Stage IV renal cell carcinoma achieves pathologic complete response after two ipilimumab plus nivolumab courses despite severe immune-related adverse events: a case report.

BACKGROUND: Ipilimumab (Ipi) plus nivolumab (Nivo) is the recommended first-line treatment for renal cell carcinoma (RCC). This report describes a case where pancreatic metastases disappeared after only two courses of Ipi + Nivo therapy. The primary tumor was cured by surgery, and a pathological Complete Response (pCR) was observed despite multiple serious immune-related Adverse Events (irAEs). CASE PRESENTATION: A 54-year-old woman with RCC and pancreatic metastasis at stage IV, diagnosed with intermediate risk according to the International Metastatic RCC Database Consortium classification, underwent initiation of Ipi + Nivo therapy. On day 26, she developed hyperthyroidism accompanied by tachycardia, leading to the commencement of metoprolol tartrate treatment. Following the resolution of tachycardia, a second course of Ipi + Nivo therapy was administered on day 50. By day 70, the patient exhibited Grade 3 hepatic dysfunction, followed by the onset of hypothyroidism on day 75, necessitating treatment with steroids and levothyroxine. After positive treatment, a Grade 3 skin disorder emerged on day 87 while tapering steroids, prompting treatment with methylprednisolone (mPSL) pulse therapy. The skin disorder responded to steroids, allowing for tapering. However, on day 113, a recurrence of Grade 3 skin disorder occurred, necessitating another mPSL pulse. The patient responded well to treatment, exhibiting improvement in her condition. On day 131, she presented at the hospital with complaints of respiratory distress, prompting a Computed Tomography (CT) scan that revealed interstitial pneumonia. By day 272, subsequent CT imaging showed the disappearance of pancreatic metastasis and shrinkage of the primary tumor. On day 294, she underwent a laparoscopic left nephrectomy. Pathological analysis confirmed a pCR in the primary tumor, indicating successful eradication of RCC through surgical intervention. CONCLUSIONS: This case report presents a scenario where multiple severe irAEs appeared in a patient, yet metastases disappeared after only two courses of Ipi + Nivo therapy. The patient was ultimately cured by surgery and achieved a pCR. This case highlights that despite the occurrence of severe irAEs during RCC treatment with Ipi + Nivo therapy, they can be managed appropriately to maximize the therapeutic effects of checkpoint inhibitors.

Measurement of the Acetabular Cup Orientation After Total Hip Arthroplasty Based on 3-Dimensional Reconstruction From a Single X-Ray Image Using Generative Adversarial Networks.

BACKGROUND: The purpose of this study was to reconstruct 3-dimensional (3D) computed tomography (CT) images from single anteroposterior (AP) postoperative total hip arthroplasty (THA) X-ray images using a deep learning algorithm known as generative adversarial networks (GANs) and to validate the accuracy of cup angle measurement on GAN-generated CT. METHODS: We used 2 GAN-based models, CycleGAN and X2CT-GAN, to generate 3D CT images from X-ray images of 386 patients who underwent primary THAs using a cementless cup. The training dataset consisted of 522 CT images and 2,282 X-ray images. The image quality was validated using the peak signal-to-noise ratio and the structural similarity index measure. The cup anteversion and inclination measurements on the GAN-generated CT images were compared with the actual CT measurements. Statistical analyses of absolute measurement errors were performed using Mann-Whitney U tests and nonlinear regression analyses. RESULTS: The study successfully achieved 3D reconstruction from single AP postoperative THA X-ray images using GANs, exhibiting excellent peak signal-to-noise ratio (37.40) and structural similarity index measure (0.74). The median absolute difference in radiographic anteversion was 3.45° and the median absolute difference in radiographic inclination was 3.25°, respectively. Absolute measurement errors tended to be larger in cases with cup malposition than in those with optimal cup orientation. CONCLUSIONS: This study demonstrates the potential of GANs for 3D reconstruction from single AP postoperative THA X-ray images to evaluate cup orientation. Further investigation and refinement of this model are required to improve its performance.

Borane-Protecting Strategy for Hydrosilylation of Phosphorus-Containing Olefins.

Ir-catalyzed hydrosilylation of the alkenyl phosphine borane complex 1 was achieved to give the corresponding products 2. Because the phosphino group coordinates with metals and is unstable under aerobic conditions, the formation of the corresponding borane adduct was effective not only to promote the target hydrosilylation but also to keep 1 stable under aerobic conditions. The removal of coordinated borane from 2 was readily performed with the treatment by 1,4-diazabicyclo[2.2.2]octane to apply to further transformations. The immobilization and following deprotection of 2 on the surface of mesoporous silica were also examined.

