Inverse columnar-equiaxed transition (CET) in 304 and 316l stainless steels melt by electron beam for additive manufacturing (AM)

According to Hunt’s columnar-to-equiaxed transition (CET) criterion, which is generally accepted, a high-temperature gradient (G) in the solidification front is preferable to a low G for forming columnar grains. Here, we report the opposite tendency found in the solidification microstructure of stainless steels partially melted by scanning electron beam for powder bed fusion (PBF)-type additive manufacturing. Equiaxed grains were observed more frequently in the region of high G rather than in the region of low G, contrary to the trend of the CET criterion. Computational thermal-fluid dynamics (CtFD) simulation has revealed that the fluid velocity is significantly higher in the case of smaller melt regions. The G on the solidification front of a small melt pool tends to be high, but at the same, the temperature gradient along the melt pool surface also tends to be high. The high melt surface temperature gradient can enhance Marangoni flow, which can apparently reverse the trend of equiaxed grain formation.Miyata Y., Okugawa M., Koizumi Y., et al. Inverse columnar-equiaxed transition (CET) in 304 and 316l stainless steels melt by electron beam for additive manufacturing (AM). Crystals 11, 856 (2021); https://doi.org/10.3390/cryst11080856

MUC4 immunohistochemistry is useful in distinguishing epithelioid mesothelioma from adenocarcinoma and squamous cell carcinoma of the lung

The differential diagnosis of epithelioid mesothelioma from lung adenocarcinoma and squamous cell carcinoma requires the positive and negative immunohistochemical markers of mesothelioma. The IMIG guideline has suggested the use of Calretinin, D2–40, WT1, and CK5/6 as mesothelial markers, TTF-1, Napsin-A, Claudin 4, CEA as lung adenocarcinoma markers p40, p63, CK5/6, MOC-31 as squamous cell markers. However, use of other immunohistochemical markers is still necessary. We evaluated 65 epithelioid mesotheliomas, 60 adenocarcinomas, and 57 squamous cell carcinomas of the lung for MUC4 expression by immunohistochemistry and compared with the previously known immunohistochemical markers. MUC4 expression was not found in any of 65 cases of epithelioid mesothelioma. In contrast, MUC4 expression was observed in 50/60(83.3%) cases of lung adenocarcinoma and 50/56(89.3%) cases of lung squamous cell carcinoma. The negative MUC4 expression showed 100% sensitivity, 86.2% specificity and accuracy rate of 91.2% to differentiate epithelioid mesothelioma from lung carcinoma. The sensitivity, specificity, and accuracy of MUC4 are comparable to that of previously known markers of lung adenocarcinoma and squamous cell carcinoma, namely CEA, Claudin 4 and better than that of MOC-31. In conclusion, MUC4 immunohistochemistry is useful for differentiation of epithelioid mesothelioma from lung carcinoma, either adenocarcinoma or squamous cell carcinoma.The authors thank Ms. Yukari Go of the Technical Center in Hiroshima University for excellent technical assistance and Ms. Naomi Fukuhara for administrative assistance. This work was supported by JSPS KAKENHI Grant Number 17K08742

Neoadjuvant hormonal therapy for low-risk prostate cancer induces biochemical recurrence after radical prostatectomy via increased lymphangiogenesis-related parameters

Background: The effects of neoadjuvant hormonal therapy (NHT) on pathological features and lymphangiogenesis in patients with prostate cancer (PCa) for each pre-operative risk classification are unclear. Methods: To clarify the anti-cancer effects of NHT, we investigated 153 patients (non-NHT group?=?80 and NHT group?=?73) who underwent radical prostatectomy (RP) in Nagasaki University Hospital. Lymph vessel density and area (evaluated by D2-40-positive vessels), vascular endothelial growth factor (VEGF)-C and VEGF-D expressions, and biochemical recurrence (BCR)-free survival were compared between these two groups for each D\u27Amico risk classification (low?=?33, intermediate?=?58, high?=?62 patients). Results: In low-risk PCa patients, the risks of lymph vessel invasion and BCR were significantly higher in the NHT group than in the non-NHT group (P?=?0.040 and 0.022, respectively). Such significant difference was not seen in the intermediate- or high-risk PCa groups. Lymph vessel density of the peri-tumoral and intra-tumoral areas and the lymph vessel area were significantly higher (P?<?0.001) in the NHT group than in the non-NHT group in low-risk PCa. In regard to the expression of VEGF-C or VEGF-D, significant difference was not detected in low-risk PCa. Conclusions: NHT stimulated cancer cell progression and BCR via up-regulation of lymphangiogenesis-related parameters in patients with low-risk PCa. Although VEGF-C and VEGF-D expressions were not changed by NHT, lymph vessel density and area were increased in low-risk PCa patients. We suggest that NHT for patients with low-risk PCa may have a high risk for BCR after RP

