Radial head prosthesis disassembly: case report and medico-legal implications.

BACKGROUND: The aim of the treatment of radial head comminuted fractures is the restoration of anatomical normalcy to avoid the risk of several complications such as joint instability. Among the options for the treatment of such fractures, it is worth mentioning osteosynthesis, resection of the radial head or prosthetic replacement. In the presence of comminution or severe dislocation of the fracture's fragments, as in our patient's type III Mason fracture, prosthesis implantation is the treatment of choice. CASE REPORT: This clinical case reports a 22-year-old volleyball player, who during training suffered a comminuted fracture of the radial head, type III according to Mason's classification. A prosthesis was implanted. The post-operative course took place regularly. However, approximately three months after surgery, the patient experienced sudden pain and functional limitation following a normal elbow extension movement, so much so that he required medical attention in our emergency room. Following all the appropriate clinical-instrumental tests, a complete dissociation of the bipolar prosthesis of the radial head was found. CONCLUSIONS: Our clinical case shows the disassembly of a bipolar radial head prosthesis, a rather rare complication. From a medicolegal perspective, the patients should be aware of the increased risk of requiring further surgery after radial head replacement. When patients are thoroughly informed, they can cooperate and comply with indications more effectively, thus taking an active role in recovery management.

Cardiac amyloidosis characterization by kinetic model fitting on [18F]florbetaben PET images.

OBJECTIVE: To evaluate the feasibility of kinetic modeling-based approaches from [18F]-Flobetaben dynamic PET images as a non-invasive diagnostic method for cardiac amyloidosis (CA) and to identify the two AL- and ATTR-subtypes. METHODS AND RESULTS: Twenty-one patients with diagnoses of CA (11 patients with AL-subtype and 10 patients with ATTR-subtype of CA) and 15 Control patients with no-CA conditions underwent PET/CT imaging after [18F]Florbetaben bolus injection. A two-tissue-compartment (2TC) kinetic model was fitted to time-activity curves (TAC) obtained from left ventricle wall and left atrium cavity ROIs to estimate kinetic micro- and macro-parameters. Combinations of kinetic parameters were evaluated with the purpose of distinguishing Control subjects and CA patients, and to correctly label the last ones as AL- or ATTR-subtype. Resulting sensitivity, specificity, and accuracy for Control subjects were: 0.87, 0.9, 0.89; as far as CA patients, the sensitivity, specificity, and accuracy were respectively 0.9, 1, and 0.97 for AL-CA patients and 0.9, 0.92, 0.97 for ATTR-CA patients. CONCLUSION: Pharmacokinetic analysis based on a 2TC model allows cardiac amyloidosis characterization from dynamic [18F]Florbetaben PET images. Estimated model parameters allows to not only distinguish between Control subjects and patients, but also between AL- and ATTR-amyloid patients.

Cardiac amyloidosis detection by early bisphosphonate (99mTc-HMDP) scintigraphy.

OBJECTIVE: To determine one or more indexes able to detect the presence of cardiac amyloidosis (CA) from planar scintigraphy images after injection of 99mTc-HMDP tracer and to identify the earliest acquisition time able to ensure an accurate diagnosis of amyloid transthyretin CA. METHODS AND RESULTS: A total of 38 patients were included: 18 subjects with a final diagnosis of ATTR-CA and 20 controls. Dynamic planar images of the anterior thorax were acquired, starting at intravenous injection of ≈ 700 MBq of 99mTc-HMDP. From time/activity curves (TAC) of regions of interest such as heart, vascular region, right ribcage, and soft tissues, several indices were considered. From the analysis, it resulted that both TACHeart/Bone(t) and RIheart-bone(t), for t > 6 minutes, well distinguish ATTR-CA patients from controls subjects. This is confirmed by the area under curves (AUC) analysis giving AUC values =.9 at t ≅ 6 minutes and AUC ≅ 1 for t > 10 minutes. CONCLUSIONS: The method proposed allows determining the presence of ATTR-CA, in an inexpensive manner both in terms of examination costs and time spent.

