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The optimal target blood pressure for kidney transplant (KT) patients remains unclear. We included 808 KT patients from the KNOW-KT as a discovery set, and 1,294 KT patients from the KOTRY as a validation set. The main exposures were baseline systolic blood pressure (SBP) at 1 year after KT and time-varying SBP. Patients were classified into five groups: SBP

Aim: We validated the prognostic performance of neuron-specific enolase (NSE) according to the recommended values in cardiac arrest (CA) survivors. Methods: We analyzed the data of adult CA survivors who underwent targeted temperature management between January 2014 and December 2020. We measured the NSE level 48 h and 72 h after CA. We performed receiver operating characteristics (ROC) and used the reference value (17 μg/L) and the guidelines-suggested value (60 μg/L) as thresholds. The primary outcome was 6-month neurological outcomes with Cerebral Performance Category (CPC), dichotomized into good (CPC 1 or 2) or poor (CPC 3–5). Results: Of the 513 included patients, 346 (67.4 %) patients had poor neurological outcomes. The area under ROC (AUC) of NSE at 48 h was 0.887 (95 % confidence intervals [CIs], 0.851–0.909) with the Youden index of 35.6 μg/L. A false positive rate (FPR) of

Abstract Background Surgically resected grade 1–2 (G1-2) pancreatic neuroendocrine tumors (PanNETs) exhibit diverse clinical outcomes, highlighting the need for reliable prognostic biomarkers. Our study aimed to develop and validate CT-based radiomics model for predicting postsurgical outcome in patients with G1-2 PanNETs, and to compare its performance with the current clinical staging system. Methods This multicenter retrospective study included patients who underwent dynamic CT and subsequent curative resection for G1–2 PanNETs. A radiomics-based model (R-score) for predicting recurrence-free survival (RFS) was developed from a development set (441 patients from one institution) using least absolute shrinkage and selection operator-Cox regression analysis. A clinical model (C-model) consisting of age and tumor stage according to the 8th American Joint Committee on Cancer staging system was built, and an integrative model combining the C-model and the R-score (CR-model) was developed using multivariable Cox regression analysis. Using an external test set (159 patients from another institution), the models’ performance for predicting RFS and overall survival (OS) was evaluated using Harrell’s C-index. The incremental value of adding the R-score to the C-model was evaluated using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results The median follow-up periods were 68.3 and 59.7 months in the development and test sets, respectively. In the development set, 58 patients (13.2%) experienced recurrence and 35 (7.9%) died. In the test set, tumors recurred in 14 patients (8.8%) and 12 (7.5%) died. In the test set, the R-score had a C-index of 0.716 for RFS and 0.674 for OS. Compared with the C-model, the CR-model showed higher C-index (RFS, 0.734 vs. 0.662, p = 0.012; OS, 0.781 vs. 0.675, p = 0.043). CR-model also showed improved classification (NRI, 0.330, p

Abstract Aims Evidence for the effectiveness of left ventricular (LV) unloading in patients who received venoaterial extracorporeal membrane oxygenation (VA‐ECMO) for acute myocardial infarction (AMI) or non‐AMI induced cardiogenic shock (CS) is limited. The aim of the present study was to compare the effect of LV unloading in AMI‐induced and non‐AMI‐induced CS. Methods and results This is a single‐centre retrospective observational study of patients with CS undergoing VA‐ECMO from January 2011 to March 2019. Patients were classified as AMI‐induced and non‐AMI‐induced CS. The association of LV unloading with 90‐day mortality in both groups was analysed using Cox proportional hazard regression analysis. Results Of the 128 CS patients, 71 (55.5%) patients received VA‐ECMO due to AMI‐induced CS, and the remaining 57 (44.5%) received VA‐ECMO due to non‐AMI‐induced CS. The modality of LV unloading was predominantly with IABP (94.5%). In the AMI‐induced CS group, LV unloading did not reduce 90‐day mortality (adjusted hazard ratio 1.96, 95% confidence interval 0.90–4.27, P = 0.089). However, in the non‐AMI‐induced CS group, LV unloading combined with VA‐ECMO significantly reduced 90‐day mortality (adjusted hazard ratio 0.37, 95% confidence interval 0.14–0.96, P = 0.041; P for interaction = 0.029) as compared with those who received VA‐ECMO alone. Conclusions LV unloading with VA‐ECMO may reduce 90‐day mortality compared with VA‐ECMO alone in patients with non‐AMI‐induced CS, but not in AMI‐induced CS.

