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The Journal of Biological Chemistry May 2024Infiltration of monocyte-derived cells to sites of infection and injury is greater in males than in females, due in part, to increased chemotaxis, the process of...
Infiltration of monocyte-derived cells to sites of infection and injury is greater in males than in females, due in part, to increased chemotaxis, the process of directed cell movement toward a chemical signal. The mechanisms governing sexual dimorphism in chemotaxis are not known. We hypothesized a role for the store-operated calcium entry (SOCE) pathway in regulating chemotaxis by modulating leading and trailing edge membrane dynamics. We measured the chemotactic response of bone marrow derived macrophages (BMDMs) migrating towards complement component 5a (C5a). Chemotactic ability was dependent on sex and inflammatory phenotype (M0, M1, M2), and correlated with SOCE. Notably, females exhibited a significantly lower magnitude of SOCE than males. When we knocked out the SOCE gene, stromal interaction molecule 1 (STIM1), it eliminated SOCE and equalized chemotaxis across both sexes. Analysis of membrane dynamics at the leading and trailing edges showed that STIM1 influences chemotaxis by facilitating retraction of the trailing edge. Using BTP2 to pharmacologically inhibit SOCE mirrored the effects of STIM1 knockout, demonstrating a central role of STIM/Orai-mediated calcium signaling. Importantly, by monitoring the recruitment of adoptively transferred monocytes in an in vivo model of peritonitis, we show that increased infiltration of male monocytes during infection is dependent on STIM1. These data support a model in which STIM1-dependent SOCE is necessary and sufficient for mediating the sex difference in monocyte recruitment and macrophage chemotactic ability by regulating trailing edge dynamics.
PubMed: 38815866
DOI: 10.1016/j.jbc.2024.107422 -
Turkish Journal of Medical Sciences 2023It wasaimed herein to investigate coronavirus disease (COVID-19) in cancer patients and compare hematological and solid organ cancer patients in terms of the course and...
BACKGROUND/AIM
It wasaimed herein to investigate coronavirus disease (COVID-19) in cancer patients and compare hematological and solid organ cancer patients in terms of the course and outcome of this disease.
MATERIALS AND METHODS
Data from cancer patients with laboratory-confirmed COVID-19 infection were analyzed retrospectively. Risk factors for poor prognosis and the effect of vaccination on the clinical outcomes of the patients were evaluated.
RESULTS
A total of 403 cancer patients who were diagnosed with COVID-19 between March 1st, 2021, and November 30th, 2022, were included, of whom 329 (81.6%) had solid and 74 (18.4%) had hematological cancers. Hospitalization and intensive care unit (ICU) admission rates were significantly higher in the hematological cancer patients compared to the solid organ cancer patients (73.0% vs. 35.9%, p< 0.001 and 25.7% vs. 14.0%, p= 0.013, respectively). The COVID-19related case fatality rate (CFR) was defined as 15.4%, and it was higher in the hematologicalcancer patientsthan inthe solid organ cancer patients (23.0% vs. 13.7%, p= 0.045) and was higher in patients with metastatic/advanced disease compared to the other cancer stages (p< 0.001). In the solid organ cancergroup, hospitalization, ICU admission, and the COVID-19 CFR were higher in patients with respiratory and genitourinary cancers (p< 0.001). A total of 288 (71.8%) patients had receivedCOVID-19 vaccination; 164 (56.94%) had≤2 doses and 124 (43.06%) had≥3 doses. The hospitalization rate was higher in patients with ≤2 doses of vaccine compared to those with ≥3 doses (48.2% vs. 29.8%,p= 0.002). Patients with COVID-19related death had higher levels of leucocyte, neutrophil, D-dimer, troponin, C-reactive protein (CRP), procalcitonin, and ferritin and lower levels of lymphocyte than the survivors. In the logistic regression analysis,the risk of COVID-19related mortality was higher in the hematological cancer patients(OR:1.726), those who were male (OR:1.757), and with the Pre-Delta/Delta variants (OR:1.817).
CONCLUSION
This study revealed that there is an increased risk of COVID-19-related serious events (hospitalization, ICU admission, or death) in patients with hematological cancerscompared with those who have solid organ cancers. It wasalso shown that receiving ≥3 doses of COVID-19 vaccine is more protective against severe illness and the need for hospitalization than ≤2 doses.
