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Advanced Materials (Deerfield Beach,... Jun 2024Abdominal aortic aneurysm (AAA) is a highly lethal cardiovascular disease that currently lacks effective pharmacological treatment given the complex pathophysiology of...
Abdominal aortic aneurysm (AAA) is a highly lethal cardiovascular disease that currently lacks effective pharmacological treatment given the complex pathophysiology of the disease. Here, single-cell RNA-sequencing data from patients with AAA and a mouse model are analyzed, which reveals pivotal pathological changes, including the M1-like polarization of macrophages and the loss of contractile function in smooth muscle cells (SMCs). Both cell types express the integrin αvβ3, allowing for their dual targeting with a single rationally designed molecule. To this end, a biocompatible nanodrug, which is termed EVMS@R-HNC, that consists of the multifunctional drug everolimus (EVMS) encapsulated by the hepatitis B virus core protein modifies to contain the RGD sequence to specifically bind to integrin αvβ3 is designed. Both in vitro and in vivo results show that EVMS@R-HNC can target macrophages as well as SMCs. Upon binding of the nanodrug, the EVMS is released intracellularly where it exhibits multiple functions, including inhibiting M1 macrophage polarization, thereby suppressing the self-propagating inflammatory cascade and immune microenvironment imbalance, while preserving the normal contractile function of SMCs. Collectively, these results suggest that EVMS@R-HNC presents a highly promising therapeutic approach for the management of AAA.
PubMed: 38923441
DOI: 10.1002/adma.202405761 -
International Urology and Nephrology Jun 2024This study evaluates the effectiveness of the Estimation of Physiologic Ability and Surgical Stress (E-PASS) scoring system in predicting postoperative complications...
INTRODUCTION
This study evaluates the effectiveness of the Estimation of Physiologic Ability and Surgical Stress (E-PASS) scoring system in predicting postoperative complications following radical cystectomy (RC).
MATERIALS AND METHODS
In this single-center retrospective study, we analyzed data from patients who underwent open RC for muscle-invasive bladder cancer by a single surgeon between 2008 and 2023. Cases involving cystectomy for non-urothelial carcinoma or urinary diversion other than ileal conduit were excluded. We recorded patient demographics, body mass index (BMI), history of abdominal/retroperitoneal surgery, ASA score, performance status (PS), and pre-existing conditions, such as hypertension (HT), coronary artery disease (CAD), diabetes mellitus (DM), and chronic kidney disease (CKD). Intraoperative data included surgery duration, blood loss, and need for blood transfusion. Post-operative complications were classified using the Clavien-Dindo system. E-PASS score was calculated using the Preoperative Risk Score (PRS), Surgical Stress Score (SSS), and Comprehensive Risk Score (CRS).
RESULTS
The study included 252 patients. Patients who experienced postoperative complications had higher age, BMI, prior surgical history, ASA score, PS, and rates of CAD, HT, DM, and CKD compared to those who did not. Surgery duration, blood loss, blood transfusion requirement, and E-PASS scores (PRS, SSS, CRS) were also higher in this group. The ROC curve for CRS revealed a predictive cutoff of 0.4911 (AUC = 0.905, p < 0.001). Independent risk factors for postoperative complications included high BMI (p = 0.031), longer surgery duration (p < 0.001), HT (p = 0.042), CKD (p = 0.017), and CRS > 0.4911 (p < 0.001).
CONCLUSION
E-PASS system effectively predicts postoperative complications in RC patients.
PubMed: 38918284
DOI: 10.1007/s11255-024-04134-1 -
The Journal of Clinical Investigation Jun 2024Aortic aneurysm is a life-threatening disease with limited interventions, closely related to vascular smooth muscle cells (VSMCs) phenotypic switching. SLC44A2, a member...
