Demand and Requirements for a Digital Healthcare System to Manage Gestational Diabetes in Patients and Healthcare Professionals: A Cross-sectional Survey.

This study aimed to assess the current status of gestational diabetes mellitus (GDM) diagnosis and management, and the demand for a digital healthcare system, in order to develop an optimal digital-based management model for GDM. An anonymous online survey was conducted targeting pregnant/postpartum women (Group W), internal medicine physicians (Group P), and obstetricians (group O) from September 6, 2022 to December 31, 2022. The survey assessed the women's knowledge of GDM and gathered information about healthcare professionals' (HCPs) current GDM management practices. All groups were asked about their acceptance of and demands for a digital healthcare system for GDM. Statistical comparisons between groups were conducted using the chi-square test or Fisher's exact test where appropriate. A total of 168 participants were in Group W, 185 in Group P, and 256 in Group O. Participants from all groups recognized the need for a digital healthcare system for GDM (Group W: 95.8%, Group P: 85.9%, Group O: 60%). However, HCPs showed less willingness to integrate these systems into their clinics than pregnant/postpartum women. Essential features identified were recording blood glucose levels and insulin, along with automatic data linkage from self-monitoring devices. Group W showed a higher preference for lab test access, search functionality, and fetal weight assessment than groups P and O (all P < .0001), while Groups P and O had a greater preference for recording insulin and maternal body weight compared to Group W (P = .0141 and .0023, respectively). Both pregnant/postpartum women and HCPs acknowledged the benefits of utilizing a digital healthcare system for managing GDM. However, there were differences in perspectives among these groups.

The associations between maternal and fetal exposure to endocrine-disrupting chemicals and asymmetric fetal growth restriction: a prospective cohort study.

Recent evidence has revealed associations between endocrine-disrupting chemicals (EDCs) and placental insufficiency due to altered placental growth, syncytialization, and trophoblast invasion. However, no epidemiologic study has reported associations between exposure to EDCs and asymmetric fetal growth restriction (FGR) caused by placenta insufficiency. The aim of this study was to evaluate the association between EDC exposure and asymmetric FGR. This was a prospective cohort study including women admitted for delivery to the Maternal Fetal Center at Seoul St. Mary's Hospital between October 2021 and October 2022. Maternal urine and cord blood samples were collected, and the levels of bisphenol-A (BPA), monoethyl phthalates, and perfluorooctanoic acid in each specimen were analyzed. We investigated linear and non-linear associations between the levels of EDCs and fetal growth parameters, including the head circumference (HC)/abdominal circumference (AC) ratio as an asymmetric parameter. The levels of EDCs were compared between fetuses with and without asymmetric FGR. Of the EDCs, only the fetal levels of BPA showed a linear association with the HC/AC ratio after adjusting for confounding variables (ß = 0.003, p < 0.05). When comparing the normal growth and asymmetric FGR groups, the asymmetric FGR group showed significantly higher maternal and fetal BPA levels compared to the normal growth group (maternal urine BPA, 3.99 µg/g creatinine vs. 1.71 µg/g creatinine [p < 0.05]; cord blood BPA, 1.96 µg/L vs. -0.86 µg/L [p < 0.05]). In conclusion, fetal exposure levels of BPA show linear associations with asymmetric fetal growth patterns. High maternal and fetal exposure to BPA might be associated with asymmetric FGR.

Compensatory Interactions between Corneal and Internal Astigmatism despite Lifestyle Changes.

