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Physiological Reports Jul 2024The central role of natriuretic peptides (NPs) in the complex cardio-renal integrated physiology and organ failure has been revealed over the last four decades. Atrial... (Review)
Review
The central role of natriuretic peptides (NPs) in the complex cardio-renal integrated physiology and organ failure has been revealed over the last four decades. Atrial natriuretic peptide (ANP), the oldest representative of the NPs family, is produced through conversion of proANP to the mature peptide by corin, a trans-membrane protease localized to the cardiac myocyte membrane. Similarly, brain natriuretic peptide (BNP) is generated by furin, which cleaves proBNP to BNP in myocytes. Though the components of NPs system, their synthesis and target organs are well established, understanding their role in the interplay between the heart and the kidney is steadily evolving. In this context, Feldman et al. (New England Journal of Medicine, 389, 1685) recently described patients with hypertension, cardiomyopathy, atrial arrhythmia and left atrial fibrosis, associated with a homozygous loss-of-function variant of the gene encoding corin (Cor). Notably, reduced baseline urinary electrolyte and creatinine excretion have been observed in one of the studied patients. This renal excretory functional impairment could be attributed to the lack of cardiac-derived ANP in these patients, as implied by Feldman et al. Yet, in this mini-review we suggest that this aberrant renal manifestation may principally stem from lack of local ANP production at renal tissue, as corin is normally expressed in proximal tubules, Henle's loop and collecting ducts, with locally produced ANP provoking Na and water exertion. Collectively, it seems that beside the classic well-established cardio-renal axis, the renal NPs system functions as local endocrine machinery in the regulation of sodium excretion.
Topics: Humans; Animals; Kidney; Serine Endopeptidases; Atrial Natriuretic Factor; Heart
PubMed: 38942727
DOI: 10.14814/phy2.16105 -
Ophthalmology. Retina Jun 2024To demonstrate the therapeutic similarity of CT-P42 compared to reference aflibercept (Eylea®) in adult patients with diabetic macular edema (DME).
OBJECTIVE
To demonstrate the therapeutic similarity of CT-P42 compared to reference aflibercept (Eylea®) in adult patients with diabetic macular edema (DME).
DESIGN
Randomized, active-controlled, double-masked, Phase III clinical trial PARTICIPANTS: Patients with a diagnosis of either type 1 or 2 diabetes mellitus (DM) with DME involving the center of the macula.
METHODS
Patients were randomized (1:1) to receive either CT-P42 or reference aflibercept (2 mg/0.05 mL) by intravitreal injection every 4 weeks (5 doses) then every 8 weeks (4 doses) in the main study period. Results up to Week 24 are reported herein.
MAIN OUTCOME MEASURES
The primary endpoint was mean change from baseline at Week 8 in best corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Equivalence between CT-P42 and reference aflibercept was to be concluded if the two-sided 95% confidence interval (CI) (global assumptions) and two-sided 90% CI (US Food and Drug Administration [FDA] assumptions) for the treatment difference fell entirely within the equivalence margin of ±3 letters, as assessed in the full analysis set.
RESULTS
Overall, 348 patients were randomized (CT-P42: 173; reference aflibercept: 175). BCVA improved from baseline to Week 8 in both groups, with a least squares mean (standard error) improvement of 9.43 (0.798) and 8.85 (0.775) letters in the CT-P42 and reference aflibercept groups, respectively. The estimated between-group treatment difference was 0.58 letters, with the CIs within the pre-defined equivalence margin of ±3 letters (95% CI -0.73, 1.88 [global]; 90% CI -0.52, 1.67 [FDA]). Through Week 24, other efficacy results for the two groups, in terms of change in BCVA and retinal central subfield thickness, as well as ETDRS Diabetic Retinopathy Severity Scale score, supported therapeutic similarity. Pharmacokinetics, usability, safety (including the proportions of patients experiencing at least one treatment-emergent adverse event [CT-P42: 50.3%; reference aflibercept: 53.7%]), and immunogenicity were also comparable between groups.
CONCLUSIONS
This study in patients with DME demonstrated equivalence between CT-P42 and reference aflibercept (2 mg/0.05 mL) in terms of efficacy, with similar pharmacokinetic, usability, safety, and immunogenicity profiles.
