Assessment of right ventricular dysfunction and its association with excess risk of cardiovascular events in patients undergoing maintenance hemodialysis.

AIMS: Recent accumulating evidence has recently documented a significant prevalence of right ventricular dysfunction (RVD) in end-stage renal disease (ESRD) patients. Tricuspid annular plane systolic excursion (TAPSE)/pulmonary-artery systolic pressure (PASP) ratio assessed with echocardiography might be a useful clinical index of right ventricular (RV) -pulmonary arterial (PA) coupling. The current study aimed to investigate the value of the TAPSE/PASP ratios in patients on maintenance hemodialysis (MHD). METHODS: We studied 83 times echocardiographic tests from 68 patients with MHD. The associations of TAPSE/PASP ratios with echocardiography variables, clinical characteristics, and biochemical parameters were analyzed, as well as the associations of TAPSE/PASP ratios with odds of all-cause mortality, cardiovascular disease (CVD) events and frequent intermittent dialysis hypotension (IDH). RESULTS: Correlation analysis showed TAPSE/PASP ratios positively correlated with LVEF and negatively correlated with E/A and E/e' values. For clinical and biochemical parameters, TAPSE/PASP ratios negatively correlated with BNP, NT-proBNP, age, CRP, and average interdialysis weight gain (ΔBW) and positively correlated with albumin. Logistic regression analysis, which induced the TAPSE/PASP ratio as a continuous variable (per 0.1 mm/mmHg increase), identified that the TAPSE/PASP ratio was associated with decreased CVD events (OR 0.386 [95% CI 0.231-0.645], p < 0.001) and frequent IDH odds (OR 0.571 [95% CI 0.397-0.820], p = 0.002). Moreover, the TAPSE/PASP ratio independently predicted CVD events (adjusted HR 0.539 [95% CI 0.391-0.743], p < 0.001) during a follow-up period of 12 months. CONCLUSIONS: RVD, assessed by echocardiography TAPSE/PASP ratio, was found to be associated with increased risks of CVD events and frequent IDH in patients with MHD.

The incidence, risk factors, management and prognosis of postoperative systemic complications after ophthalmic surgery: a retrospective study at a tertiary, academic referral hospital over a decade.

PURPOSE: To explore the incidence, risk factors, management and prognosis of systemic complications after ophthalmic surgeries. METHODS: A retrospective review of hospitalized patients undergoing ophthalmic surgeries between 2012 and 2022 at Peking Union Medical College Hospital was performed to summarize and analyse the postoperative systemic complications. Multivariate logistic and linear regression analyses were conducted to clarify the risk factors of postoperative systemic complications and factors associated with the severity of adverse events. RESULTS: A total of 34,841 patients underwent inpatient ophthalmic surgery, among which 162 systemic complications occurred in 150 patients during postoperative hospitalization. The overall incidence rate was 0.4%, with cardiovascular events (48.1%), digestive events (13.6%) and fever (12.3%) being the leading causes. About 17.3% of the cases had conditions improved after observation, 19.1% after symptomatic treatment, 54.9% had consultation with specific intervention and 8.6% were transferred to the corresponding departments for specialized treatment. For the prognosis, 93.8% had condition improved, 5.6% chose voluntary discharge without improvement, and one patient died of respiratory failure caused by postoperative pulmonary infection. The worse ADL (activities of daily living) grading, indication of primary intraocular lymphoma or intraocular tumour, surgery of simple pars plana vitrectomy (PPV), PPV with silicone oil tamponade, PPV with gas tamponade, general anaesthesia, history of diabetes mellitus (DM), chronic heart failure and digestive system disease were the risk factors positively correlated with postoperative systemic complications (p < .05). The worse ADL grading, history of DM and respiratory system disease were also positively correlated with the severity of the adverse events (p < .05). CONCLUSIONS: The incidence of postoperative systemic complications was low among patients undergoing ophthalmic surgery, most were mild and could be relieved after observation, symptomatic or specialist consultation. Patients with worse ADL and history of DM should be paid extra attention.

