[Diagnostic value of FNDC5 in patients with subclinical diabetic cardiomyopathy].

Objective: To estimate the diagnostic value of fibronectin type Ⅲ-domain containing protein 5 (FNDC5) in subclinical diabetic cardiomyopathy. Methods: A total of 94 patients with type 2 diabetes (T2DM), who were hospitalized from April 2018 to June 2019 in the Third Affiliated Hospital of Soochow University, were enrolled in this study. Patients were divided into T2DM with cardiac dysfunction (subclinical DCM) group (n=47) and T2DM without cardiac dysfunction (non-DCM) group (n=47) according to echocardiography and gated myocardial perfusion imaging results. Basic clinical data and serum FNDC5 level were compared between the two groups. Logistic regression analysis was used to establish predicting models and the diagnostic efficiency of established models was compared by ROC curve analysis. Results: Compared to non-DCM group, patients in subclinical DCM group were older, with longer duration of diabetes, and had higher levels of glycosylated hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) (all P<0.05). Serum FNDC5 level was significantly lower in subclinical DCM group than in non-DCM group (P<0.001). FNDC5 level was positively correlated with ventricular septal e'(r=0.451,P=0.005), mitral valve e'(r=0.291,P<0.001), the ratio of peak early diastolic trans-mitral flow velocity (E) to peak late diastolic trans-mitral flow velocity (A)(r=0.490,P=0.002), while negatively correlated with A(r=-0.399,P<0.001), the average ratio of E/e'(r=-0.490,P<0.001), tricuspid regurgitation velocity(r=-0.567,P<0.001), left atrial volume index(r=-0.491,P<0.001). Univariate ROC analysis showed that the diagnostic efficacy of FNDC5(AUC=0.940,95%CI 0.897-0.982)was superior to age(AUC=0.639,95%CI 0.523-0.752), diabetic duration(AUC=0.663,95%CI 0.555-0.772), HbA1c(AUC=0.740,95%CI 0.638-0.839), TG(AUC=0.661,95%CI 0.547-0.776), TC(AUC=0.675,95%CI 0.563-0.788)and LDL-C(AUC=0.644,95%CI 0.532-0.756). Model 1 was established with subclinical DCM as dependent variable, age, diabetic duration, TG, TC, LDL-C and HbA1c as independent variables. Model 2 was established by adding FNDC5 as independent variable on the basis of model 1. Diagnostic efficacy for subclinical DCM was compared between the two models by ROC analysis. The diagnostic efficiency was better with model 2 (AUC=0.980) than with model 1 (AUC=0.879, P<0.001). When sensitivity was set at 0.617, the specificity of model 2 was higher than that of model 1(0.979 vs. 0.936). When sensitivity was set at 0.532, the sensitivity of model 2 was higher than that of model 1 (1.000 vs. 0.915). Conclusions: Our findings suggest that serum FNDC5 could be used as a novel biomarker for the diagnosis of subclinical DCM.

Positive-Parity Linear-Chain Molecular Band in

An inelastic excitation and cluster-decay experiment ^{2}H(^{16}C,^{4}He+^{12}Be or ^{6}He+^{10}Be)^{2}H was carried out to investigate the linear-chain clustering structure in neutron-rich ^{16}C. For the first time, decay paths from the ^{16}C resonances to various states of the final nuclei were determined, thanks to the well-resolved Q-value spectra obtained from the threefold coincident measurement. The close-threshold resonance at 16.5 MeV is assigned as the J^{π}=0^{+} band head of the predicted positive-parity linear-chain molecular band with (3/2_{π}^{-})^{2}(1/2_{σ}^{-})^{2} configuration, according to the associated angular correlation and decay analysis. Other members of this band were found at 17.3, 19.4, and 21.6 MeV based on their selective decay properties, being consistent with the theoretical predictions. Another intriguing high-lying state was observed at 27.2 MeV which decays almost exclusively to ^{6}He+^{10}Be(∼6 MeV) final channel, corresponding well to another predicted linear-chain structure with the pure σ-bond configuration.

g Factor of the

The gyromagnetic factor of the low-lying E=251.96(9) keV isomeric state of the nucleus ^{99}Zr was measured using the time-dependent perturbed angular distribution technique. This level is assigned a spin and parity of J^{π}=7/2^{+}, with a half-life of T_{1/2}=336(5) ns. The isomer was produced and spin aligned via the abrasion-fission of a ^{238}U primary beam at RIKEN RIBF. A magnetic moment |µ|=2.31(14)µ_{N} was deduced showing that this isomer is not single particle in nature. A comparison of the experimental values with interacting boson-fermion model IBFM-1 results shows that this state is strongly mixed with a main νd_{5/2} composition. Furthermore, it was found that monopole single-particle evolution changes significantly with the appearance of collective modes, likely due to type-II shell evolution.

