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Hypophosphatasia (HPP) is a rare disorder of the bone metabolism, characterized by genetically-determined low alkaline phosphatase (ALP) activity. Low ALP may also be observed in some common causes of bone fragility, such as in osteoporosis treated with antiresorptive drugs. This study aimed to verify whether differences in bone turnover markers (BTMs) could help differentiate adult patients with HPP from those with osteoporosis undergoing antiresorptive treatment. In this multicenter study, we enrolled 23 adult patients with a diagnosis of HPP and compared them with 46 osteoporotic subjects previously treated with zoledronic acid or denosumab. BTMs such as C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type I procollagen (P1NP), total ALP, and bone ALP (bALP) were measured, and ratios between BTMs were also calculated. Considering that the control group included only females, in the primary analysis we compared their characteristics with that of the 16 female patients with HPP. Both individual BTMs (CTX and P1NP) and four BTM ratios (ALP/P1NP, bALP/P1NP, ALP/CTX, and bALP/CTX) showed satisfactory discriminatory power, outperforming ALP alone. P1NP, in particular, had an AUC of 0.962 with a cut-off of 32 μg/L, while as for the BTMs ratios, the ALP/P1NP ratio had an AUC of 0.964 with a cut-off of 1.114. Similar results were confirmed when including male HPP patients, when adjusting for age and sex, and finally when performing a sensitivity analysis only in patients with ALP less than or equal to 32 U/L (i.e., the median of the distribution of the entire population). In cases of low ALP and bone fragility, BTM and their ratios could help distinguish HPP patients from osteoporotic individuals treated with antiresorptive drugs, aiding in accurate diagnosis and reducing the risk of inappropriate treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Crystalluria is an important indicator of renal stone recurrence. Mechanisms underlying urinary stone formation are still not fully understood and raising interests has been giving to intestinal commensal bacteria for their contribute in maintaining urinary solutes equilibrium. The aim of our phase II study was to examine the administration of potassium citrate, magnesium and probiotics in order to reduce crystalluria., Materials and Methods: Since May 2021, we enrolled 23 patients candidates for ureterorenolithotripsy for calcium oxalate kidney stones with crystalluria and a normal metabolic profile. The analysis was validated by the Institution's Ethical Committee (no. approval STS CE Lazio 1/N-823). At discharge, patients were provided with daily food supplementation for 20 days of 1 billion Lactobacillus paracasei LPC09, 1 billion Lactobacillus plantarum LP01, 1 billion Bifidobacterium breve BR03, potassium (520 mg), citrate (1400 mg), and magnesium (80 mg). Crystalluria was re-assessed at 1, 3, 6, and 12-months follow-up by polarized light microscopy., Results: After one month from the oral supplementation, no patient reported crystalluria; at 3 months, among the 20 participants available for re-evaluation, still no patient reported crystalluria. Instead, crystalluria was reported in three patients (15%) at 6 months, and in five patients (25%) at 12 months follow-up., Conclusions: The oral supplementation with Lactobacillus spp. and Bifidobacterium spp. was found able to reduce the prevalence of crystalluria in a cohort of patients with diagnosis of calcium oxalate kidney stones with crystalluria candidate to ureterorenolithotripsy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Gorham-Stout disease is a very rare disorder characterized by progressive bone erosion and angiomatous proliferation; its etiopathogenesis is still unknown, and diagnosis is still performed by exclusion criteria. The alteration of bone remodeling activity has been reported in patients; in this study, we characterized circulating osteoclast and osteogenic precursors that could be important to better understand the osteolysis observed in patients., Methods: Flow cytometry analysis of PBMC (Peripheral Blood Mononuclear Cells) was performed to characterize circulating osteoclast and osteogenic precursors in GSD patients (n = 9) compared to healthy donors (n = 55). Moreover, ELISA assays were assessed to evaluate serum levels of bone markers including RANK-L (Receptor activator of NF-κB ligand), OPG (Osteoprotegerin), BALP (Bone Alkaline Phosphatase) and OCN (Osteocalcin)., Results: We found an increase of CD16 - /CD14 + CD11b + and CD115 + /CD14 + CD11b + osteoclast precursors in GSD patients, with high levels of serum RANK-L that could reflect the increase of bone resorption activity observed in patients. Moreover, no significant alterations were found regarding osteogenic precursors and serum levels of BALP and OCN., Conclusion: The analysis of circulating bone cell precursors, as well as of RANK-L, could be relevant as an