Aortic aneurysm is a life-threatening disease with limited interventions, closely related to vascular smooth muscle cells (VSMCs) phenotypic switching. SLC44A2, a member of solute carrier series 44 (SLC44) family, remains under-characterized in the context of cardiovascular diseases. Venn diagram analysis based on microarray and single-cell RNA sequencing identified SLC44A2 as a major regulator of VSMCs phenotypic switching in aortic aneurysm. Screening for Slc44a2 amongst aortic cell lineages demonstrated its predominant location in VSMCs. Elevated levels of SLC44A2 were evidenced in the aorta of both abdominal aortic aneurysm patients and angiotensin II (Ang II)-infused Apoe-/- mice. In vitro, SLC44A2 silencing promoted VSMCs towards a synthetic phenotype, while SLC44A2 overexpression attenuated VSMCs phenotypic switching. VSMCs-specific SLC44A2 knockout mice were more susceptible to aortic aneurysm under Ang II infusion, while SLC44A2 overexpression showed protective effects. Mechanistically, SLC44A2 interaction with NRP1 and ITGB3 activates TGF-β/SMAD signaling, thereby promoting contractile genes expression. Elevated SLC44A2 in aortic aneurysm is associated with upregulated runt-related transcription factor 1 (RUNX1). Furthermore, low dose of lenalidomide (LEN) suppressed aortic aneurysm progression by enhancing SLC44A2 expression. These findings reveal SLC44A2/NRP1/ITGB3 complex is a major regulator of VSMCs phenotypic switching and provide potential therapeutic approach (LEN) for aortic aneurysm treatment.
PubMed: 38916960
DOI: 10.1172/JCI173690 -
Annals of Translational Medicine Jun 2024The abdominal donor site is the most common flap used for breast reconstruction, with flap necrosis a feared complication. The technique of surgical 'delay' involves the... (Review)
Review
BACKGROUND
The abdominal donor site is the most common flap used for breast reconstruction, with flap necrosis a feared complication. The technique of surgical 'delay' involves the inducing of relative ischemia to promote neovascularisation, amongst other metabolic adaptations, and has been used to augment flap vascularity and reduce this complication. There is significant variability in the manner in which flap surgery and surgical delay may be performed, such as the vessels ligated, the presence and degree of flap elevation, and the decision to harvest muscle with the flap, amongst other factors. A formal review of techniques, however, has not yet been performed, and there is no consensus as to the optimal technique for surgical delay.
METHODS
A scoping review of the current literature was undertaken to determine the optimal surgical delay technique in abdominal-based flap surgery. A literature search was conducted across PubMed, Embase, Cochrane, and Medline databases. Data regarding the type of flap surgery, delay techniques, and corresponding clinical outcomes was collected and categorised by technique type.
RESULTS
Nine studies met the inclusion criteria and were included for review. Levels of evidence and rates of complications were compared. The range of surgical delay techniques reported in the literature was described. Surgical delay was found to reduce overall complication rates, and the available data suggests it may be particularly beneficial in high-risk patients.
CONCLUSIONS
The current data support delay as a viable method for reducing rates of complications. Further studies and data are required to compare surgical delay techniques and determine the benefit delay may pose to patients with risk factors.
PubMed: 38911569
DOI: 10.21037/atm-23-306 -
Journal of Maxillofacial and Oral... Jun 2024A prospective study was conducted to find out an effective alternative in the form of non-vascularized abdominal dermal fat graft (ADFG) and to compare its efficacy with...
INTRODUCTION
A prospective study was conducted to find out an effective alternative in the form of non-vascularized abdominal dermal fat graft (ADFG) and to compare its efficacy with the vascularised nasolabial flap (NLF) for the treatment of oral submucous fibrosis (OSMF).
METHOD
Comparative study comprising of 30 patients with Grade 3 and 4A OSMF, randomly divided into 2 groups: Group A (ADFG) and Group B (NLF). They were evaluated for mouth opening (MO), graft uptake, time taken for mucosalization, pain, intercommissure distance (ICD), scar, duration of surgery (DOS), patient satisfaction and thickness of masseter muscle on ultrasonography.
FINDINGS
At 6 months, MO improved by 22.4 and 36.2 mm in Group A and Group B, respectively. There was statistically significant difference ( < 0.05) seen for the values between the groups for all the parameters except for ICD and VAS score, which was statistically insignificant ( > 0.05). Intraoral hair growth, facial scar, orocutaneous fistula and commissure tear was seen in Group B. Complete necrosis of graft followed by recurrence was seen in three cases in Group A.
CONCLUSION
NLF holds better as compared to ADFG in the management of OSMF. However, the cornerstone of success remains habit cessation and aggressive physiotherapy. The limitations of the study are small sample size and short duration of follow-up.