Abstract Background Petersen’s hernia, which occurs after Billroth-II (B-II) or Roux-en-Y (REY) anastomosis, can be reduced by defect closure. This study aims to compare the incidence of bowel obstruction above Clavien–Dindo classification grade III due to Petersen’s hernia between the mesenteric fixation method and the conventional methods after laparoscopic or robotic gastrectomy. Methods This study was designed as prospective, single-blind, non-inferiority randomized controlled multicenter trial in Korea. Patients with histologically diagnosed gastric cancer of clinical stages I, II, or III who underwent B-II or REY anastomosis after laparoscopic or robotic gastrectomy are enrolled in this study. Participants who meet the inclusion criteria are randomly assigned to two groups: a CLOSURE group that underwent conventional Petersen’s defect closure method and a MEFIX group that underwent the mesenteric fixation method. The primary endpoint is the number of patients who underwent surgery for bowel obstruction caused by Petersen’s hernia within 3 years after laparoscopic or robotic gastrectomy. Discussion This trial is expected to provide high-level evidence showing that the MEFIX method can quickly and easily close Petersen’s defect without increased postoperative complications compared to the conventional method. Trial registration ClinicalTrials.gov NCT05105360. Registered on November 3, 2021.

Abstract We investigated (1) how nasal septal perforations (NSPs) modify nasal airflow and air-conditioning characteristics and (2) how the modifications of nasal airflow are influenced by the size and location of the NSP. Computed tomography scans of 14 subjects with NSPs were used to generate nasal cavity models. Virtual repair of NSPs was conducted to examine the sole effect of NSPs on airflow. The computational fluid dynamics technique was used to assess geometric and airflow parameters around the NSPs and in the nasopharynx. The net crossover airflow rate, the increased wall shear stress (WSS) and the surface water–vapor flux on the posterior surface of the NSPs were not correlated with the size of the perforation. After the virtual closure of the NSPs, the levels in relative humidity (RH), air temperature (AT) and nasal resistance did not improve significantly both in the choanae and nasopharynx. A geometric parameter associated with turbinate volume, the surface area-to-volume ratio (SAVR), was shown to be an important factor in the determination of the RH and AT, even in the presence of NSPs. The levels of RH and AT in the choanae and nasopharynx were more influenced by SAVR than the size and location of the NSPs.

The ongoing COhort for Childhood Origin of Asthma and allergic diseases (COCOA) study is a prospective birth cohort investigating the origin and natural courses of childhood allergic diseases, including atopic dermatitis, food allergy, allergic rhinitis and asthma, with long-term prognosis. Initiated under the premise that allergic diseases result from a complex interplay of immune development alterations, environmental exposures, and host susceptibility, the COCOA study explores these dynamic interactions during prenatal and postnatal periods, framed within the hygiene and microbial hypotheses alongside the developmental origins of health and disease (DOHaD) hypothesis. The scope of the COCOA study extends to genetic predispositions, indoor and outdoor environmental variables affecting mothers and their offsprings such as outdoor and indoor air pollution, psychological factors, diets, and the microbiomes of skin, gut, and airway. We have embarked on in-depth investigations of diverse risk factors and the pathophysiological underpinnings of allergic diseases. By employing multi-omics approaches—proteomics, transcriptomics, and metabolomics—we gain deeper insights into the distinct pathophysiological processes across various endotypes of childhood allergic diseases, incorporating the exposome using extensive resources within the COCOA study. Integration with large-scale datasets, such as national health insurance records, enhances robustness and mitigates potential limitations inherent to birth cohort studies. As part of global networks focused on childhood allergic diseases, the COCOA study fosters collaborative research across multiple cohorts. The findings from the COCOA study are instrumental in informing precision medicine strategies for childhood allergic diseases, underpinning the establishment of disease trajectories.

