Lung cancer metastasis to adrenocortical adenomas. A chance occurrence or a predilected phenomenon?

To evaluate the common belief that cancer metastasis to adrenocortical adenomas is a predilected phenomenon, we compared the real incidence of cancer metastasis obtained by analyzing the autopsy results of our 160 lung cancer cases, as well as those found by reviewing the literature, with the theoretical incidence obtained through the simulation models we made. The results disclosed that statistically, the real incidence was significantly higher than the theoretical probability. Therefore, we concluded that the metastasis of lung carcinoma to adrenocortical adenomas is indeed predilected.     

Follicle structure-dependency of thyroglobulin and thyroxin staining in the thyroid glands of Graves' disease

H.E. morphology of the thyroid glands from 170 patients with Graves' disease was studied, and the thyroid follicles were classified into two main groups: (1) F pattern, in which the follicles show circle/ellipse on cut sections; (2) P pattern, in which the follicular epithelium protrudes into the lumen or a follicle, is accompanied by proliferation of tubular or microfollicular structures. Studies on three serial sections of 88 thyroid glands stained with hematoxylin and eosin, thyroglobulin (TG), and thyroxin (T4), respectively, revealed the followings: (i) TG/T4 staining is dependent on the follicle structure (i.e., F or P); while the epithelium and colloid including scalloped vesicles in F follicles generally exhibited a direct relationship between TG and T4 staining, those in P follicles often showed an intense TG, but negative T4 staining. (ii) The results of morphological and immunohistochemical studies of P follicles among the cases are consistent with the view that P follicles are in the process of proliferation of immature daughter follicles from a main follicle and of their maturation. (iii) P follicles of Graves' thyroid glands were evaluated as possible non-neoplastic counterparts of well-differentiated follicular and papillary tumors.     

Three-dimensional distribution patterns of PRL,GH and ACTH cells in the house musk shrew ( Suncus murinus)

Despite a multitude of reports on the classification and distribution of anterior pituitary cells, no previous study has attempted to obtain the three-dimensional (3D) and computer-graphic distribution pattern of each cell type in the whole pituitary. Therefore, we mapped the anterior pituitary cells of the house musk shrew ( Suncus murinus) and found a distinct cellular distribution pattern. Serial horizontal sections of whole shrew pituitaries were stained immunohistochemically for prolactin (PRL), growth hormone (GH), and adrenocorticotropic hormone (ACTH) cells. The contours of positive cells and the anterior, intermediate, and posterior lobes in each section were digitized for 3D visualization by a volume rendering method. The reconstructed images and virtual frontal and sagittal slices were examined in detail. On the 3D reconstructed images, the PRL and GH cells had similar distribution patterns, although the former were concentrated in the dorsolateral and ventrocentral portions, and the latter in the dorsocentral portions of the anterior lobe. On both sides of the pituitary stalk, there lay portions that were conspicuous by scarcity of PRL and GH cells. ACTH cells were widely scattered throughout the whole anterior lobe, but they were very few in the above portions and the dorsocentral portions where GH cells were concentrated. No sex difference in the distribution patterns of each cell type was observed. However, PRL cells in females were more numerous than in males, whereas the opposite was true for GH and ACTH cells. We discuss the relationship between the formation of the spatial distribution patterns and anterior pituitary ontogeny.     

Association between Vitamin D and Heart Failure Mortality in 10,974 Hospitalized Individuals

A broad range of chronic conditions, including heart failure (HF), have been associated with vitamin D deficiency. Existing clinical trials involving vitamin D supplementation in chronic HF patients have been inconclusive. We sought to evaluate the outcomes of patients with vitamin D supplementation, compared with a matched cohort using real-world big data of HF hospitalization. This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). After exclusion criteria, we identified 93,692 patients who were first hospitalized with HF between April 2012 and March 2017 (mean age was 79 ± 12 years, and 52.2% were male). Propensity score (PS) was estimated with logistic regression model, with vitamin D supplementation as the dependent variable and clinically relevant covariates. On PS-matched analysis with 10,974 patients, patients with vitamin D supplementation had lower total in-hospital mortality (6.5 vs. 9.4%, odds ratio: 0.67, p < 0.001) and in-hospital mortality within 7 days and 30 days (0.9 vs. 2.5%, OR, 0.34, and 3.8 vs. 6.5%, OR: 0.56, both p < 0.001). In the sub-group analysis, mortalities in patients with age < 75, diabetes, dyslipidemia, atrial arrhythmia, cancer, renin-angiotensin system blocker, and β-blocker were not affected by vitamin D supplementation. Patients with vitamin D supplementation had a lower in-hospital mortality for HF than patients without vitamin D supplementation in the propensity matched cohort. The identification of specific clinical characteristics in patients benefitting from vitamin D may be useful for determining targets of future randomized control trials.     

