Longitudinal changes of the femoral bone mineral density from first to third trimester of pregnancy: bone health assessment by means of non-ionizing REMS technology.

BACKGROUND: Throughout the pregnancy, there is a substantial transfer of calcium from the maternal skeleton to the fetus, which leads to a transient net reduction of the maternal bone mineral density. AIMS: To assess longitudinally the changes in the bone mineral density at the femoral neck between the first and third trimester of pregnancy in a cohort of healthy participants using Radiofrequency Echographic Multi Spectrometry (REMS) technology. METHODS: Prospective, cohort study conducted at the University hospital of Parma, Italy between July 2022 and February 2023. We recruited healthy participants with an uncomplicated singleton pregnancy before 14 completed weeks of gestation. All included participants were submitted to a sonographic examination of the femoral neck to assess the bone mineral density (and the corresponding Z-score values) using REMS at 11-13 and 36-38 weeks of pregnancy. The primary outcome was the change in the bone mineral density values at the maternal femoral neck between the first and third trimester of pregnancy. RESULTS: Over a period of 7 months, a total of 65 participants underwent bone mineral density measurement at the femoral neck at first and third trimester of the pregnancy using REMS. A significant reduction of the bone mineral density at the femoral neck (0.723 ± 0.069 vs 0.709 ± 0.069 g/cm2; p < 0.001) was noted with a mean bone mineral density change of - 1.9 ± 0.6% between the first and third trimester of pregnancy. At multivariable linear regression analysis, none of the demographic or clinical variables of the study population proved to be independently associated with the maternal bone mineral density changes at the femoral neck. CONCLUSIONS: Our study conducted on a cohort of healthy participants with uncomplicated pregnancy demonstrates that there is a significant reduction of bone mineral density at femoral neck from early to late gestation.

Fragility Score: a REMS-based indicator for the prediction of incident fragility fractures at 5 years.

BACKGROUND: Accurate estimation of the imminent fragility fracture risk currently represents a challenging task. The novel Fragility Score (FS) parameter, obtained during a Radiofrequency Echographic Multi Spectrometry (REMS) scan of lumbar or femoral regions, has been developed for the non-ionizing estimation of skeletal fragility. AIMS: The aim of this study was to assess the performance of FS in the early identification of patients at risk for incident fragility fractures with respect to bone mineral density (BMD) measurements. METHODS: Data from 1989 Caucasians of both genders were analysed and the incidence of fractures was assessed during a follow-up period up to 5 years. The diagnostic performance of FS to discriminate between patients with and without incident fragility fracture in comparison to that of the BMD T-scores measured by both Dual X-ray Absorptiometry (DXA) and REMS was assessed through ROC analysis. RESULTS: Concerning the prediction of generic osteoporotic fractures, FS provided AUC = 0.811 for women and AUC = 0.780 for men, which resulted in AUC = 0.715 and AUC = 0.758, respectively, when adjusted for age and body mass index (BMI). For the prediction of hip fractures, the corresponding values were AUC = 0.780 for women and AUC = 0.809 for men, which became AUC = 0.735 and AUC = 0.758, respectively, after age- and BMI-adjustment. Overall, FS showed the highest prediction ability for any considered fracture type in both genders, resulting always being significantly higher than either T-scores, whose AUC values were in the range 0.472-0.709. CONCLUSION: FS displayed a superior performance in fracture prediction, representing a valuable diagnostic tool to accurately detect a short-term fracture risk.

Pulse-Echo Measurements of Bone Tissues. Techniques and Clinical Results at the Spine and Femur.

The aim of this chapter is to review the available pulse-echo approaches for the quantitative evaluation of bone health status, with a specific application to the assessment of possible osteoporosis presence and to the fracture risk prediction. Along with a review of the main in-vivo imaging approaches for skeletal robustness evaluation and fracture risk assessment, further understanding into Radiofrequency Echographic Multi Spectrometry (REMS), an ultrasound-based method measuring clinically relevant bone districts (i.e. lumbar vertebrae and proximal femur), is provided, and the further potentialities of this technology are discussed.Currently, the bone mineral density (BMD) provided by dual X-ray absorptiometry (DXA) is considered an established indicator for osteoporosis status assessment and fracture risk prediction, however, in order to obtain more accurate results, an additional step beyond BMD would be necessary, which means including data on bone quality for an improved evaluation of the disease and its consequences.REMS is a technology which allows both osteoporosis diagnosis, through the BMD estimation, and the prediction of fracture risk, through the computation of the Fragility Score; both measures are obtained by the automatic processing of unfiltered ultrasound signals acquired in correspondence of anatomical reference sites.

