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JPMA. the Journal of the Pakistan... Jul 2023Amyand's hernia represents an inguinal hernia containing an appendix within the hernia sac. This extremely rare condition occurs in approximately 1% of all inguinal...
Amyand's hernia represents an inguinal hernia containing an appendix within the hernia sac. This extremely rare condition occurs in approximately 1% of all inguinal hernias. This report describes the case of an 84-year-old male who presented with a right inguinal mass that intraoperatively turned out to be Amyand's hernia type-II with a gangrenous and perforated appendix. An appendectomy and peritoneal lavage were performed, followed by a hernioplasty where a modified Bassini repair was used. The patient fully recovered, and was discharged from the hospital on the fourth day. A non-reducible inguinal hernia containing a perforated appendix is a very rare emergency that requires immediate intervention to prevent abdominal sepsis. Therefore, while examining an inguinal hernia, the possibility of Amyand's hernia should always be considered.
Topics: Male; Humans; Aged, 80 and over; Hernia, Inguinal; Appendix; Appendectomy; Appendicitis; Gangrene
PubMed: 37469071
DOI: 10.47391/JPMA.6700 -
Frontiers in Cellular and Infection... 2023Patients with Human Hyper IgM syndromes (HIGM) developed pulmonary and gastrointestinal infections since infancy and most patients have mutations in the CD40 ligand...
Elevated levels of enteric IgA in an unimmunised mouse model of Hyper IgM syndrome derived from gut-associated secondary lymph organs even in the absence of germinal centres.
INTRODUCTION
Patients with Human Hyper IgM syndromes (HIGM) developed pulmonary and gastrointestinal infections since infancy and most patients have mutations in the CD40 ligand (CD40L) gene. Most HIGM patients compared to healthy subjects have higher/similar IgM and lower IgG, and IgA serum concentrations but gut antibody concentrations are unknown. CD40L on activated T-cells interacts with CD40 on B-cells, essential for the formation of germinal centres (GCs) inside secondary lymphoid organs (SLOs), where high-affinity antibodies, long-lived antibody-secreting plasma cells, and memory B-cells, are produced. C57BL6-CD40 ligand deficient mice (C57BL6- ), are a model of HIGM, because serum immunoglobulin concentrations parallel levels observed in HIGM patients and have higher faecal IgA concentrations. In mice, TGFβ and other cytokines induce IgA production.
AIMS
To compare and evaluate B-cell populations and IgA-producing plasma cells in peritoneal lavage, non-gut-associated SLOs, spleen/inguinal lymph nodes (ILN), and gut-associated SLOs, mesenteric lymph nodes (MLN)/Peyer´s patches (PP) of unimmunised C57BL6- and C57BL6-wild-type (WT) mice.
MATERIAL AND METHODS
Peritoneal lavages, spleens, ILN, MLN, and PP from 8-10 weeks old C57BL6- and WT mice, were obtained. Organ cryosections were analysed by immunofluorescence and B-cell populations and IgA-positive plasma cell suspensions by flow cytometry.
RESULTS
In unimmunised WT mice, GCs were only observed in the gut-associated SLOs, but GCs were absent in all C57BL6- SLOs. PP and MLN of C57BL6- mice exhibited a significantly higher number of IgA-producing cells than WT mice. In the spleen and ILN of C57BL6- mice IgA-producing cells significantly decreased, while IgM-positive plasma cells increased. C57BL6- B-1 cells were more abundant in all analysed SLOs, whereas in WT mice most B-1 cells were contained within the peritoneal cavity. C57BL6- B-cells in MLN expressed a higher TGFβ receptor-1 than WT mice. Mouse strains small intestine microvilli (MV), have a similar frequency of IgA-positive cells.
DISCUSSION
Together our results confirm the role of PP and MLN as gut inductive sites, whose characteristic features are to initiate an IgA preferential immune response production in these anatomical sites even in the absence of GCs. IgA antibodies play a pivotal role in neutralising, eliminating, and regulating potential pathogens and microorganisms in the gut.
