Deep Learning-Based Computer-Aided Diagnosis of Osteochondritis Dissecans of the Humeral Capitellum Using Ultrasound Images.

BACKGROUND: Ultrasonography is used to diagnose osteochondritis dissecans (OCD) of the humerus; however, its reliability depends on the technical proficiency of the examiner. Recently, computer-aided diagnosis (CAD) using deep learning has been applied in the field of medical science, and high diagnostic accuracy has been reported. We aimed to develop a deep learning-based CAD system for OCD detection on ultrasound images and to evaluate the accuracy of OCD detection using the CAD system. METHODS: The CAD process comprises 2 steps: humeral capitellum detection using an object-detection algorithm and OCD classification using an image classification network. Four-directional ultrasound images of the elbow of the throwing arm of 196 baseball players (mean age, 11.2 years), including 104 players with normal findings and 92 with OCD, were used for training and validation. An external dataset of 20 baseball players (10 with normal findings and 10 with OCD) was used to evaluate the accuracy of the CAD system. A confusion matrix and the area under the receiver operating characteristic curve (AUC) were used to evaluate the system. RESULTS: Clinical evaluation using the external dataset resulted in high AUCs in all 4 directions: 0.969 for the anterior long axis, 0.966 for the anterior short axis, 0.996 for the posterior long axis, and 0.993 for the posterior short axis. The accuracy of OCD detection thus exceeded 0.9 in all 4 directions. CONCLUSIONS: We propose a deep learning-based CAD system to detect OCD lesions on ultrasound images. The CAD system achieved high accuracy in all 4 directions of the elbow. This CAD system with a deep learning model may be useful for OCD screening during medical checkups to reduce the probability of missing an OCD lesion. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Water-Mediated on-Demand Detachable Solid-State Adhesive of Porous Hydroxyapatite for Internal Organ Retractions.

Novel adhesives for biological tissues offer an advanced surgical approach. Here, we report the development and application of solid-state adhesives consisting of porous hydroxyapatite (HAp) biocompatible ceramics as novel internal organ retractors. The operational principles of the porous solid-state adhesives were experimentally established in terms of water migration from biological soft tissues into the pores of the adhesives, and their performance was evaluated on several soft tissues with different hydration states. As an example of practical medical utility, HAp adhesive devices demonstrated the holding ability of porcine livers and on-demand detachability in vivo, showing great potential as internal organ retractors in laparoscopic surgery. This article is protected by copyright. All rights reserved.

ATP2B1 gene polymorphisms associated with resistant hypertension in the Japanese population.

Single-nucleotide polymorphisms (SNP) of ATP2B1 gene are associated with essential hypertension but their association with resistant hypertension (RHT) remains unexplored. The authors examined the relationship between ATP2B1 SNPs and RHT by genotyping 12 SNPs in ATP2B1 gene of 1124 Japanese individuals with lifestyle-related diseases. Patients with RHT had inadequate blood pressure (BP) control using three antihypertensive drugs or used ≥4 antihypertensive drugs. Patients with controlled hypertension had BP controlled using ≤3 antihypertensive drugs. The association between each SNP and RHT was analyzed by logistic regression. The final cohort had 888 (79.0%) and 43 (3.8%) patients with controlled hypertension and RHT, respectively. Compared with patients homozygous for the minor allele of each SNP in ATP2B1, a significantly higher number of patients carrying the major allele at 10 SNPs exhibited RHT (most significant at rs1401982: 5.8% vs. 0.8%, p = .014; least significant at rs11105378: 5.7% vs. 0.9%, p = .035; most nonsignificant at rs12817819: 5.1% vs. 10%, p = .413). After multivariate adjustment for age, sex, systolic BP, and other confounders, the association remained significant for rs2681472 and rs1401982 (OR: 7.60, p < .05 and OR: 7.62, p = .049, respectively). Additionally, rs2681472 and rs1401982 were in linkage disequilibrium with rs11105378. This study identified two ATP2B1 SNPs associated with RHT in the Japanese population. rs1401982 was most closely associated with RHT, and major allele carriers of rs1401982 required significantly more antihypertensive medications. Analysis of ATP2B1 SNPs in patients with hypertension can help in early prediction of RHT and identification of high-risk patients who are more likely to require more antihypertensive medications.

