Characterizing the Immune Environment in Peritoneal Carcinomatosis: Insights for Novel Immunotherapy Strategies.

BACKGROUND OR PURPOSE: Carcinomatosis, a distinct pattern of metastatic cancer in the peritoneal cavity, poses challenges for treatment and has limited therapeutic options. Understanding the immune environment of peritoneal surface malignancies is crucial for developing effective immunotherapeutic approaches. This study characterizes soluble immune mediators in the peritoneal fluid of patients with and without carcinomatosis to identify targets for novel treatment strategies. PATIENTS AND METHODS: Serum and peritoneal fluid samples were collected from surgical patients, and a multianalyte analysis was performed using the Luminex platform. Patient characteristics, tumor sites, and sample collection details were recorded. Soluble immune mediator levels were measured and compared between peritoneal fluid and serum samples and among clinical subgroups. Statistical analysis was conducted to assess differences in analyte concentrations and correlations between samples. RESULTS: There were 39 patients included in the study, with varying surgical indications. Significant differences were observed in soluble immune mediator levels between peritoneal fluid and serum, with peritoneal fluid exhibiting lower concentrations. Carcinomatosis was associated with elevated levels of proinflammatory mediators, including IL-6 and IL-8, while adaptive immune response markers were low in peritoneal fluid. CONCLUSIONS: The peritoneal immune microenvironment in carcinomatosis favors innate immunity, presenting a challenging environment for effective antitumor response. High levels of proinflammatory mediators suggest potential targets for intervention, such as the IL-6 axis, FGF2, IL-8, and CCL2; these could be explored as potential mitigators of malignant ascites and enhance anti-tumor immune responses. These findings provide valuable insights for developing immunotherapy strategies and improving outcomes in patients with peritoneal carcinomatosis.

Overexpression of Fut 2, 4, and 8, and nuclear localization of Fut 4 in ovarian cancer cell lines induced by ascitic fluids from epithelial ovarian cancer patients.

Fucosyltransferases (Fut) regulate the fucosylation process associated with tumorogenesis in different cancer types. Ascitic fluid (AF) from patients diagnosed with advanced stage of epithelial ovarian cancer (EOC) is considered as a dynamic tumor microenvironment associated with poor prognosis. Previous studies from our laboratory showed increased fucosylation in SKOV-3 and OVCAR-3, cancer-derived cell lines, when these cells were incubated with AFs derived from patients diagnosed with EOC. In the present work we studied three fucosyltransferases (Fut 2, Fut 4, and Fut 8) in SKOV-3, OVCAR-3 and CAOV-3 cell lines in combination with five different AFs from patients diagnosed with this disease, confirming that all tested AFs increased fucosylation. Then, we demonstrate that mRNAs of these three enzymes were overexpressed in the three cell lines under treatment with AFs. SKOV-3 showed the higher overexpression of Fut 2, Fut 4, and Fut 8 in comparison with the control condition. We further confirmed, in the SKOV-3 cell line, by endpoint PCR, WB, and confocal microscopy, that the three enzymes were overexpressed, being Fut 4 the most overexpressed enzyme compared to Fut 2 and Fut 8. These enzymes were concentrated in vesicular structures with a homogeneous distribution pattern throughout the cytoplasm. Moreover, we found that among the three enzymes, only Fut 4 was located inside the nuclei. The nuclear location of Fut 4 was confirmed for the three cell lines. These results allow to propose Fut 2, Fut 4, and Fut 8 as potential targets for EOC treatment or as diagnostic tools for this disease.