additional diagnostic tool for these patients and could be exploited for therapeutic purposes., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Background: There are few and controversial results on 24,25(OH) 2 D and FGF23 acute changes following supplementation with cholecalciferol., Methods: Twenty-seven subjects with 25(OH)D < 30 ng/mL were randomized into three groups to receive a single oral dose of 25,000 I.U. or 600,000 I.U. of cholecalciferol or placebo, respectively. We measured 25(OH)D, 1,25(OH) 2 D, 24,25(OH) 2 D, and FGF23 levels at baseline and after 72 h. The 1,25(OH) 2 D/25(OH)D, 1,25(OH) 2 D/24,25(OH) 2 D, and 24,25(OH) 2 D/25(OH)D ratios were also calculated., Results: There was an increase in 25(OH)D and 1,25 (OH) 2 D following both doses of cholecalciferol. In the group administered 600,000 I.U., there was a significant increase in the delta changes in 25(OH)D and 1,25(OH) 2 D compared to the placebo and in the delta 24,25(OH)D 2 compared to the placebo and 25,000 I.U. groups (all p < 0.05). A decrease in both the 1,25(OH) 2 D/25(OH)D and 1,25(OH) 2 D/24,25(OH) 2 D ratio (all p < 0.05) was observed in the 600,000 I.U. group. FGF23 values significantly increased only in the group administered 600,000 I.U., Conclusions: 25(OH)D and 1,25(OH)D levels significantly increased following 600,000 IU cholecalciferol administration compared to 25,000 I.U. and placebo. Following the massive administration of cholecalciferol, the CYP24A1 enzyme is actively involved in catabolism, thus, avoiding toxic effects.

Context: Radius quantitative ultrasound measurement, that utilized a portable low-frequency (VLF) axial transmission ultrasound for assessing the properties of radius cortical bone in a non PHPT population revealed a possible role as a screening tool prior to DXA to evaluate fragility fracture., Objective: To evaluate this portable ultrasound device as a screening tool of skeletal fragility in PHPT patients., Methods: We enrolled 117 postmenopausal women with PHPT. Every subject had a DXA of femur, lumbar spine, non-dominant distal 1/3 radius, TBS measurement, VLF with a portable device and spine x- ray., Results: The mean age of the patients was 68 ± 10 years. The measurement of agreement between radius DXA and VLF was: K = 0.43, p < 0.001. A lower radius US T-score, also adjusted for years since menopause and BMI, was associated with osteoporosis identified with DXA at lumbar and/or femoral neck sites: OR = 1.852 (CI 1.08, 3.18). All fractures were associated with femoral neck T-score: OR = 1.89 (95% CI 1.24, 2.89), as well as with total hip T-score: OR = 1.65 (95% CI 1.09, 2.50), and years since menopause: OR = 1.25 (95% CI 1.02, 1.54).Morphometric vertebral fractures were associated with years since menopause: OR = 1.28 (95% CI 1.02,1.61), femoral neck T-score OR = 1.96 (95% CI 1.227, 3.135), total hip T-score OR = 1.64 (95% CI 1.04, 2.60), TBS OR = 0.779 (95% CI 0.60-0.99), both ultra-distal radius T-score: OR = 1.50 (95% CI 1.05, 2.156), and radius US T-score: OR = 1.67 (95% CI 1.09, 2.56)., Conclusions: VLF could be used for screening purposes prior to DXA to evaluate PHPT fracture risk, only in conditions in which DXA measurement cannot be performed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

The loss of a hand disrupts the sophisticated neural pathways between the brain and the hand, severely affecting the level of independence of the patient and the ability to carry out daily work and social activities. Recent years have witnessed a rapid evolution of surgical techniques and technologies aimed at restoring dexterous motor functions akin to those of the human hand through bionic solutions, mainly relying on probing of electrical signals from the residual nerves and muscles. Here, we report the clinical implementation of an interface aimed at achieving this goal by exploiting muscle deformation, sensed through passive magnetic implants: the myokinetic interface. One participant with a transradial amputation received an implantation of six permanent magnets in three muscles of the residual limb. A truly self-contained myokinetic prosthetic arm embedding all hardware components and the battery within the prosthetic socket was developed. By retrieving muscle deformation caused by voluntary contraction through magnet localization, we were able to control in real time a dexterous robotic hand following both a direct control strategy and a pattern recognition approach. In just 6 weeks, the participant successfully completed a series of functional tests, achieving scores similar to those achieved when using myoelectric controllers, a standard-of-care solution, with comparable physical and mental workloads. This experience raised conceptual and technical limits of the interface, which nevertheless pave the way for further investigations in a partially unexplored field. This study also demonstrates a viable possibility for intuitively interfacing humans with robotic technologies.

