ABSTRACT
BACKGROUND: To compare the impact of tunneled cuffed catheters (TCCs) and arteriovenous fistulas (AVFs) on outcomes in elderly hemodialysis (HD) patients. METHODS: A retrospective matched cohort study was performed. Propensity score matching (PSM) was applied to balance the baseline conditions, and we compared all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCEs), hospitalization, and infection rates between AVF and TCC patients ≥70 years old. Cox survival analysis was used to analyze the risk factors for death. RESULTS: There were 2119 patients from our center in the Chinese National Renal Data System (CNRDS) between 1 January 2010 and 10 October 2023. Among these patients, 77 TCC patients were matched with 77 AVF patients. There was no significant difference in all-cause mortality between the TCC and AVF groups (30.1/100 vs. 33.3/100 patient-years, p = 0.124). Among the propensity score-matched cohorts, no significant differences in Kaplan-Meier curves were observed between the two groups (log-rank p = 0.242). The TCC group had higher rates of MACCEs, hospitalization, and infection than the AVF group (33.7/100 vs. 29.5/100 patient-years, 101.2/100 vs. 79.5/100 patient-years, and 30.1/100 vs. 14.1/100 patient-years, respectively). Multivariate analysis showed that high Charlson comorbidity index (CCI) score was a risk factor for death. CONCLUSIONS: There was no significant difference in all-cause mortality between elderly HD patients receiving TCCs and AVFs. Compared with those with a TCC, elderly HD patients with an AVF have a lower risk of MACCEs, hospitalization, and infection.
Subject(s)
Arteriovenous Shunt, Surgical , Kidney Failure, Chronic , Propensity Score , Renal Dialysis , Humans , Male , Female , Aged , Retrospective Studies , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/mortality , Risk Factors , Arteriovenous Shunt, Surgical/adverse effects , Aged, 80 and over , Hospitalization/statistics & numerical data , China/epidemiology , Prognosis , Kaplan-Meier EstimateABSTRACT
Aseptic abscess (AA) syndrome is a rare inflammatory disorder often associated with inflammatory bowel disease (IBD). Cases of IBD-associated AA have been reported in Japan, India, and Canada, but rarely in China. Herein, we present the case of a Chinese patient with IBD-associated AAs and review the literature on AA with underlying IBD. We report the case of a 48-year-old male patient with multiple AAs on his left hand and lungs who was successfully treated with prednisone. He had undergone cutaneous abscess incision and drainage twice in the previous 2 years. The patient presented to our hospital with ulcerative colitis and pain in the dorsum of the left hand. Pus from his hand and blood cultures revealed sterile cutaneous abscesses. Chest computed tomography examination during hospitalization revealed a lung abscess. The AA was unresponsive to cefotiam or cefoperazone-sulbactam. The patient's left hand and lung conditions did not improve until prednisone was administered. The patient was followed up as an outpatient for 3 months and recovered without any clinical symptoms. We retrieved 17 cases of IBD-associated AA from the literature. None of the patients showed evidence of infection and failed antibiotic treatment, and all improved with corticosteroid use. AA may be an extra-intestinal manifestation of IBD. Effective medications include corticosteroids and immunosuppressive agents. This case may increase the awareness of AA and aid in early identification.
ABSTRACT
Influenza A viruses continue to be a serious health risk to people and result in a large-scale socio-economic loss. Avian influenza viruses typically do not replicate efficiently in mammals, but through the accumulation of mutations or genetic reassortment, they can overcome interspecies barriers, adapt to new hosts, and spread among them. Zoonotic influenza A viruses sporadically infect humans and exhibit limited human-to-human transmission. However, further adaptation of these viruses to humans may result in airborne transmissible viruses with pandemic potential. Therefore, we are beginning to understand genetic changes and mechanisms that may influence interspecific adaptation, cross-species transmission, and the pandemic potential of influenza A viruses. We also discuss the genetic and phenotypic traits associated with the airborne transmission of influenza A viruses in order to provide theoretical guidance for the surveillance of new strains with pandemic potential and the prevention of pandemics.