This study explores whether children's refractive errors and visual behaviors reverted to pre-COVID-19 levels a year after normal schooling resumed in Hong Kong as well as the impact of corneal and internal astigmatism on refractive astigmatism development. Vision survey data and questionnaire results collected in 2022 (n = 119) and 2020 (n = 173) were compared. Cross-sectional data showed similar proportions of astigmatism (cylindrical power ≥ 0.75 D) in the 2020 (49.1%) and 2022 cohorts (55.5%). Despite a 0.28 D increase in corneal astigmatism, a compensatory 0.24 D increase in internal astigmatism of opposite direction kept refractive astigmatism relatively stable. The questionnaire data showed that children spent an additional 0.5 h/day outdoors on weekends post-resumption of normal schooling but engaged in more near-work activities, especially non-screen near-work, by approximately 1 h/day on both weekdays and weekends. These findings were supported by longitudinal data from 72 children who participated in both surveys. This study highlights the significant role of corneal and internal astigmatism in refractive astigmatism changes. Despite the return to in-person classes, children's total near-work time increased and astigmatism remained high. These findings underscore the need for comprehensive strategies to reduce the high environmental risks for refractive error development in children.

Synchronous myopia development induced by bilateral form deprivation in chicks.

Form deprivation (FD) is a widely employed experimental paradigm, typically used to induce unilateral myopia in animal models. This model is weakened by potential influence upon the FD eye from vision in the freely-viewing contralateral eye, which could be eliminated by imposing FD in both eyes; but while a few previous studies have explored the feasibility of inducing bilateral FD in chicks, substantial discrepancies in treatment outcomes were noted. Consequently, this study aimed to establish a bilateral FD myopia model in chicks, with validation by investigating the associated ocular growth patterns, feeding, and social behavior. Six-day-old chicks were treated with bilateral (n = 21) or unilateral (n = 10) FD for 12 days; the fellow untreated eyes in the unilateral FD group served as controls. Refractive error, corneal power, and ocular axial dimensions were measured at 4-day intervals after the onset of form deprivation, with a Hartinger refractometer, a custom-made videokeratography system, and a high-resolution A-scan ultrasonographer, respectively. Body weight was monitored to assess the chick's physical development. Our results showed that birds treated with bilateral FD grew as robustly as the unilaterally form-deprived chicks, with similar or slightly heavier body weights and mortalities. Unilateral FD induced significantly higher myopia in the treated eye, with stronger corneal power, deeper anterior and vitreous chambers, and longer axial length. Moreover, either bilaterally or unilaterally FD eyes developed similar refractive error (bilateral FD, left: -28.03 ± 9.06 D, right: -28.44 ± 9.45 D; unilateral FD: -29.48 ± 8.26 D) and ocular biometric changes; but choroidal thickness was thicker in bilaterally FD eyes, rather than thinner as in unilaterally FD eyes. In addition to the highly synchronized (symmetrical, parallel) development reported previously in bilateral FD, we found in this study that the correlations between bilaterally form-deprived eyes were highest for ocular biometric parameters directly contributing to myopia development, including corneal power (r = 0.74 to 0.93), anterior chamber depth (r = 0.60 to 0.85), vitreous chamber depth (r = 0.92 to 0.94), and axial length (r = 0.90 to 0.96). The remarkably synchronized growth pattern confirmed the feasibility of the bilateral FD paradigm for future research on myopia.

Characteristics of ciliary muscle profile in high myopes measured by swept-source anterior segment optical coherence tomography.

OBJECTIVE: To characterize and compare the ciliary muscle thickness (CMT) between low and high myopes using swept-source anterior segment optical coherence tomography (AS-OCT). METHODS: Forty visually healthy young Chinese adults aged 18-25 years were divided into two groups based on refractive errors: low myopia (n = 20, spherical-equivalent refractive error (SER) between -0.50 D to -3.00 D) and high myopia (n = 20, SER ≤ -6.00 D). Cycloplegic refractions were performed before axial length (AL) and CMT were measured using a partial coherence laser interferometer and an AS-OCT respectively. CMT was measured perpendicularly to the sclera-ciliary muscle interface at 1 mm (CMT_1), 2 mm (CMT_2), and 3 mm (CMT_3) posterior to the scleral spur, and at the location with maximal thickness (CMT_MAX). RESULTS: High myopes demonstrated thicker CMT at 2 mm (CMT_2, p = 0.035) and 3 mm (CMT_3, p = 0.003) posterior to the scleral spur, but thinner maximal CMT (CMT_MAX, p = 0.005) than low myopes. The apical CMT_1 and CMT_MAX were also thinner in high myopes than in low myopes (both p< 0.001). CMT_MAX, apical CMT_1, and apical CMT_MAX correlated directly with SER and inversely with AL; in contrast, CMT_2 and CMT_3 showed inverse correlations with SER but direct correlations with AL. CONCLUSION: Our findings revealed significant differences in CMT between low and high myopes, with high myopes showing thicker CMT at 2 mm and 3 mm posterior to the scleral spur, but thinner maximal CMT. These results provide new evidence of the potential structural differences in ciliary muscles during myopia development and progression.

