The correlation between chronic endometritis and Caesarean scar diverticulum.

PURPOSE: To investigate the risk factors for Caesarean Scar Diverticulum (CSD) with Chronic Endometritis (CE) and the correlation between CE and clinical symptoms of CSD. METHODS: The frequency of CE in 44 patients with CSD who underwent surgical treatment and 20 control women who underwent total hysterectomy was assessed and the clinical symptoms in the presence and absence of CE were compared. In accordance with the presence of one or more CD138-positive plasma cells per high-power field, CE was classified as mild or severe group. RESULTS: According to multivariate analysis, the presence of mild CE (OR 8.963, 95 % CI 2.177-36.907, p = 0.002) or severe CE (OR 21.773, 95 % CI 2.285-207.419, p = 0.007) was significantly associated with CSD. Mild CE (OR 12.390, 95 % CI 1.158-132.511, p = 0.037) or severe CE (OR 22.463, 95 % CI 1.657-304.541, P = 0.019) or depth of diverticulum (OR 1.294, 95 % CI 1.003-1.668, p = 0.047) was associated with prolonged menstruation in patients with CSD. The degree of CE in patients with CSD was positively correlated with the days of prolonged menstruation (r = 0.552, p < 0.001) and negatively correlated with haemoglobin level (r = -0.408, p = 0.038). CONCLUSIONS: CE was associated with CSD and its clinical symptoms, including prolonged menstruation and decreased haemoglobin. The severity of clinical symptoms of CSD is associated with endometrial inflammation.

Correlation of hysteroscopic findings of chronic endometritis with CD138 immunohistochemistry and their correlation with pregnancy outcomes.

PURPOSE: To investigate the correlation between hysteroscopic findings of chronic endometritis and CD138 immunohistochemistry positive in endometritis and to analyze the pregnancy outcomes and associated risk factors following embryo transfer in women diagnosed with chronic endometritis via hysteroscopy. METHODS: A retrospective observational study carried out at the Reproductive Medicine Center of Tangdu Hospital of Air Force Medical University, from January 2021 to December 2021, was performed by obtaining data from 194 medical records of women who underwent hysteroscopies for infertility and were diagnosed with chronic endometritis based on Delphi criteria. Spearman correlation analysis was used to evaluate the correlation between hysteroscopic findings and endometrial CD138 immunohistochemistry. The study also observed the differences in relevant indexes between the CD138-positive and CD138-negative groups after embryo transfer and analyzed factors influencing implantation failure using logistic regression analysis. RESULTS: The correlation analysis between hysteroscopic findings and CD138 immunohistochemistry showed that micropolyps were correlated with CD138 immunohistochemistry positivity. The correlation coefficient was 0.32 (P < 0.01). After embryo transfer, the clinical pregnancy rate of the CD138-positive group was lower compared to that of the CD138-negative group [64.79% (46/71) vs. 81.30% (100/123), P < 0.05]. The results of the multivariate logistic regression analysis revealed that age (P = 0.43) and CD138 immunohistochemistry positivity (P = 0.008) were the independent risk factors for predicting whether or not embryo implantation was successful. CONCLUSION: Hysteroscopic findings do not correlate strongly with endometrial CD138 immunohistochemistry, and chronic endometritis cannot be diagnosed by hysteroscopy alone. CD138 immunohistochemistry positivity is an independent factor contributing to the decrease in clinical pregnancy rate following embryo transfer.

Risk factors of chronic endometritis in women who have undergone hysteroscopy: a prospective nested case-control study.

There is limited research on risk factors for chronic endometritis regarding reproductive history and clinical symptoms. Thus, this nested case-control study identified risk factors for chronic endometritis in women who have undergone hysteroscopy. Endometrial tissue sections were obtained from 502 women with intrauterine disorders who underwent hysteroscopy. Chronic endometritis was diagnosed via CD138 immunostaining. The women were divided into two groups: 271 women without chronic endometritis and 231 women with chronic endometritis. The prevalence of chronic endometritis was 46%. Univariate logistic regression revealed that prolonged menstruation and intermenstrual bleeding were associated with chronic endometritis, and subsequent multivariate logistic regression analyses showed that these were further independently associated. With univariable logistic regression, the gravidity and abortion history were correlated with chronic endometritis; however, no significant correlation was found with the adjusted odds ratio (OR) of 0.74 (95% confidence interval [CI] 0.46-1.19) or 0.76 (95% CI 0.58-1.11), respectively. No significant correlation was found between caesarean section history and the rates of chronic endometritis. No significant difference was found in all other variables between the three groups with > 5, ≤ 5 plasma cells and in a unknown group. Prolonged menstruation and intermenstrual bleeding were risk factors associated with chronic endometritis. Chronic endometritis should be considered and CD138 immunohistochemical examination should be recommended in women with these symptoms.

