Analysis and applications of respiratory surface EMG: report of a round table meeting.

Surface electromyography (sEMG) can be used to measure the electrical activity of the respiratory muscles. The possible applications of sEMG span from patients suffering from acute respiratory failure to patients receiving chronic home mechanical ventilation, to evaluate muscle function, titrate ventilatory support and guide treatment. However, sEMG is mainly used as a monitoring tool for research and its use in clinical practice is still limited-in part due to a lack of standardization and transparent reporting. During this round table meeting, recommendations on data acquisition, processing, interpretation, and potential clinical applications of respiratory sEMG were discussed. This paper informs the clinical researcher interested in respiratory muscle monitoring about the current state of the art on sEMG, knowledge gaps and potential future applications for patients with respiratory failure.

Robotic-assisted surgery for rectal cancer results of a non-randomized study.

INTRODUCTION: The Czech Republic belongs to countries in which colorectal cancer significantly contributes to the overall oncological burden. Radical removal of tumor-affected tissues plays a key role in the multimodal therapy of rectal cancer. In the first decade of the third millennium the mini-invasive approach in rectal cancer surgery gradually expanded to include robotic-assisted surgeries. The aim of this paper is to present the results of a non-randomized study with prospectively collected data from robotically assisted rectal cancer surgeries. METHODS: 204 patients with rectal cancer (.

Assessment of anastomosis perfusion by fluorescent angiography in robotic low rectal resection: the results of a non-randomized study.

INTRODUCTION: Colorectal cancer is a major contributor to the overall cancer burden in the Czech population. Anastomotic healing defects are a feared complication which may have a fatal impact on the patient. Fundamental conditions for proper anastomotic healing include sufficient blood supply. Fluorescent angiography using indocyanine green in the spectrum of near-infrared light facilitates the monitoring of tissue perfusion during a surgery. The aim of this article is to present the results of a non-randomized study in which we assessed prospectively obtained data from a perioperative assessment of anastomosis perfusion by fluorescent angiography using indocyanine green during robotic resection of the rectum with a malignant tumor. METHOD: Thirty patients with rectal cancer who underwent a robotic resection with primary anastomosis were consecutively included in the study between 1 April 2017 and 21 June 2018. The study included patients due to undergo a minimally invasive procedure with guaranteed health insurance coverage. During the operation, we monitored and assessed the quality of perfusion of the resection line of the sigmoid colon and subsequent anastomosis by means of fluorescent angiography using indocyanine green in the spectrum of near-infrared light. The data were obtained prospectively and subsequently analyzed. RESULTS: Between 1 April 2017 and 21 June 2018, we consecutively included 30 rectal cancer patients in the project: 16 men and 14 women. Monitoring of perfusion of the resection line and anastomosis was successful in all cases and perfusion quality was satisfactory across the sample. Perfusion insufficiency requiring a change in the resection line level or anastomosis adjustments was not detected with any patient. In two cases (12.5 %) of TME, we gave up the planned protective ileostomy owing to good perfusion of the anastomosis. One patient (3.3%) suffered from defective anastomotic healing without clinical symptoms (type A). We found no technical complications related to fluorescent angiography or undesirable effects due to the application of indocyanine green. CONCLUSION: Fluorescent angiography using indocyanine green in the spectrum of near-infrared light is a fast and safe option to monitor the level of blood supply to an anastomosis during surgery, which is a fundamental condition for proper healing. Even though we did not record insufficient perfusion in our sample and hence we did not need to change the resection line level or adjust the anastomosis, we may state that fluorescent angiography performed by an experienced colorectal surgeon may potentially reduce the frequency of complications linked to defective anastomotic healing.

Multidisciplinary team in colorectal cancer treatment - analysis of our patients in 2017.

