesity underwent cardiac magnetic resonance imaging before and approximately 12 months after bariatric surgery, along with 30 age- and sex-matched healthy controls. Quantitative parameters included the non-compacted to compacted layer ratio (NC/C), trabecular mass fraction, left ventricular mass, left ventricular ejection fraction, global longitudinal strain, and diastolic filling indices. Left ventricular ejection fraction indexed to body surface area was analyzed as an exploratory parameter. Mediation analysis was performed to assess whether trabeculation statistically explained part of the association between body mass index and cardiac function, adjusting for age, sex, and blood pressure. Compared with controls, patients with obesity showed significantly higher NC/C (1.68±0.24 vs. 1.11±0.19, P<0.001) and lower left ventricular ejection fraction (57.87%±6.22% vs. 63.40%±6.94%, P<0.05). In mediation analysis, the total effect of body mass index on left ventricular ejection fraction was -0.29 [95% confidence interval (CI): -0.56 to -0.02]. The indirect effect via the NC/C was statistically significant (β=-0.46, 95% CI: -0.81 to -0.09), while the direct effect was not significant (β=0.17, 95% CI: -0.25 to 0.59). Following bariatric surgery, trabeculation and left ventricular mass decreased significantly, while left ventricular ejection fraction, global longitudinal strain, and diastolic filling indices improved (P<0.05). Quantitative cardiac magnetic resonance analysis demonstrates increased left ventricular trabeculation in obesity, which decreases following weight reduction. Trabeculation is associated with subclinical cardiac dysfunction and may contribute to the association between obesity and impaired cardiac function. These findings suggest that trabecular remodeling in obesity represents a dynamic imaging phenotype, although further studies are required to clarify underlying mechanisms.
A man in his 50s presented with worsening anterior chest pain. Serologic testing revealed active syphilis infection, and polymerase chain reaction testing was positive for COVID-19. Contrast-enhanced computed tomography demonstrated a descending thoracic aortic aneurysm with circumferential wall thickening and a characteristic double-ring sign suggestive of inflammatory aortitis. After blood pressure control and antibiotic therapy, elective descending aortic replacement was performed. Surgical inspection showed diffuse intimal thickening with a tree-bark appearance. Histopathology demonstrated lymphoplasmacytic infiltration in the media, adventitia, and around the vasa vasorum, consistent with syphilitic aortitis. This case highlights the diagnostic value of CT, particularly the double-ring sign, in identifying syphilitic aortitis and demonstrates a rare presentation of syphilitic aneurysm in the descending thoracic aorta.
A woman in her 30s presented with acute cholecystitis. Blood and radiological investigations supported the clinical diagnosis. Diagnostic laparoscopy showed a thickened inflamed gall bladder (GB). Laparotomy was performed that showed a thickened sessile inflamed GB. There was no involvement of adjacent organs, ascites or metastasis. Histopathology showed an inflammatory myofibroblastic tumour (IMT) in a sessile GB. The tumour is classified as intermediate grade of malignancy by the World Health Organization. There are eight reported cases of IMT, all of which were successfully treated with resectional surgery with only one recurrence at 13 months. One year later, our case had no evidence of recurrence. To conclude IMT could be successfully treated by open surgical resection. To the best of our knowledge, this is the first report of an IMT of the GB presenting with acute calculous cholecystitis; in addition, the cystic duct was absent.