Application of metagenomic next-generation sequencing in optimizing the diagnosis of ascitic infection in patients with liver cirrhosis.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) is an emerging technique for the clinical diagnosis of infectious disease that has rarely been used for the diagnosis of ascites infection in patients with cirrhosis. This study compared mNGS detection with conventional culture methods for the on etiological diagnosis of cirrhotic ascites and evaluated the clinical effect of mNGS. METHODS: A total of 109 patients with ascites due to cirrhosis were included in the study. We compared mNGS with conventional culture detection by analyzing the diagnostic results, pathogen species and clinical effects. The influence of mNGS on the diagnosis and management of ascites infection in patients with cirrhosis was also evaluated. RESULTS: Ascites cases were classified into three types: spontaneous bacterial peritonitis (SBP) (16/109, 14.7%), bacterascites (21/109, 19.3%) and sterile ascites (72/109, 66.1%). In addition, 109 patients were assigned to the ascites mNGS-positive group (80/109, 73.4%) or ascites mNGS-negative group (29/109, 26.6%). The percentage of positive mNGS results was significantly greater than that of traditional methods (73.4% vs. 28.4%, P < 0.001). mNGS detected 43 strains of bacteria, 9 strains of fungi and 8 strains of viruses. Fourteen bacterial strains and 3 fungal strains were detected via culture methods. Mycobacteria, viruses, and pneumocystis were detected only by the mNGS method. The mNGS assay produced a greater polymicrobial infection rate than the culture method (55% vs. 16%). Considering the polymorphonuclear neutrophil (PMN) counts, the overall percentage of pathogens detected by the two methods was comparable, with 87.5% (14/16) in the PMN ≥ 250/mm3 group and 72.0% (67/93) in the PMN < 250/mm3 group (P > 0.05). Based on the ascites PMN counts combined with the mNGS assay, 72 patients (66.1%) were diagnosed with ascitic fluid infection (AFI) (including SBP and bacterascites), whereas based on the ascites PMN counts combined with the culture assay, 37 patients (33.9%) were diagnosed with AFI (P < 0.05). In 60 (55.0%) patients, the mNGS assay produced positive clinical effects; 40 (85.7%) patients had their treatment regimen adjusted, and 48 patients were improved. The coincidence rate of the mNGS results and clinical findings was 75.0% (60/80). CONCLUSIONS: Compared with conventional culture methods, mNGS can improve the detection rate of ascites pathogens, including bacteria, viruses, and fungi, and has significant advantages in the diagnosis of rare pathogens and pathogens that are difficult to culture; moreover, mNGS may be an effective method for improving the diagnosis of ascites infection in patients with cirrhosis, guiding early antibiotic therapy, and for reducing complications related to abdominal infection. In addition, explaining mNGS results will be challenging, especially for guiding the treatment of infectious diseases.

Differential diagnosis of ascites: etiologies, ascitic fluid analysis, diagnostic algorithm.

Ascites is the pathological accumulation of fluid within the peritoneal cavity. It often occurs as results of liver cirrhosis, malignant neoplasia, tuberculous infection, cardiac insufficiency, renal diseases, etc. Determining the etiology is an essential step in the management of patients with new-onset ascites. Abdominal paracentesis with appropriate ascitic fluid analysis is probably the most cost-effective method of determining the cause of ascites. We performed a literature search of PubMed and identified articles published in the field of ascites, to evaluate diagnostic values of various parameters in defining the etiologies of ascites and then provides diagnostic algorithm for patients with new-onset ascites. In patients with ascites, the constituent ratio of underlying etiology varies between developed and developing countries. It is a challenge to define the etiologies of ascites in developing countries. Routine ascitic fluid analysis should include the serum ascites albumin gradient (SAAG), total protein concentration, cell count and differential. Optional ascitic fluid analysis includes cholesterol, fluid culture, cytology, tumor markers, lactate dehydrogenase, adenosine deaminase (ADA), triglyceride, amylase, glucose, brain natriuretic peptide (BNP), etc. Our review evaluated diagnostic values of the above parameters in defining the etiologies of ascites. Diagnostic algorithm established in this review would provide a practical and convenient diagnostic strategy for clinicians in diagnosing patients with new-onset ascites.

Comparison of microbial abundance and diversity in uterine and peritoneal fluid in infertile patients with or without endometriosis.

