Detection and evaluation of haemophilic arthropathy: Which tools may be considered more reliable.

INTRODUCTION: Progressive arthropathy is the main cause of morbidity in patients with severe haemophilia. Diagnostic imaging can detect even subclinical arthropathy and impact prophylactic treatment. However, in most clinical settings the regular joint evaluation and follow-up are based on clinical evaluation and patient's personal reporting of problems, while diagnostic imaging is not regularly employed. AIM: The aim of our prospective study was to assess how ultrasound (US), clinical examination, patient's subjective assessment and certain laboratory biomarkers correlate with magnetic resonance imaging (MRI) for detection and evaluation of haemophilic arthropathy in order to determine which tool is the most reliable. METHODS: The study included 30 patients with severe haemophilia (age range 16-49 years). MRI (IPSG), US (HEAD-US), clinical examination (HJHS 2.1) and patient's subjective assessment of elbows, knees and ankles were performed; additionally, blood samples for laboratory analysis were taken (s-25-OH vitamin D, s-ferritin, s-C-terminal telopeptide of type I collagen, s-N-terminal propeptide of type I procollagen and s-cartilage oligomeric matrix protein). MRI results were used as a reference standard for joint status. Pearson's r was used to assess correlation of other methods with MRI. RESULTS: The correlation with MRI was the highest for US (r = .92), considerably higher than for clinical evaluation (r = .62) and patient's subjective assessment (r = .66). There was no correlation between the presence or degree of haemophilic arthropathy and any of the laboratory biomarkers. CONCLUSION: The results of our study warrant the inclusion of US into the regular follow-up of patients with severe haemophilia, where the equipment and staffing permit.

Switching to Denosumab or Bisphosphonates After Completion of Teriparatide Treatment in Women With Severe Postmenopausal Osteoporosis.

OBJECTIVE: To compare bone mineral density (BMD) changes after 12 months of treatment with denosumab or bisphosphonates in postmenopausal women with severe osteoporosis after stopping teriparatide therapy. METHODS: We retrospectively analyzed 140 postmenopausal women (mean age, 74.2 years) with severe osteoporosis who had been treated with teriparatide for 18 to 24 months at our outpatient clinic in a tertiary endocrine center between 2006 and 2015. After stopping teriparatide therapy, they continued treatment with a bisphosphonate (alendronate, risedronate, ibandronate, or zoledronic acid) or denosumab while receiving daily vitamin D and calcium. BMD at the lumbar spine (LS), total hip (TH), and femoral neck (FN) was measured by dual energy x-ray absorptiometry when teriparatide therapy was discontinued (baseline) and after 12 months of further treatment. Multivariate linear regression models were used to identify the predictors of BMD gain. RESULTS: After stopping teriparatide therapy, 70 women continued treatment with bisphosphonates and 70 received denosumab. LS, but not TH or FN, BMD gain was significantly greater in the denosumab group than in the bisphosphonates group at 12 months. Multivariate analysis showed that BMD gain at the LS was negatively associated with bisphosphonate versus denosumab treatment and positively associated with baseline serum total procollagen type I N-terminal propeptide. BMD gains at the FN were predicted by higher baseline serum urate levels. BMD gains at the TH and FN were negatively associated with pretreatment BMD gains at the same site. CONCLUSION: Twelve months after stopping teriparatide therapy, sequential denosumab treatment appeared to yield higher additional LS BMD gain on average compared with bisphosphonates treatment.

Long-term recovery of muscle strength after denervation in the fibular division of the sciatic nerve.

INTRODUCTION: The probability and degree of muscle recovery after lesions of long peripheral nerves have not been assessed quantitatively. METHODS: Twelve adults with closed injuries of the fibular division of the sciatic nerve with complete denervation of associated muscles were followed-up for 2-10 years. The onset of reinnervation was detected electromyographically. Calf circumference and maximum voluntary isometric contraction (MVIC) of foot dorsiflexion were measured on both sides during 2-4 visits. RESULTS: Reinnervation occurred in 11 patients after an average of 13 months. MVIC on the affected side was 2%-27% of that on the unaffected side (average 11%) and remained stable for the following 2-3 years. Correlations and mixed-model regressions confirmed that the degree of recovery was negatively associated with duration of denervation. CONCLUSIONS: Reinnervation occurs in about 90% of patients within about 1 year. About 10% of baseline dorsiflexion strength is permanently recovered, which is functionally relevant. Muscle Nerve, 2016 Muscle Nerve 54: -, 2016 Muscle Nerve 54: 702-708, 2016.

