Enabling oral novel Taxanes-based Chemotherapy with Lipophilic prodrug Self-nanoemulsifying drug delivery system.

Larotaxel (LTX) and SB-T-1214 (SBT), two new synthetic experimental toxoids, have shown broad-spectrum antitumor activity, especially against tumors that are resistant to other drugs. However, their poor solubility, membrane permeability, and first-pass effect limits their use in oral administration. We designed and synthesized two long-chain triglyceride-mimic prodrugs of LTX (LTXSSTG) and SBT (SBTSSTG), which are bridged by disulfide bonds and efficiently incorporated them into Self-nanoemulsifying drug delivery system (SNEDDS). These prodrugs can bypass hepatic metabolism by entering the blood through intestinal lymphatic transport, following a similar oral absorption pathway to dietary lipids. It was found that LTXSSTG and SBTSSTG significantly improved oral bioavailability (about 4.5-fold for LTX and 3.4-fold for SBT) compared to their solution forms. Moreover, with LTXSSTG and SBTSSTG incorporating reduction stimulus-responsive spacer were much more effective in suppressing tumor growth in vivo with eliminated adverse effects than solution form. To sum up, this strategy provides a new avenue to enhance oral delivery of new toxoids.

Trade-off between double cleavage-stage embryos transfer and single blastocyst-stage embryo transfer in patients with few good quality embryos in antagonist cycles: a retrospective study using a propensity score matching analysis.

OBJECTIVE: This study aimed to compare the per OPU clinical outcomes for transfer of Day 3 double cleavage-stage embryos (DET) and Day 5 single blastocyst-stage (SBT) in patients with five or fewer good quality embryos on day 3 per occyte pick-up cycle (OPU) in antagonist cycles with consideration of blastocyst formation failure. METHODS: This was a retrospective, observational cohort study of 2,116 cases of OPU treated with antagonist protocol in the affiliated Chenggong Hospital of Xiamen University between January 2013 and December 2020. DET was performed in 1,811cycles and SBT was performed in 305 cycles. The DET group was matched to the SBT group by propensity score (PS) matching according to multiple maternal baseline covariates. After PS matching, there were 303 ET cycles in each group. The primary outcomes were the cumulative live birth rate (CLBR), cumulative multiple pregnancy rate(CMPR)per OPU and the number of ET to achieve live birth per OPU. Secondary outcomes were the percentage of clinical pregnancy(CPR), live birth rate(LBR), multiple pregnancy rate(MPR). RESULTS: Following PS mating, the CLBR was slightly higher (48.8% versus 40.3% ; P = 0.041) and the CMPR was significantly higher in the DET group compared to SBT group(44.2% versus 7.9%, P < 0.001). The CPR, LBR and MPR per fresh transfer were higher in DET group compared to SBT group(50.2% versus 28.7%; 41.3% versus 21.5%;29.6% versus 0%, P < 0.001). The number of ET to achieve live birth per OPU in SBT group was obiviously more than in DET group(1.48 ± 0.578 versus 1.22 ± 0.557 ,P < 0.001). CONCLUSION: With a marginal difference cumulative live birth rate, the lower live birth rate per fresh transfer and higher number of ET per OPU in the SBT group suggested that it might take longer time to achieve a live birth with single blastocyst strategy. A trade-off decision should be made between efficiency and safety.

Comparison of pregnancy outcomes among patients of different ages who underwent frozen-thawed high-quality single blastocyst transfer.