Microliths in sputum specimens and their relationship to pulmonary alveolar microlithiasis.

The sputa of 26 of 100 patients with chronic obstructive pulmonary disease contained microliths. The numbers of microliths per smear of sputum per patient ranged from one to 20. In seven of the sputum specimens containing microliths, deposition of calcium was present on the loops of Curshmann's spirals to different extents, from a single layer to the laminated appearance seen in a free microlith. Partial and complete separation of the calcified laminated masses from the spirals were also demonstrated. Based on these observations, the morphogenesis of microliths and the pathogenesis of pulmonary alveolar microlithiasis are discussed.

Vimentin-positive spider-shaped Kupffer cells. A new clue to cytologic diagnosis of primary and metastatic hepatocellular carcinoma by fine-needle aspiration biopsy.

The identification of Kupffer cells highlighted by positive immunostaining for vimentin on direct smears was found to play an important role in the diagnosis of primary and metastatic hepatocellular carcinoma by fine-needle aspiration biopsy. The Kupffer cell, identified by vimentin staining, is spider- or star-shaped with multiple elongated and slender cytoplasmic processes. Direct smears obtained by fine-needle aspiration biopsy from 14 cases of hepatocellular carcinoma and 15 cases of metastatic carcinoma were stained with vimentin. The cytologic diagnoses were verified by histologic and/or clinical follow-up. All 14 cases of hepatocellular carcinoma, including 9 primary and 5 metastatic, contained significant number of vimentin-positive spider cells within tumor clusters. There were at least three spider cells present within each tumor cluster, involving at least 50% of the tumor clusters. The spider cells were not only found in the well-differentiated type but also in the poorly differentiated and pleomorphic large cell types of the hepatocellular carcinoma. However, the tumor cells from 15 metastatic carcinomas contained no or few spider cells in the tumor clusters. The presence of numerous vimentin-positive spider-shaped Kupffer cells within tumor clusters constitutes strong evidence in favor of a diagnosis of hepatocellular carcinoma.

Aspiration needle biopsy of thoracic lesions.

We reviewed our experience with 2,114 percutaneous aspiration needle biopsies of intrathoracic lesions. Aspiration was performed for cytological diagnosis employing biplane fluoroscopy and a 20 gauge needle, 0.9 mm in outside diameter. A satisfactory specimen was obtained in 88% of biopsies, and the chance of obtaining a correct diagnosis of a malignant lesion was 81.5%. The false positive rate was 2.3%, and the cytologists could always distinguish between primary and secondary neoplasms. A false negative rare of 13.6% (36 patients) resulted in only three delayed thoracotomies and two instances of interval metastases discovered at mediastinoscopy. Cellular specificity in primary tumors was not sufficiently accurate to affect therapy. Pneumothoraces occurred frequently (31.9% of patients) but wee generally small; 10.4% of patients required chest drainage. There were no recorded instances of tumor implantation in needle tracts. We conclude that a rapid and accurate diagnosis of intrathoracic pathology can be obtained by this technique. It is associated with an acceptable morbidity and may greatly expedite both patient care and investigation.

Binding of spirolactones to human plasma proteins.

The lipophilicity and plasma binding of 16 spirolactones and 4 hydroxy acid analogs were determined. Mathematical expressions were derived to correlate quantitatively the extent of plasma binding to the lipophilicity of the drugs. The nonspecific binding of these spirolactones and their hydroxy acid analogs was also analyzed using purified serum albumin. A computer program was developed to examine the mechanism of drug-serum protein interactions. One class of binding sites was observed for the range of concentrations used. The number of binding sites and the equilibrium binding constant were computed and were sensitive to substitution at the C-6 and C7 positions. Hydrolysis of the C-17 lactone ring in spirolactones to form hydroxy acid analogs resulted in a decrease in the lipophilicity and, hence, the equilibrium constant for binding.

Aspiration biopsy cytology of mesothelioma.

