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Hematological profile and erythrocyte osmotic fragility of free-living yellow-footed tortoise Chelonoidis denticulatus (Linnaeus, 1766)

Vet Res Commun. 2024 Nov 20;49(1):19. doi: 10.1007/s11259-024-10585-9.

ABSTRACT

The yellow-footed tortoise (Chelonoidis denticulatus, Linnaeus, 1766) is among the most consumed chelonian species in the Amazon region, raising concerns about its conservation status. Furthermore, few studies have been carried out on the parameters of physiological normality of this species in free-living conditions, making it difficult to assess the impact of environmental changes on the physiology of the group. The erythrocyte osmotic fragility (EOF) test is a biomarker of environmental changes that cause membrane damage, decreasing erythrocyte resistance to osmotic stress. However, the physiology of the species is still poorly understood, and the reference ranges for hematological parameters and EOF is unknown for most species in natural conditions. Understanding the reference intervals of the physiological parameters of these animals have fundamental importance to assess when a population is under the effect of environmental stressors, such as xenobiotics, as well as to provide comparative parameters in clinical analyzes for the species. The lack of information on normal EOF values ​​makes it difficult to assess the effects of environmental and clinical changes on the physiology of the species. This study aimed to establish reference intervals for hematological parameters and EOF analysis for C. denticulatus, using thirty tortoises (n = 15 males and n = 15 females). The t-test and Mann-Whitney test were used to compare the hematological parameters between sexes, while the Kruskal-Wallis test was used in the EOF analysis, and the reference range was calculated for males and females together. No statistical differences were found in hematological values between sexes, nor in the hemolysis profile in the EOF analysis, demonstrating that in this population, these parameters of C. denticulatus are similar between sexes during the sampling period. According to the results of this study, we can consider the erythrocytes of these animals osmotically resistant, reflecting the stability of the cell membrane. This study reports for the first time hematological values and EOF analysis for the species C. denticulatus in the wild in a region of the far western Brazilian Amazon.

PMID:39562384 | DOI:10.1007/s11259-024-10585-9

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Biomarkers of systemic treatment response: MR images of intratumoral fat deposition in colorectal liver metastases (CRLM) after chemotherapy

Int J Colorectal Dis. 2024 Nov 20;39(1):185. doi: 10.1007/s00384-024-04762-0.

ABSTRACT

PURPOSE: Colorectal cancer cells containing mobile lipids are said to be an early indicator of chemotherapy effects. The objective of the study was to examine the frequency and clinical relevance of intratumoral fat deposition in colorectal liver metastases (CRLM) post-chemotherapy using dual-echo chemical shift gradient-echo magnetic resonance imaging (MRI).

METHODS: A retrospective analysis of 98 patients with CRLM diagnosed between 2017 and 2022 (69 M, mean age 62.87 ± 10.73 years old) who had an MRI after chemotherapy was performed. On dual-echo chemical shift gradient-echo MRI, intratumoral fat deposition of CRLM was evaluated. A signal intensity drop of ≥ 12% in opposed-phase images vs. in-phase images indicated intratumoral fat. After chemotherapy, the presence of fat deposition was correlated with patients’ overall survival.

RESULTS: Before and after chemotherapy, 0 (0%) and 29 (29.59%) patients exhibited intratumoral fat. The number of CRLM ranged from 1 to 25 with a median of 3 and a mean size of 32.58 ± 22.95 mm. The groups had statistically different survival times. Overall survival was shorter for patients with intratumoral fat deposition in CRLM (32 months (24-60, 95% CI)) than for patients without fat deposition in CRLM (48 months (36-NA, 95% CI)).

CONCLUSION: In our group, nearly 30% of CRLM patients exhibited intratumoral fat after chemotherapy. Patients with intratumoral fat deposition in CRLM have a shorter overall survival time. The presence of fat in CRLM correlates with a poor long-term prognosis.

PMID:39562379 | DOI:10.1007/s00384-024-04762-0

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A Data Driven Strategy for Implementation of Singlicate Analysis in Ligand Binding Assays Used for the Determination of Anti-drug Antibodies to a Multidomain Biotherapeutic

AAPS J. 2024 Nov 19;27(1):1. doi: 10.1208/s12248-024-00984-w.