Topics: Humans; COVID-19; Male; Female; Middle Aged; Neoplasms; Retrospective Studies; COVID-19 Vaccines; Aged; Hospitalization; Risk Factors; SARS-CoV-2; Intensive Care Units; Adult; Vaccination; Prognosis
PubMed: 38813483
DOI: 10.55730/1300-0144.5744 -
Central-European Journal of Immunology 2024Eosinophilia is a feature of multiple conditions, both hematologic and non-hematologic, and may be associated with organ damage. The pathogenesis of eosinophilia can... (Review)
Review
Eosinophilia is a feature of multiple conditions, both hematologic and non-hematologic, and may be associated with organ damage. The pathogenesis of eosinophilia can follow two distinct pathways. Primary eosinophilia is caused by a cell-intrinsic mechanism originating from clonal expansion of eosinophils through acquisition of a somatic mutation, such as FIP1L1-PDGFRA. In recent years, great progress has been made in the field of pathogenesis and molecularly targeted therapy of neoplastic eosinophilia. The diagnostic procedure should include, among other things, morphologic analysis of blood and bone marrow samples, cytogenetics and fluorescence in situ-hybridization tests to detect evidence of an acute or chronic myeloid or lymphoid disorder. Secondary eosinophilia follows a cell-extrinsic mechanism as a response to exogenous cytokines. In most clinical cases, peripheral blood eosinophilia is reactive and typically associated with non-hematological disorders such as infections, allergic conditions, connective tissue disorders, vasculitis, malignancy, or endocrinopathies. Nonetheless, the cause of most cases of hypereosinophilic syndrome remains unknown. In this article, we present a short review focused on differential diagnosis of eosinophilia and eosinophilic disorders. The diagnosis of eosinophilia is a challenge for physicians; thus this review may be useful in clinical practice.
PubMed: 38812609
DOI: 10.5114/ceji.2024.136512 -
BMC Musculoskeletal Disorders May 2024Osteonecrosis of the femoral head (ONFH) is a common clinical disease. Improper treatment can lead to femoral head collapse and hip joint dysfunction. Core decompression... (Review)
Review
BACKGROUND
Osteonecrosis of the femoral head (ONFH) is a common clinical disease. Improper treatment can lead to femoral head collapse and hip joint dysfunction. Core decompression is particularly important for early ONFH. However, subtrochanteric fractures after core decompression cause some clinical problems.
CASE PRESENTATION
This article describes a 34-year-old male patient with early ONFH. After core decompression, he suffered a subtrochanteric fracture of the femur while bearing weight on the affected limb when going up stairs. He was subsequently treated with open reduction and intramedullary nail fixation.
CONCLUSION
When core decompression is used to treat ONFH, the location or size of the drill hole, whether a tantalum rod or bone is inserted, and partial weight-bearing of the affected limb may directly affect whether a fracture occurs after surgery. It is hoped that this case report can provide a reference for clinical orthopedic surgeons in the treatment of early ONFH.
Topics: Humans; Male; Adult; Decompression, Surgical; Femur Head Necrosis; Hip Fractures; Fracture Fixation, Intramedullary; Treatment Outcome; Postoperative Complications
PubMed: 38811923
DOI: 10.1186/s12891-024-07536-5 -
European Respiratory Review : An... Apr 2024Recent breakthroughs in single-cell sequencing, advancements in cellular and tissue imaging techniques, innovations in cell lineage tracing, and insights into the... (Review)
Review
Recent breakthroughs in single-cell sequencing, advancements in cellular and tissue imaging techniques, innovations in cell lineage tracing, and insights into the epigenome collectively illuminate the enigmatic landscape of alveolar macrophages in the lung under homeostasis and disease conditions. Our current knowledge reveals the cellular and functional diversity of alveolar macrophages within the respiratory system, emphasising their remarkable adaptability. By synthesising insights from classical cell and developmental biology studies, we provide a comprehensive perspective on alveolar macrophage functional plasticity. This includes an examination of their ontology-related features, their role in maintaining tissue homeostasis under steady-state conditions and the distinct contribution of bone marrow-derived macrophages (BMDMs) in promoting tissue regeneration and restoring respiratory system homeostasis in response to injuries. Elucidating the signalling pathways within inflammatory conditions, the impact of various triggers on tissue-resident alveolar macrophages (TR-AMs), as well as the recruitment and polarisation of macrophages originating from the bone marrow, presents an opportunity to propose innovative therapeutic approaches aimed at modulating the equilibrium between phenotypes to induce programmes associated with a pro-regenerative or homeostasis phenotype of BMDMs or TR-AMs. This, in turn, can lead to the amelioration of disease outcomes and the attenuation of detrimental inflammation. This review comprehensively addresses the pivotal role of macrophages in the orchestration of inflammation and resolution phases after lung injury, as well as ageing-related shifts and the influence of clonal haematopoiesis of indeterminate potential mutations on alveolar macrophages, exploring altered signalling pathways and transcriptional profiles, with implications for respiratory homeostasis.
