Background and Objectives: Hyaluronan preserves the proliferation and differentiation potential of mesenchymal stem cells. Supplementation of low-concentration hyaluronan (SHA) in stem cells culture medium increases its proliferative rate, whereas coated-surface hyaluronan (CHA) maintains cells in a slow-proliferating mode. We have previously demonstrated that in CHA, the metabolic proliferative state of stem cells was influenced by upregulating mitochondrial biogenesis and function. However, the effect of SHA on stem cells’ energetic status remains unknown. In this study, we demonstrate the effect that low-concentration SHA at 0.001 mg/ml (SHA0.001) and high-concentration SHA at 5 mg/ml (SHA5) exert on stem cells’ mitochondrial function compared with CHA and noncoated tissue culture surface (control). Methods: and Results: Fast-proliferating human placenta-derived mesenchymal stem cells (PDMSCs) cultured on SHA0.001 exhibited reduced mitochondrial mass, lower mitochondrial DNA copy number, and lower oxygen consumption rate compared with slow-proliferating PDMSCs cultured on CHA at 5.0 (CHA5) or 30 μg/cm2 (CHA30). The reduced mitochondrial biogenesis observed in SHA0.001 was accompanied by a 2-fold increased ATP content and lactate production, suggesting that hyaluronan-induced fast-proliferating PDMSCs may rely less on mitochondrial function as an energy source and induce a mitochondrial functional switch to glycolysis. Conclusions PDMSCs cultured on both CHA and SHA exhibited a reduction in reactive oxygen species levels. The results from this study clarify our understandings on the effect of hyaluronan on stem cells and provide important insights into the effect of distinct supplementation methods used during cell therapies.

BACKGROUNDPrevious studies indicated that long coronary lesions are one of the key predictors of drug-eluting stent (DES) failure. The purpose of this study was to evaluate the efficacy and the safety of the long length FIREHAWK(®) stent in long coronary artery disease.

METHODSThe long cohort of TARGET I was a prospective, multicenter, single arm trial. It was planned to enroll 50 patients undergoing percutaneous coronary intervention (PCI) for the treatment of de novo long lesions in a native coronary artery. The major inclusion criteria of the trial was that patients were intended to undergo the treatment of a long target lesion(s) with diameter stenosis ≥ 70% and reference vessel diameter 2.5 mm to 4.0 mm by visual estimate, that needed to be covered by at least one 33 mm or 38 mm stent or multiple long stents overlapped. The angiographic follow-up was planned at 9-month and the clinical follow-up will be up to 5 years. The primary end point was in-stent late lumen loss at 9-month.

RESULTSFifty patients (mean age (57.6 ± 10.2) years) with 59 de novo long lesions (reference vessel diameter (2.85 ± 0.44) mm, lesion length (35.2 ± 9.4) mm, and stent length (41.8 ± 11.3) mm) were enrolled. The angiographic follow-up rate was 92% at 9-month. The in-stent late loss was (0.16 ± 0.16) mm. Proximal edge, distal edge and in-segment late loss (mm) were 0.21 ± 0.35, 0.03 ± 0.33, and 0.07 ± 0.26, respectively. No in-segment binary restenosis was observed. At 1-year no death, Q wave myocardial infarction (MI), or stent thrombosis occurred. Non-Q-wave MI occurred in two patients (4%) due to procedural complications.

CONCLUSIONSTreatment of long coronary lesions with the FIREHAWK(®) stent is able to produce similar results as observed in the FIREHAWK(®) FIM clinical trial. Based on this result, we are confident in the treatment prospect of the FIREHAWK(®) for long coronary lesions.

Aged ; Coronary Artery Disease ; drug therapy ; therapy ; Drug-Eluting Stents ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Sirolimus ; adverse effects ; therapeutic use ; Treatment Outcome

Male infertility (MI) and male sexual dysfunction (MSD) can often coexist together due to various interplay factors such as psychosexual, sociocultural and relationship dynamics. The presence of each form of MSD can adversely impact male reproduction and treatment strategies will need to be individualized based on patients’ factors, local expertise, and geographical socioeconomic status. The Asia Pacific Society of Sexual Medicine (APSSM) and the Asian Society of Men’s Health and Aging (ASMHA) aim to provide a consensus statement and practical set of clinical recommendations based on current evidence to guide clinicians in the management of MI and MSD within the Asia-Pacific (AP) region. A comprehensive, narrative review of the literature was performed to identify the various forms of MSD and their association with MI. MEDLINE and EMBASE databases were searched for the following English language articles under the following terms: “low libido”, “erectile dysfunction”, “ejaculatory dysfunction”, “premature ejaculation”, “retrograde ejaculation”, “delayed ejaculation”, “anejaculation”, and “orgasmic dysfunction” between January 2001 to June 2022 with emphasis on published guidelines endorsed by various organizations. This APSSM consensus committee panel evaluated and provided evidence-based recommendations on MI and clinically relevant MSD areas using a modified Delphi method by the panel and specific emphasis on locoregional socioeconomic-cultural issues relevant to the AP region. While variations exist in treatment strategies for managing MI and MSD due to geographical expertise, locoregional resources, and sociocultural factors, the panel agreed that comprehensive fertility evaluation with a multidisciplinary management approach to each MSD domain is recommended. It is important to address individual MI issues with an emphasis on improving spermatogenesis and facilitating reproductive avenues while at the same time, managing various MSD conditions with evidence-based treatments. All therapeutic options should be discussed and implemented based on the patient’s individual needs, beliefs and preferences while incorporating locoregional expertise and available resources.

BACKGROUNDEffective pain management among hospitalized patients is an important aspect of providing quality care and achieving optimal clinical outcomes and patient satisfaction. Common pharmacologic approaches for pain, though effective, have serious side effects and are not appropriate for all inpatients. Findings from randomized controlled trials (RCTs) support the efficacy of acupuncture for many symptoms relevant to inpatients including postoperative pain, cancer-related pain, nausea and vomiting, and withdrawal from narcotic use. However, the extent to which findings from RCTs translate to real-world implementation of acupuncture in typical hospital settings is unknown.

METHODS/DESIGNIn partnership with the launch of a clinical program offering acupuncture services to inpatients at the University of California San Francisco's Mount Zion Hospital, we are conducting a pilot study using a hybrid effectiveness-implementation design to: (1) assess the effectiveness of acupuncture to manage pain and other symptoms and improve patient satisfaction; and (2) evaluate the barriers and facilitators to implementing an on-going acupuncture service for inpatients. During a two-month pre-randomization phase, we evaluated and adapted clinical scheduling and treatment protocols with acupuncturists and hospital providers and pretested study procedures including enrollment, consent, and data collection. During a six-month randomization phase, we used a two-tiered consent process in which inpatients were first consented into a study of symptom management, randomized to be offered acupuncture, and consented for acupuncture if they accepted. We are also conducting in-depth interviews and focus groups to assess evidence, context, and facilitators of key provider and hospital administration stakeholders.

DISCUSSIONEffectiveness research in "real-world" practice settings is needed to inform clinical decision-making and guide implementation of evidence-based acupuncture practices. To successfully provide clinical acupuncture services and maintain a rigorous research design, practice-based trials of acupuncture require careful planning and attention to setting-specific, contextual factors.

TRIAL REGISTRATIONThis trial has been registered in ClinicalTrials.gov. The identifier is NCT01988194, registered on November 5, 2013.

Acupuncture Therapy ; Clinical Protocols ; Humans ; Inpatients ; Pain Management ; Pilot Projects