INTRODUCTION: Multidisciplinary teams (MDTs) have become a standard part of treating oncological patients. Based on the available data, they have lead to significantly higher survival rates in the treatment of colorectal cancer (CRC). Reported negatives include potentially longer times between diagnoses and the start of appropriate treatment, and the lack of quality controls over the MTDs actions. This report aims to assess the benefits of MDTs using our own data set for 2017. METHODS: Year 2010 saw the institution of an MDT at the Central Military University Hospital in Prague, with the obligation to refer CRC patients to the MDT before the start of treatment. Having standardized the registration, we have implemented a simple procedure to track the quality of our MDTs involvement and its patient benefits: number of patients, number of referrals with proposed diagnostic and therapeutic procedure, frequency and reason of changes to original strategies, and the frequency of variations from the MDTs conclusions. RESULTS: 405 CRC patients were referred to the MDT in 2017; we have found 499 referrals in this group. The data set was formed predominantly by men (61%), with the mean age of 63 (21-91), and the median age of 64.5 years. Surgical treatment was the most commonly proposed procedure (59%), followed by systemic treatment or, as the case may be, radiotherapy. In 24% of the cases, the conclusion did not match the originally proposed procedure. The decision not to go through with the proposed surgical treatment was the most common change (66 %). We have found a difference in the quality of referral in patients examined specifically by the referring doctor, as opposed to patients whose medical records have just been sent in. We have found therapeutic variation in the MTDs conclusions in less than 5% of patients. CONCLUSION: Having analyzed our data for CRC patients referred to the MDT in 2017, we have found out that in 24% of the patients, the MDT referral leads to a change in the originally proposed diagnostic and therapeutic procedure. Consensus among the MDTs members on the CRC patients treatment guarantees an optimum procedure. What is fundamental is that the referring doctor knows the patient. Constant tracking of the MDTs outputs forms a condition for sustaining the quality of its work and a base for assessing its benefits to the patients.

Detection of extra-regional tumour recurrence with 18F-FDG-PET/CT in patients with recurrent gynaecological malignancies being considered for radical salvage surgery.

AIM: To compare the detection rate of extra-regional metastases in patients with recurrent gynaecological malignancies being considered for radical salvage surgery with combined 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) compared to conventional imaging. MATERIALS AND METHODS: A retrospective review was performed of all patients in a provincial database with recurrent gynaecological malignancies being considered for pelvic exenteration that underwent restaging with CT/PET between March 2011 and October 2014. Findings on PET and conventional imaging (CT±pelvic MRI) were abstracted. Disease sites were classified according to the location (regional nodal metastases, extra-regional nodal metastases, peritoneum, or other distant sites) and diagnostic certainty (definitive or equivocal). The proportion of patients positive for extra-regional recurrence was calculated for PET and conventional imaging. In addition, the proportion of patients with indeterminate lesions only was calculated for each modality and the sites of indeterminate findings were tabulated. RESULTS: There were 85 patients (median age, 50 years; range: 30-81 years) with carcinoma of cervix (n=51), endometrium (n=18), vagina (n=6), or vulva (n=10). Extra-regional recurrence was detected in 8/85 (9.4%) and 24/85 (28.2%) patients on conventional imaging and PET, respectively (p=0.0017). The greatest impact of PET compared to conventional imaging was in the detection of extra-regional nodal metastases. PET had significantly fewer examinations equivocal for extra-regional recurrence versus conventional imaging (6/85 [7.1%] and 38/85 [44.7%], respectively, p<0.001). CONCLUSION: In patients with recurrent gynaecological malignancies being considered for radical salvage surgery, PET may identify significantly more extra-regional recurrence than conventional imaging. PET may also result in fewer equivocal lesions. The impact of these results on patient management and outcome should be confirmed in future prospective trials.

[Can robotic rectal cancer surgery improve quality of total mesorectal excision?] / Muze robotická asistence pri chirurgické lécbe karcinomu rekta zlepsit kvalitu totální mezorektální excize?

INTRODUCTION: The introduction of total mesorectal excision (TME) in the 1980s was pivotal in the surgical treatment for rectal carcinoma (RC). Routinely applied TME led to a significant reduction in the incidence of local recurrences. The purpose of our paper is to present the results of our non-randomized study comparing prospectively acquired data from radical resection / rectal extirpation using classic open access, laparoscopy and da Vinci robotic system. METHOD: The study group included 116 patients with RC who underwent radical surgical treatment between 1/2014-12/2016, after which the collected resection specimens were assessed in pathology laboratories of the referring hospital using the Quirkes protocol. Analysis of data collected prospectively over a period of 3 years was done. The surgical procedures were open, laparoscopic and robotic. Robotic surgery could only be performed in patients whose health insurers guaranteed to cover the robotic resection expenses. Those patients whose health insurers did not cover the costs of the robotic assisted procedure were treated using the laparoscopic technique. RESULTS: Over a period of 3 years (2014-2016), the teams at the Department of Surgery of the 2nd Faculty of Medicine, Charles University and Central Military Hospital, Prague treated 116 patients (75 men and 41 women) for RC; resected specimens of the patients were processed according to the Quirkes protocol. Mean age was 63 years (33-80). pCRO positivity was confirmed in 5 patients (4.3%) and complete or nearly complete TME was achieved in 94 patients (81%). More than a half of the procedures were performed using the minimally invasive surgery. No patient died. CONCLUSION: Despite the high rate of technically difficult cases (male sex, tumours in the distal third of the rectum), the robotic assisted treatment showed best results in our study group in terms of quality of the mesorectal excision. Our results thus provide evidence of an unequivocal benefit of robotic assistance compared to manual laparoscopy and open procedures in terms of TME as a quality indicator of surgery in patients with CR. Given the limited time span, there are no long-term results to be assessed in our patients.Key words: rectal carcinoma - TME - evaluation of surgical treatment - robotic rectal surgery.