OBJECTIVE: To investigate the feasibility of performing frozen-thawed high-quality single blastocyst transfer in women of different ages. METHODS: A total of 1,279 women were divided into four groups: a 38-40-year-old group (n = 147), 35-37-year-old group (n = 164), 30-34-year-old group (n = 483), and < 30-year-old group (n = 485). Intergroup comparisons of baseline characteristics and pregnancy and neonatal outcomes were made. RESULTS: The clinical pregnancy rate (47.6%), and live birth rate (34.0%) in the 38-40-year-old group were significantly lower than those in the 30-34-year-old group (64.4%, 50.9%, respectively; all P < 0.001) and < 30-year-old group (62.9%, 50.7%, respectively; all P < 0.001). However, the 35-37-year-old group did not differ from the other three groups in these two dimensions (all P > 0.05). Moreover, there were no differences in the rates of biochemical pregnancy, miscarriage, or obstetric or neonatal complications among the four groups (all P > 0.05). According to the multivariate logistic regression analysis, the 35-37-year-old group was not associated with non-live birth outcomes, adverse pregnancy outcomes, or obstetric or neonatal complications. However, being 38-40 years of age was a risk factor for non-live birth (OR = 2.121, 95% CI: 1.233-3.647) and adverse pregnancy outcomes (OR = 1.630, 95% CI: 1.010-2.633). Post hoc power analysis showed that the study was sufficiently powered to detect meaningful differences. CONCLUSION: Frozen-thawed high-quality single blastocyst transfer produces the same satisfactory pregnancy outcomes for women aged 35-37 years as younger patients. Future prospective randomized controlled studies with larger populations are needed to verify the feasibility and safety of this method.

Investigating the risk of reintubation by cough force assessment using cough peak expiratory flow: a single-center observational pilot study.

BACKGROUND: No objective indicator exists for evaluating cough strength during extubation of tracheally intubated patients. This study aimed to determine whether cough peak expiratory flow (CPEF) can predict the risk of reintubation due to decreased cough strength. METHODS: This was a retrospective cohort study of patients who were admitted to our Emergency Intensive Care Unit between September 1, 2020 and August 31, 2021 and were under artificial ventilation management for ≥ 24 h. The patients were divided into two groups: successful extubation and reintubation groups, and the relationship between CPEF immediately before extubation and reintubation was investigated. RESULTS: Seventy-six patients were analyzed. In the univariate analysis, CPEF was significantly different between the successful extubation (90.7 ± 25.9 L/min) and reintubation (57.2 ± 6.4 L/min) groups (p < 0.001). In the multivariate analysis with age and duration of artificial ventilation as covariates, CPEF was significantly lower in the reintubation group (p < 0.01). The cutoff value of CPEF for reintubation according to the receiver operating characteristic curve was 60 L/min (area under the curve, 0.897; sensitivity, 78.5%; specificity, 90.9%; p < 0.01). CONCLUSION: CPEF in tracheally intubated patients may be a useful indicator for predicting the risk of reintubation associated with decreased cough strength. The cutoff CPEF value for reintubation due to decreased cough strength was 60 L/min.

"Navigating the complexities of low-Grade glioma treatment: insights into SBT I-125 and novel assessment tools".

Central nervous system tumors, classified by the WHO into four grades based on their aggressiveness, present significant challenges in treatment, particularly low-grade gliomas (LGGs) which, despite their slower growth, can progress to high-grade gliomas. Lucca B. Palavani and colleagues evaluated the efficacy and safety of SBT I-125 brachytherapy for LGMs in a systematic review and meta-analysis of 20 studies involving 988 patients. The analysis revealed an overall complication rate of 10%, with headaches and cyst formation being the most frequent issues. The five-year progression-free survival (PFS) rate was 66%, while the ten-year PFS rate was 30%, and the rate of malignant transformation was 26%. The mortality rate was 33%. Despite these findings, significant limitations were noted, including data insufficiencies, study heterogeneity, lack of randomized controlled trials, and potential publication bias. Inconsistencies in follow-up durations further hindered the evaluation of long-term efficacy and safety. Recent advancements in automated tumor assessment, such as Cheng et al.'s deep learning-based pipeline, are revolutionizing glioma management by enhancing the accuracy and consistency of tumor volume and RANO measurements. These innovations facilitate improved glioma grading, genetic mutation prediction, surgical planning, real-time intraoperative guidance, and histopathological analysis. Integrating such advanced tools into clinical practice can significantly enhance the precision and efficiency of glioma management. In conclusion, while SBT I-125 brachytherapy shows promise, concerns regarding safety and efficacy underscore the need for further research with standardized methodologies. Incorporating advanced automated assessment tools could improve treatment evaluation and patient outcomes.