From 1977 to 1986, 39 cases at our institution were diagnosed as "consistent with mesothelioma" by percutaneous fine-needle aspiration biopsy. All were verified clinically and/or histologically, with no false-positive results. All mesotheliomas except four tumors of peritoneal origin originated from the pleura. On the basis of their cytomorphologic features in correlation with histopathology, the tumors were classified into four types: benign, carcinomatous, sarcomatous, and undifferentiated. Of these 39 cases of mesothelioma diagnosed by aspiration biopsy, nine were benign type; 14, carcinomatous type; 13, sarcomatous type; and three, undifferentiated type. The cytomorphologic features and patterns of different types of mesotheliomas observed in aspirate preparations are presented, and the differential diagnosis is discussed. It appears feasible to investigate pleural- or peritoneal-based lesions with fine-needle aspiration biopsy, particularly in patients without effusions or with negative results in effusion examinations. It is also possible to make a definitive diagnosis of mesothelioma on the basis of cytologic findings coupled with special and immunoperoxidase staining in combination with roentgenographic findings and clinical history.

Cytomorphologic appearances of normal endometrial cells during different phases of the menstrual cycle: a cytologic approach to endometrial dating.

From 1988 to 1992, 156 endometrial cytologic preparations were procured by directly brushing hysterectomy specimens from premenopausal women with normal endometrium and regular menstruation. These brushing smears were obtained by using the cytobrush and/or the endometrial brush. The cytologic findings were correlated with histologic endometrial dating. Of these, 56 cases were classified as proliferative phase endometrium; 89, secretory phase; and 11, menstrual phase. The cytomorphologic features of endometrial glandular and stromal cells at different stages of the menstrual cycle are summarized and compared. On the basis of the different cytomorphologic features of glandular and stromal cells seen during various phases of the cycle, cytologic differentiation between proliferative phase and secretory phase endometria can be readily established. It appears possible to date the endometrium by direct endometrial brushing technique. It is also possible to determine if the glandular and/or stromal cells seen in the endocervical smears procured by the cytobrush are normal endometrial cells from cytobrush extraction, and are consistent with the date of the menstrual cycle, which should be made clear in the cytology report.

Direct intrauterine sampling: the IUMC Endometrial Sampler.

Endometrial cytology has been studied for more than 25 years, and a variety of cytologic devices have been developed for direct sampling of the endometrium. The quality of endometrial samples procured by various devices is markedly different and greatly affects the diagnostic accuracy. A new endometrial sampling device, the IUMC Endometrial Sampler, was developed at the Indiana University Medical Center and approved by the Food and Drug Administration for general medical use. This device is intended for the early detection of endometrial carcinoma and its precursors. It can be used to monitor the endometrial condition of patients receiving estrogen replacement therapy or tamoxifen. It is also useful for the procurement of uncontaminated endometrial samples for microbiologic studies from patients with suspected endometritis. It has the potential to be used for endometrial dating for patients with infertility disorders. In our clinical trials and sampling tests using hysterectomy specimens, adequate and representative endometrial samples without contamination from endocervix and vagina were consistently obtained by this device. The procedure of endometrial sampling using this device and the preparation techniques for endometrial brushing specimens are discussed and illustrated.

HIV infection-associated lymphoepithelial lesions of the parotid gland: aspiration biopsy cytology, histology, and pathogenesis.

Two homosexual men with parotid swellings were shown to be human immunodeficiency virus (HIV)-positive. They initially presented with a painless solitary parotid mass accompanied by diffuse cervical lymphadenopathy. In case 1, the patient further developed bilateral multiple cystic lesions. Aspirate preparations from the cystic lesions contained numerous anucleate squames, and superficial and intermediate squamous cells intermingled with various follicular center cells and lymphocytes. Immunoblasts and active phagocytosis of nuclear debris were also noted. Histologically, the parotid cystic lesions showed squamous epithelium-lined clefts surrounded by abundant hyperplastic lymphoid tissue with prominent germinal centers. The cystic lesions did not involve submandibular and sublingual glands. The combination of bilateral multiple lymphoepithelial lesions of the parotid glands and diffuse cervical lymphadenopathy represents a new condition in patients who are likely to be HIV-positive. At the early stage of the disease, when the lesion is confined to a unilateral parotid gland, the cytologic findings of the parotid mass, in combination with a computed tomographic appearance of multiple cystic lesions, are distinctly different from findings in other neck and facial lesions. The patient should be tested for antibodies to the HIV virus to confirm this diagnosis, so that the appropriate precautions and treatment can be initiated.

Hepatic angiosarcoma: aspiration biopsy cytology and immunocytochemical contribution.

