A novel prognostic model of de novo metastatic hormone-sensitive prostate cancer to optimize treatment intensity.

BACKGROUND: The treatment and prognosis of de novo metastatic hormone-sensitive prostate cancer (mHSPC) vary. We established and validated a novel prognostic model for predicting cancer-specific survival (CSS) in patients with mHSPC using retrospective data from a contemporary cohort. METHODS: 1092 Japanese patients diagnosed with de novo mHSPC between 2014 and 2020 were registered. The patients treated with androgen deprivation therapy and first-generation anti-androgens (ADT/CAB) were assigned to the Discovery (N = 467) or Validation (N = 328) cohorts. Those treated with ADT and androgen-receptor signaling inhibitors (ARSIs) were assigned to the ARSI cohort (N = 81). RESULTS: Using the Discovery cohort, independent prognostic factors of CSS, the extent of disease score ≥ 2 or the presence of liver metastasis; lactate dehydrogenase levels > 250U/L; a primary Gleason pattern of 5, and serum albumin levels ≤ 3.7 g/dl, were identified. The prognostic model incorporating these factors showed high predictability and reproducibility in the Validation cohort. The 5-year CSS of the low-risk group was 86% and that of the high-risk group was 22%. Approximately 26.4%, 62.7%, and 10.9% of the patients in the Validation cohort defined as high-risk by the LATITUDE criteria were further grouped into high-, intermediate-, and low-risk groups by the new model with significant differences in CSS. In the ARSIs cohort, high-risk group had a significantly shorter time to castration resistance than the intermediate-risk group. CONCLUSIONS: The novel model based on prognostic factors can predict patient outcomes with high accuracy and reproducibility. The model may be used to optimize the treatment intensity of de novo mHSPC.

Quantum error mitigation via quantum-noise-effect circuit groups.

Near-term quantum computers have been built as intermediate-scale quantum devices and are fragile against quantum noise effects, namely, NISQ devices. Traditional quantum-error-correcting codes are not implemented on such devices and to perform quantum computation in good accuracy with these machines we need to develop alternative approaches for mitigating quantum computational errors. In this work, we propose quantum error mitigation (QEM) scheme for quantum computational errors which occur due to couplings with environments during gate operations, i.e., decoherence. To establish our QEM scheme, first we estimate the quantum noise effects on single-qubit states and represent them as groups of quantum circuits, namely, quantum-noise-effect circuit groups. Then our QEM scheme is conducted by subtracting expectation values generated by the quantum-noise-effect circuit groups from those obtained by the quantum circuits for the quantum algorithms under consideration. As a result, the quantum noise effects are reduced, and we obtain approximately the ideal expectation values via the quantum-noise-effect circuit groups and the numbers of elementary quantum circuits composing them scale polynomial with respect to the products of the depths of quantum algorithms and the numbers of register bits. To numerically demonstrate the validity of our QEM scheme, we run noisy quantum simulations of qubits under amplitude damping effects for four types of quantum algorithms. Furthermore, we implement our QEM scheme on IBM Q Experience processors and examine its efficacy. Consequently, the validity of our scheme is verified via both the quantum simulations and the quantum computations on the real quantum devices. Our QEM scheme is solely composed of quantum-computational operations (quantum gates and measurements), and thus, it can be conducted by any type of quantum device. In addition, it can be applied to error mitigation for many other types of quantum noise effects as well as noisy quantum computing of long-depth quantum algorithms.

[Tumor Lysis Syndrome in a Patient with Germ Cell Tumor : A Case Report].

A 36-year-old man presented to our hospital with right scrotal swelling. A computed tomographic scan revealed a mass in the right scrotum, multiple masses in the lung and liver, and enlarged cervical, mediastinal, and retroperitoneal lymph nodes. After right high orchiectomy, he was diagnosed with nonseminomatous germ cell tumor (pT3N3M1b), with poor risk prediction according to the International Germ Cell Consensus classification. We started chemotherapy with bleomycin, etoposide, and cisplatin. Since serum alphafetoprotein (AFP) and human chorionic gonadotropin (HCG) levels did not decrease to normal levels, second-line chemotherapy with paclitaxel, ifosfamide, and cisplatin was administered. Six days after the start of treatment, the patient became unconscious, and his blood pressure decreased. Seven days later, blood tests revealed high uric acid levels, hyperphosphatemia, and increased creatinine. This was diagnosed as tumor lysis syndrome. Following diagnosis, continuous hemodiafiltration was started, and his condition gradually improved.

How do general practitioners handle complexities? A team ethnographic study in Japan.

