Technical Sprinting in the Early Phase of Hamstring Injury Rehabilitation to Accelerate Return to Full Participation in Track and Field Athletes: A Comparative Study of Two Rehabilitation Strategies.

INTRODUCTION: Hamstring injuries are common in track and field athletes with a higher incidence in males than females. It causes a significant loss in training time and a decline in performance. This study evaluated rehabilitation strategies to accelerate return to full participation following hamstring injury. METHODS: Thirty-three athletes (22 males; 11 females) were screened from November 2021 to October 2023 until their final major competition. Out of these, 17 athletes with hamstring injuries were included in this study which were further divided into two groups, A (n=8) and B (n=9), using stratified random sampling with single blinding. Group A received technical sprints using mini hurdles as part of their training from the early stages of rehabilitation, while Group B underwent high-volume low-intensity rehabilitation before progressing to sprints. The progress of each group was monitored on a weekly basis. The average time loss was calculated using Microsoft Excel (Microsoft® Corp., Redmond, WA) and Google Forms (Google, Inc., Mountain View, CA) with built-in validation. RESULTS:  The two groups demonstrated a significant difference in recovery times. In group A, the length of hamstring tenderness (LHT) improved from 9 ± 2.7 (95% CI 2.27) to 0.15 ± 0.3 (95% CI 0.62), active total knee extension (ATKE) from 161.8 ± 7.1 (95% CI 5.95) to 175.4 ± 2 (95% CI 2.3), and Numeric Pain Rating Scale (NPRS) in the isometric test from 5.6 ± 1.09 (95% CI 0.88) to 0.6 ± 0.5 (95% CI 0.63) with p<0.05, and in Group B, LHT improved from 6.8 ± 2.1 (95% CI 1.62) to 0.6 ± 0.7 (95% CI 0.55), ATKE improved from 168.7 ± 8.2 (95% CI 6.3) to 178.7 ± 2.7 (95% CI 2.06) and NPRS with resisted isometric test improved from 6 ± 1.4 (95% CI 1.08) to 0.8 ± 0.7 (95% CI 0.51) with p<0.05. However, Group A took an average of 3.55 weeks (1.22 SD 95% CI 1.08) and Group B took an average of 4.53 weeks (1.98 SD, 95% CI 1.52) to resume full participation. Three athletes from Group A and six athletes from Group B experienced hamstring tightness during the competition, two athletes from Group B were forced to withdraw from the competition due to hamstring reinjury. CONCLUSIONS: The findings indicate that an early technical sprint program can facilitate an early return to full participation. This research can be a guide toward accelerated and integrated hamstring injury rehabilitation among track and field athletes.

Functional and structural asymmetry suggest a unifying principle for catalysis in membrane-bound pyrophosphatases.

Membrane-bound pyrophosphatases (M-PPases) are homodimeric primary ion pumps that couple the transport of Na+- and/or H+ across membranes to the hydrolysis of pyrophosphate. Their role in the virulence of protist pathogens like Plasmodium falciparum makes them an intriguing target for structural and functional studies. Here, we show the first structure of a K+-independent M-PPase, asymmetric and time-dependent substrate binding in time-resolved structures of a K+-dependent M-PPase and demonstrate pumping-before-hydrolysis by electrometric studies. We suggest how key residues in helix 12, 13, and the exit channel loops affect ion selectivity and K+-activation due to a complex interplay of residues that are involved in subunit-subunit communication. Our findings not only explain ion selectivity in M-PPases but also why they display half-of-the-sites reactivity. Based on this, we propose, for the first time, a unified model for ion-pumping, hydrolysis, and energy coupling in all M-PPases, including those that pump both Na+ and H+.

Photo-engineered optoelectronic properties of indium tin oxide via reactive laser annealing.

Transparent conductive oxides are appealing materials for optoelectronic and plasmonic applications as, amongst other advantages, their properties can be modulated by engineering their defects. Optimisation of this adjustment is, however, a complex design problem. This work examined the modification of the carrier transport properties of sputtered tin-doped indium oxide (ITO) via laser annealing in reactive environments. We relate the optical modifications to the structural, compositional, and electronic properties to elucidate the precise mechanisms behind the reactive laser annealing (ReLA) process. For sufficiently high laser fluence, we reveal an ambient-dependent and purely compositional modulation of the carrier concentration of ITO thin films. Hereby, we demonstrate that ReLA utilises the precise energy delivery of photonic processing to enhance the carrier mobility and finely tune the carrier concentration without significantly affecting the crystal structure. Exploitation of this phenomena may enable one to selectively engineer the optoelectronic properties of ITO, promising an alternative to the exploration of new materials for optoelectronic and photonic applications.

