Association Between Time From Surgery to Radiation Therapy and Multimodality Treatment Outcomes in HPV+ Head and Neck Cancer: A Multi-Institutional Cohort Experience.

Purpose: Oropharyngeal squamous cell cancers (OPSCCs) are traditionally managed with surgery and, if indicated, adjuvant radiation therapy (RT) with or without chemotherapy. NCCN recommends keeping the time from surgery to the start of RT (TSRT) within 6 weeks to avoid possibly compromising patient outcomes. HPV+ OPSCCs behave more favorably than HPV- OPSCCs. We hypothesized that TSRT beyond 6 weeks may not portend poorer outcomes for the former. Methods: We identified nonmetastatic, high-risk HPV+ OPSCCs treated with multimodal therapy at 2 institutions. Prolonged TSRT was defined as >6 weeks and was evaluated for association with recurrence-free survival (RFS). Radiation treatment time (RTT; time from the first to the last day of RT), total treatment package time (TTPT; time from surgery to the end of adjuvant treatments), de-escalated RT (dose ≤56 Gy), concurrent chemotherapy, smoking history, and treatment institution were evaluated as possible confounders. Results: In total, 96 patients were included. The median follow-up time was 62 months (4-123 months); 69 patients underwent transoral robotic surgeries, and 27 received open surgeries. The median postoperative RT dose was 60 Gy (50-70.8 Gy). The median TSRT, RTT, and TTPT were 38 days (11-208), 43 days (26-56 days), and 81 days (40-255 days), respectively. Ten patients failed treatment at a median of 8 months (4-64 months). Two locoregional and 4 distant failures occurred in the group without prolonged TSRT, whereas 2 locoregional and 2 distant failures were recorded in the prolonged TSRT group. Prolonged TTPT, de-escalated RT, chemotherapy, smoking history, and treatment institution were not associated with treatment failure. RTT was dropped from our analyses as no events appeared in the prolonged RTT group, and no reliable hazard ratio could be computed. Conclusions: TSRT > 6 weeks was not significantly associated with inferior outcomes in the postoperative management of HPV+ OPSCCs. Longer TSRT may facilitate better recovery from surgical toxicity, as needed, without compromising oncologic outcomes. The TSRT goal for these cancers should be investigated in future studies.

Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma.

BACKGROUND: The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1manifestations (e.g., neurocognitive function, growth reduction, and café-au-lait spots) are unknown. METHODS: This open-label, phase 2 trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (≥ 3 cm). Selumetinib was administered at doses of 20 or 25 mg/m2 or 50 mg q 12 hrs for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated. RESULTS: Fifty-nine children and 30 adults (median age, 16 years; range, 3-47) received an average of 22±5 (4-26) cycles of selumetinib. Eighty-eight (98.9%) out of 89 per-protocol patients showed volume reduction in the target PN (median, 40.8%; 4.2%-92.2%), and 81 (91%) patients showed partial response (≥ 20% volume reduction). The response lasted until cycle 26. Scores of neurocognitive functions (verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ) significantly improved in both pediatric and adult patients (P <0.05). Prepubertal patients showed increases in height score and growth velocity (P <0.05). Café-au-lait spot intensity decreased significantly (P <0.05). Improvements in QoL and pain scores were observed in both children and adults. All adverse events were CTCAE grade 1 or 2 and were successfully managed without drug discontinuation. CONCLUSION: Selumetinib decrease PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in non-malignant diverse NF1 manifestations.

Regulation of Hippo-YAP signaling axis by Isoalantolactone suppresses tumor progression in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a devastating malignancy characterized by aggressive tumor growth and limited treatment options. Dysregulation of the Hippo signaling pathway and its downstream effector, Yes-associated protein (YAP), has been implicated in CCA development and progression. In this study, we investigated the effects of Isoalantolactone (IALT) on CCA cells to elucidate its effect on YAP activity and its potential clinical significance. Our findings demonstrate that IALT exerts cytotoxic effects, induces apoptosis, and modulates YAP signaling in SNU478 cells. We further confirmed the involvement of the canonical Hippo pathway by generating LATS1/LATS2 knockout cells, highlighting the dependence of IALT-mediated apoptosis and YAP phosphorylation on the Hippo-LATS signaling axis. In addition, IALT suppressed cell growth and migration, partially dependent on YAP-TEAD activity. These results provide insights into the therapeutic potential of targeting YAP in CCA and provide a rationale for developing of YAP-targeted therapies for this challenging malignancy.

