Search Results (2,677)

Background/Objectives: To prevent surgical site infections, it is important to consider the concentration of the administered antibiotic in the target compartment. We measured the concentrations of cefuroxime and metronidazole in peritoneal fluid with the microdialysis technique in patients undergoing surgery for secondary peritonitis (7 patients) and for inflammatory bowel disease (11 patients). Methods: All patients received 1.5 g of cefuroxime and 0.5 g of metronidazole every 8 h during the postoperative period for at least 72 h. Microdialysates covering 8-h intervals were collected, and the concentration of cefuroxime and metronidazole was measured using liquid chromatography–mass spectrometry. Results: For metronidazole, a concentration of ≥4 μg/mL was reached in all but one sample, corresponding to the minimal inhibitory concentration (MIC) for most anaerobic bacteria strains. For cefuroxime, a value of ≥4 μg/mL was reached in 88% and 93% of the samples in the peritonitis group and the IBD group, respectively, corresponding to the MIC values for most Gram-negative bacteria, and a value of ≥16 μg/mL, corresponding to the MIC value for more resistant bacteria, was reached in only 40% and 23% of the samples, respectively. Conclusions: Our results show that the peritoneal microdialysis method is feasible for studying the diffusion of antibiotics into the peritoneal cavity. Measuring the accumulative concentration of antibiotics in the peritoneal fluid corresponding to the drug administration interval may provide important information to consider alongside traditional pharmacodynamic parameters and may be relevant to achieving an optimal therapeutic effect. Full article

Background/Objectives: Ovarian cancer is the most lethal gynecologic malignancy, largely due to late diagnosis and the high prevalence of malignant ascites, a hallmark of advanced disease that is difficult to control and contributes to immune suppression and treatment failure. Despite advances in standard care, durable responses are rare. This study investigates a novel immunotherapeutic strategy designed to overcome the suppressed peritoneal microenvironment using an oncolytic vaccinia virus engineered to express a decoy-resistant IL-18 mutein. Methods: We generated a vaccinia virus (vvDD-nsmDR-18) expressing a non-secreted, mature, decoy-resistant IL-18. Viral expression was validated via RT-qPCR and fluorescence microscopy, while cytotoxicity was confirmed using CCK-8 assays. The antitumor efficacy of vvDD-nsmDR-18 was evaluated in the aggressive murine ID8a ovarian cancer model. The underlying mechanisms of action were investigated using flow cytometry and transcriptional profiling. Results: Treatment with vvDD-nsmDR-18 significantly prolonged survival and was associated with reduced abdominal distension consistent with decreased ascites burden. Immune analyses indicated enhanced T cell activation across multiple anatomical compartments, including tumors, peritoneal cavity, and spleens, the latter recently suggested to serve as a reservoir for tumor-reactive T cells. This systemic activation was characterized by increased IFN-γ and perforin expression. In addition, vvDD-nsmDR-18 treatment was associated with expansion of CD39⁺CD103⁺CD8⁺ tumor-reactive T cells and a shift toward a lower PD-1 expression phenotype within this population. Conclusions: These findings demonstrate that nsmDR-18-expressing oncolytic viruses can remodel the immunosuppressive landscape of advanced ovarian cancer, suggesting this approach is a promising candidate for further clinical development. Full article

Metastatic colorectal cancer (mCRC) accounts for 90% of CRC-related mortality. This review synthesizes insights from comparative genomics tracing evolutionary trajectories from primary tumor to disseminated disease. Multi-region sequencing reveals metastatic seeding often occurs early—before clinical detection—challenging linear progression models. The metastatic bottleneck reduces clonal diversity while enriching for dissemination-competent traits including SMAD4 loss, PTEN inactivation and metabolic reprogramming. Organ-specific adaptation yields distinct molecular signatures: liver metastases exhibit Wnt hyperactivation and TGF-β-driven immune suppression; peritoneal tumors display mucinous features; brain metastases show HER2 enrichment. The immune microenvironment evolves toward immunosuppressive configurations, with Microsatellite instability high (MSI-H) tumors acquiring B2M or JAK1/2 mutations. Circulating tumor DNA (ctDNA) enables real-time tracking of clonal dynamics, detecting molecular residual disease months before radiographic progression. Therapeutic resistance follows predictable evolutionary trajectories—from RAS/BRAF mutations to EGFR ectodomain alterations, HER2/MET amplifications and lineage plasticity—with metastasis-specific mechanisms including microenvironmental protection and cellular dormancy. The clinical future lies in interception: leveraging liquid biopsies for early detection, targeting both tumor-intrinsic vulnerabilities and permissive metastatic niches and adapting therapy dynamically to anticipate resistance. Understanding this genomic odyssey is essential for transforming mCRC into a controllable chronic condition. Full article

