Internal medicine inpatients' prevalence of misdiagnosed severe osteoporosis.

Vertebral fractures (VF) related to osteoporosis (i.e., severe OP) increase the risk of disability and mortality, but they are often neglected. We observed a severe OP misdiagnosis in 28.9% of inpatients with previous spinal imaging positive for VFs. Diagnosing severe OP is crucial to reduce the health care costs of inpatients. INTRODUCTION: Vertebral fractures (VFs) related to osteoporosis (OP) increase the risk of additional fractures and death. In inpatients, VFs are often neglected with consequent delay in OP treatments, prolongation of hospitalization, and reduction of life expectancy. The aim of this study was to evaluate the prevalence of a misdiagnosed severe OP (i.e., with VF) in general medicine inpatients. METHODS: We evaluated inpatients of a Medicine Unit between January 2019 and December 2019 without severe OP diagnosis, who had spinal imaging. For each patient, we collected demographic data, previous or current OP treatment, and presence/number of VFs. Descriptive data were presented by medians (interquartile range [IQR]) for continuous data or as numbers (percentages) for categorical data. Differences between subgroups were analyzed with chi-square or Kruskal-Wallis tests as appropriate. p-values <0.05 were considered statistically significant. RESULTS: 793 subjects were admitted to inpatient's clinic: 235 (135 females and 100 males with a median age of 76.0 [64.0-83.0] years) were enrolled. One or more vertebral fractures were present in 28.9% (68/235) subjects; 47% (32/68) had two or more vertebral fractures. The majority of patients (55/68) with VFs had not previously received a severe OP diagnosis. CONCLUSIONS: Severe OP was misdiagnosed in at least 8.6% of inpatients. The prevalence dramatically increases (about 29%) in subjects with previous spinal imaging showing one or more VFs. More attention should be given to this co-morbidity, which is known to be an additional risk factor for disability and mortality.

Cardiac mesenchymal stromal cells are a source of adipocytes in arrhythmogenic cardiomyopathy.

AIM: Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder mainly due to mutations in desmosomal genes, characterized by progressive fibro-adipose replacement of the myocardium, arrhythmias, and sudden death. It is still unclear which cell type is responsible for fibro-adipose substitution and which molecular mechanisms lead to this structural change. Cardiac mesenchymal stromal cells (C-MSC) are the most abundant cells in the heart, with propensity to differentiate into several cell types, including adipocytes, and their role in ACM is unknown. The aim of the present study was to investigate whether C-MSC contributed to excess adipocytes in patients with ACM. METHODS AND RESULTS: We found that, in ACM patients' explanted heart sections, cells actively differentiating into adipocytes are of mesenchymal origin. Therefore, we isolated C-MSC from endomyocardial biopsies of ACM and from not affected by arrhythmogenic cardiomyopathy (NON-ACM) (control) patients. We found that both ACM and control C-MSC express desmosomal genes, with ACM C-MSC showing lower expression of plakophilin (PKP2) protein vs. CONTROLS: Arrhythmogenic cardiomyopathy C-MSC cultured in adipogenic medium accumulated more lipid droplets than controls. Accordingly, the expression of adipogenic genes was higher in ACM vs. NON-ACM C-MSC, while expression of cell cycle and anti-adipogenic genes was lower. Both lipid accumulation and transcription reprogramming were dependent on PKP2 deficiency. CONCLUSIONS: Cardiac mesenchymal stromal cells contribute to the adipogenic substitution observed in ACM patients' hearts. Moreover, C-MSC from ACM patients recapitulate the features of ACM adipogenesis, representing a novel, scalable, patient-specific in vitro tool for future mechanistic studies.

Left ventricular ejection fraction for the risk stratification of sudden cardiac death: friend or foe?

More than 450000 Americans die suddenly each year from sustained ventricular tachycardia or fibrillation. A correct identification of these patients is crucial for a rational clinical management, because the demonstrated effectiveness of implantable cardioverter-defibrillators (ICD) on the reduction of sudden cardiac death. Basing on the results of multiple clinical trials, left ventricular systolic function, measured as ejection fraction, is currently the only recommended tool to identify patients at higher risk of sudden death that would benefit from a prophylactic ICD. However, the systematic implementation of prophylactic ICD recommendations results in a substantial number of inappropriate ICD implantations, while failing to prevent the majority of sudden deaths occurring in the general population. That has been the case implementing arrhythmic risk stratification with a rough arrhythmic risk marker, such as ejection fraction, that lacks sensitivity and specificity in the prediction of sudden cardiac death. The aim of this viewpoint is to critically revise the value of ejection fraction in the identification of patients at risk of sudden cardiac death.

