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Journal of Obstetrics and Gynaecology... Jun 2024This prospective single-arm study was conducted to understand the expulsion rate of the gestational sac in the management of early pregnancy loss (EPL).
BACKGROUND
This prospective single-arm study was conducted to understand the expulsion rate of the gestational sac in the management of early pregnancy loss (EPL).
METHODS
We recruited 441 participants; 188 met eligibility criteria. Participants were 18 years of age and older who experienced a confirmed early pregnancy loss (<12 weeks gestational age) defined by an intrauterine pregnancy with a non-viable embryonic or anembryonic gestational sac with no fetal heart activity. Participants were given 200 mg of mifepristone pretreatment orally followed by two doses of misoprostol 800 mcg vaginally after 24 and 48 hours. Participants were seen in follow-up on day 14 to confirm the absence of a gestational sac, classified as treatment success. For failed treatment (defined by retained gestational sac), we offered expectant management or a third dose of misoprostol and/or dilatation and curettage (D & C). We followed all participants for 30 days. We collected data on overtreatment for retained products of conception and hospital admissions for adverse events.
RESULTS
181 participants followed the protocol, and 169 (93.3%) participants had a complete expulsion of the gestational sac by the second visit (day 14). Twelve (6.6%) failed the treatment and one had an adverse event of heavy vaginal bleeding requiring D & C. Despite the expulsion of the gestational sac, 29 cases (17.1%) at subsequent follow-up were diagnosed as retained products of conception based on ultrasound assessment of thickened endometrium.
CONCLUSION
Pretreatment with mifepristone followed by 2 doses of misoprostol with a 14-day follow-up resulted in a high expulsion rate and is a safe management option for EPL.
PubMed: 38950878
DOI: 10.1016/j.jogc.2024.102604 -
Thrombosis and Haemostasis Jul 2024Hereditary aortic diseases (hADs) increase the risk of aortic dissections and ruptures. Recently, we have established an objective approach to measure the rupture...
OBJECTIVE
Hereditary aortic diseases (hADs) increase the risk of aortic dissections and ruptures. Recently, we have established an objective approach to measure the rupture force of the murine aorta, thereby explaining the outcomes of clinical studies and assessing the added value of approved drugs in vascular Ehlers-Danlos syndrome (vEDS). Here, we applied our approach to six additional mouse hAD models.
MATERIAL AND METHODS
We used two mouse models ( and ) of Marfan syndrome (MFS) as well as one smooth-muscle-cell-specific knockout (SMKO) of and three CRISPR/Cas9-engineered knock-in models (, , and ). One of the two MFS models was subjected to 4-week-long losartan treatment. Per mouse, three rings of the thoracic aorta were prepared, mounted on a tissue puller, and uniaxially stretched until rupture.
RESULTS
The aortic rupture force of the SMKO and both MFS models was significantly lower compared with wild-type mice but in both MFS models higher than in mice modeling vEDS. In contrast, the , , and knock-in models presented no impaired aortic integrity. As expected, losartan treatment reduced aneurysm formation but surprisingly had no impact on the aortic rupture force of our MFS mice.
CONCLUSION
Our read-out system can characterize the aortic biomechanical integrity of mice modeling not only vEDS but also related hADs, allowing the aortic-rupture-force-focused comparison of mouse models. Furthermore, aneurysm progression alone may not be a sufficient read-out for aortic rupture, as antihypertensive drugs reducing aortic dilatation might not strengthen the weakened aortic wall. Our results may enable identification of improved medical therapies of hADs.
PubMed: 38950604
DOI: 10.1055/s-0044-1787957 -
The Journal of Clinical Investigation Jun 2024Research advances over the past 30 years have confirmed a critical role for genetics in the etiology of dilated cardiomyopathies (DCMs). However, full knowledge of the...
Research advances over the past 30 years have confirmed a critical role for genetics in the etiology of dilated cardiomyopathies (DCMs). However, full knowledge of the genetic architecture of DCM remains incomplete. We identified candidate DCM causal gene, C10orf71, in a large family with 8 patients with DCM by whole-exome sequencing. Four loss-of-function variants of C10orf71 were subsequently identified in an additional group of492 patients with sporadic DCM from 2 independent cohorts. C10orf71 was found to be an intrinsically disordered protein specifically expressed in cardiomyocytes. C10orf71-KO mice had abnormal heart morphogenesis during embryonic development and cardiac dysfunction as adults with altered expression and splicing of contractile cardiac genes. C10orf71-null cardiomyocytes exhibited impaired contractile function with unaffected sarcomere structure. Cardiomyocytes and heart organoids derived from human induced pluripotent stem cells with C10orf71 frameshift variants also had contractile defects with normal electrophysiological activity. A rescue study using a cardiac myosin activator, omecamtiv mecarbil, restored contractile function in C10orf71-KO mice. These data support C10orf71 as a causal gene for DCM by contributing to the contractile function of cardiomyocytes. Mutation-specific pathophysiology may suggest therapeutic targets and more individualized therapy.