Dermal papilla cells (DPCs) are located at the bottom of the hair follicle and play a critical role in hair growth, shape, and cycle. Epidermal growth factor receptor (EGFR) and Wnt/β-catenin signaling pathways are essential in promoting keratinocyte activation as well as hair follicle formation in DPCs. Piperonylic acid is a small molecule that induces EGFR activation in keratinocytes. However, the effects of piperonylic acid on DPCs in regard to the stimulation of hair growth have not been studied. In the present study, piperonylic acid was shown to activate the Wnt/β-catenin signaling pathway in addition to the EGFR signaling pathway in DPCs. Piperonylic acid suppressed DKK1 expression, which presumably promoted the accumulation of β-catenin in the nucleus. In addition, piperonylic acid promoted cyclin D upregulation and cell growth and increased the expression of alkaline phosphatase (ALP), a DPC marker. In a clinical study, the group that applied a formulation containing piperonylic acid had a significantly higher number of hairs per unit area than the placebo group. These results identify piperonylic acid as a promising new candidate for hair loss treatment.

To reveal potent ACE inhibitors, researchers screen various bioactive peptides from several sources, and more attention has been given to aquatic sources. This review summarizes the recent research achievements on marine peptides with ACE-inhibitory action and application. Marine peptides are considered excellent bioactives due to their large structural diversity and unusual bioactivities. The mechanisms by which these marine peptides inhibit ACE include competitive binding to ACEs’ active site, interfering with ACE conformational changes, and avoiding the identification of substrates. The unique 3D attributes of marine peptides confer inhibition advantages toward ACE activity. Because IC50 values of marine peptides’ interaction with ACE are low, structure-based research assumes that the interaction between ACE and peptides increased the therapeutic application. Numerous studies on marine peptides focused on the sustainable extraction of ACE-inhibitory peptides produced from several fish, mollusks, algae, and sponges. Meanwhile, their potential applications and medical benefits are worth investigating and considering. Due to these peptides exhibiting antioxidant, antihypertensive, and even antimicrobial properties simultaneously, their therapeutic potential for cardiovascular disease and other illnesses only increases. In addition, as marine peptides show better pharmacological benefits, they have increased absorption rates and low toxicity and could perhaps be modified for better stability and bioefficacy. Biotechnological advances in peptide synthesis and formulation have greatly facilitated the generation of peptide-based ACE inhibitors from marine sources, which subsequently offer new treatment models. This article gives a complete assessment of the present state of knowledge about marine organism peptides as ACE inhibitors. In addition, it emphasizes the relevance of additional investigation into their mechanisms of action, the optimization of manufacturing processes, and assessment in in vivo, preclinical, and clinical settings, underlining the urgency and value of this study. Using marine peptides for ACE inhibition not only broadens the repertory of bioactive compounds but also shows promise for tackling the global health burden caused by cardiovascular diseases.

Byline: Guoan Li, PhD (Bioengineering Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, gli1@partners.org); Ramprasad Papannagari, MS (Bioengineering Laboratory, Department of Orthopaedic Surgery, Massachusetts [...]