PubMed: 38942386
DOI: 10.1016/j.oret.2024.06.013 -
The American Journal of the Medical... Jun 2024Idiopathic edema (IE) is a disease that occurs predominantly in women. It is characterized by increasing weight gain of > 1.4 kg from morning to night, increasing edema,... (Review)
Review
Idiopathic edema (IE) is a disease that occurs predominantly in women. It is characterized by increasing weight gain of > 1.4 kg from morning to night, increasing edema, increasing truncal and abdominal girth with bloating when assuming an upright position and nocturia that is unrelated to menses. There is an increase in morbidity but not mortality. Increased capillary membrane leakage appears to be the underlying pathophysiologic abnormality that explains the myriad of clinical presentations. We present 2 cases of life-threatening complications of IE that resulted in seizures related to acute hyponatremia in one and extreme postural dizziness and fainting induced by postural hypotension in the other. The first patient was successfully treated with salt restriction, timely use of furosemide and limitation of water intake; the other was successfully treated by use of support hose. Treatment of these patients required a fundamental understanding of the intricate pathophysiological consequences of a leaky capillary membrane, an understanding of Starling forces and detailing the effectiveness of a low salt diet, use of diuretics and limited water intake in one and why support hose would be beneficial in the other patient. Both patients experienced significant physical and emotional benefits that substantially improved quality of life.
PubMed: 38942171
DOI: 10.1016/j.amjms.2024.06.024 -
Survey of Ophthalmology Jun 2024Cystoid macular edema (CME) is a sight-threatening condition often associated with inflammatory and diabetic diseases. Early detection is crucial to prevent irreversible... (Review)
Review
Cystoid macular edema (CME) is a sight-threatening condition often associated with inflammatory and diabetic diseases. Early detection is crucial to prevent irreversible vision loss. Artificial intelligence (AI) has shown promise in automating CME diagnosis through optical coherence tomography (OCT) imaging, but its utility needs critical evaluation. This systematic review assesses the application of AI to diagnosis CME, specifically focusing on disorders like postoperative CME (Irvine Gass syndrome) and retinitis pigmentosa without obvious vasculopathy, using OCT imaging. A comprehensive search was conducted across 6 databases (PubMed, Scopus, Web of Science, Wiley, ScienceDirect, and IEEE) from 2018 to November, 2023. Twenty-three articles met the inclusion criteria and were selected for in-depth analysis. We evaluate AI's role in CME diagnosis and its performance in "detection", "classification" and "segmentation" of OCT retinal images. We found that convolutional neural network (CNN)-based methods consistently outperformed other machine learning techniques, achieving an average accuracy of over 96% in detecting and identifying CME from OCT images. Despite certain limitations such as dataset size and ethical concerns, the synergy between AI and OCT, particularly through CNNs, holds promise for significantly advancing CME diagnostics.
PubMed: 38942125
DOI: 10.1016/j.survophthal.2024.06.005 -
Survey of Ophthalmology Jun 2024Diabetic macular edema (DME), defined as retinal thickening near, or involving the fovea caused by fluid accumulation in the retina, can lead to vision impairment and... (Review)
Review
Diabetic macular edema (DME), defined as retinal thickening near, or involving the fovea caused by fluid accumulation in the retina, can lead to vision impairment and blindness in patients with diabetes. Current knowledge of retina anatomy and function and DME pathophysiology has taken great advantage of the availability of several techniques for visualizing the retina. Combining these techniques in a multimodal imaging approach to DME is recommended to improve diagnosis and to guide treatment decisions. We review the recent literature about the following retinal imaging technologies: optical coherence tomography (OCT), OCT angiography (OCTA), wide-field and ultrawide-field techniques applied to fundus photography, fluorescein angiography, and OCTA. The emphasis will be on characteristic DME features identified by these imaging technologies and their potential or established role as diagnostic, prognostic, or predictive biomarkers. The role of artificial intelligence in the assessment and interpretation of retina images is also discussed.
PubMed: 38942124
DOI: 10.1016/j.survophthal.2024.06.006 -
Medicina Intensiva Jun 2024
PubMed: 38942678
DOI: 10.1016/j.medine.2024.06.010 -
Archives of Dermatological Research Jun 2024
Topics: Humans; Crohn Disease; Female; Retrospective Studies; Adult; Vulvar Diseases; Middle Aged; Young Adult
PubMed: 38941029
DOI: 10.1007/s00403-024-03172-0 -
Clinical Transplantation and Research Jun 2024Patients with chronic kidney disease (CKD) who undergo hemodialysis are predisposed to interstitial cerebral edema. Robotic-assisted laparoscopic surgery can increase...
Perioperative optic nerve sheath diameter variations in patients with end-stage renal failure undergoing robotic-assisted kidney transplant: a prospective observational study.
