-
Case Reports in Gastroenterology 2024Crohn's disease (CD) is complicated by intestinal strictures and fistula formation; however, intestinal perforation is relatively rare.
INTRODUCTION
Crohn's disease (CD) is complicated by intestinal strictures and fistula formation; however, intestinal perforation is relatively rare.
CASE PRESENTATION
Following a traffic accident in the evening, a 39-year-old woman experienced abdominal pain that worsened the following morning and was taken to the emergency department. She had a 17-year history of CD and eight endoscopic balloon dilations for descending colonic strictures. She presented with a high fever of 40.0°C, along with tenderness and rebound pain throughout her abdomen, with the most substantial point being in the lower left abdomen. Computed tomography showed thickening of the descending colon wall, increased fat concentration around the wall, and a slight presence of air in the mesentery near the intestinal wall. We diagnosed the patient with generalized peritonitis due to traumatic penetration of the mesentery of the descending colon and performed emergency surgery. Intraoperative observation of the abdominal cavity with a laparoscope revealed purulent ascites but no apparent perforation or edematous mesentery, with white moss and redness in the descending colon. This prompted the decision to perform peritoneal lavage drainage and a transverse colonic double colostomy. The postoperative course was favorable, and the patient was discharged from the hospital on the postoperative day 14. Four months after discharge, colostomy closure was performed.
CONCLUSION
Relatively minor trauma in patients with CD can result in colon injury. An injured bowel is usually accompanied by active lesions due to CD; however, caution is required, as endoscopic balloon dilatation without accompaniment may be a background factor.
PubMed: 38665146
DOI: 10.1159/000537973 -
Theranostics 2024A mature tissue resident macrophage (TRM) population residing in the peritoneal cavity has been known for its unique ability to migrate to peritoneally located injured...
Lipid nanoparticle encapsulated large peritoneal macrophages migrate to the lungs via the systemic circulation in a model of clodronate-mediated lung-resident macrophage depletion.
A mature tissue resident macrophage (TRM) population residing in the peritoneal cavity has been known for its unique ability to migrate to peritoneally located injured tissues and impart wound healing properties. Here, we sought to expand on this unique ability of large peritoneal macrophages (LPMs) by investigating whether these GATA6+ LPMs could also intravasate into systemic circulation and migrate to extra-peritoneally located lungs upon ablating lung-resident alveolar macrophages (AMs) by intranasally administered clodronate liposomes in mice. C12-200 cationic lipidoid-based nanoparticles were employed to selectively deliver a small interfering RNA (siRNA)-targeting CD-45 labeled with a cyanine 5.5 (Cy5.5) dye to LPMs via intraperitoneal injection. We utilized a non-invasive optical technique called Diffuse Flow Cytometry (DiFC) to then systemically track these LPMs in real time and paired it with more conventional techniques like flow cytometry and immunocytochemistry to initially confirm uptake of C12-200 encapsulated siRNA-Cy5.5 (siRNA-Cy5.5 (C12-200)) into LPMs, and further track them from the peritoneal cavity to the lungs in a mouse model of AM depletion incited by intranasally administered clodronate liposomes. Also, we stained for LPM-specific marker zinc-finger transcription factor GATA6 in harvested cells from biofluids like broncho-alveolar lavage as well as whole blood to probe for Cy5.5-labeled LPMs in the lungs as well as in systemic circulation. siRNA-Cy5.5 (C12-200) was robustly taken up by LPMs. Upon depletion of lung-resident AMs, these siRNA-Cy5.5 (C12-200) labeled LPMs rapidly migrated to the lungs via systemic circulation within 12-24 h. DiFC results showed that these LPMs intravasated from the peritoneal cavity and utilized a systemic route of migration. Moreover, immunocytochemical staining of zinc-finger transcription factor GATA6 further confirmed results from DiFC and flow cytometry, confirming the presence of siRNA-Cy5.5 (C12-200)-labeled LPMs in the peritoneum, whole blood and BALF only upon clodronate-administration. Our results indicate for the very first time that selective tropism, migration, and infiltration of LPMs into extra-peritoneally located lungs was dependent on clodronate-mediated AM depletion. These results further open the possibility of therapeutically utilizing LPMs as delivery vehicles to carry nanoparticle-encapsulated oligonucleotide modalities to potentially address inflammatory diseases, infectious diseases and even cancer.
