A Clinical Analysis of Anti-Programmed Death-Ligand 1 (PD-L1) Immune Checkpoint Inhibitor Treatments Combined with Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer.

Real-world clinical experience of using anti-programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (SCLC) patients has rarely been reported. In this study, we aimed to perform a retrospective multicenter clinical analysis of extensive-stage SCLC patients receiving first-line therapy with anti-PD-L1 ICIs combined with chemotherapy. Between November 2018 and March 2022, 72 extensive-stage SCLC patients receiving first-line atezolizumab or durvalumab in combination with chemotherapy, according to the cancer center databases of Linkou, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals, were retrospectively included in the analysis. Twenty-one patients (29.2%) received atezolizumab and fifty-one (70.8%) received durvalumab. Objective response (OR) and disease control (DC) rates of 59.7% and 73.6%, respectively, were observed with first-line ICI plus chemotherapy. The median progression-free survival (PFS) was 6.63 months (95% confidence interval (CI), 5.25-8.02), and the median overall survival (OS) was 16.07 months (95% CI, 15.12-17.0) in all study patients. A high neutrophil-to-lymphocyte ratio (NLR; >4) and a high serum lactate dehydrogenase (LDH) concentration (>260 UL) were identified as independent unfavorable factors associated with shorter OS in the multivariate analysis. Regarding safety, neutropenia was the most common grade 3 treatment-related adverse event (AE), but no treatment-related deaths occurred in the study patients. First-line anti-PD-L1 ICIs combined with chemotherapy are effective and safe for male extensive-stage SCLC patients. Further therapeutic strategies may need to be developed for patients with unfavorable outcomes (e.g., baseline high NLR and serum LDH level).

Epidemiology and outcomes of multidrug-resistant bacterial infection in non-cystic fibrosis bronchiectasis.

PURPOSE: Multidrug-resistant (MDR) bacteria impose a considerable health-care burden and are associated with bronchiectasis exacerbation. This study investigated the clinical outcomes of adult patients with bronchiectasis following MDR bacterial infection. METHODS: From the Chang Gung Research Database, we identified patients with bronchiectasis and MDR bacterial infection from 2008 to 2017. The control group comprised patients with bronchiectasis who did not have MDR bacterial infection and were propensity-score matched at a 1:2 ratio. The main outcomes were in-hospital and 3-year mortality. RESULTS: In total, 554 patients with both bronchiectasis and MDR bacterial infection were identified. The types of MDR bacteria that most commonly affected the patients were MDR- Acinetobacter baumannii (38.6%) and methicillin-resistant Staphylococcus aureus (18.4%), Extended-spectrum-beta-lactamases (ESBL)- Klebsiella pneumoniae (17.8%), MDR-Pseudomonas (14.8%), and ESBL-E. coli (7.5%). Compared with the control group, the MDR group exhibited lower body mass index scores, higher rate of chronic bacterial colonization, a higher rate of previous exacerbations, and an increased use of antibiotics. Furthermore, the MDR group exhibited a higher rate of respiratory failure during hospitalization (MDR vs. control, 41.3% vs. 12.4%; p < 0.001). The MDR and control groups exhibited in-hospital mortality rates of 26.7% and 7.6%, respectively (p < 0.001); 3-year respiratory failure rates of 33.5% and 13.5%, respectively (p < 0.001); and 3-year mortality rates of 73.3% and 41.5%, respectively (p < 0.001). After adjustments were made for confounding factors, the infection with MDR and MDR bacteria species were determined to be independent risk factors affecting in-hospital and 3-year mortality. CONCLUSIONS: MDR bacteria were discovered in patients with more severe bronchiectasis and were independently associated with an increased risk of in-hospital and 3-year mortality. Given our findings, we recommend that clinicians identify patients at risk of MDR bacterial infection and follow the principle of antimicrobial stewardship to prevent the emergence of resistant bacteria among patients with bronchiectasis.

Profiles of pregnant women encountering motor vehicle crashes in Taiwan, 2008-2017.