Prediction of gestational diabetes mellitus in Asian women using machine learning algorithms.

This study developed a machine learning algorithm to predict gestational diabetes mellitus (GDM) using retrospective data from 34,387 pregnancies in multi-centers of South Korea. Variables were collected at baseline, E0 (until 10 weeks' gestation), E1 (11-13 weeks' gestation) and M1 (14-24 weeks' gestation). The data set was randomly divided into training and test sets (7:3 ratio) to compare the performances of light gradient boosting machine (LGBM) and extreme gradient boosting (XGBoost) algorithms, with a full set of variables (original). A prediction model with the whole cohort achieved area under the receiver operating characteristics curve (AUC) and area under the precision-recall curve (AUPR) values of 0.711 and 0.246 at baseline, 0.720 and 0.256 at E0, 0.721 and 0.262 at E1, and 0.804 and 0.442 at M1, respectively. Then comparison of three models with different variable sets were performed: [a] variables from clinical guidelines; [b] selected variables from Shapley additive explanations (SHAP) values; and [c] Boruta algorithms. Based on model [c] with the least variables and similar or better performance than the other models, simple questionnaires were developed. The combined use of maternal factors and laboratory data could effectively predict individual risk of GDM using a machine learning model.

Influenza vaccination during pregnancy and influencing factors in Korea: A multicenter questionnaire study of pregnant women and obstetrics and gynecology doctors.

BACKGROUND: Although the World Health Organization and health authorities in most countries recommend that pregnant women receive inactivated influenza virus vaccines, coverage remains low. This study aimed to investigate (1) the proportion of pregnant women who received an influenza vaccination and influencing factors and (2) the proportion of obstetrics and gynecology (OBGYN) doctors who routinely recommend influenza vaccination to pregnant women and influencing factors. METHODS: Two separate, anonymized questionnaires were developed for physicians and pregnant and postpartum women and were distributed to multicenters and clinics in South Korea. The proportions of women who received influenza vaccination during pregnancy and OBGYN doctors who routinely recommend the influenza vaccine to pregnant women were analyzed. Independent influencing factors for both maternal influenza vaccination and OBGYN doctors' routine recommendations to pregnant women were analyzed using log-binomial regression analysis. RESULTS: The proportion of self-reported influenza vaccination during pregnancy among 522 women was 63.2%. Pregnancy-related independent factors influencing maternal influenza vaccination were "(ever) received information about influenza vaccination during pregnancy" (OR 8.9, 95% CI 4.17-19.01), "received vaccine information about from OBGYN doctors" (OR 11.44, 95% CI 5.46-24.00), "information obtained from other sources" (OR 4.38, 95% CI 2.01-9.55), and "second/third trimester" (OR 2.41, 95% CI 1.21-4.82).. Among 372 OBGYN doctors, 76.9% routinely recommended vaccination for pregnant women. Independent factors effecting routine recommendation were "working at a private clinic or hospital" (OR 5.33, 95% CI 2.44-11.65), "awareness of KCDC guidelines" (OR 3.11, 95% CI 1.11-8.73), and "awareness of the 2019 national free influenza vaccination program for pregnant women" (OR 4.88, 95% CI 2.34-10.17). OBGYN doctors most commonly chose 'guidelines proposed by the government or public health (108, 46%) and academic committees (59, 25%), as a factor which expect to affect the future recommendation CONCLUSION: This study showed that providing information about maternal influenza vaccination, especially by OBGYN doctors, is crucial for increasing vaccination coverage in pregnant women. Closer cooperation between the government and OBGYN academic societies to educate OBGYN doctors might enhance routine recommendations.