One-Year Safety Evaluation of New Hyaluronic Acid Fillers (YYS Series): A Prospective, Multicenter, Observational Study.

BACKGROUND: With the continuous increasing availability of new filler products, each hyaluronic acid filler brand has distinctive pharmacokinetics, which may be associated with different complications. Therefore, the long-term safety of new generations of fillers should be evaluated. OBJECTIVE: This prospective, multicenter, observational, postmarketing study ( ClinicalTrials.gov identifier: NCT04738019) aimed to investigate the incidence of delayed-onset nodules and adverse reactions after the injection of new hyaluronic acid fillers (YYS series) into the facial skin. METHODS: Subjects scheduled to receive an injection YYS series filler were followed up for 52 weeks. The authors aimed to determine the incidence of a self-reported delayed-onset nodule-a visible or palpable nodule or mass at the injection site that was detected beyond the 14th day following the injection-during the 1-year follow-up period. RESULTS: Among the 1,022 subjects who received an injection of the YYS series, the incidences of delayed-onset nodules were 0% for YYS 360, YYS 540, and YYS 720. A 0.21% incidence (1 delayed hypersensitivity reaction) of a delayed-onset adverse reaction was noted for YYS 720, although none were reported for YYS 360 and YYS 540. CONCLUSION: In this study, a notably low frequency of adverse reactions associated with the YYS series was observed.

A Randomized, Prospective, Split-Face Pilot Study to Evaluate the Safety and Efficacy of 532-nm and 1,064-nm Picosecond-Domain Neodymium:Yttrium-Aluminum-Garnet Lasers Using a Diffractive Optical Element for Non-Ablative Skin Rejuvenation: Clinical and Histological Evaluation.

BACKGROUND: The advent of fractionated picosecond (ps) lasers has provided an opportunity to explore new ways of creating microinjuries in the skin to induce skin rejuvenation. OBJECTIVE: To compare the efficacy and safety of diffractive optical element (DOE)-assisted ps neodymium: yttrium-aluminum-garnet (Nd:YAG) lasers with 532-nm and 1,064-nm wavelengths (532-nm and 1,064-nm Nd:YAG P-DOE) using a novel fractional handpiece for the treatment of photoaged skin. METHODS: An ex vivo guinea pig skin experiment was performed by evaluating the histology of the skin after 532-nm Nd:YAG P-DOE irradiation. A randomized, prospective, split-face study was performed on eight subjects with 532-nm and 1,064-nm Nd:YAG P-DOE. RESULTS: Based on the histological evaluation using ex vivo guinea pig skin, a reasonable safety profile and the potential to generate effective skin rejuvenation was observed using the 532-nm Nd:YAG P-DOE. Results demonstrated that both 532- and 1,064-nm Nd:YAG P-DOE were similarly effective in improving skin texture and skin pores; however, 532-nm Nd:YAG P-DOE was more effective in treating dyspigmentation. CONCLUSION: At a preliminary level, this study revealed that 532-nm and 1,064-nm ps Nd:YAG lasers using DOE fractional technology may improve photoaged skin. In conclusion, 532-nm Nd:YAG P-DOE may be especially beneficial for skin with epidermal pigmentary lesions.

Efficacy and Safety of Cold-Induced Noninvasive Targeted Fat Reduction in Pseudogynecomastia.

BACKGROUND: Treatment options for pseudogynecomastia are limited, and the demand for noninvasive breast fat reduction is increasing. OBJECTIVE: We evaluated the efficacy and safety of a cold-induced lipolysis device for treating pseudogynecomastia. METHODS: In this 16-week prospective trial, a total of 15 male patients with pseudogynecomastia were treated twice with cryolipolysis. The primary endpoint was a change in the chest circumference from baseline at posttreatment week 8. Secondary endpoints were changes in body weight, fat thickness assessed using ultrasonography, independent evaluator- and patient-rated improvement, and Simon's gynecomastia class (SGC) grading. RESULTS: The primary assessment, a reduction of 3.05 cm in the mean chest circumference at 8 weeks post-treatment compared to baseline, was statistically significant. The treatment effect was cumulative, with a steady decrease in chest circumference and fat thickness over the 16-week study period. The mean pain score immediately after the first session of treatment was 2.0±1.36, based on a scale of 0~10, with a score of 10 being the worst pain ever experienced. The pain decreased substantially after the end of the procedure. CONCLUSION: Cryolipolysis was demonstrated to be an effective and safe option for reducing breast fat in pseudogynecomastia. Male with mild to moderate breast enlargement without skin excess can be ideal candidates.