BACKGROUND: Understanding demographic profiles is essential to the assessment of health burden imposed by motor vehicle crashes (MVCs) on pregnant women. However, Asian studies that have examined it are lacking. The study aimed to describe the demographic characteristics and prevalence of MVCs involving pregnant women in Taiwan. METHODS: A cross-sectional study conducted by the Taiwan Birth Notification dataset from 2008 to 2017 was linked with the police-reported traffic collision registry to identify pregnant women involved in MVCs. The pregnant women were categorized according to their gestational age, age at delivery, the role of road user (driver, passenger, or pedestrian), and vehicle types (car, two-wheeled motor vehicle, or others). A chi-square test was performed for the significance test. RESULTS: A total of 22,134 (1.13%) pregnant women were involved in MVCs in the study period. Two-wheeled motor vehicle (47.9%) and driver (81.4%) were the mainly reported vehicle type and road user at the crash scenes, respectively. The majority of MVCs occurred in pregnant women aged 28-34 years. The number of MVCs rapidly declined after 37 weeks of gestation, especially two-wheeled motor vehicle or car crashes. However, the number of pedestrian victims climbed up during the third trimester. CONCLUSION: Pregnant women are susceptible to MVCs regardless of their gestational age, role of a road user, or type of vehicle. The findings of this study emphasize the need for increased awareness of traffic collision prevention among pregnant women aged 28-34. In addition, improving pedestrian safety is essential for the reduction of pregnant victims.

Pregnancy is associated with more severe injuries from motor vehicle crashes.

OBJECTIVE: Whether pregnancy is associated with severe injuries from motor vehicle crashes (MVCs) remains unclear. This study aimed to investigate the potential relationship between pregnancy and severity of injuries from MVCs. METHODS: We identified a total of 23,559 pregnant women victims who encountered MVCs during pregnancy as well as 94,236 age- and calendar year-at MVC matched non-pregnant women victims that are also involved in MVCs. Injury severity was assessed using the Maximum Abbreviated Injury Scale (MAIS) based on the diagnosis of medical claims after MVCs. Multinomial logistic regression models were used to estimate the odds ratio and corresponding 95 % CI of injury severity levels associated with pregnancy. RESULTS: Pregnant women had a significantly higher risk of both severe (adjusted odds ratio, aOR = 1.79, 95 % CI = 1.54-2.08) and mild injuries (aOR = 8.63, 95 % CI = 8.21-9.07) following MVCs as compared to non-pregnant women victims. Particularly, pregnant women who were riding scooters had an increased risk of severe injury (aOR = 4.25, 95 % CI = 3.58-5.04). In addition, pregnant women who experienced MVC but without any injury were more likely to visit a clinic than non-pregnant MVC victims. CONCLUSION: Pregnant women victims, particularly those who were riding scooters involved in MVCs suffered from a higher risk of severe injury as compared to their non-pregnant counterparts. Our findings suggest that women should consider avoiding riding a scooter and must use restrictive devices during pregnancy, which would help reduce the severity of injuries sustained following an MVC.

Setting up a specialized maternity unit in a tertiary hospital: An oasis for pregnant women with COVID-19 during the pandemic.

OBJECTIVE: The COVID-19 pandemic has had an enormous impact on society and the medical environment in Taiwan in 2022. As pregnant women with COVID-19 are at higher risk for multiple complications, Taiwan needs a COVID-19 specialized maternity unit to improve the quality of maternal and neonatal care. MATERIALS AND METHODS: We share our experience with specialized maternity unit for pregnant women with COVID-19 at the National Cheng Kung University Hospital, where we can have careful evaluation, safe birth, and comprehensive postpartum care. RESULTS: Our COVID-19 specialized maternity unit enrolled 253 pregnant women with COVID-19, 90 (35.6%) pregnant women were admitted to the specialized maternity unit, and 71 (28.1%) pregnant women gave birth during hospitalization in two months. All pregnant women recovery well and real-time polymerase chain reaction tests on all infants were negative for COVID-19. CONCLUSION: A specialized maternity unit can provide pregnant women with a safe birth environment, immediate maternity care, and high medical quality. It can also help health workers in non-specialized maternity units deal with COVID-19-related psychological stress. Therefore, setting up one specialized maternity unit in the city during the pandemic should be guardedly considered.

Risks of motor vehicle crash before and during pregnancy: A population-based controlled study in Taiwan.