PubMed: 38911420
DOI: 10.1007/s12663-022-01741-2 -
Drug Design, Development and Therapy 2024We aimed to evaluate the effect of intravenous esketamine combined with dexmedetomidine as supplemental analgesia in reducing intraoperative visceral pain... (Randomized Controlled Trial)
Randomized Controlled Trial
Esketamine Combined with Dexmedetomidine to reduce Visceral Pain During elective Cesarean Section Under Combined Spinal-Epidural Anesthesia: A double-Blind Randomized Controlled Study.
PURPOSE
We aimed to evaluate the effect of intravenous esketamine combined with dexmedetomidine as supplemental analgesia in reducing intraoperative visceral pain during elective cesarean section under combined spinal-epidural anesthesia (CSEA).
PATIENTS AND METHODS
A total of 269 parturients scheduled for elective cesarean section under CSEA between May 2023 and August 2023 were assessed. The parturients were randomly allocated to receiving either intravenous infusion of 0.3-mg/kg esketamine combined with 0.5-μg/kg dexmedetomidine (group ED, n=76), 0.5-μg/kg dexmedetomidine (group D, n=76), or normal saline (group C, n=76) after umbilical cord clamping. The primary outcome was intraoperative visceral pain. Secondary outcomes included the visual analog scale (VAS) score for pain evaluation and other intraoperative complications.
RESULTS
The incidence of visceral pain was lower in group ED [9 (12.7%)] than in group D [32 (43.8%)] and group C [36 (48.6%), <0.0001]. The VAS score was also lower in group ED when exploring abdominal cavity [0 (0), <0.0001] and suturing the muscle layer [0 (0), =0.036]. The mean arterial pressure was higher in group D [83 (9) mmHg] and group ED [81 (11) mmHg] than in group C [75 (10) mmHg, <0.0001] after solution infusion. The heart rate after infusion of the solution was lower in group D [80 (12) bpm] than in group C [86 (14) bpm] and group ED [85 (12) bpm, = 0.016]. The incidence of transient neurologic or mental symptoms was higher in group ED compared to group C and group D (76.1% vs 18.9% vs 23.3%, <0.0001).
CONCLUSION
During cesarean section, 0.3-mg/kg esketamine combined with 0.5-μg/kg dexmedetomidine can alleviate visceral traction pain and provide stable hemodynamics. Parturients receiving this regimen may experience transient neurologic or mental symptoms that can spontaneously resolve at the end of the surgery.
Topics: Humans; Dexmedetomidine; Ketamine; Double-Blind Method; Cesarean Section; Female; Adult; Visceral Pain; Anesthesia, Spinal; Pregnancy; Anesthesia, Epidural; Drug Therapy, Combination; Elective Surgical Procedures
PubMed: 38911034
DOI: 10.2147/DDDT.S460924 -
Poultry Science Jun 2024As an anti-myogenic factor, the myostatin (MSTN) gene was mainly considered as a genetic marker to improve meat production. Moreover, an additional effect of the MSTN...
As an anti-myogenic factor, the myostatin (MSTN) gene was mainly considered as a genetic marker to improve meat production. Moreover, an additional effect of the MSTN mutation on reducing fat deposition in various farm animals suggested a potential application of the MSTN gene on regulating fat deposition in poultry species. Although increase in muscle mass resulted from muscle hyperplasia in the MSTN mutant quail, cellular mechanism behind the decrease in fat deposition was not investigated in the quail model. In the current study, to investigate sexual dimorphic association between fat deposition and Mstn mutation in quail, leg and abdominal fat pads from 4-month-old male and female quail were histologically analyzed. Interestingly, abdominal and leg fat pad weights were significantly decreased by the MSTN mutation only in female quail, but not in male quail, showing sexual dimorphism in regulating fat deposition by the MSTN mutation in quail. Histological analysis also revealed that fat cell sizes of leg and abdominal fats were significantly reduced only in female groups aligning with the decreased fat pad weights. Sexual dimorphic effect of the MSTN mutation on fat cell hypotrophy and reduced fat pad weights in quail provided an important scientific finding to be considered on the usage of the MSTN gene as a genetic marker to reduce fat deposition in poultry species.
PubMed: 38909511
DOI: 10.1016/j.psj.2024.103951 -
Naunyn-Schmiedeberg's Archives of... Jun 2024Chronic kidney disease-mineral and bone metabolism disorder (CKD-MBD) is a common chronic kidney disease (CKD)-associated complication that increases the risk of...