Variation in diagnostic methods, criteria, and treatment for chronic endometritis: A nationwide survey in Japan.

AIM: To investigate variation in the diagnosis and treatment of chronic endometritis (CE) at the national level in Japan. METHODS: We performed a nationwide survey targeting all assisted reproductive technology (ART) facilities across Japan between 2021 and 2022. Diagnostic methods, criteria, and first- and second-line treatment protocols for CE were collected via a questionnaire. RESULTS: Among 616 ART facilities, 437 responded to the survey (response rate: 70.9%) of which 339 (77.6%) implemented diagnosis and treatment of CE. In the diagnosis of CE, 214 (63.1%) facilities used CD138 immunohistochemical staining of endometrial tissue, while hysteroscopy was the most frequently used as an adjunct diagnostic method (241 facilities, 71.1%). The most frequent cutoff value of CD138-positive cells for diagnosing CE was 3-5 cells/20 high-power fields (50%), but 7.9% (17 facilities) and 5.1% (11 facilities) used cutoff values of 1 and 2 cells, respectively. The most common first- and second-line treatment methods were doxycycline (210 facilities, 61.9%) and ciprofloxacin + metronidazole (164 facilities, 48.0%), respectively. CONCLUSIONS: There is considerable variation in the number of CD138-positive cells used for diagnosing CE. Establishing unified diagnostic criteria and therapeutic methods for CE is essential to provide standardized medicine for CE at the national level.

Clinicopathological Aspects of Dilation and Curettage (D&C) Biopsies Taken from Patients Living at High Altitude in Taif, KSA, with a Special Emphasis on Chronic Endometritis.

BACKGROUND: Chronic endometritis (CE) is a persistent inflammation of the uterine lining. Although it has a minimal clinical presentation, CE adversely affects the reproductive ability of women. The aims of this study were to detect pathological endometrial patterns in D&C biopsies and to evaluate chronic endometritis in patients living in a high-altitude area (1800 m above sea level) in order to determine the clinical pathological features and prevalence. MATERIALS AND METHODS: A cross-sectional study conducted at King Faisal Maternity Hospital included 100 samples of D&C biopsies from women complaining of various gynecological symptoms not due to gestational causes. The biopsies underwent tissue processing, H&E staining, and CD138 detection. Blood samples were taken for serological detection of infectious diseases, complete blood count, and chemical parameters. RESULTS: The mean age of women in the study with CE was 48.5 ± 8.5 years, and that of those without CE was 46.9 ± 9.7 years. The most common complaints were abnormal uterine bleeding, accounting for 83%. CE was present in 8% of cases, and there was a nonsignificant difference in hematological parameters between women with CE and those with other pathological diagnoses. There were also nonsignificant differences in chemical parameters, except for FSH and LH levels, which showed a significant difference, with p-values of 0.05 and 0.02, respectively. It can be concluded that the most common gynecological complaint of women in this study was abnormal uterine bleeding. CONCLUSIONS: The most commonly diagnosed pathological endometrial disorder in D&C biopsies was disordered proliferative endometrium, followed by endometrial polyps and endometrial hyperplasia. All of these are usually associated with hormonal disturbance, which appeared to be very common in the women in this study. The prevalence of chronic endometritis detected in our study was 8%, which is relatively high.

Multidimensional role of adapalene in regulating cell death in multiple myeloma.

