How can the orthopedic surgeon ensure optimal vitamin D status in patients operated for an osteoporotic fracture?

In this narrative review, the role of vitamin D deficiency in the pathophysiology, healing of fragility fractures, and rehabilitation is discussed. Vitamin D status can be assessed by measuring serum 25(OH)-vitamin D level with standardized assays. There is a high prevalence of vitamin D insufficiency (25(OH)D < 50 nmol/l (i.e., 20 ng/mL)) or deficiency (25(OH)D < 25 nmol/l (i.e., 10 ng/mL)) in patients with fragility fractures and especially in those with a hip fracture. The evidence on the effects of vitamin D deficiency and/or vitamin D supplementation on fracture healing and material osseointegration is still limited. However, it appears that vitamin D have a rather positive influence on these processes. The fracture liaison service (FLS) model can help to inform orthopedic surgeons, all caregivers, and fractured patients about the importance of optimal vitamin D status in the management of patients with fragility fractures. Therefore, vitamin D status should be included in Capture the Fracture® program as an outcome of FLS in addition to dual-energy X-ray absorptiometry (DXA) and specific antiosteoporosis medication. Vitamin D plays a significant role in the pathophysiology and healing of fragility fractures and in rehabilitation after fracture. Correction of vitamin D deficiency should be one of the main outcomes in fracture liaison services.

Cost-effectiveness of buffered soluble alendronate 70 mg effervescent tablet for the treatment of postmenopausal women with osteoporosis in Italy.

The use of buffered soluble alendronate 70 mg effervescent tablet, a convenient dosing regimen for bisphosphonate therapy, seems a cost-effective strategy compared with relevant alternative treatments for postmenopausal women with osteoporosis aged 60 years and over in Italy. INTRODUCTION: To assess the cost-effectiveness of buffered soluble alendronate (ALN) 70 mg effervescent tablet compared with relevant alternative treatments for postmenopausal osteoporotic women in Italy. METHODS: A previously validated Markov microsimulation model was adjusted to the Italian healthcare setting to estimate the lifetime costs (expressed in €2019) per quality-adjusted life-years (QALY) of buffered soluble ALN compared with generic ALN, denosumab, zoledronic acid and no treatment. Pooled efficacy data derived from the NICE network meta-analysis were used for bisphosphonate treatments. Two treatment duration scenarios were assessed: 1 year using persistence data derived from an Italian prospective observational study including 144 and 216 postmenopausal osteoporotic women on buffered soluble ALN and oral ALN, respectively, and 3 years. Analyses were conducted for women 60-80 years of age with a bone mineral density T-score ≤ - 3.0 or with existing vertebral fractures. RESULTS: In all simulated populations, buffered soluble ALN was dominant (more QALYs, lower costs) compared to denosumab. The cost per QALY gained of buffered soluble ALN compared to generic ALN and no treatment always falls below €20,000 per QALY gained. In the 1-year treatment scenario, zoledronic acid was associated with more QALY than buffered soluble ALN but the cost per QALY gained of zoledronic acid compared with buffered soluble ALN was always higher than €70,000, while buffered soluble ALN was dominant in the 3-year treatment scenario. CONCLUSION: This study suggests that buffered soluble ALN represents a cost-effective strategy compared with relevant alternative treatments for postmenopausal osteoporosis women in Italy aged 60 years and over.

Clinical osteoarthritis of the hip and knee and fall risk: The role of low physical functioning and pain medication.