Fascin Regulates the Hippo Pathway and Is Important for Melanoma Development.

BACKGROUND/AIM: Fascin, an actin-bundling protein, plays an essential role in cancer metastasis. The Hippo pathway is critical for carcinogenesis and cancer stem cell self-renewal. Mammalian STE20-like kinase (MST) is a core component of the Hippo pathway. However, whether fascin and MST2 affect melanoma remain largely unknown. This study aimed to investigate the role of fascin and MST2 in melanoma development. MATERIALS AND METHODS: Surgically excised skin melanomas and the adjacent non-tumorous skin tissue from 30 cases were analyzed using immunohistochemistry for fascin and MST2. The melanoma cell line WM793 was employed for fascin and MST2 knock-down followed by western blotting, and melanoma xenografting in BALB/c mice. RESULTS: Immunohistochemistry revealed increased expression of fascin and decreased expression of MST2 in melanoma. The reverse correlation of fascin and MST2 was statistically significant. Fascin siRNA upregulated MST2 expression; however, MST2 siRNA did not significantly affect fascin expression in the WM793. WM793 xenografting followed by fascin knock-down inhibited tumor growth significantly in the animal study. CONCLUSION: Fascin is a regulator of the Hippo pathway and plays an important role in melanoma development. Therefore, fascin could be a potential therapeutic target for melanoma.

Biophysical properties of corneal cells reflect high myopia progression.

Myopia is a common ocular disorder with significant alterations in the anterior ocular structure, including the cornea. The cell biophysical phenotype has been proposed to reflect the state of various diseases. However, the biophysical properties of corneal cells have not been characterized during myopia progression and their relationship with myopia remains unknown. This study characterizes the biophysical properties of corneal cells in normal, myopic, and recovered conditions, using two classical myopia models. Surprisingly, myopic corneal cells considerably reduce F-actin and microtubule content and cellular stiffness and generate elevated traction force compared with control cells. When myopia is restored to the healthy state, these biophysical properties are partially or fully restored to the levels of control cells. Furthermore, the level of chromatin condensation is significantly increased in the nucleus of myopic corneal cells and reduced to a level similar to healthy cells after recovery. These findings demonstrate that the reversible biophysical alterations of corneal cells reflect myopia progression, facilitating the study of the role of corneal cell biophysics in myopia.

Corneal proteome and differentially expressed corneal proteins in highly myopic chicks using a label-free SWATH-MS quantification approach.

Myopia, or short-sightedness, is a highly prevalent refractive disorder in which the eye's focal length is too short for its axial dimension in its relaxed state. High myopia is associated with increased risks of blinding ocular complications and abnormal eye shape. In addition to consistent findings on posterior segment anomalies in high myopia (e.g., scleral remodeling), more recent biometric and biomechanical data in myopic humans and animal models also indicate anterior segment anomalies (e.g., corneal biomechanical properties). Because the cornea is the anterior-most ocular tissue, providing essential refractive power and physiological stability, it is important to understand the biochemical signaling pathway during myopia development. This study first aimed to establish the entire chicken corneal proteome. Then, using the classical form deprivation paradigm to induce high myopia in chicks, state-of-the-art bioinformatics technologies were applied to identify eight differentially expressed proteins in the highly myopic cornea. These results provide strong foundation for future corneal research, especially those using chicken as an animal model for myopia development.

Relationship of common hemodynamic and respiratory target parameters with brain tissue oxygen tension in the absence of hypoxemia or hypotension after cardiac arrest: A post-hoc analysis of an experimental study using a pig model.