SBT-272 improves TDP-43 pathology in ALS upper motor neurons by modulating mitochondrial integrity, motility, and function.

Mitochondrial defects are one of the common underlying causes of neuronal vulnerability in neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), and TDP-43 pathology is the most commonly observed proteinopathy. Disrupted inner mitochondrial membrane (IMM) reported in the upper motor neurons (UMNs) of ALS patients with TDP-43 pathology is recapitulated in the UMNs of well-characterized hTDP-43 mouse model of ALS. The construct validity, such as shared and common cellular pathology in mice and human, offers a unique opportunity to test treatment strategies that may translate to patients. SBT-272 is a well-tolerated brain-penetrant small molecule that stabilizes cardiolipin, a phospholipid found in IMM, thereby restoring mitochondrial structure and respiratory function. We investigated whether SBT-272 can improve IMM structure and health in UMNs diseased with TDP-43 pathology in our well-characterized UMN reporter line for ALS. We found that SBT-272 significantly improved mitochondrial structural integrity and restored mitochondrial motility and function. This led to improved health of diseased UMNs in vitro. In comparison to edaravone and AMX0035, SBT-272 appeared more effective in restoring health of diseased UMNs. Chronic treatment of SBT-272 for sixty days starting at an early symptomatic stage of the disease in vivo led to a significant reduction in astrogliosis, microgliosis, and TDP-43 pathology in the ALS motor cortex. Our results underscore the therapeutic potential of SBT-272, especially within the context of TDP-43 pathology and mitochondrial dysfunction.

Identifying Predictors of Extubation on the day of Passing an SBT in Critically ill Adults.

INTRODUCTION: Many patients who pass a spontaneous awakening trial (SAT) and spontaneous breathing trial (SBT) do not undergo extubation that day. We aimed to identify predictors of extubation on the day of passing an SBT and to develop prediction models for extubation among mechanically ventilated patients. METHODS: In a cohort of mechanically ventilated patients who had passed an SBT in a single, academic medical intensive care unit (ICU) from 2018 to 2019, we developed a logistic regression model for identifying predictors of extubation. RESULTS: Of 745 patients in our study, 77% were extubated the day they passed a SBT. Independent predictors of extubation included higher Richmond Agitation Sedation Scale (RASS) (-2 compared to -4: odds ratio (OR) 1.83, 95% confidence interval (CI) 1.56 to 2.14), receipt of sedation on the day prior (OR 2.12, 95% CI 1.63 to 2.74), absence of diagnosis of sepsis or septic shock (OR 0.77, 95% CI 0.59 to 1), absence of neurological illness (OR 0.59, 95% CI 0.37 to 0.96), indication for intubation of altered mental status, seizure, or agitation (OR 1.67, 95% CI 1.05 to 2.65), and absence of hemodynamic instability or cardiac arrest (OR 0.67, 95% CI 0.47 to 0.95). CONCLUSION AND RELEVANCE: Patients on mechanical ventilation were more likely to be extubated on the day they passed an SBT if they had higher RASS scores, received sedation the day prior, or did not have diagnosis of sepsis, neurological illness, or hemodynamic instability. Future research should attempt to identify and address modifiable risk factors for failure to extubate after passing an SBT.

Ovarian serous borderline tumors with recurrent or extraovarian lesions: a Japanese, retrospective, multi-institutional, population-based study.