A NEW CLINICAL PREDICTION CRITERION ACCURATELY DETERMINES A SUBSET OF PATIENTS WITH BILATERAL PRIMARY ALDOSTERONISM BEFORE ADRENAL VENOUS SAMPLING.

OBJECTIVE: Adrenal venous sampling (AVS) is the only available method to distinguish bilateral from unilateral primary aldosteronism (PA). AVS has several drawbacks, so it is reasonable to avoid this procedure when the results would not affect clinical management. Our objective was to identify a clinical criterion that can reliably predict nonlateralized AVS as a surrogate for bilateral PA that is not treated surgically. METHODS: A retrospective diagnostic cross-sectional study conducted at Slovenian national endocrine referral center included 69 consecutive patients (mean age 56 ± 8 years, 21 females) with PA who underwent AVS. PA was confirmed with the saline infusion test (SIT). AVS was performed sequentially during continuous adrenocorticotrophic hormone (ACTH) infusion. The main outcome measures were variables associated with nonlateralized AVS to derive a clinical prediction rule. RESULTS: Sixty-seven (97%) patients had a successful AVS and were included in the statistical analysis. A total of 39 (58%) patients had nonlateralized AVS. The combined criterion of serum potassium ≥3.5 mmol/L, post-SIT aldosterone <18 ng/dL, and either no or bilateral tumor found on computed tomography (CT) imaging had perfect estimated specificity (and thus 100% positive predictive value) for bilateral PA, saving an estimated 16% of the patients (11/67) from unnecessary AVS. The best overall classification accuracy (50/67 = 75%) was achieved using the post-SIT aldosterone level <18 ng/dL alone, which yielded 74% sensitivity and 75% specificity for predicting nonlateralized AVS. CONCLUSIONS: Our clinical prediction criterion appears to accurately determine a subset of patients with bilateral PA who could avoid unnecessary AVS and immediately commence with medical treatment.

Attitudes of Slovene paediatricians to end-of-life care.

AIMS: The aims of this study were to assess the attitudes of Slovene paediatricians to aspects of end-of-life (EOL) care and compare these attitudes between paediatric intensivists, paediatric specialists and paediatric residents. METHODS: We performed a cross-sectional survey, using a specifically designed 43-item anonymous questionnaire. RESULTS: We included 323 out of 586 Slovene paediatricians and residents, while 46.7% (151 of 323) of them responded to our questionnaire. More than half of intensivists (54.2%) had sought counsel from the Committee for Medical Ethics in the past as compared with 12.0% and 12.1% of specialists and residents, respectively (P < 0.001). The decision to limit life-sustaining treatment (LST) was found to be ethically acceptable in all groups of respondents. The highest level of agreement was found in residents (90.2%), followed by 83.3% among intensivists and 73.8% among specialists (P = not statistically significant (NS)). Disagreement with termination of hydration was highest among residents (85%) and intensivists (79.2%) while it was lower among specialists (66.7%) (P = NS). Patient's best interest, good clinical practice and patient's autonomous decision were graded as the top three aspects of the EOL care, while cost effectiveness and availability of patient's bed in intensive care were the least important. CONCLUSIONS: The decision to limit LST measures was found to be ethically acceptable for Slovene paediatricians. No major differences were found among paediatric intensivists, specialist paediatricians and paediatric residents in the attitudes towards the EOL care.

Immunological status in patients with lower limb amputation due to peripheral arterial disease before and after comprehensive rehabilitation.

