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Diagnostic Pathology Jul 2024Cerebral echinococcosis is relatively rare, and it is important to distinguish cerebral cystic echinococcosis (CCE) from cerebral alveolar echinococcosis (CAE) in terms... (Comparative Study)
Comparative Study
BACKGROUND
Cerebral echinococcosis is relatively rare, and it is important to distinguish cerebral cystic echinococcosis (CCE) from cerebral alveolar echinococcosis (CAE) in terms of pathological diagnosis. We aim to describe the different clinicopathological features among patients with CCE and CAE.
METHODS
We collected 27 cases of cerebral echinococcosis which were diagnosed in the Department of Pathology of the First Affiliated Hospital of Xinjiang Medical University from January 1, 2012, to June 30, 2023. We compared the patients' clinical characteristics, MRI features, and pathologic manifestations of CCE and CAE.
RESULTS
Among 27 cases of cerebral echinococcosis, 23 cases were CAE and 4 cases were CCE. The clinical manifestations of both CCE and CAE patients mainly included headache (21 patients, 77.78%), limb movement disorders (6 patients, 22.22%), epileptic seizures (4 patients, 14.81%) and visual disturbances (2 patients, 7.41%). The average onset age of CAE cases was 34.96 ± 11.11 years, which was 9.00 ± 7.26 years in CCE cases. All CAE patients presented with multiple involvements in the brain and extracranial organs while all CCE patients observed a solitary lesion in the brain and 3 CCE cases had no extracranial involvement. Lesions of CCE in MRI showed a single isolated circular, which was well demarcated from the surrounding tissues and with no obvious edema around the lesions, whereas CAE lesions presented as multiple intracranial lesions, with blurred edges and edema around the lesions, and multiple small vesicles could be observed in the lesions. The edge of CAE lesions could be enhanced, while CCE lesions have no obvious enhancement. CCE foci were clear cysts with a wall of about 0.1 cm. Microscopically, the walls of the cysts were characterized by an eosinophilic keratin layer, which was flanked on one side by basophilic germinal lamina cells, which were sometimes visible as protocephalic nodes. While the CAE lesion was a nodular structure with a rough and uneven nodule surface, and the cut section was cystic and solid; microscopically, the CAE lesion had areas of coagulative necrosis, and the proto-cephalic nodes were barely visible. Inflammatory cell areas consisting of macrophages, lymphocytes, epithelioid cells, plasma cells, eosinophils, and fibroblasts can be seen around the lesion. Brain tissues in the vicinity of the inflammatory cell areas may show apoptosis, degeneration, necrosis, and cellular edema, while brain tissues a little farther away from the lesion show a normal morphology.
CONCLUSIONS
With the low incidence of brain echinococcosis, the diagnosis of echinococcosis and the differential diagnosis of CAE and CCE are challenging for pathologists. Grasping the different clinical pathology characteristics of CAE and CCE is helpful for pathologists to make accurate diagnoses.
Topics: Humans; Adult; Male; Female; Middle Aged; China; Echinococcosis; Young Adult; Magnetic Resonance Imaging; Diagnosis, Differential; Brain Diseases; Adolescent; Brain
PubMed: 38956596
DOI: 10.1186/s13000-024-01500-6 -
BMC Pulmonary Medicine Jul 2024Immunoglobulin light chain (AL) amyloidosis presents a clinical spectrum characterized by diverse manifestations and involvement of multiple organs, posing a significant...
INTRODUCTION
Immunoglobulin light chain (AL) amyloidosis presents a clinical spectrum characterized by diverse manifestations and involvement of multiple organs, posing a significant diagnostic challenge for physicians.
METHODS AND RESULTS
We present a case of a patient admitted to our hospital due to recurrent cough and sputum, which was initially diagnosed as refractory tuberculosis. Throughout his hospitalization, the patient experienced distressing symptoms, including uncontrollable chest tightness, hypotension, and fever. Noteworthy observations included a persistent elevation in cardiac biomarkers, indicative of cardiac damage. Bronchoalveolar lavage revealed the presence of various pathogenic microorganisms, while bone marrow flow cytometry demonstrated the existence of clonal plasma cells. Additionally, the urine free light chain assay detected the presence of M protein, and the positive congo red staining of the abdominal wall fat biopsy confirmed amyloid deposition in the tissues. Taking into account the patient's clinical presentation and the examination findings, we reached a conclusive diagnosis of immunoglobulin light chain (AL) amyloidosis.