Topics: Humans; Animals; Cardiomyopathy, Dilated; Mice; Myocytes, Cardiac; Mice, Knockout; Frameshift Mutation; Organoids; Male; Female; Myocardial Contraction; Adult; Disease Models, Animal
PubMed: 38950288
DOI: 10.1172/JCI177172 -
ASAIO Journal (American Society For... Jul 2024We report the largest pediatric multicenter experience with Impella pump use and peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support....
We report the largest pediatric multicenter experience with Impella pump use and peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. Utilizing the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) collaborative database, we conducted a retrospective, multicenter study of all patients with cardiogenic shock requiring VA-ECMO support with subsequent Impella implant between October 2014 and December 2021. The primary outcome was defined as death while on Impella support. Secondary outcomes were recovery, transplantation, and transition to durable ventricular assist device (VAD) at the time of Impella explantation. Adverse events were defined according to the ACTION registry criteria. Twenty subjects were supported with Impella; Impella 2.5 (n = 3), CP (n = 12), 5.0/5.5 (n = 5). The median Interquartile range (IQR) age, weight, and body surface area at implantation were 15.6 years (IQR = 13.9-17.2), 65.7 kg (IQR = 53.1-80.7), and 1.74 m2 (IQR = 1.58-1.98). Primary cardiac diagnoses were dilated cardiomyopathy/myocarditis in nine (45%), congenital heart disease in four (20%), graft failure/rejection in four (20%), and three (15%) others. Most common adverse events included hemolysis (50%) and bleeding (20%). There were two deaths (10%) in the cohort. Nine patients (45%) were explanted for recovery, eight (40%) were transitioned to a durable VAD, and one (5%) underwent heart transplantation. Impella percutaneous pump support should be considered in the older pediatric population supported with peripheral VA-ECMO, as a means of left heart decompression, and a strategy to come off ECMO to achieve endpoints of myocardial recovery, transition to a durable VAD, or transplantation.
Topics: Humans; Extracorporeal Membrane Oxygenation; Heart-Assist Devices; Retrospective Studies; Male; Female; Adolescent; Shock, Cardiogenic; Child; Child, Preschool; Treatment Outcome
PubMed: 38949774
DOI: 10.1097/MAT.0000000000002150 -
The Journal of Craniofacial Surgery Jul 2024Skin flap necrosis remains a significant challenge in reconstructive surgery, predominantly due to insufficient blood supply. Traditional methods like the surgical delay...
BACKGROUND
Skin flap necrosis remains a significant challenge in reconstructive surgery, predominantly due to insufficient blood supply. Traditional methods like the surgical delay procedure, while effective, are invasive and associated with considerable patient discomfort and health care costs. This study explores the efficacy of Carbon Dioxide Fractional Laser (CDFL) treatment as a novel, less invasive alternative to enhance skin flap survival.
METHODS
Twenty-nine adult male Sprague-Dawley rats were divided into 2 groups: a CDFL treatment group (n=14) and a control group (n=15). The CDFL group received laser pretreatment 1 week before flap surgery, whereas the control group underwent flap surgery without pretreatment. Flap survival was assessed 7 days postsurgery using indocyanine green fluorescence angiography. In addition, histological analysis was conducted to evaluate tissue integrity, capillary density, and VEGF expression.
RESULTS
The CDFL-treated flaps showed significantly increased survival areas compared with controls (P<0.01). Histological evaluation revealed enhanced capillary dilation and increased VEGF expression in the CDFL group (P<0.05). Although capillary density was higher in the CDFL group, it did not reach statistical significance (P=0.052).
CONCLUSION
CDFL pretreatment significantly improves skin flap survival in rats, suggesting potential as a minimally invasive alternative to traditional surgical delay techniques. This approach could offer substantial benefits in reconstructive surgery, reducing patient morbidity and associated costs. Further studies are warranted to confirm these findings in clinical settings.
PubMed: 38949251
DOI: 10.1097/SCS.0000000000010455 -
The Journal of Clinical Investigation Jul 2024Mechanical stress from cardiomyocyte contraction causes misfolded sarcomeric protein replacement. Sarcomeric maintenance utilizes localized pools of mRNAs and...
Mechanical stress from cardiomyocyte contraction causes misfolded sarcomeric protein replacement. Sarcomeric maintenance utilizes localized pools of mRNAs and translation machinery, yet the importance of localized translation remains unclear. In this issue of the JCI, Haddad et al. identify the Z-line as a critical site for localized translation of sarcomeric proteins, mediated by ribosomal protein SA (RPSA). RPSA localized ribosomes at Z-lines and was trafficked via microtubules. Cardiomyocyte-specific loss of RPSA in mice resulted in mislocalized protein translation and caused structural dilation from myocyte atrophy. These findings demonstrate the necessity of RPSA-dependent spatially localized translation for sarcomere maintenance and cardiac structure and function.