Can endometrial cytology identify patients who would benefit from immunotherapy?

INTRODUCTION: Patients with POLE (polymerase epsilon) mutation (POLEmut)-subtype, MMR-deficient (MMR-d)-subtype as classified by the Cancer Genome Atlas (TCGA), and a high tumor mutation burden (TMB-high) potentially benefit from immunotherapy. However, characteristics of the cytological morphology within these populations remain unknown. METHODS: DNA extracted from formalin fixed paraffin embedded tissues was subjected to next-generation sequencing analysis. Genomic mutations related to gynecological cancers, TMB, and microsatellite instability (MSI) were analyzed and were placed in four TCGA classification types. The following morphological cytological investigations were conducted on endometrial cancer using a liquid-based preparation method, prior to the commencement of initial treatment: i) cytological backgrounds; ii) differences between each count of neutrophils and lymphocytes as described below. RESULTS: Insignificant differences in the cytological background patterns of TCGA groups and TMB status were found. Although there was no significant difference in neutrophil count (p= 0.955) in the TCGA groups, POLEmut and MMR-d had significantly higher lymphocyte counts than no specific molecular profile (NSMP) (p= 0.019 and 0.037, respectively); furthermore, p53mut also tended to be significant (p= 0.064). Lymphocyte counts in TMB-high were also significantly greater than TMB-low (p= 0.002). POLEmut showed a positive correlation between TMB levels and lymphocyte counts. For predicting patients with POLEmut plus MMR-d, lymphocyte counts demonstrated a superior diagnostic accuracy of Area Under the Curve(AUC)(0.70, 95% CI: 0.57-0.84), with a cut-off value of 26 high-power field(HPF). CONCLUSION: Lymphocyte count using liquid-based cytology for patients with endometrial cancer may predict POLEmut plus MMR-d of TCGA groups and TMB-high in those who can benefit from immunotherapy.

Metastatic small cell bladder cancer treated with sequential systemic therapy including pembrolizumab and amrubicin: A case report.

Introduction: Small cell bladder cancer is a relatively rare tumor, representing <1% of all bladder tumors. Amrubicin monotherapy is used as second-line treatment for small cell lung cancer in Japan. Case presentation: A 79-year-old woman presented with gross hematuria and was diagnosed with small cell bladder cancer (T2 or higher). Neoadjuvant chemotherapy with etoposide and cisplatin resulted in a partial response. Robot-assisted radical cystectomy was performed, and radical resection was achieved. As we identified metastasis in the pleura 1 year later, we administered carboplatin and etoposide, which resulted in a partial response. Although pembrolizumab was initiated as maintenance therapy, it was not effective. Amrubicin was given as third-line therapy, and stable disease was achieved without serious adverse effect for 6 months. Conclusion: Although there is no established treatment for metastatic small cell bladder cancer, the current case report suggests the effectiveness of amrubicin in this setting.

Cigarette Smoking and Atherosclerotic Cardiovascular Disease.

The detrimental effects of cigarette smoking on cardiovascular health, particularly atherosclerosis and thrombosis, are well established, and more detailed mechanisms continue to emerge. As the fundamental pathophysiology of the adverse effects of smoking, endothelial dysfunction, inflammation, and thrombosis are considered to be particularly important. Cigarette smoke induces endothelial dysfunction, leading to impaired vascular dilation and hemostasis regulation. Factors contributing to endothelial dysfunction include reduced bioavailability of nitric oxide, increased levels of superoxide anion, and endothelin release. Chronic inflammation of the vascular wall is a central pathogenesis of smoking-induced atherosclerosis. Smoking systemically elevates inflammatory markers and induces the expression of adhesion molecules and cytokines in various tissues. Pattern recognition receptors and damage-associated molecular patterns play crucial roles in the mechanism underlying smoking-induced inflammation. Smoking-induced DNA damage and activation of innate immunity, such as the NLRP3 inflammasome, cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, and Toll-like receptor 9, are shown to amplify inflammatory cytokine expression. Cigarette smoke-induced oxidative stress and inflammation influence platelet adhesion, aggregation, and coagulation via adhesion molecule upregulation. Furthermore, it affects the coagulation cascade and fibrinolysis balance, causing thrombus formation. Matrix metalloproteinases contribute to plaque vulnerability and atherothrombotic events. The impact of smoking on inflammatory cells and adhesion molecules further intensifies the risk of atherothrombosis. Collectively, exposure to cigarette smoke exerts profound effects on endothelial function, inflammation, and thrombosis, contributing to the development and progression of atherosclerosis and atherothrombotic cardiovascular diseases. Understanding these intricate mechanisms highlights the urgent need for smoking cessation to protect cardiovascular health. This comprehensive review investigates the multifaceted mechanisms through which smoking contributes to these life-threatening conditions.