Topics: Animals; Clodronic Acid; Nanoparticles; Mice; Lung; Macrophages, Peritoneal; Macrophages, Alveolar; RNA, Small Interfering; GATA6 Transcription Factor; Liposomes; Mice, Inbred C57BL; Carbocyanines; Cell Movement; Flow Cytometry
PubMed: 38646640
DOI: 10.7150/thno.91062 -
BMJ Open Apr 2024Accurate baseline clinical staging is critical to inform treatment decision-making for patients with gastric cancers. Peritoneal metastasis (PM) is the most common form...
Ga-FAPI-04 positron emission tomography/CT and laparoscopy for the diagnosis of occult peritoneal metastasis in newly diagnosed locally advanced gastric cancer: study protocol of a single-centre prospective cohort study.
INTRODUCTION
Accurate baseline clinical staging is critical to inform treatment decision-making for patients with gastric cancers. Peritoneal metastasis (PM) is the most common form of metastasis in gastric cancer and mainly diagnosed by diagnostic laparoscopy and peritoneal lavage evaluation. However, diagnostic laparoscopy is invasive and less cost-effective. It is urgent to develop a safe, fast and non-invasive functional imaging method to verify the peritoneal metastasis of gastric cancer. The aim of our study was to evaluate the proportion of patients in whom Ga-FAPI-04 positron emission tomography/CT (PET/CT) led to a change in treatment strategy and to assess the diagnostic accuracy of Ga-FAPI-04 PET/CT for the detection of occult peritoneal metastasis compared with laparoscopic exploration.
METHODS AND ANALYSIS
In this single-centre, prospective diagnostic test accuracy study, a total of 48 patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma (cT4a-b, N0-3, M0, based on CT images) who are considering radical tumour surgery will be recruited. All participants will undergo Ga-FAPI-04 PET/CT before the initiation of laparoscopic exploration. The primary outcome is the proportion of patients with occult peritoneal metastatic lesions detected by Ga-FAPI-04 PET/CT, leading to a change in therapy strategy. The secondary outcomes include the diagnostic performance of Ga-FAPI-04 PET/CT for occult peritoneal metastasis, including sensitivity, specificity, accuracy, positive predictive value and negative predictive value.
ETHICS AND DISSEMINATION
The study protocol was approved by the Ethics Committee of West China Hospital, Sichuan University (2022-1484). Study results will be presented at public and scientific conferences and in peer-reviewed journals.
TRIAL REGISTRATION NUMBER
ChiCTR2300067591.
Topics: Humans; Stomach Neoplasms; Gallium Radioisotopes; Prospective Studies; Peritoneal Neoplasms; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Laparoscopy; Fluorodeoxyglucose F18; Quinolines
PubMed: 38643004
DOI: 10.1136/bmjopen-2023-075680 -
Urology Case Reports May 2024Fournier's gangrene, a rare and life-threatening soft tissue infection affecting the genitalia and perineum, results from various microorganisms. This rapidly...
Fournier's gangrene, a rare and life-threatening soft tissue infection affecting the genitalia and perineum, results from various microorganisms. This rapidly progressing necrotizing fasciitis yields higher mortality and morbidity rates. We report a case of a 1-month-old male infant with Fournier's gangrene due to perforation transverse colon complicated with septic shock and pneumonia also accompanied by patent processus vaginalis. Radiological findings of pneumonia and pneumoperitoneum were exhibited. Early diagnosis and management are demanded to mitigate life-threatening and improve the prognosis. The patient underwent incision drainage, peritoneal lavage, exploratory laparotomy, colostomy, necrotomy debridement, and patent processus vaginalis ligation after hemodynamic status stabilization.
PubMed: 38601087
DOI: 10.1016/j.eucr.2024.102721 -
Frontiers in Immunology 2024Excessive salt intake is a widespread health issue observed in almost every country around the world. A high salt diet (HSD) has a strong correlation with numerous...
