Efficacy of prophylactic antibiotics for the prevention of neutropenic fever in patients with multiple myeloma receiving high-dose cyclophosphamide for stem cell mobilization.

High-dose cyclophosphamide (HD-Cy) (3 g/m2) plus granulocyte colony-stimulating factor (G-CSF) is a very effective regimen for peripheral blood stem cell (PBSC) mobilization. Unfortunately, it is associated with an increased risk of neutropenic fever (NF). We analyzed the effect of NF on PBSC apheresis results and the efficacy of prophylactic antibiotics for the prevention of NF associated with HD-Cy plus G-CSF for PBSC mobilization in patients with newly diagnosed multiple myeloma (MM). First, patients were divided into NF ( +) and NF ( -) groups according to whether they suffered from NF during mobilization. Second, we divided patients into an antibiotic prophylaxis group and a nonantibiotic prophylaxis group according to whether antibiotic prophylaxis was used during the mobilization period. Our study showed that NF( +) patients (n = 44) had lower CD34 + cell dose collection (median 2.60 versus 5.34 × 106/kg, P < 0.001) and slower neutrophil engraftment and platelet engraftment (median 11 versus 10 days, P = 0.002, and median 13 versus 11 days, P = 0.043, respectively) than NF( -) patients (n = 234). Of note, the nonantibiotic prophylaxis group patients (n = 30) had a 26.7% incidence of NF. In the patients receiving antibiotic prophylaxis (n = 227), the incidence was reduced to 9.3% (P = 0.01). The antibiotic prophylaxis patients had higher CD34 + cell collection (median 5.41 versus 2.27 × 106/kg, P < 0.001) and lower hospitalization cost of mobilization ($ median 3108.02 versus 3702.39, p = 0.012). Thus, our results demonstrate that NF is associated with lower CD34 + cell collection and that antibiotic prophylaxis can reduce the incidence of NF and improve stem cell mobilization and collection outcomes, which reduces the hospitalization cost of mobilization.

Intrauterine transmission of SARS-CoV-2 to and prenatal ultrasound abnormal findings in the fetus of a pregnant woman with mild COVID-19.

BACKGROUND: Whether intrauterine transmission of COVID-19 occurs remains uncertain, and it remains unclear whether the disease affects fetuses. We present a case of intrauterine transmission of SARS-CoV-2 infection and the prenatal ultrasonographic findings of the fetus in a pregnant woman with mild COVID-19. CASE PRESENTATION: A 30-year-old woman was admitted to our hospital for ultrasound examination in January 2023 at 26+ 3 weeks' gestation. Twenty-one days prior, her COVID-19 nucleic acid test was positive, and she had mild symptoms, including fever (38.3 °C), headache, chills, ankle pain and cough. After receiving symptomatic treatment, she fully recovered. Prenatal ultrasound revealed that the placenta was diffusely distributed with punctate echogenic foci, hepatomegaly, and the volume of bilateral lungs decreased significantly, with enhanced echo. In addition, we found that the surface of the fetal brain demonstrated widened gyri with a flattened surface. The prenatal MRI confirmed these fetal abnormalities. Amniotic fluid was tested for SARS-CoV-2, and the sample tested was positive for the virus. After careful consideration, the pregnant woman decided to terminate the pregnancy. CONCLUSION: The intrauterine transmission of COVID-19 is certain. Moreover, the intrauterine transmission of COVID-19 may cause abnormalities in various organs of the fetus.

On-demand plerixafor added to high-dose cyclophosphamide and pegylated recombinant human granulocyte colony-stimulating factor in the mobilization of patients with multiple myeloma: a treatment with high effectiveness, convenient, and affordable cost.

