Practical Application of a New Cuffless Blood Pressure Measurement Method.

It would be useful to develop a reliable method for the cuffless measurement of blood pressure (BP), as such a method could be made available anytime and anywhere for the effective screening and monitoring of arterial hypertension. The purpose of this study is to evaluate blood pressure measurements through a CardioQVARK device in clinical practice in different patient groups. METHODS: This study involved 167 patients aged 31 to 88 years (mean 64.2 ± 7.8 years) with normal blood pressure, high blood pressure, and compensated high blood pressure. During each session, three routine blood pressure measurements with intervals of 30 s were taken using a sphygmomanometer with an appropriate cuff size, and the mean value was selected for comparison. The measurements were carried out by two observers trained at the same time with a reference sphygmomanometer using a Y-shaped connector. In the minute following the last cuff-based measurements, an electrocardiogram (ECG) with an I-lead and a photoplethysmocardiogram were recorded simultaneously for 3 min with the CardioQVARK device. We compared the systolic and diastolic BP obtained from a cuff-based mercury sphygmomanometer and smartphone-case-based BP device: the CardioQVARK monitor. A statistical analysis plan was developed using the IEEE Standard for Wearable Cuffless Blood Pressure Devices. Bland-Altman plots were used to estimate the precision of cuffless measurements. RESULTS: The mean difference between the values defined by CardioQVARK and the cuff-based sphygmomanometer for systolic blood pressure (SBP) was 0.31 ± 3.61, while that for diastolic blood pressure (DBP) was 0.44 ± 3.76. The mean absolute difference (MAD) for SBP was 3.44 ± 2.5 mm Hg, and that for DBP was 3.21 ± 2.82 mm Hg. In the subgroups, the smallest error (less than 3 mm Hg) was observed in the prehypertension group, with a slightly larger error (up to 4 mm Hg) found among patients with a normal blood pressure and stage 1 hypertension. The largest error was found in the stage 2 hypertension group (4-5.5 mm Hg). The largest error was 4.2 mm Hg in the high blood pressure group. We, therefore, did not record an error in excess of 7 mmHg, the upper boundary considered acceptable in the IEEE recommendations. We also did not reach a mean error of 5 mmHg, the upper boundary considered acceptable according to the very recent ESH recommendations. At the same time, in all groups of patients, the systolic blood pressure was determined with an error of less than 5 mm Hg in more than 80% of patients. While this study shows that the CardioQVARK device meets the standards of IEEE, the Bland-Altman analysis indicates that the cuffless measurement of diastolic blood pressure has significant bias. The difference was very small and unlikely to be of clinical relevance for the individual patient, but it may well have epidemiological relevance on a population level. Therefore, the CardioQVARK device, while being worthwhile for monitoring patients over time, may not be suitable for screening purposes. Cuffless blood pressure measurement devices are emerging as a convenient and tolerable alternative to cuff-based devices. However, there are several limitations to cuffless blood pressure measurement devices that should be considered. For instance, this study showed a high proportion of measurements with a measurement error of <5 mmHg, while detecting a small, although statistically significant, bias in the measurement of diastolic blood pressure. This suggests that this device may not be suitable for screening purposes. However, its value for monitoring BP over time is confirmed. Furthermore, and most importantly, the easy measurement method and the device portability (integrated in a smartphone) may increase the self-awareness of hypertensive patients and, potentially, lead to an improved adherence to their treatment. CONCLUSION: The cuffless blood pressure technology developed in this study was tested in accordance with the IEEE protocol and showed great precision in patient groups with different blood pressure ranges. This approach, therefore, has the potential to be applied in clinical practice.

Evaluation of microRNA Expression Features in Patients with Various Types of Arterial Damage: Thoracic Aortic Aneurysm and Coronary Atherosclerosis.

Circulating serum miRNA are increasingly used as biomarkers and potential treatment targets in several clinical scenarios, including cardiovascular diseases. However, the current data on circulating miRNA in thoracic aorta aneurism (TAA) patients are inconclusive. The aim of the present study is to compare the levels of several circulating miRNA in patients with degenerative TAA, coronary artery disease (CAD), and controls for special profile identification. We have identified several candidates for the role of new biomarkers: miR-143-3p, miR-181-5p, miR-126-3p, miR-126-5p, miR-145-5p, miR-150-5p, and miR-195-5p. MATERIALS AND METHODS: Serum samples of 100 patients were analyzed, including 388 TAA patients scheduled for elective surgery, 67 patients with stable CAD and 17 controls, were used for miRNA isolation and identification. RESULTS: More specific for TAA with very high predictive ability in ROC analysis was an increase in the levels of miR-21-5p, miR-29b-5p, miR-126-5p/-3p, miR-181b-5p, and miR-92a-3p, with the latter microRNA being investigated as a novel potential marker of TAA for the first time. CONCLUSION: TAA and CAD patients demonstrated a significant increase in the levels of circulating miR-126-5p/-3p, miR-181b-5p, and miR-29b-3p. More specific for TAA with very high predictive ability in ROC analysis was an increase in the levels of miR-21-5p, -29b-5p, -126-5p/-3p, 181b-5p, and -92a-3p, with the latter microRNA being investigated as a potential marker of TAA for the first time.