BACKGROUND: Ovarian serous borderline tumors (SBT) are typically unilateral and are primarily treated using hysterectomy and bilateral salpingooophorectomy (SO). However, most young patients prefer fertility-sparing surgeries (FSS) with tumorectomy or unilateral SO. Micropapillary morphology and invasive implants have been designated as histopathological risk indicators for recurrence or metastasis, but their clinical impact remains controversial because of limitations like diagnostic inconsistency and incomplete surgical staging. METHODS: A nationwide multi-institutional population-based retrospective surveillance was conducted with a thorough central pathology review to reveal the clinical features of SBT. Of 313 SBT patients enrolled in the Japanese Society of Clinical Oncology's Surveillance of Gynecologic Rare Tumors, 289 patient records were reviewed for clinical outcomes. The glass slides of patients at stage II-IV or with recurrence or death were re-evaluated by three gynecological pathologists. RESULT: The 10-year overall and progression-free survival (PFS) rates were 98.6% and 92.3%. The median recurrence period was 40 months and 77.0% was observed in the contralateral ovary within 60 months. Patients aged ≤ 35 years underwent FSS more frequently and relapsed more (p < .001). A clinic-pathological analysis revealed diagnosis during pregnancy, FSS, and treatment at non-university institutes as well as advanced stage and large diameter were independent risk factors of recurrence. Among patients having pathologically confirmed SBTs, PFS was not influenced by the presence of micropapillary pattern or invasive implants. CONCLUSION: The recurrence rate was lower in this cohort than previous reports, but the clinical impacts of incomplete resection and misclassification of the tumor were still significant on the treatment of SBT.

Genome-Wide Investigation and Co-Expression Network Analysis of SBT Family Gene in Gossypium.

Subtilases (SBTs), which belong to the serine peptidases, control plant development by regulating cell wall properties and the activity of extracellular signaling molecules, and affect all stages of the life cycle, such as seed development and germination, and responses to biotic and abiotic environments. In this study, 146 Gossypium hirsutum, 138 Gossypium barbadense, 89 Gossypium arboreum and 84 Gossypium raimondii SBTs were identified and divided into six subfamilies. Cotton SBTs are unevenly distributed on chromosomes. Synteny analysis showed that the members of SBT1 and SBT4 were expanded in cotton compared to Arabidopsis thaliana. Co-expression network analysis showed that six Gossypium arboreum SBT gene family members were in a network, among which five SBT1 genes and their Gossypium hirsutum and Arabidopsis thaliana direct homologues were down-regulated by salt treatment, indicating that the co-expression network might share conserved functions. Through co-expression network and annotation analysis, these SBTs may be involved in the biological processes of auxin transport, ABA signal transduction, cell wall repair and root tissue development. In summary, this study provides valuable information for the study of SBT genes in cotton and excavates SBT genes in response to salt stress, which provides ideas for cotton breeding for salinity resistance.

Quantifying salt sensitivity.

Inner surfaces of blood vessels and outer surfaces of erythrocytes are coated with a negatively charged protective film of proteoglycans, which serves as an effective buffer system for the positively charged sodium ions. If this protective coating is poorly developed or impaired, it loses its buffering capacity. As a consequence, the organism becomes increasingly sensitive to sodium, which in the long run leads to organ damage, especially if daily salt consumption is high. Recently, it has become possible to quantify salt sensitivity using a technically simple method - the salt blood test (SBT). Aim of this mini-review is to explain the physiological concept underlying the SBT and its potential practical relevance in the prevention of cardiovascular disease.

Differential gene expression identifies a transcriptional regulatory network involving ER-alpha and PITX1 in invasive epithelial ovarian cancer.