The BCAT1 CXXC Motif Provides Protection against ROS in Acute Myeloid Leukaemia Cells.

The cytosolic branched-chain aminotransferase (BCAT1) has received attention for its role in myeloid leukaemia development, where studies indicate metabolic adaptations due to BCAT1 up-regulation. BCAT1, like the mitochondria isoform (BCAT2), shares a conserved CXXC motif ~10 Å from the active site. This CXXC motif has been shown to act as a 'redox-switch' in the enzymatic regulation of the BCAT proteins, however the response to reactive oxygen species (ROS) differs between BCAT isoforms. Studies indicate that the BCAT1 CXXC motif is several orders of magnitude less sensitive to the effects of ROS compared with BCAT2. Moreover, estimation of the reduction mid-point potential of BCAT1, indicates that BCAT1 is more reductive in nature and may possess antioxidant properties. Therefore, the aim of this study was to further characterise the BCAT1 CXXC motif and evaluate its role in acute myeloid leukaemia. Our biochemical analyses show that purified wild-type (WT) BCAT1 protein could metabolise H2O2 in vitro, whereas CXXC motif mutant or WT BCAT2 could not, demonstrating for the first time a novel antioxidant role for the BCAT1 CXXC motif. Transformed U937 AML cells over-expressing WT BCAT1, showed lower levels of intracellular ROS compared with cells over-expressing the CXXC motif mutant (CXXS) or Vector Controls, indicating that the BCAT1 CXXC motif may buffer intracellular ROS, impacting on cell proliferation. U937 AML cells over-expressing WT BCAT1 displayed less cellular differentiation, as observed by a reduction of the myeloid markers; CD11b, CD14, CD68, and CD36. This finding suggests a role for the BCAT1 CXXC motif in cell development, which is an important pathological feature of myeloid leukaemia, a disease characterised by a block in myeloid differentiation. Furthermore, WT BCAT1 cells were more resistant to apoptosis compared with CXXS BCAT1 cells, an important observation given the role of ROS in apoptotic signalling and myeloid leukaemia development. Since CD36 has been shown to be Nrf2 regulated, we investigated the expression of the Nrf2 regulated gene, TrxRD1. Our data show that the expression of TrxRD1 was downregulated in transformed U937 AML cells overexpressing WT BCAT1, which taken with the reduction in CD36 implicates less Nrf2 activation. Therefore, this finding may implicate the BCAT1 CXXC motif in wider cellular redox-mediated processes. Altogether, this study provides the first evidence to suggest that the BCAT1 CXXC motif may contribute to the buffering of ROS levels inside AML cells, which may impact ROS-mediated processes in the development of myeloid leukaemia.

5-Phenyl-1,3,4-oxadiazol-2(3H)-ones Are Potent Inhibitors of Notum Carboxylesterase Activity Identified by the Optimization of a Crystallographic Fragment Screening Hit.

Carboxylesterase Notum is a negative regulator of the Wnt signaling pathway. There is an emerging understanding of the role Notum plays in disease, supporting the need to discover new small-molecule inhibitors. A crystallographic X-ray fragment screen was performed, which identified fragment hit 1,2,3-triazole 7 as an attractive starting point for a structure-based drug design hit-to-lead program. Optimization of 7 identified oxadiazol-2-one 23dd as a preferred example with properties consistent with drug-like chemical space. Screening 23dd in a cell-based TCF/LEF reporter gene assay restored the activation of Wnt signaling in the presence of Notum. Mouse pharmacokinetic studies with oral administration of 23dd demonstrated good plasma exposure and partial blood-brain barrier penetration. Significant progress was made in developing fragment hit 7 into lead 23dd (>600-fold increase in activity), making it suitable as a new chemical tool for exploring the role of Notum-mediated regulation of Wnt signaling.

Caffeine inhibits Notum activity by binding at the catalytic pocket.

Notum inhibits Wnt signalling via enzymatic delipidation of Wnt ligands. Restoration of Wnt signalling by small molecule inhibition of Notum may be of therapeutic benefit in a number of pathologies including Alzheimer's disease. Here we report Notum activity can be inhibited by caffeine (IC50 19 µM), but not by demethylated caffeine metabolites: paraxanthine, theobromine and theophylline. Cellular luciferase assays show Notum-suppressed Wnt3a function can be restored by caffeine with an EC50 of 46 µM. The dissociation constant (Kd) between Notum and caffeine is 85 µM as measured by surface plasmon resonance. High-resolution crystal structures of Notum complexes with caffeine and its minor metabolite theophylline show both compounds bind at the centre of the enzymatic pocket, overlapping the position of the natural substrate palmitoleic lipid, but using different binding modes. The structural information reported here may be of relevance for the design of more potent brain-accessible Notum inhibitors.

