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11 pages, 2805 KB  
Article
A Novel CTC-Binding Probe: Enzymatic vs. Shear Stress-Based Detachment Approaches
by Sophia Krakowski, Sara Campos, Henri Wolff, Gabi Bondzio, Felix Hehnen, Michael Lommel, Ulrich Kertzscher and Paul Friedrich Geus
Diagnostics 2025, 15(15), 1876; https://doi.org/10.3390/diagnostics15151876 - 26 Jul 2025
Viewed by 395
Abstract
Background/Objectives: Liquid biopsy is a minimally invasive alternative to tissue biopsy and is used to obtain information about a disease from a blood sample or other body fluids. In the context of cancer, circulating tumor cells (CTC) can be used as biomarkers [...] Read more.
Background/Objectives: Liquid biopsy is a minimally invasive alternative to tissue biopsy and is used to obtain information about a disease from a blood sample or other body fluids. In the context of cancer, circulating tumor cells (CTC) can be used as biomarkers to determine the nature of the tumor, its stage of progression, and the efficiency of the administered therapy through monitoring. However, the low concentration of CTCs in blood (1–10 cells/mL) is a challenge for their isolation. Therefore, a minimally invasive medical device (BMProbe™) was developed that isolates CTCs via antigen–antibody binding directly from the bloodstream. Current investigations focus on the process of detaching bound cells from the BMProbe™ surface for cell cultivation and subsequent drug testing to enable personalized therapy planning. Methods: This article presents two approaches for detaching LNCaP cells from anti-EpCAM coated BMProbes™: enzymatic detachment using TrypLE™ and detachment through enzymatic pretreatment with supplementary flow-induced shear stress. The additional shear stress is intended to increase the detachment efficiency. To determine the flow rate required to gently detach the cells, a computational fluid dynamics (CFD) simulation was carried out. Results: The experimental test results demonstrate that 91% of the bound cells can be detached enzymatically within 10 min. Based on the simulation, a maximum flow rate of 47.76 mL/min was defined in the flow detachment system, causing an average shear stress of 8.4 Pa at the probe edges. The additional flow treatment did not increase the CTC detachment efficiency. Conclusions: It is feasible that the detachment efficiency can be further increased by a longer enzymatic incubation time or higher shear stress. The influence on the integrity and viability of cells must, however, be considered. Full article
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16 pages, 1961 KB  
Article
PAI-1 Inhibitor TM5441 Attenuates Emphysema and Airway Inflammation in a Murine Model of Chronic Obstructive Pulmonary Disease
by Kyohei Oishi, Hideki Yasui, Yusuke Inoue, Hironao Hozumi, Yuzo Suzuki, Masato Karayama, Kazuki Furuhashi, Noriyuki Enomoto, Tomoyuki Fujisawa, Takahiro Horinouchi, Takayuki Iwaki, Yuko Suzuki, Toshio Miyata, Naoki Inui and Takafumi Suda
Int. J. Mol. Sci. 2025, 26(15), 7086; https://doi.org/10.3390/ijms26157086 - 23 Jul 2025
Viewed by 492
Abstract
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide, primarily driven by chronic airway inflammation due to cigarette smoke exposure. Despite its burden, however, current anti-inflammatory therapies offer limited efficacy in preventing disease progression. Plasminogen activator inhibitor-1 (PAI-1), [...] Read more.
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide, primarily driven by chronic airway inflammation due to cigarette smoke exposure. Despite its burden, however, current anti-inflammatory therapies offer limited efficacy in preventing disease progression. Plasminogen activator inhibitor-1 (PAI-1), as a key regulator of fibrinolysis, has recently been implicated in structural airway changes and persistent inflammation in patients with COPD. This study aimed to investigate the ability of the PAI-1 inhibitor TM5441 to attenuate airway inflammation and structural lung damage induced by a cigarette smoke extract (CSE) in a mouse model. Mice received intratracheal CSE or vehicle on days 1, 8, and 15, and were sacrificed on day 22. TM5441 (20 mg/kg) was administered orally from days 1 to 22. The CSE significantly increased the mean linear intercept, destructive index, airway resistance, and reductions in dynamic compliance. The CSE also increased the numbers of neutrophils and macrophages in the bronchoalveolar lavage fluid, systemic PAI-1 activity, and neutrophil elastase mRNA and protein expression in the lungs. TM5441 treatment significantly suppressed these changes without affecting coagulation time. These findings suggest that TM5441 may be a novel therapeutic agent for COPD by targeting PAI-1-mediated airway inflammation and emphysema. Full article
(This article belongs to the Special Issue Lung Diseases Molecular Pathogenesis and Therapy)
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9 pages, 623 KB  
Case Report
Prenatal Diagnosis and Management of Tuberous Sclerosis Complex with Cardiac Rhabdomyoma: A Case Report Highlighting the Role of Sirolimus and Postnatal Complications
by David Asael Rodríguez-Torres, Joel Arenas-Estala, Ramón Gerardo Sánchez-Cortés, Iván Vladimir Dávila-Escamilla, Adriana Nieto-Sanjuanero and Graciela Arelí López-Uriarte
Diagnostics 2025, 15(14), 1811; https://doi.org/10.3390/diagnostics15141811 - 18 Jul 2025
Cited by 1 | Viewed by 452
Abstract
Background and Clinical Significance: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by pathogenic variants in TSC1 or TSC2. Cardiac rhabdomyoma is a common prenatal finding and can be associated with severe complications, including pericardial effusion. We administered prenatal sirolimus to [...] Read more.