Aims: Multiple myeloma (MM) remains a challenging condition to cure, with persistent drug resistance negating the benefits of treatment advancements. The unraveling complexities in programmed cell death (PCD), inclusive of apoptosis, autophagy, and ferroptosis, have highlighted novel therapeutic avenues. Our study focuses on deciphering how adapalene (ADA), a small molecule compound, accelerates the demise of MM cells via targeting their compensatory survival mechanisms. Methods: To assess the impact of ADA on MM, we employed flow cytometry and trypan blue exclusion assays to determine cell viabilities across MM cell lines and primary patient samples post-treatment. To delineate ADA's therapeutic targets and mechanisms, we conducted RNA sequencing (RNA-seq), gene set enrichment analysis (GSEA), molecular docking, and molecular dynamics simulations. We further designed pre-clinical trials emphasizing MM, exploring the efficacy of ADA as a standalone and in combination with bortezomib (BTZ). Results: ADA elicited a dose-responsive induction of MM cell death. Building upon ADA's anti-MM capabilities as a single agent, we proposed that ADA-BTZ co-treatment might amplify this lethality. Indeed, ADA and BTZ together greatly potentiated MM cell death. ADA proved beneficial in restoring BTZ susceptibility in BTZ-resistant relapsed or refractory MM (RRMM) patient cells. Molecular simulations highlighted ADA's high affinity (-9.17 kcal/mol) for CD138, with MM-GBSA revealing a binding free energy of -27.39 kcal/mol. Detailed interaction analyses indicated hydrogen-bonding of ADA with CD138 at the Asp35 and Gln34 residues. Additionally, ADA emerged as a versatile instigator of both ferroptosis and apoptosis in MM cells. Furthermore, ADA disrupted activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway triggered by BTZ, fostering cell death in BTZ-resistant MM subsets. Conclusion: ADA demonstrates a comprehensive capability to orchestrate MM cell death, exerting pronounced anti-MM activity while disrupting NF-κB-related drug resistance. ADA sensitization of MM cells to BTZ unravels its potential as a novel therapeutic drug for MM management.

[Construction of CD138-targeted chimeric antigen receptor- modified T cells and their effect in multiple myeloma therapy].

Objective: To construct a novel chimeric antigen receptor T (CAR-T) cell targeting CD138 and to investigate its cytotoxicity against myeloma cells. Methods: The hybridoma strain that can stably secrete the CD138 monoclonal antibody (mAb) was prepared and obtained through monoclonal antibody screening technology. The hybridoma strain cells were intraperitoneally injected into mice to produce ascites containing monoclonal antibodies, which were then collected and purified to obtain pure CD138 mAb. Further examinations were performed to assess the biological characteristics of CD138 mAb. The variable region sequence of this antibody was amplified through reverse transcription polymerase chain reaction and was used as the antigen recognition domain of CD138 CAR, which was subsequently expressed on the surface of T cells by lentiviral infection. Flow cytometry was employed to assess the phenotype of CD138 CAR-T cells. In vitro cytotoxicity and degranulation assays were performed to evaluate their antitumor effects. Results: ① We successfully prepared anti-human CD138 antibody hybridoma cell lines and screened a hybridoma cell strain, 5G2, which could persistently and stably secrete the anti-CD138 antibody. ② The purified CD138 (5G2) mAb can especially recognize CD138(+) cells with a binding affinity constant (K(D)) of 6.011×10(-9) mol/L and showed no significant binding activity with CD138(-) cells. ③The variable region sequence of the CD138 (5G2) antibody was obtained using molecular cloning technology, and CD138 (5G2) CAR was successfully constructed and expressed on T cells through lentivirus infection and, concurrently, demonstrated effective binding to recombinant human CD138 protein.④ The proliferation of T cells transduced with the CD138 (5G2) CAR was highly efficient. The phenotype analysis revealed that CD138 (5G2) CAR-T cells exhibited a greater tendency to differentiate into central memory T cells and memory stem T cells, with a reduced proportion of terminally differentiated effector memory subsets. ⑤CD138 (5G2) CAR-T cells demonstrated specific cytotoxicity against CD138(+) myeloma cell line H929, whereas CD138(-) cell line K562 remained unaffected. The percentage of residual H929 cells was (12.92±8.02) % after co-culturing with CD138 (5G2) CAR-T cells, while (54.25±15.79) % was left in the Vector-T group (E∶T=1∶2; P<0.001). ⑥Results of degranulation assays demonstrated a significant activation of CD138 (5G2) CAR-T cells after co-culture with the H929 cell line, whereas no significant activation was observed in Vector-T cells [ (25.78±3.35) % vs (6.13±1.30) %, P<0.001]. ⑦After co-culturing with CD138(+) cells, CD138 (5G2) CAR-T cells exhibited a significant increase in cytokine secretion compared to the Vector-T group [interleukin-2: (1 697.52±599.05) pg/ml vs (5.07±1.17) pg/ml, P<0.001; interferon-γ: (3 312.20±486.38) pg/ml vs (9.28±1.46) pg/ml, P<0.001; and tumor necrosis factor-α: (1 837.43±640.49) pg/ml vs (8.75±1.65) pg/ml, P<0.001]. However, no significant difference was observed in cytokine secretion levels between the two groups after co-culturing with CD138(-) cells. Conclusion: This study successfully prepared a novel monoclonal antibody against CD138, and CAR-T cells constructed with the antigen recognition domain derived from this 5G2 mAb demonstrated effective antitumor activity against myeloma cells. This can be used as a new option for the detection of the CD138 antigen and proposes a novel strategy for multiple myeloma immunotherapy.