Left Ventricular Diastolic Dysfunction Screening by a Smartphone-Case Based on Single Lead ECG.

Aims: To investigate the potential of a signal processed by smartphone-case based on single lead electrocardiogram (ECG) for left ventricular diastolic dysfunction (LVDD) determination as a screening method. Methods and Results: We included 446 subjects for sample learning and 259 patients for sample test aged 39 to 74 years for testing with 2D-echocardiography, tissue Doppler imaging and ECG using a smartphone-case based single lead ECG monitor for the assessment of LVDD. Spectral analysis of ECG signals (spECG) has been used in combination with advanced signal processing and artificial intelligence methods. Wavelengths slope, time intervals between waves, amplitudes at different points of the ECG complexes, energy of the ECG signal and asymmetry indices were analyzed. The QTc interval indicated significant diastolic dysfunction with a sensitivity of 78% and a specificity of 65%, a Tpeak parameter >590 ms with 63% and 58%, a T value off >695 ms with 63% and 74%, and QRSfi > 674 ms with 74% and 57%, respectively. A combination of the threshold values from all 4 parameters increased sensitivity to 86% and specificity to 70%, respectively (OR 11.7 [2.7-50.9], P < .001). Algorithm approbation have shown: Sensitivity-95.6%, Specificity-97.7%, Diagnostic accuracy-96.5% and Repeatability-98.8%. Conclusion: Our results indicate a great potential of a smartphone-case based on single lead ECG as novel screening tool for LVDD if spECG is used in combination with advanced signal processing and machine learning technologies.

The Profile of Circulating Blood microRNAs in Outpatients with Vulnerable and Stable Atherosclerotic Plaques: Associations with Cardiovascular Risks.

Non-coding RNAs reflect many biological processes in the human body, including athero-sclerosis. In a cardiology outpatient department cohort (N = 83), we aimed to compare the levels of circulating microRNAs in groups with vulnerable plaques (N = 22), stable plaques (N = 23) and plaque-free (N = 17) depending on coronary computed tomography angiography and to evaluate associations of microRNA levels with calculated cardiovascular risks (CVR), based on the SCORE2 (+OP), ACC/AHA, ATP-III and MESA scales. Coronary computed tomography was performed on a 640-slice computed tomography scanner. Relative plasma levels of microRNA were assessed via a real-time polymerase chain reaction. We found significant differences in miR-143-3p levels (p = 0.0046 in plaque-free vs. vulnerable plaque groups) and miR-181b-5p (p = 0.0179 in stable vs. vulnerable plaques groups). Analysis of microRNA associations with CVR did not show significant differences for SCORE2 (+OP) and ATPIII scales. MiR-126-5p and miR-150-5p levels were significantly higher (p < 0.05) in patients with ACC/AHA risk >10% and miR-145-5p had linear relationships with ACC/AHA score (adjusted p = 0.0164). The relative plasma level of miR-195 was higher (p < 0.05) in patients with MESA risk > 7.5% and higher (p < 0.05) in patients with zero coronary calcium index (p = 0.036). A linear relationship with coronary calcium was observed for miR-126-3p (adjusted p = 0.0484). A positive correlation with high coronary calcium levels (> 100 Agatson units) was found for miR-181-5p (p = 0.036). Analyzing the biological pathways of these microRNAs, we suggest that miR-143-3p and miR-181-5p can be potential markers of the atherosclerosis process. Other miRNAs (miR-126-3p, 126-5p, 145-5p, 150-5p, 195-5p) can be considered as potential cardiovascular risk modifiers, but it is necessary to validate our results in a large prospective trial.

Cardiopulmonary exercise testing for cardiovascular risk assessment in patients undergoing gastric and oesophageal cancer surgery: results from a prospective interventional cohort study.

