Skip to main navigation menu Skip to main content Skip to site footer

Volume 147, No. 3334

Published August 14, 2017

Review article: Biomedical intelligence

  1. A mini-overview of single muscle fibre mechanics: the effects of age, inactivity and exercise in animals and humans

    Many basic movements of living organisms are dependent on muscle function. Muscle function allows for the coordination and harmonious integrity of movement that is necessary for various biological processes. Gross and fine motor skills are both regulated at the micro-level (single muscle fibre level), controlled by neuronal regulation, and it is therefore important to understand muscle function at both micro- and macro-levels to understand the overall movement of living organisms.

    Single muscle mechanics and the cellular environment of muscles fundamentally allow for the harmonious movement of our bodies. Indeed, a clear understanding of the functionality of muscle at the micro-level is indispensable for explaining muscular function at the macro-(whole gross muscle) level. By investigating single muscle fibre mechanics, we can also learn how other factors such Ca2+ kinetics, enzyme activity and contractile proteins can contribute to muscle mechanics at the micro- and macro-levels. Further, we can also describe how aging affects the capacity of skeletal muscle cells, as well as how exercise can prevent aging-based sarcopenia and frailty.

    The purpose of this review is to introduce and summarise the current knowledge of single muscle fibre mechanics in light of aging and inactivity. We then describe how exercise mitigates negative muscle adaptations that occur under those circumstances. In addition, single muscle fibre mechanics in both animal and human models are discussed.

  2. Inert gas washout: background and application in various lung diseases

    Multiple breath inert gas washout (MBW) is a lung function technique to measure ventilation inhomogeneity. The technique was developed more than 60 years ago, but not much used for many decades. Technical improvements, easy protocols and higher sensitivity compared with standard lung function tests in some disease groups have led to a recent renaissance of MBW.

    The lung clearance index (LCI) is a common measure derived from MBW tests, and offers information on lung pathology complementary to that from conventional lung function tests such as spirometry. The LCI measures the overall degree of pulmonary ventilation inhomogeneity. There are other MBW-derived parameters, which describe more regional airway ventilation and enable specific information on conductive or acinar ventilation inhomogeneity. How this specific ventilation distribution is exactly related to different disease processes has not entirely been examined yet.

    MBW measurements are performed during tidal breathing, making this technique attractive for children, even young children and infants. These benefits and the additional physiological information on ventilation inhomogeneity early in the course of lung diseases have led to increasing research activities and clinical application of MBW, especially in paediatric lung diseases such as cystic fibrosis (CF). In these patients, LCI detects early airway damage and enables monitoring of disease progression and treatment response. Guidelines for the standardisation of the MBW technique were recently published. These guidelines will, hopefully, increase comparability of LCI data obtained in different centres or intervention trials in children and adults.

    In this non-systematic review article, we provide an overview of recent developments in MBW, with a special focus on children. We first explain the physiological and technical background to this technique with a short explanation of several methodological aspects that are important for understanding the principle behind the technique and enable high quality measurements. We then provide examples of MBW application in different lung diseases of children and adults, with regards to both clinical application and research activities. Lastly, we report on ongoing clinical trials using MBW as outcome and give an outlook on possible future developments.

  3. Acute aortic dissection: pathogenesis, risk factors and diagnosis

    Acute aortic dissection is a rare but life-threatening condition with a lethality rate of 1 to 2% per hour after onset of symptoms in untreated patients. Therefore, its prompt and proper diagnosis is vital to increase a patient’s chance of survival and to prevent grievous complications. Typical symptoms of acute aortic dissection include severe chest pain, hypotension or syncope and, hence, mimic acute myocardial infarction or pulmonary embolism. Advanced age, male gender, long-term history of arterial hypertension and the presence of aortic aneurysm confer the greatest population attributable risk. However, patients with genetic connective tissue disorders such as Marfan, Loeys Dietz or Ehlers Danlos syndrome, and patients with bicuspid aortic valves are at the increased risk of aortic dissection at a much younger age. Imaging provides a robust foundation for diagnosing acute aortic dissection, as well as for monitoring of patients at increased risk of aortic disease. As yet, easily accessible blood tests play only a small role but have the potential to make diagnosis and monitoring of patients simpler and more cost-effective.