Screening of a Custom-Designed Acid Fragment Library Identifies 1-Phenylpyrroles and 1-Phenylpyrrolidines as Inhibitors of Notum Carboxylesterase Activity.

The Wnt family of proteins are secreted signaling proteins that play key roles in regulating cellular functions. Recently, carboxylesterase Notum was shown to act as a negative regulator of Wnt signaling by mediating the removal of an essential palmitoleate. Here we disclose two new chemical scaffolds that inhibit Notum enzymatic activity. Our approach was to create a fragment library of 250 acids for screening against Notum in a biochemical assay followed by structure determination by X-ray crystallography. Twenty fragments were identified as hits for Notum inhibition, and 14 of these fragments were shown to bind in the palmitoleate pocket of Notum. Optimization of 1-phenylpyrrole 20, guided by structure-based drug design, identified 20z as the most potent compound from this series. Similarly, the optimization of 1-phenylpyrrolidine 8 gave acid 26. This work demonstrates that inhibition of Notum activity can be achieved by small, drug-like molecules possessing favorable in vitro ADME profiles.

Drosophila OTK Is a Glycosaminoglycan-Binding Protein with High Conformational Flexibility.

The transmembrane protein OTK plays an essential role in plexin and Wnt signaling during Drosophila development. We have determined a crystal structure of the last three domains of the OTK ectodomain and found that OTK shows high conformational flexibility resulting from mobility at the interdomain interfaces. We failed to detect direct binding between Drosophila Plexin A (PlexA) and OTK, which was suggested previously. We found that, instead of PlexA, OTK directly binds semaphorin 1a. Our binding analyses further revealed that glycosaminoglycans, heparin and heparan sulfate, are ligands for OTK and thus may play a role in the Sema1a-PlexA axon guidance system.

Antiepileptic Drug Carbamazepine Binds to a Novel Pocket on the Wnt Receptor Frizzled-8.

Misregulation of Wnt signaling is common in human cancer. The development of small molecule inhibitors against the Wnt receptor, frizzled (FZD), may have potential in cancer therapy. During small molecule screens, we observed binding of carbamazepine to the cysteine-rich domain (CRD) of the Wnt receptor FZD8 using surface plasmon resonance (SPR). Cellular functional assays demonstrated that carbamazepine can suppress FZD8-mediated Wnt/ß-catenin signaling. We determined the crystal structure of the complex at 1.7 Å resolution, which reveals that carbamazepine binds at a novel pocket on the FZD8 CRD. The unique residue Tyr52 discriminates FZD8 from the closely related FZD5 and other FZDs for carbamazepine binding. The first small molecule-bound FZD structure provides a basis for anti-FZD drug development. Furthermore, the observed carbamazepine-mediated Wnt signaling inhibition may help to explain the phenomenon of bone loss and increased adipogenesis in some patients during long-term carbamazepine treatment.

Preoperative VolumE Replacement therapy in DIabetic patients undergoing coronary artery bypass grafting surgery: results from an open parallel group randomized Controlled Trial (VeRDiCT).

OBJECTIVES: To investigate the effect of preoperative volume replacement therapy (VRT) on renal function, health outcome and time to fitness for discharge in diabetic patients undergoing coronary artery bypass grafting (CABG). METHODS: In 2 parallel randomized controlled trials, diabetic patients were allocated to preoperative VRT (1 ml/kg/h of Hartmann's solution for 12 h) or usual care. Primary outcome was time to fitness for discharge. Secondary outcomes included acute kidney injury, postoperative complications, patient-reported quality of life (QoL), hospital resource use and markers of renal, cardiac and inflammatory injury. RESULTS: In total, 169 patients were randomized (84 VRT, 85 usual care; mean age 64 years; 88% male). Time to fitness for discharge was similar between groups [median 6 days; interquartile range 5.0-9.0 in both groups; hazard ratio 0.95, 95% confidence interval (CI) 0.65-1.38; P = 0.78]. Postoperative acute kidney injury was not statistically different (VRT: 27.7% vs usual care: 18.8%, odds ratio 1.72, 95% CI 0.82-3.59; P = 0.15). Estimated glomerular filtration rate (mean difference -0.92, 95% CI -4.18 to 2.25; P = 0.56), microalbumin/creatinine ratio [geometric mean ratio (GMR) 1.16, 95% CI 0.94-1.42; P = 0.16], N-acetyl-beta-d-glucosaminidase (GMR 1.08, 95% CI 0.83-1.40; P = 0.57), C-reactive protein (GMR 1.00, 95% CI 0.88-1.13; P = 0.94), troponin T (Trop-T; GMR 1.18, 95% CI 0.78-1.79; P = 0.39) and other secondary health outcomes were similar between groups. QoL improved in both groups at 3 months with no difference observed. CONCLUSIONS: The use of preoperative VRT is not superior to usual care in diabetic patients undergoing CABG. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN02159606.