Subject(s)
Host Adaptation , Influenza A virus , Influenza, Human , Humans , Influenza, Human/transmission , Influenza, Human/virology , Influenza, Human/epidemiology , Animals , Influenza A virus/genetics , Influenza A virus/physiology , Influenza in Birds/transmission , Influenza in Birds/virology , Birds/virology , PandemicsABSTRACT
Nipah virus (NiV), a highly pathogenic Henipavirus in humans, has been responsible for annual outbreaks in recent years. Experiments involving live NiV are highly restricted to biosafety level 4 (BSL-4) laboratories, which impedes NiV research. In this study, we developed transcription and replication-competent NiV-like particles (trVLP-NiV) lacking N, P, and L genes. This trVLP-NiV exhibited the ability to infect and continuously passage in cells ectopically expressing N, P, and L proteins while maintaining stable genetic characteristics. Moreover, the trVLP-NiV displayed a favourable safety profile in hamsters. Using the system, we found the NiV nucleoprotein residues interacting with viral RNA backbone affected viral replication in opposite patterns. This engineered system was sensitive to well-established antiviral drugs, innate host antiviral factors, and neutralizing antibodies. We then established a high-throughput screening platform utilizing the trVLP-NiV, leading to the identification of tunicamycin as a potential anti-NiV compound. Evidence showed that tunicamycin inhibited NiV replication by decreasing the infectivity of progeny virions. In conclusion, this trVLP-NiV system provided a convenient and versatile molecular tool for investigating NiV molecular biology and conducting antiviral drug screening under BSL-2 conditions. Its application will contribute to the development of medical countermeasures against NiV infections.
Subject(s)
Henipavirus Infections , Nipah Virus , Virus Replication , Nipah Virus/physiology , Nipah Virus/genetics , Nipah Virus/drug effects , Animals , Cricetinae , Humans , Henipavirus Infections/virology , Transcription, Genetic , Virion/genetics , Viral Proteins/genetics , Viral Proteins/metabolism , Antiviral Agents/pharmacology , Vero Cells , Chlorocebus aethiops , Cell Line , RNA, Viral/geneticsABSTRACT
BACKGROUND: The significance of tumor-secreted cytokines in tumor development has gained substantial attention. Nevertheless, the precise role of tumor-related inflammatory cytokines in prostate cancer (PCa) remains ambiguous. OBJECTIVES: To gain deeper insights into the inflammatory response in the process of PCa. METHODS: A total of 233 cases were collected, including 80 cases of prostate hyperplasia as disease control, 65 cases of postoperative prostate cancer and 36 cases of prostate cancer as PCa group. Additionally, 52 patients undergoing physical examinations during the same period were collected as the healthy control. The levels of 12 inflammatory cytokines in peripheral blood samples were analyzed using flow cytometric bead array technology. The levels of total prostate-specific antigen (TPSA) and free prostate-specific antigen (FPSA) in peripheral blood samples were analyzed using electrochemiluminescence technology. RESULTS: Our findings revealed significant increases in serum IL-8 levels in PCa group compared to the healthy control group. Additionally, IL-6, IL-10, IFN-γ and IL-12p70 levels were markedly elevated in the PCa group compared to the disease control group (all p < 0.05). Conversely, the level of IL-4, TNF-α, IL-1ß, IL-17A and IFN-α were lower in the PCa group compared to those in control group. Following surgery, the concentration of IL-6 decreased; whereas, the concentrations of IL-4, TNF-α, IL-17A, IL-1ß, IL-12p70, and IFN-α increased, demonstrating significant differences (p < 0.05). The differential upregulation of IL-6 or downregulation of IL-17A in peripheral blood exhibited diagnostic efficacy in PCa patients. Moreover, we observed a significant increase in IL-17A levels, accompanied by decreased of IL-2, IL-4, IL-10, TNF-a, IFN-γ, IL-1ß, and IL-12P70 in patients with distant metastasis. CONCLUSION: The peripheral blood cytokines are closely associated with the occurrence and development of prostate cancer, especially the serum levels of IL-6 and IL-17A may be useful as potential predictors of PCa diagnosis.