[Respiratory Muscle Training: State of the Art]. / Atemmuskeltraining: State-of-the-Art.

Specific respiratory muscle training (IMT) improves the function of the inspiratory muscles. According to literature and clinical experience, there are 3 established methods: 1.) resistive load 2.) threshold load and 3.) normocapnic hyperpnea. Each training method and the associated devices have specific characteristics. Setting up an IMT should start with specific diagnostics of respiratory muscle function and be followed by detailed individual introduction to training. The aim of this review is to take a closer look at the different training methods for the most relevant indications and to discuss these results in the context of current literature. The group of neuromuscular diseases includes muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, paralysis of the phrenic nerve, and injuries to the spinal cord. Furthermore, interstitial lung diseases, sarcoidosis, left ventricular heart failure, pulmonary arterial hypertension (PAH), kyphoscoliosis and obesity are also discussed in this context. COPD, asthma, cystic fibrosis (CF) and non-CF-bronchiectasis are among the group of obstructive lung diseases. Last but not least, we summarize current knowledge on weaning from respirator in the context of physical activity.

[Parametric monitoring of the quality of total mesorectal excision and surgical treatment of rectal carcinoma results of a multicenter study]. / Parametrické sledování kvality totální mezorektální excize a chirurgické lécby karcinomu rekta výsledky multicentrické studie.

INTRODUCTION: Tumour size and the quality of its complete surgical removal are the main prognostic factors in rectal cancer treatment. The number of postoperative local recurrences depends on whether the mesorectum has been completely removed - total mesorectal excision (TME) - and whether tumour-free resection margins have been achieved. The surgery itself and its quality depend on the accuracy of preoperative diagnosis and detection of risk areas in the rectum and mesorectum, on the surgeons skills, and finally on pathological assessment evaluating whether complete tumour excision has been accomplished including circumferential margins of the tumour, and whether mesorectal excision is complete. The aim of our study was to implement and standardize a new method of evaluation of the quality of the surgical procedure - TME - in rectal cancer treatment using an assessment of its circumferential margins (CRO) and completeness of the excision. METHODS: The study consisted of two parts. The first, multi-centre retrospective phase with 288 patients analysed individual partial parameters of the diagnosis, operations and histological examinations of the rectal cancer. Critical points were identified and a unified follow-up protocol was prepared. In the second, prospective part of this study 600 patients were monitored parametrically focusing on the quality of the TME and its effect on the oncological treatment results. RESULTS: The proportion of patients with restaging following neoadjuvant therapy increased from 60.0% to 81.7% based on preoperative diagnosis. The number of specimens missing an assessment of the mesorectal excision quality decreased from 52.9% in the retrospective part of to the study to 22.8% in the prospective part. The proportion of actually complete TMEs rose from 22.6% to 26.0%, and that of nearly complete TMEs from 10.1% to 24.0%. CONCLUSION: The introduction of parametric monitoring into routine clinical practice improved the quality of pre-treatment and preoperative diagnosis, examination of the tissue specimen, and consequently improved quality of the surgical procedure was achieved. KEY WORDS: rectal cancer TME - parametric monitoring - quality control.

Trefoil factor family (TFF) proteins as potential serum biomarkers in patients with metastatic colorectal cancer.

