Ipsilateral microcalcifications after breast-conserving surgery: is it possible to differentiate benign from malignant calcifications?

AIM: To analyse stereotactic biopsies of microcalcifications in patients with previous ipsilateral breast-conserving surgery (BCS) to identify the positivity rate, assess for an association between the patient's primary cancer or mammographic appearances of the microcalcifications, and the risk of recurrence. MATERIALS AND METHODS: Relevant patients from 2018-2020 were identified via a retrospective review of the prospectively maintained radiological procedure database. Clinicopathological features of the patients' primary tumour and new calcifications were obtained from the hospital electronic patient record system and the national integrated medical imaging system. RESULTS: Thirty-one percent of recurrences post-ipsilateral BCS presented as isolated microcalcifications on mammography. Fifty-three percent of patients undergoing stereotactic biopsy of ipsilateral calcifications had recurrence. A positive margin status was associated with new or recurrent malignancy. There was no significant correlation between oestrogen-receptor status, sentinel lymph node status, adjuvant radiotherapy or chemotherapy and the risk of recurrence. Calcifications within the tumour bed were more likely to be benign while calcifications within the same quadrant but remote from the tumour bed were more likely malignant. All coarse calcifications were benign while 67% of fine linear/fine linear branching and 89% of fine pleomorphic calcifications were malignant. CONCLUSION: Increased time since diagnosis, positive margin status, fine pleomorphic and fine linear calcifications in the same quadrant as the tumour bed were associated with malignancy. Patients with coarse calcifications and calcifications within the tumour bed may avoid stereotactic biopsy and undergo short-interval surveillance.

Variability in the measured response of bone to teriparatide.

UNLABELLED: Apparent failures of bone mineral density (BMD) response to teriparatide at spine or hip occur even in a high compliance context (15% spine and 55% hip). Apparent non-responders nevertheless show good biomarker response, suggesting that apparent BMD non-response is due to measurement imprecision. Calcium intake may be an important determinant of hip response. INTRODUCTION: Individuals vary in response to bone active agents, but that variability is poorly quantified and its basis is not well understood. The study included 203 postmenopausal women with moderately severe osteoporosis, all treated with teriparatide, calcium, and vitamin D. The study was performed at the Creighton University Medical Center, a single site. METHODS: This is a prospective study of change in bone mineral density and resorption biomarkers over a 12-month treatment period. BMD response at spine and total hip was quantified by computing slopes for each participant's values, and biomarker change by the difference in values across the 12-month study period. RESULTS: Of the total number of participants, 85.2% exhibited a significant spine BMD response, while only 44.8% had a significant change at the hip. However, mean biomarker response was marginally larger for the BMD non-responders at either site than for the responders, indicating biological, if not measurable densitometric, activity of teriparatide in essentially all participants. CONCLUSIONS: Occasional apparent failures of BMD response in patients receiving teriparatide are probably not due to failure of response at the level of the bone remodeling apparatus, but instead reflect a combination of measurement imprecision and variable bone remodeling balance. The reason for the latter remains unclear.

Need for reform in health professions accrediting.

At least 50 vocational or professional groups, exclusive of specialties within categories, now provide a health service. Many have established accrediting procedures for maintaining educational standards, and the number is increasing. So great is the demand from the accrediting bodies that universities and academic health centers find that the cost in terms of money, time, and duplication of effort has become exhorbitant, and thereby a major problem in the management of educational institutions. The duplication of effort leads to fragmentation of the entire accrediting process, and this, in turn, fosters inadequate sharing of health professions educational experiences. A model is presented that would lessen the burden of accrediting on educational institutions and simultaneously permit testing of the feasibility of a multiprofessional accrediting mechanism.

Adherence to clinical guidelines and the potential economic benefits of admission avoidance for acute uncomplicated diverticulitis.