Background and Clinical Significance: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by pathogenic variants in TSC1 or TSC2. Cardiac rhabdomyoma is a common prenatal finding and can be associated with severe complications, including pericardial effusion. We administered prenatal sirolimus to mitigate pericardial effusion, which led to postnatal complications. Case Presentation: A 28-year-old pregnant woman with no significant family history underwent routine fetal ultrasound at 28.1 weeks of gestation, which identified a large right ventricular mass consistent with rhabdomyoma. Further fetal brain MRI revealed cortical-subcortical tubers and subependymal nodules, leading to a clinical diagnosis of TSC. At 30.4 weeks, oral sirolimus (3 mg/day) was started due to the significant pericardial effusion. The effusion remained after treatment, requiring pericardiocentesis at 33.6 weeks. The sirolimus dosage was raised to 6 mg/day at 35.6 weeks, reaching a plasma level of 3.76 ng/mL, but there was no discernible improvement because of the continued fluid accumulation. The mother did not experience any adverse side effects from the procedure. Genetic testing confirmed a pathogenic variant in TSC2 (c.1372C>T). After birth, the neonate received a single dose of sirolimus but subsequently developed necrotizing enterocolitis (NEC), highlighting the potential adverse effects and the need for cautious consideration of treatment options. Conclusions: This case illustrates the complexities of managing prenatal tuberous sclerosis complex (TSC). While sirolimus has been explored for fetal cardiac rhabdomyoma and associated complications, its effectiveness in resolving pericardial effusion remains uncertain. Additionally, the development of NEC postnatally raises concerns about the safety of mTOR inhibitors in this context. Further studies are necessary to assess the risks and benefits of this approach in fetal therapy. Full article
(This article belongs to the Special Issue Diagnosis and Management in Prenatal Medicine, 3rd Edition)
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16 pages, 2252 KB  
Article
Clinical and Evolutive Features of Tuberculous Meningitis in an Immunosuppressed Adolescent During the COVID 19 Pandemic
by Dalia Dop, Vlad Pădureanu, Rodica Pădureanu, Iulia Rahela Marcu, Suzana Măceș, Anca Emanuela Mușetescu, Ștefan Adrian Niculescu and Carmen Elena Niculescu
Biomedicines 2025, 13(7), 1721; https://doi.org/10.3390/biomedicines13071721 - 14 Jul 2025
Viewed by 390
Abstract
Background/Objectives: Tuberculous meningitis is the most severe form of tuberculosis in children, with a high mortality and morbidity rate if it is not diagnosed and treated in a timely manner. The aim of this study is to highlight the challenges associated with establishing [...] Read more.
Background/Objectives: Tuberculous meningitis is the most severe form of tuberculosis in children, with a high mortality and morbidity rate if it is not diagnosed and treated in a timely manner. The aim of this study is to highlight the challenges associated with establishing a diagnosis of tuberculous meningitis in a child with immunosuppression, given the presence of nonspecific clinical manifestations. Methods: We present the case of a 15-year-old adolescent with systemic lupus erythematosus, on immunosuppressive therapy, who is diagnosed with tuberculous meningoencephalitis presenting the clinical, diagnostic and imaging characteristics, as well as the diagnostic traps and limitations associated with this condition. Antituberculosis therapy was started empirically, because there was no improvement in the clinical status with conventional antibiotic therapy; the diagnosis was established 7 days after the start of the antituberculosis treatment, with the help of an acid-fast bacilli culture from the cerebrospinal fluid. Results: The course of the tuberculous meningoencephalitis was slowly favorable, despite the superimposed COVID-19 infection. Delay in administering immunosuppressive therapy led to the onset of renal and joint manifestations. Conclusions: Tuberculous meningitis is a highly lethal, often underdiagnosed disease with nonspecific clinical and imaging manifestations, which can have a favorable outcome if the diagnosis is established early on and treatment is started promptly. Full article
(This article belongs to the Section Microbiology in Human Health and Disease)
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11 pages, 1228 KB  
Article
Diabetic Ketoacidosis Fluid Therapy Algorithm in the Golden Hours: Iatrogenic Hyperchloremic Acidosis Instead of Unmeasured Anion Acidosis
by Zeynep Tugce Sarikaya, Bulent Gucyetmez, Duran Ozdemir, Behiye Dogruel, Aykut Ayyildiz, Jozef Kesecioglu and Lutfi Telci
J. Clin. Med. 2025, 14(12), 4125; https://doi.org/10.3390/jcm14124125 - 11 Jun 2025
Viewed by 820
Abstract
Background/Objectives: In diabetic ketoacidosis (DKA), absolute insulin deficiency and elevation of counter-regulatory hormones may cause osmotic diuresis and water and electrolyte loss, which may lead to dehydration and renal failure. Fluids with high Na content are preferred in the DKA fluid therapy [...] Read more.