The immunological status before and after a comprehensive rehabilitation program was studied. Seven persons (4 males, 3 females, mean age 71.4 years) after lower limb amputation due to peripheral arterial disease (PAD) were subject to standard comprehensive rehabilitation program for amputees of four-week duration, which included training in activities of daily living, daily exercise of various types, training of crutch-assisted gait and use of leg prosthesis, and mild transcutaneous electrical stimulation. Before and after rehabilitation, peripherial blood was collected and the number and ratio of white blood cells were determined and analysed for the expression of cell surface antigens (CD3, CD4, CD8, CD19, CD25, CD69), cytokines (IFN-gamma, IL-4) and phagocytosis/oxidative killing functional tests. Due to strict patient selection criteria excluding serious accompanying disease, immunological parameters were within normal limits already before rehabilitation. After rehabilitation, an increase in oxidative burst was observed in monocytes and neutrophil granulocytes, but statistically significant only in monocytes. The expression of CD69 molecules by T cells and monocytes was significantly increased, as well as the expression of IL-4 by T cells. A significant decrease in the ratio of CD4 to CD8 cells was also found, but not a clinically critical one. It can therefore be concluded that the comprehensive rehabilitation treatment in patients with lower limb amputation due to PAD led to some--prevailingly positive--immunological changes, which were consistent with the patients' improved physical condition and clinical status.

Dexamethasone produces dose-dependent inhibition of sugammadex reversal in in vitro innervated primary human muscle cells.

BACKGROUND: Corticosteroids are frequently used during anesthesia to provide substitution therapy in patients with adrenal insufficiency, as a first-line treatment of several life-threatening conditions, to prevent postoperative nausea and vomiting, and as a component of multimodal analgesia. For these last 2 indications, dexamethasone is most frequently used. Due to the structural resemblance between aminosteroid muscle relaxants and dexamethasone, concerns have been raised about possible corticosteroid inhibition in the reversal of neuromuscular block by sugammadex. We thus investigated the influence of dexamethasone on sugammadex reversal of rocuronium-induced neuromuscular block, which could be relevant in certain clinical situations. METHODS: The unique co-culture model of human muscle cells innervated in vitro with rat embryonic spinal cord explants to form functional neuromuscular junctions was first used to explore the effects of 4 and 10 µM rocuronium on muscle contractions, as quantitatively evaluated by counting contraction units in contraction-positive explant co-cultures. Next, equimolar and 3-fold equimolar sugammadex was used to investigate the recovery of contractions from 4 and 10 µM rocuronium block. Finally, 1, 100, and 10 µM dexamethasone (normal, elevated, and high clinical levels) were used to evaluate any effects on the reversal of rocuronium-induced neuromuscular block by sugammadex. RESULTS: Seventy-eight explant co-cultures from 3 time-independent experiments were included, where the number of contractions increased to 10 days of co-culturing. Rocuronium showed a time-dependent effect on depth of neuromuscular block (4 µM rocuronium: baseline, 10, 20 minutes administration; P < 0.0001), while the dose-dependent effect was close to nominal statistical significance (4, 10 µM; P = 0.080). This was reversed by equimolar concentrations of sugammadex, with further and virtually complete recovery of contractions with 3-fold equimolar sugammadex (P < 0.0001). Dexamethasone diminished 10 µM sugammadex-induced recovery of contractions from rocuronium-induced neuromuscular block in a dose-dependent manner (P = 0.026) with a higher sugammadex concentration (30 µM) being close to statistically significantly improving recovery (P = 0.065). The highest concentration of dexamethasone decreased the recovery of contractions by equimolar sugammadex by 26%; this effect was more pronounced when 3-fold equimolar (30 µM) sugammadex was used for reversal (48%). CONCLUSIONS: This is the first report in which the effects of rocuronium and sugammadex interactions with dexamethasone have been studied in a highly accessible in vitro experimental model of functionally innervated human muscle cells. Sugammadex reverses rocuronium-induced neuromuscular block; however, concomitant addition of high dexamethasone concentrations diminishes the efficiency of sugammadex. Further studies are required to determine the clinical relevance of these interactions.

Experiences of Slovene ICU physicians with end-of-life decision making: a nation-wide survey.