INTRODUCTION: Endometriosis (EM) is a multifactorial disease that affects 10 - 15% of women of reproductive age. Additionally, 30-50% of women with EM suffer from infertility. The mechanism of infertility caused by EM has not yet been consistently explained. In recent years, studies have shown a link between infertility associated with EM and changes in the reproductive tract microbiota. METHODS: In this study, we involved 26 EM patients (8 cases of stage I-II and 18 cases of stage III-IV) and 31 control subjects who were tubal obstruction-related infertility (TORI). The samples from peritoneal fluid (PF) and uterine fluid (UF) were collected and sequenced by 16 S rRNA amplicon. RESULTS: In the comparison of microbial diversity, we found no significant differences in the microbial diversity of PF and UF between patients with stage I-II EM and those with TORI. However, there was a significant difference in microbial diversity among patients with stage III-IV EM compared to the previous two groups. Lactobacillus decreased in PF of EM compared to the control group, while it increased in UF. In PF, the abundance of Pseudomonas, Enterococcus, Dubosiella and Klebsiella was significantly higher in patients with stage III-IV compared to TORI patients. And in UF, the main differences existed between stage I-II EM compared to the other two groups. The abundance of pontibacter, aquabacterium, Rikenellaceae and so on at the genus level was significantly enriched in the EM patients with stage I-II. In the analysis based on KEGG database, EM may affect the receptivity related pathways of the endometrium by influencing changes in the uterine microbiota. CONCLUSION: Our results indicated that as EM progresses, the microorganisms in UF and PF keep changing. These changes in the microbiota, as well as the resulting alternations in gene functional classification, may play an important role in the infertility associated with EM.

Bugs' eyes and black monsters: Ascitic fluid cytology in an elderly male with hematochezia.

Anorectal malignant melanomas are rare, accounting for less than 2% of all melanomas. Malignant effusions developing secondary to malignant melanoma are highly uncommon. Herein, we present the cytomorphological features of a metastatic anorectal malignant melanoma presenting with ascites at the initial clinical presentation.

Human Amniotic MSC Response in LPS-Stimulated Ascites from Patients with Cirrhosis: FOXO1 Gene and Th17 Activation in Enhanced Antibacterial Activation.

Spontaneous bacterial peritonitis (SBP) is a severe complication in patients with decompensated liver cirrhosis and is commonly treated with broad spectrum antibiotics. However, the rise of antibiotic resistance requires alternative therapeutic strategies. As recently shown, human amnion-derived mesenchymal stem cells (hA-MSCs) are able, in vitro, to promote bacterial clearance and modulate the immune and inflammatory response in SBP. Our results highlight the upregulation of FOXO1, CXCL5, CXCL6, CCL20, and MAPK13 in hA-MSCs as well as the promotion of bacterial clearance, prompting a shift in the immune response toward a Th17 lymphocyte phenotype after 72 h treatment. In this study, we used an in vitro SBP model and employed omics techniques (next-generation sequencing) to investigate the mechanisms by which hA-MSCs modify the crosstalk between immune cells in LPS-stimulated ascitic fluid. We also validated the data obtained via qRT-PCR, cytofluorimetric analysis, and Luminex assay. These findings provide further support to the hope of using hA-MSCs for the prevention and treatment of infective diseases, such as SBP, offering a viable alternative to antibiotic therapy.

Homologous recombination deficiency (HRD) testing on cell-free tumor DNA from peritoneal fluid.

BACKGROUND: Knowing the homologous recombination deficiency (HRD) status in advanced epithelial ovarian cancer (EOC) is vital for patient management. HRD is determined by BRCA1/BRCA2 pathogenic variants or genomic instability. However, tumor DNA analysis is inconclusive in 15-19% of cases. Peritoneal fluid, available in > 95% of advanced EOC cases, could serve as an alternative source of cell-free tumor DNA (cftDNA) for HRD testing. Limited data show the feasibility of cancer panel gene testing on ascites cfDNA but no study, to date, has investigated HRD testing. METHODS: We collected ascites/peritoneal washings from 53 EOC patients (19 from retrospective cohort and 34 from prospective cohort) and performed a Cancer Gene Panel (CGP) using NGS for TP53/HR genes and shallow Whole Genome Sequencing (sWGS) for genomic instability on cfDNA. RESULTS: cfDNA was detectable in 49 out of 53 patients (92.5%), including those with limited peritoneal fluid. Median cfDNA was 3700 ng/ml, with a turnaround time of 21 days. TP53 pathogenic variants were detected in 86% (42/49) of patients, all with HGSOC. BRCA1 and BRCA2 pathogenic variants were found in 14% (7/49) and 10% (5/49) of cases, respectively. Peritoneal cftDNA showed high sensitivity (97%), specificity (83%), and concordance (95%) with tumor-based TP53 variant detection. NGS CGP on cftDNA identified BRCA2 pathogenic variants in one case where tumor-based testing failed. sWGS on cftDNA provided informative results even when tumor-based genomic instability testing failed. CONCLUSION: Profiling cftDNA from peritoneal fluid is feasible, providing a significant amount of tumor DNA. This fast and reliable approach enables HRD testing, including BRCA1/2 mutations and genomic instability assessment. HRD testing on cfDNA from peritoneal fluid should be offered to all primary laparoscopy patients.