Brain tissue oxygen tension (PbtO2)-guided care, a therapeutic strategy to treat or prevent cerebral hypoxia through modifying determinants of cerebral oxygen delivery, including arterial oxygen tension (PaO2), end-tidal carbon dioxide (ETCO2), and mean arterial pressure (MAP), has recently been introduced. Studies have reported that cerebral hypoxia occurs after cardiac arrest in the absence of hypoxemia or hypotension. To obtain preliminary information on the degree to which PbtO2 is responsive to changes in the common target variables for PbtO2-guided care in conditions without hypoxemia or hypotension, we investigated the relationships between the common target variables for PbtO2-guided care and PbtO2 using data from an experimental study in which the animals did not experience hypoxemia or hypotension after resuscitation. We retrospectively analyzed 170 sets of MAP, ETCO2, PaO2, PbtO2, and cerebral microcirculation parameters obtained during the 60-min post-resuscitation period in 10 pigs resuscitated from ventricular fibrillation cardiac arrest. PbtO2 and cerebral microcirculation parameters were measured on parietal cortices exposed through burr holes. Multiple linear mixed effect models were used to test the independent effects of each variable on PbtO2. Despite the absence of arterial hypoxemia or hypotension, seven (70%) animals experienced cerebral hypoxia (defined as PbtO2 <20 mmHg). Linear mixed effect models revealed that neither MAP nor ETCO2 were related to PbtO2. PaO2 had a significant linear relationship with PbtO2 after adjusting for significant covariates (P = 0.030), but it could explain only 17.5% of the total PbtO2 variance (semi-partial R2 = 0.175; 95% confidence interval, 0.086-0.282). In conclusion, MAP and ETCO2 were not significantly related to PbtO2 in animals without hypoxemia or hypotension during the early post-resuscitation period. PaO2 had a significant linear association with PbtO2, but its ability to explain PbtO2 variance was small.

Extracellular Acidity-mediated Expression of cPLA2γ Confers Resistance in Gastric Cancer Cells.

BACKGROUND/AIM: Extracellular acidity, a characteristic of solid tumors, has been proposed to be a critical factor for aggravating tumor malignancy and conferring resistance to therapeutics. Recently, acidity has been implicated in inflammatory responses, which are mediated through active lipid metabolites in various human tissues. In the present study, we investigated whether acidity can affect lipid-mediated signaling, and found that phospholipase A2 (PLA2) activity increased at acidic pH in SNU601 and AGS gastric carcinoma cell lines. MATERIALS AND METHODS: To identify the PLA2 isoform that is responsible for the acidity-induced activity, we assessed mRNA levels of cPLA2 isotypes through real-time qPCR, and protein levels through immunoblot assay in cells cultured in acidic medium. RESULTS: It was found that acidic pH conditions markedly elevated the PLA2γ expression. A gene interference study using specific siRNA of cPLA2γ suggested that expression of cPLA2γ in acidic culture conditions may be associated with protection of cancer cells in acidic environment, as shown by cell viability and clonogenic assays. In addition, expression of cPLA2γ appeared to confer cell resistance to anticancer drugs under acidic pH conditions. CONCLUSION: Acidity-induced cPLA2γ expression may exert protective effects by imparting resistance to the gastric cancer cells under acidic environment.

PROLOGUE (PROgnostication using LOGistic regression model for Unselected adult cardiac arrest patients in the Early stages): Development and validation of a scoring system for early prognostication in unselected adult cardiac arrest patients.

BACKGROUND: Early prognostication after cardiac arrest would be useful. We aimed to develop a scoring model for early prognostication in unselected adult cardiac arrest patients. METHODS: We retrospectively analysed data of adult non-traumatic cardiac arrest patients treated at a tertiary hospital between 2014 and 2018. The primary outcome was poor outcome at hospital discharge (cerebral performance category, 3-5). Using multivariable logistic regression analysis, independent predictors were identified among known outcome predictors, that were available at intensive care unit admission, in patients admitted in the first 3 years (derivation set, N = 671), and a scoring system was developed with the variables that were retained in the final model. The scoring model was validated in patients admitted in the last 2 years (validation set, N = 311). RESULTS: The poor outcome rates at hospital discharge were similar between the derivation (66.0%) and validation sets (64.3%). Age <59 years, witnessed collapse, shockable rhythm, adrenaline dose <2 mg, low-flow duration <18 min, reactive pupillary light reflex, Glasgow Coma Scale motor score ≥2, and levels of creatinine <1.21 mg dl-1, potassium <4.4 mEq l-1, phosphate <5.8 mg dl-1, haemoglobin ≥13.2 g dl-1, and lactate <8 mmol l-1 were retained in the final multivariable model and used to develop the scoring system. Our model demonstrated excellent discrimination in the validation set (area under the curve of 0.942, 95% confidence interval 0.917-0.968). CONCLUSIONS: We developed a scoring model for early prognostication in unselected adult cardiac arrest patients. Further validations in various cohorts are needed.