Background: The biomechanical functions of the anterolateral and posteromedial bundles of the posterior cruciate ligament over the range of flexion of the knee joint remain unclear. Hypothesis: The posterior cruciate ligament bundles have minimal length at low flexion angles and maximal length at high flexion angles. Study Design: Descriptive laboratory study. Methods: Seven knees from normal, healthy subjects were scanned with magnetic resonance, and 3-dimensional models of the femur, tibia, and posterior cruciate ligament attachment sites were created. The lines connecting the centroids of the corresponding bundle attachment sites on the femur and tibia represented the anterolateral and posteromedial bundles of the posterior cruciate ligament. Each knee was imaged during weightbearing flexion (from 0° to maximal flexion) using a dual-orthogonal fluoroscopic system. The length, elevation, deviation, and twist of the posterior cruciate ligament bundles were measured as a function of flexion. Results: The lengths of the anterolateral and posteromedial bundles increased with flexion from 0° to 120° and decreased beyond 120° of flexion. The posteromedial bundle had a lower elevation angle than the anterolateral bundle beyond 60° of flexion. The anterolateral bundle had a larger deviation angle than the posteromedial bundle beyond 75° of flexion. The femoral attachment of the posterior cruciate ligament twisted externally with increasing flexion and reached a maximum of 86.4° ± 14.7° at 135° of flexion (P < .05). Conclusion: These data suggest that there is no reciprocal function of the bundles with flexion, which is contrary to previous findings. The orientation of the anterolateral and posteromedial bundles suggests that at high flexion, the anterolateral bundle might play an important role in constraining the mediolateral translation, whereas the posteromedial bundle might play an important role in constraining the anteroposterior translation of the tibia. Clinical Relevance: These data provide a better understanding of the biomechanical function of the posterior cruciate ligament bundles and may help to improve the design of the 2-bundle reconstruction techniques of the ruptured posterior cruciate ligament. Keywords: posterior cruciate ligament; in vivo kinematics; posterior cruciate ligament reconstruction; double-bundle reconstruction, Double-bundle reconstruction of a ruptured posterior cruciate ligament (PCL) has increasingly attracted attention in the literature. (2),(9),(12),(30) A survey conducted by the Herodicus Society to assess the status of treatment [...]

Aims: Previous studies have reported that focused ultrasound (FUS) helps modulate the blood-brain barrier (BBB). These studies have generally used the paracellular pathway owing to tight junction proteins (TJPs) regulation. However, BBB transport pathways also include diffusion and transcytosis. Few studies have examined transcellular transport across endothelial cells. We supposed that increased BBB permeability caused by FUS may affect transcytosis. We investigated drug delivery through transcytosis and paracellular transport to the brain after BBB modulation using FUS. Main methods: FUS and microbubbles were applied to the hippocampus of rats, and were euthanized at 1, 4, 24, and 48 h after sonication. To investigate paracellular transport, we analyzed TJPs, including zona occludens-1 (ZO-1) and occludin. We also investigated caveola-mediated transcytosis by analyzing caveola formation and major facilitator superfamily domain-containing 2a (Mfsd2a) levels, which inhibit caveola vesicle formation. Key findings: One hour after FUS, ZO-1 and occludin expression was the lowest and gradually increased over time, returning to baseline 24 h after FUS treatment. Compared with that of TJPs, caveola formation started to increase 1 h after FUS treatment and peaked at 4 h after FUS treatment before returning to baseline by 48 h after FUS treatment. Decreased Mfsd2a levels were observed at 1 h and 4 h after FUS treatment, indicating increased caveola formation. Significance: FUS induces BBB permeability changes and regulates both paracellular transport and caveola-mediated transcytosis. However, a time difference was observed between these two mechanisms. Hence, when delivering drugs into the brain after FUS, the optimal drug administration timing should be determined by the mechanism by which each drug passes through the BBB.

Background: Herbal medicine Oryeongsan (ORS), also known as Wulingsan in Chinese, has been used for the treatment of impaired body fluid balance. However, the mechanisms involved are not clearly defined. The purpose of the present study was to identify the actions of ORS on the renal excretory function and blood pressure (BP) and to define the mechanisms involved in association with renin-angiotensin system (RAS) and natriuretic peptide system (NPS) in spontaneously hypertensive rats (SHR), an animal model of human essential hypertension. Methods: Changes in urine volume (UV), excretion of electrolytes including Na+ (urinary excretion of Na+ (UNaV)) were measured. RT-PCR was performed to trace the changes in expression of RAS, NPS and sodium (Na+)-hydrogen (H+) exchanger 3 (NHE3) in the renal cortex. Results: In the SHR treated with vehicle (SHR-V) group, UV and UNaV were suppressed and the Na+ balance was maintained at the higher levels leading to an increase in BP compared to WKY-V group. These were accompanied by an increase in NHE3 expression with an accentuation of angiotensin I converting enzyme-angiotensin II type 1 (ACE-AT1) receptor and concurrent suppression of angiotensin II type 2 (AT2) receptor/ACE2-Mas receptor expression in the renal cortex. Chronic treatment with ORS increased UV and UNaV, and decreased the Na+ and water balance with a decrease in BP in the ORS-treated SHR-ORS group compared to SHR-V. These were accompanied by a decrease in NHE3 expression with a suppression of ACE-AT1 receptor and concurrent accentuation of AT2/ACE2-Mas receptor. Conclusion: The present study shows that ORS reduced BP with a decrease in Na+ and water retention by a suppression of NHE3 expression via modulation of RAS and NPS in SHR. The present study provides pharmacological rationale for the treatment of hypertension with ORS in SHR.

