Virtual planning as a resource for correcting severe facial asymmetry ­ case report / Planejamento virtual como recurso para correção de assimetria facial severa ­ relato de caso

A hiperplasia hemimandibular é responsável por prejuízos estéticos, funcionais, motores e psicossociais. Com etiologia incerta, ocorre frente ao desequilíbrio de fatores regulatórios de crescimento presentes na camada cartilaginosa do côndilo. O relato objetiva descrever a tomada de decisões baseada em exames complementares específicos aliados à adequada intervenção cirúrgica da lesão. Paciente gênero feminino, 33 anos de idade, compareceu à clínica particular com queixa principal de "face assimétrica", foi requerido uma avaliação cintilográfica objetivando e confirmando a interrupção do crescimento condilar, descartando a hipótese de Osteocondroma e condilectomia. Após preparo ortodôntico prévio, os exames tomográficos foram utilizados na criação de um protótipo que foi impresso após a realização dos movimentos ósseos planejados. Mediante à reconstrução, foi concluído que a assimetria presente não seria totalmente corrigida somente através da intervenção ortognática, sendo necessária também uma osteotomia removendo parte da base do corpo e ângulo mandibular, através da confecção de um guia de corte, promovendo à reanatomização sem a necessidade de acesso extra oral submandibular, evitando uma cicatriz em face feminina. Paciente encontra-se em pós-operatório de 60 meses, sem queixas e satisfeita. Portanto, é evidenciado cada vez mais a influência positiva que o planejamento virtual pode trazer aos profissionais na otimização dos resultados cirúrgicos.

Hemimandibular hyperplasia is responsible for aesthetic, functional, motor, and psychosocial impairments. With an uncertain etiology, it occurs due to the imbalance of regulatory growth factors present in the cartilaginous layer of the condyle. The report aims to describe decision-making based on specific complementary exams combined with the appropriate surgical intervention for the condition. A 33-year-old female patient presented at a private clinic with the main complaint of "asymmetric face." A scintigraphic evaluation was requested to objectively confirm the interruption of condylar growth, ruling out the hypothesis of Osteochondroma and condylectomy. After prior orthodontic preparation, tomographic exams were used to create a prototype that was printed after planned bone movements. Through the reconstruction, it was concluded that the existing asymmetry would not be entirely corrected through orthognathic intervention alone, necessitating also an osteotomy to remove part of the base of the body and mandibular angle. This was done through the creation of a cutting guide, allowing for reanatomization without the need for submandibular extraoral access, thus avoiding a scar on the female face. The patient is 60 months postoperative, with no complaints and satisfied. Therefore, the increasingly positive influence of virtual planning on optimizing surgical outcomes for professionals is evident.

Successful Treatment of Angiolymphoid Hyperplasia with Eosinophilia Associated with Scalp Demodicosis Using Cryotherapy and Topical Metronidazole.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare, benign, vasoproliferative tumour. We report a 25-year-old female patient who reported in 2021 to a dermatology clinic in Rustaq, Oman, with multiple, grouped, erythematous dome-shaped papules and nodules of 6 months duration on the left temporo-occipital region. Biopsy findings were consistent with a diagnosis of ALHE with evidence of Demodex mite infestation in the sebaceous ducts. The patient demonstrated significant improvement following 7 weeks of treatment with multiple cryotherapy sessions and topical application of metronidazole gel. This case suggests that scalp demodicosis may represent a novel trigger for the development of ALHE.

Long-term results of multimodal treatment of the prostate using the Thulium Laser.