Prevalence and risk factors for chronic endometritis in patients with adenomyosis and infertility: a retrospective cohort study.

BACKGROUND: To explore the incidence of chronic endometritis (CE) in patients with infertility and different forms of adenomyosis and analyze potential high-risk factors for infection. METHODS: This retrospective cohort study included 154 patients with infertility in the Liuzhou Maternity and Child Healthcare Hospital. Among them, 77 patients with adenomyosis were divided into four subgroups based on magnetic resonance imaging (MRI): internal, exterior, intramural, and full-thickness. Meanwhile, 77 patients did not have adenomyosis. Hysteroscopy and endometrial biopsy were performed in the proliferative phase. The main outcome measures were the morphology of the endometrium, syndecan-1 (CD138) immunohistochemical staining, clinical characteristics, and prevalence of CE in the adenomyosis subgroups. RESULTS: In comparison to the non-adenomyosis group, the adenomyosis group had significantly higher body mass index (BMI) and CA125 levels. The menstrual cycle in the adenomyosis group was significantly shorter, and menarche was significantly earlier. In comparison to the non-adenomyosis group, the adenomyosis group had a significantly higher diagnostic rate of CE (75.3% vs. 46.8% according to hysteroscopy and 74.0% vs. 33.8% according to histopathology, both with p < .050). The incidence of CE was significantly lower in patients with internal adenomyosis when compared with the other three subgroups. Increased BMI contributed to a higher risk of CE. CONCLUSIONS: The prevalence of CE was significantly higher in patients with adenomyosis and infertility. The differences in the incidence of CE are closely associated with the classification of adenomyosis. When patients with infertility are diagnosed with adenomyosis, it is recommended to identify the subtype and screen for endometritis.

Impact of Diagnosis and Treatment of Chronic Endometritis on Outcomes Before Starting Assisted Reproductive Technology: A Retrospective Study.

This study aimed to investigate the effect of diagnosis and treatment of chronic endometritis (CE) on the outcome of assisted reproductive technology (ART) with or without repeated implantation failure (RIF). This retrospective analysis included patients who underwent pathological examination for diagnosis of CE at Yamagata University Hospital. The examination was performed for all patients planned for ART with or without RIF. Patients who were examined within 6 months of the first oocyte retrieval or embryo transfer were included. We counted the number of CD138-positive cells within the endometrial stroma in patients' specimens and analyzed the patients' clinical information. Clinical rates of pregnancy and implantation were determined. A total of 80 women met the inclusion criteria: 13 CE-negative patients (17.3%) and 67 CE-positive patients (83.7%). A significant decrease was noted in the CD138-positive cell count between the first biopsy and second biopsy after CE treatment (p < 0.001). In addition, no significant differences were noted in ongoing pregnancy rates between the CE-negative patients and those who underwent CE treatment. The CD138-positive cell counts at first biopsy tended to be lower in each pregnancy group than in the non-pregnancy group. For patients planned to undergo ART, examination for diagnosis of CE with or without RIF could be considered. Pathological CD138-positive cell counts were considered useful for CE diagnosis and treatment decision-making. The study findings suggest the efficacy of antimicrobial agents in CE treatment, contributing to improved pregnancy outcomes.