BACKGROUND: General practitioners (GPs) are often faced with complex problems, including patients with socio-economic and medical problems. However, the methods they use to approach these complexities are still not understood. We speculated that elucidating these methods using complex adaptive systems (CAS) methodology to comprehensively assess GPs' daily activities would contribute to improving the professional development of GPs. This study aimed to clarify how expert GPs handle complex problems and adapt to their community context through the ethnography of GPs and other healthcare professionals in terms of CAS. METHODS: We adopted the interdisciplinary team-ethnographic research approach. Five hospitals and four clinics in Japan which were considered to employ expert GPs were selected by purposive sampling. 62 individuals of various backgrounds working in these nine facilities were interviewed. Using field notes and interview data, the researchers iteratively discussed the adequacy of our interpretations. The first author (JH) prepared a draft report, which was reviewed by the GPs at the participating facilities. Through critical and iterative consideration of the different insights obtained, the final findings emerged together with representative data. RESULTS: We identified four approaches used by GPs to deal with complexities. First, GPs treat patients with complex problems as a whole being and address their problems multi-directionally. Second, GPs build horizontal, trusting relationships with other healthcare professionals and stakeholders, and thereby reduce the degree of complexity of problems. Third, GPs change the learning climate while committing to their own growth based on societal needs and by acting as role models for other professionals through daily interpersonal facilitation. Fourth, GPs share community vision with multi-professionals and thereby act as a driving force for organizational change. These various interactions among GPs, healthcare professionals, organizations and communities resulted in systematization of the healthcare and welfare network in their community. CONCLUSIONS: Expert GPs developed interconnected multidimensional systems in their community health and welfare networks to adapt to fluctuating social realities using four approaches. GPs' work environment may be considered as a complex adaptive system (CAS) and the approach of GPs to complexities is CAS-based. Our findings are expected to have practical applications for GPs.

A rare case of intestinal lymphangiectasia induced by pazopanib.

A 62-year-old man underwent left radical nephrectomy for left renal cell carcinoma at our hospital in 1999. At the age of 79 years, he was diagnosed with intra-abdominal disseminations, lung metastases, pancreas metastases, and bilateral femoral muscle metastases during a routine follow-up computed tomography scan. The patient began treatment with pazopanib. Four years later, at the age of 83 years, he developed fever, abdominal pain, and general malaise. Blood samples showed liver dysfunction, hypoalbuminemia, and anemia. Contrast-enhanced computed tomography showed thickening of the small bowel wall with marked edema of the submucosa from the third part of the duodenum to the jejunum, suggesting intestinal lymphangiectasia. The diagnosis of intestinal lymphangiectasia was confirmed by small bowel endoscopy and histological examination. The patient's general condition improved after discontinuation of pazopanib without the need for any active therapeutic interventions. The possibility of intestinal lymphangiectasia should be considered in patients with hypoalbuminemia and general malaise during treatment with multikinase inhibitors.

[How have Japanese primary care physicians carried out vaccinations against COVID-19? : Attempts at making the non-scalable 'scalable']. / 日本のプライマリ・ケア医のコロナワクチン接種の実践についての文化人類学的考察­­ã‚¹ã‚±ãƒ¼ãƒ©ãƒ“リティとノンスケーラビリティのはざまで.

Vaccine rollouts have been underway to combat the COVID-19 pandemic globally. Based on ongoing interviews with ten primary care physicians 'in the field', this paper elucidates how in practice the vaccinations were carried out in Japan in 2021 from a cultural anthropological perspective. We examine what the primary care physicians did to prepare for the rollouts, what problems they faced, and how they responded to these problems. Large-scale vaccination projects are supposed to proceed smoothly and quickly, or to have what Anna Tsing calls 'scalability'. In practice, however, they required a variety of tasks for coordination, information sharing, and promotion. Despite feeling stressed by the lack of information and exhausted by the work overload, the primary care physicians carried out the vaccinations as an important service to their patients and communities. The findings of this paper will provide valuable materials for improving future vaccine rollouts.

Primary care physicians' narratives on COVID-19 responses in Japan: Professional roles evoked under a pandemic.

Background: Within the vague system of primary care and COVID-19 infection control in Japan, we explored how primary care (PC) physicians exhibited adaptive performance in their institutions and communities to cope with the COVID-19 pandemic from January to May 2020. Methods: Narrative analysis conducted by a team of medical professionals and anthropologists. We purposefully selected 10 PC physicians in community-based hospitals and clinics and conducted a total of 17 individual and group interviews. The verbatim transcript data were analyzed using the conceptual framework of adaptive performance. Results: We identified three "phases" of the time period (January-May 2020). In Phase 1, PC physicians initially perceived the disease as a problem unrelated to them. In Phase 2, the Diamond Princess outbreak triggered adaptive performance of the physicians, who began to deal with medical issues related to COVID-19 by using social networking services and applying the collected information to their organization and/or communities. Following this, in Phase 3, the PC physicians' adaptive performance in their own communities and institutions emerged in the face of the pandemic. Reflecting their sensitivity to local context, the PC physicians were seen to exhibit adaptive performance through dealing with context-dependent problems and relationships. Conclusions: PC physicians exhibited adaptive performance in the course of coping with the realities of COVID-19 in shifting phases and in differing localities in the early stages of the pandemic. The trajectories of adaptive performance in later stages of the pandemic remain to be seen.