Pharmacokinetics of Voriconazole in Peritoneal Fluid of Critically Ill Patients.

Data on the distribution of voriconazole (VRC) in the human peritoneal cavity are sparse. This prospective study aimed to describe the pharmacokinetics of intravenous VRC in the peritoneal fluid of critically ill patients. A total of 19 patients were included. Individual pharmacokinetic curves, drawn after single (first dose on day 1) and multiple (steady-state) doses, displayed a slower rise and lower fluctuation of VRC concentrations in peritoneal fluid than in plasma. Good but variable penetration of VRC into the peritoneal cavity was observed, and the median (range) peritoneal fluid/plasma ratios of the area under the concentration-time curve (AUC) were 0.54 (0.34 to 0.73) and 0.67 (0.63 to 0.94) for single and multiple doses, respectively. Approximately 81% (13/16) of the VRC steady-state trough concentrations (Cmin,ss) in plasma were within the therapeutic range (1 to 5.5 µg/mL), and the corresponding Cmin,ss (median [range]) in peritoneal fluid was 2.12 (1.39 to 3.72) µg/mL. Based on the recent 3-year (2019 to 2021) surveillance of the antifungal susceptibilities for Candida species isolated from peritoneal fluid in our center, the aforementioned 13 Cmin,ss in peritoneal fluid exceeded the MIC90 of C. albicans, C. glabrata, and C. parapsilosis (0.06, 1.00, and 0.25 µg/mL, respectively), which supported VRC as a reasonable choice for initial empirical therapies against intraabdominal candidiasis caused by these three Candida species, prior to the receipt of susceptibility testing results.

Bacterascites confers poor patient prognosis beyond MELD prediction.

Spontaneous bacterial peritonitis (SBP) is a well-recognized clinical entity with a poor prognosis. In comparison, the prevalence, microbiological flora, and prognostic significance of bacterascites (BA) (the presence of organism on culture but ascitic PMN <250 cells/mm³) is largely unknown. We, therefore, assessed the prognosis and predictors of outcome in patients with BA in comparison with those with SBP. Ascitic fluid cultures from consecutive patients with cirrhosis from 2008 to 2018 were reviewed retrospectively, and patients with SBP and BA were identified. Baseline demographic, laboratory, and microbiological data were collated and analyzed as prognostic indicators, and clinical outcomes were recorded. Patients were censored at the time of LT, death, or last follow-up. For this study 176 and 213 cases of SBP and BA, respectively, were identified and included. Patients with SBP had significantly higher Model for End-Stage Liver Disease (MELD) ( p =<0.01), peripheral blood WCC ( p < 0.01), and higher rates of Enterobacteriaceae ( p < 0.01) and multi-drug resistant pathogens ( p < 0.01). Survival at 1 and 3 months was lower in patients with SBP ( p < 0.01) when compared with BA but at 6 months and beyond, no significant difference remained. After the exclusion of deaths within 30 days of presentation, survival between SBP and BA was equivocal at all time points. Mortality was substantially higher across all MELD groupings for both SBP and BA when compared with the predicted mortality calculated by the MELD score alone. BA has a negative impact on patient survival above that predicted by the MELD score. It has similar impact to SBP on patient survival beyond 1 month suggesting it should be seen as a poor prognostic marker and prompt consideration of LT where appropriate. Further studies evaluating the role of secondary prophylaxis in this group are required.

Autoantibody screening of plasma and peritoneal fluid of patients with endometriosis.