Antibiotics improve reproductive outcomes after frozen-thaw embryo transfer for chronic endometritis treatment, especially in those with repeated implantation failure.

PURPOSE: To investigate the impact of antibiotic treatment for chronic endometritis (CE) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycles and the relevant clinical risk factors associated with CE. METHODS: A retrospective cohort analysis was conducted on 1352 patients who underwent hysteroscopy and diagnostic curettage at Nanjing Maternal and Child Health Hospital from July 2020 to December 2021. All patients underwent CD138 immunohistochemical (IHC) testing to diagnose CE, and a subset of them underwent FET after hysteroscopy. Patient histories were collected, and reproductive prognosis was followed up. RESULTS: Out of 1088 patients, 443 (40.7%) were diagnosed with CE. Univariate and multivariate binary logistic regression analyses revealed that parity ≥ 2, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, hydrosalpinx, endometrial polyps, a history of ≥ 2 uterine operations, and RIF were significantly associated with an elevated risk of CE (P < 0.05). Analysis of the effect of CE on pregnancy outcomes in FET cycles after antibiotic treatment indicated that treated CE patients exhibited a significantly lower miscarriage rate (8.7%) and early miscarriage rate (2.9%) than untreated non-CE patients (20.2%, 16.8%). Moreover, the singleton live birth rate (45.5%) was significantly higher in treated CE patients than in untreated non-CE patients (32.7%). Survival analysis revealed a statistically significant difference in the first clinical pregnancy time between treated CE and untreated non-CE patients after hysteroscopy (P = 0.0019). Stratified analysis based on the presence of recurrent implantation failure (RIF) demonstrated that in the RIF group, treated CE patients were more likely to achieve clinical pregnancy than untreated non-CE patients (P = 0.0021). Among hysteroscopy-positive patients, no significant difference was noted in pregnancy outcomes between the treatment and control groups (P > 0.05). CONCLUSION: Infertile patients with a history of parity ≥ 2, hydrosalpinx, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, endometrial polyps, a history of ≥ 2 uterine operations, and RIF are at an increased risk of CE; these patients should be recommended to undergo hysteroscopy combined with CD138 examination before embryo transfer. Antibiotic treatment can improve the reproductive outcomes of FET in patients with CE, especially those with RIF.

Chronic endometritis - a constantly discussed issue in infertile women.

OBJECTIVE: A review of current knowledge on the pathophysiology, diagnostic and treatment options for chronic endometritis in infertile women. METHODS AND RESULTS: One of the major causes of failed in vitro fertilization (IVF) is undiagnosed intrauterine pathologies, including chronic inflammation of the uterine mucosa - chronic endometritis. However, some authors relativize the negative impact of chronic endometritis on reproductive outcomes. The etiopathogenesis of chronic endometritis is due to qualitative and quantitative changes in the endometrial microbiome with abnormal multiplication of microorganisms naturally occurring in the uterine cavity or vagina. There is no uniform consensus on the most common pathogen causing chronic endometritis. It is characterized by infiltration of plasma cells into the endometrial stroma outside the menstrual cycle, accompanied by hyperaemia and endometrial oedema. Clinical symptoms are very mild or absent. The diagnosis of chronic endometritis is often difficult because there is no specific clinical or laboratory diagnostic method. The following investigative options are commonly used for the diagnosis of chronic endometritis: diagnostic hysteroscopy, histopathological examination of the endometrium including CD 138 immunohistochemistry and culture from the uterine cavity. However, standardised international hysteroscopic and histopathological criteria for accurate diagnosis of chronic endometritis are still lacking. Empirically administered antibiotic therapy improves the success rate of pregnancy and delivery of a viable foetus in infertile patients with proven chronic endometritis. In addition to reviewing the current knowledge of chronic endometritis, this article discusses the importance of hysteroscopy in the diagnostic process. CONCLUSION: Chronic endometritis is often a clinically silent disease with negative impact on reproduction in infertile women. Although there are still many unresolved issues, the introduction of hysteroscopy into the diagnostic process is important for clinical practice; however, hysteroscopy even in combination with histological examination of the endometrium, often does not allow an unequivocal diagnosis of chronic endometritis. Further prospective randomised studies in a selected group of women with proven chronic endometritis and repeated failure to implant proven euploid embryos should refine this knowledge.