OBJECTIVE: Several studies have found an increased fall risk in persons with osteoarthritis (OA). However, most prospective studies did not use a clinical definition of OA. In addition, it is not clear which factors explain this risk. Our objectives were: (1) to confirm the prospective association between clinical OA of the hip and knee and falls; (2) to examine the modifying effect of sex; and (3) to examine whether low physical performance, low physical activity and use of pain medication are mediating these relationships. METHODS: Baseline and 1-year follow-up data from the European Project on OSteoArthritis (EPOSA) were used involving pre-harmonized data from five European population-based cohort studies (ages 65-85, n = 2535). Clinical OA was defined according to American College of Rheumatology (ACR) criteria. Falls were assessed using self-report. RESULTS: Over the follow-up period, 27.7% of the participants fell once or more (defined as faller), and 9.8% fell twice or more (recurrent faller). After adjustment for confounding, clinical knee OA was associated with the risk of becoming a recurrent faller (relative risk=1.55; 95% confidence interval: 1.10-2.18), but not with the risk of becoming a faller. No associations between clinical hip OA and (recurrent) falls were observed after adjustment for confounding. Use of opioids and analgesics mediated the associations between clinical OA and (recurrent) falls, while physical performance and physical activity did not. CONCLUSION: Individuals with clinical knee OA were at increased risk for recurrent falls. This relationship was mediated by pain medication, particularly opioids. The fall risk needs to be considered when discussing the risk benefit ratio of prescribing these medications.

The cortisol burden in elderly subjects with metabolic syndrome and its association with low-grade inflammation.

BACKGROUND: Elderly people are exposed to an increased load of stressful events and neuro-hormonal stimulation is a key finding in metabolic syndrome and its related disorders. AIMS: To determine the role of cortisol in elderly subjects, with or without metabolic syndrome (MetS), by means of a national multicentre observational study, AGICO (AGIng and Cortisol). METHODS: From 2012 to 2017, the AGICO study enrolled n.339 subjects (aged > 65), after obtaining their informed consent. The investigators assessed a cardio-metabolic panel (including electrocardiogram, carotid ultrasonography and echocardiography), the presence of MetS (on Adult Treatment Panel III criteria), a neurological examination (including brain imaging), and cortisol activity (using a consecutive collection of diurnal and nocturnal urine). RESULTS: In the patients presenting with MetS, the standardized diurnal and nocturnal cortisol excretion rates were 210.7 ± 145.5 and 173.7 ± 118.1 (mean ± standard deviation) µg/g creatinine/12 h; in those without MetS, the standardized diurnal and nocturnal cortisol excretion rates were 188.7 ± 92.7 and 144.1 ± 82.3 µg/g creatinine/12 h, respectively (nocturnal urinary cortisol in patients with MetS versus those without MetS p = 0.05, female patients with MetS vs female patients without MetS, p < 0.025). A significant positive correlation was found between the CRP levels and both the diurnal and nocturnal urinary cortisol levels with r = 0.187 (p < 0.025) and r = 0.411 (p < 0.00000001), respectively. DISCUSSION: The elderly patients with MetS showed a trend towards increased standardized nocturnal cortisol excretions, with particular regard to the female subjects. CONCLUSION: The positive correlation between cortisol excretion and low-grade inflammation suggests a common mechanism driving both hormonal and inflammatory changes.

Determinants, consequences and potential solutions to poor adherence to anti-osteoporosis treatment: results of an expert group meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Osteoporosis Foundation (IOF).

Many patients at increased risk of fractures do not take their medication appropriately, resulting in a substantial decrease in the benefits of drug therapy. Improving medication adherence is urgently needed but remains laborious, given the numerous and multidimensional reasons for non-adherence, suggesting the need for measurement-guided, multifactorial and individualized solutions. INTRODUCTION: Poor adherence to medications is a major challenge in the treatment of osteoporosis. This paper aimed to provide an overview of the consequences, determinants and potential solutions to poor adherence and persistence to osteoporosis medication. METHODS: A working group was organized by the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO) to review consequences, determinants and potential solutions to adherence and to make recommendations for practice and further research. A systematic literature review and a face-to-face experts meeting were undertaken. RESULTS: Medication non-adherence is associated with increased risk of fractures, leading to a substantial decrease in the clinical and economic benefits of drug therapy. Reasons for non-adherence are numerous and multidimensional for each patient, depending on the interplay of multiple factors, suggesting the need for multifactorial and individualized solutions. Few interventions have been shown to improve adherence or persistence to osteoporosis treatment. Promising actions include patient education with counselling, adherence monitoring with feedback and dose simplification including flexible dosing regimen. Recommendations for practice and further research were also provided. To adequately manage adherence, it is important to (1) understand the problem (initiation, implementation and/or persistence), (2) to measure adherence and (3) to identify the reason of non-adherence and fix it. CONCLUSION: These recommendations are intended for clinicians to manage adherence of their patients and to researchers and policy makers to design, facilitate and appropriately use adherence interventions.