Imaging Techniques as an Aid in the Early Detection of Cardiac Amyloidosis.

The idea that performing a proper succession of imaging tests and techniques allows an accurate and early diagnosis of cardiac amyloidosis, avoiding the need to perform the myocardial biopsy, is becoming increasingly popular. Furthermore, being imaging techniques non-invasive, it is possible to perform the follow-up of the pathology through repeated image acquisitions. In the present review, the various innovative imaging methodologies are presented, and it is discussed how they have been applied for early diagnosis of cardiac amyloidosis (CA), also to distinguish the two most frequent subtypes in CA: immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR); this allows to perform the therapy in a targeted and rapid manner.

Flutamide-induced hepatotoxicity: ethical and scientific issues.

OBJECTIVE: Flutamide (FLU) is a non-steroidal antiandrogen drug approved for the treatment of advanced prostate cancer. While this indication limits the use to male patients, FLU is widely prescribed to women, off-label, for the treatment of polycystic ovary syndrome (POCS) related hirsutism and acne. According to the literature, its assumption is associated with a higher incidence of adverse events in women than in male patients. MATERIALS AND METHODS: A literature search was conducted in main databases targeting unwilling FLU effects in hepatic and reproductive function. References in the selected paper were also considered as an additional source of data. Human- and animal-based studies were separately considered. RESULTS: Twenty-three human-based studies were evaluated: ten were case reports, six were retrospective studies, four were prospective, two were surveillance studies, while the last was an observational study. Nine animal-based studies were also evaluated. CONCLUSIONS: Scientific contributions highlight that FLU is responsible for specific hepatotoxic profiles in the female gender. From the ethical point of view, off-label prescribing of FLU in women is not only substantially unlawful, but also, without major safeguards being granted, a potential source of liability for prescribers.

Survival benefits of interferon-based therapy in patients with recurrent hepatitis C after orthotopic liver transplantation.

Recurrent hepatitis C after orthotopic liver transplantation (OLT) is universal and can lead to graft failure and, consequently, reduced survival. Hepatitis C treatment can be used to prevent these detrimental outcomes. The aim of this study was to describe rates of hepatitis C recurrence and sustained virological response (SVR) to interferon-based treatment after OLT and its relationship to survival and progression of liver disease through retrospective analysis of medical records of 127 patients who underwent OLT due to cirrhosis or hepatocellular carcinoma secondary to chronic hepatitis C between January 2002 and December 2013. Fifty-six patients were diagnosed with recurrent disease, 42 started interferon-based therapy and 37 completed treatment. Demographic, treatment- and outcome-related variables were compared between SVR and non-responders (non-SVR). There was an overall 54.1% SVR rate with interferon-based therapies. SVR was associated with longer follow-up after treatment (median 66.5 vs 37 months for non-SVR, P=0.03) and after OLT (median 105 vs 72 months, P=0.074), and lower rates of disease progression (15 vs 64.7%, P=0.0028) and death (5 vs 35.3%, P=0.033). Regardless of the result of therapy (SVR or non-SVR), there was a significant difference between treated and untreated patients regarding the occurrence of death (P<0.001) and months of survival (P<0.001). Even with suboptimal interferon-based therapies (compared to the new direct-acting antivirals) there is a 54.1% SVR rate to treatment. SVR is associated with improved survival and reduced risks of clinical decompensation, loss of the liver graft and death.

Survival benefits of interferon-based therapy in patients with recurrent hepatitis C after orthotopic liver transplantation