Background and aims: To evaluate a novel multimodal treatment (TLP) that integrates the use of a thulium laser, bipolar transurethral resection of the prostate (TURP), and "button-type" bipolar plasma vaporization for the endoscopic treatment of benign prostatic hyperplasia (BPH). Methods: From March 2018 to December 2021, we prospectively evaluated 220 patients with symptomatic BPH who underwent TLP. Patients were assessed based on the International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rate (Qmax), and postvoid residual urine (PVR). Perioperative and postoperative follow-up data were analyzed. Results: The mean age at surgery was 66.74 years (SD 8.21). The median prostate size was 80 (IQR 70 - 110). The median operative time was 45 (IQR 35 - 55) minutes and the hospital stay was 2 (IQR 1 - 2) days. Patients were discharged with the urinary catheter in place, which was removed approximately 7 days after surgery when the histopathological result was discussed with the patient. Postoperatively, IPSS, QoL, Qmax and PVR showed a significant improvement starting at 3 months and continued through the postoperative follow-up visits (6-12-24-36-48-60 months). Urethral stricture and bladder neck contracture occurred in 1 (0.45%) and 2 (0.91%) patients, respectively. Recurrence of BPH occurred in 2 patients (0.91%) who underwent a second procedure. Conclusions: In conclusion, we report that the multimodal surgical treatment of BPH consisting of combining Thulium laser vaporization, bipolar TURP and plasma vaporization (TLP) represents an efficient and durable therapeutic method for BPH patients with low a complication rate at 5-year follow-up.

Exploring the potential mechanism of Xiaojin Pill therapy for benign prostatic hyperplasia through metabolomics and gut microbiota analysis.

Background: Xiaojin Pill (XJP) is a traditional Chinese medicine prescribed for treating benign prostatic hyperplasia (BPH). It has been proven to have multiple effects, such as regulating sex hormone levels, exhibiting anti-tumor, anti-inflammatory, analgesic, and anti-platelet aggregation properties, and improving immunity. However, the material basis of XJP's therapeutic effect on BPH and its metabolic process in vivo remains to be clarified. At the same time, many microorganisms that exist in the urogenital tract, including those related to BPH, can also affect the health of the host. Methods: Using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), the chemical components of XJP were identified. A BPH model was created through bilateral testicular ablation and injections of testosterone propionate. A comprehensive evaluation of XJP efficacy was conducted using pathological ELISA, TUNEL, and immunohistochemical techniques. In addition, UPLC-MS metabolomics and 16S rRNA sequencing revealed the serum metabolic profile and intestinal microbiota composition. We performed a Spearman correlation coefficient analysis to highlight the interactions between "intestinal microbiota-serum factors" and "intestinal microbiota-metabolites." Results: XJP contains 91 compounds that alleviate pathologies of BPH in rats, decreasing prostate weight, index, and serum levels of Dihydrotestosterone (DHT), Prostate-Specific Antigen (PSA), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) levels. It inhibits prostatic epithelial cell apoptosis and downregulates Bax, TGF-ß1, and IGF-1 proteins in the caspase-3 pathway. Metabolomics studies have revealed 10 upregulated and 10 downregulated metabolites in treated rats, with 5-methylcytosine, uracil, and cytosine enriched in pyrimidine metabolism. L-arginine plays a pivotal role in metabolic pathways encompassing pyrimidine metabolism, arginine biosynthesis, and the mammalian target of rapamycin (mTOR) signaling pathway. 16S rRNA sequencing revealed that XJP optimized the diversity and balance of intestinal flora in BPH rats by decreasing the Bacteroidetes/Firmicutes (B/F) ratio, enhancing the beneficial bacteria, such as Eggerthellaceae, Anaerovoracaceae, and Romboutsia, and suppressing the dysfunctional bacteria, such as Atopobiaceae, Prevotellaceae_NK3B31_group, Dorea, and Frisingicoccus. According to the Spearman correlation coefficient analysis, Lactobacillus was found to be most associated with serum factors, whereas Romboutsia showed the highest correlation with metabolites. This finding suggests that XJP modulates pyrimidine metabolism disorders in BPH rats, a regulation that aligns closely with Romboutsia, Prevotellaceae_NK3B31_group, Lactobacillus, Chujaibacter, and Enterorhabdus, thereby providing valuable biological insights. Conclusion: In summary, these findings indicate that XJP possesses a synergistic anti-BHP effect through its multi-component, multi-target, multi-gut microbiota, and multi-metabolic pathway properties. The effect involves the regulation of sex hormone levels, growth factors, and the anti-epithelial cell apoptosis process. The modulation of specific gut microbiota by the host and the involvement of multiple metabolic pathways are likely one of the significant mechanisms of XJP in treating BPH. Notably, pyrimidine metabolism and the intestinal microbial ecosystem are closely intertwined in this process.

