Cutaneous sarcoidosis : Clinical features and management

1976年から1996年に岡山大学第2内科を受診したサルコイドーシス255例のうち,65例(71病変)の皮膚サルコイドーシス(皮膚サ症)について,臨床経過,臨床検査成績,胸部病変との関連,予後について検討した｡皮膚サ症患者の年齢は18歳から77歳で中央値は51歳であった｡女性例が42例(65%)と多 く,特に50歳代女性に43%と最も高率であった｡皮膚病型では結節型33例,皮下型16例,び慢浸潤型3例,局面型6例,結節性紅斑様皮疹3例,苔癬様型1例,瘢痕浸潤9例であった｡皮膚サ症では非皮膚サ症に比して気管支肺胞洗浄液中リンパ球の低率が見られたが,その他の臨床成績に差は認められなかった｡皮膚病型別に検討すると,局面型,び慢浸潤型では気管支肺胞洗浄液中リンパ球CD4/CD8比は高く,3年後の皮膚および肺病変の残存率は高かった｡一方皮下型ではCD4/CD8比は低く皮膚,肺病変の残存率も低かった｡Of 255 patients with clinical and histologic evidence of sarcoidosis, 65 (25percent) presented with various cutaneous manifestations of the disease. Cutaneous sarcoid patients were 42 women and 23 men ranging from 18 to 77 years in age. The skin lesions have included nodular infiltration in 33 patients, subcutaneous tumor in 16 patients, lupus pernio in 3, annual plaques in 6, erythema nodosum-like eruption in 3, lichinoid in 1, and scars in 9. There was no correlation between the presence of cutaneous lesions and chest radiolographic stages, abnormal pulmonary gallium uptake, cell differenciations of bronchoalveolar lavages and serum angiotensin converting enzyme activities. Forty-six patients followed for at least 3 years to determine the course of the disease. Subcutaneous tumors tended to heal within 3 years, while lupus pernio and plaque lesions were likely to have a protracted course

YES1 activation induces acquired resistance to neratinib in HER2-amplified breast and lung cancers

Molecular-targeted therapies directed against human epidermal growth factor receptor 2 (HER2) are evolving for various cancers. Neratinib is an irreversible pan-HER tyrosine kinase inhibitor and has been approved by the FDA as an effective drug for HER2-positive breast cancer. However, acquired resistance of various cancers to molecular-targeted drugs is an issue of clinical concern, and emergence of resistance to neratinib is also considered inevitable. In this study, we established various types of neratinib-resistant cell lines from HER2-amplified breast and lung cancer cell lines using several drug exposure conditions. We analyzed the mechanisms of emergence of the resistance in these cell lines and explored effective strategies to overcome the resistance. Our results revealed that amplification of YES1, which is a member of the SRC family, was amplified in two neratinib-resistant breast cancer cell lines and one lung cancer cell line. Knockdown of YES1 by siRNA and pharmacological inhibition of YES1 by dasatinib restored the sensitivity of the YES1-amplified cell lines to neratinib in vitro. Combined treatment with dasatinib and neratinib inhibited tumor growth in vivo. This combination also induced downregulation of signaling molecules such as HER2, AKT and MAPK. Our current results indicate that YES1 plays an important role in the emergence of resistance to HER2-targeted drugs, and that dasatinib enables such acquired resistance to neratinib to be overcome

One-step nucleic acid amplification for intraoperative diagnosis of lymph node metastasis in lung cancer patients: a single-center prospective study

One-step nucleic acid amplification (OSNA) is a rapid intraoperative molecular detection technique for sentinel node assessment via the quantitative measurement of target cytokeratin 19 (CK19) mRNA to determine the presence of metastasis. It has been validated in breast cancer but its application in lung cancer has not been adequately investigated. 214 LNs from 105 patients with 100 primary lung cancers, 2 occult primary lung tumors, and 3 metastatic lung tumors, who underwent surgical lung resection with LN dissection between February 2018 and January 2020, were assessed. Resected LNs were divided into two parts: one was snap-frozen for OSNA and the other underwent rapidly frozen histological examination. Intraoperatively collected LNs were evaluated by OSNA using loop-mediated isothermal amplification and compared with intraoperative pathological diagnosis as a control. Among 214 LNs, 14 were detected as positive by OSNA, and 11 were positive by both OSNA and intraoperative pathological diagnosis. The sensitivity and specificity of OSNA was 84.6% and 98.5%, respectively. The results of 5 of 214 LNs were discordant, and the remainder all matched (11 positive and 198 negative) with a concordance rate of 97.7%. Although the analysis of public mRNA expression data from cBioPortal showed that CK19 expression varies greatly depending on the cancer type and histological subtype, the results of the five cases, except for primary lung cancer, were consistent. OSNA provides sufficient diagnostic accuracy and speed and can be applied to the intraoperative diagnosis of LN metastasis for non-small cell lung cancer

Erfahrungen bei der Schuldrechtsmodernisierung in Deutschland (1)

監修：中田 那博、寺川

Significant Impact of Age on Mortality and Non-significant Impact of Age on Thrombosis and Major Bleeding in Patients with COVID-19: From the CLOT-COVID Study.