In prostate cancer, the bone is the most common site of metastasis, and it is essential to evaluate metastatic bone lesions to assess the tumor burden and treatment response. Castration-resistant prostate cancer refers to the state wherein the cancer continues to progress despite a significant reduction of the sex hormone level and is associated with frequent distant metastasis. The Prostate Cancer Working Group 3 (PCWG3) released guidelines that aimed to standardize the assessment of treatment effects in castration-resistant prostate cancer using bone scintigraphy. However, these guidelines can be challenging to comprehend and implement in practical settings. The purpose of this review was to provide an overview of a specific image acquisition method and treatment response assessment for bone scintigraphy-based evaluation of bone lesions in metastatic castration-resistant prostate cancer, in accordance with the PCWG3 guidelines.

PURPOSETo evaluate the safety and efficacy of percutaneous radiologic gastrostomy (PRG) with balloon-assisted tract dilatation (BATD) using a single gastropexy.METHODSThis retrospective study was approved by the institutional review board. From August 2018 to October 2022, 61 patients (53 male and 8 female, mean age 67 years, age range 27–90 years) underwent PRG with balloon-retained tubes for enteral nutrition. Single gastropexy was performed in all cases. Patients were divided into two groups based on the tract dilatation technique used. In the first group, BATD (n = 48) was performed. In the second group, a 24-Fr peel-away sheath (PAS) was used for tract dilatation (n = 13). Patient demographics, technical success rate, clinical success rate, fluoroscopy time, cumulative radiation dose, and complications were retrospectively evaluated. The Mann–Whitney U test for continuous variables and Fisher’s exact test for categorical variables were performed to compare the two groups.RESULTSAll procedures were successfully performed with 100% technical and clinical success rates in both groups. The mean fluoroscopy time for the BATD group vs. the PAS group (1.68 ± 0.93 min vs. 3.56 ± 2.41 min, P < 0.001) and mean cumulative radiation dose (12.98 ± 9.28 mGy vs. 33.01 ± 15.14 mGy, P < 0.001) were significantly lower in the BATD group compared with the PAS group. There was one major complication of peritonitis that led to death in the PAS group (1/13, 7.7%) and no major complications in the BATD group. Minor complications such as pneumoperitoneum, abdominal pain, leakage, and balloon deflation occurred in 16 patients: 12 (12/48, 25.0%) patients in the BATD group and 4 (4/13, 38.5%) patients in the PAS group. The overall rate of major and minor complications was higher in the PAS group but did not show statistically significant differences (odds ratio: 1.875, 95%; confidence interval: 0.514–6.841, P = 0.486).CONCLUSIONBATD using a single gastropexy is a safe and effective technique for PRG.

Background Endobronchial ultrasound (EBUS) is widely used to diagnose lung cancer. Monitored anesthesia care (MAC) can enhance patient comfort and procedural conditions during EBUS. EBUS under MAC is usually safe but can lead to various complications. Case A 34-year-old male who had increased sputum for two months showed an enlarged paratracheal lymph node and planned for lymph node biopsy by EBUS. During EBUS under MAC, an unexpected oxygen saturation decline required intervention. After intubation, copious frothy fluid was suctioned from the bronchi, and oxygenation was recovered. A narrowed trachea and the EBUS bronchoscope might have resulted in upper airway obstruction, and suction performed under these conditions might have caused pulmonary edema. The patient received non-invasive ventilation and high-flow nasal cannula and recovered without complications. Conclusions When there is an expected risk of upper airway obstruction during EBUS, careful preoperative evaluation and preparation are essential to prevent negative pressure pulmonary edema.