Clostridium tertium is an emerging opportunistic pathogen typically associated with immunocompromised hosts, yet it can also cause serious infections in non-neutropenic individuals. We present a case of postoperative peritonitis and bacteremia caused by C. tertium in a non-neutropenic 75-year-old woman following emergency obturator hernia repair. Diagnosis was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and successful treatment was achieved with piperacillin–tazobactam combined with levornidazole alongside surgical source control. A review of 128 cumulative cases (including ours) revealed two distinct patterns: bacteremia in severely neutropenic patients versus a broader spectrum of localized and bloodstream infections in non-neutropenic hosts, often linked to intestinal barrier disruption. Mortality was largely driven by underlying comorbidities and polymicrobial sepsis. These findings indicate that C. tertium infection should be considered in non-neutropenic patients with postoperative or gastrointestinal barrier-disruptive infections, especially when there is a poor response to initial empiric therapy. Consequently, in such clinical scenarios, empirical therapy should be guided by its unique resistance pattern, favoring carbapenems, vancomycin, or piperacillin–tazobactam, often combined with a nitroimidazole, alongside urgent source control. Full article

Background and Objectives: Sepsis-associated acute kidney injury (SA-AKI) is driven by exaggerated inflammation and oxidative stress, with the HMGB1–RAGE axis playing a pivotal role in amplifying tissue damage. This study aimed to investigate the renoprotective effects of papaverine in a feces-induced peritonitis (FIP) model of sepsis and to explore its impact on HMGB1–RAGE-mediated inflammatory and oxidative pathways. Materials and Methods: Sepsis was induced in male Wistar rats by intraperitoneal injection of fecal slurry (1 g/kg). Animals were treated with papaverine (20 or 40 mg/kg, i.p.) one hour after FIP induction and evaluated at 24 h. Renal function (BUN, creatinine, lactate), inflammatory markers (HMGB1, TNF-α, CRP), oxidative stress (MDA), circulating sRAGE levels, renal NF-κB levels, and histopathological injury scores were assessed. Results: The FIP model resulted in an early mortality rate of 20% and produced marked renal histopathological alterations. Biochemically, FIP increased plasma HMGB1, TNF-α, CRP, MDA, BUN, creatinine, and lactate levels while decreasing sRAGE. Papaverine treatment dose-dependently reduced inflammatory and oxidative markers, restored sRAGE levels, improved renal function parameters, and attenuated histopathological injury. In addition, renal NF-κB levels were significantly elevated in the FIP group compared to controls and were dose-dependently reduced following papaverine treatment. Conclusions: FIP-induced sepsis activates an HMGB1-driven inflammatory–oxidative cascade contributing to SA-AKI. Papaverine confers dose-dependent renoprotection by suppressing HMGB1–RAGE signaling, attenuating NF-κB activation, reducing oxidative stress, and preserving renal structure and function. Targeting the HMGB1–sRAGE axis may represent a promising therapeutic strategy in sepsis-associated renal injury. Full article