Objective: The combination of high-dose cyclophosphamide (HD-Cy) (3g/m2) plus granulocyte colony-stimulating factor (G-CSF) and on-demand plerixafor (PXF) has been considered an effective mobilization regimen of patients with multiple myeloma(MM). However, the daily multi-injection regimen of G-CSF poses challenges. This study delves into the efficiency and cost implications of a novel approach, using HD-Cy alongside pegylated G-CSF (PEG G-CSF) and on-demand PXF. Unlike G-CSF, which necessitates daily injections, the half-life of PEG G-CSF extended allows for a single injection. Methods: A retrospective analysis was conducted on 350 MM patients, which were categorized based on their mobilization regimens: Cy+PEG G-CSF+/-PXF (n=66), Cy+PEG G-CSF (n=91), Cy+ G-CSF (n=169), and G-CSF+PXF (n=24). Results: Mobilization with Cy+PEG G-CSF+/-PXF(8.79)yielded a notably higher median CD34+ cell count compared to the other regimens: Cy+PEG G-CSF(4.96), Cy+G-CSF (4.65), and G-CSF+PXF (2.99) (P<0.001). The percentage of patients who achieved >6×106/kg CD34+ cells was significantly higher in the Cy+PEG G-CSF+/-PXF group (77.3%) than in the other mobilization regimens: Cy+PEG G-CSF (41.8%), Cy+ G-CSF (37.3%), and G-CSF+PXF (8.3%) (P<0.001). From a cost perspective, the Cy+PEG G-CSF+/-PXF approach was more economical than the G-CSF+PXF strategy but was marginally costlier than the other two methods. A multivariate assessment highlighted that the combination of Cy+PEG G-CSF with on-demand PXF had a superior potential to achieve the desired harvest (6×106/kg) compared to the Cy+PEG G-CSF protocol without PXF. The incremental cost-effectiveness ratio for each 1% increase in the probability of achieving a successful optimal harvest was $ 97.02 per patient. The incidence of neutropenic fever was 3.0% in the Cy+PEG G-CSF+/-PXF group. Conclusion: The combination of on-demand PXF with HD-Cy and PEG G-CSF offers a cost-effective approach with a high mobilization success rate, manageable side effects, and the convenience of fewer injections. It stands as a promising mobilization strategy for MM patients.

Multimodal Imaging of Target Detection Algorithm under Artificial Intelligence in the Diagnosis of Early Breast Cancer.

This study aimed to analyze the diagnostic value of multimodal images based on artificial intelligence target detection algorithms for early breast cancer, so as to provide help for clinical imaging examinations of breast cancer. This article combined residual block with inception block, constructed a new target detection algorithm to detect breast lumps, used deep convolutional neural network and ultrasound imaging in diagnosing benign and malignant breast lumps, took breast density grading with mammography, compared the convolutional neural network (CNN) algorithm with the proposed algorithm, and then applied the proposed algorithm to the diagnosis of 120 female patients with breast lumps. According to the results, accuracy rates of breast lump detection (94.76%), benign and malignant breast lumps diagnosis (98.22%), and breast grading (93.65%) with the algorithm applied in this study were significantly higher than those (75.67%, 87.23%, and 79.54%) with CNN algorithm, and the difference was statistically significant (P < 0.05); among 62 patients with malignant breast lumps of the 120 patients with breast lumps, 37 were patients with invasive ductal carcinoma, 8 with lobular carcinoma in situ, 16 with intraductal carcinoma, and 4 with mucinous carcinoma; among the remaining 58 patients with benign breast lumps, 28 were patients with fibrocystic breast disease, 17 with intraductal papilloma, 4 with breast hyperplasia, and 9 with adenopathy; the differences in shape, growth direction, edge, and internal echo of multimodal ultrasound imaging of patients with benign and malignant breast lumps had statistical significance (P < 0.05); the malignant constituent ratios of patients with breast density grades I to IV were 0%, 7.10%, 80.40%, and 100%, respectively. In short, the multimodal imaging diagnosis under the algorithm in this article was superior to CNN algorithm in all aspects; according to the judgment on benign and malignant breast lumps and breast density with multimodal imaging features, the higher the breast density, the higher the probability of breast cancer.

Berberine Modulates Gut Microbiota and Reduces Insulin Resistance via the TLR4 Signaling Pathway.

Berberine, a natural compound extracted from several Chinese herbs including Coptis chinensis, has been shown to have anti-obesity effects and prevents insulin resistance in high-fat diet (HFD)-fed obese rats by modulating the gut microbiota; however, the molecular mechanisms underlying these activities remain unknown. We investigated the effects of berberine on obesity and insulin resistance by examining the lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4)/tumor necrosis factor (TNF)-α signaling pathway in livers of HFD-fed obese rats. Our results showed that 8-week berberine (200 mg/kg) treatment significantly reduced fasting blood glucose, triglyceride, low-density lipoprotein-cholesterol and insulin resistance in HFD-fed obese rats. However, berberine had no significant effects on body weight, visceral fat mass or the visceral fat to body weight ratio. Berberine also attenuated HFD-induced hepatic steatosis. A prolonged HFD altered the gut microbiota composition by reducing protective bacteria like Bifidobacterium and increasing gram negative bacteria like Escherichia coli, which resulted in increased LPS release into plasma. Berberine reversed these effects and inhibited LPS-induced TLR4/TNF-α activation, resulting in increased insulin receptor and insulin receptor substrate-1 expression in the liver. These findings suggested that berberine may reduce insulin resistance, at least in part by modulating the gut microbiota along with inhibiting LPS/TLR4/TNF-α signaling in the liver.