CONCLUSION
This case serves as a reminder for physicians to consider rare diseases like AL amyloidosis when patients present with symptoms involving multiple organ systems such as heart, lung and kidney that are unresponsive to conventional treatment options.
Topics: Humans; Male; Immunoglobulin Light-chain Amyloidosis; Hypotension; Diagnosis, Differential; Middle Aged; Tuberculosis; Cough; Aged
PubMed: 38956518
DOI: 10.1186/s12890-024-03127-1 -
BMC Infectious Diseases Jul 2024Severe COVID-19 is uncommon, restricted to 19% of the total population. In response to the first virus wave (alpha variant of SARS-CoV-2), we investigated whether a...
BACKGROUND
Severe COVID-19 is uncommon, restricted to 19% of the total population. In response to the first virus wave (alpha variant of SARS-CoV-2), we investigated whether a biomarker indicated severity of disease and, in particular, if variable expression of angiotensin converting enzyme 2 (ACE2) in blood might clarify this difference in risk and of post COVID -19 conditions (PCC).
METHODS
The IRB-approved study compared patients hospitalized with severe COVID-19 to healthy controls. Severe infection was defined requiring oxygen or increased oxygen need from baseline at admission with positive COVID-19 PCR. A single blood sample was obtained from patients within a day of admission. ACE2 RNA expression in blood cells was measured by an RT-PCR assay. Plasma ACE1 and ACE2 enzyme activities were quantified by fluorescent peptides. Plasma TIMP-1, PIIINP and MMP-9 antigens were quantified by ELISA. Data were entered into REDCap and analyzed using STATA v 14 and GraphPad Prism v 10.
RESULTS
Forty-eight patients and 72 healthy controls were recruited during the pandemic. ACE2 RNA expression in peripheral blood mononuclear cells (PBMC) was rarely detected acutely during severe COVID-19 but common in controls (OR for undetected ACE2: 12.4 [95% CI: 2.62-76.1]). ACE2 RNA expression in PBMC did not determine plasma ACE1 and ACE2 activity, suggesting alternative cell-signaling pathways. Markers of fibrosis (TIMP-1 and PIIINP) and vasculopathy (MMP-9) were additionally elevated. ACE2 RNA expression during severe COVID-19 often responded within hours to convalescent plasma. Analogous to oncogenesis, we speculate that potent, persistent, cryptic processes following COVID-19 (the renin-angiotensin system (RAS), fibrosis and vasculopathy) initiate or promote post-COVID-19 conditions (PCC) in susceptible individuals.
CONCLUSIONS
This work elucidates biological and temporal plausibility for ACE2, TIMP1, PIIINP and MMP-9 in the pathogenesis of PCC. Intersection of these independent systems is uncommon and may in part explain the rarity of PCC.
Topics: Humans; COVID-19; Angiotensin-Converting Enzyme 2; Male; Female; Middle Aged; Leukocytes, Mononuclear; Aged; SARS-CoV-2; Adult; Biomarkers; Tissue Inhibitor of Metalloproteinase-1; Matrix Metalloproteinase 9; Severity of Illness Index; Case-Control Studies; Peptidyl-Dipeptidase A
PubMed: 38956476
DOI: 10.1186/s12879-024-09321-0 -
PharmacoEconomics Jul 2024Immunocompromised host pneumonia (ICHP) is an important cause of morbidity and mortality, yet usual care (UC) diagnostic tests often fail to identify an infectious...
INTRODUCTION
Immunocompromised host pneumonia (ICHP) is an important cause of morbidity and mortality, yet usual care (UC) diagnostic tests often fail to identify an infectious etiology. A US-based, multicenter study (PICKUP) among ICHP patients with hematological malignancies, including hematological cell transplant recipients, showed that plasma microbial cell-free DNA (mcfDNA) sequencing provided significant additive diagnostic value.
AIM
The objective of this study was to perform a cost-effectiveness analysis (CEA) of adding mcfDNA sequencing to UC diagnostic testing for hospitalized ICHP patients.