Subject(s)
Cytokines , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/blood , Cytokines/blood , Cytokines/metabolism , Middle Aged , Aged , Diagnosis, Differential , Biomarkers, Tumor/blood , Prostate-Specific Antigen/blood , Prostatic Hyperplasia/diagnosis , Prostatic Hyperplasia/bloodABSTRACT
Monkeypox virus (MPXV) poses a global health threat. Droplet digital PCR (ddPCR) holds potential as an accurate diagnostic tool for clinical microbiology. However, there is limited literature on the applicability of ddPCR in clinical settings. In this study, the clinical features of patients with MPXV during the initial outbreak in China in June 2023 were reviewed, and an optimized ddPCR method with dilution and/or inhibitor removal was developed to enhance MPXV detection efficiency. Eighty-two MPXV samples were tested from nine different clinical specimen types, including feces, urine, pharyngeal swabs, anal swabs, saliva, herpes fluid, crust, and semen, and the viral load of each specimen was quantified. A comparative analysis was performed with qPCR to assess sensitivity and specificity and to investigate the characteristics of MPXV infection by analyzing viral loads in different clinical specimens. Consequently, common pharyngeal and gastrointestinal symptoms were observed in patients with MPXV. The optimized ddPCR method demonstrated relatively high sensitivity for MPXV quantification in the clinical materials, with a limit of detection of 0.1 copies/µL. This was particularly evident in low-concentration samples like whole blood, semen, and urine. The optimized ddPCR demonstrated greater detection accuracy compared with normal ddPCR and qPCR, with an area under the curve (AUC) of 0.939. Except for crust samples, viral loads in the specimens gradually decreased as the disease progressed. Virus levels in feces and anal swabs kept a high detection rate at each stage of post-symptom onset, and feces and anal swabs samples may be suitable for clinical diagnosis and continuous monitoring of MPXV. IMPORTANCE: The ddPCR technique proved to be a sensitive and valuable tool for accurately quantifying MPXV viral loads in various clinical specimen types. The findings provided valuable insights into the necessary pre-treatment protocols for MPXV diagnosis in ddPCR detection and the potentially suitable sample types for collection. Therefore, such results can aid in comprehending the potential characteristics of MPXV infection and the usage of ddPCR in clinical settings.
Subject(s)
Monkeypox virus , Sensitivity and Specificity , Viral Load , Humans , Viral Load/methods , Monkeypox virus/isolation & purification , Monkeypox virus/genetics , China , Mpox (monkeypox)/diagnosis , Mpox (monkeypox)/virology , Male , Feces/virology , Female , Polymerase Chain Reaction/methods , Disease Outbreaks , Adult , Real-Time Polymerase Chain Reaction/methodsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: The Niaodukang mixture (NDK) is a preparation known for its ability to lower serum creatine levels in individuals with chronic kidney disease (CKD) and is commonly administered at medical facilities like the Zhongshan Hospital of Traditional Chinese Medicine. The initial use of NDK was mainly to treat CKD. Our hospital frequently utilizes NDK, which consists of Rheum officinaleBaill., Salvia miltiorrhiza Bunge., Astragalus aaronii (Eig) Zohary., Carthamus tinctorius L., and Sanguisorba officinalis L., for treating patients with CKD-MBD. It has the effects of eliminating dampness and turbidity and dredging kidney collaterals. However, The impact and process of NDK in chronic kidney disease remain unknown. AIM OF THE STUDY: To determine whether microRNA-146a (miR-146a) is associated with CKD micro-inflammationand whether NDK protects against CKD micro-inflammation by modulating the miR-146a/nuclear factor kappa-B (NF-κB) signaling pathway. MATERIALS AND METHODS: (1) An adenine-induced rat model of chronic kidney disease was created through the use of materials and methods. The levels of miR-146a in exosomes from plasma and ileum were determined by RT-PCR. (2) Human cloned colon adenocarcinoma (Caco-2)cellswere stimulated with lipopolysaccharide (LPS)and transfected with miR-146a mimic and inhibitor. Following that, the Western blot and RT-PCR techniques were used to measure the protein and mRNA quantities of Toll-like receptor 4 (TLR4), NF-κB, and TNF receptor-associated factor 6 (TRAF6). (3) Enzyme-linked immunosorbent assay (ELISA) was used to identify serum levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). (4) Plasma exosomes were extracted, and the exosomes in intestinal tissues were extracted via ultrahigh-speed centrifugation.Negative staining electron microscopy was used to analyze the morphology of exosomes and the ultrastructure of intestinal tissue and exosomes. The particle size of the exosomes was measured using nanoparticle tracking analysis. RESULTS: The pathological characteristics of CKD rats included those associated with systemic micro-inflammation, which may be associated with the release of exosomes in intestinal tissue. NDK suppressed the inflammatory response in Caco-2 cells and decreased the levels of IL-1ß, IL-6, and TNF-α in rats with CKD. The expression of miR-146a, which regulates inflammation, differed between plasma-derived and enterogenous exosomes in CKD rats, which may be due to stimulation of ileal exosome release into the blood. NDK effectively reduced the levels of TRAF6, NF-κB, and TLR4 in the ileum tissue of CKD rats. CONCLUSION: NDK can effectively improve micro-inflammation in CKD ratsby enhancing the release of enterogenous exosomes, thereby enhancing the release of exosome-associated miR-146a and inhibiting micro-inflammation.
Subject(s)
Drugs, Chinese Herbal , Exosomes , Inflammation , MicroRNAs , NF-kappa B , Rats, Sprague-Dawley , Renal Insufficiency, Chronic , Toll-Like Receptor 4 , Animals , Exosomes/metabolism , Exosomes/drug effects , MicroRNAs/genetics , MicroRNAs/metabolism , Male , Humans , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/metabolism , NF-kappa B/metabolism , Drugs, Chinese Herbal/pharmacology , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/genetics , Inflammation/drug therapy , Rats , Caco-2 Cells , Anti-Inflammatory Agents/pharmacology , Signal Transduction/drug effects , Disease Models, AnimalABSTRACT
AIM: To analyze efficacy of endoscopic lithotripsy combined with drug lithotripsy as compared with drug lithotripsy for the treatment of phytobezoars. METHODS: We collected and evaluated case records of 165 patients with phytobezoars from 2014 to 2023. And we analyzed demographic and clinical characteristics, imaging features, endoscopic features, complications of phytobezoars, and compared efficacy between endoscopic lithotripsy combined with drug lithotripsy (Group A) and drug lithotripsy (sodium bicarbonate combined with proton pump inhibitor) (Group B). RESULTS: The median age of patients with phytobezoars was 67.84 ± 4.286 years old. Abdominal pain was the most common symptom and peptic ulcers (67.5%) were the most common complication. Bezoar-induced ulcers were more frequent in the gastric angle. The success rate of phytobezoars vanishing in Group A and Group B were similar (92.3% vs. 85.1% within 48 h, 98.7% vs. 97.7% within a week), while the average hospitalization period, average hospitalization cost, second endoscopy rate, and average endoscopic operation time were significantly lower in patients in Group B than in Group A. CONCLUSION: Drug lithotripsy is the preferred effective and safe treatment option for phytobezoars. We advise that an endoscopy should be completed after 48 h for drug lithotripsy.