Chronic kidney disease-mineral and bone metabolism disorder (CKD-MBD) is a common chronic kidney disease (CKD)-associated complication that increases the risk of metabolic bone diseases, fractures, osteoblastic trans-differentiation of vascular smooth muscle cells, and cardiovascular events. SD rats were randomised into five groups with six rats per group: sham, CKD, CKD + advanced glycosylation end products (AGEs), CKD + Quercetin, and CKD + AGEs + Quercetin. The protective effects of AGEs and quercetin on SD rats were assessed by renal function, renal pathology, bone metabolism, osteoblastic trans-differentiation of vascular smooth muscle cells, and the receptor for AGE (RAGE) expression. Compared with the control group, rats in the CKD and CKD + AGEs groups had significantly lower body weight, higher serum AGEs levels, impaired renal function, increased levels of oxidative stress in the kidney and bone marrow tissues, lower femoral bone mineral density (BMD), callus mineralised volume fraction (mineralised bone volume/total volume), abnormal serum bone metabolism levels, and increased renal tissue, bone tissue, and abdominal aorta RAGE expression levels, and the RAGE downstream NF-κB signalling pathway was upregulated. Quercetin significantly improved renal dysfunction, attenuated serum AGE levels, reduced oxidative stress levels in the kidney and bone marrow tissues, and downregulated RAGE expression in the kidney, bone, and abdominal aorta and the RAGE downstream NF-κB signalling pathway in rats with CKD. AGEs are involved in the pathogenesis of CKD-MBD by promoting osteoblastic trans-differentiation of vascular smooth muscle cells and abnormal bone metabolism. Quercetin plays a role in the prevention and treatment of CKD-MBD by reducing the production of AGEs.
PubMed: 38907848
DOI: 10.1007/s00210-024-03217-1 -
Biomaterials Jun 2024Biohybrid tissue-engineered vascular grafts (TEVGs) promise long-term durability due to their ability to adapt to hosts' needs. However, the latter calls for sensitive...
Biohybrid tissue-engineered vascular grafts (TEVGs) promise long-term durability due to their ability to adapt to hosts' needs. However, the latter calls for sensitive non-invasive imaging approaches to longitudinally monitor their functionality, integrity, and positioning. Here, we present an imaging approach comprising the labeling of non-degradable and degradable TEVGs' components for their in vitro and in vivo monitoring by hybrid H/F MRI. TEVGs (inner diameter 1.5 mm) consisted of biodegradable poly(lactic-co-glycolic acid) (PLGA) fibers passively incorporating superparamagnetic iron oxide nanoparticles (SPIONs), non-degradable polyvinylidene fluoride scaffolds labeled with highly fluorinated thermoplastic polyurethane (F-TPU) fibers, a smooth muscle cells containing fibrin blend, and endothelial cells. H/F MRI of TEVGs in bioreactors, and after subcutaneous and infrarenal implantation in rats, revealed that PLGA degradation could be faithfully monitored by the decreasing SPIONs signal. The F signal of F-TPU remained constant over weeks. PLGA degradation was compensated by cells' collagen and α-smooth-muscle-actin deposition. Interestingly, only TEVGs implanted on the abdominal aorta contained elastin. XTT and histology proved that our imaging markers did not influence extracellular matrix deposition and host immune reaction. This concept of non-invasive longitudinal assessment of cardiovascular implants using H/F MRI might be applicable to various biohybrid tissue-engineered implants, facilitating their clinical translation.
PubMed: 38906013
DOI: 10.1016/j.biomaterials.2024.122669 -
Journal of Ultrasound Jun 2024Abdominal pain is a common symptom with a spectrum of causes. Anterior cutaneous nerve entrapment syndrome (ACNES) is a commonly overlooked and underdiagnosed cause for...
Abdominal pain is a common symptom with a spectrum of causes. Anterior cutaneous nerve entrapment syndrome (ACNES) is a commonly overlooked and underdiagnosed cause for anterior abdominal pain. Among the patients of chronic abdominal wall pain, the incidence of ACNES is 10-30% and the most common cause is nerve entrapment at the lateral border of the rectus muscle. We describe two cases covering varied location of entrapment, one at the medial border of rectus and another at lateral border explaining the need of ultrasound for successful management of both. This case report illustrates the difficulty of making this diagnosis, utility of ultrasound and a brief review of literature.
PubMed: 38904734
DOI: 10.1007/s40477-024-00881-0