STUDY QUESTION: Are there specific autoantibody profiles in patients with endometriosis that are different from those in controls? SUMMARY ANSWER: This study did not reveal a significantly higher prevalence of autoantibodies in the studied groups of patients. WHAT IS KNOWN ALREADY: Various inflammatory factors are postulated to be involved in the pathomechanisms of endometriosis, and a potential link exists with autoimmune diseases, which may also play an important role. As the diagnosis of endometriosis remains invasive, it can only be confirmed using laparoscopy with histopathological examination of tissues. Numerous studies have focused on identifying useful biomarkers to confirm the disease, but without unequivocal effects. Autoantibodies are promising molecules that serve as potential prognostic factors. STUDY DESIGN, SIZE, DURATION: A multicentre, cross-sectional study was conducted over 18 months (between 2018 and 2019), at eight Departments of Obstetrics and Gynaecology in several cities across Poland on 137 patients undergoing laparoscopic examination for the diagnosis of endometriosis. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: During laparoscopy, we obtained plasma samples from 137 patients and peritoneal fluid (PF) samples from 98 patients. Patients with autoimmune diseases were excluded from the study. Autoantibody profiling was performed using HuProt v3.1 human proteome microarrays. MAIN RESULTS AND THE ROLE OF CHANCE: We observed no significant differences in the expression of autoantibodies in the plasma or PF between the endometriosis and control groups. The study revealed that in the PF of women with Stage II endometriosis, compared with other stages, there were significantly higher reactivity signals for ANAPC15 and GABPB1 (adj. P < 0.016 and adj. P < 0.026, respectively; logFC > 1 in both cases). Comparison of the luteal and follicular phases in endometriosis patients revealed that levels of NEIL1 (adj. P < 0.029), MAGEB4 (adj. P < 0.029), and TNIP2 (adj. P < 0.042) autoantibody signals were significantly higher in the luteal phase than in the follicular phase in PF samples of patients with endometriosis. No differences were observed between the two phases of the cycle in plasma or between women with endometriosis and controls. Clustering of PF and plasma samples did not reveal unique autoantibody profiles for endometriosis; however, comparison of PF and plasma in the same patient showed a high degree of concordance. LIMITATIONS, REASONS FOR CAUTION: Although this study was performed using the highest-throughput protein array available, it does not cover the entire human proteome and cannot be used to study potentially promising post-translational modifications. Autoantibody levels depend on numerous factors, such as infections; therefore the autoantibody tests should be repeated for more objective results. WIDER IMPLICATIONS OF THE FINDINGS: Although endometriosis has been linked to different autoimmune diseases, it is unlikely that autoimmune responses mediated by specific autoantibodies play a pivotal role in the pathogenesis of this inflammatory disease. Our study shows that in searching for biomarkers of endometriosis, it may be more efficient to use higher-throughput proteomic microarrays, which may allow the detection of potentially new biomarkers. Only research on such a scale, and possibly with different technologies, can help discover biomarkers that will change the method of endometriosis diagnosis. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a grant from the Polish Ministry of Health (grant no. 6/6/4/1/NPZ/2017/1210/1352). It was also funded by the Estonian Research Council (grant PRG1076) and the Horizon 2020 Innovation Grant (ERIN; grant no. EU952516), Enterprise Estonia (grant no. EU48695), and MSCA-RISE-2020 project TRENDO (grant no. 101008193). The authors declare that there is no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Meta-analyses reveal serum or plasma Interleukin-6 as a biomarker for malignant ovarian neoplasia.

BACKGROUND: Interleukin-6 (IL-6) has been implicated in various malignancies, including ovarian cancer. However, mixed results have been observed regarding IL-6 levels in different ovarian conditions. This meta-analysis was performed to determine IL-6 levels in the peritoneal fluid and peripheral blood among patients with various adnexal masses. METHODS: Most popular English databases were searched using a predefined search formula. All studies comparing IL-6 levels in plasma, serum or peritoneal fluid of patients with benign tumors, ovarian neoplasms, and healthy controls were included based on inclusion and exclusion criteria. RESULTS: 5953 patients from 22 primary publications raging from 1994 to 2021 were included in the meta-analyses. A pooled IL-6 Mean Difference (MD) of 41 pg/mL for malignant tumors compared to benign ones, with a Confidence Interval (CI) between 19.8 and 62.2, a Z-score of 3.79, and statistical significance with a p = 0.0002 was observed. Pooled results for healthy versus benign ovarian conditions showed an MD of 5.45 pg/mL for serum or plasma IL-6 measurements in favor of benign tumors (CI:0.66-10.25, Z = 2.23 and p = 0.03). The analysis showed an MD for IL-6 levels of 19.59 pg/mL for healthy controls versus malignant ovarian tumors. Peritoneal fluid measurements regarding IL-6's levels showed no significant difference between benign or malignant masses. DISCUSSION/CONCLUSIONS: Higher levels of plasma or serum IL-6 in ovarian neoplasia patients compared to benign conditions or healthy controls identify IL-6 as a discerning factor between benign or malignant ovarian tumors and a potential biomarker for ovarian malignancy.