Background: Endometrial cancer (EC) is the most common gynecological malignancy in Western countries. Although international guidelines recommend that patients with EC be treated at specialized oncology centers, many are still managed by general gynecologists. This study aimed to evaluate the influence of facility volume on treatment strategies and survival outcomes among EC patients. Methods: This is a retrospective multicenter study comparing 971 patients with EC treated at medium-volume centers (CVMs) (11–29 cases/year) with 1431 patients treated at high-volume centers (CVAs) (≥30 cases/year). Patient characteristics were recorded, including age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, comorbidities, surgical approach, lymphadenectomy, total number of lymph nodes removed, number of positive lymph nodes, length of hospital stay, histological characteristics, ESMO-ESGO (European Society for Medical Oncology–European Society of Gynaecological Oncology) classification system, adjuvant treatment, recurrence, progression-free survival (PFS), and overall survival (OS). Postoperative fever, hemoglobin changes, and blood transfusions were also reported. Results: Compared with patients treated at the MVCs, patients treated at the HVCs were younger (mean age, 65 vs. 66.4 years, p = 0.03) and had a lower rate of comorbidities (41% vs. 55%, p < 0.001). Patients treated at HVCs were mostly in higher ESMO-ESGO recurrence risk classes (p < 0.001), were treated mostly laparoscopically (58% vs. 47%, p < 0.001) and had better staging (higher number of lymph nodes harvested (mean 19 vs. 11, p < 0.001) and more peritoneal biopsies performed (27% vs. 14%, p < 0.001). HVC patients had fewer complications and received less adjuvant therapy (40% vs. 50%, p < 0.001) but, when treated, received chemotherapy more frequently, showed mostly loco-regional recurrences (34% vs. 14%) and fewer extra-abdominal recurrences (34% vs. 54%). HVC patients had better PFS and OS. Center volume was found to be an independent factor influencing PFS in multivariate analysis. Conclusions: All EC patients should be centrally managed to receive superior treatment to improve postoperative recovery and oncological outcomes, particularly for patients with more-aggressive tumors. Full article

Inflammatory-oxidative stress generated by immune cells plays an important role in aging and in age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Triple-transgenic mice for AD (3xTg-AD) are a suitable model for mimicking this disease in an age-dependent manner. We previously showed that peritoneal leukocyte functions and their redox-inflammatory state are altered early in female 3xTg-AD mice, which exhibit premature aging compared to non-transgenic (NTg) animals. However, their characteristics at 9 months of age, when they present an early neuropathological state, and the sex differences are not known. Here, we analyzed several spleen and thymus leukocyte functions (chemotaxis, natural killer activity, and lymphoproliferation in response to mitogens), pro-inflammatory (IL-1B, TNF-alpha) and anti-inflammatory (IL-10) released cytokine concentrations, and redox parameters (glutathione concentrations and glutathione peroxidase, glutathione reductase, and xanthine oxidase activities) in male and female 3xTg-AD mice compared to age-matched controls. We also analyzed the effects of voluntary physical exercise on immune functions. Our results show that 9-month-old male and female 3xTg-AD mice have worse immune functions, redox state, and inflammation than NTg counterparts. Physical exercise improves immune function. Thus, accelerated aging reflected by peripheral immunosenescence and oxidation-inflammation in 3xTg-AD mice precedes hallmark neuropathology, and exercise can slow down AD progression. Full article

Scavenger Receptors (SRs) comprise a structurally diverse group of pattern recognition receptors (PRRs) involved in sensing non-self (microbial-associated molecular patterns) or altered-self ligands. CD5 and CD6 are class I SRs (SR-I) preferentially expressed by lymphoid cells and characterized by the presence of several tandem scavenger receptor cysteine-rich (SRCR) domain repeats. Both receptors interact with diverse microbial structures, including tegumental antigens from Echinococcus granulosus sensu lato (s.l.), the cestode parasite responsible for cystic echinococcosis (CE). This is notable as very few PRRs are currently known to detect parasitic helminths and because the infusion of recombinant soluble CD5 and CD6 proteins has shown prophylactic effects in murine secondary CE. Herein, the role of CD5 and CD6 in early immune responses to E. granulosus s.l. tegumental antigens (PSEx) was analyzed using CD5 (Cd5^−/−) and CD6 (Cd6^−/−)-deficient mice. Peritoneal B cells and macrophages from wild-type mice displayed specific and dose-dependent PSEx binding, which was impaired in those from Cd5^−/− and Cd6^−/− mice, supporting direct and/or indirect roles in parasite recognition. Additionally, in vivo exposure of peritoneal exudate cells (PECs) from Cd5^−/− and Cd6^−/− mice to PSEx showed altered activation profiles, including changes in CD80/CD86 expression, impaired early production of natural polyreactive antibodies, and cytokine shift from a Th1/Th17 to a Th2 profile. These findings strongly support the involvement of CD5 and CD6 receptors in the early immune recognition of E. granulosus s.l. antigens by PECs and influence immune responses critical for host resistance, highlighting their relevance in host–parasite interactions. Full article