BACKGROUND: The heterogeneous subtypes and stages of epithelial ovarian cancer (EOC) differ in their biological features, invasiveness, and response to chemotherapy, but the transcriptional regulators causing their differences remain nebulous. METHODS: In this study, we compared high-grade serous ovarian cancers (HGSOCs) to low malignant potential or serous borderline tumors (SBTs). Our aim was to discover new regulatory factors causing distinct biological properties of HGSOCs and SBTs. RESULTS: In a discovery dataset, we identified 11 differentially expressed genes (DEGs) between SBTs and HGSOCs. Their expression correctly classified 95% of 267 validation samples. Two of the DEGs, TMEM30B and TSPAN1, were significantly associated with worse overall survival in patients with HGSOC. We also identified 17 DEGs that distinguished stage II vs. III HGSOC. In these two DEG promoter sets, we identified significant enrichment of predicted transcription factor binding sites, including those of RARA, FOXF1, BHLHE41, and PITX1. Using published ChIP-seq data acquired from multiple non-ovarian cell types, we showed additional regulatory factors, including AP2-gamma/TFAP2C, FOXA1, and BHLHE40, bound at the majority of DEG promoters. Several of the factors are known to cooperate with and predict the presence of nuclear hormone receptor estrogen receptor alpha (ER-alpha). We experimentally confirmed ER-alpha and PITX1 presence at the DEGs by performing ChIP-seq analysis using the ovarian cancer cell line PEO4. Finally, RNA-seq analysis identified recurrent gene fusion events in our EOC tumor set. Some of these fusions were significantly associated with survival in HGSOC patients; however, the fusion genes are not regulated by the transcription factors identified for the DEGs. CONCLUSIONS: These data implicate an estrogen-responsive regulatory network in the differential gene expression between ovarian cancer subtypes and stages, which includes PITX1. Importantly, the transcription factors associated with our DEG promoters are known to form the MegaTrans complex in breast cancer. This is the first study to implicate the MegaTrans complex in contributing to the distinct biological trajectories of malignant and indolent ovarian cancer subtypes.

Breast Cancer Is Associated with Increased HLA-DRB1*11:01 and HLA-DRB1*10:01 Allele Frequency in a Population of Patients from Central Italy.

The relationship between HLA-DRB1 allele polymorphism and breast cancer (BC) development is still unclear and needs further investigation. To address this issue, we analyzed HLA-DRB1 allele frequency (AF) by sequence-based typing (SBT) in 47 patients from central Italy with BC and 156 sex and age-matched healthy controls. Two hundred ninety-seven individuals from the same region were utilized as historical controls. Pearson's chi-square analysis with Yate's correction or Fisher's Exact test with Bonferroni's correction, as appropriate, were used to compare HLA-DRB1 AF differences in patients and controls. A total of 36 HLA-DRB1 alleles were identified. A detailed study showed that HLA-DRB1*11:01 and HLA-DRB1*10:01 alleles are significantly associated with increased BC risk. In particular, HLA-DRB1*11:01 AF was significantly higher in patients with BC than in healthy females and historical controls, even following Bonferroni's correction (stage I-II BC patients vs historical controls p<0.00; stage III-IV BC patients vs female healthy controls p=0.025 and historical controls p<0.00). The HLA-DRB1*10:01 allele was also positively associated with BC as evidenced by a significantly higher AF in patients with BC than in healthy controls (BC patients stage I-II vs historical controls corrected p =0.01). These results suggest that both HLA-DRB1*11:01 and HLA-DRB1*10:01 AF could represent interesting markers in patients at risk of developing BC.

Distribution of Diego blood group alleles and genotypes in the Chinese Korean population and sequence-based identification.

OBJECTIVE: To investigate Diego blood group alleles in the Chinese Korean population. The Diego blood group system plays an important role in transfusion medicine, but the distribution of the blood group in many Chinese ethnic populations remains unclear. METHODS: Sequence Specific Primer Polymerase Chain Reaction (SSP-PCR) was used for Diego genotyping and sequence-based typing PCR (PCR-SBT) was used to verify single nucleotide polymorphisms in the coding region of SLC4A1 starting from exon 19. Nine hundred and ten samples from the Chinese Korean population were investigated. RESULTS: The frequency of the DI*01 and DI*02 alleles in the Chinese Korean population was 0.0516 and 0.9484, respectively. The most predominant genotype was DI*02/DI*02, with a frequency of 90.22 % (821/910). The frequency of DI*01/DI*02 was 9.23 % (84/910) and that of DI*01 /DI*01 was 0.55 % (5/910). The genotype distributions of the Diego blood group conformed to the Hardy-Weinberg equilibrium (P > 0.05). CONCLUSION: The data obtained from this study will be helpful for the creation of a donor database to provide antigen-negative blood to patients with allo-antibodies. Genotyping can be used as a substitute for the serological technique when antisera are unavailable and is suitable for screening a large number of donors for rare-blood-group databases.