ABSTRACT

A stepwise, data-driven approach for Anti-Drug Antibodies (ADA) singlicate assays has been developed to evaluate the feasibility of singlicate ligand binding assay (LBA) method development, qualification and validation to support our clinical programs. With initial precision runs in method validation and subsequent statistical analysis to directly compare duplicate and singlicate formats, our results indicated no meaningful difference in assay precision between duplicate and singlicate. Consequently, the rest of the ADA method validation proceeded with singlicate analysis yielding acceptable validation results. The validated ADA assay in singlicate has been employed to support a Phase I study. The appropriateness of singlicate analyses is further supported by Signal-to-Noise (S/N) data from the three tiers of the confirmatory positive samples, which showed strong correlation in S/N values.

PMID:39562377 | DOI:10.1208/s12248-024-00984-w

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Efficacy and safety of stereotactic radiosurgery with gamma knife machine in patients with essential tremor: a systematic review and single-arm meta-analysis

Neurosurg Rev. 2024 Nov 20;47(1):862. doi: 10.1007/s10143-024-03094-5.

ABSTRACT

Essential tremor (ET) is identified as the most prevalent movement disorder, primarily characterized by tremors in both upper extremities. The spectrum of surgical options for ET includes gamma knife radiosurgery (GKRS) and other stereotactic radiosurgery (SRS) modalities. Despite the limitations of these options, SRS is deemed an essential and indispensable approach. Our research aimed to assess the safety and efficacy of SRS, such as GKRS, on tremor control and the spectrum of associated adverse events in the treatment of ET, also focusing on long term outcomes of the procedure. We systematically conducted an extensive search across esteemed databases, which included PubMed, Cochrane Library, Embase, and Web of Science. We included studies involving individuals diagnosed with ET who had undergone GRKS treatment. A proportional rate was used to evaluate the outcomes in a 95% confidence interval. We included 12 studies comprising 414 patients. The treatment success rate with SRS was 86.6% (95% CI: 72.4-100%). Conversely, the overall failure rate was 13.4% (95% CI: 0.00 to 27.6%). Notably, post-procedure complications were observed in 9.7% of patients (95% CI: 5.8-13.6%). A meta-analysis of five studies revealed a statistically significant reduction of tremor from the FTM scale after treatment with GKRS (MD -2.1; 95% CI -2.5 to -1.6; p < 0.01; I² = 81%). A meta-analysis of eight studies revealed a statistically significant reduction in writing tremor from the FTM scale after treatment with GKRS (MD -1.7; 95% CI -2.3 to -1.2; p < 0.01; I² = 93%). A meta-analysis of six studies revealed a statistically significant reduction in drawing tremor from the FTM scale after treatment with GKRS (MD -1.9; 95% CI -2.5 to -1.4; p < 0.01; I² = 80%). Finally, a meta-analysis of three studies revealed a statistically significant reduction in drinking tremor from the FTM scale after treatment with GKRS (MD -1.6; 95% CI -1.9 to -1.3; p < 0.01; I² = 11%). Our findings show a high success rate and low failure of GKRS for ET. Thus, GKRS is a seemingly effective and safe option for managing these patients. The importance of this research lies in its contribution to the evolving landscape of radiosurgery, providing a robust basis for the clinical application of GKRS.

PMID:39562373 | DOI:10.1007/s10143-024-03094-5

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Machine learning approach in canine mammary tumour classification using rapid evaporative ionization mass spectrometry

Anal Bioanal Chem. 2024 Nov 19. doi: 10.1007/s00216-024-05656-4. Online ahead of print.