Background and Objectives: High-grade serous ovarian carcinoma (HGSOC) remains the most lethal gynecologic malignancy, with outcomes heavily dependent on early diagnosis and timely multimodal treatment. The COVID-19 pandemic profoundly disrupted oncologic care, leading to diagnostic delays, modified treatment algorithms, and deferred surgeries. This study aimed to assess how these disruptions influenced disease presentation, surgical complexity, and postoperative outcomes during the pandemic and post-pandemic periods in a Romanian tertiary oncology center. Materials and Methods: A retrospective, single-center cohort analysis was conducted on 112 patients with histologically confirmed HGSOC who underwent surgical treatment between 26 February 2020 and 25 February 2024. The cohort was divided into two equal groups: a pandemic cohort (2020–2022) and a post-pandemic cohort (2022–2024). Clinical, pathological, and therapeutic parameters were compared, including FIGO and T staging, surgical duration, ICU admissions, and treatment intervals. Results: The post-pandemic period was marked by a significant rise in advanced-stage presentations (FIGO IV: 17.8% vs. 33.9%, p = 0.003), peritoneal carcinomatosis (58.9% vs. 82.1%, p = 0.004), and multiorgan invasion (7.1% vs. 16.0%, p = 0.039). Mean operative time increased significantly post-pandemic (94.0 ± 36.3 vs. 123.5 ± 52.5 min, p = 0.003), as did ICU admissions (35.7% vs. 60.7%, p = 0.002). While the number of neoadjuvant and adjuvant chemotherapy cycles remained consistent between cohorts, a greater surgical complexity and longer postoperative recovery characterized the post-pandemic cases, suggesting cumulative disease progression and increased treatment demands. Conclusions: The findings indicate an association between the post-pandemic period and more advanced disease profiles at presentation, as well as increased surgical complexity, highlighting potential long-term effects of healthcare disruption. These results highlight the necessity for resilient cancer care systems emphasizing early detection, multidisciplinary coordination, and adaptive treatment models to mitigate future systemic disruptions and preserve survival outcomes in women with HGSOC. Full article

Background: There is limited information about treatment success and outcomes in retrovirus-positive cats diagnosed with feline infectious peritonitis (FIP). Methods: A survey was distributed to caretakers of cats with feline leukemia virus (FeLV) and/or feline immunodeficiency virus (FIV) that were treated with GS-441524 for presumptive effusive FIP based on survey responses. Results: Cats with FIV developed FIP at an older age and longer after retrovirus infection than cats with FeLV. The average starting dosage (7 mg/kg/d) was increased in 65% of cats, and treatment was extended in 35%. Three cats relapsed (18%). There was a 94% (16/17) twelve-week survival rate and 82% (14/17) one-year survival rate. Seven cats were alive at follow-up, a median of 1306 days (range 983–2069) after FIP diagnosis, but many cats succumbed to neoplasia. Conclusions: Treatment success for retrovirus-positive cats with presumptive FIP was similar to previously reported outcomes for FIP alone. This could support current evidence of successful antiviral therapy for similar populations, if noncurrent, unstandardized protocols and unlicensed product use are considered. Additional studies are needed to determine ideal protocols for rapid resolution of FIP, good long-term survival, and limited relapse in retrovirus-positive cats, and the impact of the FeLV proviral load. Full article