Is the social status a new prognostic factor in the Fournier's gangrene?

Fournier's gangrene is a life-threatening acute necrotizing fasciitis of perianal, genitourinary and perineal areas. Local symptoms are scrotal swelling, erythema of scrotal skin and pain with generalized constitutional symptoms. The gangrene may extends to abdominal wall, intra-abdominal structures, and even in the retroperitoneal tissues. Urgent surgical debridement is crucial to warrant a good outcome since delayed intervention carries a poor prognosis. We report the case of a not diabetic patient with Fournier's disease presented with severe sepsis and successfully treated with urgent deep debridement and reconstructive surgery. We propose the social status of the patient as a prognostic factor with high impact for survival rate.

Oncological outcomes in oncoplastic breast surgery: a single institution analysis.

Oncoplastic surgery is a well-acknowledged technique that combines conserving treatment in breast cancer with plastic surgery reconstruction. The aim of our analysis is to evaluate the safety of this surgical procedure in the setting of invasive primary breast cancer, and then compare breast oncoplastic surgery with the Veronesi quadrantectomy.We have analyzed 1541 patients who underwent breast surgery for primary breast tumor between October 2004 and May 2018 at Sant'Andrea University Hospital in Rome: 880 women experienced the breast oncoplastic approach, while 660 patients received conservative surgery alone. The median follow-up time was 14 years with a completeness of 70% (1067 pts vs 1554). The statistic comparison across these subpopulations suggested that there are no statistically significant results in term of Overall Survival, Disease Related Survival, Local recurrence or positive margins. Therefore oncoplastic surgery for primary invasive breast cancer represents a feasible procedure and an oncological safe surgical option.

Cine 4DCT imaging artifacts: Quantification and correlations with scanning parameters and target kinetics.

To study temporal resolved computed tomography imaging (4-Dimensional Computed Tomography: 4DCT) artifacts correlations with scanning parameters and target kinetics and to assess uncertainty introduced by 4DCT in radiotherapy treatment planning. In this work we classified 4DCT artifacts as finite gantry rotation speed related (FGS) and finite sampling frequency related (FSF). We studied FGS artifacts using a respiratory phantom and FSF artifacts using a Monte Carlo simulation of acquisition timing. From our analysis FGS localization error is comparable with image resolution determined by voxel dimensions. Remaining FGS artifacts are correlated with gantry rotation time (Trot), target velocity (v) and their interaction. FSF artifacts occurrence is correlated with sampling ratio (SR), i.e. the ratio of patient respiratory period (Tresp) and sampling time (Ts). In the studied velocity range (0-2 cm/s), using a Trot of 0,5s and a SR higher than 15, FGS and FSF artifacts became comparable with other sources of uncertainty. Our considerations are valid for "ideal" breathing pattern only. When variations from periodical breathing, high target velocity (more than 2 cm/s) or high peak to peak amplitude (more than 2 cm) are present, patient specific images artifacts analysis is recommended.

A global call to action to improve the care of people with fragility fractures.

The ageing of society is driving an enormous increase in fragility fracture incidence and imposing a massive burden on patients, their families, health systems and societies globally. Disrupting the status quo has therefore become an obligation and a necessity. Initiated by the Fragility Fracture Network (FFN) at a "Presidents' Roundtable" during the 5th FFN Global Congress in 2016 several leading organisations agreed that a global multidisciplinary and multiprofessional collaboration, resulting in a Global Call to Action (CtA), would be the right step forward to improve the care of people presenting with fragility fractures. So far global and regional organisations in geriatrics/internal medicine, orthopaedics, osteoporosis/metabolic bone disease, rehabilitation and rheumatology were contacted as well as national organisations in five highly populated countries (Brazil, China, India, Japan and the United States), resulting in 81societies endorsing the CtA. We call for implementation of a systematic approach to fragility fracture care with the goal of restoring function and preventing subsequent fractures without further delay. There is an urgent need to improve: To address this fragility fracture crisis, the undersigned organisations pledge to intensify their efforts to improve the current management of all fragility fractures, prevent subsequent fractures, and strive to restore functional abilities and quality of life.