Deep learning-based osteochondritis dissecans detection in ultrasound images with humeral capitellum localization.

PURPOSE: Osteochondritis dissecans (OCD) of the humeral capitellum is a common cause of elbow disorders, particularly among young throwing athletes. Conservative treatment is the preferred treatment for managing OCD, and early intervention significantly influences the possibility of complete disease resolution. The purpose of this study is to develop a deep learning-based classification model in ultrasound images for computer-aided diagnosis. METHODS: This paper proposes a deep learning-based OCD classification method in ultrasound images. The proposed method first detects the humeral capitellum detection using YOLO and then estimates the OCD probability of the detected region probability using VGG16. We hypothesis that the performance will be improved by eliminating unnecessary regions. To validate the performance of the proposed method, it was applied to 158 subjects (OCD: 67, Normal: 91) using five-fold-cross-validation. RESULTS: The study demonstrated that the humeral capitellum detection achieved a mean average precision (mAP) of over 0.95, while OCD probability estimation achieved an average accuracy of 0.890, precision of 0.888, recall of 0.927, F1 score of 0.894, and an area under the curve (AUC) of 0.962. On the other hand, when the classification model was constructed for the entire image, accuracy, precision, recall, F1 score, and AUC were 0.806, 0.806, 0.932, 0.843, and 0.928, respectively. The findings suggest the high-performance potential of the proposed model for OCD classification in ultrasonic images. CONCLUSION: This paper introduces a deep learning-based OCD classification method. The experimental results emphasize the effectiveness of focusing on the humeral capitellum for OCD classification in ultrasound images. Future work should involve evaluating the effectiveness of employing the proposed method by physicians during medical check-ups for OCD.

Mitochondrial DNA is a key driver in cigarette smoke extract-induced IL-6 expression.

Smoking is an independent risk factor for atherosclerosis, the primary pathogenesis of which is inflammation. We recently reported that cigarette smoke extract (CSE) causes cytosolic and extracellular accumulation of both nuclear (n) and mitochondrial (mt) DNA, which leads to inflammation in human umbilical vein endothelial cells (HUVECs). In this study, we examined whether inflammation induction depends more on cytosolic nDNA or mtDNA, and which chemical constituents of CSE are involved. Acrolein (ACR), methyl vinyl ketone (MVK), and 2-cyclopenten-1-one (CPO) were used in the experiments, as these are the major cytotoxic factors in CSE in various cell types. Stimulation with ACR, MVK, or CPO alone resulted in the accumulation of DNA double-strand breaks (DSBs), but not oxidative DNA damage, accumulation of cytosolic DNA, or increased expression of inflammatory cytokines. Simultaneous administration of all three constituents (ALL) resulted in oxidative DNA damage in both the nucleus and mitochondria, accumulation of DSBs, reduced mitochondrial membrane potential, induction of minority mitochondrial outer membrane permeabilization, accumulation of cytosolic free DNA, and increased expression of inflammatory cytokines such as IL-6 and IL-1α. Treatment with N-acetyl-L-cysteine, a reactive oxygen species scavenger, suppressed oxidative DNA damage and the increased expression of IL-6 and IL-1α induced by ALL or CSE. The ALL- or CSE-induced increase in IL-6 expression, but not that of IL-1α, was suppressed by mtDNA depletion. In conclusion, ACR, MVK, and CPO may strongly contribute to CSE-induced inflammation. More importantly, cytosolic free mtDNA is thought to play an important role in IL-6 expression, a central mediator of inflammation.

