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Breast Care (Basel, Switzerland) May 2023Granulomatous lobular mastitis (GLM) is a rare, benign, and complex breast disease that can be easily misdiagnosed as breast cancer. The etiology of GLM is unclear, and...
BACKGROUND
Granulomatous lobular mastitis (GLM) is a rare, benign, and complex breast disease that can be easily misdiagnosed as breast cancer. The etiology of GLM is unclear, and optimal treatment has not been established.
METHODS
Medical records for 333 patients with GLM in recent 5 years at Longhua Hospital, Shanghai, China, were analyzed. Potential pathogens in 33 fresh tissue specimens were also analyzed using 16S rDNA sequencing technology, matrix-assisted laser desorption ionization time of flight mass spectrometry, and bacterial cultures.
RESULTS
The median age of patients was 32 years (range 22-47 years). Among 333 patients, 38.7% displayed elevated prolactin, while 23.7% displayed high interleukin-2. In the granulomatous lesion, CD3-positive T lymphocytes were significantly more than CD20-positive B lymphocytes around the vacuoles or microabscesses. Gram-positive organisms were observed in 82 cases, including in 22 cases from fresh tissue specimens. Thirty-three cases yielded associated pathogens and all displayed multiple pathogenic infections, as identified using 16S rDNA sequencing technology. Pathogenic infections were further identified as belonging to 16 main genera and 8 main pathogenic species.
CONCLUSIONS
GLM displays distinct histological and clinical features similar to those that have been previously reported in the literature. Using 16S rDNA sequencing technology, all of our cases demonstrated multiple pathogenic infections, which provided more useful information for clinical treatment.
PubMed: 37261131
DOI: 10.1159/000529391 -
The Ultrasound Journal Jun 2023Focused Assessment with Sonography for HIV-associated TB (FASH) is a diagnostic tool for extra-pulmonary tuberculosis (TB) in symptomatic patients with advanced HIV. As...
BACKGROUND
Focused Assessment with Sonography for HIV-associated TB (FASH) is a diagnostic tool for extra-pulmonary tuberculosis (TB) in symptomatic patients with advanced HIV. As Kaposi's sarcoma (KS) is also prevalent in this patient population, changes due to KS may mimic TB findings and clinical interpretation of target FASH findings can be challenging. We aimed to describe sonographic findings in patients with KS.
METHODS
We performed a prospective observational study at Lighthouse clinic at Kamuzu Central Hospital, Lilongwe, Malawi, in consecutive patients with newly diagnosed KS, without known diagnosis of TB, referred for paclitaxel treatment. All patients underwent FASH and abdominal ultrasound to assess for effusions and changes in liver and spleen, as well as systematic sonographic assessment for lymphadenopathy.
RESULTS
We included 30 patients. We found inguinal lymph nodes using ultrasound in 20 patients; in 3 (10%) additionally abdominal lymph nodes were found. Pathological effusions were seen in eight patients (27%): pericardial effusion in one (3%), pleural effusion in six (20%) and ascites in four (13%) patients. We found focal spleen lesions in three (10%) patients. Most of these lesions were echogenic, but in one patient, we saw hypoechoic lesions with an echogenic center. In three (10%) patients an unusual "sponge-like pattern" of the splenic vasculature was found. Six (20%) patients had echogenic focal lesions in the liver resembling hemangiomas, individual lesions showing a hypoechoic center. In two patients echogenic portal fields were seen.
CONCLUSIONS
The majority of patients with newly diagnosed KS demonstrate sonographic features of disease, predominantly lymphadenopathy. Effusions were observed in a significant minority, as well as focal lesions in liver or spleen, which commonly resemble hemangiomas, but hypoechoic lesions were also observed and can easily be mistaken for extra-pulmonary TB. A 'sponge-like pattern' of the spleen should not be confused with micro-abscesses. In conclusion, this case series illustrates the diverse nature of ultrasound features in patients with KS, which can be difficult to distinguish from other opportunistic diseases, including TB.
PubMed: 37258984
DOI: 10.1186/s13089-023-00323-8 -
Journal of Translational Medicine Apr 2023A causal link between microbiota composition (dysbiosis) and oncogenesis has been demonstrated for several types of cancer. Neutrophils play a role in both immune...
BACKGROUND
A causal link between microbiota composition (dysbiosis) and oncogenesis has been demonstrated for several types of cancer. Neutrophils play a role in both immune protection against bacterial threats and carcinogenesis. This study aimed to characterise intratumoral bacteria in vulvar squamous cell carcinoma (VSCC) and their putative effect on neutrophil recruitment and cancer progression.