Structural characterization of melatonin as an inhibitor of the Wnt deacylase Notum.

The hormone melatonin, secreted from the pineal gland, mediates multiple physiological effects including modulation of Wnt/ß-catenin signalling. The Wnt palmitoleate lipid modification is essential for its signalling activity, while the carboxylesterase Notum can remove the lipid from Wnt and inactivate it. Notum enzyme inhibition can therefore upregulate Wnt signalling. While searching for Notum inhibitors by crystallographic fragment screening, a hit compound N-[2-(5-fluoro-1H-indol-3-yl)ethyl]acetamide that is structurally similar to melatonin came to our attention. We then soaked melatonin and its precursor N-acetylserotonin into Notum crystals and obtained high-resolution structures (≤1.5 Å) of their complexes. In each of the structures, two compound molecules bind with Notum: one at the enzyme's catalytic pocket, overlapping the space occupied by the acyl tail of the Wnt palmitoleate lipid, and the other at the edge of the pocket opposite the substrate entrance. Although the inhibitory activity of melatonin shown by in vitro enzyme assays is low (IC50 75 µmol/L), the structural information reported here provides a basis for the design of potent and brain accessible drugs for neurodegenerative diseases such as Alzheimer's disease, in which upregulation of Wnt signalling may be beneficial.

The Effects of Preoperative Volume Replacement in Diabetic Patients Undergoing Coronary Artery Bypass Grafting Surgery: Protocol for a Randomized Controlled Trial (VeRDiCT Trial).

BACKGROUND: Diabetes mellitus is a major risk factor for prolonged hospital stays, renal failure, and mortality in patients having coronary artery bypass grafting (CABG). Complications pose a serious threat to patients and prolong intensive care and hospital stays. Low glomerular filtration rate (GFR) due to existing renal impairment or volume depletion may exacerbate acute renal impairment/failure in these patients. Preoperative volume replacement therapy (VRT) is reported to increase the GFR and we hypothesize that VRT will reduce renal impairment and related complications in diabetic patients. OBJECTIVE: The objective of this study is to establish the efficacy of preoperative VRT in reducing postoperative complications in diabetic patients undergoing CABG surgery. Time to "fit for discharge", incidence of postoperative renal failure, cardiac injury, inflammation, and other health outcomes will be investigated. METHODS: In this open parallel group randomized controlled trial, 170 diabetic patients undergoing elective or urgent CABG surgery received 1 mL/kg/hour of Hartmann's solution for 12 consecutive hours prior to surgery, versus routine care. The primary outcome was time until participants were "fit for discharge", which is defined as presence of: normal temperature, pulse, and respiration; normal oxygen saturation on air; normal bowel function; and physical mobility. Secondary outcomes included: incidence of renal failure; markers of renal function, inflammation, and cardiac damage; operative morbidity; intensive care stay; patient-assessed outcome, including the Coronary Revascularization Outcome Questionnaire; and use of hospital resources. RESULTS: Recruitment started in July 2010. Enrolment for the study was completed in July 2014. Data analysis commenced in December 2016. Study results will be submitted for publication in the summer of 2017. CONCLUSIONS: VRT is a relatively easy treatment to administer in patients undergoing surgical procedures who are at risk of renal failure. This experimental protocol will increase scientific and clinical knowledge of VRT in diabetic patients undergoing elective or urgent CABG surgery. Findings supporting the efficacy of this intervention could easily be implemented in the health care system. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 02159606; http://www.controlled-trials.com/ISRCTN02159606 (Archived by WebCite at http://www.webcitation.org/6rDkSSkkK).

Off-pump versus on-pump coronary artery bypass surgery in patients with actively treated diabetes and multivessel coronary disease.