Ift88 regulates enamel formation via involving Shh signaling.

OBJECTIVES: The ciliopathies are a wide spectrum of human diseases, which are caused by perturbations in the function of primary cilia. Tooth enamel anomalies are often seen in ciliopathy patients; however, the role of primary cilia in enamel formation remains unclear. MATERIALS AND METHODS: We examined mice with epithelial conditional deletion of the ciliary protein, Ift88, (Ift88fl / fl ;K14Cre). RESULTS: Ift88fl / fl ;K14Cre mice showed premature abrasion in molars. A pattern of enamel rods which is determined at secretory stage, was disorganized in Ift88 mutant molars. Many amelogenesis-related molecules expressing at the secretory stage, including amelogenin and ameloblastin, enamelin, showed significant downregulation in Ift88 mutant molar tooth germs. Shh signaling is essential for amelogenesis, which was found to be downregulated in Ift88 mutant molar at the secretory stage. Application of Shh signaling agonist at the secretory stage partially rescued enamel anomalies in Ift88 mutant mice. CONCLUSION: Findings in the present study indicate that the function of the primary cilia via Ift88 is critical for the secretory stage of amelogenesis through involving Shh signaling.

Successful treatment of BK virus-associated severe hemorrhagic cystitis with bilateral single-J ureteral stenting.

Introduction: BK virus-associated hemorrhagic cystitis is a significant complication of hematopoietic stem cell transplantation. Although severe BK virus-associated hemorrhagic cystitis is associated with treatment-related mortality, sufficient evidence regarding its management is lacking. Case presentation: A 14-year-old boy presented with BK virus-associated hemorrhagic cystitis and bladder clot retention after hematopoietic stem cell transplantation. Various urological interventions failed to improve cystitis. While bladder clot retention frequently recurred, surgical intervention was difficult because of the underlying hematological disorder. Hence, bilateral single-J ureteral stenting followed by Foley catheter placement was performed as a urinary diversion. The bladder clot completely disappeared 27 days after stenting. No additional procedure was required. BK virus-associated hemorrhagic cystitis did not recur after the blood clot disappeared. Conclusion: Bilateral single-J ureteral stenting followed by Foley catheter placement is a simple and effective treatment method and should be considered before surgical intervention for severe BK virus-associated hemorrhagic cystitis.

[The Method for Estimation of Radiation Dose of Eye Lens Covered by Radiation Protection Glasses Using Personal Dosimeter for Trunk of the Body and X-ray Shielding Material].

PURPOSE: Radiation protection glasses is a useful tool for dose reduction of eye lens. However, the method to evaluate the dose of eye lens, which is covered with radiation protection glasses in actual radiation management situation, has not been established. We invented the easy-to-use procedure to estimate the dose of eye lens inside of radiation protection glasses for occupationally exposed person using an X-ray shielding material and an additional personal dosimeter for trunk of the body. The objective of this study was to evaluate the feasibility of the new method. METHODS: The radiation field in interventional radiology (IR) was reconstructed. A personal dosimeter was set to the eye position and neck position of medical staff phantom. Each dosimeter was covered by radiation protection glasses or X-ray shielding material, and the 1 cm or 70 mm dose equivalent quantity in the neck position was compared to the 3 mm dose equivalent quantity in the eye position. RESULTS: The dose equivalent quantity measured inside of X-ray shielding material in the neck position was similar to that of inside radiation protection glasses. Thus, the X-ray attenuation by radiation protection glasses was able to be simulated using the X-ray shielding material. CONCLUSION: It was suggested that the dose of eye lens inside of radiation protection glasses could be easily estimated by covering the conventional personal dosimeter for trunk of the body with the X-ray shielding material.

Bacteremia Caused by Both Legionella pneumophila Serogroup 2 and Helicobacter cinaedi.

A 74-year-old woman with a history of pure red cell aplasia and hypogammaglobulinemia developed pneumonia. A urine antigen test and sputum subculture on buffered charcoal yeast extract (BCYE)α agar were positive for Legionella pneumophila. Serological testing identified L. pneumophila serogroup 2. An aerobic blood culture also became positive on day 5; its subculture on BCYEα agar revealed the same pathogen, but that on blood agar revealed Helicobacter cinaedi. We thus diagnosed her with bacteremia caused by both pathogens. Hence, in cases of H. cinaedi bacteremia along with pneumonia, the screening of other pathogens including L. pneumophila is needed.