Comparison of ceftriaxone plus macrolide and ampicillin/sulbactam plus macrolide in treatment for patients with community-acquired pneumonia without risk factors for aspiration: an open-label, quasi-randomized, controlled trial.

BACKGROUND: Ceftriaxone (CTRX) and ampicillin/sulbactam (ABPC/SBT) are recommended by various guidelines as the first-line antibiotics for community-acquired pneumonia (CAP). However, which of these antibiotics is more effective for treating non-aspiration CAP remains unclear. METHODS: This study was a prospective, single-center, open-label, quasi-randomized controlled trial. Patients with adult CAP without risk for aspiration were allocated to either a CTRX or ABPC/SBT group based on the date of hospital admission. Macrolide was added to patients in each group. The primary outcome was the clinical response in the validated per-protocol (VPP) population at end of treatment (EOT). The secondary outcomes were clinical response during treatment and at end of study (EOS) in the VPP population, and mortality rate at day 30 in the modified intention-to-treat (MITT) population. RESULTS: Of 696 screened patients, 433 patients were excluded and 263 patients were allocated to receive either of the treatments. Males comprised 54% of patients and mean age and PSI were 62.1 ± 19.8 years and 69.3 ± 30.0, respectively, with 124 patients allocated to the CTRX group and 138 patients allocated to the ABPC/SBT group. The clinical effectiveness rate for the VPP population at EOT was 90% in the CTRX and 96% in the ABPC/SBT group (p = 0.072, 95% confidence interval [CI] of risk difference [RD]: - 12.6-0.8%). No significant difference in effectiveness at day 4 was observed between the CTRX and ABPC/SBT groups (p = 0.079, 95%CI of RD: - 12.1-0.4%), but at day 7, ABPC/SBT was significantly more effective than CTRX in the VPP population (p = 0.047, 95%CI of RD: - 13.3--0.4%). No significant difference in late response at EOS was seen between CTRX and ABPC/SBT groups: cure (89 [86%] and 102 [94%]), relapse (5 [5%] and 1 [1%]) and failure (10 [10%] and 5 [5%]; p = 0.053). Deaths within 30 days in MITT population was higher in CTRX group (4 [3%]) than in ABPC/SBT group (0 [0%]) (p = 0.048, 95%CI of RD: 0.1-6.3%). CONCLUSION: No significant difference in effectiveness was found between ABPC/SBT and CTRX at EOT. However, ABPC/SBT might be more effective in the early phase of treatment. TRIAL REGISTRATION: UMIN-CTR, UMIN000037464. Registered 25 July 2019 - Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042262.

Probiotic Lactobacillus gasseri SBT2055 improves insulin secretion in a diabetic rat model.