Background/Objectives: In diabetic ketoacidosis (DKA), absolute insulin deficiency and elevation of counter-regulatory hormones may cause osmotic diuresis and water and electrolyte loss, which may lead to dehydration and renal failure. Fluids with high Na content are preferred in the DKA fluid therapy algorithm due to the association of Na with β-Hydroxybutyrate (β-HB) and the renal excretion of Na-β-HB. However, these fluids may cause hyperchloremic metabolic acidosis due to their high chloride concentration. In the literature, base-excess chloride (BECl) has been suggested as a better approach for assessing the effect of chloride on acid–base status. Our aim in this study was to investigate the effect of fluids with BECl values less than zero versus those with values equal to or greater than zero on the metabolic acid–base status in the first 6 h of DKA. Methods: This retrospective study included DKA cases managed in the tertiary intensive care units of five hospitals in the last 10 years. Patients were divided into two groups according to the Na-Cl difference of the administered fluids during the first 6 h of treatment: Group I [GI, fluids with Na-Cl difference = 0, chloride-rich group] and Group II [GII, fluids with Na-Cl difference > 32 mmol, chloride non-rich group]. Demographic data, blood gas analysis results, types and amounts of administered fluids, urea–creatinine values, and urine ketone levels were recorded. Results: Thirty-five patients with DKA in the ICU were included in the study (GI; 22 patients, GII; 13 patients). There was no difference between the patients in the two groups in terms of age, gender, and LOS-ICU. According to the distribution of the administered fluids, the main fluid administered in GI was 0.9% NaCl, whereas in the GII, it was bicarbonate, Isolyte-S, and 0.9% NaCl. In GI, the chloride load administered was higher; the BECl level of the fluids was lower than in GII. At the end of the first 6 h, although sodium and strong ion gap values were similar, patients in GI were more acidotic due to iatrogenic hyperchloremia and, as a result, were more hypocapnic than GII. Conclusions: In conclusion, administering chloride-rich fluids in DKA may help reduce unmeasured anion acidosis. Still, risks cause iatrogenic hyperchloremic acidosis, which can hinder the expected resolution of acidosis and increase respiratory workload. Therefore, it is suggested that DKA guidelines be revised to recommend an individualized approach that avoids chloride-rich fluids and includes monitoring of metabolic parameters like Cl and BECl. Full article
(This article belongs to the Section Intensive Care)
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12 pages, 2461 KB  
Article
Morphology of Macular Neovascularization in Age-Related Macular Degeneration Influences Treatment Requirement and Visual Outcome After 1 Year
by Michael Grün, Kai Rothaus, Martin Ziegler, Albrecht Lommatzsch, Clemens Lange and Henrik Faatz
J. Pers. Med. 2025, 15(6), 246; https://doi.org/10.3390/jpm15060246 - 11 Jun 2025
Viewed by 533
Abstract
Background/Objectives: To evaluate the potential of Optical Coherence Tomography (OCT) and OCT angiography parameters in predicting treatment requirements and visual outcomes after one year in therapy-naïve eyes with neovascular age-related macular degeneration (nAMD). Methods: A retrospective study of 96 therapy-naïve eyes [...] Read more.