Adenomyoepithelioma of the breast: case report and literature review.

Adenomyoepithelioma are uncommon tumors. The majority of them occur in women in the fifth and sixth decades who usually present with a self-palpated, solitary breast mass or a lesion identified on mammography. We report the case of adenomyoepithelioma of the breast with malignant transformation of both myoepitheliel and epithelial components diagnosed as malignancy during the preoperative stage in a seventy-six year old woman.

Status of Geriatrics in 22 Countries.

OBJECTIVES: The aim of this article is to describe the current status of geriatrics and position of geriatricians in 22 countries of three continents, and to portray their attitudes towards and resources allocated to geriatrics. METHODS: An electronic survey was delivered to a convenience sample of 22 geriatricians in leading positions of their countries. RESULTS: The time required in post graduation specialist training to become a geriatrician varied from one year (subspecialty in the USA) to six years (independent specialty in Belgium). The number in the population aged 80+ per geriatrician varied from 450 (Austria) to 25,000 (Turkey). Of respondents, 55% reported that geriatrics is not a popular specialty in their country. Acute geriatric wards, rehabilitation and outpatient clinics were the most common working places for geriatricians. Nearly half of the respondents had an opinion that older patients who were acutely ill, were receiving subacute rehabilitation or had dementia should be cared for by geriatricians whereas half of the respondents would place geriatricians also in charge of nursing home and orthogeriatric patients. The biggest problems affecting older people's clinical care in their countries were: lack of geriatric knowledge, lack of geriatricians, and attitudes towards older people. Half of respondents thought that older people's health promotion and comprehensive geriatric assessment were not well implemented in their countries, although a majority felt that they could promote good geriatric care in their present position as a geriatrician. CONCLUSION: The position of geriatric, geriatricians' training and contents of work has wide international variety.

Osteoarthristis Increases the Risk of Cardiovascular Disease: Data from the Osteoarthritis Initiative.

OBJECTIVES: Although osteoarthritis (OA) is a common condition in older adults, the role of OA in increasing cardiovascular disease (CVD) incidence is still debated. The aim of this study was to investigate the association between OA and the onset of CVD in a large database of American adults. DESIGN: Longitudinal. SETTING: Community-dwelling. PARTICIPANTS: People with OA or at high risk of OA. MEASUREMENTS: Osteoarthritis was defined as the presence of OA of the hand, knee, hip, back/neck or of other sites. CVD was defined as self-reported presence of heart attack, heart failure, stroke and other cerebral atherosclerotic conditions, and peripheral artery disease. RESULTS: A total 4,265 persons without CVD (mean age=60.8 years, females=59.2%) at baseline were analyzed (1,775 with OA versus 2,490 without). Over a mean of 8.2 years, according to an adjusted Cox's regression analysis for 11 potential baseline confounders, study participants with OA of any joint had a significantly higher risk of developing CVD compared to those without OA (Hazard ratio (HR): =1.27; 95% CI: 1.03-1.56). The presence of hand OA was associated with a higher risk of developing CVD (HR=1.31; 95%CI: 1.01-1.68) with respect to those who had no OA. Knee, hip and back/neck OA did not, instead, increase the risk of developing CVD. The association between OA and CVD was significant in the women, but not in the men. CONCLUSIONS: OA, in particular, when it affects the hand and in women, was associated with a higher risk of developing CVD.

Management of diabetes in older adults.

Type 2 diabetes prevalence is high in older adults and is expected to rise in the next decades. Diabetes in the population of frail older adults is accompanied by functional disability, several comorbidities, and premature mortality. A comprehensive geriatric assessment, including functional, cognitive, mental and social status, is advisable for identifying the glycemic targets and glucose-lowering therapies, focused on patient preferences, needs, and risks. The therapeutic options for older adults with diabetes are like those for the adult population. However, the pharmacological treatments must be carefully prescribed and monitored, taking into consideration the patient cognitive capacities, the potentially life-threatening drug-drug interactions, the cardiovascular risk, and with the main goal of avoiding hypoglycemia. Also, a careful nutritional evaluation with appropriate tools, as well as a balanced and periodically monitored physical activity, contribute to an effective tailored care plan, as needed by older adults with diabetes. This review evaluates the currently available hypoglycemic drugs and the current indications to the Italian diabetology community, specifically with regard to the treatment of adults aged 75 years or older with diabetes, including the unmet needs by the guidelines.