Background: Pediatric kidney failure, whether acute or chronic, constitutes a major public health issue because of its impact on survival, linear growth, neurocognitive development, and long-term quality of life. While high-income countries have markedly improved outcomes through early diagnosis, advanced dialysis technologies, and kidney transplantation, management remains limited in low- and middle-income countries, particularly in the Maghreb region. Objective: This review aims to provide an updated synthesis of pediatric kidney failure, with emphasis on renal replacement therapy modalities and the specific challenges encountered in resource-limited contexts, particularly in Algeria. Methods and Content: We successively address the pathophysiological and clinical bases of pediatric acute kidney injury and chronic kidney disease, followed by a discussion of available therapeutic strategies: peritoneal dialysis, intermittent hemodialysis, continuous renal replacement therapy, and pediatric kidney transplantation. Particular attention is given to organizational constraints, actual availability of modalities, limited access to consumables and immunosuppressive therapies, and the specificities of pediatric kidney care in the Maghreb region in comparison with international recommendations. Perspectives: Improving outcomes for children with kidney failure in Maghreb countries requires a multidimensional approach integrating early screening, strengthening peritoneal dialysis programs, structured development of pediatric kidney transplantation, and enhanced regional and international collaboration. Reinforcing local research capacity and participation in international registries are essential steps toward reducing disparities in care and adapting global guidelines to local realities. Full article

Background: Primary peritoneal carcinoma (PPC) is an uncommon malignancy typically diagnosed in postmenopausal women, accounting for less than 1% of all gynecologic cancers. Its occurrence in adolescents is extremely rare. We present a case of a 16-year-old female with low-grade serous carcinoma (LGSC) arising from the anterior rectal peritoneum, highlighting diagnostic challenges and therapeutic considerations. Case Presentation: A 16-year-old girl presented with a 7-day history of lower abdominal pain. Ultrasound revealed an 8 cm mixed cystic–solid pelvic mass anterior to the rectum. Laboratory tests showed elevated CA-125 (106 U/mL). Exploratory laparotomy demonstrated an 8 cm solid mass attached to the anterior rectal wall, extending into the right mesorectum with peritoneal nodules at the bladder reflection. The uterus and adnexa appeared grossly normal. Frozen section analysis revealed adenocarcinoma with psammoma body formation. Histopathology and immunohistochemistry confirmed low-grade serous carcinoma: PAX8(+), WT1(+), CK7(+), ER(60%), PR(40%), CK20(–), and P53 wild-type. Peritoneal washings contained rare malignant cells. Postoperatively, the patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. Final pathology confirmed low-grade serous carcinoma involving the anterior rectal wall, bilateral adnexal surfaces, and peritoneum. She completed six cycles of adjuvant chemotherapy (paclitaxel + carboplatin, TC regimen). No recurrence was observed during follow-up. Conclusions: This case underscores the importance of considering PPC in the differential diagnosis of pelvic masses in young females, even when the ovaries appear normal. Full article

Encephalitozoon cuniculi is an atypical, opportunistic, obligate intracellular fungal pathogen that infects vertebrates. It survives within the host by modulating the host immune response. Crotoxin (CTX), a bioactive compound isolated from the venom of Crotalus durissus terrificus, has been reported to modulate immune responses. This study evaluated the effects of CTX on the immune response of mice infected with E. cuniculi. Mice were immunosuppressed with cyclophosphamide (Cy), infected with E. cuniculi spores, and treated with a single dose of CTX on the day of experimental. The animals were euthanized on day 14 post-infection. Levels of T helper (Th1, Th2, and Th17) cytokines were measured in plasma, and macrophage and lymphocyte populations were analyzed in peritoneal lavage fluid and spleen. In addition, histopathological alterations, hepatic fungal burden, and mRNA expression levels of NLRP3 inflammasome–related genes were assessed. CTX upregulated NLRP3 inflammasome expression and increased IL-18 production, while reducing fungal burden in E. cuniculi-infected mice. Moreover, CTX increased the proportions of macrophages and B cells and enhanced IFN-γ expression in CD4⁺ and CD8⁺ T lymphocytes. Collectively, these findings indicate that CTX reduces fungal load in Cy-immunosuppressed mice infected with E. cuniculi by priming the NLRP3 inflammasome complex and upregulating IL-18 production. Full article