Automatic measurement of head-perineum distance during intrapartum ultrasound: description of the technique and preliminary results.

OBJECTIVES: To evaluate the accuracy and reliability of a new ultrasound technique for the automatic assessment of the head-perineum distance (HPD) during childbirth. METHODS: HPD was measured on a total of 40 acquisition sessions in 30 laboring women both automatically by an innovative algorithm and manually by trained sonographers, assumed as gold standard. RESULTS: A significant correlation was found between manual and automatic measurements (Intra-CC = 0.994). High values of the coefficient of determination (r2=0.98) and low residual errors: RMSE = 2.01 mm (4.9%) were found. CONCLUSION: The automatic algorithm for the assessment of the HPD represents a reliable technique.

First assessment of bone mineral density in healthy pregnant women by means of Radiofrequency Echographic Multi Spectrometry (REMS) technology.

OBJECTIVE: The maternal bone structure is the largest calcium reserve for the fetus during pregnancy, and this is claimed to lead to a bone mineral density (BMD) reduction in pregnant women. The primary outcome of the present work was to assess the BMD in a group of healthy pregnant women. STUDY DESIGN: In this prospective case - control observational study, a non-consecutive group of pregnant women with uncomplicated pregnancy at or >37 weeks were enrolled at the unit of Obstetrics and Gynecology, University of Parma, from February to December 2020. The study subjects were submitted to a sonographic examination of the proximal femur with Radiofrequency Echographic Multi Spectrometry (REMS) technology to quantify the BMD of the femur. The BMD values obtained in the study group were compared with those of a control group of non-pregnant women matched for age, ethnicity and pre-pregnant body mass index (BMI). RESULTS: Overall, 78 pregnant women at 39.1 ±â€¯1.5 weeks were assessed. Compared with non-pregnant women, the femoral BMD values measured in pregnancy using REMS were significant lower (0.769 ±â€¯0.094 g/cm2 vs 0.831 ±â€¯0.101 g/cm2, p = 0.0001) with a mean BMD reduction of 8.1%. The femoral neck BMD presented a positive correlation with the pre-pregnant BMI (p = 0.0004) and a negative correlation with the maternal age (p < 0.0001). In addition, a lower femoral neck BMD in Caucasian ethnicity compared with non-Caucasian was noted (p < 0.0001). CONCLUSION: In this exploratory and proof of concept study, for the first time, a decreased BMD has been objectively demonstrated in pregnant compared with non-pregnant women by means of REMS technology. New studies are required to assess the longitudinal changes of maternal bone density throughout the pregnancy.

The surgical approach to nodule Thyr 3-4 after the 2.2014 NCCN and 2015 ATA guidelines.

BACKGROUND: The incidence of palpables thyroid nodules in general population is 5% and the prevalence of non -palpable nodules is higher (35-60%) in the endemic goiter area. In the last years the new guidelines and new classification related to thyroid nodule have changed the indication to treat it. MATERIAL AND METHOD: We analyzed the patients treated from January 2013 to June 2016 for Thyr 3 and Thyr 4 thyroid nodule sec. Bethesda system. We have divided in I and II period related to the 2.2014 and 2015 ATA guidelines and we have evaluated the indication to treat, the type of surgical procedure, the incidence of thyroid carcinoma and the adverse events. RESULTS: We selected from 909 cases, 252 cases surgically treated with preoperative diagnosis of Thyr 3(80 cases) and Thyr 4(172 cases); carcinoma was found in 21/80 (26.2%) and in 62/172 (26.05%). The period was divided from January 2013 to December 2014 and from January 2015 to june 2016 (first and second period). In II period we found carcinoma in 8/40 Thyr3 and in 26/88 Thyr 4. The incidence of lobectomy in II period was higher than I period (p < 0.0001) sec.guidelines indications. No difference in adverse events. The number of cancer is lower in patients treated with lobectomy than those who underwent total thyroidectomy (12,5%vs 21,8% in Thyr 3; 15,3% vs 32% in Thyr 4). CONCLUSIONS: The indications to treat related to Thyr 3 and Thyr4 are changed in the two periods. The number of cancer is lower in patients treated with lobectomy. The new guidelines have changed the surgical approach to thyroid nodule.