ABSTRACT

Rapid evaporative ionization mass spectrometry (REIMS) coupled with a monopolar handpiece used for surgical resection and combined with chemometrics has been previously explored by our research group (Mangraviti et al. in Int J Mol Sci 23(18):10562, 2022) to identify several mammary gland pathologies. Here, the increased sample size allowed the construction of three statistical models to distinguish between benign and malignant canine mammary tumours (CMTs), facilitating a more in-depth investigation of changes in cellular metabolic phenotype during neoplastic transformation and biological behaviour. The results demonstrate that REIMS is effective in identifying neoplastic tissues with an accuracy of 97%, with differences in MS spectra characterized by the relative abundance of phospholipids compared to triglycerides more commonly identified in normal mammary glands. The increased rate of phospholipid synthesis represents an informative feature for tumour recognition, with phosphatidylcholine and phosphatidylethanolamine, the two major phospholipid species identified here together with sphingolipids, playing a crucial role in carcinogenesis. REIMS technology allowed the classification of different histotypes of benign CMTs with an accuracy score of 95%, distinguishing them from normal glands based on the increase in sphingolipids, glycolipids, phospholipids, and arachidonic acid, demonstrating the close association between cancer and inflammation. Finally, dysregulation of fatty acid metabolism with increased signalling for saturated, mono- and polyunsaturated fatty acids characterized the metabolic phenotype of neoplastic cells and their malignant transformation, supporting the increased formation of new organelles for cell division. Further investigations on a more significant number of tumour histotypes will allow for the creation of a more extensive database and lay the basis for how understanding metabolic alterations in the tumour microenvironment can improve surgical precision.

PMID:39562368 | DOI:10.1007/s00216-024-05656-4

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Left-sided portal hypertension: what an interventional radiologist can offer?

Eur Radiol. 2024 Nov 19. doi: 10.1007/s00330-024-11196-3. Online ahead of print.

ABSTRACT

Left-sided portal hypertension (LPH) refers to increased splenic venous pressure caused by splenic vein stenosis or occlusion. Pancreatitis is the leading cause of LPH. Typically, LPH remains asymptomatic, but it can lead to life-threatening hemorrhage from ruptured fundal varices in about 10% of patients. Further, it may be complicated by hypersplenism. Interventional radiology plays an essential role in LPH patients with failed endoscopic treatment. Variceal embolization is an effective salvage measure in bleeding gastric varices, but it carries a risk of recurrence and worsening of hypersplenism. Considering the pathophysiology, splenic vein recanalization (SVR) appears to be the best treatment; nevertheless, its lower technical success rate limits its utility only to a subgroup of LPH patients. Partial splenic embolization (PSE), a non-surgical alternative to splenectomy, reduces the splenic volume and venous outflow, thereby lowering variceal pressure. PSE is technically easier, which may explain its widespread use. Nonetheless, PSE can be complicated by life-threatening sepsis and portal vein thrombosis. Despite all attempts, some LPH patients eventually require a splenectomy. Importantly, the choice of therapy requires multidisciplinary discussion and is often influenced by availability, expertise, and clinical context. This article discusses various interventional strategies for managing LPH with the available evidence. KEY POINTS: Question Pressure within the main portal vein is normal in left-sided portal hypertension; thus, transjugular intrahepatic portosystemic shunt is ineffective. Findings Splenic vein stent placement can restore hepatopetal splenic blood flow and decompress splenic venous pressure. Clinical relevance Partial splenic embolization (PSE) is the most widely used interventional approach to manage left-sided portal hypertension-related complications.

PMID:39562367 | DOI:10.1007/s00330-024-11196-3

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Screening for Fabry disease in patients with hypertrophic cardiomyopathy using cardiac magnetic resonance imaging

Eur Radiol. 2024 Nov 19. doi: 10.1007/s00330-024-11203-7. Online ahead of print.

ABSTRACT

BACKGROUND: Fabry disease (FD) usually mimics hypertrophic cardiomyopathy (HCM). Decreased native T1 mapping and a unique late gadolinium enhancement (LGE) pattern by cardiac magnetic resonance (CMR) imaging are specific imaging markers for FD.

PURPOSE: Explore the performance of multiparametric CMR imaging in screening for FD in patients with a HCM phenotype.

MATERIALS AND METHODS: A prospective cohort of 602 patients with a HCM phenotype was assessed from April 2012 to December 2022. Participants underwent CMR imaging and genetic testing. FD diagnosis was according to genetic testing and enzyme-activity test of α-galactosidase A. Multiparameter CMR imaging included cardiac function, native T1 mapping, extracellular volume (ECV), T2 mapping, LGE, and myocardial strains. Diagnostic performance of CMR parameters in identifying FD from HCM was done by analysis of receiver operating characteristic (ROC) curves.