The probiotic Lactobacillus gasseri SBT2055 (LG2055) has a protective effect against metabolic syndrome in rats and humans. Metabolic syndrome increases the risk of type 2 diabetes mellitus. In this study, Goto-Kakizaki rats were used as a diabetic model and fed diets containing LG2055-fermented or nonfermented skim milk for 4 wk. Indices of diabetes such as blood glucose levels, serum glucagon levels, plasma levels of insulin, C-peptide, and glucagon-like peptide-1, tissue glycogen contents, and pancreatic mRNA levels were measured. The plasma C-peptide levels and pancreatic mRNA levels of insulin genes (Ins1 and Ins2) and Pdx1 (a transcriptional factor of insulin genes) were increased in LG2055 diet-fed rats. The increase in insulin secretion corresponded to an improvement in serum and pancreatic inflammatory status, associated with decreases in serum levels of serum amyloid P and pancreatic levels of granulocyte colony-stimulating factor. Insulin resistance in Goto-Kakizaki rats was ameliorated by increased glycogen storage in the liver and quadriceps femoris muscles and decreased serum free fatty acid levels. This improvement may be related to the increased cecal production of short-chain fatty acids. In conclusion, dietary LG2055 improved insulin secretion in diabetic rats by improving the inflammatory status in the pancreas and serum.

Influence of human embryo cultivation in a classic CO2 incubator with 20% oxygen versus benchtop incubator with 5% oxygen on live births: the randomized prospective trial.

SummaryOur objective was to assess the effect of benchtop incubators with low oxygen concentrations on the clinical and embryological parameters of our patients. We conducted a prospective, randomized, opened controlled trial on infertile patients in stimulated cycles. In total, 738 infertile patients were assessed for eligibility and, after final exclusions, 230 patients were allocated either to a 5% O2 group (benchtop incubator) or a 20% O2 group (classic incubator). Finally, 198 patients in the 5% O2 group and 195 in the 20% O2 group were analysed. The outcomes measured were fertilization rate, clinical pregnancy rate, and live birth rate. The primary outcome - live birth rate per all transfers - did not show any improvement in the 5% oxygen group over the 20% oxygen group (25.3% versus 22.6%, P=0.531), but the number of day 5 blastocysts was significantly higher (P=0.009). Fertilization rate did not show any beneficial effect of reduced oxygen (5%) (73.4%±22.4% versus 74.6%±24.0%, P=0.606) per all transfers but there was statistically significant difference in the day 5 SET subgroup (85.3±15.1 versus 75.1±17.5; P=0.004). Clinical pregnancy rate showed results in favour of the 5% oxygen group for all subgroups (day 3: 23.7% versus 21.1%, P=0.701; day 5 SET: 35.0% versus 30.6%. P=0.569) but showed statistical significance only in the day 5 SET subgroup (51.1% versus 29.8%; P=0.038). Culturing of embryos in benchtop incubators under low oxygen produced more blastocysts and therefore was a better alternative for embryo selection, which resulted in higher pregnancy rates. To achieve higher live birth rates, embryo quality is not the only factor.

Hepatic gas gangrene caused by Clostridium novyi.

We report the case of a patient with advanced gastric cancer and multiple liver metastases, who presented with bacteremia and hepatic gas gangrene caused by Clostridium novyi (C. novyi). The gas gangrene caused abscesses to form within metastatic lesions. This case highlights the antitumor effects of C. novyi in human.

HNA-3a and HNA-3b antigens among 9 ethnic populations and the Han population in Southwest China.

BACKGROUND: Human neutrophil antigen 3 (HNA-3) is encoded by the SLC44A2 gene. Antibodies against HNAs can cause severe, often fatal, transfusion reactions, known as transfusion-related acute lung injury, and neonatal neutropenia. We explored the 2 common HNA-3 variants in 9 ethnic populations residing in Sichuan and Yunnan provinces of China as compared to the Han population. METHODS: We genotyped for SLC44A2 (rs2288904) by polymerase chain reaction sequence-based typing among blood donors, for a total of 2206 individuals in Yunnan and 376 in Sichuan. RESULTS: The SLC44A2*02 allele (HNA-3b antigen) frequency varied between 0.24 and 0.33 for all 9 ethnic populations in Yunnan, including Zhuang, Derung, Hani, Lisu, Bai, Miao, Dai, Naxi, and Yi. Specifically, the Yi ethnicity did not present an unusually great SLC44A2*02 frequency at any of the 4 locations examined in Yunnan. Except of the Yi ethnicity in Sichuan (0.40), the Han ethnicity, as the majority population group, had the greatest SLC44A2*02 frequency with 0.39 in Yunnan and 0.35 in Sichuan. CONCLUSION: The ethnic populations in Southwest China are not at an increased risk for anti-HNA3a compared to the Han population, with the possible exception of Yi in Sichuan. Our data, however, corroborated the known high prevalence of SLC44A2*02 in Han populations. Hence, the Han populations in Yunnan, Sichuan and elsewhere in China are at a comparatively great risk for developing HNA-3a antibodies.