Abstract We aimed to investigate the detection rate of brain MR and MR angiography for neuroimaging abnormality in newly diagnosed left-sided infective endocarditis patients with/without neurological symptoms. This retrospective study included consecutive patients with definite or possible left-sided infective endocarditis according to the modified Duke criteria who underwent brain MRI and MR angiography between March 2015 and October 2020. The detection rate for neuroimaging abnormality on MRI was defined as the number of patients with positive brain MRI findings divided by the number of patients with left-sided infective endocarditis. Positive imaging findings included acute ischemic lesions, cerebral microbleeds, hemorrhagic lesions, and infectious aneurysms. In addition, aneurysm rupture rate and median period to aneurysm rupture were evaluated on follow-up studies. A total 115 patients (mean age: 55 years ± 19; 65 men) were included. The detection rate for neuroimaging abnormality was 77% (89/115). The detection rate in patients without neurological symptoms was 70% (56/80). Acute ischemic lesions, cerebral microbleeds, and hemorrhagic lesions including superficial siderosis and intracranial hemorrhage were detected on MRI in 56% (64/115), 57% (66/115), and 20% (23/115) of patients, respectively. In particular, infectious aneurysms were detected on MR angiography in 3% of patients (4/115), but MR angiography in 5 patients (4.3%) was insignificant for infectious aneurysm, which were detected using CT angiography (n = 3) and digital subtraction angiography (n = 2) during follow-up. Among the 9 infectious aneurysm patients, aneurysm rupture occurred in 4 (44%), with a median period of aneurysm rupture of 5 days. The detection rate of brain MRI for neuroimaging abnormality in newly diagnosed left-sided infective endocarditis patients was high (77%), even without neurological symptoms (70%).

Abstract Prostate cancer is the most prevalent cancer in men worldwide and is promoted by the sex hormone androgen. Expression of androgen from the testis can be significantly reduced through castration. However, as most prostate cancer patients acquire castration resistance, additional therapeutic solutions are necessary. Although anti-androgens, such as enzalutamide, have been used to treat castration-resistant prostate cancer (CRPC), enzalutamide-resistant CRPC (Enz-resistant CRPC) has emerged. Therefore, development of novel treatments for Enz-resistant CRPC is urgent. In this study, we found a novel anti-androgen called pinostilbene through screening with a GAL4-transactivation assay. We confirmed that pinostilbene directly binds to androgen receptor (AR) and inhibits its activation and translocalization. Pinostilbene treatment also reduced the protein level and downstream gene expression of AR. Furthermore, pinostilbene reduced the protein level of AR variant 7 in the Enz-resistant prostate cancer cell line 22Rv1 and inhibited cell viability and proliferation. Our results suggest that pinostilbene has the potential to treat Enz-resistant CRPC.

The application of venoarterial extracorporeal membrane oxygenation (ECMO) in patients unresponsive to conventional cardiopulmonary resuscitation (CPR) has significantly increased in recent years. To date, three published randomized trials have investigated the use of extracorporeal CPR (ECPR) in adults with refractory out-of-hospital cardiac arrest. Although these trials reported inconsistent results, they suggest that ECPR may have a significant survival benefit over conventional CPR in selected patients only when performed with strict protocol adherence in experienced emergency medical services–hospital systems. Several studies suggest that identifying suitable ECPR candidates and reducing the time from cardiac arrest to ECMO initiation are key to successful outcomes. Prehospital ECPR or the rendezvous approach may allow more patients to receive ECPR within acceptable timeframes than ECPR initiation on arrival at a capable hospital. ECPR is only one part of the system of care for resuscitation of cardiac arrest victims. Optimizing the chain of survival is critical to improving outcomes of patients receiving ECPR. Further studies are needed to find the optimal strategy for the use of ECPR.