BACKGROUND: Advances in intensive care medicine have enormously improved ability to successfully treat seriously ill patients. However, intensive treatment and prolongation of life is not always in the patient's best interest, and many ethical dilemmas arise in end-of-life (EOL) situations. We aimed to assess intensive care unit (ICU) physicians' experiences with EOL decision making and to compare the responses according to ICU type. MATERIAL AND METHODS: A cross-sectional survey was performed in all 35 Slovene ICUs, using a questionnaire designed to assess ICU physician experiences with EOL decision making, focusing on limitations of life-sustaining treatments (LST). RESULTS: We distributed 370 questionnaires (approximating the number of Slovene ICU physicians) and 267 were returned (72% response rate). The great majority of ICU physicians reported using do-not-resuscitate (DNR) orders (97%), withholding LST (94%), and withdrawing antibiotics (86%) or inotropes (95%). Fewer ICU physicians reported withdrawing mechanical ventilation (52%) or extubating patients (27%). Hydration was reported to be only rarely terminated (76% of participants reported never terminating it). In addition, 63% of participants had never encountered advance directives, and 39% reported to "never" or "rarely" participating in decision making with relatives of patients. Nurses were reported to be "never" or "rarely" involved in the EOL decision making process by 84% of participants. CONCLUSIONS: Limitation of LST was regularly used by Slovene ICU physicians. DNR orders and withholding of LST were the most commonly used measures. Hydration was only rarely terminated. In addition, use of advance directives was almost non-existent in practice, and the patients' relatives and nurses only infrequently participated in the decision making.

Body mass index and anthropometric characteristics of the hand as risk factors for carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) is the most common peripheral entrapment compressive neuropathy in the upper limbs. It is often correlated with personal factors of individuals, not only with certain medical conditions and jobs. The study aimed at clarifying the association of carpal tunnel syndrome with anthropometric characteristics of the hand and body mass index (BMI) as independent risk factors. A total of 100 subjects participated: 50 patients with electro-diagnostically confirmed CTS and 50 healthy volunteers without CTS symptoms as control group, each group including 37 women and 13 men. Height, weight, BMI, wrist depth and width, wrist index, hand shape index, digit index, palm length, palm width, third finger length and ratio of hand length to body height were assessed in all participants. To determine independent risk factors for CTS, multiple logistic regression was used. Wrist index and wrist width were significantly higher in CTS patients than in the control group. The estimated optimal threshold of wrist index for prediction of CTS was 0.69, above which the odds for CTS were estimated to increase 42-fold. Elevated BMI correlated with bilateral CTS in both genders. The study identified wrist index, BMI and ratio of hand length to body height ratio as independent risk factors for CTS.

Differences in respiratory function, depressive symptoms and quality of life between patients with hereditary motor and sensory neuropathy and myotonic dystrophy undergoing maintenance rehabilitation.

Hereditary motor and sensory neuropathy (HMSN) and myotonic dystrophy (MD) are chronic neuromuscular diseases that cause progressive muscular impairment and impact patient's quality of life. Conflicting findings in existing literature underscore the need for focussed research on specific health aspects in these patients. The aim of the study was to explore the differences in respiratory function, depressive symptoms and quality of life between patients with HMSN and MD undergoing maintenance rehabilitation. Our prospective observational study included 62 HMSN patients (median age 53.5, range 19-79 years; 38 women) and 50 MD patients (median age 54.0, range 18-77 years; 34 women) undergoing maintenance rehabilitation. They performed respiratory function tests (vital capacity, forced vital capacity, forced expiratory volume and peak expiratory flow) and respiratory muscle strength tests (maximum inspiratory pressure, maximum expiratory pressure and sniff nasal inspiratory force). The Center for Epidemiological Studies-Depression Scale was used to evaluate depression, and their health-related quality of life was assessed using the Quality of Life in Genetic Neuromuscular Disease Questionnaire. Using logistic regression, we examined group-difference in presence of depressive symptoms while accounting for age, symptoms duration, and marital status. Multiple linear regression was used to assess the difference in quality-of-life scores, adjusting for age, gender, and symptoms' duration. The HMSN group achieved statistically significantly better results than the MD group on all respiratory measures (about 17% absolute difference in the respiratory function measures and 30% relative difference in the respiratory muscle strength measures on average). Both groups exhibited a high level of depression symptoms (HMSN 24%, MD 44%; estimated adjusted odds-ratio MD vs. HMSN 1.9, 95% CI 0.8-4.5, P  = 0.127). We did not find a statistically significant difference between the groups regarding quality-of-life domains, though a trend towards better quality-of-life among the HMSN patients could be observed. The implication for future practice is that the MD patients would potentially benefit the most from targeted respiratory-rehabilitation interventions, and both groups could benefit from focussed mental-health interventions.