Recurrent hepatitis C after orthotopic liver transplantation (OLT) is universal and can lead to graft failure and, consequently, reduced survival. Hepatitis C treatment can be used to prevent these detrimental outcomes. The aim of this study was to describe rates of hepatitis C recurrence and sustained virological response (SVR) to interferon-based treatment after OLT and its relationship to survival and progression of liver disease through retrospective analysis of medical records of 127 patients who underwent OLT due to cirrhosis or hepatocellular carcinoma secondary to chronic hepatitis C between January 2002 and December 2013. Fifty-six patients were diagnosed with recurrent disease, 42 started interferon-based therapy and 37 completed treatment. Demographic, treatment- and outcome-related variables were compared between SVR and non-responders (non-SVR). There was an overall 54.1% SVR rate with interferon-based therapies. SVR was associated with longer follow-up after treatment (median 66.5 vs 37 months for non-SVR, P=0.03) and after OLT (median 105 vs 72 months, P=0.074), and lower rates of disease progression (15 vs 64.7%, P=0.0028) and death (5 vs 35.3%, P=0.033). Regardless of the result of therapy (SVR or non-SVR), there was a significant difference between treated and untreated patients regarding the occurrence of death (P<0.001) and months of survival (P<0.001). Even with suboptimal interferon-based therapies (compared to the new direct-acting antivirals) there is a 54.1% SVR rate to treatment. SVR is associated with improved survival and reduced risks of clinical decompensation, loss of the liver graft and death.

Detection of metastases from differentiated thyroid cancer by different imaging techniques (neck ultrasound, computed tomography and [18F]-FDG positron emission tomography) in patients with negative post-therapeutic ¹³¹I whole-body scan and detectable serum thyroglobulin levels.

INTRODUCTION: DTC patients having detectable Tg and negative post-therapeutic (131)I-WBS have to be investigated by different imaging techniques to detect metastases. PURPOSE: Comparison of neck US, CT and [18F]-FDG PET scan. METHODS: In 49 DTC patients with biochemical disease, neck was examined by US, CT and [18F]-FDG PET. FNA was performed and Tg was determined by FNA-Tg in selected cases of suspicious lymph nodes. Thorax was examined by CT and PET. Serum Tg was measured on LT4 therapy (basal Tg) and after the stimulation with recombinant human TSH (peak Tg). RESULTS: A thyroid remnant was seen by US, CT and PET in eight patients; recurrences were seen by US, CT and PET in six, five and five patients, respectively. Two metastatic nodes were identified by US and CT but not by PET. Lung micronodules were detected by CT in 7/49 (14.3 %) patients and by FDG PET in three of them. Basal Tg ranged from 0.5-1,725 ng/ml while peak Tg ranged from 0.5 to 2,135 ng/ml: the distribution between positive and negative patients was similar. Bone scan was negative in all cases. CONCLUSIONS: In DTC patients with detectable Tg and negative I-131 post-therapy WBS, imaging examination revealed remnant or metastases in 43 % of cases. Remnant and recurrences were equally detected by the three techniques; US was better than [18F]-FDG PET for lymph node metastases since this latter method can give false both positive and negative results; chest examination is best made by CT versus FDG PET due to its higher spatial resolution.

Complete meiosis from human induced pluripotent stem cells.

Gamete failure-derived infertility affects millions of people worldwide; for many patients, gamete donation by unrelated donors is the only available treatment. Embryonic stem cells (ESCs) can differentiate in vitro into germ-like cells, but they are genetically unrelated to the patient. Using an in vitro protocol that aims at recapitulating development, we have achieved, for the first time, complete differentiation of human induced pluripotent stem cells (hiPSCs) to postmeiotic cells. Unlike previous reports using human ESCs, postmeiotic cells arose without the over-expression of germline related transcription factors. Moreover, we consistently obtained haploid cells from hiPSCs of different origin (keratinocytes and cord blood), produced with a different number of transcription factors, and of both genetic sexes, suggesting the independence of our approach from the epigenetic memory of the reprogrammed somatic cells. Our work brings us closer to the production of personalized human gametes in vitro.

Structural model and ligand interactions of the Xanthomonas axonopodis pv. citri oligopeptide-binding protein

The oligopeptide-binding protein, OppA, ushers oligopeptide substrates to the membrane-associated oligopeptide permease (Opp), a multi-component ABC-type transporter involved in the uptake of oligopeptides by several bacterial species. In the present study, we report a structural model and an oligopeptide docking analysis of the OppA protein expressed by Xanthomonas axonopodis pv. citri (X. citri), the etiological agent of citrus canker. The X. citri OppA structural model showed a conserved three-dimensional structure, irrespective of the low amino acid identities with previously defined structures of Bacillus subtilis and Salmonella typhimurium orthologs. Oligopeptide docking analysis carried out with the proposed model indicated that the X. citri OppA preferentially binds tri- and tetrapeptides. The present study represents the first structural analysis of an OppA ortholog expressed by a phytopathogen and contributes to the understanding of the physiology and nutritional strategies of X. citri.