Di- and tripeptide transport in vertebrates: the contribution of teleost fish models.

Solute Carrier 15 (SLC15) family, alias H+-coupled oligopeptide cotransporter family, is a group of membrane transporters known for their role in the cellular uptake of di- and tripeptides (di/tripeptides) and peptide-like molecules. Of its members, SLC15A1 (PEPT1) chiefly mediates intestinal absorption of luminal di/tripeptides from dietary protein digestion, while SLC15A2 (PEPT2) mainly allows renal tubular reabsorption of di/tripeptides from ultrafiltration, SLC15A3 (PHT2) and SLC15A4 (PHT1) possibly interact with di/tripeptides and histidine in certain immune cells, and SLC15A5 has unknown function. Our understanding of this family in vertebrates has steadily increased, also due to the surge of genomic-to-functional information from 'non-conventional' animal models, livestock, poultry, and aquaculture fish species. Here, we review the literature on the SLC15 transporters in teleost fish with emphasis on SLC15A1 (PEPT1), one of the solute carriers better studied amongst teleost fish because of its relevance in animal nutrition. We report on the operativity of the transporter, the molecular diversity, and multiplicity of structural-functional solutions of the teleost fish orthologs with respect to higher vertebrates, its relevance at the intersection of the alimentary and osmoregulative functions of the gut, its response under various physiological states and dietary solicitations, and its possible involvement in examples of total body plasticity, such as growth and compensatory growth. By a comparative approach, we also review the few studies in teleost fish on SLC15A2 (PEPT2), SLC15A4 (PHT1), and SLC15A3 (PHT2). By representing the contribution of teleost fish to the knowledge of the physiology of di/tripeptide transport and transporters, we aim to fill the gap between higher and lower vertebrates.

An Advanced Quantitative Echosound Methodology for Femoral Neck Densitometry.

The aim of this paper was to investigate the clinical feasibility and the accuracy in femoral neck densitometry of the Osteoporosis Score (O.S.), an ultrasound (US) parameter for osteoporosis diagnosis that has been recently introduced for lumbar spine applications. A total of 377 female patients (aged 61-70 y) underwent both a femoral dual X-ray absorptiometry (DXA) and an echographic scan of the proximal femur. Recruited patients were sub-divided into a reference database used for ultrasound spectral model construction and a study population for repeatability assessments and accuracy evaluations. Echographic images and radiofrequency signals were analyzed through a fully automatic algorithm that performed a series of combined spectral and statistical analyses, providing as a final output the O.S. value of the femoral neck. Assuming DXA as a gold standard reference, the accuracy of O.S.-based diagnoses resulted 94.7%, with k = 0.898 (p < 0.0001). Significant correlations were also found between O.S.-estimated bone mineral density and corresponding DXA values, with r(2) up to 0.79 and root mean square error = 5.9-7.4%. The reported accuracy levels, combined with the proven ease of use and very good measurement repeatability, provide the adopted method with a potential for clinical routine application in osteoporosis diagnosis.

Major osteoporotic fragility fractures: Risk factor updates and societal impact.

Osteoporosis is a silent disease without any evidence of disease until a fracture occurs. Approximately 200 million people in the world are affected by osteoporosis and 8.9 million fractures occur each year worldwide. Fractures of the hip are a major public health burden, by means of both social cost and health condition of the elderly because these fractures are one of the main causes of morbidity, impairment, decreased quality of life and mortality in women and men. The aim of this review is to analyze the most important factors related to the enormous impact of osteoporotic fractures on population. Among the most common risk factors, low body mass index; history of fragility fracture, environmental risk, early menopause, smoking, lack of vitamin D, endocrine disorders (for example insulin-dependent diabetes mellitus), use of glucocorticoids, excessive alcohol intake, immobility and others represented the main clinical risk factors associated with augmented risk of fragility fracture. The increasing trend of osteoporosis is accompanied by an underutilization of the available preventive strategies and only a small number of patients at high fracture risk are recognized and successively referred for therapy. This report provides analytic evidences to assess the best practices in osteoporosis management and indications for the adoption of a correct healthcare strategy to significantly reduce the osteoporosis burden. Early diagnosis is the key to resize the impact of osteoporosis on healthcare system. In this context, attention must be focused on the identification of high fracture risk among osteoporotic patients. It is necessary to increase national awareness campaigns across countries in order to reduce the osteoporotic fractures incidence.