Topics: Humans; Mice; Animals; CD40 Ligand; Hyper-IgM Immunodeficiency Syndrome; Germinal Center; Intestine, Small; Immunoglobulin A; Immunoglobulin M; Transforming Growth Factor beta
PubMed: 37457961
DOI: 10.3389/fcimb.2023.1172021 -
Molecular Medicine (Cambridge, Mass.) Jul 2023Abnormal activation of NLRP3 inflammasome is related to a series of inflammatory diseases, including type 2 diabetes, gouty arthritis, non-alcoholic steatohepatitis...
BACKGROUND
Abnormal activation of NLRP3 inflammasome is related to a series of inflammatory diseases, including type 2 diabetes, gouty arthritis, non-alcoholic steatohepatitis (NASH), and neurodegenerative disorders. Therefore, targeting NLRP3 inflammasome is regarded as a potential therapeutic strategy for many inflammatory diseases. A growing number of studies have identified tanshinone I (Tan I) as a potential anti-inflammatory agent because of its good anti-inflammatory activity. However, its specific anti-inflammatory mechanism and direct target are unclear and need further study.
METHODS
IL-1β and caspase-1 were detected by immunoblotting and ELISA, and mtROS levels were measured by flow cytometry. Immunoprecipitation was used to explore the interaction between NLRP3, NEK7 and ASC. In a mouse model of LPS-induced septic shock, IL-1β levels in peritoneal lavage fluid and serum were measured by ELISA. Liver inflammation and fibrosis in the NASH model were analyzed by HE staining and immunohistochemistry.
RESULTS
Tan I inhibited the activation of NLRP3 inflammasome in macrophages, but had no effect on the activation of AIM2 or NLRC4 inflammasome. Mechanistically, Tan I inhibited NLRP3 inflammasome assembly and activation by targeting NLRP3-ASC interaction. Furthermore, Tan I exhibited protective effects in mouse models of NLRP3 inflammasome-mediated diseases, including septic shock and NASH.
CONCLUSIONS
Tan I specifically suppresses NLRP3 inflammasome activation by disrupting the association of NLRP3 and ASC, and exhibits protective effects in mouse models of LPS-induced septic shock and NASH. These findings suggest that Tan I is a specific NLRP3 inhibitor and may be a promising candidate for treating NLRP3 inflammasome-related diseases.
Topics: Animals; Mice; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Non-alcoholic Fatty Liver Disease; Lipopolysaccharides; Shock, Septic; Diabetes Mellitus, Type 2; Anti-Inflammatory Agents; Disease Models, Animal; Interleukin-1beta; Mice, Inbred C57BL
PubMed: 37400760
DOI: 10.1186/s10020-023-00671-0 -
Journal of Surgical Case Reports Jun 2023Idiopathic omental hemorrhage is a rare cause of an acute abdomen, which is potentially life threatening. Here, we report a case of a 34-year-old male who presented to...
Idiopathic omental hemorrhage is a rare cause of an acute abdomen, which is potentially life threatening. Here, we report a case of a 34-year-old male who presented to the emergency department with sudden, severe pain abdomen and abdominal distension for 1 day. There was no history of trauma, abdominal surgeries or any significant past medical history. The diagnosis was suspected on contrast computed tomography, which revealed hyperdense areas of blood in the peritoneal cavity with contrast extravasation from the omentum. The patient underwent successful emergency laparotomy, peritoneal lavage and greater omentectomy to achieve hemostasis.
PubMed: 37397069
DOI: 10.1093/jscr/rjad380 -
Antioxidants (Basel, Switzerland) Jun 2023Asthma is a chronic airway inflammatory disease listed as one of the top global health problems. BÂN is a well-known medicinal plant in Vietnam with its anti-oxidant,...