BACKGROUND: The treatment paradigm for acute diverticulitis is changing. There is an increasing trend towards managing patients with uncomplicated diverticulitis in the community. AIMS: The aim of this study was to analyse how acute diverticulitis is managed in our institution and also to analyse national data pertaining to treatment of acute diverticulitis. METHODS: A prospective database of all patients admitted to our institution over a 2-year period (2014-2016) with acute diverticulitis was maintained. Severity of disease, treatment received and average length of stay (LOS) were analysed for all patients. Contemporaneous hospital inpatient enquiry (HIPE) data was interrogated to analyse current management for acute diverticulitis at a national level. RESULTS: One hundred twenty-six patients were admitted to our institution with acute diverticulitis during the study period (inpatient stay = €1277/night). Of patients, 59.5% had uncomplicated diverticulitis while 40.5% had complicated disease. The median LOS was 4 (range 1-34) days and 8 (range 2-51) days in the uncomplicated and complicated group, respectively. Based on HIPE data, there were 11,357 patients with uncomplicated diverticulitis and 526 patients with complicated diverticulitis admitted to Irish hospitals in the year 2015. Nationally, the median LOS for those with uncomplicated diverticulitis was 3 (range 1-142) days and for those with complicated diverticulitis the median LOS was 7 (range 1-308) days. Projected total cost for hospital stay nationally for uncomplicated diverticulitis amounted to €43.5 million for the year 2015. CONCLUSIONS: At present, uncomplicated diverticulitis in Ireland is not being managed as per evidence-based guidelines. Changing practice could result in significant cost savings for surgical departments.

Timing of peak bone mass in Caucasian females and its implication for the prevention of osteoporosis. Inference from a cross-sectional model.

To determine the timing of peak bone mass and density, we conducted a cross-sectional study of bone mass measurements in 265 premenopausal Caucasian females, aged 8-50 yr. Bone mass and bone mineral density were measured using dual X-ray absorptiometry and single-photon absorptiometry at the spine (anteroposterior, lateral), proximal femur, radius shaft, distal forearm, and the whole body. Bone mass parameters were analyzed using a quadratic regression model and segmented regression models with quadratic-quadratic or quadratic-linear form. The results show that most of the bone mass at multiple skeletal locations will be accumulated by late adolescence. This is particularly notable for bone mineral density of the proximal femur and the vertebral body. Bone mass of the other regions of interest is either no different in women between the age of 18 yr and the menopause or it is maximal in 50-yr-old women, indicating slow but permanent bone accumulation continuing at some sites up to the time of menopause. This gain in bone mass in premenopausal adult women is probably the result of continuous periosteal expansion with age. Since rapid skeletal mineral acquisition at all sites occurs relatively early in life, the exogenous factors which might optimize peak bone mass need to be more precisely identified and characterized.

Magnitude of non-operative surgical emergency admissions; service implications for surgical and radiological practice.

BACKGROUND: Financial sustainability is an area of sharp ongoing focus across the broad spectrum of the Irish Health Service. Recent attention has been drawn to the financial implications of non-operative surgical admissions, suggesting that some of these may be unnecessary. AIMS: In this study, we aim to determine the volume of emergency surgical admissions to Mayo University Hospital (MUH), in particular, to identify the scale of non-operative admissions and to assess the wider inherent implications for acute hospital services. METHODS: An electronic handover system for emergency surgical admissions was introduced in MUH in September 2014. All surgical admissions from September 1st 2014 to August 31st 2015 were identified from this prospectively maintained database. HIPE (Hospital Inpatient Enquiry) data were not used in this study. Theatre logbooks confirmed those patients who required operative intervention. RESULTS: 1466 patients were admitted as emergencies during the study period. 58 % (850) were male and median age was 48 years (0-100). Average length of stay was 5 days (range 1-125). 327 patients (22.3 %) required operative intervention. The most commonly performed procedure was appendicectomy (52.5 %). 48 (3.3 %) patients were transferred to other hospitals. 131 (8.9 %) admissions related to the acute urological conditions. Of the 1466 admissions, 546 underwent a CT scan, while 342 patients proceeded to ultrasound. CONCLUSION: Almost 80 % of all surgical emergency admissions were discharged without undergoing a formal operative procedure while generating a significant workload for the radiology department. Changes in working practices and hospital network structures will be required to reduce the burden of non-operative emergency admissions.

Post-chemotherapy retroperitoneal lymph node dissection in the management of metastatic testis cancer: the 16-year experience in an Irish setting.