BACKGROUND: Cardiopulmonary exercise testing (CPET) has shown to be useful for preoperative risk stratification in various types of intra-abdominal and thoracic surgery. However, data about the predictive value of CPET for cardiovascular outcome after gastric or oesophageal cancer surgery are inconclusive. The aim of this study was to evaluate the prognostic value of CPET parameters for the prediction of cardiovascular complications in patients with this type of surgery. METHODS: This is a prospective single-centre interventional cohort study including 200 consecutive patients who underwent elective surgery for oesophageal and/or gastric cancer. Symptom-limited CPET was performed preoperatively to evaluate the potential of various test-derived parameters including anaerobic threshold (AT) to predict cardiovascular complications within 30 days after surgery. RESULTS: 200 patients (mean age 68±14.2 years) met inclusion and exclusion criteria: oesophageal surgery 54 pts, gastric surgery 132 pts and combined oesophageal/gastric surgery 14 pts. 41/200 pts (20.5%) experienced cardiovascular complications during and within 30 days after surgery including 4 non-fatal myocardial infarctions (2%), 1 stroke (0.5%); 6 dead from cardiovascular causes (3%) and less serious complications in 30 patients (15%) including angina attacks and antiarrhythmic therapy for ventricular arrhythmias or for atrial fibrillation/flutter. Results from preoperative CPET indicate that an AT level below 11 mL/kg/min was highly predictive for any cardiovascular complication (p=0.02, OR 6.33, 95% CI 1.78 to 22.47). An AT level <9.5 had the best predictive accuracy for major perioperative cardiac complications (sensitivity 93%, specificity 68%, positive predicative value 75%, negative predicative value 98.8%). CONCLUSION: CPET is a useful perioperative risk assessment tool for patients undergoing surgery for oesophageal and gastric cancer, which carries a particularly high risk for cardiovascular complications. An AT <9.5 mL/kg/min turned out to be the most reliable predictor for major cardiovascular complications.

Intermittent Hypoxic-Hyperoxic Exposures Effects in Patients with Metabolic Syndrome: Correction of Cardiovascular and Metabolic Profile.

The aim of this study was to evaluate efficacy and applicability of the "intermittent hypoxic-hyperoxic exposures at rest" (IHHE) protocol as an adjuvant method for metabolic syndrome (MS) cardiometabolic components. A prospective, single-center, randomized controlled clinical study was conducted on 65 patients with MS subject to optimal pharmacotherapy, who were randomly allocated to IHHE or control (CON) groups. The IHHE group completed a 3-week, 5 days/week program of IHHE, each treatment session lasting for 45 min. The CON group followed the same protocol, but was breathing room air through a facial mask instead. The data were collected 2 days before, and at day 2 after the 3-week intervention. As the primary endpoints, systolic (SBP) and diastolic (DBP) blood pressure at rest, as well as arterial stiffness and hepatic tissue elasticity parameters, were selected. After the trial, the IHHE group had a significant decrease in SBP and DBP (Cohen's d = 1.15 and 0.7, p < 0.001), which became significantly lower (p < 0.001) than in CON. We have failed to detect any pre-post IHHE changes in the arterial stiffness parameters (judging by the Cohen's d), but after the intervention, cardio-ankle vascular indexes (RCAVI and LCAVI) were significantly lowered in the IHHE group as compared with the CON. The IHHE group demonstrated a medium effect (0.68; 0.69 and 0.71 Cohen's d) in pre-post decrease of Total Cholesterol (p = 0.04), LDL (p = 0.03), and Liver Steatosis (p = 0.025). In addition, the IHHE group patients demonstrated a statistically significant decrease in pre-post differences (deltas) of RCAVI, LCAVI, all antropometric indices, NTproBNP, Liver Fibrosis, and Steatosis indices, TC, LDL, ALT, and AST in comparison with CON (p = 0.001). The pre-post shifts in SBP, DBP, and HR were significantly correlated with the reduction degree in arterial stiffness (ΔRCAVI, ΔLCAVI), liver fibrosis and steatosis severity (ΔLFibr, ΔLS), anthropometric parameters, liver enzymes, and lipid metabolism in the IHHE group only. Our results suggested that IHHE is a safe, well-tolerated intervention which could be an effective adjuvant therapy in treatment and secondary prevention of atherosclerosis, obesity, and other components of MS that improve the arterial stiffness lipid profile and liver functional state in MS patients.

Misdiagnosed and maltreated scaphoid fractures - costly both for society and patients: A review of filed claims to the Swedish National Patient Insurance Company 2011-2018.