BACKGROUND: Changes in risk of motor vehicle crashes (MVCs) during pregnancy are less known, and very few studies have assessed this issue by using unselected population-based datasets and adopting a before-and-during design. The study aimed to address the risk of MVC events in association with pregnancy using a national pregnant women cohort in Taiwan. METHODS: We conducted a self-matched design in which each woman served as a driver before and during pregnancy. A total of 1,372,664 pregnant women with live birth(s) at 18-50 years of age between 2008 and 2017 were identified from the Birth Notification dataset. MVC events as a driver were ascertained from the Police-reported Traffic Accident Registry dataset. We calculated the rate ratio (RR) with a 95 % confidence interval (CI) using the conditional Poisson regression model to compare the MVC event rates between pre-pregnancy and pregnancy periods. RESULTS: The overall rate of MVC events was significantly reduced during pregnancy (RR = 0.69, 95 % confidence interval (CI) = 0.68-0.71). Mothers with alcoholism during pregnancy were associated with an increased RR at 2.00 but with a very wide CI. Reduction in RR was primarily attributed to the reduced MVC event rate involving scooter crashes (0.60, 95 % CI = 0.58-0.62). CONCLUSION: Although MVC event rates decreased during women became pregnant, many women drivers were still involved in MVCs during pregnancy. Their potential maternal and perinatal conditions along with their offspring's health outcomes need further investigations.

Associations of maternal motor vehicle crashes during pregnancy with offspring's neonatal birth outcomes.

BACKGROUND: Adverse events in fetuses are well researched but studies on the follow-up health outcomes of infants exposed to maternal motor vehicle crashes (MVCs) during pregnancy have yielded inconsistent results. This study aimed to investigate the association of maternal exposure to MVCs during pregnancy with the risk of adverse neonatal outcomes. METHODS: This population-based cohort study used data from birth notifications in Taiwan. A total of 19 277 offspring with maternal exposure to MVCs during pregnancy and 76 015 randomly selected comparison offspring without such exposure were selected. Neonatal adverse outcomes were identified from National Health Insurance medical claims data. Conditional logistic regression was used to estimate the unadjusted and adjusted odds ratios (aORs) of neonatal adverse outcomes. RESULTS: Offspring exposed to maternal MVCs during pregnancy had a higher risk of birth defects (aOR, 1.21; 95% CI, 1.04-1.41) than offspring without such exposure. This positive association was sustained with exposure to an MVC during the first or second trimester. A dose-response relationship (P = 0.0023) was observed between the level of injury severity and the risk of birth defects. CONCLUSIONS: In the early stages of pregnancy, maternal exposure to MVCs may entail a risk of birth defects in the offspring. The potential mechanisms for the associations of maternal exposure to MVCs with birth defects need further investigation.

The CD133 and CD34 cell types in human umbilical cord blood have the capacity to produce infectious dengue virus particles.

Although dengue virus (DENV) can establish infections in hematopoietic stem progenitor cells (HSPCs), there is little information on dengue virus persistent infection in CD34+ and CD133+ cell surface glycoproteins of hematopoietic stem cells (HSCs). CD34 and CD133 also function as cell-cell adhesion factors, which are present in umbilical cord blood (UCB). In this study, we sought to establish a persistent infection model of DENV infection in UCB using a prolonged period of infection lasting 30 days. Post-infection, the results exhibited a productive and non-productive phase of DENV production. Using a plaque assay, Western blot, and confocal microscopy, we demonstrated that CD133 and CD34 cells are target cells for DENV infection. Moreover, we showed that DENV particles can be recovered from the non-productive phase of DENV-infected CD34 and CD133 cells after co-incubation with Vero cells. We concluded that CD133 and CD34 retain their capacity to produce the infectious virus due to proliferation and their ability to repopulate, as deduced from a BrdU proliferation assay and flow cytometry analysis using t-distributed stochastic neighbor embedding. In summary, the platform to co-culture infected primitive HSCs from their non-productive phase onto Vero cells will give new insights into understanding the DENV dynamics in cell-to-cell transmission and reactivation of the virus.

Maternal outcomes in association with motor vehicle crashes during pregnancy: a nationwide population-based retrospective study.

BACKGROUND: Limited studies have assessed the association of motor vehicle crashes (MVCs) during pregnancy with adverse maternal outcomes using a population-based nationwide dataset that covers all MVCs. METHODS: A total of 20 844 births from women who had been involved in MVCs during pregnancy were obtained from the National Birth Notification (BN) Database in Taiwan. We randomly selected 83 274 control births from women in the BN matched on age, gestational age and crash date. All study subjects were linked to medical claims and the Death Registry to identify the maternal outcomes after crashes. Conditional logistic regression models were used to estimate the adjusted odds ratio (aOR) and 95% CI of adverse outcomes associated with MVCs during pregnancy. RESULTS: Pregnant women involved in MVCs had significantly higher risks of placental abruption (aOR=1.51, 95% CI 1.30 to 1.74), prolonged uterine contractions (aOR=1.31, 95% CI 1.11 to 1.53), antepartum haemorrhage (aOR=1.19, 95% CI 1.12 to 1.26) and caesarean delivery (aOR=1.05, 95% CI 1.02 to 1.09) than the controls. Such elevated risks tended to be higher in the MVCs with greater severity. Scooter riders had higher ORs of various adverse maternal outcomes than car drivers. CONCLUSIONS: Women involved in MVCs during pregnancy were at increased risk of various adverse maternal outcomes, especially in those with severe MVCs and riding scooters at MVCs. These findings suggest that clinicians should be aware of these effects, and educational materials that include the above information should be provided as part of prenatal care.