INTRODUCTION: Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is an important tool in the management of advanced germ cell testis cancer, particularly non-seminoma. AIM: We present the 16-year experience with PC-RPLND in a single Irish tertiary referral centre, and compare our results to the major speciality centres worldwide. METHODOLOGY: All 78 patients undergoing PC-RPLND for the treatment of metastatic testis cancer between January 1996 and December 2011 were included. Medical records were reviewed and up to date follow-up obtained from primary referral centres, patient's GPs and individual patient interview. RESULTS: The mean age at diagnosis was 28.5 ± 7 years. Initial pathology included non-seminoma 62.8 %, seminoma 6.4 % and combined 19.2 %. All patients underwent pre-operative chemotherapy. The resection template utilised was bilateral infra-hilar in 29.5 %, unilateral infra-hilar in 46.2 % and supra-hilar in 20.5 %. Complete abdominal remission was achieved in all but one patient. Additional procedures were required in 38.5 % of patients (n = 30). Clavien Dindo grade three or four complications were seen in 8.9 %, including five patients who required early reoperation. Histology of RPLND specimen showed mature teratoma (41 %) and active cancer (11.5 %). Follow-up data were available for 66 patients (85 %). Median follow-up was 101 (11-207) months. Nine patients relapsed with median time to relapse 15 (8-60) months. Overall 5-year survival rate was 95.2 % (four deaths). CONCLUSION: In this relatively small series due to small population and low disease incidence, we have shown acceptable peri-operative course, morbidity and oncological outcomes with PC-RPLND compared to major international centres.

Incidence rate of type 2 diabetes is >50% lower in GrassrootsHealth cohort with median serum 25-hydroxyvitamin D of 41 ng/ml than in NHANES cohort with median of 22 ng/ml.

Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with lower risk of type 2 diabetes. This study compared incidence rates of type 2 diabetes among participants aged ≥20 years in two U.S. cohorts with markedly different median 25(OH)D concentrations. The median 25(OH)D concentration in the GrassrootsHealth (GRH) cohort was 41 ng/ml (N=4933) while in the 2005-6 National Health and Nutrition Examination Survey (NHANES) it was 22 ng/ml (N=4078) (P<0.0001). The adjusted annual incidence rate of type 2 diabetes was 3.7 per 1000 population (95% confidence interval=1.9, 6.6) in the GRH cohort, compared to 9.3 per 1000 population (95% confidence interval=6.7, 12.6) in NHANES. In the NHANES cohort, the lowest 25(OH)D tertiles (<17, 17-24 ng/ml) had higher odds of developing diabetes than the highest tertile (OR: 4.9, P=0.02 and 4.8, P=0.01 respectively), adjusting for covariates. Differences in demographics and methods may have limited comparability. Raising serum 25(OH)D may be a useful tool for reducing risk of diabetes in the population.

The isolation and characterisation of hyaluronic acid in egg shell.

Analysis showed that the organic part of the chicken's egg shell consisted of a series of proteins and polysaccharides, probably present as glycoproteins and glycosaminoglycans. A purified preparation of a glycosaminoglycan (minimum mol. wt. 25 000), homogeneous by sedimentation velocity analysis and sedimentation to equilibrium in a density gradient, contained equimolar amounts of N-acetylglucosamine (36.3% s/w) and glucuronic acid 35.6% w/w). Digestion with testicular and streptomyces hyaluronidases and identification of the degradation products showed the glycosaminoglycan to be hyaluronidases and identification of the degradation products showed the glycosaminoglycan to be hyaluronic acid.

Vitamin D inadequacy among post-menopausal women: a systematic review.

BACKGROUND: Vitamin D inadequacy has been studied extensively, due to concerns about ageing populations, associations with osteoporosis and other disorders (including non-musculoskeletal), and high prevalence. AIM: To review recent reports on the prevalence of vitamin D inadequacy among post-menopausal women with and without osteoporosis and/or other musculoskeletal diseases. DESIGN: Systematic review. METHODS: We reviewed publications in the past 10 years reporting prevalence estimates for vitamin D inadequacy, reported as serum 25(OH)D values below various levels. Thirty published studies in the English language were identified, from January 1994 through April 2004. RESULTS: In osteoporotic populations, the prevalence of 25(OH) vitamin D concentration <12 ng/ml ranged from 12.5% to 76%, while prevalence rates reached 50% to 70% of patients with a history of fracture(s) using a cut-off of 15 ng/ml. In post-menopausal women, the prevalence of 25(OH) vitamin D concentrations

Early results of the use of collagenase in the treatment of Dupuytren's contracture.