Misdiagnosed and maltreated scaphoid fractures filed to the Swedish National Patient Insurance Company (LÖF) 2011-2018 were analyzed in terms of complications and costs for society. All filed claims are database-registered (altogether 200 000 claims since 2000). This database was assessed in June 2019 through injury ICD10-SWE-diagnoses. Demographics, complications, complaints, corrective surgeries and costs were analyzed. The numbers of claims for scaphoid fractures were reviewed and compared with all claims. There was a statistically significant trend towards decreasing numbers of notified scaphoid fracture cases during this time. This is not the case compared with the total annually notified injuries to LÖF during the same time, where we instead can see statistically significant increased numbers. Median age for the 128 patients was 24 years. Men represented 76%. Seventy-eight of the 128 (61%) claims were judged as avoidable, compared with 42% in terms of all notified injuries. Pseudoarthrosis dominated as complication (n = 71). Total numbers of complications were 117, and 47 of the 78 patients had medical invalidity as a consequence. Up to six secondary corrective surgeries per patient were required. Complications and disabilities were more severe if patients needed more than one surgery. The total costs were calculated to €1 226 193. Level of Evidence: LoE III, Therapeutic.

Hair Lead, Aluminum, and Other Toxic Metals in Normal-Weight and Obese Patients with Coronary Heart Disease.

The objective of the present study was to evaluate hair toxic metal levels in patients with obesity and/or coronary heart disease (CHD). Following a 2 × 2 factorial design, subjects without CHD were grouped into normal weight control (n = 123) and obese groups (n = 140). Patients suffering from CHD were divided into normal weight (n = 180) and obese CHD subjects (n = 240). Hair Al, As, Cd, Hg, Ni, and Pb levels were evaluated using inductively-coupled plasma mass-spectrometry. The data demonstrate that hair Al and Hg levels were higher in obese subjects as compared to normal weight controls. Normal weight CHD patients were characterized by significantly higher hair Al, As, Cd, and Pb levels when compared to healthy subjects. The highest hair Al, As, and Pb levels were observed in obese CHD patients, significantly exceeding the respective values in other groups. Factorial analysis revealed significant influence of factorial interaction (CHD*obesity) only for hair Pb content. Given the role of obesity as a risk factor for CHD, it is proposed that increased toxic metal accumulation in obesity may promote further development of cardiovascular diseases.

Cuffless Blood Pressure Measurement Using a Smartphone-Case Based ECG Monitor with Photoplethysmography in Hypertensive Patients.

The availability of simple, accurate, and affordable cuffless blood pressure (BP) devices has the potential to greatly increase the compliance with measurement recommendations and the utilization of BP measurements for BP telemonitoring. The aim of this study is to evaluate the correlation between findings from routine BP measurements using a conventional sphygmomanometer with the results from a portable ECG monitor combined with photoplethysmography (PPG) for pulse wave registration in patients with arterial hypertension. METHODS: The study included 500 patients aged 32-88 years (mean 64 ± 7.9 years). Mean values from three routine BP measurements by a sphygmomanometer with cuff were selected for comparison; within one minute after the last measurement, an electrocardiogram (ECG) was recorded for 3 min in the standard lead I using a smartphone-case based single-channel ECG monitor (CardioQVARK®-limited responsibility company "L-CARD", Moscow, Russia) simultaneously with a PPG pulse wave recording. Using a combination of the heart signal with the PPG, levels of systolic and diastolic BP were determined based on machine learning using a previously developed and validated algorithm and were compared with sphygmomanometer results. RESULTS: According to the Bland-Altman analysis, SD for systolic BP was 3.63, and bias was 0.32 for systolic BP. SD was 2.95 and bias was 0.61 for diastolic BP. The correlation between the results from the sphygmomanometer and the cuffless method was 0.89 (p = 0.001) for systolic and 0.87 (p = 0.002) for diastolic BP. CONCLUSION: Blood pressure measurements on a smartphone-case without a cuff are encouraging. However, further research is needed to improve the accuracy and reliability of clinical use in the majority of patients.

Noninvasive Assessment of the Fractional Flow Reserve with the CT FFRc 1D Method: Final Results of a Pilot Study.