Background/Objectives: To evaluate the potential of Optical Coherence Tomography (OCT) and OCT angiography parameters in predicting treatment requirements and visual outcomes after one year in therapy-naïve eyes with neovascular age-related macular degeneration (nAMD). Methods: A retrospective study of 96 therapy-naïve eyes newly diagnosed with nAMD was carried out. All eyes received baseline OCT and OCTA. Follow-up OCT after initial upload was then carried out, involving three intravitreal injections (IVIs) with anti-Vascular Endothelial Growth Factor (anti-VEGF) at four-week intervals. OCT parameters, including intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelium detachment (PED), and central retinal thickness (CRT), were assessed qualitatively and quantitatively. Macular Neovascularization (MNV) morphology at baseline was described in terms of area, total vessel length, flow density, and fractal dimension. OCT and OCTA parameters were correlated with best corrected visual acuity (BCVA) and number of administered IVIs after 1 year of treatment. Results: Eyes with persistent subretinal fluid (SRF) or both intraretinal fluid (IRF) and SRF after upload showed a significantly higher need for IVIs (p < 0.01). Also, pigment epithelium detachment (PED) presence at baseline (p < 0.05), PED height at baseline (p < 0.01), PED presence after upload (p < 0.01), and PED height after upload (p < 0.01) were each correlated with a greater number of IVIs. Decrease in PED height during upload was accompanied by a lower number of IVIs (p < 0.01). All the aforementioned parameters had no influence on BCVA after 1 year (p > 0.05). Baseline central retinal thickness (CRT) was linked to worse BCVA at 12 months (p < 0.05), but not the number of IVIs. Follow-up CRT correlated with worse BCVA (p < 0.01) and more IVIs (p < 0.01), while CRT decrease was associated with better BCVA (p < 0.05) and fewer IVIs (p < 0.01) at 1 year. In OCTA, area and total vessel length of MNVs were correlated with BCVA after 1 year (p < 0.01) but had no influence on number of IVIs (p > 0.05). Flow density had no influence on either outcome parameter (p > 0.05). Fractal dimension was associated with BCVA (p < 0.01) and number of IVIs (p < 0.05) after 1 year. Conclusions: MNV area, vessel length, and fractal dimension in OCTA, along with fluid distribution in OCT at baseline and after follow-up, may serve as indicators of treatment needs and visual outcomes after one year. Further studies with longer observation periods and the use of deep learning models are needed to improve analyses and to verify the applicability of these findings to clinical practice. Full article
(This article belongs to the Special Issue Personalized Medicine in Retinal Diseases)
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14 pages, 1522 KB  
Article
Single Injection of Highly Concentrated Hyaluronic Acid Provides Improvement of Knee Joint Arthrokinematic Motion and Clinical Outcomes in Patients with Osteoarthritis—Non-Randomized Clinical Study
by Krzysztof Falkowski and Dawid Bączkowicz
J. Clin. Med. 2025, 14(10), 3557; https://doi.org/10.3390/jcm14103557 - 19 May 2025
Viewed by 1383
Abstract
Background/Objectives: Intra-articularly administered hyaluronic acid (HA) products improve the mechanical properties of the synovial fluid (SF) in an osteoarthritic (OA) joint and thus improve joint motion quality. However, current diagnostic methods, used to assess the clinical effectiveness of HA-based therapy are based [...] Read more.
Background/Objectives: Intra-articularly administered hyaluronic acid (HA) products improve the mechanical properties of the synovial fluid (SF) in an osteoarthritic (OA) joint and thus improve joint motion quality. However, current diagnostic methods, used to assess the clinical effectiveness of HA-based therapy are based on subjective tools, and are unable to deliver solid data about the actual impact of this molecule on joint functioning. Consequently, the aim of this study was to objectively assess the effect of HA IA injection on joint motion quality with vibroarthrography (VAG) and the subsequent evaluation of patient clinical status. Methods: A total of 40 patients with knee OA and 50 healthy individuals as the control group were enrolled in this non-randomized clinical and were subjected to therapy consisting of a single IA administration of highly concentrated HA gel (Biolevox™ HA ONE). The therapy assessment included an evaluation of joint motion quality with the VAG method and a subsequent evaluation of the knee joint function using the WOMAC questionnaire for up to 60 days after the therapy. Results: A single IA injection of HA led to an immediate and sustained improvement of the motion quality of OA-affected synovial joints, as proven by the significant reduction in all measured vibroacoustic emissions (VMS, R4, P1, and P2). Furthermore, this was followed by a significant improvement in all WOMAC sub-scales, observed at 30 and 60 days after the therapy. Conclusions: The results of this study demonstrate that an IA-HA injection can improve the motion quality of OA-affected joints. Importantly, the observed improvement in joint motion quality is directly correlated with early recovery of joint function. These findings provide objective evidence that HA effectively enhances OA-affected joint biomechanics, contributing to a better understanding of the actual impact of this prevalent OA therapy on knee joint motion quality. Full article
(This article belongs to the Section Orthopedics)
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14 pages, 5530 KB  
Article
Intranasal Application of Foxp3 Introduced with Poly(d,l-lactic-co-glycolic acid) (PLGA) Nanoparticles (Foxp3 NPs) Attenuates Allergic Inflammation in a Mouse Model of Allergic Rhinitis
by Seung Cheol Han, Sunhee Yeon, Hyejeen Kim and Sookyoung Park
Pharmaceutics 2025, 17(5), 575; https://doi.org/10.3390/pharmaceutics17050575 - 27 Apr 2025
Cited by 1 | Viewed by 648
Abstract
Background: Allergic rhinitis (AR) is a common disease that requires more convenient, safe, and effective therapy. This study aimed to investigate the therapeutic effect of Forkhead box protein3 (Foxp3) introduced with poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (Foxp3 NPs) in [...] Read more.