Chronic endometritis multiplies the recurrence risk of endometrial polyps after transcervical resection of endometrial polyps: a prospective study.

BACKGROUND: To investigate the impact of chronic endometritis (CE) on the recurrence of endometrial polyps (EPs) in premenopausal women after transcervical resection of endometrial polyps (TCRP). METHODS: This prospective study enrolled 507 women who underwent TCRP between January 1, 2022 and December 31, 2022. The patients were divided into a CE group (n = 133) and non-CE group (n = 374) based on the expression of CD138 in the endometrium. The EP recurrence rate at 1 year after TCRP was compared between the CE and non-CE groups and between groups with mild CE and severe CE. The impact of CD138 expression by resected EPs on EP recurrence also was investigated. RESULTS: The EP recurrence rate at 1 year post-TCRP was higher in the CE group than in the non-CE group (25.6% vs. 10.4%) and also higher in the severe CE group than in the mild CE group (34.5% vs. 18.7%). Additionally, the EP recurrence rate was higher among patients with CD138-expressing EPs than among those with EPs lacking CD138 expression (30.5% vs. 6.5%). The odds ratio (OR) for EP recurrence in the CE cohort compared with the non-CE cohort was 3.10 (95% confidence interval [CI] 1.84-5.23) after adjustment for EP number and precautions against EP recurrence. The ORs for EP recurrence in patients with mild CE and severe CE were 2.21 (95%CI 1.11-4.40) and 4.32 (95%CI 2.26-8.26), respectively. Similarly, the OR for EP recurrence in cases with CD138-expressing EPs relative to cases with EPs lacking CD138 expression was 6.22 (95%CI 3.59-10.80) after adjustment for EP number and precautions against EP recurrence. CONCLUSIONS: CE multiplied the recurrence rate of EPs in premenopausal women after TCRP, and this effect positively correlated with CE severity. CD138 expression by EPs also was associated with a higher risk for EP recurrence.

AI-algorithm training and validation for identification of endometrial CD138+ cells in infertility-associated conditions; polycystic ovary syndrome (PCOS) and recurrent implantation failure (RIF).

Background: Endometrial CD138+ plasma cells serve as a diagnostic biomarker for endometrial inflammation, and their elevated occurrence correlates positively with adverse pregnancy outcomes. Infertility-related conditions like polycystic ovary syndrome (PCOS) and recurrent implantation failure (RIF) are closely associated with systemic and local chronic inflammatory status, wherein endometrial CD138+ plasma cell accumulation could also contribute to endometrial pathology. Current methods for quantifying CD138+ cells typically involve laborious and time-consuming microscopic assessments of only a few random areas from a slide. These methods have limitations in accurately representing the entire slide and are susceptible to significant biases arising from intra- and interobserver variations. Implementing artificial intelligence (AI) for CD138+ cell identification could enhance the accuracy, reproducibility, and reliability of analysis. Methods: Here, an AI algorithm was developed to identify CD138+ plasma cells within endometrial tissue. The AI model comprised two layers of convolutional neural networks (CNNs). CNN1 was trained to segment epithelium and stroma across 28,363 mm2 (2.56 mm2 of epithelium and 24.87 mm2 of stroma), while CNN2 was trained to distinguish stromal cells based on CD138 staining, encompassing 7345 cells in the object layers (6942 CD138- cells and 403 CD138+ cells). The training and performance of the AI model were validated by three experienced pathologists. We collected 193 endometrial tissues from healthy controls (n = 73), women with PCOS (n = 91), and RIF patients (n = 29) and compared the CD138+ cell percentages based on cycle phases, ovulation status, and endometrial receptivity utilizing the AI model. Results: The AI algorithm consistently and reliably distinguished CD138- and CD138+ cells, with total error rates of 6.32% and 3.23%, respectively. During the training validation, there was a complete agreement between the decisions made by the pathologists and the AI algorithm, while the performance validation demonstrated excellent accuracy between the AI and human evaluation methods (intraclass correlation; 0.76, 95% confidence intervals; 0.36-0.93, p = 0.002) and a positive correlation (Spearman's rank correlation coefficient: 0.79, p < 0.01). In the AI analysis, the AI model revealed higher CD138+ cell percentages in the proliferative phase (PE) endometrium compared to the secretory phase or anovulatory PCOS endometrium, irrespective of PCOS diagnosis. Interestingly, CD138+ percentages differed according to PCOS phenotype in the PE (p = 0.03). On the other hand, the receptivity status had no impact on the cell percentages in RIF samples. Conclusion: Our findings emphasize the potential and accuracy of the AI algorithm in detecting endometrial CD138+ plasma cells, offering distinct advantages over manual inspection, such as rapid analysis of whole slide images, reduction of intra- and interobserver variations, sparing the valuable time of trained specialists, and consistent productivity. This supports the application of AI technology to help clinical decision-making, for example, in understanding endometrial cycle phase-related dynamics, as well as different reproductive disorders.