Performance of the Multidimensional Geriatric Assessment and Multidimensional Prognostic Index in predicting negative outcomes in older adults with cancer.

The Multidimensional Geriatric Assessment (MGA) is currently used for assessing geriatric oncological patients, but a new prognostic index - the Multidimensional Prognostic Index (MPI) - has a demonstrated prognostic value in cancer patients too. The present work was designed to compare the MPI and MGA as predictors of 12-month mortality. 160 patients ≥70 years old with locally-advanced or metastatic solid cancers consecutively joining our Geriatric Oncology Program were administered a Comprehensive Geriatric Assessment to calculate their MGA and MPI scores. SETTINGS: Geriatric Clinic, Geriatric Surgery Clinic, Medical Oncology Unit, Padova Hospital, Italy. Using Cohen's Kappa coefficient, there was a poor concordance between the MPI and MGA. Severe MPI being associated with a higher mortality risk than Frail in the MGA. The ROC curves indicated that the MPI had a greater discriminatory power for 12-month mortality than the MGA. In our population of elderly cancer patients, the MPI performed better than the MGA in predicting mortality. Further evidence from larger prospective trials is needed to establish whether other geriatric scales, such as the GDS and CIRS-SI, could enhance the value of prognostic indexes applied to elderly cancer patients.

Pro-inflammatory dietary pattern is associated with fractures in women: an eight-year longitudinal cohort study.

In this study, during 8 years of follow-up, we reported that higher dietary inflammatory index values were associated with a higher risk of incident fractures in women, but not in men, after adjusting for potential confounders. INTRODUCTION: Inflammation is a key risk factor for many adverse outcomes in older people. While diet is a potential source of inflammation, little is known about the impact of inflammatory diet on fractures. Thus, we investigated whether higher Dietary Inflammatory Index (DII)™ ® scores are associated with fractures in a cohort of North American people. METHODS: This longitudinal study with a follow-up of 8 years included 3648 participants (1577 males and 2071 females; mean age = 60.6 years) with/at risk of knee osteoarthritis participating with in the Osteoarthritis Initiative. DII scores were calculated using the validated Block Brief 2000 Food Frequency Questionnaire, categorized into sex-specific quintiles. Information on fractures was obtained through self-reported history of fractures at hip, spine, and forearm. The relationship between baseline DII score and incident fracture was assessed through a Cox's regression analysis, adjusted for potential baseline confounders, and reported as hazard ratios (HRs). RESULTS: During 8 years of follow-up, 560 individuals developed fractures (15.4%). Adjusting for 10 potential confounders, women in the highest DII score quintile (i.e., most pro-inflammatory diet) had a significantly higher risk for fractures (HR = 1.46; 95% CI = 1.02-2.11) compared to women in the lowest quintile. An increase in one standard deviation of DII scores significantly predicted fracture onset in women (adjusted HR = 1.14; 95% CI = 1.02-1.27). The association between DII score and fractures was not significant among men or in the sample as whole. CONCLUSION: Pro-inflammatory diet is associated with a higher incidence of fractures in women but not men.

Adherence to the Mediterranean Diet and All-Cause Mortality Risk in an Elderly Italian Population: Data from the ILSA Study.