RESULTS: FD prevalence was 1.8% (11 cases) in this cohort with HCM. Native T1 mapping was significantly lower in FD compared with HCM (FD vs. HCM: native T1 mapping: 1174.08 ± 60.60 vs. 1293.94 ± 55.86, p < 0.001). Ventricular function, mass, ventricular wall thickness, and strains did not show significant differences between the two groups. Binary logistic regression and analysis of ROC curves demonstrated myocardial native T1 mapping of the left ventricular basal slice had the best performance in screening for FD in patients with a HCM phenotype (cutoff: 1216 ms; AUC: 0.947; sensitivity: 91%; specificity: 90%).

CONCLUSION: Native T1 mapping is the best parameter for screening FD in a Chinese population with a HCM phenotype.

KEY POINTS: Question The prevalence of Fabry Disease (FD) in the study population is unknown and the efficacy of cardiac MRI (CMR) parameter screening for FD needs validating. Findings We report the prevalence of FD among a Chinese hypertrophic cardiomyopathy (HCM) cohort and found T1 mapping is the best CMR parameter for screening FD. Clinical relevance Native T1 mapping is the best CMR parameter for screening FD in the HCM cohort, providing an effective method for rapid screening of FD in clinic, which may help identify patients for early treatment of FD.

PMID:39562366 | DOI:10.1007/s00330-024-11203-7

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Performance of novel multiparametric second-generation dual-layer spectral detector CT in gouty arthritis

Eur Radiol. 2024 Nov 19. doi: 10.1007/s00330-024-11205-5. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to compare the performance of different dual-energy computed tomography (DECT) technologies in detecting monosodium urate (MSU) crystals and evaluate the potential clinical value of novel second-generation dual-layer spectral detector CT (dlDECT) in gouty arthritis.

METHODS: Using data collected from a tertiary hospital, we examined the diagnostic accuracy of different DECT technologies for the diagnosis of MSU. We used two standards: (1) demonstration of MSU crystals in synovial fluid (gold) and (2) 2015 ACR/EULAR gout classification criteria (silver). Furthermore, six novel spectral parameters derived from dlDECT were quantitatively calculated and analyzed for MSU diagnostic efficiency.

RESULTS: Of the 243 patients with 387 joints, 68 (27.98%) had synovial fluid analysis. Compared with the gold standard, MSU diagnostic accuracy statistics for dlDECT, dual-source DECT (dsDECT) and rapid kilovolt peak switching DECT (rsDECT) were as follows: area under the curve (AUC): 0.85, 0.80 and 0.75, respectively. Findings were replicated compared with the silver standard. Multiparametric analysis in dlDECT demonstrated the highest MSU detection rate (92.86%), significantly higher than rsDECT (42.08%) and dsDECT (85.80%). Among novel parameters in dlDECT, Calcium-suppressed index 25 (CaSupp-I 25) exhibited the best performance in distinguishing materials (MSU, muscle, and bone), with an AUC of 0.992. The differentiation was also aided by histograms, scatter plots, and attenuation curves.

CONCLUSION: The novel dlDECT is likely not inferior to other DECT technologies in MSU detection, especially its spectral parameter CaSupp-I 25. Multiparameter analysis showed the potential value for detecting MSU crystals in gouty arthritis, providing valuable clinical insights for gout diagnosis.

KEY POINTS: Question The performance of different DECT technologies in detecting monosodium urate (MSU), and the value of dual-layer spectral detector CT (dlDECT) in gouty arthritis remains unclear. Findings The dlDECT was likely not inferior to other DECT technologies in MSU detection, and its multiparametric analysis provided valuable information for MSU diagnosis. Clinical relevance Novel dlDECT may improve the accurate detection of MSU crystals in gouty arthritis compared to other DECT technologies, providing valuable clinical insights and potentially improving patient outcomes for more precise gout diagnosis.

PMID:39562365 | DOI:10.1007/s00330-024-11205-5

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Embolization with gelatin foam in the management of vascularized retained products of conception: a multicenter study by the French Society of Cardiovascular Imaging

Eur Radiol. 2024 Nov 19. doi: 10.1007/s00330-024-11199-0. Online ahead of print.