A homology model of the pore region of HCN channels.

HCN channels are activated by membrane hyperpolarization and regulated by cyclic nucleotides, such as cyclic adenosine-mono-phosphate (cAMP). Here we present structural models of the pore region of these channels obtained by using homology modeling and validated against spatial constraints derived from electrophysiological experiments. For the construction of the models we make two major assumptions, justified by electrophysiological observations: i), in the closed state, the topology of the inner pore of HCN channels is similar to that of K(+) channels. In particular, the orientation of the S5 and S6 helices of HCN channels is very similar to that of the corresponding helices of the K(+) KcsA and K(+) KirBac1.1 channels. Thus, we use as templates the x-ray structure of these K(+) channels. ii), In the open state, the S6 helix is bent further than it is in the closed state, as suggested (but not proven) by experimental data. For this reason, the template of the open conformation is the x-ray structure of the MthK channel. The structural models of the closed state turn out to be consistent with all the available electrophysiological data. The model of the open state turned out to be consistent with all the available electrophysiological data in the filter region, including additional experimental data performed in this work. However, it required the introduction of an appropriate, experimentally derived constraint for the S6 helix. Our modeling provides a structural framework for understanding several functional properties of HCN channels: i), the cysteine ring at the inner mouth of the pore may act as a sensor of the intracellular oxidizing/reducing conditions; ii), the bending amplitude of the S6 helix upon gating appears to be significantly smaller than that found in MthK channels; iii), the reduced ionic selectivity of HCN channels, relative to that of K(+) channels, may be caused, at least in part, by the larger flexibility of the inner pore of HCN channels.

Positron emission tomography (PET) in the staging of head neck cancer: comparison between PET and CT.

Standard pre-treatment clinical staging (TNM) of head and neck squamous cell carcinoma includes clinical and instrumental objective examination of primary tumour and of the cervical lymph nodes (inspection, palpation of neck, panendoscopy, biopsy of tumour, fine needle aspiration of nodes) and computed tomography or magnetic resonance imaging. Albeit, this procedure presents diagnostic limitations in the identification of approximately 1/3 of T1, of small sized nodes and in the diagnosis of metastases. Positron emission tomography-fluorodesoxy-glucose imaging, in the diagnostic workup of these cases, appears to offer an important contribution, however, its use is limited due to poor availability of this equipment and the high cost of the examination. In the present study, a comparison is made of results of standard clinical staging and positron emission tomography-fluorodesoxy-glucose in 22 patients with head and neck carcinoma prior to surgical treatment, with the results of pathological staging (pTNM) carried out on surgical specimens. In the staging of the tumour, computed tomography shows a sensitivity of 71% and positron emission tomography of 81%. In the staging of nodes, computed tomography imaging shows a sensitivity of 73%, a specificity of 57% and an accuracy of 68%, whereas positron emission tomography shows a sensitivity of 93%, a specificity of 100% and an accuracy of 95%. Furthermore, positron emission tomography identified 1/5 occult tumours and one tumour revealed at objective endoscopic examination, but not by computed tomography. The risk of occult nodes following positron emission tomography was found to be 7%. Overall, these results are in keeping with those reported in the literature, thus confirming the usefulness of positron emission tomography-fluorodesoxy-glucose in identifying occult tumours and nodes, in which computed tomography appears to be limited. Indications of positron emission tomography-fluorodesoxy-glucose may play a role in the choice of therapeutic options for the clinically N0 neck.

Clinical oncological applications of Positron Emission Tomography (PET) using fluorine-18-fluoro-2-deoxy-D-glucose.