Peripheral blood BRCA1 methylation profiling to predict familial ovarian cancer.

OBJECTIVE: Familial cancer appears at a young age and its incidence is increasing. About 12% of familial ovarian cancer cases are associated with BRCA1/2 mutations (BRCAm). In this study, we investigated BRCA1 methylation may predict ovarian cancer in those with a family history of cancer (FHC) but without BRCA1/2 mutations (BRCAwt). METHODS: Using peripheral blood DNA from 55 subjects without a history of cancer [cancer(-)] and 52 ovarian cancer patients, we examined BRCA1 promoter methylation through bisulfite sequencing of the promoter and expressed the results as the cumulative methylation index. Then, we evaluated the BRCA1 promoter methylation according to BRCA1/2 germline mutations. RESULTS: BRCA1 methylation was more prevalent in the BRCAm cancer(-) group than in the BRCAwt cancer(-) group and ovarian cancer patients (p=0.031 and p=0.019, respectively). In the BRCAwt cancer(-) group, BRCA1 methylation was more prevalent in those with an FHC than in those without one and in the BRCAm cancer(-) group with an FHC (p=0.001 and p<0.001, respectively). CONCLUSION: Our data suggest a predictive role of BRCA1 methylation profile for ovarian cancer in those without a history of cancer but with an FHC. BRCA1 methylation has important implications for diagnostic and predictive testing of those with BRCAwt cancer(-) status with FHC.

Classification of cervical neoplasms on colposcopic photography using deep learning.

Colposcopy is widely used to detect cervical cancers, but experienced physicians who are needed for an accurate diagnosis are lacking in developing countries. Artificial intelligence (AI) has been recently used in computer-aided diagnosis showing remarkable promise. In this study, we developed and validated deep learning models to automatically classify cervical neoplasms on colposcopic photographs. Pre-trained convolutional neural networks were fine-tuned for two grading systems: the cervical intraepithelial neoplasia (CIN) system and the lower anogenital squamous terminology (LAST) system. The multi-class classification accuracies of the networks for the CIN system in the test dataset were 48.6 ± 1.3% by Inception-Resnet-v2 and 51.7 ± 5.2% by Resnet-152. The accuracies for the LAST system were 71.8 ± 1.8% and 74.7 ± 1.8%, respectively. The area under the curve (AUC) for discriminating high-risk lesions from low-risk lesions by Resnet-152 was 0.781 ± 0.020 for the CIN system and 0.708 ± 0.024 for the LAST system. The lesions requiring biopsy were also detected efficiently (AUC, 0.947 ± 0.030 by Resnet-152), and presented meaningfully on attention maps. These results may indicate the potential of the application of AI for automated reading of colposcopic photographs.

Data on corneal proteome and differentially expressed corneal proteins in highly myopic chicks using a data independent quantification approach.

Myopia is an abnormal refractive status, explained by an excessive ocular lengthening mostly in posterior segments. Although growing evidence of anterior segments, specifically altered corneal geometries with biomechanical properties in myopes have been reported, the mechanism behind is poorly understood. We hereby prepared experimentally induced highly myopic chicks to investigate the molecular basis of corneal remodeling by applying a novel proteomic approach integrated with information dependent acquisition (IDA) and data independent quantification (SWATH-MS) analysis. As a result, differentially expressed protein biomarkers that might be involved in structural changes were screened based on the first of its kind unique chicken corneal proteome. All generated raw data from IDA and SWATH-MS are accessible at Peptide Atlas public repository (http://www.peptideatlas.org/PASS/PASS01410) for general release.