ABSTRACT

OBJECTIVES: Vascularized retained products of conception (vRPOC) are the most frequent cause of delayed hemorrhage after abortion, spontaneous miscarriage, or delivery. This study evaluated the efficacy of uterine artery embolization (UAE) with gelatin foam in the management of symptomatic of vRPOC.

MATERIALS AND METHODS: This retrospective study included patients who underwent UAE with gelatin foam for vRPOCs with vaginal bleeding between January 2018 and December 2022 in 11 French university hospitals. Embolization was performed using either gelatin foam torpedoes or sludge. The primary endpoint was the clinical success of embolization (cessation of bleeding at approximately 1 month after UAE). The secondary objectives were the success of imaging (no persistent vRPOC at imaging follow-up), the safety of UAE, and the predictive factors of clinical and imaging failure.

RESULTS: Two hundred twenty-four patients (median age, 30.5 years ± 5.7 [standard deviation]) were included. Clinical success was achieved in 212 patients (94.2%). One hundred sixty-five patients had imaging follow-ups, among whom 12 patients (7.3%) had persistent vascularization. According to the SIR classification, 30 patients (13.4%) had minor complications, and two patients (0.8%) had major complications (endometritis n = 1; ischemic uterine necrosis n = 1). No predictive factors of clinical success were found, but the presence of a hypertrophic uterine artery (OR = 0.6 [0.38-0.97], p = 0.045) and the use of gelatin foam torpedoes (OR = 0.57 [0.42-0.77], p = 0.0012) were associated with a greater risk of persistent vRPOC on imaging control.

CONCLUSION: UAE with gelatin foam is safe and effective for treating hemorrhagic vRPOC.

KEY POINTS: Question Uterine vacuity is frequently observed on ultrasound after UAE for vRPOC. Findings A hypertrophic uterine artery and the use of gelatin foam torpedoes are associated with an increased risk of persistent vRPOC. Clinical relevance Embolization with gelatin foam is efficient and safe for treating bleeding in vRPOC.

PMID:39562364 | DOI:10.1007/s00330-024-11199-0

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Optimizing resources: low-dose nivolumab combinations in the management of relapsed/refractory Hodgkin lymphoma

Ann Hematol. 2024 Nov 19. doi: 10.1007/s00277-024-06098-9. Online ahead of print.

ABSTRACT

Up to one-third of patients with classical Hodgkin lymphoma (cHL) are not responsive to first-line therapy or eventually relapse. Immune checkpoint inhibitors (ICIs) have been successfully employed to treat relapsed/refractory cHL (r/r cHL) but place patients at risk of financial toxicity. Early-phase trials and observational data suggest that low doses of ICIs may achieve similar results to those obtained with high doses. In this study, we report a single-center experience using low-dose nivolumab (LD-Nivo) in different combinations for r/r cHL, including monotherapy, LD-Nivo plus brentuximab vedotin (BV), and LD-Nivo plus chemotherapy. The primary outcome was to assess the efficacy of LD-nivo in patients with r/r cHL. We included 23 consecutive patients (median age 27 years; 57% female). LD-Nivo was prescribed in 40, 100, and 140 mg fixed doses Q2W. Survival analysis was performed employing the Kaplan-Meier method. 73% of patients achieved an overall response, 43% complete response, and 30% partial response. One-year overall survival was 94.4% (95% CI, 0.84-1), and the 1-year progression-free survival was 89.4% (95% CI, 0.77-1). OS and PFS were similar accross combinations. The median dose of nivolumab was 0.78 mg/kg (range, 0.62-1.11), and the median number of cycles until a response was documented was 6 (range, 2-9). During follow-up, 18 patients received transplantation (11 autologous, 6 allogeneic). No statistically significant differences in survival or response were detected between nivolumab combinations or doses. Adverse events were observed in 61% of the patients, with none grade 3-4. LD-Nivo demonstrated promising results in relapsed/refractory HL, highlighting its potential as a cost-effective treatment option. Further research is needed to validate these findings and guide clinical practice.

PMID:39562359 | DOI:10.1007/s00277-024-06098-9