SGLT2 Inhibitor and Urinary Tract Infection in Men at Risk for Voiding Dysfunction: A VigiBase Analysis.

INTRODUCTION: We investigated the risk of UTIs and complex UTIs associated with SGLT2 (sodium-glucose cotransporter-2) inhibitors in men, emphasizing older men at higher risk for voiding dysfunction. METHODS: Utilizing a pharmacovigilance case-noncase design, we analyzed VigiBase reports from 1967 to 2022 among male patients. VigiBase is a comprehensive global database for drug safety. Disproportionality analysis, which compares the frequency of reported adverse events for specific drugs against other drugs, was conducted using reporting odds ratio (ROR) and empirical Bayes estimator (EBE). Age was stratified at 65 years as a threshold for increased susceptibility to male voiding dysfunctions. Sensitivity analyses were performed to compare SGLT2 inhibitor with other diabetes medications and years 2013 to 2022. RESULTS: There were 484 UTIs (ROR 6.75 [95% CI: 6.17-7.39]; EBE 6.78) and 165 complex UTIs (ROR 8.09 [95% CI: 6.94-9.43]; EBE 8.60). In men under 65, there were 178 UTIs (ROR 6.82 [95% CI: 5.88-7.91]; EBE 6.99) and 65 complex UTIs (ROR 7.30 [95% CI: 5.71-9.32]; EBE 7.90). In men 65 and over, we found 153 UTIs (ROR 5.11 [95% CI: 4.35-5.99]; EBE 5.44) and 59 complex UTIs (ROR 8.79 [95% CI: 6.79-11.37]; EBE 9.60). Sensitivity analyses consistently showed significant signals. CONCLUSIONS: This study suggests an elevated risk for both UTIs and complex UTIs in men taking SGLT2 inhibitors, with a more pronounced risk for complex UTI in older men who may have benign prostatic hyperplasia-related voiding dysfunction. These findings highlight the need for a balanced approach in prescribing SGLT2 inhibitors, particularly in populations potentially more susceptible to UTIs.

Fertility-sparing treatment in MSI-H/MMRd endometrial carcinoma or atypical endometrial hyperplasia: A systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis aimed to describe the oncological and reproductive outcomes of patients with MSI-H/MMRd endometrial carcinoma (EC) or atypical endometrial hyperplasia (AEH) undergoing fertility-sparing treatment. METHODS: The study protocol was registered with the PROSPERO database (No: CRD42024530406). A systematic literature search in major electronic databases (PubMed, Embase, and Cochrane Library) was conducted from January 1, 2013 to August 10, 2024. The primary outcomes were complete remission (CR) rate and recurrence rate. Other outcomes included oncological outcomes in patients with Lynch syndrome and overall patient fertility status. RESULTS: The study included ten retrospective studies summarizing 66 patients with MSI-H/MMRd undergoing fertility-sparing treatment. The publication bias analysis was low. The length of follow-up varied from 3 to 164 months according to the different studies analyzed. After fertility-sparing treatment, 61.8 % of patients achieved CR, and 41.2 % of patients relapsed. Twelve patients were identified with germline mutations in Lynch syndrome, nine (75 %) achieved CR, and seven (77.8 %) relapsed. Only one study with active use of assisted reproductive technology reported a 1-year cumulative pregnancy rate of more than 60 % and more than half live births, while the remaining five studies assessed fertility outcomes and reported only one live birth. CONCLUSION: EC and AEH patients with the MSI-H/MMRd subtype had a low remission rate and high recurrence rate compared to conservative treatment. Caution is recommended when evaluating fertility-sparing therapy for patients with the MSI-H/MMRd subtype.

Managing Newborn Screening Repeat Collections for Sick and Preterm Neonates.