Excessive salt intake is a widespread health issue observed in almost every country around the world. A high salt diet (HSD) has a strong correlation with numerous diseases, including hypertension, chronic kidney disease, and autoimmune disorders. However, the mechanisms underlying HSD-promotion of inflammation and exacerbation of these diseases are not fully understood. In this study, we observed that HSD consumption reduced the abundance of the gut microbial metabolite L-fucose, leading to a more substantial inflammatory response in mice. A HSD led to increased peritonitis incidence in mice, as evidenced by the increased accumulation of inflammatory cells and elevated levels of inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and monocyte chemotactic protein-1 (MCP-1, also known as C-C motif chemokine ligand 2 or CCL2), in peritoneal lavage fluid. Following the administration of broad-spectrum antibiotics, HSD-induced inflammation was abolished, indicating that the proinflammatory effects of HSD were not due to the direct effect of sodium, but rather to HSD-induced alterations in the composition of the gut microbiota. By using untargeted metabolomics techniques, we determined that the levels of the gut microbial metabolite L-fucose were reduced by a HSD. Moreover, the administration of L-fucose or fucoidan, a compound derived from brown that is rich in L-fucose, normalized the level of inflammation in mice following HSD induction. In addition, both L-fucose and fucoidan inhibited LPS-induced macrophage activation . In summary, our research showed that reduced L-fucose levels in the gut contributed to HSD-exacerbated acute inflammation in mice; these results indicate that L-fucose and fucoidan could interfere with HSD-promotion of the inflammatory response.
Topics: Mice; Animals; Sodium Chloride, Dietary; Fucose; Inflammation; Diet; Polysaccharides
PubMed: 38596683
DOI: 10.3389/fimmu.2024.1333848 -
Annals of Medicine and Surgery (2012) Apr 2024Ileocecal knot syndrome, a rare cause of small bowel obstruction where the ileum wraps around the cecum, poses a significant challenge for preoperative diagnosis. Prompt...
INTRODUCTION
Ileocecal knot syndrome, a rare cause of small bowel obstruction where the ileum wraps around the cecum, poses a significant challenge for preoperative diagnosis. Prompt intervention is crucial due to the risk of rapid bowel deterioration and increased mortality.
CASE PRESENTATION
A 45-year-old female presented with central abdominal pain associated with vomiting, abdominal distension, and obstipation. On examination, she was ill-looking with hypotension, tachycardia with a feeble pulse, direct and rebound abdominal tenderness, and absent bowel sounds. Aggressive fluid resuscitation was done. Based on the clinical presentation and abdominal radiograph suggestive of intestinal obstruction, an emergency exploratory laparotomy was done, which showed an ileocecal knot and 130 cm of gangrenous ileum. Peritoneal lavage followed by resection of non-viable ileum with double barrel ileostomy was done.
DISCUSSION
Ileosigmoid, appendico-ileal, ileoileal, and ileocecal knotting are the various types of intestinal knotting, with very few cases of ileocecal knotting being reported. Intestinal knotting causes severe bowel obstruction, resulting in reduced mucosal perfusion, progressive ischemia, and peritonitis, leading to high mortality. X-ray findings of multiple air-fluid levels are non-specific, and for definitive diagnosis, laparotomy is required. Assessing bowel viability before definitive surgery is essential. Despite positive outcomes, extensive resection can lead to malabsorption and ileus, with potential risk for developing short bowel syndrome.
CONCLUSION
Despite its rarity, the possibility of ileocecal knotting should be considered in cases of small bowel obstruction due to its potential for rapid deterioration. Prompt resuscitation followed by emergency laparotomy is necessary to prevent mortality.
PubMed: 38576991
DOI: 10.1097/MS9.0000000000001800 -
Scientific Reports Apr 2024The vagus nerve is the only pathway for transmitting parasympathetic signals between the brain and thoracoabdominal organs, thereby exhibiting anti-inflammatory...