Association Between Autistic Symptoms and Self-Stigma in Patients with Schizophrenia Spectrum Disorders.

PURPOSE: Self-stigma negatively influences self-esteem, quality of life, self-efficacy, treatment adherence, and recovery in psychiatric patients. By revealing personality traits that influence self-stigma, we can gain useful knowledge for the management of self-stigma. A previous meta-analysis indicated that patients with schizophrenia have higher scores on the Autism-Spectrum Quotient (AQ) than healthy controls. However, the relationship between autistic symptoms and self-stigma in patients with schizophrenia spectrum disorders remains unclear. Therefore, the present study aimed to reveal the association between autistic symptoms and self-stigma in patients with schizophrenia spectrum disorders. PATIENTS AND METHODS: We recruited 127 patients with schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, and delusional disorder). We assessed participants' self-stigma and autistic symptoms using the Internalized Stigma for Mental Illness (ISMI) scale and the Autism-Spectrum Quotient (AQ), respectively. The differences in the scores of ISMI and AQ according to patient characteristics were investigated. Multiple regression analysis controlling for age and gender was performed to determine the relationship between the total scores on the AQ and IMSI scale. RESULTS: Female patients showed a higher level of self-stigma than males. Unmarried patients showed a significantly higher score on the AQ than married patients. Multiple regression analysis adjusted for age and gender indicated that the total score on AQ might be a predictor of the overall rating on ISMI in patients with schizophrenia spectrum disorders. CONCLUSION: This study is the first to reveal the association between autistic symptoms and self-stigma in patients with schizophrenia spectrum disorders. Our results highlight the importance of considering autistic symptoms in the assessment and management of self-stigma in patients with schizophrenia spectrum disorders.

A case of pembrolizumab-induced hemophagocytic lymphohistiocytosis successfully treated with pulse glucocorticoid therapy.

Treatments using immune checkpoint inhibitors such as pembrolizumab lead to immune mediated adverse effects including hemophagocytic lymphohistiocytosis (HLH). Herein, we present a case where HLH developed after pembrolizumab administration, which was treated using high dose prednisolone. He developed high-grade fever complicated with liver dysfunction and diarrhea 7 days after pembrolizumab administration. Although treatment with oral prednisolone alleviated the symptoms, other adverse effects arose owing to a tapered prednisolone dose. Hyperferritinemia suggested the diagnosis of HLH and met the criteria for HLH diagnosis. He was thus administered intravenous pulses of methylprednisolone followed by high-dose oral prednisolone, which resolved these symptoms.

A comparison of the features of fluorine-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) between IgG4-related disease with bilateral hilar lymphadenopathy and sarcoidosis.

We aimed to show the differentiation of the degree and distribution on Fluorine-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) between patients with immunoglobulin G4-related disease (IgG4-RD) and sarcoidosis, though both diseases frequently show bilateral hilar lymphadenopathy (BHL). The clinical records were retrospectively reviewed in 25 patients with IgG4-RD with BHL and 15 patients with sarcoidosis (stage I-II) diagnosed at Shinshu University Hospital. All patients underwent FDG-PET at Aizawa Hospital from January 2004 to December 2015. The FDG accumulation pattern and maximum standardized uptake value (SUVmax) of the hilar lymph nodes were compared between the two groups. The IgG4-RD group (21 men; median age 69 years) showed a significant male predominance and older age compared with the sarcoidosis group (3 men, median age 55.4 years). The IgG4-RD group showed a significantly higher incidence of FDG accumulation in the lachrymal gland, submandibular gland, pancreas, prostate and periurethral and periarterial regions compared with the sarcoidosis group. In contrast, the sarcoidosis group showed a significantly higher incidence of FDG accumulation in the supraclavicular and abdominal lymph nodes, muscle and soft tissues compared with the IgG4-RD group. Furthermore, the SUVmax of the hilar lymph nodes was significantly higher in the sarcoidosis group (median 7.20) than in the IgG4-RD group (median 4.20, p=0.002). In conclusion, significant differences were observed in the FDG accumulation patterns and SUVmax values of the hilar lymph nodes between IgG4-RD with BHL and sarcoidosis, although both diseases develop through the lymphatic routes of the lungs and are frequently associated with BHL.