Asthma is a chronic airway inflammatory disease listed as one of the top global health problems. BÂN is a well-known medicinal plant in Vietnam with its anti-oxidant, anti-microbial, anti-inflammatory potential, and gastro-protective properties. However, there is no study about extract (PVE) on asthma disease. Here, an OVA-induced asthma mouse model was established to evaluate the anti-inflammatory and anti-asthmatic effects and possible mechanisms of PVE. BALB/c mice were sensitized by injecting 50 μg OVA into the peritoneal and challenged by nebulization with 5% OVA. Mice were orally administered various doses of PVE once daily (50, 100, 200 mg/kg) or dexamethasone (Dex; 2.5 mg/kg) or Saline 1 h before the OVA challenge. The cell infiltrated in the bronchoalveolar lavage fluid (BALF) was analyzed; levels of OVA-specific immunoglobulins in serum, cytokines, and transcription factors in the BALF were measured, and lung histopathology was evaluated. PVE, especially PVE 200mg/kg dose, could improve asthma exacerbation by balancing the Th1/Th2 ratio, reducing inflammatory cells in BALF, depressing serum anti-specific OVA IgE, anti-specific OVA IgG1, histamine levels, and retrieving lung histology. Moreover, the PVE treatment group significantly increased the expressions of antioxidant enzymes Nrf2 and HO-1 in the lung tissue and the level of those antioxidant enzymes in the BALF, decreasing the oxidative stress marker MDA level in the BALF, leading to the relieving the activation of MAPK signaling in asthmatic condition. The present study demonstrated that Phaeanthus vietnamensis BÂN, traditionally used in Vietnam as a medicinal plant, may be used as an efficacious agent for treating asthmatic disease.
PubMed: 37372031
DOI: 10.3390/antiox12061301 -
Updates in Surgery Aug 2023The aim of this study is to define the importance of peritoneal CEA (pCEA) as a prognostic factor of overall survival (OS) and disease-free survival (DFS) in gastric...
The aim of this study is to define the importance of peritoneal CEA (pCEA) as a prognostic factor of overall survival (OS) and disease-free survival (DFS) in gastric cancer (GC) patients surgically treated with a curative intent In our department. A total of 64 patients affected by gastric cancer with intraoperatively measurement of CEA on peritoneal lavage were enrolled in the study. Patients were divided into two groups: (A) the peritoneal lavage CEA ( -) with CEA < 0.5 ng/ml and (B) the peritoneal lavage CEA ( +) with CEA ≥ 0.5 ng/ml. Then we analyzed OS and DFS of the two groups correlating them to others clinico-pathological features. Furthermore, we investigated the correlation between pCEA and peritoneal cytology. We demonstrated a strong significant difference in OS and in DFS in CEA ( +) patients. We emphasized that pCEA had a strong survival impact, in both OS and DFS, in selected patients affected by diffuse histotype GC (p = 0.0048 and p = 0.0030 respectively), stage III (p = 0.015 and p = 0.021, respectively) and distal gastric cancer (p = 0.0036 and p = 0.0017, respectively). There is a strong need to recognize prognostic factors that can help clinicians to stratify patients at high risk to develop post-surgical recurrences and moreover to recognize who could benefit from an aggressive surgical treatment of cytoreductive surgery and intra-peritoneal chemotherapy.pCEA is a good predictor of survival in advanced gastric cancer and could discriminate which patients need a more accurate follow-up program and an intensive therapeutic strategy.
Topics: Humans; Carcinoembryonic Antigen; Prognosis; Stomach Neoplasms; Peritoneal Lavage; Peritoneum
PubMed: 37347355
DOI: 10.1007/s13304-023-01542-3 -
JCI Insight Jun 2023The omentum contains immune cell structures called milky spots that are niches for transcoelomic metastasis. It is difficult to remove the omentum completely, and there...