Review article: Medical guidelines

  1. Osteoporosis drug treatment: duration and management after discontinuation. A position statement from the Swiss Association against Osteoporosis (SVGO/ASCO)

    Antiosteoporotic drugs are recommended in patients with fragility fractures and in patients considered to be at high fracture risk on the basis of clinical risk factors and/or low bone mineral density. As first-line treatment most patients are started with an antiresorptive treatment, i.e. drugs that inhibit osteoclast development and/or function (bisphosphonates, denosumab, oestrogens or selective oestrogen receptor modulators). In the balance between benefits and risks of antiresorptive treatment, uncertainties remain regarding the optimal treatment duration and the management of patients after drug discontinuation. Based on the available evidence, this position statement will focus on the long-term management of osteoporosis therapy, formulating decision criteria for clinical practice.

Original article

  1. Early complications after living donor nephrectomy: analysis of the Swiss Organ Living Donor Health Registry

    BACKGROUND

    We evaluated the prospectively collected data about the incidence of early peri- and postoperative complications, and potential risk factors for adverse outcomes after living kidney donation in Switzerland.

    METHODS

    Peri- and postoperative events were prospectively recorded on a questionnaire by the local transplant teams of all Swiss transplant centres and evaluated by the Swiss Organ Living Donor Health Registry. Complications were classified according to the Clavien grading system. A total of 1649 consecutive donors between 1998 and 2015 were included in the analysis.

    RESULTS

    There was no perioperative mortality observed. The overall complication rate was 13.5%. Major complications defined as Clavien ≥3 occurred in 2.1% of donors. Obesity was not associated with any complications. Donor age >70years was associated with major complications (odds ratio [OR] 3.99) and genitourinary complications (urinary tract infection OR 5.85; urinary retention OR 6.61). There were more major complications observed in donors with laparoscopic surgery versus open surgery (p = 0.048), but an equal overall complication rate (p = 0.094).

    CONCLUSION

    We found a low rate of major and minor complications, independent of surgical technique, after living donor nephrectomy. There was no elevated complication rate in obese donors. In contrast, elderly donors >70 years had an elevated risk for perioperative complications.

  2. Right retroperitoneoscopic living donor nephrectomy does not increase surgical complications in the recipient and leads to excellent long-term outcome

    BACKGROUND

    Right-sided retroperitoneoscopic living donor nephrectomy (LDN) has been shown to be safe for the donor but it is unknown whether the short renal vein is associated with complications or an impaired long-term outcome in the recipient.

    METHODS

    In this retrospective cohort study, consecutive transplant recipients after retroperitoneoscopic LDN were enrolled. Complications occurring within 1 year were classified according to the Clavien-Dindo Classification for Surgical Complications and analysed using multivariable logistic regression. Predictors of 1-year creatinine clearance were analysed with multivariable linear regression. Cox proportional hazard models were used to analyse graft survival.

    RESULTS

    Of the 251 recipients, 193 (77%) received a left kidney and 58 (23%) a right kidney. Surgical complications of Clavien-Dindo grade 3 or higher were comparable in recipients of right and left kidneys (33% vs 29%, odds ratio 0.98, 95% confidence interval [CI] 0.50, 1.94). The occurrence of a surgical complication had a significant impact on creatinine clearance at 1 year (decrease of 6 ml/min/m2, p = 0.016). Vascular complications in right kidneys were more common but were all corrected without impact on graft survival. One-year graft-survival was similar in recipients of right (98.3%) and left (96.9%) kidneys, as was creatinine clearance one year after transplantation (mean difference 3.3 ml/min/m2, 95% CI ˗1.5, 8.1; p = 0.175). After a median follow-up of 5 years, neither the side (hazard ratio 1.56, 95% CI 0.67, 3.63) nor surgical complications (hazard ratio 1.44, 95% CI 0.65, 3.19) were associated with graft failure.

    CONCLUSION

    Right retroperitoneoscopic LDN does not compromise the outcome of transplantation. Surgical complications, long-term graft function and graft survival were comparable in right and left kidneys.