Background: Allergic rhinitis (AR) is a common disease that requires more convenient, safe, and effective therapy. This study aimed to investigate the therapeutic effect of Forkhead box protein3 (Foxp3) introduced with poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (Foxp3 NPs) in an AR mouse model. Methods: A murine model of allergic rhinitis was established using BALB/c mice through initial sensitization by intraperitoneal administration of ovalbumin (OVA), followed by repeated intranasal OVA challenges. Foxp3 plasmid-loaded PLGA nanoparticles were subsequently administered via either the intranasal or intraperitoneal route to evaluate therapeutic efficacy. Episodes of sneezing and nose rubbing were counted. The serum total IgE, OVA-specific IgE, and cytokine levels in nasal lavage fluid (NALF) were determined by ELISA (Enzyme-Linked ImmunoSorbent Assay). Nasal mucosa from each group were analyzed using protein, reverse transcriptase–polymerase chain reaction (RT-PCR), and histological analyses. Result: Rubbing and sneezing symptoms improved in the Foxp3 NPs intranasal administration group. Foxp3 NPs intranasal administration markedly ameliorated OVA-induced nasal allergic inflammation. The total IgE and OVA-specific IgE serum level and IL-4, IL-13 expression levels of NALF were significantly decreased in the treated Foxp3 NPs group. The histopathological results of nasal mucosa were also normal, with no cellular infiltration and no inflammation in the Foxp3 NPs group. Conclusions: These results suggest that Foxp3 NPs alleviate nasal allergic inflammation and may have therapeutic value in the treatment of AR. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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14 pages, 496 KB  
Review
Retrospective Review of Intra-Cerebrospinal Fluid (CSF) Drug Delivery in CNS Malignancies: Safety, Clinical Efficacy and Pharmacokinetic Profiles of Intracerebroventricular (ICV), Lumbar Intrathecal (LIT), and Intra-Cisterna Magna (ICM) Injections
by Grace Y. Lee, Marcie A. Glicksman, Rajan Patel, Saaz Malhotra, Nathan Moelis, Nisheka N. Vanjani and Priya Kumthekar
Cancers 2025, 17(8), 1263; https://doi.org/10.3390/cancers17081263 - 9 Apr 2025
Viewed by 1139
Abstract
Background/Objectives: The blood–brain barrier and blood-CSF barrier limit the uptake of CNS-targeted therapeutics, warranting utilization of intra-cerebrospinal fluid (CSF) drug delivery. Here we review and compare the safety and distribution of different intra-CSF delivery methods reported in clinical literature. Methods: A [...] Read more.
Background/Objectives: The blood–brain barrier and blood-CSF barrier limit the uptake of CNS-targeted therapeutics, warranting utilization of intra-cerebrospinal fluid (CSF) drug delivery. Here we review and compare the safety and distribution of different intra-CSF delivery methods reported in clinical literature. Methods: A retrospective literature review of three common CSF access methods was performed. A search consisting of clinical trials published on PubMed from 2000–2024 using the following search terms—intracerebroventricular/intraventricular/ICV, intrathecal/IT, intralumbar/lumbar puncture, cisterna magna/ICM/IT-CM, drug delivery, drug administration, and CSF—yielded 38 intracerebroventricular (ICV), 110 lumbar intrathecal (LIT), and six intra-cisterna magna (ICM) studies. Results: After final exclusion criteria were applied, there were 12 ICV, two LIT, and zero ICM publications remaining for analysis. ICV-specific safety was addressed in 11 ICV publications, with headache, nausea, and vomiting being among the most frequently mentioned procedure-associated adverse events (AEs). LIT-specific safety was provided in only one of the two studies, reporting mostly grade 1/2 AEs but also an instance of grade 4 myelosuppression. For clinical efficacy, progression-free survival (PFS), overall survival (OS), and disease progression rates were largely variable across studies. Pharmacokinetics were analyzed in four ICV studies. Conclusions: The safety profiles of both ICV and LIT injections are acceptable, showing mostly mild to moderate procedure-associated AEs and less common treatment-related AEs than systemically administered therapies. Additionally, ICV achieves therapeutic goals more consistently than the other intra-CSF delivery methods. To date, there are insufficient data to show dose-related response with intra-CSF delivery. Novel tools are being developed to improve upon intra-CSF delivery that will ideally lead to improved patient outcomes in the near future. Full article
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
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13 pages, 1565 KB  
Review
Volume Kinetic Analysis in Living Humans: Background History and Answers to 15 Questions in Physiology and Medicine
by Robert G. Hahn
Fluids 2025, 10(4), 86; https://doi.org/10.3390/fluids10040086 - 28 Mar 2025
Cited by 1 | Viewed by 728
Abstract
Volume kinetics is a pharmacokinetic method for analysis of the distribution and elimination of infusion fluids. The approach has primarily been used to improve the planning of fluid therapy during surgery but is also useful for answering physiological questions. The kinetics is based [...] Read more.