Different Characteristics and Clinical Outcomes between Early-Onset and Late-Onset Asthma: A Prospective Cohort Study.

Late-onset asthma (LOA) differs from early-onset asthma (EOA) in terms of prognosis and the treatment response because it has a much worse prognosis and a poorer response to standard asthma treatment. This study sought to investigate the characteristics and clinical outcomes of asthma patients with phenotypes distinguished by age at onset and atopy status. We prospectively recruited patients with asthma who were registered in a pay-for-performance program operated by Taiwan's National Health Insurance Administration (NHIA). These patients received regular outpatient treatment for at least 1 year at every outpatient clinic visit since 2019. Baseline characteristics and clinical outcomes were compared between patients with LOA (≥40 years) and those with EOA (<40 years). Of the consecutive 101 patients with asthma, 21 patients (20.7%) had EOA and 80 (79.3%) had LOA. In the 12-month period, patients with EOA had higher declines in forced expiratory volume in one second (FEV1; −2.1 ± 8.4 vs. 6.8 ± 13.1, % of predicted value, p = 0.037) and forced vital capacity (FVC; −4.6 ± 12.0 vs. 6.1 ± 13.6, % of predicted value, p = 0.023) than patients with LOA. Patients with nonatopic EOA had a significantly higher exacerbation rate at 12 months than patients with nonatopic LOA (50% vs. 11.8%, p = 0.012). Identification of different phenotypes of asthma is important in clinical practice because treatment responses may differ.

Clinical outcomes and prognostic factors of bronchiectasis rheumatoid overlap syndrome: A multi-institution cohort study.

The information regarding bronchiectasis with RA (BROS) is limited in Asia. The objective of this study was to investigate the clinical characteristics and outcomes of BROS in Taiwan. This multi-institute cohort study included patients with BROS from January 2006 to December 2017. The clinical, functional and microbiological data of these patients were retrieved from the Chang Gung Research Database. Respiratory failure and mortality were the primary outcomes. Severe exacerbation was defined as bronchiectasis- related hospitalizations or emergency department visits. A total of 343 patients with BROS were identified. One hundred and eight patients had severe exacerbation and exhibited significantly more previous exacerbations, a lower FEV1 and higher BACI score (11.1 vs. 7.5) than patients without severe exacerbation. The most prevalent species in sputum were Non-tuberculous mycobacteria (NTM) (14.8 %), Pseudomonas aeruginosa (14.2 %), and fungus (5.9%). 68.8% of BROS patients used disease modifying antirheumatic drugs (DMARD), 7.9% used biological DMARD. NTM and tuberculosis infection rates were higher in bDMARD group compared with nbDMARD group and others. Overall, the 3-year respiratory failure rate and mortality rate were 14.6 and 25.7% respectively. Patients with RA diagnosed before bronchiectasis had a significantly higher cumulative incidence of mortality in a 3-year follow-up than those with RA diagnosed after bronchiectasis. In Cox regression, age, higher RF value and systemic steroid use were independent risk factors for mortality in BROS. BROS patients with severe exacerbation had a high mortality rate in Taiwan. bDMARD is associated with a trend of increased risk of NTM and TB infections.

Hemolytic disease of the fetus and newborn caused by irregular antibody: A mortality case report and case series during the past 15 years in NCKUH.

OBJECTIVE: Hemolytic disease of the fetus and newborn (HDFN) caused by irregular antibodies is a rare, but possibly life-threatening condition. We report a case of severe intrauterine hemolysis caused by anti-E alloimmunization, and review 16 cases in the past 15 years of our hospital. CASE REPORT: A woman with gestational age 28 weeks and 5 days, received emergent Cesarean section because of fetal distress. The baby was expired at the next day after delivery and the comprehensive study showed severe anemia and alloimmunization related hemolysis caused by anti-E due to high antibody titer (1: 4096). CONCLUSION: Anti-E antibody is one of the most common non-Rhesus D antibodies in the pathogenesis of HDFN, but rarely leads to severe hemolysis. However, our case has the highest reported anti-E titer in HDFN and is the first case of mortality during the past 15 years in NCKUH.