Exosomes as novel player in dermatologic field.

Exosomes are nano-sized extracellular vesicles released by the majority of the cell types. Exosomes play a major role in intercellular communication via transferring cargoes between cells and altering specific functions of the target cells. The interest in the biological activities of exosomes has been increasing and their therapeutic role has already been demonstrated in various diseases. Recently, there is growing evidence that stem cell-derived exosomes (including mesenchymal stem cell, umbilical cord-derived mesenchymal cell, adipose-derived stem cell, and pluripotent stem cell) can also be used in a variety of skin conditions due to their regenerative and anti-inflammatory capacity. In this paper, we will provide a brief overview of recent studies on practical applications of exosomes in several dermatologic conditions and their potential mechanisms. By elucidating the different mechanisms and therapeutic roles of exosomes in various disease conditions, we hope dermatologists and other clinicians to establish better strategies for disease treatment with further research.

MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer.

BACKGROUND: The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC. METHODS: We designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma. RESULTS: MHY4571 inhibited PKA activity (> 70% inhibition) and suppressed the expression of p-PKA and p-CREB dose-dependently. MHY4571 treatment reduced lung cancer cell viability and promoted caspase 3-dependent apoptotic cell death. Orally administered MHY4571 significantly suppressed lung tumor growth in xenograft and orthotopic mouse models. PKA catalytic subunit alpha-silencing by siRNA (siPKA) strongly attenuated CREB phosphorylation; siCREB did not alter PKA protein levels or its phosphorylation, suggesting that PKA is an upstream regulator of CREB activity. MHY4571 acted synergistically with cisplatin (on co-treatment) to induce apoptotic cell death in lung cancer cells. CONCLUSIONS: Our results imply that MHY4571 may be a potential drug candidate for squamous cell lung cancer treatment.

Quantitative Evaluation of Volume Augmentation and Durational Changes in the Anteromedial Cheek with Hyaluronic Acid Fillers Using Three-Dimensional Measurement: 2-Year Results from a Comparative Split-Face Study.

SUMMARY: Hyaluronic acid fillers are widely used for the augmentation of facial soft tissues. Hyaluronic acid fillers can be monophasic or biphasic and have different characteristics, especially regarding volumetric effects and maintenance potential. However, there is paucity of long-term quantitative and objective data on clinical outcomes following hyaluronic acid injection. In this study, the authors evaluated volumetric changes over 2 years and the maintenance potentials of both types of fillers on the anteromedial cheek using objective three-dimensional measurements. This comparative split-face study enrolled participants aged 30 to 50 years who received a midfacial injection of the test filler (Belotero Volume) on one side and a random control filler (Juvéderm, Restylane SubQ, or Yvoire Contour) on the contralateral side. The authors conducted three-dimensional scanning assessments at baseline and after 30 minutes; 3 days; 2, 4, 12, and 24 weeks; and 2 years. The volume augmentation effects for the anteromedial cheek of two monophasic fillers (Belotero Volume and Juvéderm Voluma) were maintained for at least 2 years (81 percent and 66 percent, respectively, compared to the volume at 4 weeks). Two biphasic fillers (Yvoire Contour and Restylane SubQ) maintained over 50 percent volume compared to the volume 4 weeks after injection. Monophasic fillers showed better outcomes than biphasic fillers; however, both types of hyaluronic acid fillers demonstrated superior efficacy, safety, and durability for volumetric augmentation in the anteromedial cheek. Objective data obtained using three-dimensional imaging analysis will enable dermatologists to better demonstrate the results of the procedure to patients, through the provision of visual aids. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

A prospective, split-face study comparing 1,064-nm picosecond Nd:YAG laser toning with 1,064-nm Q-switched Nd:YAG laser toning in the treatment of melasma.

BACKGROUND: Recently, a low-fluence picosecond (ps) laser is an emerging option for removing pigmented lesions. OBJECTIVES: We aimed to evaluate the efficacy and safety of a 1,064-nm ps Nd:YAG laser as compared to a 1,064-nm Qs Nd:YAG laser for melasma treatment in an Asian. METHODS: Twenty Korean patients with facial melasma were enrolled and randomly treated with a 1,064-nm ps Nd:YAG laser on one side of the face and 1,064-nm Qs Nd:YAG on the other side at 2-week intervals for five sessions. At each visit, the modified Melasma Area Severity Index (mMASI), patient satisfaction scores, visual analogue scale (VAS) scores, and adverse events were assessed. RESULTS: Both groups showed significant clinical improvement and decreased mMASI scores compared to the baseline. No statistically significant difference was observed in the mMASI score between the two treatment techniques at any time point. The melanin index showed no statistically significant improvement in both groups, and no significant differences were observed in patient satisfaction scores and VAS scores between both modalities. CONCLUSIONS: A 1,064 nm ps Nd:YAG laser is as effective and safe as a conventional 1,064 nm Qs Nd:YAG laser in the treatment of melasma in Asian skin, but no superior outcome was observed.