The vagus nerve is the only pathway for transmitting parasympathetic signals between the brain and thoracoabdominal organs, thereby exhibiting anti-inflammatory functions through the cholinergic anti-inflammatory pathway. Despite often being resected during lymph node dissection in upper gastrointestinal cancer surgery, the impact of vagotomy on postoperative outcomes in gastric cancer patients remains unclear. Sub-diaphragmatic vagotomy was performed on C57BL/6 mice. Three weeks later, syngeneic murine gastric cancer cell line YTN16P was injected into the peritoneal cavity, and the number of peritoneal metastases (PM) on the mesentery and omentum compared with control mice. The phenotypes of immune cells in peritoneal lavage and omental milky spots one day after tumor inoculation were analyzed using flow cytometry and immunohistochemistry. Intraperitoneal transfer of 3 × 10 YTN16P significantly increased the number of metastatic nodules on the mesentery in the vagotomy group compared to the control group. The omental metastasis grade was also significantly higher in the vagotomy group. Phenotypic analysis of immune cells in peritoneal lavage did not reveal significant differences after vagotomy. However, vagotomized mice exhibited a notable increase in milky spot area, with a higher presence of cytokeratin(+) tumor cells, F4/80(+) macrophages, and CD3(+) T cells. Vagus nerve signaling appears to regulate the immune response dynamics within milky spots against disseminated tumor cells and inhibits the development of PM. Preserving the vagus nerve may offer advantages in advanced gastric cancer surgery to reduce peritoneal recurrence.
Topics: Humans; Mice; Animals; Peritoneal Neoplasms; Stomach Neoplasms; Mice, Inbred C57BL; Omentum; Vagus Nerve
PubMed: 38570542
DOI: 10.1038/s41598-024-58440-w -
Frontiers in Immunology 2024Sepsis is one of the major causes of death and increased health care burden in modern intensive care units. Immune checkpoints have been prompted to be key modulators of...
BACKGROUND
Sepsis is one of the major causes of death and increased health care burden in modern intensive care units. Immune checkpoints have been prompted to be key modulators of T cell activation, T cell tolerance and T cell exhaustion. This study was designed to investigate the role of the negative immune checkpoint, T cell immunoglobulin and ITIM domain (TIGIT), in the early stage of sepsis.
METHOD
An experimental murine model of sepsis was developed by cecal ligation and puncture (CLP). TIGIT and CD155 expression in splenocytes at different time points were assessed using flow cytometry. And the phenotypes of TIGIT-deficient (TIGIT) and wild-type (WT) mice were evaluated to explore the engagement of TIGIT in the acute phase of sepsis. In addition, the characteristics were also evaluated in the WT septic mice pretreated with anti-TIGIT antibody. TIGIT and CD155 expression in tissues was measured using real-time quantitative PCR and immunofluorescence staining. Proliferation and effector function of splenic immune cells were evaluated by flow cytometry. Clinical severity and tissue injury were scored to evaluate the function of TIGIT on sepsis. Additionally, tissue injury biomarkers in peripheral blood, as well as bacterial load in peritoneal lavage fluid and liver were also measured.
RESULTS
The expression of TIGIT in splenic T cells and NK cells was significantly elevated at 24 hours post CLP.TIGIT and CD155 mRNA levels were upregulated in sepsis-involved organs when mice were challenged with CLP. In CLP-induced sepsis, CD4 T cells from TIGIT mice shown increased proliferation potency and cytokine production when compared with that from WT mice. Meanwhile, innate immune system was mobilized in TIGIT mice as indicated by increased proportion of neutrophils and macrophages with potent effector function. In addition, tissue injury and bacteria burden in the peritoneal cavity and liver was reduced in TIGIT mice with CLP induced sepsis. Similar results were observed in mice treated with anti-TIGIT antibody.
CONCLUSION
TIGIT modulates CD4 T cell response against polymicrobial sepsis, suggesting that TIGIT could serve as a potential therapeutic target for sepsis.
Topics: Animals; Mice; CD4-Positive T-Lymphocytes; Killer Cells, Natural; Receptors, Immunologic; Sepsis; T-Lymphocytes
PubMed: 38545097
DOI: 10.3389/fimmu.2024.1290564 -
Veterinary Research Mar 2024The increase in the emergence of antimicrobial resistance has led to great challenges in controlling porcine extraintestinal pathogenic Escherichia coli (ExPEC)...
Antibacterial activity of the antimicrobial peptide PMAP-36 in combination with tetracycline against porcine extraintestinal pathogenic Escherichia coli in vitro and in vivo.