Bladder stone formation around polyethylene glycol after use of SpaceOAR Hydrogel.

Introduction: Radiation therapy is used as primary, adjuvant, and salvage therapy for prostate cancer. When using radiation therapy, the SpaceOAR® system is considered easy to use and useful for reducing the irradiated dose and toxicity to the rectum. Although SpaceOAR® system have been reported some adverse event including death. Case presentation: A 74-year-old male was diagnosed with prostate cancer of clinical stage cT2aN0M0 and intermediate risk by the National Comprehensive Cancer Network guidelines. We inserted the SpaceOAR® Hydrogel before performing intensity-modulated radiation therapy, as the patient had ulcerative colitis. We did not recognize any complications during or after the procedure, although magnetic resonance imaging revealed hydrogel in the bladder retrospectively. Fourteen months after the procedure, the patient was presented with macrohematuria and we found a bladder stone including hydrogel. Conclusion: We report the first case of a bladder stone after use of SpaceOAR® Hydrogel. We must be careful of taking place it.

Safety and efficacy of 5-aminolevulinic acid phosphate/iron in mild-to-moderate coronavirus disease 2019: A randomized exploratory phase II trial.

BACKGROUND: 5-aminolevulinic acid (5-ALA), a natural amino acid that is marketed alongside sodium ferrous citrate (SFC) as a functional food, blocks severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proliferation in vitro and exerts anti-inflammatory effects. In this phase II open-label, prospective, parallel-group, randomized trial, we aimed to evaluate the safety and efficacy of 5-ALA in patients with mild-to-moderate coronavirus disease 2019. METHODS: This trial was conducted in patients receiving 5-ALA/SFC (250/145 mg) orally thrice daily for 7 days, followed by 5-ALA/SFC (150/87 mg) orally thrice daily for 7 days. The primary endpoints were changes in SARS-CoV-2 viral load, clinical symptom scores, and 5-ALA/SFC safety (adverse events [AE] and changes in laboratory values and vital signs). RESULTS: A total of 50 patients were enrolled from 8 institutions in Japan. The change in SARS-CoV-2 viral load from baseline was not significantly different between the 5-ALA/SFC (n = 24) and control (n = 26) groups. The duration to improvement was shorter in the 5-ALA/SFC group than in the control group, although the difference was not significant. The 5-ALA/SFC group exhibited faster improvement rates in "taste abnormality," "cough," "lethargy," and "no appetite" than the control group. Eight AEs were observed in the 5-ALA/SFC group, with 22.7% of patients experiencing gastrointestinal symptoms (decreased appetite, constipation, and vomiting). AEs occurred with 750/435 mg/day in 25.0% of patients in the first phase and with 450/261 mg/day of 5-ALA/SFC in 6.3% of patients in the second phase. CONCLUSION: 5-ALA/SFC improved some symptoms but did not influence the SARS-CoV-2 viral load or clinical symptom scores over 14 days. The safety of 5-ALA/SFC in this study was acceptable. Further evaluation using a larger sample size or modified method is warranted.

Acute compartment syndrome caused by hematoma with minor trauma in hemodialysis patients: Two case reports.

INTRODUCTION: Acute compartment syndrome is a condition that requires an immediate diagnosis and surgical management. Compartment syndrome related to hematoma caused by minor trauma in hemodialysis patients is rarely reported. CASE PRESENTATION: We present two cases of hemodialysis patients diagnosed with compartment syndrome of the forearm due to hematoma caused by the disruption of blood vessels after a minor trauma. The removal of the hematoma and fasciotomy with adequate skin care significantly improved soft tissue heeling with no functional impairment. DISCUSSION: A long-term history of hemodialysis may increase the vascular vulnerability and have the potential risk of disruption by minor trauma. When the blood vessel is disrupted, a hematoma is formed and necessitating emergent surgical intervention. CONCLUSION: Surgeons should be aware of the potential risk of damage to blood vessels with minor trauma that results in the formation of a hematoma and compartment syndrome in hemodialysis patients.

Clinical availability and characteristics of multigene panel testing for recurrent/advanced gynecologic cancer.