Topics: Sarcomeres; Animals; Ribosomal Proteins; Mice; Protein Biosynthesis; Myocytes, Cardiac; Ribosomes; Humans; Microtubules
PubMed: 38949021
DOI: 10.1172/JCI181996 -
Journal of Geriatric Cardiology : JGC May 2024
PubMed: 38948895
DOI: 10.26599/1671-5411.2024.05.005 -
BioRxiv : the Preprint Server For... Jun 2024Kidney tubular cells are submitted to two distinct mechanical forces generated by the urine flow: shear stress and hydrostatic pressure. In addition, the mechanical...
Kidney tubular cells are submitted to two distinct mechanical forces generated by the urine flow: shear stress and hydrostatic pressure. In addition, the mechanical properties of the surrounding extracellular matrix modulate tubule deformation under constraints. These mechanical factors likely play a role in the pathophysiology of kidney diseases as exemplified by autosomal dominant polycystic kidney disease, in which pressure, flow and matrix stiffness have been proposed to modulate the cystic dilation of tubules with mutations. The lack of systems recapitulating the mechanical environment of kidney tubules impedes our ability to dissect the role of these mechanical factors. Here we describe a perfused kidney-on-chip with tunable extracellular matrix mechanical properties and hydrodynamic constraints, that allows a decoupling of shear stress and flow. We used this system to dissect how these mechanical cues affect tubule dilation. Our results show two distinct mechanisms leading to tubular dilation. For PCT cells (proximal tubule), overproliferation mechanically leads to tubular dilation, regardless of the mechanical context. For mIMCD-3 cells (collecting duct), tube dilation is associated with a squamous cell morphology but not with overproliferation and is highly sensitive to extracellular matrix properties and hydrodynamic constraints. Surprisingly, flow alone suppressed mIMCD-3 tubule dilation observed in static conditions, while the addition of luminal pressure restored it. Our model emulating nephron geometrical and mechanical organization sheds light on the roles of mechanical constraints in ADPKD and demonstrates the importance of controlling intraluminal pressure in kidney tubule models.
PubMed: 38948811
DOI: 10.1101/2024.06.18.599137 -
BioRxiv : the Preprint Server For... Jun 2024A ketogenic diet (KD) is a very low-carbohydrate, very high-fat diet proposed to treat obesity and type 2 diabetes. While KD grows in popularity, its effects on...
A ketogenic diet (KD) is a very low-carbohydrate, very high-fat diet proposed to treat obesity and type 2 diabetes. While KD grows in popularity, its effects on metabolic health are understudied. Here we show that, in male and female mice, while KD protects against weight gain and induces weight loss, over long-term, mice develop hyperlipidemia, hepatic steatosis, and severe glucose intolerance. Unlike high fat diet-fed mice, KD mice are not insulin resistant and have low levels of insulin. Hyperglycemic clamp and GSIS revealed cell-autonomous and whole-body impairments in insulin secretion. Major ER/Golgi stress and disrupted ER-Golgi protein trafficking was indicated by transcriptomic profiling of KD islets and confirmed by electron micrographs showing a dilated Golgi network likely responsible for impaired insulin granule trafficking and secretion. Overall, our results suggest long-term KD leads to multiple aberrations of metabolic parameters that caution its systematic use as a health promoting dietary intervention.
PubMed: 38948738
DOI: 10.1101/2024.06.14.599117 -
Journal of Family Medicine and Primary... May 2024Flow-mediated dilation (FMD) of the brachial artery is an ultrasonography test that assesses the endothelial response to reactive hyperemia. The aim of this study was to...
INTRODUCTION
Flow-mediated dilation (FMD) of the brachial artery is an ultrasonography test that assesses the endothelial response to reactive hyperemia. The aim of this study was to assess the changes in FMD in preeclamptic pregnant patients and compare them with normotensive pregnant females.
METHODS
An analytical cross-sectional comparative study was conducted in the Department of Obstetrics and Gynaecology at King George's Medical University (KGMU) after obtaining ethical approval. A total of 110 normotensive and 100 preeclamptic patients were recruited for the study. Using a Toshiba Ultrasound Machine with a 7-12 MHz probe, the baseline diameter of the brachial artery D1 was measured. Afterward, the cuff of the sphygmomanometer was placed distally on the forearm and it was inflated up to ≥250 mm of Hg pressure and later slowly deflated. At 90 seconds after cuff deflation, the mean of three measurements of vessel caliber (D2) was obtained. The FMD% was obtained by the following equation: FMD (%) = [(D2 - D1)/D1] ×100, where D1 = basal diameter and D2 = post-occlusion diameter. All patients were followed till delivery for maternofetal outcome.
RESULTS
FMD% was significantly lower in the preeclampsia group, and it went on decreasing with increasing severity of preeclampsia. At the cutoff of 9.4 for FMD%, its sensitivity for the prediction of preeclampsia was 65.3%, specificity was 89.3%, positive predictive value (PPV) was 94%, and negative predictive value (NPV) was 50%.
DISCUSSION
FMD is a noninvasive test, and it gets decreased before clinical signs of preeclampsia, so it can be used as a predictor of preeclampsia.
PubMed: 38948563
DOI: 10.4103/jfmpc.jfmpc_773_23