Validation of a new simple scoring system to predict spontaneous bacterial peritonitis in patients with cirrhosis and ascites.

BACKGROUND: Recently, a simple scoring system named the Mansoura scoring system was developed to predict spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and ascites. However, the efficacy of this newly developed system has not been extensively investigated. We aimed to validate a new simple scoring system for the rapid diagnosis or exclusion of SBP without paracentesis. METHODS: Adult patients with cirrhosis and ascites admitted to Cho Ray Hospital between November 2021 and May 2022 were included. The area under the receiver operating characteristic (AUROC) curve of the Mansoura simple scoring system for predicting SBP was calculated using the Stata software. Other independent laboratory tests for predicting SBP (C-reactive protein [CRP], neutrophil-to-lymphocyte ratio [NLR], and mean platelet volume [MPV]) were assessed and compared using the Mansoura scoring system. RESULTS: A total of 121 patients were included in this study. The Mansoura scoring system showed good performance in predicting SBP in patients with cirrhosis and ascites (AUROC:0.89). At the cut-off ≥ 4 points, the scoring system achieved a specificity of 97.7% with a positive predictive value for the diagnosis of SBP of 93.5%. Multivariate analysis was performed using our data and showed that NLR, CRP level, and MPV were independent factors related to SBP. CONCLUSION: The Mansoura scoring system demonstrated good performance in predicting SBP in patients with cirrhosis and ascites and may help guide management decisions.

A case of ascetic fluid Mycobacterium aubagnense infection in a patient with severe peritoneal effusion.

BACKGROUND: Mycobacterium aubagnense, which was first characterized in 2006, is a non-tuberculosis mycobacterium (NTM) that has only been isolated from respiratory secretions and joint fluid. With only four cases globally, the microbe has rarely been reported in human clinical cases and the strain has not been isolated from ascites. CASE PRESENTATION: To the best of our knowledge, this is the first time that M. aubagnense has been isolated from ascites samples of a patient with severe peritoneal effusion and normal liver functions. Anti-NTM therapy with moxifloxacin, ethambutol, and isoniazid combined with furosemide and spironolactone diuretic therapy relieved the symptoms after six months. CONCLUSIONS: Increased puncture and drainage of ascites combined with diuretic treatment did not significantly relieve the ascites, leading to relapse with aggravated symptoms. The subsequent anti-NTM treatment with moxifloxacin, ethambutol, and isoniazid alleviated the degree of ascites. Therefore, we postulated that M. aubagnense infection was the potential cause of the difficult reduction of ascites in this patient. However, the ascites repeatedly occurred in the patient, which was attributed to M. aubagnense resistance due to insufficient medication time and repeated medication. The patient's underlying diseases may also result in ascites. Therefore, there is a need for careful analysis of the clinical significance of M. aubagnense.

Impact of Bacteria Types on the Clinical Outcomes of Spontaneous Bacterial Peritonitis.

BACKGROUND AND AIMS: Cirrhotic patients presenting with spontaneous bacterial peritonitis (SBP) have elevated risk of short-term mortality. While high Model for End-Stage Liver Disease-Sodium score (MELD-Na) and ascites culture yielding multi-drug resistance (MDR) bacteria are well established risk factors for further aggravating mortality, the impact of individual, causative microorganisms and their respective pathogenesis have not been previously investigated. METHODS: This is a retrospective study of 267 cirrhotic patients at two tertiary care hospitals undergoing paracentesis from January 2015 to January 2021 who presented with ascitic PMN count > 250 cells/mm3. The primary outcome was SBP progression defined as death or liver transplantation within 1-month of paracentesis stratified by microorganism type. RESULTS: Of 267 patients with SBP, the ascitic culture yielded causative microorganism in 88 cases [median age 57 years (IQR 52-64)]; 68% male; median MELD-Na 29 (IQR 23-35). The microbes isolated were E. coli (33%), Streptococcus (15%), Klebsiella (13%), Enterococcus (13%), Staphylococcus (9%) and others (18%); 41% were MDR. Cumulative incidence of SBP progression within 1-month was 91% (95% CI 67-100) for Klebsiella, 59% (95% CI 42-76) for E. coli, and 16% (95% CI 4-51) for Streptococcus. After adjusting for MELD-Na and MDR, risk of SBP progression remained elevated for Klebsiella (HR 2.07; 95% CI 0.98-4.24; p-value = 0.06) and decreased for Streptococcus (HR 0.28; 95% CI 0.06-1.21; p-value = 0.09) compared to all other bacteria. CONCLUSION: Our study found Klebsiella-associated SBP had worse clinical outcomes while Streptococcus-associated SBP had the most favorable outcomes after accounting for MDR and MELD-Na. Thus, identification of the causative microorganism is crucial not only for optimizing the treatment but for prognostication.