BACKGROUND: Japan's health insurance covers multigene panel testing. This study aimed to determine the potential availability and utility of gene panel testing clinically in gynecologic oncology. METHODS: We analyzed the characteristics of patients with gynecologic cancer who underwent gene panel testing using FoundationOne® CDx or OncoGuide™ NCC Oncopanel between November 2019 and October 2022. RESULTS: Out of 102 patients analyzed, 32, 18, 43, 8, and 1 had cervical, endometrial, ovarian cancers, sarcoma, and vaginal cancer, respectively. Druggable gene alteration was found in 70 patients (68.6%; 21 with cervical cancer, 15 with endometrial cancer, 28 with ovarian cancer, 5 with sarcoma, and 1 with other). The most common druggable gene alteration was PIK3CA mutation (n = 21), followed by PTEN mutation (n = 12) and high tumor mutation burden (TMB-H) (n = 11). TMB-H was detected in 5 patients with cervical cancer, 5 with endometrial cancer, and 1 with endometrial stromal sarcoma. Eleven patients (10.8%) received molecularly targeted therapy according to their gene aberrations. Gene panel testing was mostly performed when the second-line treatment was ineffective. Of all 102 patients, 60 did not have recommended treatment, and 15 died or had worsened conditions before obtaining the test results. CONCLUSION: Through multigene panel testing, although many patients had druggable gene alterations, 10.8% of them received the recommended treatment. TMB-H was mainly observed in cervical/endometrial cancer, suggesting its potential as a therapeutic biomarker of immune checkpoint inhibitors. Furthermore, patients' prognosis and performance status should be considered before performing the test.

Molecular biological analysis revealed a case of synchronous endometrial and ovarian cancer with different histological grade as metastatic ovarian cancer from endometrial cancer: Case report and review of literature.

The diagnosis of synchronous endometrial and ovarian cancer or metastatic cancer of the same histological type is difficult. In this study, molecular biology analysis was performed to determine ovarian metastasis from endometrial cancer. A 38-year-old woman had pathological evidence of endometrial cancer (endometrioid carcinoma, grade 1) and ovarian cancer (endometrioid carcinoma, grade 3); a disseminated nodule in the serosa uteri was also diagnosed as endometrioid carcinoma (grade 3). Customized panel sequencing revealed a common mutation pattern in ovarian cancer and disseminated nodules. Furthermore, endometrial cancer showed the same mutation patterns for FGFR3 and PTEN as ovarian cancer and disseminated nodules. All tumors were microsatellite instability high. Clinicopathological and molecular biology analyses suggested that the patient had ovarian metastasis from endometrial cancer. The patient underwent adjuvant chemotherapy with paclitaxel and carboplatin, with no recurrence. Molecular biology techniques may enable appropriate treatment based on clinically accurate diagnosis.

Chapter 2:indications and dosing of anticancer drug therapy in patients with impaired kidney function, from clinical practice guidelines for the management of kidney injury during anticancer drug therapy 2022.

This comprehensive review discusses the dosing strategies of cancer treatment drugs for patients with impaired kidney function, specifically those with chronic kidney disease (CKD), undergoing hemodialysis, and kidney transplant recipients. CKD patients often necessitate dose adjustments of chemotherapeutic agents, e.g., platinum preparations, pyrimidine fluoride antimetabolites, antifolate agents, molecularly targeted agents, and bone-modifying agents, to prevent drug accumulation and toxicity due to diminished renal clearance of the administered drugs and their metabolites. In hemodialysis patients, factors such as drug removal from hemodialysis and altered pharmacokinetics demand careful optimization of anticancer drug therapy, including dose adjustment and timing of administration. While free cisplatin is removed by hemodialysis, most of the tissue- and protein-bound cisplatin remains in the body and rebound cisplatin elevations are observed after hemodialysis. It is not recommended hemodialysis for drug removal, regardless of timing. Kidney transplant patients encounter unique challenges in cancer treatment, as maintaining the balance between reduction of immunosuppression, switching to mTOR inhibitors, and considering potential drug interactions with chemotherapeutic agents and immunosuppressants are crucial for preventing graft rejection and achieving optimal oncologic outcomes. The review underscores the importance of personalized, patient-centric approaches to anticancer drug therapy in patients with impaired kidney function.