Some preterm and sick neonates have altered biochemical profiles and follow-up newborn screening (NBS) collections are recommended. The Victorian NBS program historically recommended repeat collections for babies with birth weight < 1500 g (managed by the maternity service provider) and 3 weeks post-transfusion (managed by the laboratory). We aimed to determine adherence to current guidelines and review the guidelines to improve NBS performance. To do this, we audited data from 348,584 babies between January 2018 and June 2022. Babies with a recorded birth weight of <1500 g were filtered for inclusion. For the overall review and visualization of the protocol, we sourced information from the literature, our professional society and tertiary hospital services. A total of 2647 babies had a birth weight recorded between 200 and 1499 g. Of these, 2036 (77%) had a second sample collected, indicating that >1 in 5 babies were not receiving a follow-up collection. Our timing of repeat collections for transfused babies, requiring a 3-week follow-up collection, was longer than in other Australasian jurisdictions. A new combined "sick-prem protocol" was launched to support repeat collections and after a 1-year review achieved 95% compliance. We recommend NBS laboratories audit preterm and sick neonate repeat collections to ensure appropriate follow-up. This should be supported with a visual process map to aid education and compliance.

Comparative Assessment of the Influence of Embolizing Agents on the Adrenal Parenchyma.

A comparative analysis of morphological and functional changes in the adrenal glands after embolization of supplying arteries with Lifepearl microspheres (100±25 µm; Terumo) and with a solution of polidocanol (Aethoxysklerol, Kreussler Pharma) was performed in male Vietnamese Lop-Bellied pigs (n=20). The introduction of the microspheres into the arterial bed did not affect the adrenal parenchyma. However, the injection of the liquid sclerosing agent caused foci of productive inflammation leading to the formation of sclerotic tissue and reduction of the volume of glandular tissue. Administration of the sclerosant was accompanied by arterial hypotension, an indirect indication of a decrease in vasoactive hormone production by the adrenal cortex. These findings suggest that polidocanol can be used as an embolization agent for hyperplastic diseases of the adrenal cortex.

Non-functional alpha-cell hyperplasia with glucagon-producing NET: a case report.

Introduction: Alpha-cell hyperplasia (ACH) is a rare pancreatic endocrine condition. Three types of ACH have been described: functional or nonglucagonoma hyperglucagonemic glucagonoma syndrome, reactive or secondary to defective glucagon signaling, and non-functional. Few cases of ACH with concomitant pancreatic neuroendocrine tumors (pNETs) have been reported and its etiology remains poorly understood. A case report of non-functional ACH with glucagon-producing NET is herein presented. Case report: A 72-year-old male was referred to our institution for a 2 cm single pNET incidentally found during imaging for acute cholecystitis. The patient's past medical history included type 2 diabetes (T2D) diagnosed 12 years earlier, for which he was prescribed metformin, dapagliflozin, and semaglutide. The pNET was clinically and biochemically non-functioning, apart from mildly elevated glucagon 217 pg/ml (<209), and 68Ga-SSTR PET/CT positive uptake was only found at the pancreatic tail (SUVmax 11.45). The patient underwent a caudal pancreatectomy and the post-operative 68Ga-SSTR PET/CT was negative. A multifocal well-differentiated NET G1, pT1N0M0R0 (mf) strongly staining for glucagon on a background neuroendocrine alpha-cell hyperplasia with some degree of acinar fibrosis was identified on pathology analysis. Discussion and conclusion: This case reports the incidental finding of a clinically non-functioning pNET in a patient with T2D and elevated glucagon levels, unexpectedly diagnosed as glucagon-producing NET and ACH. A high level of suspicion was required to conduct the glucagon immunostaining, which is not part of the pathology routine for a clinically non-functioning pNET, and was key for the diagnosis that otherwise would have been missed. This case highlights the need to consider the diagnosis of glucagon-producing pNET on an ACH background even in the absence of glucagonoma syndrome.

Nomogram using human epididymis protein 4 predicted concurrent endometrial cancer from endometrial atypical hyperplasia before surgery.