Trefoil factor family (TFF) is composed of three secretory proteins (TFF1, TFF2 and TFF3) that play an important role in mucosal protection of gastrointestinal tract. Their overexpression in colorectal tumors seems to be associated with more aggressive disease. We collected serum samples from 79 healthy controls and 97 patients with metastatic colorectal cancer at the time of diagnosis or at progression. Serum levels of TTF1-3, CEA and CA19-9 were measured by ELISA. Serum TFF1 and TFF3 levels were significantly higher in patients with colorectal cancer compared to healthy controls (p < 0.0001). Moreover, serum levels of TFF3 correlated with extent of liver involvement in patient without pulmonary metastases and patients with higher TFF3 levels had significantly worse outcome (p < 0.0001). Compared to CEA and CA19-9, TFF3 had higher sensitivity and the same specificity. Our results indicate that TFF3 is an effective biomarker in patients with metastatic colorectal cancer with higher sensitivity than CEA a CA19-9. TFF3 levels strongly correlate with extension of liver disease and seem to have prognostic value.

[Bile leakage after liver resection: A retrospective cohort study]. / Biliární leak po jaterních resekcích: retrospektivní analýza vlastního souboru.

INTRODUCTION: Many previous reports have focused on bile leakage after liver resection. Despite the improvements in surgical techniques and perioperative care the incidence of this complication rather keeps increasing. A number of predictive factors have been analyzed. There is still no consensus regarding their influence on the formation of bile leakage. The objective of our analysis was to evaluate the incidence of bile leakage, its impact on mortality and duration of hospitalization at our department. At the same time, we conducted an analysis of known predictive factors. METHOD: The authors present a retrospective review of the set of 146 patients who underwent liver resection at the Department of Surgery of the 2nd Faculty of Medicine of the Charles University and Central Military Hospital Prague, performed between 20102013. We used the current ISGLS (International Study Group of Liver Surgery) classification to evaluate the bile leakage. The severity of this complication was determined according to the Clavien-Dindo classification system. Statistical significance of the predictive factors was determined using Fishers exact test and Students t-test. RESULTS: The incidence of bile leakage was 21%. According to ISGLS classification the A, B, and C rates were 6.5%, 61.2%, and 32.3%, respectively. The severity of bile leakage according to the Clavien-Dindo classification system - I-II, IIIa, IIIb, IV and V rates were 19.3%, 42%, 9.7%, 9.7%, and 19.3%, respectively. We determined the following predictive factors as statistically significant: surgery for malignancy (p<0.001), major hepatic resection (p=0.001), operative time (p<0.001), high intraoperative blood loss (p=0.02), construction of HJA (p=0.005), portal venous embolization/two-stage surgery (p=0.009) and ASA score (p=0.02). Bile leakage significantly prolonged hospitalization time (p<0.001). In the group of patients with bile leakage the perioperative mortality was 23 times higher (p<0.001) than in the group with no leakage. CONCLUSION: Bile leakage is one of the most serious complications of liver surgery. Most of the risk factors are not easily controllable and there is no clear consensus on their influence. Intraoperative leak tests could probably reduce the incidence of bile leakage. In the future, further studies will be required to improve the perioperative management and techniques to prevent such serious complications. Multidisciplinary approach is essential in the treatment.

[Da Vinci assisted surgery for rectal cancer - preliminary results of nonrandomized trial]. / Da Vinci asistovaná lécba karcinomu rekta - prubezné výsledky nerandomizované studie.

INTRODUCTION: The incidence of colorectal cancer (CRC) in the Czech Republic is reported to be one of the highest on the global scale. Radical tumor removal has been observed to be the most effective part in the context of current multimodal therapy. The authors present their preliminary results of robotic assisted treatment of rectal carcinoma (RC). METHOD: The observed group includes 61 patients who underwent robotic assisted treatment for rectal cancer. The data were collected prospectively in the last 31 patients. Analyses were conducted on epidemiological data, perioperative outcomes, complications and oncological results. RESULTS: Robotic assisted treatment of RC was performed in 61 patients: 34 men and 27 women, mean age of 62 years (33-80). Neoadjuvant oncological treatment was indicated in 46% of the patients. Average blood loss was 187 ml, transfusions were administered in three cases. Conversion to open procedure was performed 6 times, and 16 patients had postoperative complications. Anastomotic leak was observed in 10% of the patients, and 4 patients undewent surgical treatment. No patient died. Local recurrence of the cancer was diagnosed in 3 (5%) patients. The quality of mesorectal excision (ME) and the circumferential resection margin [(y)pCRM] have been determined in 27 patients since 2013. Positive (y)pCRM was recorded in two cases and incomplete ME was observed in 25.8% of the patients. CONCLUSION: Surgical treatment for RC is pivotal in multimodal therapy. Our preliminary results are similar to the conclusions in other published studies. The da Vinci robotic system is a safe manipulator in the treatment of RC and provides indisputable benefits to the surgeon when operating in the narrow pelvic space. However, the benefits of robotic treatment in abdominal surgery are yet to be evaluated in patients (with respect to long-term results, sufficient number of patients or a high EBM level of evidence). The high purchase price of the robotic device, individual instruments with equipment and non-systemic compensation constitute a significant hindrance that prevents wider use of the robotic system in the treatment of RC and other abdominal malignancies in the Czech Republic.