Effect assessment of a type of xeno-free and serum-free human adipose-derived mesenchymal stem cells culture medium by proliferation and differentiation capacities.

Human mesenchymal stem cells (hMSCs) possess broad prospects in pre-clinical research. In vitro amplification of hMSCs requires appropriate medium to reach the number of seed cells with clinical significance. However, the uncertainty of the heterologous components of the traditional fetal bovine serum (FBS) culture medium has great safety risks. Moreover, existing commercial hMSCs medium is very expensive, therefore a safer and more optimal hMSCs medium is urgently needed. Accordingly, we developed five components adipose-derived hMSCs (hADMSCs) medium without xenogenic components, named E5 SFM. which is mainly composed of knockout serum replacement (KSR), and additionally four components such as fibroblast growth factor and transferrin. Here, we mainly compared the E5 SFM with traditional FBS-containing medium and a commercial medium by surface markers testing, proliferation assay as well as osteogenic, adipogenic and chondrogenic differentiation assessment. We demonstrated that hADMSCs cultured in the E5 SFM showed similar morphological characteristics and immunophenotypes to those in other media. Notably, cell proliferative capability was similar to that in the commercial medium, but higher than that in the FBS-containing medium and other media. Additionally, their capabilities of adipogenic and osteogenic differentiation were significantly higher than those of other media. Consequently, we concluded that the E5 SFM medium can not only effectively promote cell proliferation of hMSCs, but also has optimal differentiative capacity and clear and simple ingredients.

Efficacy and Safety of Generic Dasatinib in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase: A Multicenter Prospective Study in China.

BACKGROUND: Brand-name dasatinib was approved for newly diagnosed chronic myeloid leukemia-chronic phase (CML-CP) patients due to its deeper and faster molecular response than imatinib. Generics, as the alternative, low-cost forms, are much in demand. This study aimed to evaluate the efficacy and safety of generic dasatinib (Yinishu) as a first-line treatment in CML-CP. MATERIALS AND METHODS: This was a prospective, multicenter, single-arm study from May 2016 to October 2018 with a 2-year follow-up analysis. All patients were given 100 mg/d (initial dose) of the generic dasatinib once a day. The primary endpoint was the major molecular response (MMR) calculated based on the BCR-ABL1 gene mutation rate of ≤ .1% at 12 months. RESULTS: Among 55 patients in CP observed for at least 3 months, 80.4% achieved MMR at 12 months. The cumulative MR4.5 was 58.2% by 24 months. Responses occurred rapidly, with 69.1% of patients achieving complete cytogenetic response (CCyR) by 3 months and 70.9% achieving CCyR by 6 months. The estimated 2-year PFS and OS were both 96%, with a median follow-up time of 24 months. Grade 3 neutropenia occurred in 8.5% of patients, and thrombocytopenia occurred in 11.9% of patients. Nonhematologic toxicity was usually mild and manageable. Pleural effusion occurred in 20.3% of patients, and only 1 patient (1.7%) had a grade 3 pleural effusion. No grade 4 adverse events were observed. CONCLUSION: Generic dasatinib is an effective option for newly diagnosed CML-CP patients, producing an MMR early in a greater number of patients during their therapy.

Pseudo-Starvation Driven Energy Expenditure Negatively Affects Ovarian Follicle Development.