OBJECTIVE: The aim of this study was to evaluate adherence to the Mediterranean Diet (MD) and its association with all-cause mortality in an elderly Italian population. DESIGN: Data analysis of a longitudinal study of a representative, age stratified, population sample. SETTING: Study data is based upon the Italian Longitudinal Study on Aging (ILSA) a prospective, community-based cohort study. The baseline evaluation was carried out in 1992 and the follow-up in 1996 and 2000. PARTICIPANT: Participant food intake assessment was available at baseline for 4,232 subjects; information on survival was available for 2,665 at the 2000 follow-up. MEASUREMENTS: Adherence to the MD was evaluated with an a priori score based on the Mediterranean pyramid components. Cox proportional hazard models were used to assess the relationship between the MD score and all-cause mortality. Six hundred and sixty five subjects had died at the second follow-up (identified up to the first and second follow-up together; mean follow-up: 7.1±2.6 years). RESULTS: At the 2000 follow-up, adjusting for other confounding factors, participants with a high adherence to MD (highest tertile of the MD score distribution) had an all-cause mortality risk that was of 34% lower with respect to the subjects with low adherence (Hazard Ratio=0.66; 95% CI: 0.49-0.90; p=0.0144). CONCLUSION: According to study results, a higher adherence to the MD was associated with a low all-cause mortality risk in an elderly Italian population.

A machine learning tool for re-planning and adaptive RT: A multicenter cohort investigation.

PURPOSE: To predict patients who would benefit from adaptive radiotherapy (ART) and re-planning intervention based on machine learning from anatomical and dosimetric variations in a retrospective dataset. MATERIALS AND METHODS: 90 patients (pts) treated for head-neck cancer (H&N) formed a multicenter data-set. 41 H&N pts (45.6%) were considered for learning; 49 pts (54.4%) were used to test the tool. A homemade machine-learning classifier was developed to analyze volume and dose variations of parotid glands (PG). Using deformable image registration (DIR) and GPU, patients' conditions were analyzed automatically. Support Vector Machines (SVM) was used for time-series evaluation. "Inadequate" class identified patients that might benefit from replanning. Double-blind evaluation by two radiation oncologists (ROs) was carried out to validate day/week selected for re-planning by the classifier. RESULTS: The cohort was affected by PG mean reduction of 23.7±8.8%. During the first 3weeks, 86.7% cases show PG deformation aligned with predefined tolerance, thus not requiring re-planning. From 4th week, an increased number of pts would potentially benefit from re-planning: a mean of 58% of cases, with an inter-center variability of 8.3%, showed "inadequate" conditions. 11% of cases showed "bias" due to DIR and script failure; 6% showed "warning" output due to potential positioning issues. Comparing re-planning suggested by tool with recommended by ROs, the 4th week seems the most favorable time in 70% cases. CONCLUSIONS: SVM and decision-making tool was applied to overcome ART challenges. Pts would benefit from ART and ideal time for re-planning intervention was identified in this retrospective analysis.

Effect of magnesium supplementation on glucose metabolism in people with or at risk of diabetes: a systematic review and meta-analysis of double-blind randomized controlled trials.

Although higher dietary intakes of magnesium (Mg) seem to correspond to lower diabetes incidence, research concerning Mg supplementation in people with or at risk of diabetes is limited. Thus, we aimed to investigate the effect of oral Mg supplementation on glucose and insulin-sensitivity parameters in participants with diabetes or at high risk of diabetes compared with placebo. A literature search in PubMed, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials and Clinicaltrials.gov without language restriction, was undertaken. Eligible studies were randomized controlled trials (RCTs) investigating the effect of oral Mg supplementation vs placebo in patients with diabetes or at high risk of diabetes. Standardized mean differences (SMD) and 95% confidence intervals (CIs) were used for summarizing outcomes with at least two studies; other outcomes were summarized descriptively. Eighteen RCTs (12 in people with diabetes and 6 in people at high risk of diabetes) were included. Compared with placebo (n=334), Mg treatment (n=336) reduced fasting plasma glucose (studies=9; SMD=-0.40; 95% CI: -0.80 to -0.00; I2=77%) in people with diabetes. In conditions in people at high risk of diabetes (Mg: 226; placebo=227 participants), Mg supplementation significantly improved plasma glucose levels after a 2 h oral glucose tolerance test (three studies; SMD=-0.35; 95% CI: -0.62 to -0.07; I2=0%) and demonstrated trend level reductions in HOMA-IR (homeostatic model assessment-insulin resistance; five studies; SMD=-0.57; 95% CI: -1.17 to 0.03; I2=88%). Mg supplementation appears to have a beneficial role and improves glucose parameters in people with diabetes and also improves insulin-sensitivity parameters in those at high risk of diabetes.