To predict the risk of diabetic macular edema (DME) onset and to identify features of the risk subgroups. Population-based observational study with a case-control design. Health checkup and diagnosis data from the JMDC claims database (January 2005-July 2020), one of the largest Japanese epidemiological databases, were used. From 272 337 individuals diagnosed with type 2 diabetes (International Classification of Diseases, 10th Revision E11), we analyzed 2368 pairs of DME and non-DME individuals, which matched 1:1 by the balancing score calculated from regression analysis of DME with sex, age, months of observation, number of checkups, duration of diabetes, and months until the first checkup. We employed a multivariate Cox proportional hazards model, regularized Cox models, and a random survival forest (RSF). These models were trained via ID-level bootstrap resampling using 43 health checkup variables (missing ratio <50%) and 404 high-incidence diseases within 6 months, along with age, sex, and duration of diabetes mellitus, to assess DME risk. Temporal changes in RSF-predicted risk scores were analyzed using nonlinear modeling techniques. Concordance index (C-index), integrated Brier score (IBS), and cumulative/dynamic mean area under the receiver operating characteristic curve (AUC). Thirteen checkup items and 44 disease history variables were significantly associated with the onset of DME. The RSF identified 43.8% of DME cases >5 years prior to onset, with a specificity of 85.5%. The RSF achieved median C-index, IBS, and mean AUC values of 0.694 (95% confidence interval, 0.688-0.697), 0.181 (0.179-0.184), and 0.750 (0.739-0.756), respectively, outperforming both multivariate and univariate Cox models. Three distinct DME risk subgroups were suggested by temporal changes in the RSF-predicted risk score. Predictors of DME onset varied markedly among these subgroups. In the explicit high-risk subgroup, urinary protein and urinary sugar were highly important, and liver function-related blood tests, such as alanine transaminase and γ-gultamyltransferase, were also ranked high in variable importance metrics. Anemia-related laboratory tests were associated with DME development only in this subgroup. Random survival forest demonstrated superior performance in relative risk prediction of DME using health checkup data. External validation remains an essential prerequisite before any clinical application. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Current Type 2 diabetes therapies inadequately address multi-organ complications. We evaluated bivalent nanoparticles encapsulating curcumin, combined with insulin, against diabetic complications. Our data indicate shared pathophysiological mechanisms driving the association between retinal and cardiac injury, specifically systemic inflammation and mitochondrial dysregulation across both organs. Retinal stress (HIF1α, REDD1, VEGF) preceded cardiac remodeling, characterized by lymphangiogenesis (LYVE1, VEGFR3) and impaired PPARα/ PGC1α signaling. Furthermore, we identified a strong pathological correlation between intraocular and systemic blood pressures as an in-vivo physiological readout of widespread vascular dysregulation. While males exhibited an earlier onset, females progressed more rapidly to complications. The combination therapy proved highly effective in both sexes. While females exhibited a more pronounced reduction in systemic inflammation and pathological pressure correlation, males demonstrated robust metabolic and structural preservation. These findings highlight ocular hemodynamics as an early physiological indicator of cardiac complications, supporting this sex-specific nanotherapeutic strategy, combined with insulin, to mitigate diabetic complications.
Hematopoietic stem cell transplantation (HSCT) of genetically engineered cells is a promising treatment modality for monogenic diseases. However, hematopoietic stem cell (HSC)-directed lentiviral vector (LV) gene therapies remain limited by genotoxicities associated with standard non-targeted conditioning using irradiation or alkylating chemotherapy. We and others developed an antibody drug conjugate (ADC) with anti-CD117 and saporin (sap), which selectively depletes CD117-expressing HSC and progenitor cells (HSPCs). Since anti-CD117-sap does not generally provide engraftment comparable to conventional conditioning, we investigated the hypothesis anti-CD117-sap is not effective as a single conditioning agent due to insufficient HSPC depletion. We show anti-CD117-sap induces nearly complete residual HSPC entry into a non-G0 proliferative state and postulated agents targeting cycling cells would enhance engraftment. When we administered the antimetabolite 5-fluorouracil with anti-CD117-sap, anti-thymocyte globulin, and an immunoglobulin-degrading enzyme, we achieved >90% peripheral blood chimerism of unmodified cultured donor cells. Additional immunosuppression combined with an increase in transplanted cells further permitted ∼70% engraftment of HSPCs transduced with an LV encoding a high-expression, immunogenic factor VIII (FVIII) transgene. Copy numbers of ∼1.0 and normal FVIII plasma activity levels (>50%) by 6 months post-HSCT were achieved. Collectively, we show ADC and antimetabolite administration can augment LV-engineered HSPC engraftment by targeting cycling cells.