In the present investigation, we examined whether a change in whole body energy fluxes could affect ovarian follicular development, employing mice ectopically expressing uncoupling protein 1 in skeletal muscle (UCP1-TG). Female UCP1-TG and wild-type (WT) mice were dissected at the age of 12 weeks. Energy intake and expenditure, activity, body weight and length, and body composition were measured. Plasma insulin, glucose, leptin, plasma fibroblast growth factor 21 (FGF21) and plasma insulin-like growth factor 1 (IGF1) levels were analyzed and ovarian follicle and corpus luteum numbers were counted. IGF1 signaling was analyzed by immunohistochemical staining for the activation of insulin receptor substrate 1/2 (IRS1/2) and AKT. UCP1-TG female mice had increased energy expenditure, reduced body size, maintained adiposity, and decreased IGF1 concentrations compared to their WT littermates, while preantral and antral follicle numbers were reduced by 40% and 60%, respectively. Corpora lutea were absent in 40% of the ovaries of UCP1-TG mice. Phospho-IRS1, phospho-AKT -Ser473 and -Thr308 immunostaining was present in the granulosa cells of antral follicles in WT ovaries, but faint to absent in the antral follicles of UCP1-TG mice. In conclusion, the reduction in circulating IGF1 levels due to the ectopic expression of UCP1 is associated with reduced immunostaining of the IRS1-PI3/AKT pathway, which may negatively affect ovarian follicle development and ovulation.

Validation of preimplantation genetic tests for aneuploidy (PGT-A) with DNA from spent culture media (SCM): concordance assessment and implication.

BACKGROUND: Spent culture medium (SCM) as a source of DNA for preimplantation genetic tests aneuploidy (PGT-A) has been widely discussed. METHODS: Seventy-five blastocysts that were donated for research provided a unique possibility in which multiple specimens, including trophectoderm (TE) biopsy, SCM, and paired corresponding whole blastocyst (WB) specimens from the same blastocyst source, could be utilized for the purpose of this preclinical validation. RESULTS: To conduct a validation ploidy concordance assessment, we evaluated the full chromosomal concordance rates between SCM and WB (SCM-to-WB), and between TE and WB (TE-to-WB) as well as sensitivity, specificity and overall diagnostic accuracy. 78.67% (59/75) of NGS results in the SCM group were interpretable, a significantly lower percentage than their corresponding TE and WB groups. This discrepancy manifests itself in intrinsically low quantity and poor integrity DNA from SCM. Subsequently, remarkable differences in full concordance rates (including mosaicism, and segmental aneuploidies) are seen as follows: 32.2% (SCM-to-WB, 19/59) and 69.33% (TE-to-WB, 52/75), (p < 0.001). In such cases, full concordance rates were 27.27% (15/55) in SCM-to-WB, and, 76% (57/75) in TE-to-WB (p < 0.001). Collectively, the NGS data from SCM also translated into lower sensitivities, Positive Predictive Value (PPV), Negative Predictive Value (NPV), overall diagnostic accuracies, and higher Negative Likelihood Ratio (NLR). CONCLUSIONS: Our study reveals that DNA is detectable in the majority of SCM samples. Individual chromosomal aberration, such as segmental aneuploidy and mosaicism, can be quantitatively and qualitatively measured. However, TE still provides a more accurate and reliable high-throughput methodology for PGT-A. Meanwhile, cell-free DNA in SCM reporting lacks uniform diagnostic interpretations. Considering that this test is meant to determine which embryos are relegated to be discarded, PGT-A with cell-free DNA in SCM should not be permitted to be applied in routine clinical settings for diagnosis purpose.