BACKGROUND
Patients with chronic kidney disease (CKD) who undergo hemodialysis are predisposed to interstitial cerebral edema. Robotic-assisted laparoscopic surgery can increase optic nerve sheath diameter (ONSD) and intracranial pressure. The impact of robotic-assisted kidney transplant (RAKT) on ONSD is complicated by the presence of CKD, the administration of furosemide and mannitol, and the manipulation of hemodynamics. We examined ONSD variations in patients undergoing RAKT over a 1-year period at our institution. Furthermore, we attempted to identify any perioperative hemodynamic factors influencing these changes.
METHODS
This prospective study included 20 patients undergoing RAKT. ONSD, heart rate, central venous pressure, systolic blood pressure, diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured following intubation (T1), after assuming the steep Trendelenburg position (T2), 1 hour after docking (T3), upon reperfusion (T4), after transition to the supine position (T5), and 3 hours postextubation (T6). Repeated measures analysis of variance with post hoc Bonferroni correction was employed to compare variables at each time point. Pearson correlation analysis was utilized to assess relationships between variables. P-values ≤0.05 were considered to indicate statistical significance.
RESULTS
ONSD (in mm) increased from T1 (3.60±0.44) to T3 (4.06±0.45, P=0.002) and T4 (3.99±0.62, P=0.046), before falling to its lowest value at T6 (3.42±0.64, P=0.002). Pearson correlation analysis revealed significant correlations (P<0.05) between changes in ONSD at T3 and both DBP (r=0.637) and MAP (r=0.522).
CONCLUSIONS
During RAKT with open ureteric anastomosis, ONSD initially increased, then decreased following reperfusion. DBP and MAP displayed positive correlations with ONSD changes at T3.
PubMed: 38940687
DOI: 10.4285/ctr.24.0007 -
Cancer Biology & Medicine Jun 2024Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in... (Review)
Review
Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer treatments, exacerbation of tumor hypoxia, decreased effective drug concentrations within tumors, and immune-related mechanisms. Antiangiogenic therapy can counteract these breast cancer resistance factors by promoting tumor vascular normalization. The combination of antiangiogenic therapy with chemotherapy, targeted therapy, or immunotherapy has emerged as a promising approach for overcoming drug resistance in breast cancer. This review examines the mechanisms associated with angiogenesis and the interactions among tumor angiogenesis, the hypoxic tumor microenvironment, drug distribution, and immune mechanisms in breast cancer. Furthermore, this review provides a comprehensive summary of specific antiangiogenic drugs, and relevant studies assessing the reversal of drug resistance in breast cancer. The potential mechanisms underlying these interventions are discussed, and prospects for the clinical application of antiangiogenic therapy to overcome breast cancer treatment resistance are highlighted.
PubMed: 38940663
DOI: 10.20892/j.issn.2095-3941.2023.0515 -
Neurosurgery Jun 2024Pleomorphic xanthoastrocytoma (PXA) is a rare low-grade glial tumor primarily affecting young individuals. Surgery is the primary treatment option; however, managing...
BACKGROUND AND OBJECTIVES
Pleomorphic xanthoastrocytoma (PXA) is a rare low-grade glial tumor primarily affecting young individuals. Surgery is the primary treatment option; however, managing residual/recurrent tumors remains uncertain. This international multi-institutional study retrospectively assessed the use of stereotactic radiosurgery (SRS) for PXA.
METHODS
A total of 36 PXA patients (53 tumors) treated at 11 institutions between 1996 and 2023 were analyzed. Data included demographics, clinical variables, SRS parameters, tumor control, and clinical outcomes. Kaplan-Meier estimates summarized the local control (LC), progression-free survival, and overall survival (OS). Secondary end points addressed adverse radiation effects and the risk of malignant transformation. Cox regression analysis was used.
RESULTS
A total of 38 tumors were grade 2, and 15 tumors were grade 3. Nine patients underwent initial gross total resection, and 10 received adjuvant therapy. The main reason for SRS was residual tumors (41.5%). The median follow-up was 34 months (range, 2-324 months). LC was achieved in 77.4% of tumors, with 6-month, 1-year, and 2-year LC estimates at 86.7%, 82.3%, and 77.8%, respectively. Younger age at SRS (hazard ratios [HR] 3.164), absence of peritumoral edema (HR 4.685), and higher marginal dose (HR 6.190) were significantly associated with better LC. OS estimates at 1, 2, and 5 years were 86%, 74%, and 49.3%, respectively, with a median OS of 44 months. Four patients died due to disease progression. Radiological adverse radiation effects included edema (n = 8) and hemorrhagic change (n = 1). One grade 3 PXA transformed into glioblastoma 13 months after SRS.
CONCLUSION
SRS offers promising outcomes for PXA management, providing effective LC, reasonable progression-free survival, and minimal adverse events.
PubMed: 38940575
DOI: 10.1227/neu.0000000000003083