Subject(s)
Bezoars , Lithotripsy , Humans , Bezoars/therapy , Male , Female , Lithotripsy/methods , Aged , Middle Aged , Retrospective Studies , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/administration & dosage , Treatment Outcome , Sodium Bicarbonate/administration & dosage , Sodium Bicarbonate/therapeutic use , Combined Modality Therapy , Abdominal Pain/etiology , Abdominal Pain/therapyABSTRACT
Ebola virus (EBOV) belongs to Filoviridae family possessing single-stranded negative-sense RNA genome, which is a serious threat to human health. Nowadays, no therapeutics have been proven to be successful in efficiently decreasing the mortality rate. RNA binding proteins (RBPs) are reported to participate in maintaining cell integrity and regulation of viral replication. However, little is known about whether and how RBPs participate in regulating the life cycle of EBOV. In our study, we found that RNA binding motif protein 4 (RBM4) inhibited the replication of EBOV in HEK293T and Huh-7 cells by suppressing viral mRNA production. Such inhibition resulted from the direct interaction between the RRM1 domain of RBM4 and the "CU" enrichment elements located in the PE1 and TSS of the 3'-leader region within the viral genome. Simultaneously, RBM4 could upregulate the expression of some cytokines involved in the host innate immune responses to synergistically exert its antiviral function. The findings therefore suggest that RBM4 might serve as a novel target of anti-EBOV strategy.
Subject(s)
Ebolavirus , Hemorrhagic Fever, Ebola , Humans , Ebolavirus/genetics , RNA , HEK293 Cells , Virus Replication , RNA-Binding Motifs , Genomics , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolismABSTRACT
OBJECTIVES: The purpose of this study is to examine the impact of structured pelvic floor muscle training (PFMT) on pelvic floor muscle (PFM) contraction and the treatment of pelvic organ prolapse (POP) in postpartum women. METHODS: Sixty patients who volunteered for a PFMT assessment at 6-8 weeks after delivery were included in this retrospective analysis. For 5 weeks, all patients had structured PFMT, which included supervised daily pelvic muscle contractions, biofeedback therapy, and electrical stimulation. The main outcomes were POP stage assessed by POP quantification (POP-Q), pelvic organ position and hiatus area (HA) assessed by transperineal ultrasound, PFM contraction assessed by Modified Oxford scale (MOS), surface electromyography (EMG), and sensation of PFM graded using visual analog scale (VAS). RESULTS: Structured PFMT was associated with better POP-Q scores in Aa, Ba, C, and D (p values were 0.01, 0.001, 0.017, and 0.001 separately). The bladder neck at rest and maximum Valsalva, the cervix position and HA at maximum Valsalva in transperineal ultrasound were significantly better than before (p values were 0.031, < 0.001, 0.043, and < 0.001 separately). PFM contraction assessed by MOS, EMG, and PFM VAS score were significantly improved (all p values were < 0.001). However, no significant improvement was observed in POP-Q stage. CONCLUSIONS: Structured PFMT can increase PFM function in postpartum women but cannot modify the POP-Q stage. Transperineal ultrasonography is a useful method for evaluating therapy efficacy objectively. More randomized controlled trials are needed before definitive conclusions can be drawn about the effect of structured PFMT on POP in postpartum women.
Subject(s)
Pelvic Floor , Pelvic Organ Prolapse , Humans , Female , Pelvic Floor/diagnostic imaging , Retrospective Studies , Postpartum Period , Muscle Contraction/physiology , Pelvic Organ Prolapse/diagnostic imaging , Pelvic Organ Prolapse/therapy , Pelvic Organ Prolapse/complications , UltrasonographyABSTRACT
Our patient, a 48-year-old man from Guangdong's coastal region, worked selling and processing oysters and other seafood. He started experiencing swelling and pain in his left knee on October 4, 2022, and they got worse over time. The findings of mNGS test showed Vibrio vulnificus infection. The patient had AIDS, hepatitis A and hepatitis B concurrently. He was admitted to the hospital's intensive care unit (ICU) for treatment as his symptoms worsened. We refrained from performing an amputation because the family members expressed a desire to keep the limb. The limb was managed with regular dressing changes, thorough debridement, wound closure, ongoing VSD drainage, and local antibiotic irrigation. The patient's organ function eventually returned to normal, and the systemic infection got better. On November 1, the wound's new granulation tissue had grown well and had gradually crept to cover 80% of the wound. The tissue's blood flow had also improved, indicating a trend of growth and healing.