THE INCIDENCE, CHARACTERISTICS, MANAGEMENT, PROGNOSIS, AND CLASSIFICATION OF BREAKTHROUGH VITREOUS HEMORRHAGE SECONDARY TO POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To describe breakthrough vitreous hemorrhage secondary to polypoidal choroidal vasculopathy (PCV). METHODS: Patients with the diagnosis of PCV from January 2005 to March 2020 at Peking Union Medical College Hospital were retrospectively reviewed, cases with breakthrough vitreous hemorrhage were analyzed. Subgroup analysis was conducted regarding pachychoroid PCV and nonpachychoroid PCV. RESULTS: Among 722 PCV patients (834 eyes), 103 eyes with breakthrough vitreous hemorrhage (12.4%) were included. Pars plana vitrectomy and proper further interventions could significantly improve the best-corrected visual acuity from logMAR 2.15 ± 0.48 (Snellen 20/2825) to 1.65 ± 0.67 (20/893). Hemorrhagic retinal detachment, baseline central macular thickness, and best-corrected visual acuity were factors associated with final best-corrected visual acuity (P < 0.05). In the pachychoroid PCV group, patients were younger, all had hemorrhagic pigment epithelial detachment, with a higher prevalence of choroidal vascular hyperpermeability and hemorrhagic retinal detachment, thicker subfoveal choroidal thickness, and thinner central macular thickness; besides, the initial pars plana vitrectomy were more complicated, more additional surgeries had to be performed. More eyes in the nonpachychoroid PCV group had received anti-vascular endothelial growth factor or photodynamic therapy, mostly fibrovascular pigment epithelial detachment, the best-corrected visual acuity and the status of the fellow eye were significantly worse. For the final ocular status, more eyes in nonpachychoroid PCV group were taking anti-vascular endothelial growth factor monotherapy, whereas more eyes in pachychoroid PCV group were stable. The choroidal parameters of these two groups were all significantly different. CONCLUSION: Breakthrough vitreous hemorrhage is a troublesome complication of PCV. Pars plana vitrectomy and additional interventions are required for better prognosis. Vitreous hemorrhage secondary to pachychoroid PCV or nonpachychoroid PCV have different characteristics and prognosis.

Feasibility Study of the Low-Cost Motion Tracking System for Assessing Endoscope Holding Skills.

BACKGROUND: The ability to hold an endoscope is an important skill for surgeons and assistants performing endoscopic neurosurgery. Motion tracking can provide an objective assessment for surgical skills and may aid in endoscopic neurosurgery. We developed a cost-effective system to study the feasibility of objectively distinguishing performance levels for operating an endoscope. METHODS: The study was divided into 2 parts. First, a video motion tracking analysis tool was built based on a printed mark and free software (Kinovea 0.8.15). Second, the tool was used to distinguish the holding endoscope performance of the robotic arm by experts (surgeon, n = 3) and novice users (residents, n = 6) under both 0' and 30' endoscopes. RESULTS: Through the printed mark and free software, we successfully built a system for video motion tracking. The data analysis showed that for both 0' and 30' endoscopes, the experts had a shorter total distance and depth, smaller average speed and maximum acceleration, and a fewer number of extreme accelerations than their novice counterparts. Compared with experts and residents, the fixed arm had better results. CONCLUSIONS: The simple low-cost video motion tracking system can provide an objective assessment of an endoscope holding skill, which allows for discrimination between an expert and a novice, and can be used by clinical neurosurgeons to select a qualified assistant.

Novel Cost-Effective Tubular Port Based on Glove and Syringe for Endoscopic Surgery of Intracerebral Hematomas.

BACKGROUND: Intracerebral hematomas (ICH) is a common disease in the developing countries, and minimally invasive transportal resection of ICH is a widely accepted surgical technique. Many port systems are available, but most are disposable and expensive. We present a safe and cost-effective glove-syringe substitute for endoscopic hematoma evacuation, suitable for developing countries such as China. METHODS: A port substitute of different sizes and lengths was constructed using sterile gloves and syringes, commonly found in a surgical environment. RESULTS: We successfully performed endoscopic hematoma removal in 7 patients including 1 cerebellar hemorrhage case and the remaining 6 supratentorial basal ganglia cases (1 patient taking oral aspirin). Bipolar electrocoagulation was used to control bleeding from the ruptured blood vessels. There were no postsurgical complications. CONCLUSIONS: The glove-syringe port is a convenient, safe, and cost-effective tubular port system for endoscopic surgery of ICH. Such ports can be used as substitutes when commercial sleeves are unavailable, especially in rural areas and developing countries.