AIM: There is scarce data on the impact of age on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). METHOD: The CLOT-COVID Study was a retrospective, multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. We divided the entire cohort into five groups according to age strata; -19, 20-39, 40-59, 60-79, and 80- years. RESULTS: Most patients under 19 had mild COVID-19 on admission (99%), while older patients had more severe COVID-19. The incidence rates of clinical outcomes during hospitalization in patients aged ≤ 19, 20-39, 40-59, 60-79, and 80 ≥ years were 0.0%, 0.5%, 2.2%, 2.7%, and 1.5% for thrombosis; 0.0%, 1.2%, 1.5%, 3.4%, and 2.0% for major bleeding; and 0.0%, 0.4%, 2.0%, 12.1%, and 16.8% for all-cause death, respectively. In the stratified analysis according to COVID-19 severity on admission, the incidences of thrombosis were generally higher among patients with more severe status, although those were not significantly different among age strata in all sub-types of COVID-19 severity. However, the incidences of all-cause death were significantly higher with increasing age in all sub-types of COVID-19 severity. CONCLUSIONS: In the current large observational study of patients with COVID-19, the risk of mortality became markedly higher with increased age. However, the risks of thrombosis and major bleeding did not necessarily increase as age increases, which seemed to be consistent irrespective of COVID-19 severity on admission

The current status of thrombosis and anticoagulation therapy in patients with COVID-19 in Japan: From the CLOT-COVID study

BACKGROUND: Data on thrombosis and current real-world management strategies for anticoagulation therapy are scarce but important for understanding current issues and unmet needs of an optimal management of patients with coronavirus disease 2019 (COVID-19). METHOD: The CLOT-COVID Study (thrombosis and antiCoaguLatiOn Therapy in patients with COVID-19 in Japan Study: UMIN000045800) was a retrospective, multicenter cohort study enrolling consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021, and we tried to capture the status of the patients in the fourth and fifth waves of the COVID-19 infections in Japan. We enrolled consecutive hospitalized patients who were diagnosed with COVID-19 and had a positive polymerase chain reaction test obtained from the hospital databases. RESULTS: Among 2894 patients with COVID-19, 1245 (43%) received pharmacological thromboprophylaxis. The proportion of pharmacological thromboprophylaxis increased according to the severity of the COVID-19 in 9.8% with mild COVID-19, 61% with moderate COVID-19, and 97% with severe COVID-19. The types and doses of anticoagulants varied widely across the participating centers. During the hospitalization, 38 patients (1.3%) and 126 (4.4%) underwent ultrasound examinations for the lower extremities and contrast-enhanced computed tomography examinations, respectively, and 55 (1.9%) developed thrombosis, mostly venous thromboembolism (71%). The incidence of thrombosis increased according to the severity of the COVID-19 in 0.2% with mild COVID-19, 1.4% with moderate COVID-19, and 9.5% with severe COVID-19. Major bleeding occurred in 57 patients (2.0%) and 158 (5.5%) died, and 81% of them were due to respiratory failure from COVID-19 pneumonia. CONCLUSIONS: In the present large-scale observational study, pharmacological thromboprophylaxis for hospitalized patients with COVID-19 was common especially in patients with severe COVID-19, and management strategies varied widely across the participating centers. The overall incidence of thrombosis was substantially low with an increased incidence according to the severity of the COVID-19

Down-Sizing in Galaxy Formation at z~1 in the Subaru/XMM-Newton Deep Survey (SXDS)

We use the deep wide-field optical imaging data of the Subaru/XMM-Newton Deep Survey (SXDS) to discuss the luminosity (mass) dependent galaxy colours down to z'=25.0 (5 x 10^9 h_{70}^{-2} Msun) for z~1 galaxies in colour-selected high density regions. We find an apparent absence of galaxies on the red colour-magnitude sequence below z'~24.2, corresponding to ~M*+2 (~10^{10} Msun) with respect to passively evolving galaxies at z~1. Galaxies brighter than M*-0.5 (8 x 10^{10} Msun), however, are predominantly red passively evolving systems, with few blue star forming galaxies at these magnitudes. This apparent age gradient, where massive galaxies are dominated by old stellar populations while less massive galaxies have more extended star formation histories, supports the `down-sizing' idea where the mass of galaxies hosting star formation decreases as the Universe ages. Combined with the lack of evolution in the shape of the stellar mass function for massive galaxies since at least z~1, it appears that galaxy formation processes (both star formation and mass assembly) should have occurred in an accelerated way in massive systems in high density regions, while these processes should have been slower in smaller systems. This result provides an interesting challenge for modern CDM-based galaxy formation theories which predict later formation epochs of massive systems, commonly referred to as ``bottom-up''.Comment: proof corrected version (MNRAS in press), 10 pages, 12 figures (of which 3 are in jpg format