  3. Treatment strategies and outcome of surgery for synchronous colorectal liver metastases

    OBJECTIVES

    To report survival following different operative strategies and perioperative chemotherapy in patients with synchronous colorectal liver metastases in a tertiary academic referral centre.

    METHODS

    We performed a retrospective analysis, based on a prospective database, of patients who presented with synchronous colorectal liver metastases. Follow-up data were obtained from medical records, letters or telephone contacts. The main endpoint was overall survival. An additional event of interest was postoperative mortality according to treatment strategy. Predefined variables were analysed to identify associated risk factors.

    RESULTS

    Overall, 109 patients undergoing liver resection for synchronous colorectal liver metastases between 2000 and 2010 were identified. The majority of patients had resection of the primary tumour first (n = 82), the classic approach; notably fewer were treated according to a combined (n = 20) or a reverse “liver first” strategy (n = 7). Most patients (92%) received preoperative, interval and/or postoperative chemotherapy. Median overall survival of the entire population was 33.6 months (interquartile range [IQR] 11–92.7 months). Patients undergoing classic surgery had a median overall survival of 40.3 months (IQR 14.9–96.6 months). The 3-year survival rates of the three patient groups were 53% in the classic, 47% in the combined and 58% in the reverse group. The lowest rate of 180-day mortality (9%) was after the classic surgical approach. On a multivariate Cox proportional hazards regression analysis, patient age >60 years (hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.1–3.9; p = 0.018), R2-status (HR 2.08, 95% CI 1.03–4.2; p = 0.040), and >4 liver metastases (HR 2.4, 95% CI 1.2–4.6; p = 0.011) were associated significantly with worse overall survival.

    CONCLUSIONS

    In patients undergoing surgical resection for synchronous colorectal liver metastases, promising survival rates could be achieved, irrespective of the chosen surgical strategy. The presence of five or more liver metastases, patient age over 60 years and R2-status were found to be adverse risk factors.

  4. First trimester combined screening for preeclampsia and small for gestational age – a single centre experience and validation of the FMF screening algorithm

    AIM OF THE STUDY

    Preeclampsia (PE) is associated with severe maternal and fetal morbidity in the acute presentation and there is increasing evidence that it is also an important risk factor for cardiovascular disease later in life. Therefore, preventive strategies are of utmost importance. The Fetal Medicine Foundation (FMF) London recently developed a first trimester screening algorithm for placenta-related pregnancy complications, in particular early onset preeclampsia (eoPE) requiring delivery before 34 weeks, and preterm small for gestational age (pSGA), with a birth weight <5th percentile and delivery before 37 weeks of gestation, based on maternal history and characteristics, and biochemical and biophysical parameters. The aim of this study was to test the performance of this algorithm in our setting and to perform an external validation of the screening algorithm.

    MATERIAL AND METHODS

    Between September 2013 and April 2016, all consecutive women with singleton pregnancies who agreed to this screening were included in the study. The proposed cut-offs of ≥1:200 for eoPE, and ≥1:150 for pSGA were applied. Risk calculations were performed with Viewpoint® program (GE, Mountainview, CA, USA) and statistical analysis with GraphPad version 5.0 for Windows.

    RESULTS

    1372 women agreed to PE screening; the 1129 with complete data and a live birth were included in this study. Nineteen (1.68%) developed PE: 14 (1.24%) at term (tPE) and 5 (0.44%) preterm (pPE, <37 weeks), including 2 (0.18%) with eoPE. Overall, 97/1129 (8.6%) screened positive for eoPE, including both pregnancies that resulted in eoPE and 4/5 (80%) that resulted in pPE. Forty-nine of 1110 (4.41%) pregnancies without PE resulted in SGA, 3 (0.27%) of them in pSGA. A total of 210/1110 (18.9%) non-PE pregnancies screened positive for pSGA, including 2/3 (66.7%) of the pSGA deliveries and 18/46 (39.1%) of term SGA infants.

    CONCLUSION

    Our results show that first trimester PE screening in our population performs well and according to expectations, whereas screening for SGA is associated with a high false positive rate.