Assessment of sarcopenia in virally suppressed HIV-infected Asians receiving treatment.

OBJECTIVES: In a clinic-based, treated HIV-infected cohort, we identified individuals with sarcopenia and compared with age, sex and ethnically matched controls; and investigated associated risk factors and health outcomes. DESIGN: Sarcopenia (age-related muscle loss) causes significant morbidity to the elderly, leading to frequent hospitalizations, disability and death. Few have characterized sarcopenia in the HIV-infected who experience accelerated aging. METHODS: Sarcopenia was defined as low muscle mass with weak grip strength and/or slow gait speed using lower 20th percentiles of controls. Multivariate logistic and linear regression analyses were used to explore risk factors and health-related outcomes associated with sarcopenia among HIV-infected individuals. RESULTS: We recruited 315 HIV-infected individuals aged at least 25 years with at least 1-year history of undetectable viral load on treatment (HIV RNA <50 copies/ml). Percentage of sarcopenia in 315 HIV-infected was 8%. Subsequently, 153 of the 315 were paired with age, sex and ethnically matched HIV-uninfected. The percentage of sarcopenia in the HIV-infected (n = 153) compared with uninfected (n = 153) were 10 vs. 6% (P = 0.193) respectively, whereas of those at least 50 years of age among them were 17% vs. 4% (P = 0.049), respectively. Associated risk factors among the HIV-infected include education level, employment status, BMI, baseline CD4 cell count, duration on NRTIs and GGT levels. Identified negative outcomes include mortality risk scores [5.42; 95% CI 1.46-9.37; P = 0.007) and functional disability (3.95; 95% CI 1.57-9.97; P = 0.004). CONCLUSION: Sarcopenia is more prevalent in HIV-infected at least 50 years old compared with matched controls. Our findings highlight associations between sarcopenia with loss of independence and greater healthcare burden among treated HIV-infected individuals necessitating early recognition and intervention.

Utility of Using the Montreal Cognitive Assessment (MoCA) as a Screening Tool for HIV-Associated Neurocognitive Disorders (HAND) In Multi-Ethnic Malaysia.

This study determines the optimal cut-off scores for the Montreal Cognitive Assessment (MoCA) to detect HIV-associated neurocognitive disorders (HAND) in a multi-ethnic Malaysian HIV-positive cohort by developing demographically corrected normative standards among 283 HIV-negative community-based controls with overlapping demographic characteristics. The norms (corrected for age, sex, education, ethnicity) were applied to 342 HIV-positive virally suppressed individuals on cART. Impairment rates were classified using the Global Deficit Score (GDS ≥ .5) method. The MoCA was also scored according to the recommended cut-off of ≤ 26, and functional decline was applied to both impairment definitions to classify HAND per the Frascati criteria. The ≤ 26 cut-off considerably overestimated cognitive impairment in both samples (59.4% HIV-negative; 69.3% HIV-positive). In contrast, corrected scores yielded impairment rates consistent with what has been reported internationally in virally suppressed cohorts (23.4% with 83.3% mild impairment, 16.7% moderate impairment). A supplemental file allowing the computation of corrected MoCA scores and impairment status is included.

Quality of life and clinical correlates in older adults living in the community and in nursing homes in Macao.