Topics: Humans; Macrophages, Alveolar; Homeostasis; Animals; Phenotype; Signal Transduction; Lung; Pneumonia; Regeneration; Cell Plasticity; Inflammation Mediators
PubMed: 38811033
DOI: 10.1183/16000617.0263-2023 -
Revista Da Sociedade Brasileira de... 2024Musculoskeletal inflammatory lesions in chronic Chikungunya virus (CHIKV) infection have not been thoroughly assessed using whole-body magnetic resonance imaging...
BACKGROUND
Musculoskeletal inflammatory lesions in chronic Chikungunya virus (CHIKV) infection have not been thoroughly assessed using whole-body magnetic resonance imaging (WBMRI). This study aimed to determine the prevalence of these lesions in such patients.
METHODS
From September 2018 to February 2019, patients with positive Chikungunya-specific serology (Immunoglobulin M/Immunoglobulin G anti-CHIKV), with a history of polyarthralgia for > 6 months prior to MRI with no pre-existing rheumatic disorders, underwent 3T WBMRI and localized MRI. The evaluation focused on musculoskeletal inflammatory lesions correlated with chronic CHIKV infection. Pain levels were assessed using a visual analogue scale on the same day as WBMRI.
RESULTS
The study included 86 patients of whom 26 met the inclusion criteria. All patients reported pain and most (92.3%) categorized it as moderate or severe. The most common finding across joints was effusion, particularly in the tibiotalar joint (57.7%) and bursitis, with the retrocalcaneal bursa most affected (48.0%). Tenosynovitis was prevalent in the flexor compartment of the hands (44.2%), while Kager fat pad and soleus edema were also observed. Bone marrow edema-like signals were frequently seen in the sacroiliac joints (19.2%). Most WBMRI findings were classified as mild.
CONCLUSIONS
This study represents the first utilization of 3T WBMRI to assess musculoskeletal inflammatory disorders in chronic CHIKV infection. The aim was to identify the most affected joints and prevalent lesions, providing valuable insights for future research and clinical management of this condition regarding understanding disease pathophysiology, developing targeted treatment strategies, and using advanced imaging techniques in the assessment of musculoskeletal manifestations.
Topics: Humans; Chikungunya Fever; Magnetic Resonance Imaging; Male; Female; Middle Aged; Adult; Chronic Disease; Whole Body Imaging; Aged; Musculoskeletal Diseases; Young Adult
PubMed: 38808799
DOI: 10.1590/0037-8682-0090-2024 -
Cureus Apr 2024Meningitis is the inflammation of meninges either septic or aseptic depending on the source of infection. Typical signs and symptoms of meningitis in children...
Meningitis is the inflammation of meninges either septic or aseptic depending on the source of infection. Typical signs and symptoms of meningitis in children include fever, headache, neck stiffness, nuchal rigidity represented by positive Kernig and Brudzinski signs, photophobia, nausea, vomiting, confusion, lethargy, and irritability. Bacterial meningitis is commonly caused by in children over the age of three months. Although there has been a decline in infections due to the introduction of the pneumococcal conjugate and pneumococcal polysaccharide vaccines, there are still reported cases of invasive pneumococcal infections mostly with non-vaccine serotypes. We report a fully immunized six-year-old male patient with a presentation of classic meningitis signs and symptoms who developed rapid progression of disease including sudden and dramatic change in physical exam and subsequent respiratory depression within 12 hours of admission. Our patient had a history of extensive traumatic facial bone fractures six months prior. Our case demonstrates a unique presentation of rapidly progressing pneumococcal meningitis due to a suspected complication of septic thrombophlebitis and subsequent brain herniation in a fully immunized patient six months after a severe traumatic facial injury.
PubMed: 38807822
DOI: 10.7759/cureus.59204 -
Frontiers in Bioengineering and... 2024We aimed to evaluate the efficacy of antibiotic-loaded calcium sulfate combined with autologous iliac bone transplantation in the treatment of limb-localized...
OBJECTIVE
We aimed to evaluate the efficacy of antibiotic-loaded calcium sulfate combined with autologous iliac bone transplantation in the treatment of limb-localized osteomyelitis (Cierny-Mader type III) and analyze the causes and risk factors associated with infection recurrence.