High myopia induced by form deprivation is associated with altered corneal biomechanical properties in chicks.

The cornea is a soft, transparent, composite organic tissue, which forms the anterior outer coat of the eyeball. Although high myopia is increasing in prevalence worldwide and is known to alter the structure and biomechanical properties of the sclera, remarkably little is known about its impact on the biomechanics of the cornea. We developed and validated a novel optical-coherence-tomography-indentation probe-to measure corneal biomechanical properties in situ, in chicks having experimentally-induced high myopia, while maintaining intraocular pressure at levels covering the physiological range. We found that the cornea of highly myopic chicks was more steeply curved and softer, at all tested intraocular pressures, than that in contralateral, non-myopic eyes, or in age-matched normal, untreated eyes. These results indicate that the biomechanical properties of the cornea are altered in chicks developing experimentally-induced myopia.

The impact of the centrifuge characteristics and centrifugation protocols on the cells, growth factors, and fibrin architecture of a leukocyte- and platelet-rich fibrin (L-PRF) clot and membrane.

L-PRF (leukocyte- and platelet-rich fibrin) is one of the four families of platelet concentrates for surgical use and is widely used in oral and maxillofacial regenerative therapies. The first objective of this article was to evaluate the mechanical vibrations appearing during centrifugation in four models of commercially available table-top centrifuges used to produce L-PRF and the impact of the centrifuge characteristics on the cell and fibrin architecture of a L-PRF clot and membrane. The second objective of this article was to evaluate how changing some parameters of the L-PRF protocol may influence its biological signature, independently from the characteristics of the centrifuge. In the first part, four different commercially available centrifuges were used to produce L-PRF, following the original L-PRF production method (glass-coated plastic tubes, 400 g force, 12 minutes). The tested systems were the original L-PRF centrifuge (Intra-Spin, Intra-Lock, the only CE and FDA cleared system for the preparation of L-PRF) and three other laboratory centrifuges (not CE/FDA cleared for L-PRF): A-PRF 12 (Advanced PRF, Process), LW-UPD8 (LW Scientific) and Salvin 1310 (Salvin Dental). Each centrifuge was opened for inspection, two accelerometers were installed (one radial, one vertical), and data were collected with a spectrum analyzer in two configurations (full-load or half load). All clots and membranes were collected into a sterile surgical box (Xpression kit, Intra-Lock). The exact macroscopic (weights, sizes) and microscopic (photonic and scanning electron microscopy SEM) characteristics of the L-PRF produced with these four different machines were evaluated. In the second part, venous blood was taken in two groups, respectively, Intra-Spin 9 ml glass-coated plastic tubes (Intra-Lock) and A-PRF 10 ml glass tubes (Process). Tubes were immediately centrifuged at 2700 rpm (around 400 g) during 12 minutes to produce L-PRF or at 1500 rpm during 14 minutes to produce A-PRF. All centrifugations were done using the original L-PRF centrifuge (Intra-Spin), as recommended by the two manufacturers. Half of the membranes were placed individually in culture media and transferred in a new tube at seven experimental times (up to 7 days). The releases of transforming growth factor ß-1 (TGFß-1), platelet derived growth factor AB (PDGF-AB), vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2) were quantified using ELISA kits at these seven experimental times. The remaining membranes were used to evaluate the initial quantity of growth factors of the L-PRF and A-PRF membranes, through forcible extraction. Very significant differences in the level of vibrations at each rotational speed were observed between the four tested centrifuges. The original L-PRF centrifuge (Intra-Spin) was by far the most stable machine in all configurations and always remained under the threshold of resonance, unlike the three other tested machines. At the classical speed of production of L-PRF, the level of undesirable vibrations on the original centrifuge was between 4.5 and 6 times lower than with other centrifuges. Intra-Spin showed the lowest temperature of the tubes. A-PRF and Salvin were both associated with a significant increase in temperature in the tube. Intra-Spin produced the heaviest clot and quantity of exudate among the four techniques. A-PRF and LW produced much lighter, shorter and narrower clots and membranes than the two other centrifuges. Light microscopy analysis showed relatively similar features for all L-PRF types (concentration of cell bodies in the first half). However, SEM illustrated considerable differences between samples. The original Intra-Spin L-PRF showed a strongly polymerized thick fibrin matrix and all cells appeared alive with a normal shape, including the textured surface aspect of activated lymphocytes. The A-PRF, Salvin and LW PRF-like membranes presented a lightly polymerized slim fibrin gel and most of the visible cell bodies appeared destroyed (squashed or shrunk). In the second part of this study, the slow release of the three tested growth factors from original L-PRF membranes was significantly stronger (more than twice stronger, p<0.001) at all experimental times than the release from A-PRF membranes. No trace of BMP2 could be detected in the A-PRF. A slow release of BMP2 was detected during at least 7 days in the original L-PRF. Moreover, the original L-PRF clots and membranes (produced with 9 mL blood) were always significantly larger than the A-PRF (produced with 10 mL blood). The A-PRF membranes dissolved in vitro after less than 3 days, while the L-PRF membrane remained in good shape during at least 7 days. Each centrifuge has its clear own profile of vibrations depending on the rotational speed, and the centrifuge characteristics are directly impacting the architecture and cell content of a L-PRF clot. This result may reveal a considerable flaw in all the PRP/PRF literature, as this parameter was never considered. The original L-PRF clot (Intra-Spin) presented very specific characteristics, which appeared distorted when using centrifuges with a higher vibration level. A-PRF, LW and Salvin centrifuges produced PRF-like materials with a damaged and almost destroyed cell population through the standard protocol, and it is therefore impossible to classify these products in the L-PRF family. Moreover, when using the same centrifuge, the original L-PRF protocol allowed producing larger clots/membranes and a more intense release of growth factors (biological signature at least twice stronger) than the modified A-PRF protocol. Both protocols are therefore significantly different, and the clinical and experimental results from the original L-PRF shall not be extrapolated to the A-PRF. Finally, the comparison between the total released amounts and the initial content of the membrane (after forcible extraction) highlighted that the leukocytes living in the fibrin matrix are involved in the production of significant amounts of growth factors. The centrifuge characteristics and centrifugation protocols impact significantly and dramatically the cells, growth factors and fibrin architecture of L-PRF.