Recurrent Fetal Anophthalmia Caused by retinoids acid gene 6 mutations: Correlation between prenatal ultrasonography, magnetic resonance imaging, and pathology.

OBJECTIVE: Anophthalmia is an extreme form on the spectrum of anophthalmia-microphthalmia (A/M) syndrome. Most articles define fetal microphthalmia by an ocular diameter (OD) less than fifth percentile. Diagnosis of fetal microphthalmia using only orbital measurements such as interocular distance (IOD), and OD may neglect the presence or morphology of the fetal lens, hence failing to identify abnormalities of the fetal globe. CASE REPORT: We hereby present a case of isolated fetal anophthalmia in two consecutive pregnancies from the same mother. Both fetuses presented as full-sized globes with absence or small size of lens under fetal ultrasound examination. Magnetic resonance imaging and pathology of the second fetus further revealed a thorough view of the underdeveloped globes. Whole exon sequencing (WES) analysis for the parents-fetus trio revealed compound heterozygous mutations of the retinoids acid gene 6 (STRA6). CONCLUSION: Detailed examination for intraocular structures including fetal lens, in addition to orbital measurements by ultrasound is crucial for diagnosis of diseases in the A/M spectrum.

Risk of Mortality in Association with Pregnancy in Women Following Motor Vehicle Crashes: A Systematic Review and Meta-Analysis.

The aim of the study was to provide a systematic review and meta-analysis of studies examining the association between mortality risk and motor vehicle crashes (MVCs) in pregnant women compared with nonpregnant women. We used relevant MeSH terms to identify epidemiological studies of mortality risk in relation to MVCs from PubMed, Embase, and MEDLINE databases. The Newcastle-Ottawa Scale (NOS) was used for quality assessment. For comparison of mortality from MVCs between pregnant and nonpregnant women, the pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random effects model. The eight studies selected met all inclusion criteria. These studies included 14,120 injured victims who were pregnant at the time of the incident and 207,935 victims who were not pregnant. Compared with nonpregnant women, pregnant women had a moderate but insignificant decrease in mortality risk (pooled OR = 0.68, 95% CI = 0.38-1.22, I2 = 88.71%). Subgroup analysis revealed that the pooled OR significantly increased at 1.64 (95% CI = 1.16-2.33, I2 < 0.01%) for two studies with a similar difference in the mean injury severity score (ISS) between pregnant and nonpregnant women. Future studies should further explore the risk factors associated with MVCs in pregnant women to reduce maternal mortality.

Prenatal Diagnosis of Fetal Congenital Mesoblastic Nephroma and Neonatal Follow-up.

We describe a case of fetal congenital mesoblastic nephroma (CMN) who was diagnosed with ultrasound at 32 weeks of gestation; after delivery, the neonate received left radical nephrectomy, and pathology report confirmed the diagnosis. All cross-sectional imaging studies, such as ultrasonography, computed tomography (CT) scanning, and magnetic resonance imaging, may help to define the organ of origin and the relationship to the ipsilateral kidney. To our knowledge, this is the first case of fetal CMN who was diagnosed in the third trimester and then with a live-born baby in Taiwan. The prenatal examination such as three-dimensional ultrasound and CT image was performed to help us for prenatal diagnosis.

Evidence that hematopoietic stem cells in human umbilical cord blood is infectable by dengue virus: proposing a vertical transmission candidate.