Prehension movements in primates have been extensively studied for decades, and hand transport and hand grip adjustment are usually considered as the main components of any object reach-to-grasp action. Evident temporal patterns were found for the velocity of the hand during the transport phase and for the digits kinematics during pre-shaping and enclosing phases. However, such kinematics were always analysed separately in regard to time, and never studied in terms of dependence one from another. Nevertheless, if a reliable one-to-one relationship is proven, it would allow reconstructing the digit velocity (and position) simply by knowing the hand acceleration during reaching motions towards the target object, ceasing the usual dependence seen in literature from time of movement and distance from the target. In this study, the aim was precisely to analyse reach-to-grasp motions to explore if such relationship exists and how it can be formulated. Offline and real-time results not only seem to suggest the existence of a time-independent, one-to-one relationship between hand transport and hand grip adjustment, but also that such relationship is quite resilient to the different intrinsic and extrinsic properties of the target objects such as size, shape and position., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Prof. Christian Cipriani (last author) is the founder of Prensilia SRL, a university spin-off that develops multi-articulated and sensorized robotic hands. All authors declare this research was conducted in the absence of any commercial or financial relationships that could constitute a potential conflict of interest]., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction and Objectives: To evaluate the oncological and functional outcomes of transperineal laser ablation (TPLA) as the focal therapy for localized prostate cancer (PCa) after a 12-month follow-up., Materials and Methods: Patients with low- and intermediate-risk localized PCa were prospectively treated with focal TPLA between July 2021 and December 2022. The inclusion criteria were the following: clinical stage < T2b; PSA < 20 ng/mL; International Society of Urological Pathology (ISUP) grade ≤ 2; MRI-fusion biopsy-confirmed lesion classified as PI-RADS v2.1 ≥ 3. Intra-, peri-, and post-operative data were collected. Variables including age, PSA, prostate volume (PVol), Charlson's Comorbidity Index (CCI), International Prostate Symptom Score (IPSS) with QoL score, International Index of Erectile Function (IIEF-5), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), and Male Sexual Health Questionnaire-Ejaculatory Dysfunction Short Form (MSHQ-EjD) were collected at baseline and at 3, 6 and 12 months after TPLA. Post-operative mpMRI was performed at 3 and 12 months. Finally, all patients underwent prostatic re-biopsy under fusion guidance at 12 months. The success of this technique was defined as no recurrence in the target treated lesion at the 12-month follow up., Results: Twenty-four patients underwent focal TPLA. Baseline features were age [median 67 years (IQR 12)], PSA [5.7 ng/mL (3.9)], PVol [49 mL (27)], CCI [0 (0)], IPSS [11 (9)], IPSS-QoL [2 (2)], IIEF-5 [21 (6)], ICIQ-SF [0 (7)], MSHQ-EjD ejaculation domain [14 (4)] and bother score [0 (2)]. Median operative time was 34 min (IQR 12). Median visual analogue scale (VAS) 6 h after TPLA was 0 (IQR 1). The post-operative course was regular for all patients, who were discharged on the second post-operative day and underwent catheter removal on the seventh post-operative day. No patient had incontinence at catheter removal. A significant reduction in PSA ( p = 0.01) and an improvement in IPSS ( p = 0.009), IPSS-QoL ( p = 0.02) and ICIQ-SF scores ( p = 0.04) compared to baseline were observed at the 3-month follow-up. Erectile and ejaculatory functions did not show any significant variation during the follow-up. No intra- and peri-operative complications were recorded. Three Clavien-Dindo post-operative complications were recorded (12%): grade 1 (two cases of urinary retention) and grade 2 (one case of urinary tract infection). At the 12-month follow-up, eight patients showed mpMRI images referable to suspicious recurrent disease (PIRADS v2.1 ≥ 3). After re-biopsy, 7/24 patients' (29%) results were histologically confirmed as PCa, 3 of which were recurrences in the treated lesion (12.5%). The success rate was 87.5%., Conclusions: The focal TPLA oncological and functional results seemed to be encouraging. TPLA is a safe, painless, and effective technique with a good preservation of continence and sexual outcomes. Recurrence rate at 12 months was about 12.5%.