METHODS
A semi-Markov model was utilized from the US third-party payer's perspective such that only direct costs were included, using a lifetime time horizon with discount rates of 3% for costs and benefits. Three comparators were considered: (1) All UC, which included non-invasive (NI) and invasive testing and early bronchoscopy; (2) All UC & mcfDNA; and (3) NI UC & mcfDNA & conditional UC Bronch (later bronchoscopy if the initial tests are negative). The model considered whether a probable causative infectious etiology was identified and if the patient received appropriate antimicrobial treatment through expert adjudication, and if the patient died in-hospital. The primary endpoints were total costs, life-years (LYs), equal value life-years (evLYs), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio per QALY. Extensive scenario and probabilistic sensitivity analyses (PSA) were conducted.
RESULTS
At a price of $2000 (2023 USD) for the plasma mcfDNA, All UC & mcfDNA was more costly ($165,247 vs $153,642) but more effective (13.39 vs 12.47 LYs gained; 10.20 vs 9.42 evLYs gained; 10.11 vs 9.42 QALYs gained) compared to All UC alone, giving a cost/QALY of $16,761. NI UC & mcfDNA & conditional UC Bronch was also more costly ($162,655 vs $153,642) and more effective (13.19 vs 12.47 LYs gained; 9.96 vs 9.42 evLYs gained; 9.96 vs 9.42 QALYs gained) compared to All UC alone, with a cost/QALY of $16,729. The PSA showed that above a willingness-to-pay threshold of $50,000/QALY, All UC & mcfDNA was the preferred scenario on cost-effectiveness grounds (as it provides the most QALYs gained). Further scenario analyses found that All UC & mcfDNA always improved patient outcomes but was not cost saving, even when the price of mcfDNA was set to $0.
CONCLUSIONS
Based on the evidence available at the time of this analysis, this CEA suggests that mcfDNA may be cost-effective when added to All UC, as well as in a scenario using conditional bronchoscopy when NI testing fails to identify a probable infectious etiology for ICHP. Adding mcfDNA testing to UC diagnostic testing should allow more patients to receive appropriate therapy earlier and improve patient outcomes.
PubMed: 38955978
DOI: 10.1007/s40273-024-01409-4 -
Doklady Biological Sciences :... Jul 2024The fine structure of echiurid blood vessels in the proboscis is known in detail, but the circulatory system of the trunk is still understood mainly at the level of...
The fine structure of echiurid blood vessels in the proboscis is known in detail, but the circulatory system of the trunk is still understood mainly at the level of general anatomy. The trunk circulatory system was studied in Bonellia viridis females, and specialized podocytes were found to form the walls of the ring vessel and the anterior part of the ventral vessel. Podocytes were for the first time described in the echiurid circulatory system. Podocytes of B. viridis displayed a typical cell architecture, which is known for other bilaterians. A podocyte consists of a cell body; primary processes; and pedicels, which extend from the primary processes and are interconnected via specialized slit diaphragms. The presence of podocytes indicates that the ventral and ring vessels act as ultrafiltration sites, where the plasma is filtered through the basal lamina into the body cavity.
PubMed: 38955882
DOI: 10.1134/S0012496624701023 -
Annals of Hematology Jul 2024We aimed to evaluate if circulating plasma cells (CPC) detected by flow cytometry could add prognostic value of R2-ISS staging. We collected the electronic medical...
We aimed to evaluate if circulating plasma cells (CPC) detected by flow cytometry could add prognostic value of R2-ISS staging. We collected the electronic medical records of 336 newly diagnosed MM patients (NDMM) in our hospital from January 2017 to June 2023. The median overall survival (OS) for patients and R2-ISS stage I-IV were not reached (NR), NR, 58 months and 53 months, respectively. There was no significant difference in OS between patients with stage I and patients with stage II (P = 0.309) or between patients with stage III and patients with stage IV (P = 0.391). All the cases were re-classified according to R2-ISS stage and CPC numbers ≥ 0.05% (CPC high) or<0.05% (CPC low) into four new risk groups: Group 1: R2-ISS stage I + R2-ISS stage II and CPC low, Group 2: R2-ISS stage II and CPC high + R2-ISS stage III and CPC low, Group 3: R2-ISS stage III and CPC high + R2-ISS stage IV and CPC low, Group 4: R2-ISS stage IV and CPC high. The median OS were NR, NR, 57 months and 32 months. OS of Group 1 was significantly longer than that of Group 2 (P = 0.033). OS in Group 2 was significantly longer than that of Group 3 (P = 0.007). OS in Group 3 was significantly longer than that of Group 4 (P = 0.041). R2-ISS staging combined with CPC can improve risk stratification for NDMM patients.