Automatic Echographic Detection of Halloysite Clay Nanotubes in a Low Concentration Range.

Aim of this work was to investigate the automatic echographic detection of an experimental drug delivery agent, halloysite clay nanotubes (HNTs), by employing an innovative method based on advanced spectral analysis of the corresponding "raw" radiofrequency backscatter signals. Different HNT concentrations in a low range (5.5-66 × 1010 part/mL, equivalent to 0.25-3.00 mg/mL) were dispersed in custom-designed tissue-mimicking phantoms and imaged through a clinically-available echographic device at a conventional ultrasound diagnostic frequency (10 MHz). The most effective response (sensitivity = 60%, specificity = 95%), was found at a concentration of 33 × 1010 part/mL (1.5 mg/mL), representing a kind of best compromise between the need of enough particles to introduce detectable spectral modifications in the backscattered signal and the necessity to avoid the losses of spectral peculiarity associated to higher HNT concentrations. Based on theoretical considerations and quantitative comparisons with literature-available results, this concentration could also represent an optimal concentration level for the automatic echographic detection of different solid nanoparticles when employing a similar ultrasound frequency. Future dedicated studies will assess the actual clinical usefulness of the proposed approach and the potential of HNTs for effective theranostic applications.

New perspectives in echographic diagnosis of osteoporosis on hip and spine.

Currently, the accepted "gold standard" method for bone mineral density (BMD) measurement and osteoporosis diagnosis is dual-energy X-ray absorptiometry (DXA). However, actual DXA effectiveness is limited by several factors, including intrinsic accuracy uncertainties and possible errors in patient positioning and/or post-acquisition data analysis. DXA employment is also restricted by the typical issues related to ionizing radiation employment (high costs, need of dedicated structures and certified operators, unsuitability for population screenings). The only commercially-available alternative to DXA is represented by "quantitative ultrasound" (QUS) approaches, which are radiation-free, cheaper and portable, but they cannot be applied on the reference anatomical sites (lumbar spine and proximal femur). Therefore, their documented clinical usefulness is restricted to calcaneal applications on elderly patients (aged over 65 y), in combination with clinical risk factors and only for the identification of healthy subjects at low fracture risk. Literature-reported studies performed some QUS measurements on proximal femur, but their clinical translation is mostly hindered by intrinsic factors (e.g., device bulkiness). An innovative ultrasound methodology has been recently introduced, which performs a combined analysis of B-mode images and corresponding "raw" radiofrequency signals acquired during an echographic scan of the target reference anatomical site, providing two novel parameters: Osteoporosis Score and Fragility Score, indicative of BMD level and bone strength, respectively. This article will provide a brief review of the available systems for osteoporosis diagnosis in clinical routine contexts, followed by a synthesis of the most promising research results on the latest ultrasound developments for early osteoporosis diagnosis and fracture prevention.

A novel ultrasound methodology for estimating spine mineral density.

We investigated the possible clinical feasibility and accuracy of an innovative ultrasound (US) method for diagnosis of osteoporosis of the spine. A total of 342 female patients (aged 51-60 y) underwent spinal dual X-ray absorptiometry and abdominal echographic scanning of the lumbar spine. Recruited patients were subdivided into a reference database used for US spectral model construction and a study population for repeatability and accuracy evaluation. US images and radiofrequency signals were analyzed via a new fully automatic algorithm that performed a series of spectral and statistical analyses, providing a novel diagnostic parameter called the osteoporosis score (O.S.). If dual X-ray absorptiometry is assumed to be the gold standard reference, the accuracy of O.S.-based diagnoses was 91.1%, with k = 0.859 (p < 0.0001). Significant correlations were also found between O.S.-estimated bone mineral densities and corresponding dual X-ray absorptiometry values, with r(2) values up to 0.73 and a root mean square error of 6.3%-9.3%. The results obtained suggest that the proposed method has the potential for future routine application in US-based diagnosis of osteoporosis.

