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Frontiers in Immunology 2024Loss of NADPH oxidase activity results in proinflammatory macrophages that contribute to hyperinflammation in Chronic Granulomatous Disease (CGD). Previously, it was...
INTRODUCTION
Loss of NADPH oxidase activity results in proinflammatory macrophages that contribute to hyperinflammation in Chronic Granulomatous Disease (CGD). Previously, it was shown in a zymosan-induced peritonitis model that gp91 (CGD) monocyte-derived macrophages (MoMacs) fail to phenotypically mature into pro-resolving MoMacs characteristic of wild type (WT) but retain the ability to do so when placed in the WT milieu. Accordingly, it was hypothesized that soluble factor(s) in the CGD milieu thwart appropriate programming.
METHODS
We sought to identify key constituents using culture of peritoneal inflammatory leukocytes and their conditioned media. MoMac phenotyping was performed via flow cytometry, measurement of efferocytic capacity and multiplex analysis of secreted cytokines. Addition of exogenous TNFα, TNFα neutralizing antibody and TNFR1-/- MoMacs were used to study the role of TNFα: TNFR1 signaling in MoMac maturation.
RESULTS
More extensive phenotyping defined normal MoMac maturation and demonstrated failure of maturation of CGD MoMacs both and . Protein components, and specifically TNFα, produced and released by CGD neutrophils and MoMacs into conditioned media was identified as critical to preventing maturation. Exogenous addition of TNFα inhibited WT MoMac maturation, and its neutralization allowed maturation of cultured CGD MoMacs. TNFα neutralization also reduced production of IL-1β, IL-6 and CXCL1 by CGD cells though these cytokines played no role in MoMac programming. MoMacs lacking TNFR1 matured more normally in the CGD milieu both and following adoptive transfer .
DISCUSSION
These data lend mechanistic insights into the utility of TNFα blockade in CGD and to other diseases where such therapy has been shown to be beneficial.
Topics: Animals; Mice; Culture Media, Conditioned; Cytokines; Granulomatous Disease, Chronic; Macrophages; NADPH Oxidases; Receptors, Tumor Necrosis Factor, Type I; Tumor Necrosis Factor-alpha
PubMed: 38404573
DOI: 10.3389/fimmu.2024.1354836 -
The Journal of Maternal-fetal &... Dec 2024The purpose of this study was to improve diagnostic and therapeutic standards by examining the clinical features, treatment, and prognosis of fetal meconium peritonitis...
BACKGROUND
The purpose of this study was to improve diagnostic and therapeutic standards by examining the clinical features, treatment, and prognosis of fetal meconium peritonitis (FMP), as well as the diagnostic efficacy of ultrasound for FMP.
METHODS
The clinical data of 41 infants and pregnant women diagnosed with meconium peritonitis (MP) and treated at the Fujian Maternal and Child Health Hospital from January 2013 to January 2020 were analyzed retrospectively. Clinical data, imaging data, complications, treatment strategies, pregnancy outcomes, neonatal prognoses, and follow-up outcomes were all analyzed.
RESULTS
The MP prenatal diagnosis rate was 56.1% (23/41), the neonatal surgery rate was 53.7% (22/41), and the survival rate was 85.4% (35/41). Intraperitoneal calcification (23 pregnant women, 56.1%), intestinal dilatation (13 pregnant women, 31.7%), peritoneal effusion (22 pregnant women, 53.7%), intraperitoneal pseudocyst (7 pregnant women, 17.1%), and polyhydramnios were diagnosed prenatal ultrasound (18 pregnant women, 43.9%). Twenty-two pregnant women were assigned to the surgical treatment (operation) group, while 18 were assigned to the conservative treatment group. In the operation group, there were 9 cases of ileal atresia (40.9%), 7 cases of jejunal atresia (31.8%), 2 cases of atresia at the jejunum-ileum junction (9.1%), 2 cases of ileal perforation (9.1%), 1 case of ileal necrosis (4.5%), and 1 case of adhesive obstruction (4.5%). There was no statistically significant difference ( > .05) in the occurrence of various prenatal ultrasound findings by etiology.
CONCLUSION
Multiple prenatal ultrasound markers have been identified for MP. To improve the efficacy of newborn treatment for FMP and reduce neonatal mortality, dynamic monitoring of ultrasound image alterations and strengthened integrated perinatal management are necessary.