PAK1 inhibition reduces tumor size and extends the lifespan of mice in a genetically engineered mouse model of Neurofibromatosis Type 2 (NF2).

Neurofibromatosis Type II (NF2) is an autosomal dominant cancer predisposition syndrome in which germline haploinsufficiency at the NF2 gene confers a greatly increased propensity for tumor development arising from tissues of neural crest derived origin. NF2 encodes the tumor suppressor, Merlin, and its biochemical function is incompletely understood. One well-established function of Merlin is as a negative regulator of group A serine/threonine p21-activated kinases (PAKs). In these studies we explore the role of PAK1 and its closely related paralog, PAK2, both pharmacologically and genetically, in Merlin-deficient Schwann cells and in a genetically engineered mouse model (GEMM) that develops spontaneous vestibular and spinal schwannomas. We demonstrate that PAK1 and PAK2 are both hyper activated in Merlin-deficient murine schwannomas. In preclinical trials, a pan Group A PAK inhibitor, FRAX-1036, transiently reduced PAK1 and PAK2 phosphorylation in vitro, but had insignificant efficacy in vivo. NVS-PAK1-1, a PAK1 selective inhibitor, had a greater but still minimal effect on our GEMM phenotype. However, genetic ablation of Pak1 but not Pak2 reduced tumor formation in our NF2 GEMM. Moreover, germline genetic deletion of Pak1 was well tolerated, while conditional deletion of Pak2 in Schwann cells resulted in significant morbidity and mortality. These data support the further development of PAK1-specific small molecule inhibitors and the therapeutic targeting of PAK1 in vestibular schwannomas and argue against PAK1 and PAK2 existing as functionally redundant protein isoforms in Schwann cells.

Non-Invasive Diagnosis of a Facial Tumor Using Dermoscopy and Successful Treatment with 595 nm Pulsed Dye Laser.

Clear cell acanthoma (CCA) is an uncommon, benign epithelial tumor presenting as a well-defined, slow-growing solitary nodule. The diagnosis of CCA is usually based on clinical and histopathological evaluation of the tumor. However, when such type of benign tumor occurs on an exposed area, a biopsy is not always the best diagnostic option since it may leave scar. The recent advent of dermoscopy has offered an accurate and non-invasive method to diagnose CCA without resorting to skin biopsy. A 40-year-old male presented with a shiny, erythematous-to-brown, flattened nodule on the left cheek. Dermoscopic examination revealed a 'string of pearls' vascular pattern, a characteristic dermoscopic feature of CCA. Under the clinical and dermoscopic impression of CCA, a 595 nm pulsed dye laser (PDL) therapy targeting the vascular tissue in the superficial dermis of the lesion was chosen for a minimally invasive treatment. After repeated sessions of PDL, an optimal cosmetic outcome was achieved and no recurrence was recorded during the follow-up period. Herein, we report a case of presumed CCA which was successfully diagnosed and treated by utilizing non-invasive modalities.

N6 -Methyladenosine mRNA methylation is important for salt stress tolerance in Arabidopsis.

As the most abundant internal modification of mRNA, N6 -methyladenosine (m6 A) methylation of RNA is emerging as a new layer of epitranscriptomic gene regulation in cellular processes, including embryo development, flowering-time control, microspore generation and fruit ripening, in plants. However, the cellular role of m6 A in plant responses to environmental stimuli remains largely unexplored. In this study, we show that m6 A methylation plays an important role in salt stress tolerance in Arabidopsis. All mutants of m6 A writer components, including MTA, MTB, VIRILIZER (VIR) and HAKAI, displayed salt-sensitive phenotypes in an m6 A-dependent manner. The vir mutant, in which the level of m6 A was most highly reduced, exhibited salt-hypersensitive phenotypes. Analysis of the m6 A methylome in the vir mutant revealed a transcriptome-wide loss of m6 A modification in the 3' untranslated region (3'-UTR). We demonstrated further that VIR-mediated m6 A methylation modulates reactive oxygen species homeostasis by negatively regulating the mRNA stability of several salt stress negative regulators, including ATAF1, GI and GSTU17, through affecting 3'-UTR lengthening linked to alternative polyadenylation. Our results highlight the important role played by epitranscriptomic mRNA methylation in the salt stress response of Arabidopsis and indicate a strong link between m6 A methylation and 3'-UTR length and mRNA stability during stress adaptation.