Subject(s)
Coinfection , HIV Infections , Hepatitis B , Hepatitis C , Vibrio Infections , Vibrio vulnificus , Male , Humans , Middle Aged , Coinfection/diagnosis , Coinfection/complications , Vibrio Infections/diagnosis , Vibrio Infections/therapy , HIV Infections/complicationsABSTRACT
BACKGROUND: Studies comparing the survival of hemodialysis (HD) and peritoneal dialysis (PD) patients are controversial. This study evaluated the impact of initial dialysis modality on the survival of patients with end-stage renal disease (ESRD) in a matched-pair cohort. METHODS: A retrospective cohort study was performed on ESRD patients who initiated renal replacement treatment between January 1, 2010, and December 31, 2018. Propensity score matching was applied to balance the baseline conditions, and multivariate Cox regression analysis was applied to compare mortality between HD and PD patients and evaluate correlations between mortality and various baseline characteristics. Subgroup analysis was performed with respect to diabetes status. RESULTS: There were 739 patients in our center in the Chinese National Renal Data System (CNRDS) between 2010 and 2018. Of these, 125 PD patients were matched with 125 HD patients. The 1-, 2-, and 3-year survival rates were 96.5%, 90.7%, and 82.5%, respectively, in the HD group and 99.5%, 97.8%, and 92.5%, respectively, in the PD group (log-rank P < 0.001). Among the propensity score-matched cohorts, no significant differences in Kaplan-Meier curves were observed between the two groups (log-rank P = 0.514). Age at dialysis initiation, CCI, congestive heart failure and cerebrovascular disease were risk factors in the multivariable-adjusted model. In subgroups defined by diabetes status, the KaplanâMeier survival curve showed that PD survival was significantly higher than that of HD (log-rank P = 0.022). CONCLUSIONS: HD and PD were not significantly different regarding the survival of patients with ESRD. PD was associated with better survival in diabetic ESRD patients.
Subject(s)
Diabetes Mellitus , Kidney Failure, Chronic , Humans , Renal Dialysis , Retrospective Studies , Propensity Score , Kidney Failure, Chronic/complications , Risk Factors , Proportional Hazards ModelsABSTRACT
Magnitude and diversity of gut microbiota and metabolic systems are critical in shaping human health and diseases, but it remains largely unclear how complex metabolites may selectively regulate gut microbiota and determine health and diseases. Here, we show that failures or compromised effects of anti-TNF-α therapy in inflammatory bowel diseases (IBD) patients were correlated with intestinal dysbacteriosis with more pro-inflammatory bacteria, extensive unresolved inflammation, failed mucosal repairment, and aberrant lipid metabolism, particularly lower levels of palmitoleic acid (POA). Dietary POA repaired gut mucosal barriers, reduced inflammatory cell infiltrations and expressions of TNF-α and IL-6, and improved efficacy of anti-TNF-α therapy in both acute and chronic IBD mouse models. Ex vivo treatment with POA in cultured inflamed colon tissues derived from Crohn's disease (CD) patients reduced pro-inflammatory signaling/cytokines and conferred appreciable tissue repairment. Mechanistically, POA significantly upregulated the transcriptional signatures of cell division and biosynthetic process of Akkermansia muciniphila, selectively increased the growth and abundance of Akkermansia muciniphila in gut microbiota, and further reprogrammed the composition and structures of gut microbiota. Oral transfer of such POA-reprogrammed, but not control, gut microbiota induced better protection against colitis in anti-TNF-α mAb-treated recipient mice, and co-administration of POA with Akkermansia muciniphila showed significant synergistic protections against colitis in mice. Collectively, this work not only reveals the critical importance of POA as a polyfunctional molecular force to shape the magnitude and diversity of gut microbiota and therefore promote the intestinal homeostasis, but also implicates a new potential therapeutic strategy against intestinal or abenteric inflammatory diseases.