Topics: Female; Humans; Infant; Infant, Newborn; Pregnancy; Intestinal Perforation; Meconium; Peritonitis; Retrospective Studies; Ultrasonography, Prenatal
PubMed: 38403928
DOI: 10.1080/14767058.2023.2250045 -
Scientific Reports Feb 2024Over the past 15 years, there has been a noticeable uptick in incidents involving children ingesting multiple magnetic foreign bodies which can cause injuries and... (Observational Study)
Observational Study
Over the past 15 years, there has been a noticeable uptick in incidents involving children ingesting multiple magnetic foreign bodies which can cause injuries and gastrointestinal complications including death. The current study aimed to identify the prevalence, clinical presentation, and management of single or multiple magnet ingestions. A retrospective multi-central cross-sectional study was conducted to include all pediatric patients < 18 years presented to the emergency department with ingestion of single or multiple magnets and admitted across hospitals in Qatar, UAE, KSA, Tunisia, and Turkey between January 2011 and December 2021. Demographics, symptoms, management, and outcomes were analyzed. There were 189 magnet ingestions, of which 88 (46.6%) were multiple magnet ingestions. Most patients (55.6%) were male, and the median age was 3.9 (IQR 2-7) years. An abdominal X-ray was obtained in all cases. 119 (62%) patients were conservatively treated, 53 (28%) required surgical intervention and 17 (8.9%) underwent gastroscopy. None of the patients with single magnet ingestions experienced morbidity or severe outcomes. Multiple magnet ingestions led to significant morbidity including hospitalizations, perforations (44.3%), severe intestinal necrosis (19.3%), peritonitis (13.6%), severe abdominal infection (10.2%), and septic shock (4.5%). The rate of surgical intervention (59.1% vs. 1.0%) and gastroscopy (15.9% vs. 3.0%) was significantly higher in the multiple ingestion group compared to the single magnet ingestion group. No deaths were identified. A high risk of serious complications, including the need for surgery to remove the magnets and substantial morbidity may result from swallowing more than one magnet. Magnet safety requirements, public education, and improved legislation are urgently required.
Topics: Humans; Child; Male; Child, Preschool; Female; Magnets; Retrospective Studies; Cross-Sectional Studies; Foreign Bodies; Eating
PubMed: 38403623
DOI: 10.1038/s41598-024-55127-0 -
Journal of Pharmacological Sciences Mar 2024Imidazole derivatives are commonly used as antifungal agents. Here, we aimed to investigate the functions of imidazole derivatives on macrophage lineage cells. We...
Imidazole derivatives are commonly used as antifungal agents. Here, we aimed to investigate the functions of imidazole derivatives on macrophage lineage cells. We assessed the expression levels of inflammatory cytokines in mouse monocyte/macrophage lineage (RAW264.7) cells. All six imidazole derivatives examined, namely ketoconazole, sulconazole, isoconazole, luliconazole, clotrimazole, and bifonazole, reduced the expression levels of inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-α, after induction by lipopolysaccharide (LPS) in RAW264.7 cells. These imidazole derivatives also induced cell death in RAW264.7 cells, regardless of the presence or absence of LPS. Since the cell death was characteristic in morphology, we investigated the mode of the cell death. An imidazole derivative, sulconazole, induced gasdermin D degradation together with caspase-11 activation, namely, pyroptosis in RAW264.7 cells and peritoneal macrophages. Furthermore, priming with interferon-γ promoted sulconazole-induced pyroptosis in RAW264.7 cells and macrophages and reduced the secretion of the inflammatory cytokine, IL-1β, from sulconazole-treated macrophages. Our results suggest that imidazole derivatives suppress inflammation by inducing macrophage pyroptosis, highlighting their modulatory potential for inflammatory diseases.
Topics: Mice; Animals; Pyroptosis; Interferon-gamma; Monocytes; Lipopolysaccharides; Macrophages; Imidazoles; Cytokines
PubMed: 38395517
DOI: 10.1016/j.jphs.2024.01.006 -
International Journal of Surgery Case... Mar 2024Necrotizing fasciitis (NF) is a rare and rapidly progressing soft tissue infection. The commonly involved body parts are the extremities and trunk. Necrotizing fasciitis...
INTRODUCTION
Necrotizing fasciitis (NF) is a rare and rapidly progressing soft tissue infection. The commonly involved body parts are the extremities and trunk. Necrotizing fasciitis (NF) involving the retroperitoneum is very uncommon but associated with higher morbidity and mortality. There are only a few patients survived according to the report.
PRESENTATION OF CASE
This is a 19-year-old male patient presented with abdominal pain, high-grade fever, vomiting and abdominal distension for 3 days. On physical examination, he was hypotensive, tachycardic and febrile. He had a distended, tender abdomen, and hypoactive bowel sound. There were no significant pertinent findings on the other systems. Laboratory tests showed leukocytosis, thrombocytopenia, and elevated liver enzymes. After optimizing with resuscitation and initiating antibiotics, a laparotomy was performed. The finding was 300 ml of hemorrhagic fluid, ischemic cecum and ascending colon, and retroperitoneal necrosis. Subsequently, multiple debridement and right hemicolectomy with stoma was performed. Despite the close monitoring in the ICU, the patient died of uncontrolled sepsis.