METHODS
Clinical data of 163 patients with localized osteomyelitis of the extremities treated with antibiotic-loaded calcium sulfate combined with autologous iliac bone transplantation in Xi'an Honghui Hospital from January 2017 to December 2022 were retrospectively analyzed. All patients were diagnosed with localized osteomyelitis through clinical examination and treated with antibiotic-loaded calcium sulfate combined with autologous iliac bone. Based on the infection recurrence status, the patients were divided into the recurrence group and the non-recurrence group. The clinical data of the two groups were compared using univariate analysis. Subsequently, the distinct datasets were included in the binary logistic regression analysis to determine the risk and protective factors.
RESULTS
This study included 163 eligible patients, with an average age of 51.0 years (standard deviation: 14.9). After 12 months of follow-up, 25 patients (15.3%) experienced infection recurrence and were included in the recurrence group; the remaining 138 patients were included in the non-recurrence group. Among the 25 patients with recurrent infection, 20 required reoperation, four received antibiotic treatment alone, and one refused further treatment. Univariate analysis showed that education level, smoking, hypoproteinemia, open injury-related infection, and combined flap surgery were associated with infection recurrence ( < 0.05). Logistic regression analysis showed that open injury-related infection (odds ratio [OR] = 35.698; 95% confidence interval [CI]: 5.997-212.495; < 0.001) and combined flap surgery (OR = 41.408; 95% CI: 5.806-295.343; < 0.001) were independent risk factors for infection recurrence. Meanwhile, high education level (OR = 0.009; 95% CI: 0.001-0.061; < 0.001) was a protective factor for infection recurrence.
CONCLUSION
Antibiotic-loaded calcium sulfate combined with autologous iliac bone transplantation is an effective method for treating limb-localized osteomyelitis. Patients without previous combined flap surgery and non-open injury-related infections have a relatively low probability of recurrence of infection after treatment with this surgical method. Additionally, patients with a history of smoking and hypoproteinemia should pay attention to preventing the recurrence of infection after operation. Providing additional guidance and support, particularly in patients with lower education levels and compliance, could contribute to the reduction of infection recurrence.
PubMed: 38807650
DOI: 10.3389/fbioe.2024.1368818 -
Cureus Apr 2024Vertebral fractures remain a diagnostic challenge nowadays. The first and most common diagnosis needed to be ruled out is osteoporosis. Other diagnoses to rule out...
Vertebral fractures remain a diagnostic challenge nowadays. The first and most common diagnosis needed to be ruled out is osteoporosis. Other diagnoses to rule out involve pathological fractures. Pathological fractures are a group of pathologies that result in a spine fracture as part of an underlying disease process that affects the spine. This group includes Paget's disease, tumors, osteomyelitis, and vertebral compression fractures. Fractures secondary to vertebral osteomyelitis are presented as collapsed vertebral bodies secondary to bone destruction and the formation of lytic lesions. Clinical presentation includes severe back pain refractory to analgesic therapy, persistent unexplained fever, and leukocytosis without any other obvious focus of infection. In cases like the one presented here, early biopsy and culture should be performed on every patient that fits these criteria. However, as it presents unspecific symptoms most of the time, it is not suspected, and therefore it is associated with high morbidity and mortality.
PubMed: 38803779
DOI: 10.7759/cureus.59141 -
Frontiers in Pediatrics 2024infection of the bloodstream and intestine is a rare and severe opportunistic infection in immunocompromised people. In Southwest China, we first reported a case of...
infection of the bloodstream and intestine is a rare and severe opportunistic infection in immunocompromised people. In Southwest China, we first reported a case of bloodstream and intestinal infection with multidrug-resistant (MDR) in a 4-year-old child with T-cell acute lymphoblastic leukemia. Blood and stool cultures were used to identify the infection. The selection of antibiotics was based on clinical expertise and medication sensitivity tests. We used linezolid, levofloxacin, and polymyxin B to treat the patient aggressively. infection is uncommon in juvenile acute lymphoblastic leukemia. Doctors should be aware of the likelihood of opportunistic infection during the post-chemotherapy bone marrow suppression period. We further conducted a review of the literature and performed a detailed analysis of s infection in pediatric leukemia. It is becoming increasingly apparent that antibiotic is abused domestically and abroad, resulting in the sharp increase of MDR bacteria. In general, most of the isolates are susceptible to third- or fourth-generation cephalosporins, aminoglycosides, quinolones, and carbapenem, but drug-resistant strains are being reported increasingly. We summarized the drug resistance rate of s caviae and in China in the last 10 years. Early recognition and effective treatment will improve prognosis and reduce mortality.
PubMed: 38803640
DOI: 10.3389/fped.2024.1233600