Intracardiac echocardiography in electrophysiology.

Intracardiac echocardiography (ICE) is a recent, invaluable tool which can provide real-time anatomical guidance in electrophysiological procedures. By inserting intravenously an ultrasound probe and advancing it into the heart, various different views can be obtained which allow to better visualize patient anatomy, to guide the placement of electrophysiological catheters, and to detect immediately procedural complications as they occur. In atrial fibrillation ablation, ICE proves particularly useful to achieve a safer trans-septal puncture (especially in the presence of anatomical anomalies of the interatrial septum) and to help to monitor the visualization of the mapping catheters (circular, high density), or the monitoring of the balloons catheter (Cryo, Laser) position. In ventricular tachycardia ablation, on the other hand, ICE allows for continuous correlation between electrophysiological and structural findings (such as wall motion anomalies or changes in echodensity), and helps to ensure correct catheter contact and to position it, particularly around delicate structures such as the aortic cusps. In any procedure, ICE is also useful to immediately detect procedural complications, such as thrombus formation along catheters, or pericardial effusion. Thanks to its real-time morphological information, ICE provides an ideal complement to simple fluoroscopy or to more complex electroanatomic mapping techniques and is set to gain a wider role in a broad range of electrophysiological procedures.

Impact of coercive tactics on the decision-making of adolescents with intellectual disabilities.

BACKGROUND: High rates of victimization have raised concerns about the ability of adolescents with intellectual disabilities (ID) to avoid and escape from harmful situations and to make decisions in their own best interest. The present study was designed to assess the impact of specific coercive tactics on the decision-making of adolescents with ID. METHOD: Forty-eight adolescents with ID participated in the study. They were asked to respond to a series of brief vignettes depicting equal numbers of situations involving coercion with a lure, coercion with a threat, and no specific coercive tactic. Performance was assessed in terms of independent, prevention-focused decisions, reporting decisions and responses to fact and inference comprehension questions. RESULTS: Overall, participants suggested independent, prevention-focused decisions only about half the time. They were more likely to suggest independent, prevention-focused decisions in situations with no specific coercive tactic or coercion with a lure than in situations involving a threat. However, reporting decisions were more likely in situations involving coercion with a threat than in the other two conditions and both fact and inference comprehension were best in situations involving coercion with a threat. CONCLUSIONS: Results indicated that adolescents with ID are not well-prepared to handle situations on their own that involve coercion, especially coercion with a threat. Because comprehension did not appear to be a key source of the decision-making difficulty in this study, further research is needed to examine all aspects of the decision-making process as a basis for the design of effective interventions.

Breast cancer in young women: case report and a review.

BACKGROUND: Breast cancer in patients under 40 years is uncommon. Surveillance, Epidemiology and End Results (SEER) program reveals that 75% of breast tumors occur in women age > 50 years, only 6.5% in women age < 40 years, and a mere 0.6% in women age < 30 years. Breast-conserving surgery with subsequent chemo-radiotherapy has become the treatment of choice in women with breast neoplasm. CASE REPORT: Two young patients, 30 and 28 years respectively, with breast cancer. One patient with an atypical medullary breast carcinoma diagnosis, pT2 pN1 bipMx, Grade 3 Stage IIB, negative for receptors, Ki 67: 47%, cERB-2 negative; the other with an intraductal breast carcinoma, pT1c pN0 pMx, Grade 2 Stage I, negative for receptors, Ki 67: 85%, cERB-2 negative, p53 negative, Bcl-2 negative. The first patient underwent right radical mastectomy sec. Madden and axillary lymphoadenectomy in October 2001, started six cycles of adjuvant chemotherapy and radiotherapy on the right side of the chest and on axillary and supraclavicular lymph nodes area. After 2 years an ecotomography revealed small hypoechogenic nodules in the left breast. In December the patient underwent left radical mastectomy with positioning of an expander device. The histological exam revealed a not much differentiated intraductal carcinoma, pT1a N0 Mx, Stage I. After the surgical therapy, she follows another adjuvant chemotherapy. The second patient underwent left quadrantectomy with axillary limphoadenectomy in November 2004. Like the first-will follow several cycles of adjuvant chemotherapy and radiotherapy. DISCUSSION: Breast cancer in women under 40 years of age differ from breast cancer in older women in numerous clinical, pathological and biological features. The studies demonstrate that breast cancer arising in women under 40 years have a more aggressive profile than those of older patients. In both our patients family history of breast cancer was reported. That suggests a possible genetic susceptibility of these patients through BRCA1 and BRCA2 germ-line mutations. Breast conservative surgery with chemio-radiotherapy is the most commonly used treatment breast cancer, expecially in consideration of the aggressiveness of the lesions.