Cabozantinib for neurofibromatosis type 1-related plexiform neurofibromas: a phase 2 trial.

Neurofibromatosis type 1 (NF1) plexiform neurofibromas (PNs) are progressive, multicellular neoplasms that cause morbidity and may transform to sarcoma. Treatment of Nf1fl/fl;Postn-Cre mice with cabozantinib, an inhibitor of multiple tyrosine kinases, caused a reduction in PN size and number and differential modulation of kinases in cell lineages that drive PN growth. Based on these findings, the Neurofibromatosis Clinical Trials Consortium conducted a phase II, open-label, nonrandomized Simon two-stage study to assess the safety, efficacy and biologic activity of cabozantinib in patients ≥16 years of age with NF1 and progressive or symptomatic, inoperable PN ( NCT02101736 ). The trial met its primary outcome, defined as ≥25% of patients achieving a partial response (PR, defined as ≥20% reduction in target lesion volume as assessed by magnetic resonance imaging (MRI)) after 12 cycles of therapy. Secondary outcomes included adverse events (AEs), patient-reported outcomes (PROs) assessing pain and quality of life (QOL), pharmacokinetics (PK) and the levels of circulating endothelial cells and cytokines. Eight of 19 evaluable (42%) trial participants achieved a PR. The median change in tumor volume was 15.2% (range, +2.2% to -36.9%), and no patients had disease progression while on treatment. Nine patients required dose reduction or discontinuation of therapy due to AEs; common AEs included gastrointestinal toxicity, hypothyroidism, fatigue and palmar plantar erythrodysesthesia. A total of 11 grade 3 AEs occurred in eight patients. Patients with PR had a significant reduction in tumor pain intensity and pain interference in daily life but no change in global QOL scores. These data indicate that cabozantinib is active in NF1-associated PN, resulting in tumor volume reduction and pain improvement.

Comparison of Monotherapy Versus Combination of Intravenous Ibuprofen and Propacetamol (Acetaminophen) for Reduction of Postoperative Opioid Administration in Children Undergoing Laparoscopic Hernia Repair: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Extensive efforts have been made toward reducing postoperative opioid use in children. In this study, we assessed whether propacetamol, or a nonsteroidal anti-inflammatory drug (NSAID), or their combination could effectively reduce opioid use in children after laparoscopic inguinal hernia repair. METHODS: This randomized, double-blind clinical trial included 159 children aged 6 months to 6 years. Children were allocated into 1 of the following 3 groups: group I was treated with 10 mg·kg-1 ibuprofen, group P was treated with 30 mg·kg-1 propacetamol, and group I + P was treated with both drugs in their respective concentrations. If the face-legs-activity-crying-consolability (FLACC) score was ≥4 during the postanesthesia care unit stay, 1.0 µg·kg-1 fentanyl was administered as a rescue analgesic. The number of patients who received rescue fentanyl in the postanesthesia care unit was defined as the primary outcome; this was analyzed using the χ2 test. The secondary outcomes included the FLACC and the parents' postoperative pain measure (PPPM) scores until the 24-hour postoperative period. RESULTS: Among the 144 enrolled patients, 28.6% in group I, 66.7% in group P, and 12.8% in group I + P received rescue fentanyl in the postanesthesia care unit (P < .001). The highest FLACC score was lower in group I + P than in either group I or P (P = .007 and P < .001, respectively). Group I + P presented significantly lower PPPM scores than group P at 4 and 12 hours postoperative (P = .03 and .01, respectively). CONCLUSIONS: The use of ibuprofen plus propacetamol immediately following laparoscopic hernia repair surgery in children resulted in the reduced use of an opioid drug compared with the use of propacetamol alone.

Ca2+-activated mitochondrial biogenesis and functions improve stem cell fate in Rg3-treated human mesenchymal stem cells.