Are we changing our inclusion criteria for the minimally invasive videoassisted thyroidectomy?

AIM: The first cases treated with Minimally Invasive videoassisted thyroidectomy (MIVAT) were characterized by inclusion and exclusion criteria that are changing with the experience. MATERIALS AND METHODS: We have analyzed the patients treated from july 2005 to december 2010 with MIVAT All these cases were treated in accord with Miccoli's technique with a minicervicotomy of 1.5-2 cm above the sternal notch. We have divided the cases on the surgical period highlighting changing in the inclusion criteria and the adverse events (0-211 cases; 212-300 cases). All the cases treated were followed up at days 7 (ambulatory visit) and days 30-12 months (ambulatory visit or telephone contatct). The patients classified in the II° period were chracterized by the exclusion of the clinical thyroiditis. We have related these cases with the cases treated with conventional thyroidectomy(CT). RESULTS: No differences in postoperative pain,nerve palsy and hypocalcemia in MIVAT group and CT group. We have registered a postoperative pain at 24 hours lower in MIVAT group. The percentage of transitory nerve palsy in the MIVAT group in the first period was 2,84 % versus 1,12 % in the second period. CONCLUSION: MIVAT technique is safe and reproducible, with an excellent cosmetic results. In our experience MIVAT remains the better surgical options for the patients that meet the inclusion criteria.These cases are 15% of patients treated with thyroidectomy in our Endocrine surgery Unit.

Screening and early diagnosis of osteoporosis through X-ray and ultrasound based techniques.

Effective prevention and management of osteoporosis would require suitable methods for population screenings and early diagnosis. Current clinically-available diagnostic methods are mainly based on the use of either X-rays or ultrasound (US). All X-ray based methods provide a measure of bone mineral density (BMD), but it has been demonstrated that other structural aspects of the bone are important in determining fracture risk, such as mechanical features and elastic properties, which cannot be assessed using densitometric techniques. Among the most commonly used techniques, dual X-ray absorptiometry (DXA) is considered the current "gold standard" for osteoporosis diagnosis and fracture risk prediction. Unfortunately, as other X-ray based techniques, DXA has specific limitations (e.g., use of ionizing radiation, large size of the equipment, high costs, limited availability) that hinder its application for population screenings and primary care diagnosis. This has resulted in an increasing interest in developing reliable pre-screening tools for osteoporosis such as quantitative ultrasound (QUS) scanners, which do not involve ionizing radiation exposure and represent a cheaper solution exploiting portable and widely available devices. Furthermore, the usefulness of QUS techniques in fracture risk prediction has been proven and, with the last developments, they are also becoming a more and more reliable approach for assessing bone quality. However, the US assessment of osteoporosis is currently used only as a pre-screening tool, requiring a subsequent diagnosis confirmation by means of a DXA evaluation. Here we illustrate the state of art in the early diagnosis of this "silent disease" and show up recent advances for its prevention and improved management through early diagnosis.

Sonographic markers for early diagnosis of fetal malformations.

Fetal malformations are very frequent in industrialized countries. Although advanced maternal age may affect pregnancy outcome adversely, 80%-90% of fetal malformations occur in the absence of a specific risk factor for parents. The only effective approach for prenatal screening is currently represented by an ultrasound scan. However, ultrasound methods present two important limitations: the substantial absence of quantitative parameters and the dependence on the sonographer experience. In recent years, together with the improvement in transducer technology, quantitative and objective sonographic markers highly predictive of fetal malformations have been developed. These markers can be detected at early gestation (11-14 wk) and generally are not pathological in themselves but have an increased incidence in abnormal fetuses. Thus, prenatal ultrasonography during the second trimester of gestation provides a "genetic sonogram", including, for instance, nuchal translucency, short humeral length, echogenic bowel, echogenic intracardiac focus and choroid plexus cyst, that is used to identify morphological features of fetal Down's syndrome with a potential sensitivity of more than 90%. Other specific and sensitive markers can be seen in the case of cardiac defects and skeletal anomalies. In the future, sonographic markers could limit even more the use of invasive and dangerous techniques of prenatal diagnosis (amniocentesis, etc.).