Comparison of benign and malignant insulinoma

BackgroundHow malignant insulinomas present relative to benign insulinomas is unknown.MethodsA single-institution retrospective study identified patients with insulinoma. Malignancy was defined by distant metastases, positive lymph node(s), T stage of 4, direct invasion into surrounding peripancreatic tissue, or presence of lymphovascular invasion. Wilcoxon Rank Sum tests and Kaplan-Meier analysis were used.ResultsA total of 311 patients were identified: 51 malignant and 260 benign. Patients with malignant insulinoma presented with higher levels of insulin, proinsulin, and c-peptide. Malignant lesions were larger: 4.2 ± 3.2 vs 1.8 ± 0.8 cm in benign lesions, p < 0.01. Overall survival at 5 years was 66.8% vs 95.4% for malignant and benign insulinoma respectively, p < 0.01.ConclusionsLarger size of insulinoma and increased serum β-cell polypeptide concentrations were associated with malignancy. Malignant insulinoma has poorer survival. Further work-up to rule out malignancy may be indicated for larger pancreatic lesions and for patients with higher pre-operative insulin and pro-insulin.     

New vaccine production platforms used in developing SARS-CoV-2 vaccine candidates

The threat of the current coronavirus disease pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is accelerating the development of potential vaccines. Candidate vaccines have been generated using existing technologies that have been applied for developing vaccines against other infectious diseases. Two new types of platforms, mRNA- and viral vector-based vaccines, have been gaining attention owing to the rapid advancement in their methodologies. In clinical trials, setting appropriate immunological endpoints plays a key role in evaluating the efficacy and safety of candidate vaccines. Updated information about immunological features from individuals who have or have not been exposed to SARS-CoV-2 continues to guide effective vaccine development strategies. This review highlights key strategies for generating candidate SARS-CoV-2 vaccines and considerations for vaccine development and clinical trials.     

Dose-response relation and time course of

The dose-response relation of pipecuronium, the time course of its neuromuscular blocking effects, and the reversibility of the residual block by neostigmine have been investigated in patients under sevoflurane/N₂O Anesthesia using a neuromuscular transmission analyzer (Accelograph^®, Biometer, Denmark). After an initial dose of pipecuronium (0.04mg·kg^–1, i.v.), the maximum block rate, onset time, the time from administration until 25% recovery and 50% recovery of control twitch height of the first response to train-of-four nerve stimulation and the interval time of administration of maintenance dose (0.005mg·kg^–1, i.v.) were 93.7 ± 7.68%, 5.0 ± 1.84, 55.4 ± 23.92, 73.0 ± 29.44 and 38.7 ± 15.50 minutes, respectively. The average intubation score (excellent; 0, good; 1 fair; 2, poor; 3) was 0.63 ± 0.56 at the level of 95.88 ± 5.06% block. Neostigmine (1.5mg) promptly reversed the residual neuromuscular blockade induced by pipecuronium (reversal time: 10.1 ± 2.98 minutes). No side effects attributable to pipecuronium was seen in this study.In conclusion, pipecuronium is a very useful nondepolarizing neuromuscular blocking agent especially for moderately long surgical procedure over 4–5 hours.(Ueda N, Masuda Y, Muteki T, et al.: Does-response relation and time course of action of pipecuronium in patients anesthetized with nitrous oxide and sevoflurane. J Anesth 7: 151–156, 1993)     

Experimental study and clinical use of poly(vinyl acetate) emulsion as liquid embolisation material

A new material, an emulsion of poly(vinyl acetate) was experimentally developed and clinically used to overcome several disadvantages in currently used liquid embolisation materials. The emulsion microparticles, 0.3–0.7 m in size, possessed cationic charge on the surface and hence aggregated immediately on contact with fluids containing anions. This inert polymer has the advantage that it does not induce a deleterious reaction in living tissue. Moreover, its medium is water and it is not adhesive, like the cyanoacrylates. Several concentrations of emulsion were injected into the renal arteries of dogs. For the investigation of tissue reactions and the possibility of recanalisation, the emulsion was injected into rats both subcutaneously and into the renal arteries. The renal artery injections in dogs showed adequate radiopacity and consistent complete occlusion. The lower the concentration of the emulsion, the smaller the arteries which could be occluded. Even at very low concentrations, however, venous occlusion did not occur. Histological study of the embolised rat kidney revealed no detectable damage in the vessel wall and no recanalisation for up to 6 months. The subcutaneously injected PVAc emulsion elicited mononuclear cell infiltration and gradual centripetal fibrosis, without any deleterious effect on the surrounding tissue. A cerebral arteriovenous malformation (AVM) was embolised using the material. Histology of the resected nidus showed findings similar to those in the animal experiments.