INTRODUCTION: In recent years, the enzyme collagenase has been developed for the percutaneous treatment of Dupuytren's contracture, allowing management of the condition as an outpatient. We present early results on the treatment of Dupuytren's contracture using injectable collagenase. METHODS: Patients awaiting Fasciectomy for Dupuytren's Contracture were selected for enrolment. Contracture cords were then marked and injected with collagenase in the outpatients department. Twenty-four hours later, patients returned for an extension procedure, performed under regional anaesthesia. Hand therapy was then commenced as for surgical release. Contracture angles were measured pre-injection and at follow-up. RESULTS: Thirteen fingers were treated in 10 patients with a mean age of 66 years. Eight little fingers and five ring fingers were treated. Four fingers had isolated metacarpophalangeal joint (MCPJ) contracture, one finger had isolated proximal interphalangeal joint (PIPJ) contracture and the remainder had combined contractures. Mean pre-treatment MCPJ contracture was 58.6° and the mean pre-treatment PIPJ contracture was 39°. Post-treatment contracture was 4.23° and 9° for the MCPJ and PIPJ, respectively. All patients were satisfied with their results. COMPLICATIONS: Significant post-injection bruising occured in one patient. Skin tears occurred in 11 digits, and in all cases healed without intervention. No tendon rupture occurred. CONCLUSIONS: Collagenase is a safe and effective outpatient-based treatment for Dupuytren's contracture, which may be useful in controlling surgical waiting lists. We recommend its use as first-line treatment in patients who are unsuitable more invasive treatment alternatives.

The bone-remodeling transient: implications for the interpretation of clinical studies of bone mass change.

A computer simulation of the bone-remodeling transient is described, in which the focus is explicitly on changes in clinically measurable bone mass (or density). Based upon quantitative remodeling data accumulated by histomorphometry and calcium tracer kinetics, the simulation shows that much of the apparent gain in bone produced by several agents currently employed to treat osteoporosis can be explained as a remodeling transient rather than as a fundamental alteration of remodeling balance. Even gains as large as 30% or more can be produced by nothing more than the remodeling transient under certain plausible combinations of basal remodeling rate, remodeling period, and degree of bone loss. The simulation further highlights the importance, in evaluating bone-active agents, of separating the response across the first remodeling period from bone changes that may ensue thereafter.

Fecal calcium density: a measure of calcium compliance.

We evaluated fecal calcium density (mass of calcium per g dry weight of feces) as a measure of compliance with a prescribed calcium intake regimen using 4 day fecal pools collected on a metabolic research unit from subjects ingesting measured, constant intakes. Fecal calcium density was highly correlated with intake (r = 0.897, P less than 0.001). Intake estimates based on fecal calcium density exhibited a standard error of the mean equal to 3.76 mmol calcium. Since a typical calcium supplement table contains 12.5 mmol calcium, the measurement of fecal calcium density is sensitive enough to detect regular omission of one or more pills daily. Applicability of this approach to convenience samples of feces was evaluated in 15 individuals by testing homogeneity of fecal calcium density values on up to six different 3-9 g portions (wet weight) of each volunteer's fecal sample. The within-sample coefficient of variation was 9.5% for all subsamples and 7.3% for samples from individuals with intakes above 25 mmol calcium per day. Thus feces are reasonably homogeneous in regard to calcium density. Accordingly, reasonably small fecal collections should suffice for its measurement.

Determinants of endogenous fecal calcium in healthy women.

Endogenous fecal calcium (EFC) excretion was measured in 518 studies in 191 normal perimenopausal women, most studied two to three times over a 15 year period. EFC averaged 102 +/- 25 mg/day. Absorption fraction was simultaneously determined by both double-isotope and balance methods. EFC was found to vary inversely with absorption fraction, and the observed relationship was used to calculate the total amount of calcium (TIC) entering the gut from endogenous sources. TIC averaged 140 +/- 34 mg/day and was found to be correlated with a number of intake and body size variables. Phosphorus intake was the most strongly correlated of all the variables (r = 0.404; P < 0.0001), each increment of 0.1 g phosphorus intake being associated with an increase in TIC of 6 mg. Lean body mass was the best correlated of the body size variables, with TIC rising by 1.6 mg/day for every kg lean mass. There were also small but significant correlations with protein and energy intakes, the latter suggesting that some of the variation of TIC is related to the amount of food consumed. Caffeine, previously reported as elevating TIC, did not exhibit a significant relationship in this study.