The Comparative Safety of TNF Inhibitors in Ankylosing Spondylitis-a Meta-Analysis Update of 14 Randomized Controlled Trials.

TNF inhibitors have been used in ankylosing spondylitis (AS). The efficacy of TNF inhibitors was already evaluated by meta-analysis of randomized controlled trials (RCTs). However, the safety of TNF inhibitors is still unclear. Therefore, we aimed to evaluate and update the safety data from RCTs of TNF inhibitors in patients treated for AS. A systematic literature search was conducted from 1990 through May 31, 2016. All studies included were randomized, double-blind, controlled trials of patients with ankylosing spondylitis that evaluated adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab treatment. The overall serious adverse events, the risk of serious infection events, and the risk of malignancy and discontinuation rates were abstracted, and risk estimates were calculated by Peto odds ratios (ORs). Fourteen randomized controlled trials involving 2032 subjects receiving TNF inhibitors and 1030 subjects receiving placebo and/or traditional disease-modifying anti-rheumatic drugs (DMARDs) were included. The overall serious adverse events (OR, 1.34; 95% CI, 0.87-2.05), the risk of serious infection events (OR, 1.59; 95% CI, 0.63-4.01), the risk of malignancy (OR, 0.98; 95% CI, 0.25-3.85), and discontinuation due to adverse events (OR, 1.55; 95% CI, 0.95-2.54) in patients treated with TNF inhibitors as a group were not significantly different from those treated with placebo in the control group. TNF inhibitors were generally safe for treatment of ankylosing spondylitis. These data may help guide clinical comparative decision making in the management of AS.

Garlic intake lowers fasting blood glucose: meta-analysis of randomized controlled trials.

Garlic is a common spicy flavouring agent also used for certain therapeutic purposes. Garlic's effects on blood glucose have been the subject of many clinical and animal studies, however, studies reporting hypoglycemic effects of garlic in humans are conflicting. A comprehensive literature search was conducted to identify relevant trials of garlic or garlic extracts on markers of glycemic control [fasting blood glucose (FBG), postprandial glucose (PPG), glycosylated haemoglobin (HbA1c)]. A meta-analysis of the effect of garlic intake on human was done to assess garlic's effectiveness in lowering glucose levels. Two reviewers extracted data from each of the identified studies. Seven eligible randomized controlled trials with 513 subjects were identified. Pooled analyses showed that garlic intake results in a statistically significant lowering in FBG [SMD=-1.67; 95% CI (-2.80, -0.55), p=0.004]. Our pooled analyses did not include PPG control and HbA1c outcomes. Because only 1 study included in the meta-analysis reported PPG variables and only 2 studies reported HbA1c variables. In conclusion, the current meta-analysis showed that the administration of garlic resulted in a significant reduction in FBG concentrations. More trials are needed to investigate the effectiveness of garlic on HbA1c and PPG.

Efficacy and safety of sitagliptin compared with sulfonylurea therapy in patients with type 2 diabetes showing inadequately controlled glycosylated hemoglobin with metformin monotherapy: A meta-analysis.

Previous randomized controlled trials (RCTs) have reported conflicting results for the efficacy of sitagliptin and sulfonylurea therapy in patients with type 2 diabetes mellitus showing inadequate glycemic control with metformin monotherapy. To clarify these findings, a meta-analysis was conducted of the outcomes of all published RCTs comparing sitagliptin with sulfonylureas in the treatment of type 2 diabetes mellitus. Standard medical databases were searched to identify relevant English- and Chinese-language RCTs. RCT results were compared regarding the mean change in glycated hemoglobin (HbA1c) level; the proportion achieving <7% HbAlc; and a change in body weight. No significant differences were found between the metformin plus sitagliptin and metformin plus sulfonylurea groups regarding HbAlc or the proportion achieving <7% HbAlc, while the metformin plus sitagliptin group experienced fewer hypoglycemic events (P<0.00001) and a greater reduction in body weight (P<0.00001). Metformin plus sitagliptin therapy may decrease HbAlc values in patients with type 2 diabetes mellitus who are not achieving their glycemic targets with metformin monotherapy in a manner similar to metformin plus sulfonylurea therapy, whilst posing a lower risk of hypoglycemia, and yielding a more beneficial effect on body weight.

[Changes of plasma glucagon level in individuals with different glucose metabolism].