Subject(s)
Colitis , Gastrointestinal Microbiome , Inflammatory Bowel Diseases , Humans , Animals , Mice , Tumor Necrosis Factor Inhibitors/metabolism , Colitis/microbiology , Inflammatory Bowel Diseases/microbiology , Verrucomicrobia/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Biological Therapy , Dextran Sulfate , Mice, Inbred C57BL , Disease Models, AnimalABSTRACT
Post-neurosurgical infections caused by multidrug-resistant Enterobacterales are difficult to treat due to limited therapeutic options. Ceftazidime-avibactam (CAZ-AVI), a combination of cephalosporin and a novel ß-lactamase inhibitor, has exhibited potential activity against multi/extensive drug-resistant (MDR/XDR) gram-negative bacilli. Several reports have described the successful treatment of central infections caused by MDR/XDR Pseudomonas aeruginosa or Enterobacterales. However, data on the efficacy and effective drug distribution of CAZ-AVI in the central nervous system (CNS), particularly in children, are lacking. We report a case of a 4-year-old girl with post-neurosurgical meningitis and abscess caused by extended-spectrum ß-lactamase-producing Escherichia coli successfully treated with CAZ-AVI. CAZ-AVI therapeutic drug monitoring was performed to evaluate its efficacy and effective drug distribution in the CNS. We measured CAZ (15.6, 7.1, and 3.5 µg/mL) and AVI (4.0, 2.1, and 1.2 µg/mL) in cerebrospinal fluid (CSF) samples obtained 3, 5, and 7 h after the administration of the 15th CAZ-AVI dose (2.5 g, q8h, iv), respectively. We also measured CAZ (57.0 and 25.8 µg/mL) and AVI (11.3 and 4.5 µg/mL) in serum samples obtained 3 and 5 h after the administration, respectively. CAZ-AVI achieved an adequate CSF concentration throughout the drug interval. Our case provides evidence for using CAZ-AVI to treat CNS infections.
ABSTRACT
BACKGROUND: We have updated the guideline for preventing and managing perioperative infection in China, given the global issues with antimicrobial resistance and the need to optimize antimicrobial usage and improve hospital infection control levels. METHODS: We conducted a comprehensive evaluation of the evidence for prevention and management of perioperative infection, based on the concepts of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The strength of recommendations was graded and voted using the Delphi method and the nominal group technique. Revisions were made to the guidelines in response to feedback from the experts. RESULTS: There were 17 questions prepared, for which 37 recommendations were made. According to the GRADE system, we evaluated the body of evidence for each clinical question. Based on the meta-analysis results, recommendations were graded using the Delphi method to generate useful information. CONCLUSIONS: This guideline provides evidence to perioperative antimicrobial prophylaxis that increased the rational use of prophylactic antimicrobial use, with substantial improvement in the risk-benefit trade-off.
Subject(s)
Antibiotic Prophylaxis , Infections , Perioperative Care , China , Infections/drug therapy , Infection Control , Hospitals , Delphi TechniqueABSTRACT
Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.