Measurements of growth hormone and insulin-like growth factor 1 in cats with diabetes mellitus.

Serum concentrations of insulin-like growth factor 1 (IGF-1) and growth hormone were measured in 25 cats with untreated diabetes mellitus (11 of which were used for follow-up measurements, one to three, four to eight, nine to 12 and 13 to 16 weeks after their treatment with insulin began), 14 diabetic cats that had previously been treated with insulin, and seven diabetic cats that also had hypersomatotropism, two of which had not previously been treated with insulin; 18 healthy cats were used as controls. In the untreated diabetic cats the concentration of IGF-1 ranged from 13.0 to 433.0 ng/ml (median 170.5 ng/ml), which was significantly lower than the concentrations in the control cats (196.0 to 791.0 ng/ml, median 452.0 ng/ml). Their IGF-1 concentrations increased significantly when they were treated with insulin and after four to eight weeks were not different from those in the control cats. In the diabetic cats that had previously been treated with insulin the IGF-1 concentrations were 33.0 to 476.0 ng/ml (median 316.0 ng/ml), which was significantly lower than the concentrations in the control cats, but significantly higher than in the untreated diabetic cats. The IGF-1 concentrations in the two previously untreated diabetic cats with hypersomatotropism were low and low-normal but increased markedly after treatment with insulin. In the five previously treated cats with hypersomatotropism the concentration of IGF-1 was above the normal range. The concentrations of growth hormone in the treated and untreated diabetic cats without hypersomatotropisms were not significantly different and there was an overlap in its concentrations in the diabetic cats with and without hypersomatotropism.

Giant mesenteric fibromatosis.

Mesenteric fibromatosis is a proliferative fibroblastic neoplasia of the small intestine mesentery which may occur as a unique or multiple formation. Mesenteric fibromatosis represents the 8% of all desmoid neoplasm. Giant mesenteric fibromatosis is uncommon by itself (2-4 case/milion/year). Since the rarity of this tumor and the difficulties in diagnostic and therapeutic ambit, we believe it justified to describe a case of giant mesenteric fibromatosis which came to our observation.

Diagnostic and surgical management of submandibular gland sialolithiasis: report of a stone of unusual size.

Sialolithiasis of the salivary glands is a relatively rare occurrence. It is the most common cause of acute and chronic infections. Sialoliths occurs in the submandibular gland in 80% of the cases and its etiology is associated with some anatomical factors proper of it. In many cases the diagnosis is easy due to obvious clinical features but, for treatment, imaging studies are always necessary. The most of the sialoliths are usually of 5 mm in maximum diameter and all the stones over 10 mm should be reported as a sialolith of unusual size. For these reason we considered useful to report our case in the managing of a stone 13 mm placed in the submandibular gland context and its treatment by surgical resection of the entire gland.

Substernal goiters.

BACKGROUND: Substernal goiter, also said cervico-mediastinic goiter, is a thyroid formation with cervical departure that goes beyond, with stretched neck, the superior thoracic strait for at least 3 cm and that preserves, generally, the parenchimal or fibrous connections between the cervical and thoracic portion, maintaining a direct vascularization supplied by the thyroid arteries. The prevalence of this pathology is very variable and fluctuates between 1.7% and 30% of all thyroid damages. The actual classification is provided by the radiologic examination of the chest and, above all, by the new techniques of imaging. METHODS: In the period between January 1998 and December 2003, 332 patients with thyroid pathology have been treated surgically. Forthy-five (13.5%) of these were afflicted with a cervico-mediastinic goiter. In 32/45 (71.1%) cases a total thyroidectomy has been performed by collar carving in accordance with Kocher; in 11/45 (24.5%) cases an hemithyroidectomy has been performed by collar incision; in 2/45 (4.4%) cases, already submitted to surgical intervention of isthmus-lobectomy a totalization has been performed. RESULTS: The surgical technique foresees always an anterior collar neck incision. This way of access is to prefer in the substernal goiters, both for the presence of a cervical vascularization easy to control and for the possibility, nearly always realizable, to dislocate the goiter by that way. As for what concerns the results of the histological examination, in 2/45 (4.5%) cases it has been set a diagnosis of follicular carcinoma (one of them surely invading and the other, leastly invading), in 3/45 (6.6%) cases papillary carcinoma, in 4/45 (8.8%) cases colloido-cystic goiter, in 33/45 (73.5%) cases micro-macrofollicular hyperplasia (in one of which contemporarily compromise from lymphoma of Hodgkin); in 3/45 (6.6%) cases of adenomatous hyperplasia of the thyroid. DISCUSSION: The surgical approach has been in all cases the collar neck incision in accordance to Kocher, and it has never been necessary to associate a sternotomy or thoracotomy. After the intervention, in all the patients the symptomatology tied to the mediastinal compression has disappeared. The goiter showed signs of neoplastic degeneration in 11.1% of the cases, with prevalence of the papillary carcinoma in the 6.6% and, in the remaining 4.5%, of follicular carcinoma. These data are superimposable to the data gathered in other surveys. All the patients passed the post-operating hospitalization in optimal conditions and have been discharged during the fourth post-operating day with the prescription of increasing levothyroxine doses according to the body weigh.