Relaxation to Negative Temperatures in Double Domain Systems.

The engineering of quantum systems and their environments has led to our ability now to design composite or complex systems with the properties one desires. In fact, this allows us to couple two or more distinct systems to the same environment where potentially unusual behavior and dynamics can be exhibited. In this Letter we investigate the relaxation of two giant spins or collective spin ensembles individually coupled to the same reservoir. We find that, depending on the configuration of the two individual spin ensembles, the steady state of the composite system does not necessarily reach the ground state of the individual systems, unlike what one would expect for independent environments. Further, when the size of one individual spin ensemble is much larger than the second, collective relaxation can drive the second system to an excited steady state even when it starts in the ground state; that is, the second spin ensemble relaxes towards a negative-temperature steady state.

[A Case of Metastatic Clear Cell Renal Cell Carcinoma Showing Long-Term Complete Response after the Discontinuation of Tyrosine Kinase Inhibitor].

Randomized phase III trials demonstrated superiority of targeted therapy with tyrosine kinase inhibitors over cytokine-based therapy as first-line therapy for metastatic renal cell carcinoma. However, the rate of complete response (CR) with targeted therapy is smaller than that with cytokine-based therapy. A 47-year-old man was referred to our hospital with a 12 cm left renal tumor and polycythemia. He was diagnosed with renal cancer, cT3aN0M1, with multiple lung metastases. He underwent cytoreductive nephrectomy, with the histopathological diagnosis of clear cell renal cell carcinoma, Fuhrman nuclear grade 2, INFb, pT2b. Three months postoperatively, spontaneous regression of lung metastases was observed. Seventeen months postoperatively, a 17×13 mm retroperitoneal tumor facing the pancreas recurred. CR of the recurrent tumor was achieved by targeted therapy with sunitinib for 12 months. This CR was maintained for 32 months after the discontinuation of targeted therapy with sunitinib.

[Prostate Cancer Diagnosed during Androgen Replacement Therapy for Late-Onset Hypogonadism Treatment: A Case Report].

We report a 60-year-old man with prostate cancer diagnosed during androgen replacement therapy (ART) for late onset hypogonadism after surgery for pituitary adenoma. He was refered to the department of urology since prostate specific antigen values were elevated after 6 months of ART. After the diagnosis of prostate cancer, ART was discontinued, and robot-asssited laparoscopic radical prostatectomy with pelvic lymphadenoctomy was performed. Pathological examination revealed Gleason score 4 + 5 prostate adenocarcinoma with seminal vesicle invasion and lymph node metastasis(pT3bN1). He has stayed biochemically and radiologically disease-free 33 months postoperatively.

p62/SQSTM1 levels predicts radiotherapy resistance in hypopharyngeal carcinomas.

Hypopharyngeal carcinoma is one of the worst prognostic malignancies among head and neck carcinomas. Therefore, a good biomarker should be identified to predict the best therapeutic option before starting the treatment. In cell models, p62/SQSTM1 levels affected the Nrf2-Keap1 pathway, ROS levels, GSH/GSSG ratios and cell growth, especially under irradiation rather than under CDDP exposure, which was toxic despite p62/SQSTM1 status. In a clinical cohort of hypopharyngeal carcinomas, high levels of p62/SQSTM1 significantly predicted poor prognosis (log-rank test, Chi-square value = 6.750, P = 0.0094) and maximum critical risk (Cox proportional hazard ratio = 4.405, P = 0.0086), especially in the radiotherapy group. Therefore, when p62/SQSTM1 is elevated in the biopsy section, hypopharyngeal carcinoma should be treated with surgical and/or chemotherapeutic options.

Preparation of mouse monoclonal antibody for RB1CC1 and its clinical application.

RB1-inducible coiled-coil 1 (RB1CC1; also known as FIP200) plays important roles in several biological pathways such as cell proliferation and autophagy. Evaluation of RB1CC1 expression can provide useful clinical information on various cancers and neurodegenerative diseases. In order to realize the clinical applications, it is necessary to establish a stable supply of antibody and reproducible procedures for the laboratory examinations. In the present study, we have generated mouse monoclonal antibodies for RB1CC1, and four kinds of antibodies (N1-8, N1-216, N3-2, and N3-42) were found to be optimal for clinical applications such as ELISA and immunoblots and work as well as the pre-existing polyclonal antibodies. N1-8 monoclonal antibody provided the best recognition of RB1CC1 in the clinico-pathological examination of formalin-fixed paraffin-embedded tissues. These monoclonal antibodies will help to generate new opportunities in scientific examinations in biology and clinical medicine.