The cancer burden and cancer control in developing countries.

Substantial changes in large parts of the developing world have materialised in the last three decades. These are extremely diverse countries with respect to culture, societal values and political arrangements, but sharing one feature--prevalent poverty and limited resources to protect the health of individuals. The control of emerging chronic diseases in low-resource countries is a formidable challenge. For this reason any intervention should be kept logistically simple and incorporated into a general plan aiming at building gradually the infrastructure that is necessary to bring care to the population at large. The present contribution summarizes some of the priorities in cancer prevention in developing countries and the underlying evidence base, and addresses some of the challenges.

Marriage and parenthood among childhood cancer survivors: a report from the Italian AIEOP Off-Therapy Registry.

BACKGROUND: The aim of this study was to describe the patterns of marriage and parenthood in a cohort of childhood cancer survivors included in the Off-Therapy Registry maintained by the Italian Association of Pediatric Hematology and Oncology. DESIGN AND METHODS: We analyzed a cohort of 6,044 patients diagnosed with cancer between 1960 and 1998, while aged 0 to 14 years and who were 18 years old or older by December 2003. They were followed up through the regional vital statistics registers until death or the end of follow up (October 30, 2006), whichever occurred first, and their marital status and date of birth of their children were recorded. The cumulative probabilities of being married and having a first child were computed by gender and compared by tumor type within the cohort. Marriage and fertility rates (the latter defined as the number of live births per woman-year) were compared with those of the Italian population of the same age, gender, area of residence and calendar period by means of the observed to expected (O/E) ratios. RESULTS: During the follow-up period, 4,633 (77%) subjects had not married. The marriage O/E ratios were 0.56 (95% CI: 0.51-0.61) and 0.70 (95% CI: 0.65-0.76) among men and women, respectively. Overall, 263 men had 367 liveborn children, and 473 women had 697 liveborn children. The female fertility O/E ratio was 0.57 (95% CI: 0.53-0.62) overall, and 1.08 (95% CI: 0.99-1.17) when analyses were restricted to married/cohabiting women CONCLUSIONS: Childhood cancer survivors are less likely to marry and to have children than the general population, confirming the life-long impact of their previous disease on their social behavior and choices. The inclusion of counseling in the strategies of management and long-term surveillance of childhood cancer patients could be beneficial to survivors as they approach adulthood.

The role of parents, friends and teachers in adolescents' cigarette smoking and tombak dipping in Sudan.

OBJECTIVE: To assess the influence of smoking and tombak (local smokeless tobacco) dipping by parents, teachers and friends on cigarette smoking and tombak dipping by school-going Sudanese adolescents. METHODS: This was a school-based cross-sectional survey was conducted in 2005-2006. Logistic regression was used for the analysis. A total of 4277 Sudanese school-going adolescents (aged 11-17 years) from 23 schools who completed an anonymous self-administered questionnaire on the use of tobacco products. Main outcome measures were self-reported tobacco use during the previous month defined current tobacco use. Ever smoking, tombak dipping and other tobacco products were also considered as outcomes. RESULTS: After adjusting for sex, age and school grade, adolescents' smoking habits were strongly associated with the habit in their parents and friends and, more weakly, with tombak dipping by teachers. When adjusted for each other, the association with smoking in friends was unaffected and remained significant (prevalence OR (POR) of having ever smoked was 1.94, 95% CI 1.64 to 2.29; OR of being current smoker was 3.77, 95% CI 2.80 to 5.07). Tobacco smoking in friends was positively associated with adolescents ever tombak dipping (POR 1.81, 95% CI 1.41 to 2.33) and current dipping (OR 3.33, 95% CI 2.20 to 5.05). The association with parental habits was reduced but still significantly elevated. Tombak dipping by teachers was only associated with adolescents ever tobacco smoking. CONCLUSIONS: Tobacco use by parents, teachers and friends was associated with adolescents' tobacco habits. The influence of friends was the strongest. In developing programmes against adolescents' tobacco habits, there is need to target the influence of these 'significant others'. Sudan needs to develop and implement comprehensive anti-smoking and anti-tombak dipping legislation to reduce the growing prevalence of such habits.