BACKGROUND: Recent studies have shown that dengue virus (DENV) can efficiently infect bone marrow hematopoietic stem cells (HSCs) as well as the placenta of pregnant women. Although mother-to-infant vertical transmission of DENV through the placenta has been well documented, the evidence of cell-associated vertical transmission is still unknown. Whether DENV can infect umbilical cord blood (UCB) cells before reaching the fetus remains to be explored. Here, we proposed that human UCB cells were permissive to the DENV infection and DENV infected CD133+ and CD34+ HSCs are reservoir of the virus that could be reactivated upon re-culturing in suitable cells. METHODS: Human UCB cells were freshly obtained and subjected to DENV infection. Multicolor flow cytometry (MFCM) was used to demonstrate the phenotypes of the infected HSC populations. Immunofluorescence analysis (IFA) and T-distributed Stochastic Neighbor Embedding (t-SNE) were used to show the association of the DENV antigen, non-structural protein1 (NS1) with HSCs. KEY FINDINGS: UCB cells were highly permissive to DENV infection. DENV altered the phenotype of the infected HSC population, increased the expression of HSCs, and affected the balance of transcription factors (TFs, GATA1/2/3). IFA revealed the association of the DENV antigen, non-structural protein1 (NS1), with CD34+ and CD133+ cells. T-distributed Stochastic Neighbor Embedding (t-SNE) analysis revealed heterogeneity in the distribution of CD133+NS1+, and CD34+ NS1+ cells. DENV particles were recovered from CD133+ and CD34+ cells even when virus production in the supernatant was negligible. SIGNIFICANCE: We predict that infection of CD133+ and CD34+ cells in the UCB serve as reservoirs for the amplification of DENV in UCB prior to the virus reaching the fetus and facilitate vertical transmission.

Factors Associated with Exercise-Induced Desaturation in Patients with Chronic Obstructive Pulmonary Disease.

Purpose: The 6-min walk test (6MWT) is a useful tool to assess the physiologic function in patients with chronic obstructive pulmonary disease (COPD). The recent study showed that patients with COPD with oxygen desaturation during the 6MWT had an increased risk of exacerbation and death compared with those without oxygen desaturation. This study aimed to explore the potential risk factors for exercise-induced desaturation (EID) in patients with COPD. Patients and Methods: Adult patients with COPD were enrolled from the Chang Gung Research Database between January 2013 and January 2017. Age, sex, body mass index, underlying diseases, medications, and results of the pulmonary function tests and 6MWT were retrospectively collected and analyzed. Results: Among 1768 patients with COPD, 932 (52.7%) had oxygen desaturation, and the other 836 (47.3%) had no desaturation during the 6MWT. The patients with EID had a shorter 6-min walk distance than those without desaturation (352.08±120.29 vs 426.56±112.56, p<0.0001). In the multivariate logistic regression analysis, older age, female sex, lower forced expiratory volume in 1 s, and comorbidity with atrial fibrillation (AF) were associated with oxygen desaturation during the 6MWT. Patients with EID had higher exacerbation frequency than those without desaturation in the 1-year follow-up period (0.59±1.50 vs 0.34±1.26, p<0.0001). Patients with COPD with AF also had a higher rate of exacerbation requiring emergency department visit or hospitalization in the 1-year follow-up. Conclusion: This study demonstrates that older age, low FEV1, and female sex are risk factors for EID. Desaturation during 6MWT is related to frequent acute exacerbation of COPD in the 1-year follow-up.

Hyaluronan Induces a Mitochondrial Functional Switch in Fast-Proliferating Human Mesenchymal Stem.

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.

Assessment of the blood flow in kidneys of growth-restricted fetuses using quantitative three-dimensional power Doppler ultrasound.

OBJECTIVE: Fetuses with fetal growth restrictions have higher perinatal mortality rates than fetuses without fetal growth restrictions. Vascularization of the fetal kidney is crucial to fetal growth. Hence, we assessed blood flow and vascularization of fetal kidneys in non-growth-restricted as well as growth-restricted fetuses using quantitative three-dimensional power Doppler ultrasound. MATERIALS AND METHODS: We undertook a prospective study to evaluate the vascular indices of fetal kidneys; i.e., the vascularization index, flow index and vascularization-flow index, in growth-restricted and non-growth-restricted fetuses using three-dimensional power Doppler ultrasound and quantitative three-dimensional histogram analysis. All fetuses from 20 to 40 weeks of gestation were singletons with a normal pregnancy and were followed up to delivery. RESULTS: In total, 209 fetuses without fetal growth restriction and 50 fetuses with fetal growth restriction were included. Our results showed the fetal renal vascularization index, flow index, and vascularization-flow index evaluated by three-dimensional power Doppler ultrasound can differentiate fetuses with fetal growth restriction from fetuses without fetal growth restriction. CONCLUSION: The fetal renal vascularization index, flow index, and vascularization-flow index measured by three-dimensional power Doppler ultrasound can be applied to prenatally detect fetal growth restriction. Our data support assessment of the fetal renal vascularization index, flow index, and vascularization-flow index using three-dimensional power Doppler ultrasound as a useful test for detecting fetuses with fetal growth restriction.