Pharmacokinetics of cefmetazole in plasma, peritoneal fluid, peritoneum, and subcutaneous adipose tissue of patients scheduled for lower gastrointestinal surgery: Dosing considerations based on site-specific pharmacodynamic target attainment.

INTRODUCTION: Cefmetazole (CMZ) has gained interest as a carbapenem-sparing alternative to the epidemic of extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales (ESBL-E). In this study, we investigated the pharmacokinetics (PK) of CMZ in plasma, peritoneal fluid, peritoneum, and subcutaneous adipose tissue to assess the dosing regimen needed to achieve pharmacodynamic (PD) goals at the target site. METHODS: Patients scheduled for elective lower gastrointestinal surgery were intravenously administered CMZ. Plasma, peritoneal fluid, peritoneum, and subcutaneous adipose tissue samples were collected after CMZ infusion and during the surgery, and CMZ concentrations were measured. The non-compartmental and compartmental PK parameters were estimated and used to evaluate site-specific PD target attainment. RESULTS: A total of 38 plasma, 27 peritoneal fluid, 36 peritoneum, and 38 subcutaneous adipose tissue samples were collected from 10 patients. The non-compartmental PK analysis revealed the ratios of the mean area under the drug concentration-time curve (AUC0-3.5 h) of peritoneal fluid-to-plasma, peritoneum-to-plasma, and subcutaneous adipose tissue-to-plasma were 0.60, 0.36, and 0.11, respectively. The site-specific PD target attainment analyses based on the breakpoints for ESBL-E per the Japanese surgical site infection (SSI) surveillance (MIC90 = 8 mg/L) revealed that 2 g CMZ every 3.5 h achieved desired bactericidal effect at all sites and 2 g CMZ every 6 h achieved PD goals at peritoneum and peritoneal fluid. CONCLUSION: These findings clarify the PK of CMZ in abdominal tissues and could help decide optimal dosing regimens to treat intra-abdominal infection and prophylaxis of SSI.

Pharmacokinetics of flomoxef in plasma, peritoneal fluid, peritoneum, and subcutaneous adipose tissue of patients undergoing lower gastrointestinal surgery: Dosing considerations based on site-specific pharmacodynamic target attainment.

INTRODUCTION: Flomoxef is generally used to treat abdominal infections and as antibiotic prophylaxis during lower gastrointestinal surgery. It is reportedly effective against extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and an increasingly valuable alternative to carbapenems. However, its abdominal pharmacokinetics remain unclear. Herein, pharmacokinetic analysis of flomoxef in the abdominal tissue was conducted to simulate dosing regimens for pharmacodynamic target attainment in abdominal sites. METHODS: Flomoxef (1 g) was administered intravenously to a patient 30 min before commencing elective lower gastrointestinal surgery. Samples of plasma, peritoneal fluid, peritoneum, and subcutaneous adipose tissue were collected during surgery. The flomoxef tissue concentrations were measured. Accordingly, non-compartmental and compartmental pharmacokinetic parameters were calculated, and simulations were conducted to evaluate site-specific pharmacodynamic target values. RESULTS: Overall, 41 plasma samples, 34 peritoneal fluid samples, 38 peritoneum samples, and 41 subcutaneous adipose samples from 10 patients were collected. The mean peritoneal fluid-to-plasma ratio in the areas under the drug concentration-time curve was 0.68, the mean peritoneum-to-plasma ratio was 0.40, and the mean subcutaneous adipose tissue-to-plasma was 0.16. The simulation based on these results showed the dosing regimens (q8h [3 g/day] and q6h [4 g/day]) achieved the bactericidal effect (% T > minimum inhibitory concentration [MIC] = 40%) in all tissues at an MIC of 1 mg/L. CONCLUSIONS: We elucidated the pharmacokinetics of flomoxef and simulated pharmacodynamics target attainment in the abdominal tissue. This study provides evidence concerning the use of optimal dosing regimens for treating abdominal infection caused by strains like ESBL-producing bacteria.