CLINICAL DISCUSSION
Necrotizing fasciitis (NF) is a rapidly progressing infectious condition that requires urgent intervention. While it is rare for the retroperitoneum to be affected by NF, it is associated with a high mortality rate. The symptoms of retroperitoneal NF are not specific, making it difficult to diagnose. Here, we present a case of retroperitoneal NF with signs and symptoms of generalized peritonitis, resembling perforated appendicitis.
CONCLUSION
When patients are presented with a case of generalized peritonitis, it is important to include retroperitoneal NF as a potential differential diagnosis.
PubMed: 38382145
DOI: 10.1016/j.ijscr.2024.109412 -
Idiopathic myointimal hyperplasia of mesenteric veins: radiological evaluation using CT angiography.BJR Case Reports Jan 2024A 44-year-old man presented with a chief complaint of constipation. Initial contrast-enhanced CT showed extensive bowel wall thickening, mainly in the left colon, with a...
A 44-year-old man presented with a chief complaint of constipation. Initial contrast-enhanced CT showed extensive bowel wall thickening, mainly in the left colon, with a thin cord-like inferior mesenteric vein (IMV), in contrast to ectatic mesenteric venous branches, suggesting bowel ischaemia owing to venous stasis. One month later, at the time of symptom exacerbation, CT angiography showed a cord-like IMV and ectatic mesenteric venous branches with early enhancement, suggesting the presence of an arteriovenous fistula (AVF). Owing to the progression of bowel ischaemia and necrosis with peritonitis, emergency surgery was performed. Surgical specimens showed focal myointimal hyperplasia of the proximal mesenteric veins in both ischaemic and non-ischaemic lesions of the resected colon, thus leading to the diagnosis of idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) when combined with the clinical and imaging findings. IMHMV is a bowel ischaemic disease caused by non-thrombotic venous obstruction that requires bowel resection and has been suggested to be associated with AVF. Cord-like IMV and AVF in the mesentery are important CT findings that characterize IMHMV. CT angiography is useful in diagnosing IMHMV.
PubMed: 38352257
DOI: 10.1093/bjrcr/uaad009 -
Polski Przeglad Chirurgiczny Oct 2023<b><br>Introduction:</b> Acute appendicitis is one of the most frequent emergencies in hospitals around the world; it requires early surgical treatment... (Review)
Review
<b><br>Introduction:</b> Acute appendicitis is one of the most frequent emergencies in hospitals around the world; it requires early surgical treatment in complicated cases. One of the challenges that the surgeon faces during appendectomy is when the base of the appendix is compromised by either a perforation or gangrene. To show the surgical strategies that have been reported, as well as the complications associated with a compromised appendicular base in a complicated acute appendicitis.</br> <b><br>Methods:</b> A bibliographic search was carried out in the databases of Pubmed, Embase, Web of Science, and Google Scholar. The search expression ("appendiceal stump closure" OR "Closure of the appendiceal stump" OR "Management of appendiceal stump") was used to search for articles. The inclusion criteria were observational studies (case reports, case series, or cross-sectional, case-control, or cohort studies).</br> <b><br>Discussion:</b> Different techniques have been reported for the treatment of a compromised appendicular base. Among the most used are primary closure, partial resection of the cecum, cecostomy tube, ileocecectomy, and right hemicolectomy. The most frequent complications are surgical site infection, intra-abdominal abscess, postoperative ileus, intestinal obstruction, and others.</br> <b><br>Conclusions:</b> The appendicular base, compromised by necrosis or perforation, requires adequate treatment in order to prevent dehiscence of the appendicular stump sutures and fecal peritonitis. A number of surgical options have been reported.</br>.
Topics: Humans; Appendicitis; Cross-Sectional Studies; Laparoscopy; Appendix; Appendectomy; Postoperative Complications
PubMed: 38348988
DOI: 10.5604/01.3001.0053.6868 -
Clinical Case Reports Feb 2024Brucellosis, caused by gram-negative coccobacilli of the genus , is a zoonotic disease with bone and joint complications being common. However, acute abdomen with...