The increase in the emergence of antimicrobial resistance has led to great challenges in controlling porcine extraintestinal pathogenic Escherichia coli (ExPEC) infections. Combinations of antimicrobial peptides (AMPs) and antibiotics can synergistically improve antimicrobial efficacy and reduce bacterial resistance. In this study, we investigated the antibacterial activity of porcine myeloid antimicrobial peptide 36 (PMAP-36) in combination with tetracycline against porcine ExPEC PCN033 both in vitro and in vivo. The minimum bactericidal concentrations (MBCs) of AMPs (PMAP-36 and PR-39) against the ExPEC strains PCN033 and RS218 were 10 μM and 5 μM, respectively. Results of the checkerboard assay and the time-kill assay showed that PMAP-36 and antibiotics (tetracycline and gentamicin) had synergistic bactericidal effects against PCN033. PMAP-36 and tetracycline in combination led to PCN033 cell wall shrinkage, as was shown by scanning electron microscopy. Furthermore, PMAP-36 delayed the emergence of PCN033 resistance to tetracycline by inhibiting the expression of the tetracycline resistance gene tetB. In a mouse model of systemic infection of PCN033, treatment with PMAP-36 combined with tetracycline significantly increased the survival rate, reduced the bacterial load and dampened the inflammatory response in mice. In addition, detection of immune cells in the peritoneal lavage fluid using flow cytometry revealed that the combination of PMAP-36 and tetracycline promoted the migration of monocytes/macrophages to the infection site. Our results suggest that AMPs in combination with antibiotics may provide more therapeutic options against multidrug-resistant porcine ExPEC.
Topics: Animals; Swine; Mice; Extraintestinal Pathogenic Escherichia coli; Antimicrobial Peptides; Anti-Bacterial Agents; Anti-Infective Agents; Tetracyclines; Escherichia coli Infections; Rodent Diseases; Swine Diseases; Antimicrobial Cationic Peptides
PubMed: 38520031
DOI: 10.1186/s13567-024-01295-w -
Journal of Infection and Public Health May 2024The genus Mycobacterium includes well-known bacteria such as M. tuberculosis causing tuberculosis and M. leprae causing leprosy. Additionally, various species...
BACKGROUND
The genus Mycobacterium includes well-known bacteria such as M. tuberculosis causing tuberculosis and M. leprae causing leprosy. Additionally, various species collectively termed non-tuberculous mycobacteria (NTM) can cause infections in humans and animals, affecting individuals across all age groups and health conditions. However, information on NTM infection prevalence in Panama is limited.
METHODS
This study conducted a retrospective analysis of clinical records from 2017 to 2021, specifically focusing on patients with NTM isolates. Data were categorized by variables like sex, age, HIV status, and sample source.
RESULTS
Among the 4430 clinical records analyzed, 698 were linked to patients with NTM isolates. Of these patients, 397 were male, and 301 were female. Most female patients with NTM isolates (n = 190) were aged >45 to 85 years, while most male patients (n = 334) fell in the >25 to 75 years age group. A noteworthy proportion of male patients (n = 65) were aged 25-35 years. A significant age difference between male (median [min-max] = 53 years [3-90]) and female (median [61 years [6-94]) patients was observed (p < 0.001). Regarding HIV status, 77 positive individuals were male, and 19 were female (p < 0.001). Most samples (n = 566) were sputum samples, with additional pulmonary-associated samples such as broncho-alveolar lavage, tracheal secretions, and pleural fluid samples. Among extrapulmonary isolates (n = 48), sources included catheter secretions, intracellular fluids, peritoneal fluid, blood cultures, cerebrospinal fluid, bone marrow samples, and capillary transplant lesions. Specifically, the analysis identified the pathogenic microorganisms responsible for mycobacteriosis in Panama during the specific period 2017-2021, as M. fortuitum (34.4%), M. intracellulare (20.06%), and M. abscessus (13.75%), respectively.
CONCLUSIONS
This study highlights the growing public health concern of NTM infections in Panama. The research provides valuable insights into the prevalence and distribution of NTM species in the country, offering a foundation for the development and implementation of effective prevention and control strategies for NTM infections in Panama.
Topics: Animals; Humans; Male; Female; Adult; Middle Aged; Aged; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Retrospective Studies; Mycobacterium tuberculosis; Mycobacterium leprae; Panama; Tuberculosis; HIV Infections
PubMed: 38518684
DOI: 10.1016/j.jiph.2024.03.004