Construction of deep learning-based convolutional neural network model for automatic detection of fluid hysteroscopic endometrial micropolyps in infertile women with chronic endometritis.

OBJECTIVE(S): Chronic endometritis (CE) is a localized mucosal inflammatory disorder associated with female infertility of unknown etiology, endometriosis, tubal factors, repeated implantation failure, and recurrent pregnancy loss, along with atypical uterine bleeding and iron deficiency anemia. Diagnosis of CE has traditionally relied on endometrial biopsy and detection of CD138(+) endometrial stromal plasmacytes. To develop a less invasive diagnostic system for CE, we aimed to construct a deep learning-based convolutional neural network (CNN) model for the automatic detection of endometrial micropolyps (EMiP), a fluid hysteroscopy (F-HSC) finding recognized as tiny protrusive lesions that are closely related to this disease. STUDY DESIGN: This is an in silico study using archival images of F-HSC performed at an infertility center in a private clinic. A total of 244 infertile women undergoing F-HSC on the days 6-12 of the menstrual cycle between April 2019 and December 2021 with histopathologically-confirmed CE with the aid of immunohistochemistry for CD138 were utilized. RESULTS: The archival F-HSC images of 208 women (78 with EMiP and 130 without EMiP) who met the inclusion criteria were finally subjected to analysis. Following preprocessing of the images, half a set was input into a CNN architecture for training, whereas the remaining images were utilized as the test set to evaluate the performance of the model, which was compared with that of the experienced gynecologists. The sensitivity, specificity, accuracy, precision, and F1-score of the CNN model-aided diagnosis were 93.6 %, 92.3 %, 92.8 %, 88.0 %, and 0.907, respectively. The area under the receiver operating characteristic curves of the CNN model-aided diagnosis (0.930) was at a similar level (p > .05) to the value of conventional diagnosis by three experienced gynecologists (0.927, 0.948, and 0.906). CONCLUSION: These findings indicate that our deep learning-based CNN is capable of recognizing EMiP in F-HSC images and holds promise for further development of the computer-aided diagnostic system for CE.

Multifocal Extramedullary Plasmacytoma of the Thyroid With Cervical and Paratracheal Lymph Node Involvement and Progression to Multiple Myeloma.

Extramedullary plasmacytomas without evidence of systemic illness make up less than 5% of all plasma cell neoplasms. The incidence of extramedullary plasmacytoma of the thyroid region is exceedingly rare. This report discusses the case of a 72-year-old male with extramedullary plasmacytoma of the thyroid. The patient underwent a total thyroidectomy for an enlarging right-sided thyroid nodule, and intraoperatively, the plasmacytoma was found to have an extracapsular component with adherence to the regional soft tissue as well as involvement of the right laryngeal nerve and regional lymph nodes. Despite a comprehensive negative workup for multiple myeloma initially, including a bone marrow biopsy and hematologic workup, the disease progressed to multiple myeloma following definitive radiation therapy, as evidenced by the development of hypermetabolic lytic lesions and further pathological examination. The patient's treatment course included systemic chemotherapy and an autologous stem cell transplant, resulting in a favorable treatment response. The progression to multiple myeloma despite established guidelines highlights the need for close observation and the potential for innovative therapeutic strategies to manage this rare entity.