PubMed: 38955826
DOI: 10.1007/s00277-024-05806-9 -
Physiological Reports Jul 2024Cardiotrophin-1 (CT-1), a member of the interleukin (IL)-6 cytokine family, has renoprotective effects in mouse models of acute kidney disease and tubulointerstitial...
Cardiotrophin-1 (CT-1), a member of the interleukin (IL)-6 cytokine family, has renoprotective effects in mouse models of acute kidney disease and tubulointerstitial fibrosis, but its role in glomerular disease is unknown. To address this, we used the mouse model of nephrotoxic nephritis to test the hypothesis that CT-1 also has a protective role in immune-mediated glomerular disease. Using immunohistochemistry and analysis of single-cell RNA-sequencing data of isolated glomeruli, we demonstrate that CT-1 is expressed in the glomerulus in male mice, predominantly in parietal epithelial cells and is downregulated in mice with nephrotoxic nephritis. Furthermore, analysis of data from patients revealed that human glomerular disease is also associated with reduced glomerular CT-1 transcript levels. In male mice with nephrotoxic nephritis and established proteinuria, administration of CT-1 resulted in reduced albuminuria, prevented podocyte loss, and sustained plasma creatinine, compared with mice administered saline. CT-1 treatment also reduced fibrosis in the kidney cortex, peri-glomerular macrophage accumulation and the kidney levels of the pro-inflammatory mediator complement component 5a. In conclusion, CT-1 intervention therapy delays the progression of glomerular disease in mice by preserving kidney function and inhibiting renal inflammation and fibrosis.
Topics: Animals; Male; Cytokines; Mice; Kidney Glomerulus; Mice, Inbred C57BL; Disease Models, Animal; Humans; Fibrosis; Glomerulonephritis
PubMed: 38955668
DOI: 10.14814/phy2.16129 -
Clinical Lymphoma, Myeloma & Leukemia Jun 2024The effect of thrombocytopenia has not been studied in the era of novel treatments in multiple myeloma (MM).
BACKGROUND
The effect of thrombocytopenia has not been studied in the era of novel treatments in multiple myeloma (MM).
OBJECTIVE
To evaluate the clinical characteristics and outcomes in MM patients presenting with thrombocytopenia.
MATERIALS
Newly diagnosed MM patients between 2008 and 2018 who received at least 2 novel agents at induction. Thrombocytopenia was defined as a platelet count of less than < 150,000/mm.
RESULTS
A total of 648 patients were identified. Thrombocytopenia was found in 120 patients (18.5%). Baseline disease characteristics associated with higher rates of thrombocytopenia at baseline included IgA myeloma, P < .01, ISS 3 versus 1 or 2, P < .01, R-ISS 3 versus 1 or 2, P < .01, renal failure (CrCl < 30 mL/min), P < .01, hypercalcemia (Ca > 11.5 mg/dL), P < .01, elevated LDH, P < .03, anemia (Hb < 10 g/dL), P < .01, higher serum monoclonal protein, P < .02, and > 60% plasma cells in the bone marrow, P < .01. Thrombocytopenia was more prevalent across patients with t(4;14) and t(14;16), but was not associated with an overall high-risk fluorescence in situ hybridization (FISH) classification. Median OS was significantly lower among patients with thrombocytopenia (64.4 vs. 145.0 months, P < .01). In multivariable Cox regression, thrombocytopenia was associated with mortality (HR = 2.45, 95% CI, 1.7-3.6) independently of age, sex, high-risk FISH, ISS stage, response at induction, percentage of plasma cells in the BM, and anemia.