Cadmium (Cd) is a non-essential and highly toxic heavy metal widely present in aquatic environments. However, studies investigating the toxic effects of Cd on crucian carp (Carassius auratus) are relatively few. This study aimed to evaluate the toxic effects of Cd by assessing hematological parameters, antioxidant responses, and the expression of stress-related genes in C. auratus exposed to waterborne Cd. A total of 180 healthy C. auratus (19.43 ± 1.5 cm and 170.00 ± 3.04 g) were exposed to Cd at concentrations of 0, 2, and 4 mg/L for 8 weeks, with three replicates per treatment. The exposure to Cd resulted in significant reductions in red blood cell (RBC) count, hemoglobin (Hb) concentration, and hematocrit (Hct) values. Moreover, the levels of total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GPx) in the liver also decreased significantly, whereas malondialdehyde (MDA) content was increased significantly. The expression levels of CAT, copper (Cu)/zinc (Zn)-superoxide dismutase (Cu/Zn-SOD), heat shock protein 70 (HSP70), heat shock protein 90 (HSP90), and metallothionein (MT2) genes were significantly upregulated. Overall, Cd exposure adversely affected the hematological parameters, induced oxidative stress, and altered the expression levels of stress-related genes. This study not only provides new insights into the toxic effects of Cd in C. auratus but also contributes to environmental monitoring research.
Chronic urinary schistosomiasis is an important cause of hematuria and genitourinary morbidity in individuals from endemic regions. In advanced disease, computed tomography (CT) may show circumferential calcification of the bladder and distal ureters, a classic pattern that can suggest the diagnosis even when laboratory tests are negative. A 38-year-old man from Mozambique, living in Portugal with human immunodeficiency virus and hepatitis B virus infections, presented with 2 months of painless gross hematuria. He denied dysuria, fever, flank pain, weight loss, prior urinary tract instrumentation, tuberculosis, or recent travel, and baseline blood tests and renal function were normal. Urinalysis showed hematuria and leukocyturia, but multiple urine examinations for Schistosoma ova and a urine Schistosoma-specific polymerase chain reaction were negative. Noncontrast CT of the abdomen and pelvis was obtained and demonstrated diffuse circumferential calcification of the urinary bladder wall with distal ureteral involvement, producing a classic "eggshell" appearance without hydronephrosis, renal stones, or intraluminal mass. Cystoscopy showed yellowish plaques and nodular mucosal lesions, and targeted bladder biopsies revealed numerous calcified Schistosoma haematobium ova within the urothelium and submucosa with chronic inflammation and stromal calcification, confirming chronic inactive infection. The patient received a single dose of praziquantel 40 mg/kg and 3 months later, hematuria had resolved and renal function was stable. This case highlights that in chronic urinary schistosomiasis, CT findings can be decisive when urine-based tests are negative.
Pulmonary arteriovenous fistula (PAVF) and hepatopulmonary syndrome (HPS) both cause right-to-left shunting, allowing pathogens to bypass the pulmonary filtration barrier and enter systemic circulation, leading to brain abscess. Despite distinct etiologies, both share the same pathological pathway-right-to-left shunt-resulting in the same devastating neurological complication. Two male patients with cryptogenic brain abscesses caused by PAVM (59 years old) and HPS (52 years old), respectively, are reported. The patient with PAVM presented with fever, dyspnea, and headache, and was diagnosed by contrast-enhanced chest computed tomography. Fusobacterium nucleatum was detected in cerebrospinal fluid (CSF). The patient recovered following anti-infective therapy combined with surgical resection of pulmonary lesions, achieving a favorable prognosis at the 3-month follow-up. The HPS patient had a history of hepatitis C complicated by liver cirrhosis. He presented with headache, fever, and orthostatic hypoxemia. Diagnosis was confirmed by a contrast-enhanced transcranial Doppler bubble test (c-TCD). Blood culture identified Streptococcus intermedius. The brain abscess recurred after antibiotic treatment due to refusal of liver transplantation. At the 3-year follow-up, the patient could maintain only a sedentary lifestyle. Both pulmonary arteriovenous fistula (PAVM) and hepatopulmonary syndrome (HPS) can cause cryptogenic brain abscess through right-to-left shunt. PAVM can be eradicated by intervention or surgery, while HPS fundamentally requires liver transplantation. Notably, Clinical and radiological improvement following antimicrobial therapy may not represent definitive cure if the underlying right-to-left shunt remains untreated, and recurrence remains possible.