CD20highCD138low tumor-infiltrating lymphocytes predominantly related to cytokine‒cytokine receptor interactions are associated with favorable outcomes in neuroblastoma patients.

Recent advances have revealed that the role of the immune system is prominent in the antitumor response. In the present study, it is aimed to provide an expression profile of tumor-infiltrating lymphocytes (TILs), including mature B cells, plasma cells, and their clinical relevance in neuroblastoma. The expression of CD20 and CD138 was analyzed in the Cangelosi786 dataset (n = 769) as a training dataset and in our cohort (n = 120) as a validation cohort. CD20 high expression was positively associated with favorable overall survival (OS) and event-free survival (EFS) (OS: P < 0.001; EFS: P < 0.001) in the training dataset, whereas CD138 high expression was associated with poor OS and EFS (OS: P < 0.001; EFS: P < 0.001) in both the training and validation datasets. Accordingly, a combined pattern of CD20 and CD138 expression was developed, whereby neuroblastoma patients with CD20highCD138low expression had a consistently favorable OS and EFS compared with those with CD20lowCD138high expression in both the training and validation cohorts (P < 0.0001 and P < 0.01, respectively). Examination of potential molecular functions revealed that signaling pathways, including cytokine‒cytokine receptor interactions, chemokine, and the NF-kappa B signaling pathways, were involved. Differentially expressed genes, such as BMP7, IL7R, BIRC3, CCR7, CXCR5, CCL21, and CCL19, predominantly play important roles in predicting the survival of neuroblastoma patients. Our study proposes that a new combination of CD20 and CD138 signatures is associated with neuroblastoma patient survival. The related signaling pathways reflect the close associations among the number of TILs, cytokine abundance and patient outcomes and provide therapeutic insights into neuroblastoma.

Expression of Potential Antibody-Drug Conjugate Targets in Cervical Cancer.

(1) Background: There is a huge unmet clinical need for novel treatment strategies in advanced and recurrent cervical cancer. Several cell membrane-bound molecules are up-regulated in cancer cells as compared to normal tissue and have revived interest with the introduction of antibody-drug conjugates (ADCs). (2) Methods: In this study, we characterize the expression of 10 potential ADC targets, TROP2, mesotheline, CEACAM5, DLL3, folate receptor alpha, guanylatcyclase, glycoprotein NMB, CD56, CD70 and CD138, on the gene expression level. Of these, the three ADC targets TROP2, CEACAM5 and CD138 were further analyzed on the protein level. (3) Results: TROP2 shows expression in 98.5% (66/67) of cervical cancer samples. CEACAM5 shows a stable gene expression profile and overall, 68.7% (46/67) of cervical cancer samples are CEACAM-positive with 34.3% (23/67) of cervical cancer samples showing at least moderate or high expression. Overall, 73.1% (49/67) of cervical cancer samples are CD138-positive with 38.8% (26/67) of cervical cancer samples showing at least moderate or high expression. (4) Conclusions: TROP2, CEACAM5 or CD138 do seem suitable for further clinical research and the data presented here might be used to guide further clinical trials with ADCs in advanced and recurrent cervical cancer patients.

Still Far to Go With Characterisation of Molecular and Genetic Features of Diffuse Large B-Cell Lymphoma in People Living With HIV: A Scoping Review.

Diffuse large B-cell lymphoma (DLBCL) accounts for half of non-Hodgkin lymphoma cases in people living with human immunodeficiency syndrome (PLWH). The interplay of viremia, immune dysregulation and co-infection with oncogenic viruses play a role in pathogenesis of DLBCL in PLWH (HIV-DLBCL). This scoping review aimed to describe the molecular landscape of HIV-DLBCL, investigate the impact of biomarker on clinical outcomes and describe technologies used to characterise HIV-DLBCL. Thirty-two papers published between 2001 and 2023 were included in this review. Samples of HIV-DLBCL were relatively small (16-110). Cohort effects influenced frequencies of molecular characteristics hence their impact on survival was not clear. Molecular features were distinct from HIV-unrelated DLBCL. The most frequently assessed characteristic was cell of origin (81.3% of studies). Somatic mutations were the least researched (6.3% of studies). Overall, biomarker identification in HIV-DLBCL requires broader richer data from larger or pooled samples using more powerful techniques such as next-generation sequencing.