Pylephlebitis in patient with covered perforated rectosigmoid cancer.

Acute portal vein thrombosis and septic thrombophlebitis of the portal vein represent serious, although rare cases in the non-cirrhotic population. The authors present a case report, in which nonspecific clinical and CT scan findings led to the difficult diagnosis of pylephlebitis due to perforated rectosigmoid cancer.

[The benefit of the da Vinci robotic system in abdominal oncosurgery - our preliminary results]. / Prínos robotického systému da Vinci v abdominální onkochirurgii - nase predbezné výsledky.

INTRODUCTION: The robotization of minimally invasive treatment in surgery has been evident since the beginning of the third Millennium. The authors present their current evaluation of the benefits of the da Vinci robotic system in the treatment of abdominal malignancy. MATERIAL AND METHODS: The authors summarize published studies in the Medline and Pubmed databases that compare robotic, laparoscopic and open approaches in the treatment of abdominal malignancy. Epidemiological data, intraoperative blood loss, complications and oncological outcomes are monitored in a group of 30 patients with carcinoma of rectum. RESULTS: The results measured in the evaluated parameters (open conversion, perioperative and non - surgery complications, intraoperative blood loss, histological findings, lethality) are similar in the published studies, i.e. without significant differences in both groups subject to the robotic and laparoscopic treatment. The operative time in the group of robotic surgery has been is slightly longer (a non-significant difference) in most of published studies. 30 patients underwent the robotic assisted treatment of the carcinoma of the rectum (14 men and 16 women, average age of 60 years (33-80). Neoadjuvant treatment was indicated in 50% of the patients. Average blood loss was 260 ml, transfusion was administered in one case. Conversion to laparotomic treatment was performed twice, four patients had post-operative complications, no patient has died. We have not found any relapse of oncological disease in the observed set to this date. CONCLUSION: The Da Vinci robotic system is a safe manipulator in the treatment of abdominal malignancy (including HPB surgery). Randomized clinical trials (RCT) have confirmed (short-term clinical and oncological) results comparable to the laparoscopic or open approach treatment. The benefits of robotic surgery for patients in abdominal surgery (long-term results, sufficient number of patients and high-grade EBM) are yet to be evaluated, however. It is necessary to implement more randomized clinical trials going forward. Our preliminary results are similar to the results reached in other, published studies.

Exercise training after lung transplantation improves participation in daily activity: a randomized controlled trial.

The effects of exercise training after lung transplantation have not been studied in a randomized controlled trial so far. We investigated whether 3 months of supervised training, initiated immediately after hospital discharge, improve functional recovery and cardiovascular morbidity of patients up to 1 year after lung transplantation. Patients older than 40 years, who experienced an uncomplicated postoperative period, were eligible for this single blind, parallel group study. Sealed envelopes were used to randomly allocate patients to 3 months of exercise training (n = 21) or a control intervention (n = 19). Minutes of daily walking time (primary outcome), physical fitness, quality of life and cardiovascular morbidity were compared between groups adjusting for baseline assessments in a mixed models analysis. After 1 year daily walking time in the treated patients (n = 18) was 85 ± 27 min and in the control group (n = 16) 54 ± 30 min (adjusted difference 26 min [95%CI 8-45 min, p = 0.006]). Quadriceps force (p = 0.001), 6-minute walking distance (p = 0.002) and self-reported physical functioning (p = 0.039) were significantly higher in the intervention group. Average 24 h ambulatory blood pressures were significantly lower in the treated patients (p ≤ 0.01). Based on these results patients should be strongly encouraged to participate in an exercise training intervention after lung transplantation.

Evaluate the safety and efficacy of dura sealant patch in reducing cerebrospinal fluid leakage following elective cranial surgery (ENCASE II): study protocol for a randomized, two-arm, multicenter trial.