AIM: There have been no previous studies of quality of life (QOL) in older adults in Macao. This study aimed to examine QOL in relation to the sociodemographic and clinical characteristics of adults aged ≥50 years in Macao. METHODS: A sample of 451 subjects (203 living in the community, 248 living in nursing homes) was interviewed using standardized instruments. Basic sociodemographic and clinical data including QOL were collected. RESULT: There were no significant differences between the community and nursing home groups in any of the QOL domains. Multiple linear regression analyses revealed that poor physical QOL was significantly predicted by severe depressive symptoms, insomnia, major medical conditions, unmarried status, and lower education ( F 11,438 = 26.2, P < 0.001), which accounted for 38.2% of the variance. Poor psychological QOL was significantly predicted by severe depressive symptoms and lower educational level ( F 11,438 = 24.3, P < 0.001), which accounted for 36.4% of the variance. Poor social QOL was significantly predicted by severe depressive symptoms, male gender, and unmarried status ( F 11,438 = 5.6, P < 0.001), which accounted for 12.5% of the variance. Poor environment QOL was significantly predicted by lower educational level, severe depressive symptoms, and younger age ( F 11,438 = 6.6, P < 0.001), which accounted for 12.1% of the variance. CONCLUSION: Older Macanese adults had poorer scores on physical and social QOL domains than the general Hong Kong Chinese population. Their QOL was more strongly related to severe depressive symptoms, major medical conditions, and insomnia.

Integrating differential pathway analysis with Monte Carlo cross-validation reveals seed cross-talks in non-small cell lung carcinoma.

PURPOSE: The objective of this study was to identify seed pathway cross-talks in non-small cell lung carcinoma (NSCLC), and to reveal potential pathological mechanism at molecular level systematically. METHODS: Differentially expressed genes (DEGs) between NSCLC and normal controls were identified using quantile- adjusted conditional maximum likelihood (QCML) method. Subsequently, differential pathways (DPs) enriched by DEGs were determined according to the Ingenuity Pathways Analysis )IPA) pathways and Fisher's exact test. A discriminating score )DS) was computed for each pair of DPs also called as cross-talk, and random forest )RF) algorithm was implemented to investigated hub cross-talks. Finally, global cross-talks with repeated times > 5 were calculated by Monte Carlo Cross-Validation )MCCV). By taking intersections between hub cross-talks and global crosstalks, we obtained seed cross-talks. RESULTS: We obtained 122 DEGs and 5 DPs between NSCLC samples and normal controls. Based on DS and RF algorithm, 5 hub cross-talks with best area under the curve )AUC) were identified, of which Agranulocyte Adhesion and Diapedesis, and IL-17A Signaling in Fibroblasts were the best with AUC=0.996. After intersected with global cross-talks, we gained 2 seed cross-talks (Agranulocyte Adhesion and Diapedesis, Granulocyte Adhesion and Diapedesis and Agranulocyte Adhesion and Diapedesis, Glutathione Redox Reactions I). CONCLUSIONS: Two seed cross-talks were identified and validated by MCCV, which may give insights for revealing pathological mechanism and potential biomarkers for target therapy in NSCLC.

Gender-specific responses to social determinants associated with self-perceived health in Taiwan: a multilevel approach.

There are well-documented gender differences in health. However, few studies have considered that the associations of personal and household characteristics with perceived health may vary between men and women because of their different socialized gender roles. This study investigates gender differences in health and addresses gender-specific responses to individual- and household-level determinants of health. We analyze the data of the 2001 Social Development Survey on Health and Safety, which consists of a representative sample of all registered households in Taiwan. Our findings give limited support to the hypothesis that women and men are differently associated with social determinants of health. We observe a significant gender gap in self-perceived health even after controlling for various health determinants. Notwithstanding, men and women are similar in many important aspects in relation to social determinants of health. Gender-specific responses are found only in the impacts of employment status, stressful life events, own disability, and number of family members with a disability. Men report having poorer health than women when being disabled and facing stressful events. Women's perceived health is at a higher risk when family members require short-term, intensive care. Further consideration of the observed, gender-specific responses to health determinants shed insight on the possible social and cultural relevance behind gender differences in self-perceived health.

A home-made low-cost hydraulic swivel and catheter assembly for blood pressure recording and drug infusion in freely moving mice.

We constructed a chassis that tightly fixes catheters for cannulation to the muscle. It can buffer pulling forces to avoid a mechanical tearing of the skin of mice as a result of movement. A simple hydraulic swivel was also made for blood pressure recording and drug infusion in freely moving mice.