In the absence of previously documented sarcoma, the initial diagnosis of angiosarcoma (AS) on fine-needle aspiration (FNA) biopsy of the liver is difficult. However, awareness of its occurrence and the assistance of immunocytochemical stains may aid in arriving at the correct diagnosis. In this paper, a 59-yr-old smoker and alcoholic woman presented after a syncopal episode and was found to have a palpable right abdominal mass. An abdominal CT scan confirmed multiple centrally necrotic liver masses, from which an FNA biopsy was obtained. The smears were bloody with groups of relatively dishesive and singly dispersed spindle cells in a somewhat necrotic background. The nuclei were elongated to ovoid-round with small nucleoli. The cytoplasm was ample and ill-defined. The cells were reactive for factor VIII-related antigen and CD31 but negative for cytokeratin immunocytochemical stains, and a diagnosis of "suspicious for angiosarcoma" was entertained. The patient declined further studies or treatment but presented 4 mo later with light-headedness and hypoglycemia. Laparoscopic tissue biopsies of the liver/abdominal masses were obtained and revealed AS. Rarely, liver masses may represent AS. Pathologists should be aware of their cytomorphology and characteristic immunostaining to avoid their misinterpretation.

Fine-needle aspiration biopsy using a newly-developed pencil-grip syringe holder.

Until now, commercially available syringe holders for fine-needle aspiration (FNA) were designed to be held in a pistol-grip manner. A newly developed, pencil-grip syringe holder, the Tao Aspirator, was tested. The device is equipped with a release button for automatically drawing back the syringe plunger and a regulating knob for adjusting negative pressure for the aspiration. After direct smears were made for on-site examination, the remaining aspirated material was collected by rinsing the needle and syringe with CytoRich red fixative. Hettich cytocentrifuge preparations were then prepared. The quality of the first 150 FNA specimens procured by this device and prepared with liquid fixation was evaluated in terms of adequacy of specimen, amount of obscuring blood, preservation of cells, and ease of screening and interpretation. These 150 specimens included 32 from thyroids; 34 from breasts; 40 from lymph nodes; 24 from subcutaneous nodules; and 20 from salivary glands. There were no unsatisfactory specimens. In Hettich preparations, red blood cells were lysed, making interpretation easier. All cellular elements and tissue fragments were adequately fixed, showing excellent cellular morphology. Specimens fixed in liquid fixative yielded uniform cell suspensions, resulting in cytocentrifuge preparations with evenly distributed cells, and so the screening was also easier. The aspiration techniques using pistol-grip and pencil-grip FNA syringe holders were also compared in terms of control in tissue sampling, ease of use, and safety. The pencil-grip syringe holder allowed greater tactile sensation of the texture of the lesion, and enabled the operator to use a single hand to place a needle into a target lesion with minimal error. This device placed the hand relatively close to the needle tip while the hand was in a position of natural function, imparting more control in tissue sampling. It was more easily manipulated, and could prevent dripping when cystic fluid was aspirated. Specimen collection using the Tao Aspirator and processing with liquid fixation in addition to direct smear preparations allowed the laboratory to consistently produce adequate cytologic preparations and cell blocks.

Cytologic diagnosis of malignant mesothelioma, with particular emphasis on the epithelial noncohesive cell type.

The effusion cytologies from 21 cases of malignant mesothelioma (MM) (15 pleural, 6 peritoneal) diagnosed at the Indiana University Medical Center during 1990-1997 were reviewed. Using the classification of Tao (Acta Cytol 1979;23:209-213), 13 cases of MM were of the epithelial cohesive cell type and 8 were of the epithelial noncohesive cell type. While the epithelial cohesive cell type has been discussed in the literature, the epithelial noncohesive cell type has not. The cytomorphologic features for both types are presented with particular emphasis on the noncohesive cell type. The differential diagnosis and use of ancillary confirmatory laboratory tests are briefly discussed. Because of its resemblance to florid reactive mesothelial hyperplasia and the general lack of awareness of the existence of the single-cell pattern of mesothelioma, this diagnosis can often be missed.

Are oral contraceptive-associated liver cell adenomas premalignant?