Hip fractures are a major health issue considerably impacting patients' quality of life and well-being. This is particularly evident in elderly subjects, in which the decline in bone and muscle mass coexists and predisposes individuals to fall and fracture. Among interventions to be implemented in hip fractured patients, the assessment and management of nutritional status is pivotal, particularly in subjects older than 65. Nutrition plays a central role in both primary and secondary preventions of fracture. An adequate protein intake improves muscle mass and strength and the intestinal absorption of calcium. Other nutrients with recognized beneficial effects on bone health are calcium, vitamins D, K, and C, potassium, magnesium, folate, and carotenoids. With reference to calcium, results from longitudinal studies showed that the consumption of dairy foods has a protective role against fractures. Moreover, the most recent systematic reviews and meta-analyses and one umbrella review demonstrated that the combination of calcium and vitamin D supplementation significantly reduces hip fracture risk, with presumed higher efficacy in older and institutionalized subjects. Owing to these reasons, the adequate intake of calcium, vitamin D, protein, and other macro and micronutrients has been successfully implemented in the Fracture Liaison Services (FLSs) that represent the most reliable model of management for hip fracture patients. In this narrative review, papers (randomized controlled trials, prospective and intervention studies, and systematic reviews) retrieved by records from three different databases (PubMed, Embase, and Medline) have been analyzed, and the available information on the screening, assessment, and management of nutritional and vitamin D status and calcium intake in patients with hip fractures is presented along with specific prevention and treatment measures.

Background: We assessed the long-term (24 months) efficacy and safety of monthly calcifediol (0.266 mg) in the correction and maintenance of total 25(OH)D levels in postmenopausal women with basal values <30 ng/mL., Methods: We initially enrolled 45 consecutive patients during the period September 2019-September 2020. After an initial visit, patients were instructed to return at 3, 6, 9, 12 and 24 months for measuring serum total 25(OH)D, ionised calcium, creatinine and isoenzyme of alkaline phosphatase (bALP). Here, we report only the per-protocol analysis, because the COVID-19 pandemic precluded adherence to the scheduled visits for some patients., Results: The patients' mean age was 62.4 ± 9.0 years. Mean basal 25(OH)D levels were 20.5 ± 5.3 ng/mL. There was a continuous increase of mean 25(OH)D values ( p for trend < 0.001). However, mean values at month 24 (36.7 ± 15.9) were not significantly different in respect to values at month 12 (41.2 ± 11.18). At 24 months, only 1 out 19 patients had a value <20 ng/mL. There was a significant decrease with time of mean values of bALP ( p < 0.0216), with no significant changes between 12 and 24 months. No significant changes were observed as far as ionised calcium or creatinine were concerned., Conclusions: The long-term administration of calcifediol maintains stable and sustained 25(OH)D concentrations, with no safety concerns.

A 47-year-old postmenopausal woman with osteoporosis was treated with denosumab, which was discontinued due to side effects. She was therefore transitioned to a yearly intravenous infusion of zoledronic acid. An increase in bone turnover markers together with bone loss at the lumbar spine was observed before the second infusion, suggesting an overshooting of bone resorption due to denosumab discontinuation. On physical examination, the patient was restless and reported having lost about 10 kg since the last visit. A solitary left inferior thyroid nodule was noted on neck palpation. Circulating thyroid hormone levels were elevated, with suppressed thyroid-stimulating hormone. A thyroid scan showed increased uptake in the left inferior nodule with suppression of the remainder of the thyroid gland. A diagnosis of hyperthyroidism due to toxic adenoma was made. The patient was treated with radioactive iodine ablation, with consequent complete normalization of thyroid function. She continued yearly treatment with zoledronic acid. She remained clinically well with no further fractures. Bone turnover markers were appropriately suppressed and bone mineral density increased in the spine and hip. This case illustrates how the overshooting phenomenon following denosumab discontinuation may be compounded by the development of secondary conditions, which can result in suboptimal response to antiresorptive osteoporosis medications., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The search for a physiologically appropriate interface for the control of dexterous hand prostheses is an ongoing challenge in bioengineering. In this context, we proposed an interface, named myokinetic control interface, based on the localization of magnets implanted in the residual limb muscles, to monitor their contractions and send appropriate commands to the artificial hand. As part of such concept, this interface requires a transcutaneous magnet localizer that can be integrated in a self-contained limb prosthesis, a feature yet to be realized within the current state of the art., Methods: In an attempt to cover this gap, here we present a modular embedded system consisting of a computation unit able to acquire synchronized samples captured by up to eight acquisition units, so to localize multiple magnets., Results: The system exhibits short computation times (<60ms) and power consumption (0.6-1.2W) which are suitable for use in a clinically viable prosthetic arm. The system proved able to localize magnets while moving at speeds in the range of physiological movements (<0.24m/s), with high accuracy (<1mm) and precision (<0.5mm)., Conclusion: We demonstrated a system suitable for the implementation of a self-contained myokinetic prosthetic hand., Significance: These results pave the way towards the clinical implementation of the myokinetic interface, with amputees controlling an artificial arm by means of implanted magnets.