Emergency medicine updates: Spontaneous bacterial peritonitis.

INTRODUCTION: Spontaneous bacterial peritonitis (SBP) is a common infection in patients with cirrhosis and ascites and is associated with significant risk of mortality. Therefore, it is important for emergency medicine clinicians to be aware of the current evidence regarding the diagnosis and management of this condition. OBJECTIVE: This paper evaluates key evidence-based updates concerning SBP for the emergency clinician. DISCUSSION: SBP is commonly due to Gram-negative bacteria, but infections due to Gram-positive bacteria and multidrug resistant bacteria are increasing. The typical presentation of SBP includes abdominal pain, worsening ascites, fever, or altered mental status in a patient with known liver disease; however, some patients may be asymptomatic or present with only mild symptoms. Paracentesis is the diagnostic modality of choice and should be performed in any patient with ascites and concern for SBP or upper gastrointestinal bleeding, or in those being admitted for a complication of cirrhosis. Ultrasound should be used to optimize the procedure. An ascites absolute neutrophil count (ANC) ≥ 250 cells/mm3 is diagnostic of SBP. Ascitic fluid should be placed in blood culture bottles to improve the culture yield. Leukocyte esterase reagent strips can be used for rapid diagnosis if available. While many patients will demonstrate coagulation panel abnormalities, routine transfusion is not recommended. Management traditionally includes a third-generation cephalosporin, but specific patient populations may require more broad-spectrum coverage with a carbapenem or piperacillin-tazobactam. Albumin infusion is associated with reduced risk of renal impairment and mortality. CONCLUSIONS: An understanding of literature updates can improve the care of patients with suspected SBP.

The Abundance and Function of Neutrophils in the Endometriosis Systemic and Pelvic Microenvironment.

Endometriosis is a common inflammatory illness in which endometrial tissue grows outside the uterine cavity. Immune dysfunction is now widely acknowledged as the primary cause of endometriosis. The immune cell population represented by neutrophils is thought to play an essential role in the etiology, pathophysiology, and associated clinical outcome. There is growing evidence that neutrophils have a role in chronic and aseptic inflammatory diseases, and endometriosis patients have increased levels of neutrophils in plasma, peritoneal fluid, and ectopic endometrium. Here, we sought to review the function of neutrophils in the pathogenesis of endometriosis, with an emphasis on the role of neutrophils in regulating endometrial angiogenesis and the local inflammatory microenvironment.

Categorisation of peritoneal serous effusions using the International System for Reporting Serous Fluid Cytopathology-A study on gynaecological samples.

BACKGROUND: Cytology of serous effusions is an indispensable diagnostic tool for the diagnosis of non-neoplastic as well as neoplastic effusions, aiding in the categorisation, staging, and prognostication of the patient. This study focuses on reclassifying cases of peritoneal fluid cytology following the International System for Reporting Serous Fluid Cytopathology (TIS), highlighting various challenges encountered and adding to the body of data regarding the risk of malignancy (ROM), focussing on peritoneal effusions due to gynaecological causes. METHODS: Peritoneal effusion samples were retrieved from our department's archives and reclassified according to the TIS. The ROM for each category was calculated based on available surgical follow-up. RESULTS: A total of 818 peritoneal effusions were studied. Following the definitions and guidelines of the TIS, the cases were reclassified with 125 (15.2%) in the category of non-diagnostic (ND), 595 (72.7%) as negative for malignancy (NFM), 26 (3.2%) as atypia of undetermined significance (AUS), 12 (1.5%) as suspicious for malignancy (SFM), and 60 (7.3%) as malignant (MAL). The respective ROM values for each category were 16.9%, 12.1%, 50%, 80%, and 100%, respectively. By considering the MAL and SFM groups as positive, and the ND, NFM, and AUS groups as negative, the diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values were determined as 85.2%, 36.7%, 99.1%, 91.7%, and 84.5%, respectively. CONCLUSIONS: Peritoneal cytology categorisation following the proposed TIS offered a practical approach for categorisation of the fluids received. The ROMs reported in our study were mostly concordant with those published according to the TIS.