Volume kinetics is a pharmacokinetic method for analysis of the distribution and elimination of infusion fluids. The approach has primarily been used to improve the planning of fluid therapy during surgery but is also useful for answering physiological questions. The kinetics is based on 15–35 serial measurements of the blood hemoglobin concentration during and after the fluid is administered intravenously. Crystalloid fluid, such as isotonic saline and Ringer’s lactate, distributes between three compartments that are filled in succession depending on how much fluid is administered. The equilibration of fluid between these three compartments is governed by five rate constants. The compartments are the plasma (Vc), and a fast-exchange (Vt1) and a slow-exchange interstitial compartment (Vt2). The last compartment operates like an overflow reservoir and, if filled, markedly, prolongs the half-life of the fluid. By contrast, the volume of a colloid fluid distributes in a single compartment (Vc) from where the expansion is reduced by capillary leakage and urinary excretion. This review gives 15 examples of physiological or medical questions where volume kinetics has provided answers. These include why urine flow is low during general anesthesia, the inhibitory effects of anesthetics on lymphatic pumping, the influence of dopamine and phenylephrine on urine output, fluid maldistribution in pre-eclampsia, plasma volume oscillations, and issues related to the endothelial glycocalyx layer. Full article
(This article belongs to the Special Issue Biological Fluid Dynamics, 2nd Edition)
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11 pages, 1018 KB  
Article
Multidisciplinary Treatment for Lymphorrhea and Chylorrhea Following Lymph Node Dissection for Genitourinary Cancer
by Naoto Kamiya, Takahide Noro, Taro Okazaki, Naoki Ishitsuka, Yuta Suzuki, Shota Iijima, Yuka Sugizaki, Takatoshi Somoto, Ryo Oka, Takanobu Utsumi, Takumi Endo, Shusuke Kasuya, Nobuyuki Hiruta and Hiroyoshi Suzuki
Cancers 2025, 17(4), 592; https://doi.org/10.3390/cancers17040592 - 10 Feb 2025
Viewed by 1500
Abstract
Background: Lymph node dissection (LND) is often performed in genitourinary cancer to improve accurate staging. However, the resultant lymphatic damage often leads to postoperative lymphorrhea and chylorrhea. Further, since lymphatic fluid lacks platelets, it has very few clotting factors, and it is often [...] Read more.
Background: Lymph node dissection (LND) is often performed in genitourinary cancer to improve accurate staging. However, the resultant lymphatic damage often leads to postoperative lymphorrhea and chylorrhea. Further, since lymphatic fluid lacks platelets, it has very few clotting factors, and it is often difficult to treat postoperative lymphatic leakage. Treatments for lymphorrhea include conservative treatment (e.g., fasting, total parenteral nutrition, and drug therapy), interventional radiology (IR) and surgical treatment. However, there is no guideline of refractory lymphorrhea, and no clear criteria for switching to the next treatment. Methods: We reviewed the records of 28 patients at Toho University Sakura Medical Center with postoperative lymphorrhea or chylorrhea after LND that did not improve with conservative treatment. Based on this analysis, we partially revised the treatment algorithm for lymphorrhea developed by Rose et al. Results: The cases consisted of 26 men and two women, aged 65.0 ± 9.9 years. The mean number of lymph nodes removed was 25.3 ± 15.0. Octreotide was administered in 27 patients, lymphangiography was performed in three patients, and lymphatic embolization was performed in two patients. The mean duration of octreotide administration was 9.7 ± 6.1 days, and the mean dose was 211.1 µg/day. The treatment success rates with octreotide and IR were 78.6% and 100%, respectively. The mean duration of drain placement after surgery for primary cancer was 18.3 ± 14.3 days. Conclusions: Patients with lymphorrhea and chylorrhea should be initially treated conservatively, with IR performed if conservative treatment is unsuccessful. Surgical treatment should be a last resort. Full article
(This article belongs to the Section Cancer Therapy)
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11 pages, 1261 KB  
Article
Nephrogenic Diabetes Insipidus Affecting Three Males in Two Generations—Case Report and Review of the Literature
by Ramona Stroescu, Adela Chiriţă-Emandi, Maria Puiu, Flavia Chisavu, Ruxandra Steflea, Gabriela Doroş and Mihai Gafencu
Children 2025, 12(2), 195; https://doi.org/10.3390/children12020195 - 6 Feb 2025
Viewed by 1084
Abstract
Background: Nephrogenic diabetes insipidus (NDI) is defined as the inability of the kidney to concentrate urine owing to the insensitivity of the distal nephron to the antidiuretic hormone, arginine vasopressin. NDI is a heterogeneous rare autosomal dominant or X-linked disease. Objective: We present [...] Read more.