The loss of sensitivity of the upper limb due to neurological injuries severely limits the ability to manipulate objects, hindering personal independence. Non-invasive augmented sensory feedback techniques are used to promote neural plasticity hence to restore the grasping function. This work presents a wearable device for restoring sensorimotor hand functions based on Discrete Event-driven Sensory Control policy. It consists of an instrumented glove that, relying on piezoelectric sensors, delivers short-lasting vibrotactile stimuli synchronously with the relevant mechanical events (i.e., contact and release) of the manipulation. We first performed a feasibility study on healthy participants (20) that showed overall good performances of the device, with touch-event detection accuracy of 96.2% and a response delay of 22 ms. Later, we pilot tested it on two participants with limited sensorimotor functions. When using the device, they improved their hand motor coordination while performing tests for hand motor coordination assessment (i.e., pick and place test, pick and lift test). In particular, they exhibited more coordinated temporal correlations between grip force and load force profiles and enhanced performances when transferring objects, quantitatively proving the effectiveness of the device.

Aim: This guideline (GL) is aimed at providing a clinical practice reference for the management of sporadic primary hyperparathyroidism (PHPT) in adults. PHPT management in pregnancy was not considered., Methods: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) and Società Italiana dell'Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro (SIOMMMS) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for the clinical practice recommendations., Results: The present GL provides recommendations about the roles of pharmacological and surgical treatment for the clinical management of sporadic PHPT. Parathyroidectomy is recommended in comparison to surveillance or pharmacologic treatment in any adult (outside of pregnancy) or elderly subject diagnosed with sporadic PHPT who is symptomatic or meets any of the following criteria: • Serum calcium levels >1 mg/dL above the upper limit of normal range. • Urinary calcium levels >4 mg/kg/day. • Osteoporosis disclosed by DXA examination and/or any fragility fracture. • Renal function impairment (eGFR <60 mL/min). • Clinic or silent nephrolithiasis. • Age ≤50 years. Monitoring and treatment of any comorbidity or complication of PHPT at bone, kidney, or cardiovascular level are suggested for patients who do not meet the criteria for surgery or are not operated on for any reason. Sixteen indications for good clinical practice are provided in addition to the recommendations., Conclusion: The present GL is directed to endocrinologists and surgeons - working in hospitals, territorial services or private practice - and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Highly impaired individuals stand to benefit greatly from cutting-edge bionic technology, however concurrent functional deficits may complicate the adaptation of such technology. Here, we present a case in which a visually impaired individual with bilateral burn injury amputation was provided with a novel transradial neuromusculoskeletal prosthesis comprising skeletal attachment via osseointegration and implanted electrodes in nerves and muscles for control and sensory feedback. Difficulties maintaining implant hygiene and donning and doffing the prosthesis arose due to his contralateral amputation, ipsilateral eye loss, and contralateral impaired vision necessitating continuous adaptations to the electromechanical interface. Despite these setbacks, the participant still demonstrated improvements in functional outcomes and the ability to control the prosthesis in various limb positions using the implanted electrodes. Our results demonstrate the importance of a multidisciplinary, iterative, and patient-centered approach to making cutting-edge technology accessible to patients with high levels of impairment.