Ovarian cancer (OC) is frequently diagnosed at an advanced stage and characterized by high rates of recurrence despite aggressive cytoreductive surgery and chemotherapy. Relapse is driven by microscopic residual tumors that are disseminated most often throughout the peritoneal cavity, posing significant challenges with conventional systemic therapy. Targeted alpha-particle therapy (TAT) combines molecular targeting with alpha-emitting radionuclides to deliver highly potent and localized cellular damage, uniquely suited for the eradication of small OC tumor clusters within the peritoneal cavity. We conducted an extensive literature search for clinical trials (clinicaltrials.gov) and pre-clinical studies (PubMed, Scopus, Google Scholar) between September 2025 and November 2025. Peer-reviewed articles published in English over the past 20 years that used OC mouse models with reported treatment data were included. Review articles without original data and clinical trials that have been terminated or withdrawn were excluded. In this review, we (1) summarize the biological and physical rationale supporting the use of TAT in OC, (2) discuss the relevant molecular and immunological anti-tumor mechanisms, and (3) critically evaluate early treatment outcomes of 19 pre-clinical and four clinical studies with respect to efficacy, safety, and feasibility. Despite the progress and promising survival outcomes, several challenges remain, including heterogeneous antigen expression, delivery and retention within the peritoneal cavity, off-target toxicity, radiation resistance, radionuclide availability, dosimetry uncertainties, and limitations in clinical trial design. We highlight future directions to overcome these barriers and the continued multidisciplinary efforts essential to translate TAT into effective clinical strategies to treat advanced stages of OC and other solid tumors resistant to conventional treatment. This work was supported with funding available to Kurt R. Zinn as the Hickman Family Endowed Chair in Oncology at Michigan State University. Full article

Pregnancy (HP), defined as the coexistence of intrauterine and ectopic gestations, is a rare condition, especially in spontaneous conception, but it is a life-threatening obstetric emergency when rupture occurs, with a reported maternal mortality rate of 0.03%. Diagnosis is often delayed because confirmation of an intrauterine pregnancy can mask clinical signs of a concurrent ectopic gestation. Early recognition and prompt surgical intervention are therefore critical to maternal safety and preservation of intrauterine viability. This case highlights the diagnostic challenges and successful management of a spontaneous ruptured heterotopic pregnancy. Case presentation: A 34-year-old Middle Eastern woman, gravida 4, with a spontaneous conception, presented with sudden severe lower abdominal pain and signs of acute hemoperitoneum (hypotension, tachycardia, and marked peritoneal signs). Transvaginal ultrasound demonstrated a viable intrauterine pregnancy at 9 weeks 4 days gestation, together with a ruptured left tubal ectopic pregnancy of similar gestational age. The patient underwent urgent laparoscopic left salpingectomy with evacuation of approximately 1200 mL of intraperitoneal blood and clots. Postoperatively, she developed significant anemia (hemoglobin drop from 11.2 g/dL on admission to 6.5 g/dL) requiring transfusion of four units of packed red blood cells. Serial ultrasonographic follow-up confirmed ongoing viability of the intrauterine pregnancy, which ultimately resulted in a live birth at term. Progressive resolution of the postoperative pelvic hematoma was also noted. Conclusions: Ruptured heterotopic pregnancy remains a diagnostic and therapeutic challenge. This case, along with a synthesis of the contemporary literature, demonstrates that a high clinical index of suspicion, timely ultrasound diagnosis, and immediate minimally invasive surgical management are paramount. Furthermore, rigorous postoperative monitoring and resuscitation, including targeted transfusion, are essential to achieve maternal stabilization while allowing continuation of a viable intrauterine pregnancy, with reported live birth rates exceeding 70% following timely intervention. Full article