Background: Until recently, Russia did not utilize noninvasive fractional flow reserve (FFR) assessment. We developed an automated algorithm for noninvasive assessment of FFR based on a one-dimensional (1D) mathematical modeling. Objective: The research aims to evaluate the diagnostic accuracy of this algorithm. Methods: The study enrolled 80 patients: 16 of them underwent 64-slice computed tomography - included retrospectively, 64 - prospectively, with a 640-slice CT scan. Specialists processed CT images and evaluated noninvasive FFR. Ischemia was confirmed if FFR < 0.80 and disproved if FFR ≥ 0.80. The prospective group of patients was hospitalized for invasive FFR assessment as a reference standard. If ischemic, patients underwent stent implantation. In the retrospective group, patients already had invasive FFR values.Statistical analysis was performed using GraphPad Prism 8. We compared two methods using a Bland-Altman plot and per-vessel ROC curve analysis. Considering the abnormality of distribution by the Kolmogorov-Smirnov test, we have used Spearman's rank correlation coefficient. Results: During data processing, three patients of the retrospective and 46 patients of the prospective group were excluded. The sensitivity of our method was 66.67% (95% CI: 46.71-82.03); the specificity was 78.95% (95% CI: 56.67-91.49), p = 0.0052, in the per-vessel analysis. In per-patient analysis, the sensitivity was 69.57% (95% CI: 49.13-84.40); the specificity was 87.50% (95% CI: 52.91-99.36), p = 0.0109. The area under the ROC curve in the per-vessel analysis was 77.52% (95% CI: 66.97-88.08), p < 0.0001. Conclusion: The obtained indices of sensitivity, specificity, PPV, and NPV are, in general, comparable to those in other studies. Moreover, the noninvasive values of FFR yielded a high correlation coefficient with the invasive values. However, the AUC was not high enough, 77.52 (95% CI: 66.97-88.08), p < 0.0001. The discrepancy is probably attributed to the initial data heterogeneity and low statistical power.

Relationship Between Elevated Hair Mercury Levels, Essential Element Status, and Metabolic Profile in Overweight and Obese Adults.

The objective of the present study was to evaluate hair essential and trace element levels and metabolic risk markers in overweight and obese subjects in relation to body mercury burden. According to 2 × 2 factorial design a total of 440 adults were distributed to four groups: (i) low-Hg normal-weight subjects (n = 114); (ii) high-Hg normal weight subjects (n = 113); (iii) low-Hg overweight (BMI > 25) subjects (n = 110); (iv) high-Hg overweight (BMI > 25) subjects (n = 110). Hg-exposed groups consisted of subjects characterized by frequent seafood consumption (> 4 times/week) subsequently evaluated by hair analysis (> 0.58 µg/g). Dietary-exposed subjects were characterized by a more than 3-fold higher hair Hg content irrespectively of body weight values. Both low-Hg and high-Hg overweight subjects were characterized by significantly higher ALT activity, as well as elevated serum glucose, LDL, and triglyceride levels as compared to the respective groups of normal weight subjects. High Hg body burden had a more significant effect on metabolic parameters in overweight and obese adults. Particularly, high-Hg overweight subjects were characterized by significantly higher serum creatinine and uric acid levels, as well as increased GGT and CK activity as compared to low-Hg overweight counterparts. In addition, hair Mg, Mn, and Sr content in high-Hg overweight subjects was significantly lower than that in low-Hg normal weight and overweight examinees. In turn, high Hg levels in overweight subjects were associated with significantly higher hair Se and Zn levels when compared to unexposed overweight adults. Generally, the obtained data demonstrate that increased hair Hg levels in overweight and obese subjects is associated with adverse metabolic profile. It is proposed that observed metabolic alterations may be at least partially mediated by Hg-associated disturbances in essential trace element and mineral metabolism.

Serum zinc, copper, zinc-to-copper ratio, and other essential elements and minerals in children with attention deficit/hyperactivity disorder (ADHD).