The omentum contains immune cell structures called milky spots that are niches for transcoelomic metastasis. It is difficult to remove the omentum completely, and there are no effective strategies to minimize the risk of colonization of preserved omental tissues by cancer cells that circulate in the peritoneal fluid. Normal saline is commonly administered into the peritoneal cavity for diagnostic and intraoperative lavage. Here we show that normal saline, when administered into the peritoneal cavity of mice, is prominently absorbed by the omentum, exfoliates its mesothelium, and induces expression of CX3CL1, the ligand for CX3CR1, within and surrounding the omental vasculature. Studies using CX3CR1-competent and CX3CR1-deficient mice showed that the predominant response in the omentum following saline administration is an accumulation of CX3CR1+ monocytes/macrophages that expand milky spots and promote neoangiogenesis within these niches. Moreover, saline administration promoted the implantation of cancer cells of ovarian and colorectal origin onto the omentum. By contrast, these deleterious effects were not observed following i.p. administration of lactated Ringer's solution. Our findings suggest that normal saline stimulates the receptivity of the omentum for cancer cells and that the risk of colonization can be minimized by using a biocompatible crystalloid for lavage procedures.
Topics: Animals; Mice; Saline Solution; Omentum; Ascitic Fluid; Embryo Implantation; Epithelium
PubMed: 37345662
DOI: 10.1172/jci.insight.167336 -
International Journal of Colorectal... Jun 2023The safety of intraperitoneally administrated paclitaxel (op PTX) was demonstrated in the phase I trial of ip PTX combined with conventional systemic chemotherapy for...
Intraperitoneal paclitaxel combined with FOLFOX/CAPOX plus bevacizumab for colorectal cancer with peritoneal carcinomatosis (the iPac-02 trial): study protocol of a single arm, multicenter, phase 2 study.
BACKGROUND
The safety of intraperitoneally administrated paclitaxel (op PTX) was demonstrated in the phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis. Moreover, the median survival time was 29.3 months, which was longer than that observed in previous studies. Here, we planned the phase II trial of ip PTX: the iPac-02 trial.
METHODS
This multicenter, open-label, single assignment interventional clinical study includes patients with colorectal cancer with unresectable peritoneal carcinomatosis. FOLFOX-bevacizumab or CAPOX-bevacizumab is administered concomitantly as systemic chemotherapy. PTX 20 mg/m is administered weekly through the peritoneal access port in addition to these conventional systemic chemotherapies. The response rate is the primary endpoint. Progression-free survival, overall survival, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, safety, and response rate to peritoneal metastases are the secondary endpoints. A total of 38 patients are included in the study. In the interim analysis, the study will continue to the second stage if at least 4 of the first 14 patients respond to the study treatment. The study has been registered at the Japan Registry of Clinical Trials (jRCT2031220110).
RESULTS
We previously conducted phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis [1]. In the study, three patients underwent mFOLFOX, bevacizumab, and weekly ip PTX, and the other three patients underwent CAPOX, bevacizumab, and weekly ip PTX treatment. The dose of PTX was 20 mg/m [2]. The primary endpoint was the safety of the chemotherapy, and secondary endpoints were response rate, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, progression-free survival, and overall survival. Dose limiting toxicity was not observed, and the adverse events of ip PTX combined with oxaliplatin-based systemic chemotherapy were similar to those described in previous studies using systemic chemotherapy alone [3, 4]. The response rate was 25%, peritoneal cancer index improvement rate was 50%, and cytology in peritoneal lavage turned negative in all the cases. The progression-free survival was 8.8 months (range, 6.8-12 months), and median survival time was 29.3 months [5], which was longer than that observed in previous studies.
CONCLUSION
Here, we planned the phase II trial of ip paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: the iPac-02 trial.
Topics: Humans; Peritoneal Neoplasms; Bevacizumab; Paclitaxel; Colorectal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Multicenter Studies as Topic; Clinical Trials, Phase II as Topic
PubMed: 37340243
DOI: 10.1007/s00384-023-04434-5 -
World Journal of Surgical Oncology Jun 2023The long-term prognosis of minimally invasive surgery and open surgery for early cervical cancer is controversial. This study mainly discusses the feasibility and... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of modified radical laparoscopic hysterectomy versus open radical hysterectomy on short-term clinical outcomes in early-stage cervical cancer: a single-center, prospective, randomized controlled trial.