Positron emission tomography (PET) has initially developed as a research tool, primarily for cardiological and neurological application. In the past decade, the paramount clinical potential of this imaging procedure has been recognized, reaching its full expression in the oncological field. The number of scientific publications demonstrating the clinical accuracy of the tracer [fluorine-18]-fluoro-2-deoxy-D-glucose ([18F]FDG) in the diagnosis, grading, staging, monitoring the response to treatment and in prognostic stratification of the oncological patient is continuously expanding. Nowadays, the clinical use of PET with [18F]FDG is approved in the majority of the countries (even in those with strict health regulations) for the metabolic imaging of proliferative diseases of the lung, breast, colon, and for the adequate diagnostic and prognostic evaluation of the patient with lymphoma and melanoma. Encouraging results have been also obtained in cancers of the head and neck, ovary and musculoskeletal system. Although about 90% of clinical investigations in oncology are performed using [18F]FDG as the tracer, radiopharmaceutical research is continuously developing new and more specific tumor targeting agents, whose efficacy is being explored more and more in the wide scale.

28. Accuracy of Qualitative and Semiquantitative Analysis of 18FDG Positron Emission Tomography Scans in the Evaluation of Primary and Metastatic Lesions.

Background: 18FDG PET scans are often interpreted on the basis of visual estimation of regional tracer uptake. Whether semiquantitative analysis may help clinicians in the recognition of neoplastic masses still remains debated.Materials and Methods: 134 patients with 144 dubious lesions on CT scans (89 pulmonary, 16 hepatic, 39 soft tissue) were studied by means of PET and 18(F)fluorodeoxyglucose. PET images were qualitatively interpreted by the consensus of two nuclear physicians. Standardized uptake value (SUV) and SUV lean were quantified in both normal and suspicious tissues. SUVs results in the lesion were also expressed as normalized values for the normal mean value in each organ (SUVs/org) and for the overall mean value in normal tissues (SUVs/norm).Results: All patients underwent cytological and/or hystological evaluation of the lesions: 53/144 (37%) were recognized as negative while 91/144 (63%) as positive for primary or metastatic disease. Qualitative analysis resulted in 75% specificity and 93% sensitivity. SUVs, SUVs lean, SUVs/org and SUVs/norm resulted significantly (p < 0.001) higher in positive than in negative lesions by cytology/histology. ROC curves analysis provided optimal cut-off values of 2.5, 0.8, 2.5 and 3, for SUVs, SUVs lean, SUVs/org and SUVs/norm, respectively. Using these cut-offs, specificity and sensitivity resulted 90 and 94%, 83 and 97%, 88 and 93%, 94 and 93%, respectively.Conclusion: Our data suggest that, in patients with CT scan suspicious lesions, visual analysis of PET scans is affected by a high number of false negative results. Semiquantitative assessment of regional metabolic activity has an incremental value and should be used in PET scan interpretation of dubious lesions.

Developmental potential of somatic stem cells in mammalian adults.

Traditionally, somatic tissue-derived stem cells of mammalian adults have been viewed as pluripotent precursors capable of lifelong maintenance of cellular compartments typical of the tissue in which they reside. However in recent years, in vitro cultures and in vivo transplantation assays have indicated that adult somatic stem cell of various species are capable of adopting multiple fates. Bone marrow cells can give rise to a wide array of phenotypes, including blood, endothelial, bone, cartilage, fat, tendon, lung, liver, muscle, marrow stroma, and even brain cells. Conversely, neural stem cells as well as progenitors present in the muscle may contribute to blood cell production, indicating that adult stem cells present in numerous tissues may generate multiple cell types even of different dermal origin. Therefore, the developmental potential of adult somatic stem cells might be reassessed, although the mechanisms that ultimately lead to determination of cell fate are not completely defined. The successful long-term culturing and expansion of somatic adult stem cells together with their intrinsic versatility leads to future hope of stem cell therapeutic use in a wide spectrum of diseases and disorders of several, even not easily accessible, tissues.

Role of 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the early assessment of response to chemotherapy in metastatic breast cancer patients.