BACKGROUND: Essential trace elements and minerals play a significant role in neurodevelopment. Although certain studies demonstrated impaired essential trace element and mineral status in children with ADHD, the existing data are insufficient. The objective of the present study was to assess serum trace element and mineral levels in children with ADHD. METHODS: Serum trace element and mineral levels in 68 children with ADHD and 68 neurotypical controls were assessed using ICP-MS at NexION 300D (PerkinElmer Inc., USA) equipped with ESI SC-2 DX4 autosampler (Elemental Scientific Inc., USA). RESULTS: Serum Cr, Mg, and Zn levels in children with ADHD were 21 % (p = 0.010), 4 % (p = 0.005), and 7 % (p = 0. 001) lower as compared to the healthy controls, respectively. In turn, serum Cu/Zn values were 11 % higher than those in the control group. Age and gender had a significant impact on serum element levels in ADHD. Particularly, preschool children were characterized by significantly increased Cu (+8 %; p = 0.034), and Cu/Zn (+19 %; p < 0.001) values, whereas serum Zn (-9 %; p = 0.004) level was decreased. In primary school-aged children only 6 % (p = 0.007) lower Mg levels were observed. Both boys and girls with ADHD were characterized by 8 % (p = 0.016) lower serum Zn levels and 10 % (p = 0.049) higher Cu/Zn values when compared to neurotypical girls. Boys with ADHD also had significantly higher Cu/Zn, exceeding the respective control values by 12 % (p = 0.021), predominantly due to a 7 % (p = 0.035) decrease in serum Zn. Serum Mg levels were also found to be significantly lower than those in neurotypical children by 5 % (p = 0.007). In adjusted regression models serum Cr (ß=-0.234; p = 0.009) and Cu/Zn (ß = 0.245; p = 0.029) values were significantly associated with ADHD, respectively. Two-way ANOVA revealed a significant impact of ADHD on Cr, Mg, Zn, and Cu/Zn, whereas age was associated with Cu, I, Mg, Mo, and Cu/Zn, whereas gender accounted only for variability in serum Mn levels. Principal component analysis (PCA) also revealed significant contributions of Mg, Zn, and Cu/Zn values to ADHD variability. CONCLUSIONS: Hypothetically, the observed decrease of essential trace elements, namely Mg and Zn, and elevation of Cu/Zn may significantly contribute to the risk of ADHD or its severity and/or comorbidity.

Retroelement-Linked H3K4me1 Histone Tags Uncover Regulatory Evolution Trends of Gene Enhancers and Feature Quickly Evolving Molecular Processes in Human Physiology.

BACKGROUND: Retroelements (REs) are mobile genetic elements comprising ~40% of human DNA. They can reshape expression patterns of nearby genes by providing various regulatory sequences. The proportion of regulatory sequences held by REs can serve a measure of regulatory evolution rate of the respective genes and molecular pathways. METHODS: We calculated RE-linked enrichment scores for individual genes and molecular pathways based on ENCODE project epigenome data for enhancer-specific histone modification H3K4me1 in five human cell lines. We identified consensus groups of molecular processes that are enriched and deficient in RE-linked H3K4me1 regulation. RESULTS: We calculated H3K4me1 RE-linked enrichment scores for 24,070 human genes and 3095 molecular pathways. We ranked genes and pathways and identified those statistically significantly enriched and deficient in H3K4me1 RE-linked regulation. CONCLUSION: Non-coding RNA genes were statistically significantly enriched by RE-linked H3K4me1 regulatory modules, thus suggesting their high regulatory evolution rate. The processes of gene silencing by small RNAs, DNA metabolism/chromatin structure, sensory perception/neurotransmission and lipids metabolism showed signs of the fastest regulatory evolution, while the slowest processes were connected with immunity, protein ubiquitination/degradation, cell adhesion, migration and interaction, metals metabolism/ion transport, cell death, intracellular signaling pathways.

Surgical fasciectomy versus collagenase injection in treating recurrent Dupuytren disease: study protocol of a randomised controlled trial.

INTRODUCTION: There is no definitive cure for Dupuytren disease (DD), and recurrence of finger contractures after treatment is common. Surgical fasciectomy is considered the standard treatment method for recurrence, although associated with a high incidence of complications. Collagenase injection, a non-surgical treatment option, has been shown to be a safe and effective method; however, most studies regarding collagenase have involved first-time treatment. Collagenase efficacy in patients with recurrent DD beyond the immediate effect has not yet been determined. The aim of our study is to compare surgical fasciectomy and collagenase injection in treating recurrent DD. METHODS AND ANALYSIS: The study is a single-centre randomised controlled trial. Inclusion criteria are recurrence of DD in one or more fingers after previous treatment with fasciectomy or collagenase injection, a passive extension deficit ≥30° in the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joint, and a palpable cord causing the recurrent contracture. A total of 56 patients will be randomised to either surgical fasciectomy or collagenase injection. A hand therapist blinded to patients' group allocation will measure range of motion at baseline, 3 months, 12 months, 24 months and 60 months. The primary outcomes are the total active extension deficit (MCP plus PIP) at 3 months and the proportion of patients with contracture worsening ≥20° in the treated finger joint at 2 years compared with 3 months. The secondary outcomes include changes in total active motion, active and passive extension deficit from baseline up to 5 years, scores on patient-reported outcome measures, adverse events and costs of treatment. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Regional Ethical Review Board, Lund University, Sweden(2017/623). The trial will be conducted according to the Helsinki Declaration of 1975, revised in 2000. The results of the trial will be disseminated as published articles in peer-reviewed journals. TRIAL REGISTRATION: NCT03406338; Pre-results.