From January 1977 to June 1990, 1,670 patients with a liver mass or masses underwent transabdominal fine needle aspiration biopsy of the liver. Of those cases, 99 were diagnosed cytologically as "hepatocellular carcinoma" and 9 as "consistent with liver cell adenoma." Among the 99 patients with hepatocellular carcinoma, 3 were users of oral contraceptives. The nine patients with liver cell adenoma were all users of oral contraceptives. Of them, two developed foci or areas of liver cell dysplasia within the adenomas. The mean periods of oral contraceptive use among these three groups of patients were different. It appeared that patients started to develop liver cell adenoma after five years of oral contraceptive use (mean, 6.3 years). Foci or areas of liver cell dysplasia began to arise within liver cell adenomas after 8 years of oral contraceptive use (mean, 9 years), and the patients started to develop hepatocellular carcinoma after 10 years of contraceptive use (mean, 11 years). The cytologic features of liver cell dysplasia strikingly mimicked those of hepatocellular carcinoma. From this study, the foci or areas of liver cell dysplasia appear to be the missing link responsible for the transformation of liver cell adenoma to carcinoma. It is believed that liver cell adenomas are not premalignant and may undergo reversible change after withdrawal of causative agents, whereas foci or areas of liver cell dysplasia within the adenomas are irreversible, premalignant changes and may transform into hepatocellular carcinoma.

Pulmonary metastases from intracranial meningioma diagnosed by aspiration biopsy cytology.

A case of rare extracranial metastasis from a recurrent intracranial meningioma is described. Incidentally discovered asymptomatic pulmonary metastases were diagnosed as meningioma by transthoracic fine needle aspiration (FNA) biopsy. The aspirate contained spindle-shaped tumor cells and other forms that seemed to correspond to the fibroblastic, syncytial and angioblastic areas seen in the histologic sections of the primary tumor. Cytomorphologically, metastatic meningioma appears to be sufficiently distinctive to permit its cytologic differentiation from other spindle-cell tumors. Although meningiomas metastasize rarely, this diagnosis should be considered in the interpretation of a transthoracic FNA biopsy of a pulmonary nodule or nodules in a patient with a history of recurrent intracranial meningioma, especially when the aspirate mainly consists of spindle-shaped neoplastic cells.

The cytopathology of mesothelioma.

Fifty-seven cases of mesothelioma from the Toronto General Hospital during the period 1965 to 1976 have been reviewed. Pleural effusions or ascites were present in 34 patients. The value of cytologic examination of effusion specimens was assessed, and the criteria for cytologic diagnosis were elucidated. It appears that patients with predominantly fibrous or sarcomatous mesothelioma were not prone to develop pleural effusions or ascites; few tumor cells, if any, from these mesotheliomas were exfoliated into effusions. Cytologic examinations of effusion specimens were positive in 12 of 14 cases of carcinomatous mesothelioma and in three of four cases of undifferentiated mesothelioma. However, only four of seven casee of benign mesothelioma (mostly epithelial type) showed positive results, as did two of four cases of sarcomatous mesothelioma. It appears that cytologic diagnosis of mesothelioma is more useful for the carcinomatous and undifferentiated types. The cytomorphologic features of the various types of mesothelioma are different, and by cytologic examination of effusion specimens, typing of mesothelioma is possible and correlates well with the histologic typing.

Aspiration biopsy cytology of smooth muscle tumors. A cytologic approach to the differentiation between leiomyosarcoma and leiomyoma.

From 1970 to 1991, 51 cases of smooth muscle tumors were diagnosed by fine needle aspiration biopsy. All were verified histologically and/or clinically, with no false-positive results. Of the 51 tumors, 41 were leiomyosarcoma and 10 leiomyoma. Among the 41 cases of leiomyosarcoma, 29 were the well-differentiated type; 8, poorly differentiated type; and 4, epithelioid type. Of the 10 cases of leiomyoma, 2 were the epithelioid type. The cytomorphologic features and cytologic patterns of various types of smooth muscle tumors observed in aspirate preparations are presented and compared in order to establish the cytologic criteria for differentiating malignant from benign smooth muscle tumors. Cytomorphologically the various types of smooth muscle tumors were different, and their cytologic features were sufficiently distinctive to distinguish one from the others. It appears possible to differentiate a well-differentiated leiomyosarcoma from a leiomyoma on the basis of cytologic findings observed in aspirate preparations. The recognition of different cytomorphologic features of various types of smooth muscle tumors is important in establishing an accurate cytologic diagnosis, which may be of practical significance to clinical management.

Cytopathology of papillary carcinoma of the thyroid with anaplastic transformation. A case report.

A case of papillary carcinoma of the thyroid with anaplastic transformation was diagnosed by fine needle aspiration. The atypical history and presentation of this case, the initially problematic cytologic and immunohistochemical findings, and the definitive cytologic and histologic features are described. The diagnostic problems posed by papillary carcinoma of the thyroid with anaplastic transformation are discussed. This diagnosis must be included in the differential diagnosis of poorly differentiated tumors of the neck.