Objective: To establish a nomogram based on presurgical predictors of concurrent endometrial cancer (EC) for patients diagnosed with endometrial atypical hyperplasia before definitive surgery (preoperative-EAH) to improve the risk stratification and clinical application. Methods: Preoperative-EAH patients who underwent hysterectomy in a tertiary hospital from January 2020 to December 2022 were retrospectively analyzed. Independent predictors from the multivariate logistic regression model were used to establish a nomogram, and bootstrap resampling was used for internal validation. Results: Of 370 preoperative-EAH patients, 23.4% were diagnosed with EC after definitive surgery (final-EC). Multivariate analyses found three independent predictors of final EC: human epididymis protein 4 (HE4) ≥43.50 pmol/L [odds ratio (OR) = 3.70; 95% confidence intervals (CI) = 2.06-6.67], body mass index (BMI) ≥ 28 kg/m2 (OR = 2.05; 95% CI = 1.14-3.69), and postmenopausal status, particularly at postmenopausal time ≥5 years (OR = 5.84, 95% CI = 2.51-13.55), which were used to establish a nomogram model. The bootstrap-corrected C-index of the nomogram was 0.733 (95% CI = 0.68-0.79), which was significantly higher than that of each individual factor. The calibration curve and decision curve showed good consistency and clinical net benefit of the model. At the maximum Youden index, 49.4% (43/87) of women in the high-risk group defined by nomogram had concurrent EC, versus 16.6% in the low-risk group (P< 0.001). Conclusion: The nomogram based on HE4, menopausal status, and BMI was found with an improved predictive value to stratify preoperative-EAH patients at high risk of concurrent EC for better clinical management.

Idiopathic Gingival Fibromatosis: Report of a Rare Case.

The progressive overgrowth of the gingiva is the hallmark of idiopathic gingival fibromatosis (IGF). Excess gingival tissue can obscure the crown of a tooth, resulting in spaces between teeth, displacement, retention of primary or permanent teeth, and difficulties with feeding, speaking, and appearance. The diagnosis and management of inherited gingival fibromatosis are the focus of this case report. A 12-year-old girl was referred from the Department of Orthodontics to Oral Medicine as a result of progressive gingival enlargement, which impeded orthodontic treatment for misaligned lower front teeth. The patient underwent a conservative periodontal treatment regimen that encompassed gingivectomy and debridement. The excised gingival tissues were submitted for histopathological examination. Tissue sections stained with hematoxylin and eosin showed connective tissue with dense bundles of collagen fibers and little inflammation. The patient was reviewed after three months, and advised of orthodontic management for further aesthetic correction. The findings indicated that the oral symptoms of gingival fibromatosis are influenced by the severity of the condition and the age at which it begins. Early intervention helps mitigate potential difficulties for younger individuals.

Cost Comparison of Prostatic Artery Embolization Between In-Hospital and Outpatient-Based Lab Settings.

Purpose This study aimed to determine the costs associated with prostatic artery embolization (PAE) performed in hospital and outpatient-based lab (OBL) settings. Methods Procedures were performed in similarly equipped procedure suites located within a tertiary hospital or OBL. Time-driven activity-based costing (TDABC) was utilized to calculate procedural costs incurred by the institution. Process maps were created describing personnel, space, equipment, and materials. The time duration of each procedural step was recorded independently by a nurse caring for the patient at the time of the procedure, and mean values were included in our model. Using institutional and publicly available financial data, costs, and capacity cost rates were determined. Results Thirty-seven PAE procedures met inclusion criteria with a mean patient age of 70.4 (+/- 6.7) years and a mean prostate gland size of 129.7 (+/-56.4) cc. Twenty-six procedures were performed within the hospital setting, and 11 procedures were performed within the OBL. Reduction in International Prostate Symptom Score (IPSS) was not significantly different following hospital and OBL procedures (57.2% vs. 82.4%, P = 0.0796). Mean procedural time was not significantly different between the hospital and OBL settings (136.6 vs. 147.3 minutes, P = 0.1893). However, the duration between admission and discharge was significantly longer for procedures performed in a hospital (468.8 vs. 325.4 minutes, P <0.0001). Total costs for hospital-based procedures were marginally higher ($3,858.28 vs. $3,642.67). Conclusion Total PAE cost was similar between the hospital and OBL settings. However, longer periprocedural times for hospital-based procedures and differences in reimbursement may favor the performance of PAE in an OBL setting.

Attenuation of testosterone-induced benign prostatic hyperplasia with Andrographis paniculata (burm.f.) leaf extract in Wistar rats.