Intermittent systemic hypoxic-hyperoxic training for myocardial protection in patients undergoing coronary artery bypass surgery: first results from a single-centre, randomised controlled trial.

Background: Although remote ischaemic preconditioning (RIP) provides protection against myocardial ischaemia and reperfusion injury during cardiac surgery, it is not widely used. Systemic intermittent hypoxic-hyperoxic training (IHHT) may be a suitable alternative. Methods: This is a prospective, single-centre, randomised controlled trial. 127 patients with ischaemic heart disease and indication for coronary artery bypass graft (CABG) surgery from the Cardiology Clinic IM Sechenov First Moscow State Medical University were randomly assigned to IHHT, IHHT-control or RIP. Primary endpoint was serum concentration of troponin I and lactate 2 and 24 hours after surgery. Results: Median value for troponin I 24 hours after surgery was 1.068 (0.388-1.397) ng/mL in the IHHT group and was significantly lower compared with IHHT-controls with 1.980 (1.068-3.239) ng/mL (p=0.012) and to the RIP group with 1.762 (1.288-2.186) ng/mL (p=0.029), while there was no significant difference between RIP and the IHHT-control. Serum lactate after surgery was 1.74 (1.23-2.04) mmol/L in the IHHT group and was also significantly lower compared with IHHT-controls with 2.10 (1.80-2.29) mmol/L (p=0.045) and RIP with 2.12 (1.91-2.33) mmol/L (p=0.032). No significant complications or serious adverse events were observed during IHHT. Intraoperative and early postoperative complications did not differ significantly between groups. Conclusions: The results of this first trial using IHHT for myocardial protection against perioperative ischaemic myocardial injury in patients undergoing CABG surgery are promising and further larger trials should be done with adequate power to detect clinical rather than surrogate marker benefits.

One-Dimensional Mathematical Model-Based Automated Assessment of Fractional Flow Reserve in a Patient with Silent Myocardial Ischemia.

BACKGROUND Noninvasive assessment of the fractional flow reserve (FFR) in patients with coronary artery disease plays an important role in determining the need for revascularization. It is particularly relevant for patients with a borderline stenoses and painless myocardial ischemia. Our article describes the first clinical experience in the Russian Federation of using an automated method of noninvasive assessment of the fractional flow reserve (FFRct) with a one-dimensional (1-D) mathematical model in a patient with painless myocardial ischemia. CASE REPORT A 58-year-old male patient who underwent stent implantation in the left circumflex coronary artery (LCX) due to an acute non-ST-elevation posterior myocardial infarction had borderline stenoses of the left anterior descending artery (LAD). After stent implantation, there were no relapse angina symptoms on drug treatment, and according to our examination guideline for patients with borderline stenoses, a treadmill test was performed. The test was positive; therefore, FFR assessment was recommended, with coronary multi-slice CT being performed. The following results were obtained: FFRct LAD - 0.57; FFRct LCX - 0.88. An invasive assessment of FFR was also performed as a reference standard and revealed: FFR LAD - 0.6; FFR LCX - 0.88, and simultaneously a LAD percutaneous coronary intervention (PCI) was performed. Three months later, the patient underwent a stress test, which revealed no evidence of induced ischemia. CONCLUSIONS Our method of noninvasive assessment of FFR has shown encouraging results, but we believe that larger-scale studies are needed to establish it as common clinical practice.

Similar 1-year subjective outcome after a distal radius fracture during the 10-year-period 2003-2012.

Background and purpose - During the last decades, treatment of distal radius fractures (DRFs) has changed, with surgical intervention being more common and with new techniques. We investigated whether this change has influenced the subjective outcome. Here we report, year by year, the 1-year score after a DRF over a 10-year-period, using a patient-reported outcome measure. Patients and methods - Patients aged 18 years or more with a DRF between 2003 and 2012 were prospectively and consecutively registered in a longitudinal outcome database. 1 year after the fracture, all the patients were sent a validated subjective outcome questionnaire, the Disabilities of the Arm, Shoulder, and Hand (DASH). The lower the score (0-100), the better the outcome. Results - Between 2003 and 2012, 3,666 patients (2,833 of them women; mean age 62 (18-98) years) were included. 22% were operated and the rate remained constant over the years. The surgical methods shifted from external fixators (42%) and fragment-specific plates (45%) in 2003, to mainly volar locking plates (65%) in 2012. 70% of the patients responded to the 1-year DASH questionnaire. The median DASH score was 9 (IQR: 2-25) for the cohort, both in surgically treated patients (9 (IQR: 3-25)) and in non-surgically treated patients (9 (IQR 2-27)). Subgroup analysis showed a higher median DASH score for women than for men; for patients with AO type C fractures rather than type B or type A fractures; for patients with external fixation or fragment-specific fixation than for those who underwent surgery using volar locking plates; and for patients who were operated by a general orthopedic surgeon rather than a hand surgeon. Interpretation - The shift in surgical treatment had no influence on the subjective outcome for the cohort.