OBJECTIVE: To determine the levels of plasma glucagon and associated factors in individuals with different glucose metabolism. METHODS: One hundred and ten outpatient patients received an oral glucose tolerance test (OGTT) voluntarily. The patients were divided into three groups according to their OGTT results: normal glucose golerance (NGT) group (n=33), impaired glucose regulation (IGR) group (n=35), newly diagnosed type 2 diabetes (DM2) group (n=42). Plasma glucagon (GLC) and insulin (INS) at 0 min (0 h), 30 min (0.5 h), 60 min (1 h) and 120 min (2 h) were measured by radio immunity and electrochemiluminescence assay, respectively. We calculated the area of glucagon under the curve (AUCglc), the value of early phase glucagon secretion (deltaGLC = GLC(0.5 h) - GLC(0 h)) and the ratio of insulin to glucagon (INS/GLC). RESULTS: (1) There was no significant difference in the level of GLC(0 h) among the three groups (P > 0.05). (2) Patients in the IGR group had higher levels of GLC(0.5 h) and GLC(1 h), greater values of AUC(glc), and deltaGLC, and lower values of INS(0.5 h)/GLC(0.5 h) than those in the NGT group (P < 0.05). (3) Patients in the DM2 group had higher levels of GLC(0.5 h) and GLC(1 h), greater values of AUC(glc) and deltaGLC, and lower values of INS(0.5 h)/GLC(0.5 h) and INS(1 h)/GLC(1 h) than those in the NGT group (P < 0.05). (4) Patients in the DM2 group had higher levels of GLC(1 h), greater values of AUC(glc), and lower values of INS(0.5 h)/GLC(0.5 h), INS(1 h)/GLC(1 h), and INS(2 h)/GLC(2 h), than those in the IGR group (P < 0.05). (5) The multiple linear regression analysis showed that the value of AUC(glc). was positively correlated with HOMA-IR (adjust R2 = 0.219, P = 0.001). CONCLUSION: There are no significant differences in fasting plasma glucagon levels among the individuals with different glucose metabolism. Hypersecretion of glucagon and reduced glucagon suppressing effect of insulin occur in IGR patients, which is exacerbated when DM2 are developed. HOMA-IR is an important factor associated with glucagon hypersecretion.

[Change and correlated factors of fasting level of the plasma endotoxin in subjects with different glucose tolerances and body mass indices].

OBJECTIVE: To investigate the change of the levels of fasting plasma endotoxin (ET) and assess its correlated factors in individuals with different glucose tolerances and body mass indices. METHODS: The levels of fasting plasma ET were assayed by the endpoint chromogenic limulus amebocyte lysate method in subjects with type 2 diabetes (T2DM), impaired glucose regulation (IGR) and normal glucose tolerance (NGT). The height, body mass, waist, hips, systolic blood pressure and diastolic blood pressure were measured with the conventional methods; body mass index (BMI) and waist hip ratio (WHR) were calculated. All groups were divided into obesity (BMI>or=25 kg/m2) and non-obesity (BMI<25 kg/m2) subgroups. The levels of fasting blood glucose (FBG), 2 hours plasma glucose (2 hPG), fasting insulin (FINS), postprandial insulin (PINS), hemoglobin Alc (HbAlc), blood lipids, free fatty acids (FFA), serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also analyzed, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The relationship of the levels of plasma ET with age, BMI, WHR, blood pressure, FBG, 2 hPG, FINS, PINS, HOMA-IR, HbA1c, blood lipids, FFA, AST and ALT were also analyzed. RESULTS: (1) The levels of plasma ET in T2DM group (n=37) was significantly higher than that in NGT group (n=37) [7. 1 (3. 7-11. 8) EU/mL vs. 4. 5 (2.2-6.3) EU/mL, P<0.05]. The levels of plasma ET in IGR group (n=23) C5.0 (2.4-10.3) EU/mLU was lower than that in T2DM group and higher than NGT group but the differences were not significant (P>0. 05). (2) The levels of plasma ET in the obesity T2DM subgroup was higher than that in the non-obesity T2DM subgroup but the differences were not significant [7. 3 (3. 8-13. 3) EU/mL vs. 7.0 (3. 6-10. 4) EU/mL, P>0. 05]. There was a remarkable difference in the levels of plasma ET between obesity and non-obesity subgroup of IGR (6.8 (2.9-13.2) EU/mL vs. 2.7 (1.6-5. 5) EU/mL, P<0. 05), similarly between obesity and non-obesity subgroup of NGT (6.2 (3. 4-12. 7) EU/mL vs. 2. 8 (1. 8-4. 9) EU/mL, P<0. 05). (3) Multiple linear regression analysis demonstrated that ET wasn' t the important factor influencing FBG and 2 hPG. But BMI and FBG were the important factors influencing ET. 2 hPG and WHR weren't the important factors influencing ET. CONCLUSION: With the increase in glucose metabolic abnormalities and BMI, the levels of plasma ET are gradually increased. ET isn't the important factor influencing FBG and 2 hPG. BMI and FBG are the important factors in influencing ET.