Characterization of perimenopausal bone loss: a prospective study.

This study characterized the change in bone mass, bone markers, pituitary/gonadal hormones, vitamin D, parathyroid hormone, and anthropometric variables in a cohort of healthy women as they passed through normal menopause. We recruited 75 women > 46 years old who had premenopausal estradiol (E2) and gonadotropin levels and regular menses. During 9.5 years of observation, 54 experienced normal menopause (PM group) and 21 remained estrogen replete (ER group). Before the beginning of the menopausal drop and after its completion, the slope of bone mass on time in the PM group was 0% for the spine, -0.61% per year for the total body, and -0.45 % per year for the femoral neck. Designating these losses as "age related," there were 0, 4.88, and 3.40% losses for spine, total body bone mineral (TBBM), and femoral neck, respectively, in the 8-year period for which the data were analyzed. Across menopause, we found a sigmoid pattern of bone loss in the PM group beginning about 2-3 years before the last menses and ending about 3-4 years after the last menses. The total estrogen-deprivation bone losses were 10.50, 7.73, and 5.30% for the spine, TBBM, and femoral neck, respectively. In the ER group, we found a 0, 0.59, and 0.93% per year loss in spine, TBBM, and femoral neck, respectively. Serum osteocalcin rose 77%, serum total alkaline phosphatase rose 34%, and urinary hydroxyproline/creatinine (Hypro/Cr) ratio rose 44% in the PM group, while remaining stable in the ER group. We conclude that menopausal bone loss is a composite of loss caused by estrogen deprivation and age per se for the hip and total body, but is caused by estrogen deprivation alone for the spine.

Comparison of speed of sound ultrasound with single photon absorptiometry for determining fracture odds ratios.

The purpose of this study was to compare the ability of ultrasound velocity measurement with that of single photon absorptiometry to determine the odds of history of fracture since age 40, for a population-based study. To do this we computed odds ratios and 95% confidence intervals for 809 women and 502 men, aged 50 years and older, who are participants in the prospective phase of the Saunders County Bone Quality Study. These participants received both the ultrasound and single photon absorptiometry bone measurements at the initiation of the study. In addition, a history of all fractures that had occurred to participants since age 40 was obtained. The two bone assessment methods were compared by examining the magnitude of the odds ratios, to determine which produces the highest estimate of the probability of odds of fracture, and by examining widths of the respective confidence intervals to show which estimate of odds ratio is the most precise. Ultrasound velocity estimates a higher probability of odds of both low-trauma fractures and all fractures than distal radius and ulna bone mineral content, but lower than bone mineral density at the same sites for both women and men. However, the ultrasound measure is more precise than bone mineral density, but less precise than bone mineral content. We conclude that ultrasound velocity is as good as single photon absorptiometry in estimating odds of fracture.

Bisphosphonate effects and the bone remodeling transient.

Published randomized clinical trial data for alendronate, given at a dose of 10 mg/day, were fitted by a computer algorithm to the currently accepted model of the bone remodeling process. The purpose was to determine how much of the reported improvement in lumbar spine bone density could be attributed to the inevitable remodeling transient and how much might represent positive bone balance. Very good fits to the clinical data were easily obtained, indicating the general validity of current syntheses of bone remodeling biology. The best fit was provided by simulations produced by combinations of 36-38% suppression of remodeling activation and positive remodeling balance ranging from 1.1 to 1.4% per year. Whole body bone biomarker changes would have suggested both a slightly greater degree of suppression and a higher baseline level of remodeling than could be provided by any of the simulations if they were to fit the clinical data. Either regional skeletal heterogeneity or lack of a one-to-one quantitative relationship between remodeling changes and biomarker changes may explain the discrepancies between the two approaches.