Fragment-Specific Fixation Versus Volar Locking Plates in Primarily Nonreducible or Secondarily Redisplaced Distal Radius Fractures: A Randomized Controlled Study.

PURPOSE: To compare the patient-reported, clinical, and radiographic outcome of 2 methods of internal fixation in distal radius fractures. METHODS: Fifty patients, mean age 56 years (range, 21-69 years) with primarily nonreducible or secondarily redisplaced distal radius fractures were randomized to open reduction internal fixation using volar locking plates (n = 25) or fragment-specific fixation (n = 25). The patients were assessed on grip strength, range of motion, patient-reported outcome (Quick Disabilities of the Arm, Shoulder, and Hand), pain (visual analog scale), health-related quality of life (Short Form-12 [SF-12]), and radiographic evaluation. Grip strength at 12 months was the primary outcome measure. RESULTS: At 12 months, no difference was found in grip strength, which was 90% of the uninjured side in the volar plate group and 87% in the fragment-specific fixation group. No differences were found in range of motion and the median Quick Disabilities of the Arm, Shoulder, and Hand score was 5 in both groups. The overall complication rate was significant, 21% in the volar locking plate group, compared with 52% in the fragment-specific group. CONCLUSIONS: In treatment of primarily nonreducible or secondarily redisplaced distal radius fractures, volar locking plates and fragment-specific fixation both achieve good and similar patient-reported outcomes, although more complications were recorded in the fragment-specific group. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Individualized outcome measures of daily activities are sensitive tools for evaluating hand surgery in rheumatic diseases.

OBJECTIVES: To explore the ability of six outcome measures to capture clinically important changes in patients with rheumatic diseases undergoing hand surgery and to study predictors of changes in activity performance in different patient and surgery strata. METHODS: A total of 172 patients (median age 59 years, disease duration 18 years) were stratified into subgroups: diagnosis, age, general function, type of surgery. Performance of daily activities and satisfaction were assessed by the Canadian Occupational Performance Measure (COPM). Clinically important improvement was defined as a two-step improvement in COPM. Hand function was assessed by reference to grip strength (Grippit), pinch strength (pinch gauge), hand pain (visual analogue scale) and grip ability (Grip Ability Test). Responsiveness was calculated as effect size (ES) at 6-month follow-up compared with baseline. RESULTS: Clinically important improvement was reached by 25-69% depending on outcome measure and type of surgery. Improvement was smaller in patients with multiple simultaneous procedures. Regardless of diagnosis, age, general function and type of surgery, patients improved significantly in all measures, with the largest changes in COPM(performance) and COPM(satisfaction) (ES 0.7-1.9). The ES of pain ranged from 0.2 to 0.7, Grippit from 0.1 to 0.5 and pinch gauge from 0.4 to 0.8. Hand pain was the only significant predictor of clinically important improvement of COPM(performance): odds ratio 0.71, 95% CI 0.51, 0.98 (P = 0.041). CONCLUSION: COPM was the most sensitive instrument to capture clinically important improvement, and hand pain was a significant predictor of improvement, irrespective of diagnosis, age, general functional level and type of surgery.

External or internal fixation in the treatment of non-reducible distal radial fractures?

BACKGROUND AND PURPOSE: We have previously shown in a randomized study that in the first year after treatment, open reduction and internal fixation resulted in better grip strength and forearm rotation than closed reduction and bridging external fixation. In the present study, we investigated whether this difference persists over time. PATIENTS AND METHODS: The 50 patients included in the original study (mean age 53 years, 36 women) were sent a QuickDASH questionnaire and an invitation to a radiographic and clinical examination after a mean of 5 (3-7) years. RESULTS: All 50 patients returned the QuickDASH questionnaire and 45 participated in the clinical and radiographic examination. In the internal fixation group, the grip strength was 95% (SD 12) of the uninjured side and in the external fixation group it was 90% (SD 21) of the uninjured side (p = 0.3). QuickDASH score, range of motion, and radiographic parameters were similar between the groups. INTERPRETATION: The difference originally found between internal and external fixation in distal radial fractures at 1 year regarding grip strength and range of motion was found to diminish with time. At 5 years, both groups had approached normal values.