BACKGROUND
The long-term prognosis of minimally invasive surgery and open surgery for early cervical cancer is controversial. This study mainly discusses the feasibility and effectiveness of the endocutter in radical laparoscopic hysterectomy for early cervical cancer.
METHODS
A single-center, prospective, randomized controlled trial of modified radical laparoscopic hysterectomy on patients with FIGO stage IA1 (lymphovascular invasion), IA2, and IB1 cervical cancer, between January 2020 and July 2021. Patients were randomly assigned into laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) groups. The ORH group used right-angle sealing forceps for vaginal stump closure, whereas the LRH group used endoscopic staplers. The primary outcomes included the evaluation of the patient's perioperative indicators, as well as short- and long-term complications. Recurrence and overall survival were considered secondary outcomes.
RESULTS
As of July 2021, 17 patients were enrolled in the laparoscopic surgery group and 17 in the open surgery group. The hospitalization time of the laparoscopic group was significantly shorter than those of the open group (15 min vs. 9 min, P < 0.001). The vaginal stump closure time in the laparoscopic group was longer than that in the open surgery group, and the difference was statistically significant (P < 0.001). Post-operative catheter removal (P = 0.72), drainage tube removal time (P = 0.27), number of lymph node dissections (P = 0.72), and incidence of intraoperative and post-operative complications between the two groups (P > 0.05). The median blood loss in the laparoscopic group was 278 ml, and it was 350 ml in the laparotomy group. The intraoperative blood transfusion rate was lower in the laparoscopic group; however, these differences did not reach statistical significance (P = 0.175). Vaginal margin pathology and peritoneal lavage cytology were negative, and all the patient's vaginal stumps healed without infection. The median follow-up time of the laparoscopic group was 20.5 months, and it was 22 months for the open surgery group. There was no recurrence in all patients during the follow-up period.
CONCLUSIONS
Modified LRH with endocutter closure of the vaginal stump is an effective approach and not inferior to ORH in treating patients with early-stage cervical cancer.
TRIAL REGISTRATION
ChiCTR2000030160, date of registration February 26, 2020 ( https://www.chictr.org.cn/showprojen.aspx?proj=49809 ).
Topics: Female; Humans; Uterine Cervical Neoplasms; Prospective Studies; Retrospective Studies; Neoplasm Staging; Laparoscopy; Hysterectomy; Disease-Free Survival
PubMed: 37270549
DOI: 10.1186/s12957-023-03044-3 -
Biomolecules May 2023Mitochondrial ROS (mitoROS) control many reactions in cells. Biological effects of mitoROS can be investigated by modulation via mitochondria-targeted antioxidants...
Mitochondrial ROS (mitoROS) control many reactions in cells. Biological effects of mitoROS can be investigated by modulation via mitochondria-targeted antioxidants (mtAOX, mitoTEMPO). The aim of this study was to determine how mitoROS influence redox reactions in different body compartments in a rat model of endotoxemia. We induced inflammatory response by lipopolysaccharide (LPS) injection and analyzed effects of mitoTEMPO in blood, abdominal cavity, bronchoalveolar space, and liver tissue. MitoTEMPO decreased the liver damage marker aspartate aminotransferase; however, it neither influenced the release of cytokines (e.g., tumor necrosis factor, IL-4) nor decreased ROS generation by immune cells in the compartments examined. In contrast, mitoTEMPO treatment substantially reduced ROS generation. Examination of liver tissue revealed several redox paramagnetic centers sensitive to LPS and mitoTEMPO treatment and high levels of nitric oxide (NO) in response to LPS. NO levels in blood were lower than in liver, and were decreased by mitoTEMPO treatment. Our data suggest that (i) inflammatory mediators are not likely to directly contribute to ROS-mediated liver damage and (ii) mitoTEMPO is more likely to affect the redox status of liver cells reflected in a redox change of paramagnetic molecules. Further studies are necessary to understand these mechanisms.
Topics: Rats; Animals; Reactive Oxygen Species; Lipopolysaccharides; Endotoxemia; Oxidation-Reduction; Liver Diseases
PubMed: 37238664
DOI: 10.3390/biom13050794