We investigated the role of 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the early evaluation of response to chemotherapy in metastatic breast cancer patients. Breast cancer patients who received an epirubicin/paclitaxel--containing regimen as first-line treatment for metastatic disease were included in this study. A PET study was performed within 1 week before the start of treatment, at day 8 after the first course, and at the end of the planned program of chemotherapy. Tumor response was determined clinically and radiographically every 2 courses of treatment. Thirteen patients with metastatic breast cancer who were referred for treatment protocols with gemcitabine/epirubicin/paclitaxel or epirubicin/paclitaxel chemotherapy regimens were included in this study. All metastatic sites were easily visualized on the baseline FDG-PET images, obtained 50 to 60 minutes after tracer injection. Nine patients who completed the planned courses of chemotherapy and the FDG-PET studies were available for analysis. In the six patients who achieved a response to treatment, median glucose standard uptake value (SUV) (semiquantitative analysis) was 7.65 (range, 3.4-12.3) at baseline, 5.7 (range, 2.8-7.6) at day 8 after the first course, and 1.2 (range, 0.99-1.3) at the end of the 6 planned courses of chemotherapy. Three patients who obtained a stable disease as best response had no significant decrease in tumor glucose SUV compared to baseline levels. Qualitative visual analysis in the six responding patients showed a decrease in delineation of tumor mass from background activity soon after the first course, while the nonresponding patients had no significant modification from basal levels. Semiquantitative FDG-PET scanning of metastatic breast cancer sites showed a rapid and significant decrease in tumor glucose metabolism soon after the first course of treatment in patients who achieved a response to first-line chemotherapy. On the contrary, no significant decrease was observed in nonresponding patients.

Different tracers and stressors in patients with coronary artery disease: how to standardize clinical questions and nuclear cardiology answers.

The recent introduction of new tracers and stressors has increased the number of combinations of techniques that can be used for the diagnostic and prognostic stratification of patients with coronary artery disease. However, these new techniques still need to be standardized for clinical use. Thallium-201 scintigraphy is at present the most common method to assess transient ischemia and viability in patients. Dynamic exercise and dipyridamole show similar incidence of major cardiac complications and their use can be considered sufficiently safe. Further experimental and multicenter clinical studies are needed for 99mTc-Sestamibi and 99mTc-Teboroxime and for new stressors such as adenosine and dobutamine.

[Comparison of two methods to determine beta-lactoglobulin antibodies in children with cow's milk protein intolerance]. / Comparazione tra due metodiche di determinazione degli anticorpi anti-beta-lattoglobulina in bambini affetti da intolleranza alle proteine del latte vaccino.

In the last years the evaluation of IgG against beta-lactoglobulin (beta LG-IgG) has been proposed as reliable test to diagnose Cow's Milk Protein Intolerance (CMPI). This test, associated with other diagnostic tools (such as eosinophilia, hemoccult, RAST, challenge, etc.) showed a good sensibility, but less specificity. In fact antibodies against beta-lactoglobulin were found in other gastrointestinal diseases (coeliac disease, inflammatory bowel diseases, cystic fibrosis, etc.). To determine the specificity of the test some Authors attributed great importance to the laboratory method (IFL, ELISA). They retained IFL more specific. In order to verify the behaviour of the two methods and their concordance we carried out a double bind determination of IgG against beta-lactoglobulin (beta LG-IgG) on serum samples from children affected by CMPI. For this study we chose 16 children, aged from 3 months and 6 years, suffering from CMPI of which 11 with gastrointestinal complaints and 5 from extraintestinal ones. All children were diagnosed on the basis of the following criteria: clinical picture, blood eosinophilia, positivity of hemoccult, amelioration after the withdrawal of cow's milk proteins from the diet, positivity of challenge test. All children at the time of the assessment assuming a diet containing cow's milk proteins. beta LG-IgG were measured using simultaneously immunofluorescent and micro-ELISA methods. The obtained data showed that 12 children (75%) had IgG versus beta-lactoglobulin in the serum. This result was obtained both with IFL and ELISA methods, showing a 100% of concordance.(ABSTRACT TRUNCATED AT 250 WORDS)