BACKGROUND: Cerebrospinal fluid (CSF) leakage is a frequent and challenging complication in neurosurgery, especially in the posterior fossa, with a prevalence of 8%. It is associated with substantial morbidity and increased healthcare costs. A novel dural sealant patch (LIQOSEAL) was developed for watertight dural closure. The objective of this study is to clinically assess the safety and effectiveness of LIQOSEAL as a means of reducing intra- as well as postoperative CSF leakage in patients undergoing elective posterior fossa intradural surgery with a dural closure procedure compared to the best currently available dural sealants. METHODS: We will conduct a two-arm, randomized controlled, multicenter study with a 90-day follow-up. A total of 228 patients will be enrolled in 19 sites, of which 114 will receive LIQOSEAL and 114 an FDA-approved PEG sealant. The composite primary endpoint is defined as intraoperative CSF leakage at PEEP 20 cm H2O, percutaneous CSF leakage within 90 days of, wound infection within 90 days of or pseudomeningocele of more than 20cc on MRI or requiring intervention. We hypothesize that the primary endpoint will not be reached by more than 10 patients (9%) in the investigational arm, which will demonstrate non-inferiority of LIQOSEAL compared to control. DISCUSSION: This trial will evaluate whether LIQOSEAL is non-inferior to control as a means of reducing CSF leakage and safety TRIAL REGISTRATION: ClinicalTrials.gov NCT04086550 . Registered on 11 September 2019.

[Biliary complications after major liver resection]. / Biliární komplikace po velkých resekcích jater.

INTRODUCTION: Major liver resection involves operations where three or more liver segments are resected. The decrease of perioperative and early lethality enlarged indicator conditions, especially in patients with colorectal cancer liver metastasis. Bile leakage belongs to major postoperative complications. AIM: Authors present literary experience and retrospective analysis of patients with emphasis on biliary complications and their treatment. RESULTS: 96 patients underwent major hepatic resections between April 2004 and December 2009 at the Surgery Department of the Central Military Hospital in Prague. The average age of patients was 61 (25-84). Patients with an oncology disease dominated the set, representing 78% of all the patients. One half of the patients were formed by patients with colorectal cancer liver metastasis. Fourteen patients (14.6%) suffered from postoperative biliary complications. Non-surgical treatment was successful in nine cases. Surgical treatment was necessary in five cases. Combinations of these methods were essential in half of the patients. Two patients died (2.1%). CONCLUSION: Bile leakage after major liver resection is a quite common and serious postoperative complication. Conservative treatment (ERCP, CT - navigated drainage) is the method of choice. Surgical treatment is necessary where conservative management fails or where the size of the bile leakage is large. Multidisciplinary approach to treatment of these patients is essential.

Inhibition of VEGF- and NO-dependent angiogenesis does not impair liver regeneration.

Angiogenesis occurs through a convergence of diverse signaling mechanisms with prominent pathways that include autocrine effects of endothelial nitric oxide (NO) synthase (eNOS)-derived NO and vascular endothelial growth factor (VEGF). However, the redundant and distinct roles of NO and VEGF in angiogenesis remain incompletely defined. Here, we use the partial hepatectomy model in mice genetically deficient in eNOS to ascertain the influence of eNOS-derived NO on the angiogenesis that accompanies liver regeneration. While sinusoidal endothelial cell (SEC) eNOS promotes angiogenesis in vitro, surprisingly the absence of eNOS did not influence the angiogenesis that occurs after partial hepatectomy in vivo. While this observation could not be attributed to induction of alternate NOS isoforms, it was associated with induction of VEGF signaling as evidenced by enhanced levels of VEGF ligand in regenerating livers from mice genetically deficient in eNOS. However, surprisingly, mice that were genetically heterozygous for deficiency in the VEGF receptor, fetal liver kinase-1, also maintained unimpaired capacity for liver regeneration. In summary, inhibition of VEGF- and NO-dependent angiogenesis does not impair liver regeneration, indicating signaling redundancies that allow liver regeneration to continue in the absence of this canonical vascular pathway.

Skeletal muscle weakness, exercise tolerance and physical activity in adults with cystic fibrosis.