Double-balloon enteroscopy in elderly patients: is it safe and useful?

BACKGROUND/AIMS: Providers may be hesitant to perform double-balloon enteroscopy (DBE) in the elderly because the increased number of co-morbidities in this population poses a greater risk of complications resulting from sedation. There are limited data on the use of DBE in the elderly. Here, we assessed the safety and efficacy of DBE in the elderly compared to those in younger patients. METHODS: We retrospectively analyzed the medical records of 158 patients who underwent 218 DBEs. Patients were divided into an elderly group (age ≥65 years; mean 71.4±5.4; n=34; 41 DBEs) and a younger group (age <65 years; mean 39.5±13.5; n=124; 177 DBEs). RESULTS: In both groups, the most common indication for DBE was obscure gastrointestinal bleeding. Mucosal lesions (33.3% vs. 60.9%; P=0.002) were the most common finding in both groups, followed by tumors (30.8% vs. 14.1%; P=0.036). The elderly were more likely to receive interventional therapy (51.3% vs. 23.5%; P=0.001). The diagnostic yield of DBE was slightly higher in the elderly group (92.3% vs. 86.5%; P=0.422), but was not statistically significant. The therapeutic success rate of DBE was 100% in the elderly group compared to 87.5% in the younger group (P=0.536). The overall DBE complication rate was 1.8% overall, and this rate did not differ significantly between the groups (2.6% vs. 1.7%; P=0.548). CONCLUSIONS: DBE is safe and effective in the elderly, and has a high diagnostic yield and high therapeutic success rate.