Rate-control or rhythm-control: where do we stand?

Atrial fibrillation is the most common sustained rhythm disturbance and its prevalence is increasing worldwide due to the progressive aging of the population. Current guidelines clearly depict the gold standard management of acute symptomatic atrial fibrillation but the best-long term approach for first or recurrent atrial fibrillation is still debated with regard to quality of life, risk of new hospitalizations, and possible disabling complications, such as thromboembolic stroke, major bleeds and death. Some authors propose that regaining sinus rhythm in all cases, thus re-establishing a physiologic cardiac function not requiring a prolonged antithrombotic therapy, avoids the threat of intracranial or extracranial haemorrhages due to Vitamin K antagonists or aspirin. On the contrary, advocates of a rate control approach with an accurate antithrombotic prophylaxis propose that such a strategy may avoid the risk of cardiovascular and non cardiovascular side effects related to antiarrhythmic drugs. This review aims to explore the state of our knowledge in order to summarize evidences and issues that need to be furthermore clarified.

[Home monitoring of blood glucose concentrations by owners of diabetic dogs and cats]. / Heimmonitoring des Blutglukosespiegels durch Besitzer diabetischer Hunde und Katzen.

Generation of blood glucose curves is essential to monitor glycemic control in dogs and cats with diabetes mellitus. Up till now blood collection and blood glucose measurements could only be performed in a hospital. However, glucose concentrations measured in a hospital environment can markedly differ from concentrations measured at home, due to reduced appetite, different activity level and stressful handling. At the Clinic of Small Animal Internal Medicine, University of Zurich, a new method to collect capillary blood from the ear and to measure blood glucose by means of a portable glucose meter has been developed. This method enables owners of diabetic dogs or cats to determine blood glucose concentrations and generate blood glucose curves at home. Three cases demonstrate, how much blood glucose concentrations at home may differ from those in the hospital and how home monitoring can help to establish diabetic control in dogs and cats.

Spontaneous chromosome loss and colcemid resistance in lymphocytes from patients with myotonic dystrophy type 1.

Myotonic Dystrophy type 1 (DM1) is one of the many inherited human diseases whose molecular defect is the expansion of a trinucleotide DNA sequence. DM1 shares with fragile X syndrome (FMR1), another "unstable triplet syndrome", several molecular features not present in the remaining triplet diseases. As FMR1 is also characterised by chromosome instability at the site of the expanded triplet, lymphocytes from DM1 patients and healthy donors were cultured for micronucleus (MN) analysis, in order to verify if DM1 is also prone to chromosome instability. A FISH analysis was also carried out to detect the presence of centromeric sequences in the observed MN. The data indicate that DM1 patients present a percentage of centromere-positive MN significantly higher than controls, suggesting that chromosome loss is the main mechanism underlying the origin of the increased spontaneous instability. To further assess the proneness to instability of cells of DM1 patients, cultures from patients and controls were treated in vitro with growing concentrations of two different mutagens: colcemid, a "pure" aneugen compound whose target is tubulin, and mytomicin C, a strong clastogen. The results show that the patient group is significantly less sensitive to colcemid. These data, together with FISH analysis, suggest the presence, in DM1 patients, of an already damaged tubulin, which becomes no more sensitive to the effect of colcemid and which could be the main defect underlying the aneugenic effects in DM1.

Home monitoring of blood glucose concentration by owners of diabetic dogs.