Brucellosis, caused by gram-negative coccobacilli of the genus , is a zoonotic disease with bone and joint complications being common. However, acute abdomen with intestinal perforation is rare. We present a case of a 69-year-old man diagnosed with acute diffuse peritonitis and intestinal perforation due to infection. Surgical intervention revealed ileocecal perforation with wheel spoke-like necrosis. The patient underwent partial resection, ileum closure, and ileostomy. Positive blood culture and agglutination confirmed the diagnosis. Targeted tetracycline and aminoglycoside treatment led to recovery.
PubMed: 38344359
DOI: 10.1002/ccr3.8496 -
Journal of Pharmacological Sciences Feb 2024In our previous study, we reported that 2, 5-dimethyl-celecoxib (DM-C), a derivative of celecoxib, prevents cardiac remodeling in different mouse models of heart...
2,5-Dimethyl-celecoxib induces early termination of inflammatory responses by transient macrophage accumulation and inhibits the progression of cardiac remodeling in a mouse model of cryoinjury-induced myocardial infarction.
In our previous study, we reported that 2, 5-dimethyl-celecoxib (DM-C), a derivative of celecoxib, prevents cardiac remodeling in different mouse models of heart failure, including myocardial infarction (MI). The inflammatory response after MI affects the progression of cardiac remodeling, wherein the immune cells, mainly macrophages, play crucial roles. Therefore, we evaluated the effect of DM-C on macrophages in a cryoinjury-induced myocardial infarction (CMI) mouse model. We observed that DM-C attenuated the deterioration of left ventricular ejection fraction and cardiac fibrosis 14 d after CMI. Gene expression of pro-inflammatory cytokines at the infarct site was reduced by DM-C treatment. Analysis of macrophage surface antigens revealed that DM-C induced transient accumulation of macrophages at the infarct site without affecting their polarization. In vitro experiments using peritoneal monocytes/macrophages revealed that DM-C did not directly increase the phagocytic ability of the macrophages but increased their number, thereby upregulating the clearance capacity. Moreover, DM-C rapidly excluded the cells expressing necrotic cell marker from the infarct site. These results suggested that DM-C enhanced the clearance capacity of macrophages by transiently increasing their number at the infarct site, and terminated the escape from the inflammatory phase earlier, thereby suppressing excessive cardiac remodeling and ameliorating cardiac dysfunction.
Topics: Animals; Mice; Celecoxib; Stroke Volume; Ventricular Remodeling; Ventricular Function, Left; Myocardial Infarction; Macrophages; Disease Models, Animal; Pyrazoles; Sulfonamides
PubMed: 38246733
DOI: 10.1016/j.jphs.2024.01.001 -
BMC Surgery Jan 2024Acute mesenteric ischemia is a rare but lethal disease. Acute occlusive mesenteric ischemia consists of mesenteric artery embolism, mesenteric artery thrombosis, and...
BACKGROUND
Acute mesenteric ischemia is a rare but lethal disease. Acute occlusive mesenteric ischemia consists of mesenteric artery embolism, mesenteric artery thrombosis, and mesenteric vein thrombosis. This study aimed to investigate the factors that may affect the outcome of acute occlusive mesenteric ischemia.
METHODS
Data from acute occlusive mesenteric ischemia patients admitted between May 2016 and May 2022 were reviewed retrospectively. Patients were divided into 2 groups according to whether complications(Clavien‒Dindo ≥ 2) occurred within 6 months of the first admission. Demographics, symptoms, signs, laboratory results, computed tomography angiography features, management and outcomes were analyzed.
RESULTS
59 patients were enrolled in this study. Complications(Clavien‒Dindo ≥ 2) occurred within 6 months of the first admission in 17 patients. Transmural intestinal necrosis, peritonitis, white blood cell count, percentage of neutrophils, percentage of lymphocytes, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, creatine kinase isoenzyme, cardiac troponin I, laparoscopic exploration rate, open embolectomy rate, enterostomy rate, length of necrotic small bowel, length of healthy small bowel, surgical time and intraoperative blood loss differed significantly between groups. Creatine kinase isoenzyme (OR = 1.415, 95% CI: 1.060-1.888) and surgical time (OR = 1.014, 95% CI: 1.001-1.026) were independent risk factors associated with complications(Clavien‒Dindo ≥ 2).
CONCLUSIONS
Our analysis suggests that acute occlusive mesenteric ischemia patients with a creatine kinase isoenzyme level greater than 2.22 ng/mL or a surgical time longer than 156 min are more likely to experience complications'(Clavien‒Dindo ≥ 2) occurrence within 6 months of the first admission.
Topics: Humans; Mesenteric Ischemia; Retrospective Studies; Isoenzymes; Thrombosis; Acute Disease; Ischemia; Creatine Kinase; Mesenteric Vascular Occlusion
PubMed: 38218808
DOI: 10.1186/s12893-024-02310-9