Andrographis paniculata (Burm.f.) Nees has been used traditionally in treating many diseases. This study investigated its potential to attenuate benign prostatic hyperplasia (BPH) in male rats. Rats were castrated, divided into five groups and orally treated for 14 days with: normal saline,10 mg/kg testosterone propionate sc, finasteride (0.5 mg/kg), 500 mg, and 1500 mg/kg of Andrographis paniculata. Relative prostate weights, the correlation between prostatic index and volume and the prostates' histopathology as well as Prostate Specific Antigen (PSA) were evaluated. Following treatment with Andrographis paniculata, the prostate weights were significantly reduced (p < 0.05) and the lost correlation observed in the untreated group was restored. Histopathological assessment showed reduced epithelial hyperplasia following treatment with a resultant thin layer of epithelial cells, similar to the healthy normal control group. The level of PSA was also reduced. Andrographis paniculata, thus, has the potential to inhibit the proliferation observed in testosterone-induced BPH.

Predictors of Postoperative Urinary Incontinence After Holmium Laser Enucleation of the Prostate (HoLEP) for Surgeons Early in Their Experience.

OBJECTIVES: To evaluate factors impacting continence recovery following holmium laser enucleation of the prostate (HoLEP) for surgeons early in their HoLEP experience. METHODS: Predefined factors were evaluated from a prospectively maintained database for their impact on the recovery of continence after HoLEP. Both surgeons had performed fewer than 150 HoLEPs as attending physicians. Inclusion criteria were subjects with at least 6 months of incontinence data or documented recovery of continence. One or fewer pads per day was defined as continence. Statistical analyses were performed using R and Prism and included Spearman correlations, linear modeling, and Mantel-Cox log-rank testing as appropriate. RESULTS: From December 2020 to May 2023, 152 subjects met inclusion criteria with a median age of 70 (range: 51-93). The median case number was 56 (1-146). Within the study period, 144/152 (94.7%) recovered continence at a median of 1.6 months postoperatively. Linear modeling demonstrated that younger age (p = 0.01) and shorter enucleation time (p = 0.001) predicted recovery. Enucleation time less than 100 min predicted earlier continence recovery based on Mantel-Cox testing (p = 0.0004). CONCLUSIONS: During the surgeons' HoLEP learning curve, age, and enucleation time were predictive of the recovery of continence. Enucleation time under 100 min predicted a faster rate of continence recovery. The relationship between enucleation time and continence recovery may be demonstrative of case difficulty or may be a result of pressure on the external urethral sphincter during enucleation. These findings further our understanding of HoLEP outcomes early in a surgeon's learning curve.

Androgenic Alopecia Is Associated With More Severe Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

OBJECTIVES: To evaluate the possible association between androgenic alopecia (AGA) and lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). METHODS: A total of 148 patients aged over 45 with LUTS secondary to BPH were prospectively enrolled in this study. According to the Norwood-Hamilton classification, the patients were divided into two groups: AGA (n = 69) and non-AGA (n = 79). In addition, the cases of AGA were categorized as vertex (n = 39) and frontal baldness (n = 30). The International Prostate Symptom Score (IPSS), uroflowmetry parameters, prostate volume, serum total testosterone (TT), and free and total prostate-specific antigen concentrations of all patients were assessed and compared between the groups. Correlations between the AGA grade and other variables were also investigated. RESULTS: The serum TT level (354 ± 97.1 vs. 308.6 ± 73.1 ng/dL, p = 0.01), total IPSS (16.1 ± 8.1 vs. 13.4 ± 7.7, p = 0.04), IPSS storage subscore (IPSS-S) (7.1 ± 3.5 vs. 5.8 ± 3.6, p = 0.03), and number of nocturia episodes (2.5 ± 1.4 vs. 1.8 ± 1.4, p < 0.01) were significantly higher in the AGA group than in the non-AGA group. There were no significant differences in any of the parameters between the patients with vertex and frontal baldness. The AGA grade showed a significant positive correlation with the TT level (r = 0.407, p = 0.003), IPSS-S (r = 0.164, p = 0.04), and number of nocturia episodes (r = 0.203, p = 0.015). CONCLUSIONS: This study demonstrated that among patients with LUTS, those with AGA had worse symptoms and higher TT levels compared with those without AGA of similar age. Furthermore, the AGA grade was positively correlated with the TT level and storage symptoms.