Background: Nephrogenic diabetes insipidus (NDI) is defined as the inability of the kidney to concentrate urine owing to the insensitivity of the distal nephron to the antidiuretic hormone, arginine vasopressin. NDI is a heterogeneous rare autosomal dominant or X-linked disease. Objective: We present a family with nephrogenic diabetes affecting three males in two generations. Methods: We report two boys with NDI: a 4-month-old infant who was treated for fever, vomiting, and failure to thrive, and his 10-year-old uncle (the mother’s brother), who was admitted concurrently for consuming 11 L of fluid per day. According to family history, the mother’s sibling passed away at the age of two from severe hypernatremic dehydration. Results: The infant’s clinical and laboratory evaluation revealed a 7.8 mL/kg/h urine output, hypernatremic hyperchloremic alkalosis, extremely low urine density (1002), and elevated copeptin level. In contrast, the uncle’s clinical and laboratory evaluation revealed marked polyuria, low urine density, and elevated copeptin, all of which were suggestive of diabetes insipidus. After starting hydrochlorothiazide treatment (2 mg/kg/body), the infant’s urine production reduced (2.85 mL/kg/h); however, severe hypokalemia and alkalosis followed. Spironolactone, an aldosterone antagonist, were added, with good therapeutic response. Hydrochlorothiazide was administered to the uncle, and his daily fluid intake decreased to 3–4 L. Given the family history, Sanger sequencing for the AVPR2 variant was performed on the boys and the infant’s mother. Analysis showed hemizygous likely pathogenic variant c.335G>A p. (Cys112Tyr) in the 2 boys and heterozygous (carrier) status of the mother. Within the same family, we observed phenotypic heterogeneity: one child died at the age of two, another lived well into ten years without therapy, and a four month-old baby could have had a poor outcome without specific treatment. Conclusions: NDI is a rare and possibly fatal genetic disorder with heterogeneous manifestations. In families with a history of NDI, molecular genetic testing is crucial for family planning. Full article
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15 pages, 730 KB  
Article
Does the Administration of Intravenous Fluid Matter in the Context of the Incidence of Postoperative Complications After Radical Cystectomy?
by Paweł Lipowski, Adam Ostrowski, Jan Adamowicz, Przemysław Jasiewicz, Filip Kowalski, Tomasz Drewa and Kajetan Juszczak
Cancers 2025, 17(1), 102; https://doi.org/10.3390/cancers17010102 - 31 Dec 2024
Cited by 1 | Viewed by 1083
Abstract
Introduction: Intravenous fluid management is integral to perioperative care, particularly under enhanced recovery after surgery (ERAS) protocols. In radical cystectomy (RC), which carries high risks of complications and mortality, optimizing fluid management poses a significant challenge due to the absence of definitive guidelines. [...] Read more.
Introduction: Intravenous fluid management is integral to perioperative care, particularly under enhanced recovery after surgery (ERAS) protocols. In radical cystectomy (RC), which carries high risks of complications and mortality, optimizing fluid management poses a significant challenge due to the absence of definitive guidelines. Aim: the purpose of this study was to investigate the effects of intravenous fluid administration on postoperative complications in patients undergoing RC. Material and methods: This study involved 288 patients who underwent laparoscopic RC and urinary diversion from 2018 to 2022. ERAS protocols were implemented for all patients. Participants were divided into four groups based on the type of urinary diversion (ureterocutaneostomy vs. ileal conduit) and the intraoperative fluid volume input (less than 1000 mL vs. more than 1000 mL). Postoperative complications were evaluated at 30 and 90 days post-surgery using the Clavien-Dindo scale. The fluid management effectiveness was measured using the absolute Vascular Bed Filling Index (aVBFI) and the adjusted Vascular Bed Filling Index (adjVFBI). Results: The UCS is associated with a lower risk of increased severity of postoperative complications. The administration of more than 1000 mL of fluids was associated with a higher risk of complications (p = 0.035). However, after adjusting for the duration of the surgery and BMI, this association did not hold statistical significance, indicating that fluid volume alone is not a direct predictor of postoperative complications. At aVBFI values between zero and eight, urinary diversion using the UCS method is associated with a lower risk of complications compared to the IC. When aVBFI equals eight, the differences in the severity of complications between the UCS and the IC are minimal. However, when aVBFI exceeds eight, the IC is associated with fewer complications during the 30 days post-operation compared to the UCS. The correlation between the adjVFBI (B = −0.27; 95% CI: −0.45 to −0.08; p = 0.005) and the severity of complications up to 30 days postoperatively is similar to that seen with the aVBFI. Similarly, the correlation of the adjVFBI with the method of urinary diversion (B = 0.24; 95% CI: 0.06 to 0.43; p = 0.011) resembles that of the aVBFI. The volume of fluids administered and the indices aVBFI and adjVFBI did not influence the occurrence of complications 90 days postoperatively. Conclusions: The volume of fluids administered is not a factor directly affecting the occurrence of complications following RC when the ERAS protocol is used. The amount of intraoperative fluid administration should be adjusted according to the intraoperative blood loss. Our findings endorse the utility of aVBFI and adjVFBI as valuable tools in guiding fluid therapy within the framework of ERAS protocols. However, further multicenter randomized trials are needed to definitively determine the best fluid therapy regimen for patients undergoing RC. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Genitourinary Cancers)
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12 pages, 1479 KB  
Article
The Importance of Bright Spotty Lesions on Magnetic Resonance Imaging in Predicting Chronic Neuropathic Pain in Myelitis
by Je Hong Min, Sung-Yeon Sohn and In Soo Joo
J. Clin. Med. 2024, 13(24), 7820; https://doi.org/10.3390/jcm13247820 - 21 Dec 2024
Viewed by 882
Abstract
Background/Objectives: Chronic neuropathic pain (CNP) stands as one of the most debilitating complications in patients with myelitis owing to its challenging management. Bright spotty lesions (BSLs) are frequently observed in neuromyelitis optica spectrum disorder (NMOSD), but few reports have discussed CNP in [...] Read more.