CONCLUSION
We found that thrombocytopenia was seen among one-fifth of MM patients and was more common in patients with (t[4; 14] and t[14; 16]). Thrombocytopenia had an independent association with worse survival.
PubMed: 38955580
DOI: 10.1016/j.clml.2024.05.020 -
Journal For Immunotherapy of Cancer Jul 2024Tertiary lymphoid structures (TLSs) are thought to stimulate antitumor immunity and positively impact prognosis and response to immune checkpoint blockade. In gastric...
BACKGROUND
Tertiary lymphoid structures (TLSs) are thought to stimulate antitumor immunity and positively impact prognosis and response to immune checkpoint blockade. In gastric cancers (GCs), however, TLSs are predominantly found in GC with poor prognosis and limited treatment response. We, therefore, hypothesize that immune cell composition and function of TLS depends on tumor location and the tumor immune environment.
METHODS
Spatial transcriptomics and immunohistochemistry were used to characterize the phenotype of CD45 immune cells inside and outside of TLS using archival resection specimens from GC primary tumors and peritoneal metastases.
RESULTS
We identified significant intrapatient and interpatient diversity of the cellular composition and maturation status of TLS in GC. Tumor location (primary vs metastatic site) accounted for the majority of differences in TLS maturity, as TLS in peritoneal metastases were predominantly immature. This was associated with higher levels of tumor-infiltrating macrophages and Tregs and less plasma cells compared with tumors with mature TLS. Furthermore, mature TLSs were characterized by overexpression of antitumor immune pathways such as B cell-related pathways, MHC class II antigen presentation while immature TLS were associated with protumor pathways, including T cell exhaustion and enhancement of DNA repair pathways in the corresponding cancer.
CONCLUSION
The observation that GC-derived peritoneal metastases often contain immature TLS which are associated with immune suppressive regulatory tumor-infiltrating leucocytes, is in keeping with the lack of response to immune checkpoint blockade and the poor prognostic features of peritoneal metastatic GC, which needs to be taken into account when optimizing immunomodulatory strategies for metastatic GC.
Topics: Humans; Stomach Neoplasms; Tertiary Lymphoid Structures; Peritoneal Neoplasms; Male; Female; Tumor Microenvironment
PubMed: 38955417
DOI: 10.1136/jitc-2024-009243 -
Biofabrication Jul 2024Plasma cells (PCs) in bone marrow (BM) play an important role in both protective and pathogenic humoral immune responses, e.g., in various malignant and non-malignant...
Plasma cells (PCs) in bone marrow (BM) play an important role in both protective and pathogenic humoral immune responses, e.g., in various malignant and non-malignant diseases such as multiple myeloma (MM), primary and secondary immunodeficiencies and autoimmune diseases. Dedicated microenvironmental niches in the BM provide PCs with biomechanical and soluble factors that support their long-term survival. There is a high need for appropriate and robust model systems to better understand PCs biology, to develop new therapeutic strategies for PCs-related diseases and perform targeted preclinical studies with high predictive value. Most preclinical data have been derived from in vivo studies in mice, as in vitro studies of human PCs are limited due to restricted survival and functionality in conventional 2D cultures that do not reflect the unique niche architecture of the BM. We have developed a microphysiological, dynamic 3D BM culture system (BM-MPS) based on human primary tissue (femoral biopsies), mechanically supported by a hydrogel scaffold casing. While a bioinert agarose casing did not support PCs survival, a photo-crosslinked collagen-hyaluronic acid (Col-HA) hydrogel preserved the native BM niche architecture and allowed PCs survival in vitro for up to 2 weeks. Further, the Col-HA hydrogel was permissive to lymphocyte migration into the microphysiological system´s circulation. Long-term PCs survival was related to the stable presence in the culture of soluble factors, as APRIL, BAFF, and IL-6. Increasing immunoglobulins concentrations in the medium confirm their functionality over culture time. To the best of our knowledge, this study is the first report of successful long-term maintenance of primary-derived non-malignant PCs in vitro. Our innovative model system is suitable for in-depth in vitro studies of human PCs regulation and exploration of targeted therapeutic approaches such as CAR-T cell therapy or biologics.
PubMed: 38955197
DOI: 10.1088/1758-5090/ad5dfe