The aim of the present study was to investigate the prevalence of muscle weakness and the importance of physical inactivity in cystic fibrosis (CF), and its relationship to exercise tolerance and muscle strength. Exercise tolerance, skeletal and respiratory muscle strength were studied in a group of 64 adults with CF (age 26+/-8 yrs, FEV(1 % predicted) 65+/-19) and in 20 age-matched controls. Physical activity (PA) was assessed in 20 patients and all controls. Quadriceps muscle weakness was present in 56% of the patients. Peak oxygen uptake and 6-min walking distance were below normal in 89 and 75% of patients, respectively. Respiratory muscle strength was normal. The differences remained after correcting for PA. Quadriceps force was correlated to the 6-min walking distance but not to peak oxygen uptake. "Mild" PA (>3 metabolic equivalents (METS)) and the number of steps overlapped with controls, but CF patients had less moderate PA (>4.8 METS). Moderate PA was related to peak oxygen uptake and quadriceps force. Skeletal muscle weakness and exercise intolerance are prevalent in cystic fibrosis. Physical inactivity is a factor significantly contributing to exercise tolerance and skeletal muscle force in adults with cystic fibrosis, but these impairments are in excess to that expected from physical inactivity only.

Skeletal muscle force and functional exercise tolerance before and after lung transplantation: a cohort study.

We investigated the impact of lung transplantation and outpatient pulmonary rehabilitation after lung transplantation on skeletal muscle function and exercise tolerance. Skeletal muscle force (Quadriceps force, QF), exercise tolerance (six minute walking distance, 6MWD) and lung function were assessed in 36 patients before and after lung transplantation. Seventeen male and 19 female patients (age 57 +/- 4) showed skeletal muscle weakness before the transplantation. A further 32 +/- 21% reduction was seen 1.2 (interquartile range 0.9 to 2.0) months after LTX. The number of days on the intensive care unit was significantly related to the observed deterioration in muscle force after LTX. At this time point 6MWD was comparable to pre-LTX. Rehabilitation started 37 (IQR 29 to 61) days after LTX. 6MWD and QF improved significantly (140 +/- 91 m, and 35 +/- 48%, respectively; p < 0.05) with rehabilitation. QF remained below pre-LTX values. The evolution of the 6MWD with the transplantation and the subsequent rehabilitation was less in female compared to male subjects. We conclude that muscle strength deteriorates after lung transplantation, particularly in patients with long ICU stay. Outpatient pulmonary rehabilitation is feasible after lung transplantation and leads to recovery of skeletal muscle function. In female patients this recovery is significantly less compared to male recipients.

The ectonucleotidases alkaline phosphatase and nucleoside triphosphate diphosphohydrolase 2 are associated with subsets of progenitor cell populations in the mouse embryonic, postnatal and adult neurogenic zones.

Subventricular zone (SVZ)-derived adult neurospheres express two ectonucleotidases, nucleoside triphosphate diphosphohydrolase 2 (NTPDase2) and tissue non-specific alkaline phosphatase (TNAP). Agonists of the nucleotide receptors P2Y(1) and P2Y(2) as well as adenosine augment growth factor-mediated progenitor cell proliferation. NTPDase2 converts ATP and UTP to ADP and UDP, respectively, which are all P2Y receptor agonists. TNAP hydrolyzes nucleoside triphosphates and diphosphates and produces the P1 receptor agonist adenosine. In the SVZ, NTPDase2 is specifically expressed by type B cells. In order to further scrutinize the association of key molecules of the purinergic signaling pathway with neurogenic regions, we analyzed the expression of TNAP at the lateral ventricles of the adult and developing mouse brain. In the adult brain, TNAP was expressed by type B, type A and at least subsets of type C cells of the SVZ and throughout the rostral migratory stream. Almost 100% of the proliferating, Ki-67-positive cells of the adult SVZ stained for TNAP, supporting the notion of a ubiquitous association of TNAP with SVZ progenitors. In contrast, NTPDase2-positive progenitors of the dentate gyrus were TNAP-negative. Essentially all cells of the telencephalic vesicle at embryonic day (E) 14 revealed TNAP activity, including doublecortin-positive neuroblasts. During further embryonic development, enhanced TNAP activity became restricted to cells of the ventricular and SVZ. In contrast to TNAP, NTPDase2 was first expressed in the SVZ perinatally, in association with TNAP-positive SVZ border cells. During later development, NTPDase2-positive cells disappeared from the ventricular surface and began to form sheaths around clusters of subventricular doublecortin-positive cells, apparently transforming into type B cells. Our results identify TNAP and NTPDase2 as novel markers for subsets of progenitors in the adult and developing mouse brain. They further support the notion that signaling via extracellular nucleotides and nucleosides contributes to embryonic and adult neurogenesis.