Background/Objectives: Chronic neuropathic pain (CNP) stands as one of the most debilitating complications in patients with myelitis owing to its challenging management. Bright spotty lesions (BSLs) are frequently observed in neuromyelitis optica spectrum disorder (NMOSD), but few reports have discussed CNP in myelitis. We aim to demonstrate that BSLs could be one of the potential prognostic factors for CNP development in myelitis. Methods: We examined 63 patients diagnosed with myelitis. Patients were categorized into CNP and non-CNP groups. We assessed the severity of clinical symptoms and the oral steroid dose administered after pulse therapy. Spine magnetic resonance imaging (MRI) of each patient was reviewed to analyze the characteristics of myelitis. Serological and cerebrospinal fluid (CSF) findings were also examined to confirm the etiology. Results: CNP was observed in 27 patients (42.9%). The mean onset age of patients with CNP was 45.26 ± 14.16 years. The MRI lesions exhibited more enhanced features and bright spotty lesions (BSLs) in the CNP group (χ2 test, p < 0.05). Patients with CNP received a lower oral steroid dose during the first month after symptom onset (χ2 test, p < 0.05). Multivariate logistic regression analysis revealed that patients with CNP exhibited significant BSLs in their myelitis lesions on spine MRI (OR 4.965; 95% CI, 1.282 to 19.235, p = 0.02). Conclusions: Although the exact mechanism remains unknown, the presence of BSLs on spine MRI could serve as an independent prognostic factor for CNP development. Additionally, our study suggests that lower oral steroid doses administered immediately after symptom onset are associated with CNP development. Further investigation with a larger cohort is warranted to validate our findings. Full article
(This article belongs to the Special Issue Clinical Perspectives for Headache and Neuropathic Pain)
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6 pages, 1660 KB  
Case Report
Difficult Diagnosis of Spontaneous Intracranial Hypotension with Nausea and Lower Abdominal Pain as Main Complaints: A Case Report
by Misaki Yokoi, Tsuneaki Kenzaka, Mari Asano, Ryu Sugimoto and Hogara Nishisaki
Reports 2024, 7(4), 115; https://doi.org/10.3390/reports7040115 - 16 Dec 2024
Viewed by 1110
Abstract
Background and Clinical Significance: Symptoms of spontaneous intracranial hypotension include orthostatic headaches due to decreased cerebrospinal fluid (CSF) levels. Here, we present a 24-year-old female admitted to an obstetrics and gynecology department with primary complaints of lower abdominal pain and dysmenorrhea with [...] Read more.
Background and Clinical Significance: Symptoms of spontaneous intracranial hypotension include orthostatic headaches due to decreased cerebrospinal fluid (CSF) levels. Here, we present a 24-year-old female admitted to an obstetrics and gynecology department with primary complaints of lower abdominal pain and dysmenorrhea with subsequent diagnosis of spontaneous intracranial hypotension (SIH). Case Presentation: The patient had experienced nausea and lower abdominal pain independent of her menstrual cycle 5 days before admission, for which she visited the emergency department 3 days later. On admission, her symptoms were temporarily relieved by administering analgesics; thus, she was discharged. However, later, the symptoms worsened. Consequently, she returned to the emergency department for further evaluation, including blood tests, imaging, and endoscopy, which revealed no nausea- or abdominal pain-related organic abnormalities. On day 10, she developed a headache, aggravated by lying in the supine position and improved by sitting. Additional history revealed a diagnosis of SIH owing to the worsening abdominal pain in the supine position. An 111In CSF cavity scintigram showed no spinal fluid leakage; early intrabladder radioisotope (RI) accumulation was observed, and the residual 24 h CSF cavity RI was >30%. At a referral specialist hospital, an epidural saline infusion test was performed, which improved her headache and lower abdominal pain. Blood patch therapy improved her lower abdominal pain, headache, and dysmenorrhea. Conclusions: The final diagnosis was SIH, with symptoms attributed to CSF depletion. The patient also experienced rare paradoxical postural-related headaches and lower abdominal pain, aggravated by lying in the supine position, contributing to the final diagnosis. Full article
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