Subject(s)
COVID-19 , Humans , Adult , SARS-CoV-2 , Interleukin-8 , CytokinesABSTRACT
PURPOSE: Colorectal cancer (CRC) is the second most common cause of cancer death worldwide. Trifluridine (FTD) remained at higher concentrations longer when administered along with tipiracil (TPI) compared with FTD alone. Lonsurf® is a combination formulation consisting of FTD and TPI. This study aimed to investigate the bioequivalence of FTD/TPI formulations in Chinese metastatic colorectal cancer (mCRC) patients. METHODS: In this phase I, randomized, open-label, single-dose, two-sequence, four-cycle crossover study in mCRC patients, the bioequivalence of 60 mg (20 mg tablet, 3 tablets) of the test formulation and the reference formulation (Lonsurf®) was evaluated. Due to its high variability, the method of reference-scaled average bioequivalence (RSABE) was used to investigate the bioequivalence of the test and reference formulations. RESULTS: Thirty-two patients were enrolled. 78.1% of the subjects were male, and the mean (standard deviation) age was 53.9 (SD = ± 9.0) years old. The time to reach the maximum plasma concentration (Tmax) was almost 2.0 h post-dose. The geometric least-squares mean ratios (GMRs) (test/reference) of Cmax and AUC0-t for FTD were 95.3% and 102.9%, respectively, with 90% confidence intervals (CIs) for the natural log-transformed ratios of Cmax and AUC0-t of 90.0-100.9% and 99.9-105.9%, while the GMRs of Cmax and AUC0-t for TPI were 95.7% and 100.7%, respectively, with 90% CIs of 90.5-101.2% and 97.0-104.7%. In addition, the GMRs of Cmax and AUC0-t for FTD's major metabolite, trifluorothymine (FTY), were 94.8 (90% CI 90.3-99.5%) and 99.33 (90% CI 96.9-101.9%), respectively. These were in accord with the FDA bioequivalence definition interval of 80-125%. CONCLUSION: The test and reference FTD/TPI formulations were bioequivalent in Chinese mCRC patients under fed conditions.
Subject(s)
Colorectal Neoplasms , Trifluridine , Female , Humans , Male , Middle Aged , Area Under Curve , Colorectal Neoplasms/drug therapy , Cross-Over Studies , East Asian People , Tablets , Therapeutic Equivalency , Trifluridine/pharmacokinetics , Drug Combinations , AdultABSTRACT
This article is concerned with the stability and stabilization of nonlinear hybrid stochastic systems. First, the concepts of synchronous and asynchronous switching parameters to the system states are proposed for a generalization of the asynchronous control. As preliminaries, a hybrid nonlinear differential inequality is established for coping with the synchronous models, and the [Formula: see text]-continuity of the system parameters driven by Markov chains is established for coping with the asynchronous models by the attribute of Markov chains for less conservativeness. Second, stability criteria with moment exponential estimates are established for two kinds of system models under the nonlinear growth condition. Third, the stabilization problem is illustrated based on the stability criteria and Riccati like matrix equations. A corollary is given to improve some stability theorems obtained in the related literature. New initial condition is formally proposed and explained for the nonlinear stochastic systems. Finally, a numerical example with simulation is proposed to illustrate the method, verify the conclusions of this article, and show the superiority of this work.
ABSTRACT
Monkeypox is a zoonotic disease caused by the monkeypox virus (MPXV), which is a potential biological warfare agent of bioterrorism and poses the greatest threat to the world's public biosafety and health after variola virus (VARV). While the coronavirus disease 2019 (COVID-19) pandemic has not ended yet, monkeypox is spreading menacingly. The first case of monkeypox in a nonendemic country was confirmed on May 6th, 2022, while the first imported case from Asia was found on June 21st. There were more than 16 thousand reported cases as of July 23rd, the day the World Health Organization (WHO) declared the global monkeypox outbreak a public health emergency of international concern (PHEIC) at the same level as smallpox and COVID-19; while there were more than 53 thousand cases as of September 1st. Therefore, we will propose relevant biosafety prevention and control strategies after analyzing the etiology of the 2022 multi-country monkeypox outbreak from the biological feature, transmissibility, epidemic, and variability of MPXV.