Renin-angiotensin-aldosterone system inhibitors as a risk factor for chronic subdural hematoma recurrence: A matter of debate.

OBJECTIVES: Chronic subdural hematoma (cSDH) is a common central nervous system condition. Recent reports indicate that cSDH affects long-term prognosis; however, its definitive risk factors remain unknown. An antihypertensive drug, renin-angiotensin-aldosterone system inhibitors (RAASi), can affect vascular permeability and cell proliferation processes, which may suppress the recurrence of cSDH. However, several studies have reported negative results to this effect. Therefore, we aimed to evaluate antihypertensive drugs, including RAASi, as risk factors for recurrent cSDH. MATERIALS AND METHODS: A total of 203 consecutive cases of surgically treated cSDH were retrospectively reviewed. Clinical and radiological parameters were compared between the groups with and without cSDH recurrence to identify risk factors. RESULTS: Of the included cases, 68 (33.5%) used RAASi and 37 (18.2%) developed recurrence within 60 days of surgery. In the multiple logistic regression analysis adjusted by composite risk score, the odds ratios (95% confidence interval) of RAASi, calcium channel blockers, diuretics, ß and α blockers, for the recurrent risk of cSDH after surgery were 2.49 (1.16, 5.42), 1.79 (0.84, 3.82), 1.83 (0.62, 4.87), 0.90 (0.28, 2.44), and 0.96 (0.21, 3.20), respectively. The Cox proportional hazard model also demonstrated that RAASi-use was an independent risk factor for cSDH recurrence. CONCLUSIONS: Present series suggests RAASi-use as a risk factor for cSDH recurrence, although the role of RAASi-use in cSDH remains debatable. Further studies for deeper understanding of the microenvironment of hematoma and the surroundings are preferable. (235 words).

Gastrointestinal Bleeding Due to the Rupture of Splenic Artery Caused by Pancreatic Carcinoma: A Case Requiring Repeated Transcatheter Arterial Embolization in a Short Period of Time.

In this report, we present a case of gastrointestinal bleeding due to splenic artery rupture, which required repeated transcatheter arterial embolization (TAE) within a short period of time. A 75-year-old man with pancreatic carcinoma was transported to our hospital with active hematemesis and vital signs consistent with shock. Contrast-enhanced computed tomography images showed a pancreatic tumor that had caused a pseudoaneurysm of the splenic artery to rupture. The pseudoaneurysm was embolized using only an N-butyl-2-cyanoacrylate (NBCA) and lipiodol mixture. However, hematemesis with signs of shock recurred 13 h later, and angiography showed rebleeding from the origin of the splenic artery. The splenic artery was subsequently embolized using an NBCA and lipiodol mixture. Repeated TAE finally controlled the hemorrhage; however, asymptomatic splenic infarction and hepatic infarction occurred due to nontarget embolization.

Dual Chalcogen-Bonding Interactions for the Conformational Control of Urea.

Dual chalcogen-bonding interactions is proposed as a novel means for the conformational control of urea derivatives. The formation of a chalcogen-bonding interaction at both sides of the urea carbonyl group was unambiguously confirmed by X-ray diffraction as well as computational studies including non-covalent interaction (NCI) plot index analysis, quantum theory of atoms in molecules (QTAIM) analysis, and natural bond orbital (NBO) analysis via DFT calculations. By virtue of this dual interaction, urea derivatives that bear chalcogen atoms (X=S and Se) adopt a planar structure via the carbonyl oxygen (O) with an X⋅⋅⋅O⋅⋅⋅X arrangement on the same side of the molecule. The rigidity of the conformational lock was evaluated using the molecular arrangement in the crystal and the rotational barrier of benzochalcogenophene ring, which indicated a stronger conformational lock in benzoselenophene than in benzothiophene urea derivatives. Furthermore, the acidity of the urea derivatives increases according to the Lewis-acidic properties of the chalcogen-bonding interactions, whereby benzoselenophene urea is more acidic than benzothiophene urea. Tweezer-shaped urea derivatives were prepared, and their stereostructure proved the viability of the conformational control for defining the location of the substituents on the urea framework.