Legionella pneumophila recurrently isolated in a Spanish hospital: Two years of antimicrobial resistance surveillance.

OBJECTIVES: The aim of this study was to monitor the spread, persistence and antibiotic resistance patterns of Legionella spp. strains found in a hospital water distribution system. These environmental studies are intended to help detect the presence of antibiotic resistant strains before they infect patients. METHODS: Antimicrobial surveillance tests were performed at 27 different sampling points of the water network of a large Spanish hospital over two years. Water samples were screened for Legionella according to ISO 11731:2007. Legionella spp. isolates were identified by serotyping and by mass spectrometry (MALDI-ToF). Epidemiological molecular typing was done by Pulse-Field Gel Electrophoresis (PFGE) and by Sequence-Based Typing (SBT). Antibiotic susceptibility tests were performed using disk diffusion and ETEST®. RESULTS: Legionella spp. were recurrently isolated for 2 years. All isolates belonged the same group, L. pneumophila serogroups 2-14. Isolates were all attributed by SBT to sequence type (ST) ST328, although PFGE revealed 5 different patterns. No significant change in antibiotic susceptibility could be observed for this study period, irrespectively of the method used. CONCLUSION: Colonization of water systems by Legionella spp. is still occurring, although all the prevention rules were strictly followed. Antibiotic resistance monitoring may help us to find resistance in bacteria with environmental reservoirs but difficult to isolate from patients. The knowledge of the antibiotic susceptibility in environmental strains may help us to predict changes in clinical strains. This study might also help reconsidering Legionnaires' disease (LD) diagnostic methods. L. pneumophila serogroups 2-14 present all along the time of the investigation in the water distribution system can cause LD. However, they may not be detected by routine urine tests run on patients, thereby missing an ongoing LD infection.

Extubating the Neurocritical Care Patient: A Spontaneous Breathing Trial Algorithmic Approach.

BACKGROUND: Delaying extubation in neurologically impaired patients otherwise ready for extubation is a source for significant morbidity, mortality, and costs. There is no consensus to suggest one spontaneous breathing trial (SBT) over another in predicting extubation success. We studied an algorithm using zero pressure support and zero positive end-expiratory pressure (ZEEP) SBT followed by 5-cm H2O pressure support and 5-cm H2O positive end-expiratory pressure (i.e., 5/5) SBT in those who failed ZEEP SBT. METHODS: This is a retrospective analysis of intubated patients in a neurosciences intensive care unit. All eligible patients were initially challenged with ZEEP SBT. If failed, a 5/5 SBT was immediately performed. If passed either the ZEEP SBT or the subsequent 5/5 SBT, patients were liberated from mechanical ventilation. RESULTS: In total, 108 adult patients were included. The majority of patients were successfully liberated from mechanical ventilation using ZEEP SBT alone (82.4%; p = 0.0007). Fifteen (13.8%) patients failed ZEEP SBT but immediately passed 5/5 SBT (p = 0.0005). One patient (0.93%) required reintubation. We found high sensitivity of this extubation algorithm (100; 95% CI 95.94-100%) but poor specificity (6.67; 95% CI 0.17-31.95%). CONCLUSION: This study showed that the majority of patients could be successfully liberated from mechanical ventilation after a ZEEP SBT. In those who failed, a 5/5 SBT increased the successful liberation from mechanical ventilation.