METHODS
Clinical material was obtained from 89 patients with VSCC. Next-generation sequencing (NGS) of 16S rRNA and quantitative polymerase chain reaction (qPCR) were used to detect bacterial species in VSCC. To verify neutrophil activation, CD66b expression in tumour specimens was analysed by immunohistochemistry (IHC). Subsequently, IHC was applied to detect the main neutrophil serine proteases (NSPs), cathepsin G (CTSG), neutrophil elastase (ELANE), and proteinase 3 (PRTN3) in VSCC.
RESULTS
Fusobacterium nucleatum and Pseudomonas aeruginosa were identified as tumour-promoting bacteria, and their presence was found to be associated with a shorter time to progression in VSCC patients. Furthermore, high abundance of CD66b, the neutrophil activation marker, in VSCC samples, was found to relate to poor survival of patients with VSCC. The selected NSPs were shown to be expressed in vulvar tumours, also within microabscess. The increased numbers of microabscesess were correlated with poor survival in VSCC patients.
CONCLUSIONS
Our results show that neutrophilic inflammation seem to be permissive for tumour-promoting bacteria growth in VSCC. The findings provide new therapeutic opportunities, such as based on shifting the balance of neutrophil populations to those with antitumorigenic activity and on targeting NSPs produced by activated neutrophils at the inflammation sites.
Topics: Female; Humans; Vulvar Neoplasms; RNA, Ribosomal, 16S; Carcinoma, Squamous Cell; Inflammation; Epithelial Cells; Tumor Microenvironment
PubMed: 37118737
DOI: 10.1186/s12967-023-04113-7 -
Reproductive Sciences (Thousand Oaks,... Oct 2023The purpose of this study was to investigate the prevalence of abnormal vaginal colonization in women with cervical incompetence and to analyze its impact on obstetric...
The purpose of this study was to investigate the prevalence of abnormal vaginal colonization in women with cervical incompetence and to analyze its impact on obstetric and neonatal outcomes and placental inflammation. We included 138 pregnant women diagnosed with cervical incompetence and delivered in our hospital. Patients with major fetal anomaly or multifetal pregnancy were excluded. Upper vaginal culture was performed on the day of admission. A total of 60.9% (84/138) of cervical incompetence patients had abnormal bacterial colonization, and Escherichia coli (E. coli) was the most common colonized pathogen (33.3%, 46/138). The positive vaginal E. coli group had a higher rate of prior preterm birth (p = 0.021) and an earlier gestational age at which cervical incompetence was diagnosed (p < 0.01) than the negative group. The positive vaginal E. coli group had higher rates of clinical chorioamnionitis (p = 0.008) and subchorionic microabscess of the placenta (p = 0.012). Importantly, the positive vaginal E. coli group had significantly higher rates of proven early-onset neonatal sepsis (EONS) (p = 0.046), necrotizing enterocolitis (NEC) (p = 0.001), and neonatal mortality (p = 0.023). After adjusting for confounding variables, the positive vaginal E. coli group had significantly higher risk for proven EONS (OR: 3.853, 95% CI: 1.056-14.055) and NEC (OR: 12.410, 95% CI: 1.290-119.351). In conclusion, E. coli was the most common vaginal microorganism isolated from patients with cervical incompetence. Maternal vaginal E. coli colonization was associated with adverse neonatal outcomes including proven EONS and NEC and was characterized by a higher rate of placental subchorionic microabscess.
Topics: Humans; Pregnancy; Infant, Newborn; Female; Premature Birth; Escherichia coli; Placenta; Vagina; Uterine Cervical Incompetence
PubMed: 37118059
DOI: 10.1007/s43032-023-01242-8 -
Cytotherapy Aug 2023The most clinically trialed cells, mesenchymal stromal cells (MSCs), are now known to mainly exert their therapeutic activity through paracrine secretions, which include...
The most clinically trialed cells, mesenchymal stromal cells (MSCs), are now known to mainly exert their therapeutic activity through paracrine secretions, which include exosomes. To mitigate potential regulatory concerns on the scalability and reproducibility in the preparations of MSC exosomes, MSC exosomes were produced using a highly characterized MYC-immortalized monoclonal cell line. These cells do not form tumors in athymic nude mice or exhibit anchorage-independent growth, and their exosomes do not carry MYC protein or promote tumor growth. Unlike intra-peritoneal injections, topical applications of MSC exosomes in a mouse model of IMQ-induced psoriasis alleviate interleukin (IL)-17, IL-23 and terminal complement complex, C5b9 in psoriatic skin. When applied on human skin explants, fluorescence from covalently labeled fluorescent MSC exosomes permeated and persisted in the stratum corneum for about 24 hours with negligible exit out of the stratum corneum into the underlying epidermis. As psoriatic stratum corneums are uniquely characterized by activated complements and Munro microabscesses, we postulated that topically applied exosomes permeate the psoriatic stratum corneum to inhibit C5b9 complement complex through CD59, and this inhibition attenuated neutrophil secretion of IL-17. Consistent with this, we demonstrated that assembly of C5b9 on purified human neutrophils induced IL-17 secretion and this induction was abrogated by MSC exosomes, which was in turn abrogated by a neutralizing anti-CD 59 antibody. We thus established the mechanism of action for the alleviation of psoriatic IL-17 by topically applied exosomes.