Although mitochondrial functions are essential for cell survival, their critical roles in stem cell fate, including proliferation, differentiation, and senescence, remain elusive. Ginsenoside Rg3 exhibits various biological activities and reportedly increases mitochondrial biogenesis and respiration. Herein, we observed that Rg3 increased proliferation and suppressed senescence of human bone marrow-derived mesenchymal stem cells. Osteogenic, but not adipogenic, differentiation was facilitated by Rg3 treatment. Rg3 suppressed reactive oxygen species production and upregulated mitochondrial biogenesis and antioxidant enzymes, including superoxide dismutase. Consistently, Rg3 strongly augmented basal and ATP synthesis-linked respiration with high spare respiratory capacity. Rg3 treatment elevated cytosolic Ca2+ concentration contributing to mitochondrial activation. Reduction of intracellular or extracellular Ca2+ levels strongly inhibited Rg3-induced activation of mitochondrial respiration and biogenesis. Taken together, Rg3 enhances capabilities of mitochondrial and antioxidant functions mainly through a Ca2+-dependent pathway, which improves the proliferation and differentiation potentials and prevents the senescence of human mesenchymal stem cells.

Comparison of Intracardiac Echocardiography and Transesophageal Echocardiography for Image Guidance in Percutaneous Patent Foramen Ovale Closure.

Background and Objectives: Transesophageal echocardiography (TEE) guidance is the current gold standard for catheter-based procedures in the treatment of structural heart diseases. Intracardiac echocardiography (ICE), which can be performed under local anesthesia, has been recently introduced and is becoming more widely used. We aimed to compare the efficacy and safety of ICE and TEE in patent foramen ovale (PFO) device closure. Materials and Methods: All 74 patients with a history of cryptogenic stroke undergoing PFO closure for secondary prophylaxis were selected from our registry. Intraprocedural TEE was performed by echocardiographer-cardiologists with the patient under general anesthesia. Conversely, ICE was performed with the patient under local anesthesia. Baseline characteristics, procedural details, and immediate outcomes were compared between the TEE and ICE groups (n = 49 and n = 25, respectively). Results: Although patients in the ICE group were older (47 ± 10 vs. 57 ± 7 years, p < 0.001), sex and comorbidity variables were similar between the two groups. The degree of inducible right-to-left shunt via the PFO, assessed using preprocedural TEE, was also comparable. Notably, fluoroscopy time (22 ± 18 vs. 16 ± 7 min, p = 0.030), radiation dose (498 ± 880 vs. 196 ± 111 mGy, p = 0.022), and total procedural time in the catheter laboratory (99 ± 30 vs. 67 ± 12 min, p < 0.001) were significantly lower in the ICE group than those in the TEE group. The entire hospital stay was similar between groups (3.8 ± 2.2 vs. 3.4 ± 1.3 days, p = 0.433). No procedural complications, such as device embolization, pericardial hemorrhage, major bleeding, mortality, or access-related vascular injury were reported in either group. Conclusions: ICE-guided PFO device closure is quicker and less hazardous in terms of radiation exposure than the TEE-guided procedure, with similar procedural outcomes and duration of hospital stay.

Bone Marrow-Derived Mesenchymal Stem Cells Isolated from Patients with Cirrhosis and Healthy Volunteers Show Comparable Characteristics.

BACKGROUND AND OBJECTIVES: Autologous or allogeneic bone marrow-derived mesenchymal stem cells (BMSCs) have been applied in clinical trials to treat liver disease. However, only a few studies are comparing the characteristics of autologous MSCs from patients and allogeneic MSCs from normal subjects. METHODS AND RESULTS: We compared the characteristics of BMSCs (BCs and BPs, respectively) isolated from six healthy volunteers and six patients with cirrhosis. In passage 3 (P3), senescent population and expression of p53 and p21 were slightly higher in BPs, but the average population doubling time for P3-P5 in BPs was approximately 65.3±11.1 h, which is 18.4 h shorter than that in BCs (83.7±9.2 h). No difference was observed in the expression of CD73, CD90, or CD105 between BCs and BPs. Adipogenic differentiation slightly increased in BCs, but the expression levels of leptin, peroxisome proliferator-activated receptor γ, and CCAAT-enhancer-binding protein α did not vary between differentiated BCs and BPs. While ATP and reactive oxygen species levels were slightly lower in BPs, mitochondrial membrane potential, oxygen consumption rate, and expression of mitochondria-related genes such as cytochrome c oxidase 1 were not significantly different between BCs and BPs. CONCLUSIONS: Taken together, there are marginal differences in the proliferation, differentiation, and mitochondrial activities of BCs and BPs, but both BMSCs from patients with cirrhosis and healthy volunteers show comparable characteristics.