Long-term results of a randomized controlled trial comparing neoadjuvant Adriamycin, cisplatin, and 5-fluorouracil vs docetaxel, cisplatin, and 5-fluorouracil followed by surgery for esophageal cancer (OGSG1003)

Sugimura, K, Yamasaki, M, Yasuda, T, et al. Long‐term results of a randomized controlled trial comparing neoadjuvant Adriamycin, cisplatin, and 5‐fluorouracil vs docetaxel, cisplatin, and 5‐fluorouracil followed by surgery for esophageal cancer (OGSG1003). Ann. Gastroenterol. Surg. 2020; 00: 1– 8. https://doi.org/10.1002/ags3.12388

Efficacy and survival of nivolumab treatment for recurrent/unresectable esophageal squamous-cell carcinoma: real-world clinical data from a large multi-institutional cohort

The version of record of this article, first published in Esophagus, is available online at Publisher’s website: https://doi.org/10.1007/s10388-024-01056-w.Background: Real-world clinical outcomes of and prognostic factors for nivolumab treatment for esophageal squamous-cell carcinoma (ESCC) remain unclear. This study aimed to evaluate real-world outcomes of nivolumab monotherapy in association with relevant clinical parameters in recurrent/unresectable advanced ESCC patients. Methods: This population-based multicenter cohort study included a total of 282 patients from 15 institutions with recurrent/unresectable advanced ESCC who received nivolumab as a second-line or later therapy between 2014 and 2022. Data, including the best overall response, progression-free survival (PFS), and overall survival (OS), were retrospectively collected from these patients. Results: Objective response and disease control rates were 17.0% and 47.9%, respectively. The clinical response to nivolumab treatment significantly correlated with development of overall immune-related adverse events (P <.0001), including rash (P <.0001), hypothyroidism (P =.03), and interstitial pneumonia (P =.004). Organ-specific best response rates were 20.6% in lymph nodes, 17.4% in lungs, 15.4% in pleural dissemination, and 13.6% in primary lesions. In terms of patient survival, the median OS and PFS was 10.9 and 2.4 months, respectively. Univariate analysis of OS revealed that performance status (PS; P <.0001), number of metastatic organs (P =.019), C-reactive protein-to-albumin ratio (CAR; P <.0001), neutrophil–lymphocyte ratio (P =.001), and PMI (P =.024) were significant. Multivariate analysis further identified CAR [hazard ratio (HR) = 1.61, 95% confidence interval (CI) 1.15–2.25, P =.0053)] in addition to PS (HR = 1.65, 95% CI 1.23–2.22, P =.0008) as independent prognostic parameters. Conclusions: CAR and PS before nivolumab treatment are useful in predicting long-term survival in recurrent/unresectable advanced ESCC patients with second-line or later nivolumab treatment

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

(Table 1) Wet and dry density and porosity of mudstone at DSDP 84 holes

Vein structure and related small fractures in muddy sedimentary Oligocene to Miocene rocks of Sites 568 and 569 have been analyzed to study the deformation and tectonics of the Middle America Trench landward slope area off Guatemala. These veins are filled with fine, clayey materials and essentially developed as extensional fracture cleavages perpendicular to the minimum principal compressive stress axis. Three stages are recognized; early stage fractures parallel to bedding (probably caused by bedding parallel slip), abundant fractures highly oblique or perpendicular to bedding, and veins formed at various angles during tilting. Most of the veins show drag or rotation features, which mostly show downdip sliding and probably occurred during stages of large-scale folding related to faulting or draping of the middle Trench slope area. Veins are concentrated only in the middle part of the Trench landward slope of the late Oligocene to middle Miocene sections, where high sedimentation rates and possible normal faulting and folding caused by local uplift of the basement occurred. This may indicate that the veins required rapid sediment consolidation, which caused abnormal lithificatio