Topics: Animals; Mice; Humans; Exosomes; Interleukin-17; Mice, Nude; Reproducibility of Results; Psoriasis; Mesenchymal Stem Cells
PubMed: 37115163
DOI: 10.1016/j.jcyt.2023.03.015 -
Journal of Pediatric Hematology/oncology May 2023Immune reconstitution inflammatory syndrome (IRIS) occurs when there is immune recovery after a prolonged period of leucopenia as a response to an underlying latent or...
Subcutaneous Microabscesses and Myositis as Part of Immune Reconstitution Inflammatory Syndrome due to Chronic Disseminated Candidiasis in a Child With Acute Lymphoblastic Leukemia.
BACKGROUND
Immune reconstitution inflammatory syndrome (IRIS) occurs when there is immune recovery after a prolonged period of leucopenia as a response to an underlying latent or chronic infection due to a proinflammatory cascade. It can occur in a child on chemotherapy for acute lymphoblastic leukemia (ALL) with underlying chronic disseminated candidiasis (CDC).
OBSERVATION
We present a 7-year-old girl with pre-B ALL on chemotherapy who had prolonged febrile neutropenia and CDC with microabscesses in the liver, spleen, and kidney and a prolonged intensive care unit stay. Upon neutrophil recovery, she continued to have high-grade fever (blood and urine cultures negative). She also presented severe myositis of bilateral thigh muscles and developed unusual granulomas in the subcutaneous region of the lower back and right thigh. Although IRIS was suspected, she could not be initiated on steroids due to right upper lobe collapse consolidation due to multidrug-resistant Acinetobacter baumanni, which was treated with sensitive antibiotics. Treatment with steroids resolved her fever and normalized inflammatory markers. She is currently well on maintenance chemotherapy.
CONCLUSIONS
IRIS can complicate the treatment of ALL in children. Diagnosing it while having a concurrent bacterial infection is challenging. Rarely CDC can present with subcutaneous granulomas. Treatment with steroids at the right time is very crucial.
Topics: Female; Humans; Child; Persistent Infection; Immune Reconstitution Inflammatory Syndrome; Abscess; Fever; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Candidiasis; Myositis
PubMed: 37083275
DOI: 10.1097/MPH.0000000000002640 -
International Journal of Surgical... Feb 2024Recently, an increased risk of celiac disease or eosinophilic esophagitis has been postulated among patients with either of these disorders, prompting some to suggest a...
Recently, an increased risk of celiac disease or eosinophilic esophagitis has been postulated among patients with either of these disorders, prompting some to suggest a common underlying mechanism, whereas others maintain that their co-existence is coincidental. We compared clinical and pathological features of 29 patients meeting criteria for both celiac disease and eosinophilic esophagitis to 26 celiac disease and 26 eosinophilic esophagitis controls to determine whether any distinguished study patients from controls. Eight (28%) study patients presented with symptoms of both celiac disease and eosinophilic esophagitis, whereas 14 (48%) had celiac disease symptoms only and 5 had (17%) esophageal symptoms only. Study patients had similar autoimmune and atopic conditions seen in both control groups. Histological severity of disease, including Marsh II-III duodenal histology (study specimens: 87%; controls: 89%), mean peak esophageal eosinophil counts (study specimens: 55/400x field; controls: 80/400X field, = .1), and presence of eosinophil microabscesses, scale crust, and subepithelial fibrosis were also similar to controls. Gluten-free diet resolved celiac disease-related symptoms (19 of 20, 95%) and histology (10 of 12, 83%), but not esophageal symptoms or eosinophilia in most study patients. Patients with concomitant celiac disease and eosinophilic esophagitis lack distinguishing features compared to controls with celiac disease or eosinophilic esophagitis alone. The occurrence of both disorders is likely coincidental in most cases.
Topics: Humans; Eosinophilic Esophagitis; Celiac Disease; Duodenum; Enteritis; Eosinophilia; Gastritis
PubMed: 37050846
DOI: 10.1177/10668969231167526 -
Journal of Gastrointestinal and Liver... Mar 2023Some eosinophilic esophagitis (EoE) patients can have a decline in eosinophil count after proton pump inhibitor (PPI) treatment without achieving histologic response,...