An antibody-drug conjugate for endometrioid carcinoma based on the expression of cell adhesion molecule 1.

Cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is expressed in endometrial glandular cells highly during the proliferative phase but lowly during the secretory phase. Previously, a CADM1-targeting antibody-drug conjugate (ADC) was generated, in which a humanized anti-CADM1 ectodomain antibody h3E1 was linked with monomethyl auristatin E (h3E1-MMAE ADC). The present study aimed at probing whether this ADC could be useful for the treatment of endometrial neoplasm. Firstly, immunohistochemistry for CADM1 was conducted on proliferative-phase endometrium (n = 13), endometrial hyperplasia (n = 35), and endometrioid carcinoma at various stages (n = 166). CADM1 immunostaining intensity was highest in atypical endometrial hyperplasia and endometrioid carcinoma confined within the endometrium and was decreased stepwise as the carcinoma stage progressed. Next, h3E1-MMAE ADC was examined for its cytotoxicity in vitro using human endometrial adenocarcinoma cell lines expressing CADM1; HEC-1B, HEC-50B, JHUM-3, and OMC-2. The ADC killed these cells in a dose-dependent manner with half maximal inhibitory concentration (IC50) of 12.02 nM for HEC-1B and 2.04 nM for HEC-50B. Collectively, h3E1-MMAE ADC may serve as a noninvasive alternative to simple hysterectomy in the treatment of endometrioid carcinoma confined within the endometrium.

Few-shot learning to identify atypical endometrial hyperplasia and endometrial cancer based on transvaginal ultrasonic images.

Objective: It is challenging to accurately distinguish atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) under routine transvaginal ultrasonic (TVU) detection. Our research aims to use the few-shot learning (FSL) method to identify non-atypical endometrial hyperplasia (NAEH), AEH, and EC based on limited TVU images. Methods: The TVU images of pathologically confirmed NAEH, AEH, and EC patients (n = 33 per class) were split into the support set (SS, n = 3 per class) and the query set (QS, n = 30 per class). Next, we used dual pretrained ResNet50 V2 which pretrained on ImageNet first and then on extra collected TVU images to extract 1*64 eigenvectors from the TVU images in SS and QS. Then, the Euclidean distances were calculated between each TVU image in QS and nine TVU images of SS. Finally, the k-nearest neighbor (KNN) algorithm was used to diagnose the TVU images in QS. Results: The overall accuracy and macro precision of the proposed FSL model in QS were 0.878 and 0.882 respectively, superior to the automated machine learning models, traditional ResNet50 V2 model, junior sonographer, and senior sonographer. When identifying EC, the proposed FSL model achieved the highest precision of 0.964, the highest recall of 0.900, and the highest F1-score of 0.931. Conclusions: The proposed FSL model combining dual pretrained ResNet50 V2 eigenvectors extractor and KNN classifier presented well in identifying NAEH, AEH, and EC patients with limited TVU images, showing potential in the application of computer-aided disease diagnosis.

Silencing of PCK1 mitigates the proliferation and migration of vascular smooth muscle cells and vascular intimal hyperplasia by suppressing STAT3/DRP1-mediated mitochondrial fission.