The objective of this study was to investigate whether home monitoring of blood glucose of diabetic dogs by owners would be possible on a long-term basis. The owners of 12 diabetic dogs were each asked to generate four glucose curves by taking capillary blood samples from their dog's ear, at three- to four-week intervals. Within one week of each curve being produced by the owner, an additional curve was produced by a veterinarian in the hospital. Ten owners were able to generate blood glucose curves; three of them needed a second demonstration, and two telephoned for further guidance. The blood glucose concentrations obtained from the first two 'hospital' curves were significantly lower than those measured at home. Overall, in 42 per cent of cases, the treatment based on the hospital curves would have been different from that based on 'home' curves. The results of this study indicate that the majority of owners were able and willing to perform long-term monitoring of the blood glucose concentrations of their dogs.

Warthin's tumor of parotid gland: treatment of a retroneural lesion by enucleation.

The papilliferous cystadenomas lymphomatosum or Warthin's tumor is a relatively rare and generally benign neoformation whose incidence is second only to the pleomorfic adenoma. 84% of all Warthin's tumor strikes the parotid gland. We report the two cases that come to our observation paying particular attention to the second one in which occurred a synchronous bilateral manifestation, a rarity in the clinical circle. We want to highlight that enucleation should be the preferred treatment in most cases due to extremely small dimension of Warthin's tumor. Moreover it is possible to perform this kind of surgical treatment even in the case of a retroneural lesion without causing any damage to the facial nerve and its main branches. As regards complications and sequelae we noticed neither a permanent nor a temporary injury of the facial mimicry and sensibility.

Fully parametric and semi-parametric regression models for common events with covariate measurement error in main study/validation study designs.

The derivation of the likelihood function for binary data from two types of main study/validation study designs where model covariates are measured with error is elaborated. Rather than limiting consideration to a restricted family of models with convenient mathematical properties, we suggest that empirical considerations, customized to the data at hand, should drive model choices. The joint likelihood function for the main study, in which the covariates are measured with error, and the validation study, in which they are not, is maximized, and estimation and inference proceeds using standard theory. Although the choice of the measurement error model is driven by empirical considerations, the relatively small validation study sizes typically seen may lead to misspecification, resulting in bias in estimation and inference about exposure-disease relationships. By using a nonparametric form for the measurement error model, the resulting semi-parametric methods suggested by Robins, Rotnitzky, and Zhao (1994, Journal of the American Statistical Association 89, 864-866) and Robins, Hsieh, and Newey (1995, Journal of the Royal Statistical Society, Series B 57, 409-424) are free from bias due to misspecification of the measurement error model, trading efficiency for robustness as usual. These fully and semi-parametric methods are illustrated with a detailed example from a main study/validation study of the health effects of occupational exposure to chemotherapeutics among pharmacists (Valanis et al., 1993, American Journal of Hospital Pharmacy 50, 455-462). A constant, prevalence ratio model for common binary events, with gamma covariate measurement error, is derived and empirically verified by the available data. A careful reanalysis of the data, taking measurement error fully into account, leads to a threefold increase in the log relative risk and no loss of statistical power. The semi-parametric estimates are consistent with the parametric results, providing reassurance that important bias due to misspecification of the measurement error model is unlikely.

Wernicke's encephalopathy post subtotal extended gastrectomy.

Wernicke's encephalopathy, neuropathy caused by a deficiency of thiamine is a syndrome characterized by memory troubles, mental confusion, ophthalmoplegia and nystagmus. The authors present a case that came up in a patient who underwent a subtotal gastrectomy because of malignant neoplasm of the stomach. More or less three months after the intervention the patient's general conditions were considerably declined and characterised by alimentary vomit, sensory obnubilation and neuromuscular deficit. After appropriate diagnostic ascertainments a repetition of the neoplastic disease was to be excluded locally and at a distance. So the authors analysed the different etiopathogenic possibilities to get a better clinical view of the syndrome in the surgical patient.

[Spectrum analysis of the r-r interval using a PC]. / L'analisi spettrale degli intèrvalli r-r mediante PC.

Spectral analysis of r-r variability has been recently proposed as a clinical tool to assess the autonomic nervous system function. In this article we present the results obtained using an equipment and an analysis software (based on Maximum Entropy Method) developed in our laboratory. Analyzing the tachograms derived from prolonged ECG registrations of 12 young healthy subjects, 24 to 36 years old (mean 31 +/- 4), we observed the two classic components of the signal: a low frequency component (0.7 +/- 0.2 Hz) and a high frequency component (0.21 +/- 16.6 Hz). As expected, standing, a simple manoeuvre augmenting sympathetic activity, caused a stronger predominance of the low frequency component. We conclude that our method is reliable to evaluate, by means of spectral analysis, rhythmical oscillations of r-r variability.