BACKGROUND AND AIMS
Some eosinophilic esophagitis (EoE) patients can have a decline in eosinophil count after proton pump inhibitor (PPI) treatment without achieving histologic response, but little is known about this group. We aimed to determine the effect of PPIs on reducing esophageal eosinophilia in patients deemed non-responsive to PPI therapy.
METHODS
We analyzed prospectively collected cohort data from newly diagnosed adults with EoE who were histologic non-responders (≥15 eos/hpf) to PPI-only therapy. Symptoms, endoscopic histologic features were assessed before and after PPI. Pre- and post-PPI treatment esophageal biopsies were read by pathologists to determine peak eosinophil counts and other histologic findings.
RESULTS
Of 125 patients, peak eosinophil counts were 102.1 ± 69.8 and 102.9 ± 101.1 (p=0.93) before and after PPI treatment, respectively, but lamina propria fibrosis decreased from 97% to 41% (p<0.001). Heartburn frequency also decreased (19% to 11%; p=0.006), though endoscopic findings did not change. There were 75 patients (60%) who had some decrease in eosinophil counts, with 30 patients (24%) having ≥50% decrease in counts. When comparing the ≥50% and <50% decrease groups, differences in endoscopic features were identified, but the ≥50% group had improvement in eosinophil degranulation, microabscesses, spongiosis, and basal cell hyperplasia.
CONCLUSION
Peak eosinophil counts did not decrease overall after PPI treatment, but symptoms of heartburn improved. Approximately a quarter had ≥50% decrease in eosinophil counts, with associated decreases in other histologic findings. Further research may consider what role PPIs have in this subset of non-responders or in combination therapies.
Topics: Adult; Humans; Eosinophilic Esophagitis; Proton Pump Inhibitors; Heartburn; Treatment Outcome
PubMed: 37004219
DOI: 10.15403/jgld-4746 -
European Annals of Allergy and Clinical... Mar 2023Eosinophilic esophagitis (EoE) is an immune-mediated chronic esophageal disease, with frequent association with atopy. A validated non/minimally invasive biomarker of...
Eosinophilic esophagitis (EoE) is an immune-mediated chronic esophageal disease, with frequent association with atopy. A validated non/minimally invasive biomarker of disease severity has not been identified. We aimed to determine if sensitization to airborne and food allergens correlates with disease severity, and to evaluate the association between clinical and laboratory characteristics with the severity of EoE. Retrospective study of EoE patients observed in a differentiated center, 2009-2021. The association between patients' diagnosis age, disease duration before diagnosis, sensitization to airborne/food allergens, serum total IgE and peripheral blood eosinophil values and severe clinical disease (presence of symptoms with a significant impact on quality of life and/or ≥ 1 hospital admission due to EoE complications, namely severe dysphagia, food impaction or esophageal perforation) and histological severe disease (≥ 55 eos/hpf and/or microabscesses in esophageal biopsies) was evaluated. 92 patients were observed, 83% male, 87% atopic. There was a mean delay in diagnosis of 4 years (range 0-31). 84% had aeroallergen sensitization and 71% food sensitization. Food impaction and dysphagia were the most frequent symptoms, and severe clinical disease was observed in 55%. Histologically, 37% had severity criteria. Patients with severe clinical disease had a significantly longer mean disease duration before diagnosis than patients without severe clinical disease (79 15 months, p = 0.021). Patients who described food impaction were significantly older at time of diagnosis than those who have never had impaction (18 9 years, p less than 0.001). There was no significant association (p less than 0.05) between sensitization, serum total IgE and peripheral blood eosinophil values and clinical or histological severity. An older age at diagnosis and a longer disease duration before diagnosis appear to be useful for predicting EoE clinical severity. Despite having been demonstrated a high prevalence of allergic disease, the presence of sensitization to airborne and/or food allergens do not seem to be useful for predicting clinical or histological severity.
PubMed: 36975751
DOI: 10.23822/EurAnnACI.1764-1489.292 -
Cureus Feb 2023Though rare, phlegmonous gastritis (PG) is a serious and life-threatening infection of the gastric submucosa and mucosa. Many factors have been associated with PG,...
Though rare, phlegmonous gastritis (PG) is a serious and life-threatening infection of the gastric submucosa and mucosa. Many factors have been associated with PG, including malignancy, chronic alcohol use, and immunocompromised states. Clinical presentation of PG is often non-specific, and diagnosis is often delayed. Early recognition and starting antibiotics significantly reduce overall mortality. We describe a case of a previously healthy male who presented with moderate abdominal pain and was found to have PG that was treated with an extensive course of antibiotics and total parental nutrition. Contrary to previously described cases in the literature, our patient had no predisposing factors, highlighting the importance of suspecting PG even in the absence of such factors and demonstrating the effectiveness of antibiotics in this disease.
PubMed: 36938228
DOI: 10.7759/cureus.35013