The pathological proliferation and migration of vascular smooth muscle cells (VSMCs) are key processes during vascular neointimal hyperplasia (NIH) and restenosis. Phosphoenolpyruvate carboxy kinase 1 (PCK1) is closely related to a variety of malignant proliferative diseases. However, the role of PCK1 in VSMCs has rarely been investigated. This study aims to examine the role of PCK1 in the proliferation and migration of VSMCs and vascular NIH after injury. In vivo, extensive NIH and increased expression of PCK1 within the neointima are observed in injured arteries. Interestingly, the administration of adeno-associated virus-9 (AAV-9) carrying Pck1 short hairpin RNA (sh Pck1) significantly attenuates NIH and stenosis of the vascular lumen. In vitro, Pck1 small interfering RNA (si Pck1)-induced PCK1 silencing inhibits VSMC proliferation and migration. Additionally, silencing of PCK1 leads to reduced expression of dynamin-related protein 1 (DRP1) and attenuated mitochondrial fission. Lentivirus-mediated DRP1 overexpression markedly reverses the inhibitory effects of PCK1 silencing on VSMC proliferation, migration, and mitochondrial fission. Finally, PCK1 inhibition attenuates the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Activation of STAT3 abolishes the suppressive effects of PCK1 silencing on DRP1 expression, mitochondrial fission, proliferation, and migration in VSMCs. In conclusion, PCK1 inhibition attenuates the mitochondrial fission, proliferation, and migration of VSMCs by inhibiting the STAT3/DRP1 axis, thereby suppressing vascular NIH and restenosis.

Kimura disease: A rare case in Vietnamese woman.

Kimura disease (KD) is a rare benign chronic inflammatory condition that predominantly affects Asian males. It is characterized by subcutaneous tissue masses in the head and neck region, enlarged lymph nodes, increased blood eosinophilia, and elevated serum total IgE levels. In this report, we describe a rare case of KD in a young Vietnamese female. A 31-year-old Vietnamese woman presented to the hospital with 2 masses in the bilateral cheeks and 1 mass behind the left ear that persisted for 15 years, recurrent skin itching, elevated serum total IgE levels, and increased blood eosinophilia. No medical history of the individual or family was recorded. We performed an excision biopsy of the postauricular mass that revealed follicular hyperplasia with small vessel hyperplasia, diffuse infiltration of eosinophils in lymphoid follicles, and several eosinophilic microabscesses. After a comprehensive review, the final diagnosis for this patient was KD and atopic dermatitis comorbidity. In conclusion, KD is not limited to males, as this report demonstrated. The histopathological examination plays an important role in the diagnosis of KD. This case illustrated the characteristic description of KD and highlights the need for awareness of this rare disease in Asian women.

Incidental Prostate Cancer in Patients Undergoing Surgery for Benign Prostatic Hyperplasia: A Predictive Model.

BACKGROUND AND OBJECTIVE: Histopathological examination of surgical specimens for benign prostatic hyperplasia (BPH) can detect incidental prostate cancer (iPCa). The aim of our study was to develop a predictive model for iPCa diagnosis for patients for whom BPH surgery is being considered. METHODS: We conducted a retrospective analysis of medical files for patients who underwent BPH surgery in three academic centers between 2012 and 2022. Patients diagnosed with PCa before surgery were excluded. We calculated the global iPCa rate, and the clinically significant iPCa rate (grade group ≥2). Univariate and multivariable regression models were used to assess factors predictive of iPCa. The area under the receiver operating characteristic curve (AUC) was compared for each risk factor and for the global model. We used χ2 automated interaction detection (CHAID) for decision tree analysis. KEY FINDINGS AND LIMITATIONS: We included 2452 patients in the analysis, of whom 247 (10.0%) had iPCa, which was clinically significant in 49/247 cases (20.2%). Multivariable analysis revealed that age and prostate-specific antigen density (PSAD) were independent predictive factors for iPCa diagnosis. The AUC for a model including age and PSAD was 0.65. CHAID analysis revealed that patients with PSAD >0.1 ng/ml/cm3 had an iPCa risk of 23.4% (χ2 = 52.6; p < 0.001). For those patients, age >72 yr increased the iPCa risk to 35.4% (χ2 = 11.1, p = 0.008). Our study is mainly limited by its retrospective design. CONCLUSIONS AND CLINICAL IMPLICATIONS: Age and PSAD were independent risk factors for iPCa diagnosis. The combination of age >72 yr and PSAD >0.1 ng/ml/cm3 was associated with an iPCa rate of 35.4%. PATIENT SUMMARY: We performed a study to find predictors of prostate cancer for patients undergoing surgery for benign enlargement of the prostate. Our model can identify patients at risk, and diagnose their cancer before surgery. This could avoid unnecessary or harmful procedures.