OBJECTIVES: We conducted a single-center analysis on short-term outcomes and long-term survival in actively treated diabetic patients undergoing off-pump coronary artery bypass versus on-pump coronary artery bypass surgery. METHODS: The final population consisted of 2450 patients with actively treated diabetes (mean age, 66 ± 9 years; female/male 545/1905, 22%). Of those, 1493 subjects were orally treated and 1011 subjects were taking insulin. Off-pump coronary artery bypass and on-pump coronary artery bypass were performed in 1253 and 1197 patients, respectively. Propensity score matching was used to compare the 2 matched groups. RESULTS: When compared with on-pump coronary artery bypass, off-pump coronary artery bypass was associated with a significant risk reduction for postoperative cerebrovascular accident (odds ratio, 0.49; 95% confidence interval [CI], 0.25-0.99; P = .04), need for postoperative intra-aortic balloon pump (odds ratio, 0.48; 95% CI, 0.30-0.77; P = .002), and reexploration for bleeding (odds ratio, 0.55; 95% CI, 0.33-0.94; P = .02). Off-pump coronary artery bypass did not significantly affect early (hazard ratio [HR], 1.32; 95% CI, 0.73-2.40; P = .36) and late (HR, 1.08; 95% CI, 0.92-1.28; P = .32) mortality. However, off-pump coronary artery bypass with incomplete revascularization was associated with reduced survival when compared with off-pump coronary artery bypass with complete revascularization (HR, 1.82; 95% CI, 1.34-2.46; P = .0002) and on-pump coronary artery bypass with complete revascularization (HR, 1.83; 95% CI, 1.36-2.47; P < .0001). CONCLUSIONS: Off-pump coronary artery bypass is a safe and feasible option for diabetic patients with multivessel disease, reduces the incidence of early complications including postoperative cerebrovascular events, and provides excellent long-term survival similar to on-pump coronary artery bypass surgery in case of complete revascularization.

Propofol cardioplegia: A single-center, placebo-controlled, randomized controlled trial.

OBJECTIVES: Cardiac surgery with cardiopulmonary bypass and cardioplegic arrest is an effective treatment for coronary artery and aortic valve diseases. However, the myocardium sustains reperfusion injury after ischemic cardioplegic arrest. Our objective was to assess the benefits of supplementing cardioplegia solution with the general anesthetic propofol in patients undergoing either coronary artery bypass grafting (CABG) or aortic valve replacement (AVR). METHODS: A single-center, double-blind randomized controlled trial was carried out to compare cardioplegia solution supplemented with propofol (concentration 6 µg/mL) versus intralipid (placebo). The primary outcome was cardiac troponin T release over the first 48 hours after surgery. RESULTS: We recruited 101 participants (51 in the propofol group, 50 in the intralipid group); 61 underwent CABG and 40 underwent AVR. All participants were followed to 3 months. Cardiac troponin T release was on average 15% lower with propofol supplementation (geometric mean ratio, 0.85; 95% confidence interval [CI], 0.73-1.01; P = .051). There were no differences for CABG participants but propofol-supplemented participants undergoing AVR had poorer postoperative renal function (geometric mean ratio, 1.071; 95% CI, 1.019-1.125; P = .007), with a trend toward longer intensive care stay (median, 89.5 vs 47.0 hours; hazard ratio, 0.58; 95% CI, 0.31-1.09; P = .09) and fewer with perfect health (based on the EQ-5D health utility index) at 3 months (odds ratio, 0.26; 95% CI, 0.06-1.05; P = .058) compared with the intralipid group. Safety profiles were similar. There were no deaths. CONCLUSIONS: Propofol supplementation in cardioplegia appears to be cardioprotective. Its influence on early clinical outcomes may differ between CABG and AVR surgery. A larger, multicenter study is needed to confirm or refute these suggestions.

The effects of propofol cardioplegia on blood and myocardial biomarkers of stress and injury in patients with isolated coronary artery bypass grafting or aortic valve replacement using cardiopulmonary bypass: protocol for a single-center randomized controlled trial.

BACKGROUND: Despite improved myocardial protection strategies, cardioplegic arrest and ischemia still result in reperfusion injury. We have previously published a study describing the effects of propofol (an anesthetic agent commonly used in cardiac surgery) on metabolic stress, cardiac function, and injury in a clinically relevant animal model. We concluded that cardioplegia supplementation with propofol at a concentration relevant to the human clinical setting resulted in improved hemodynamic function, reduced oxidative stress, and reduced reperfusion injury when compared to standard cardioplegia. OBJECTIVE: The Propofol cardioplegia for Myocardial Protection Trial (ProMPT) aims to translate the successful animal intervention to the human clinical setting. We aim to test the hypothesis that supplementation of the cardioplegic solution with propofol will be cardioprotective for patients undergoing isolated coronary artery bypass graft or aortic valve replacement surgery with cardiopulmonary bypass. METHODS: The trial is a single-center, placebo-controlled, randomized trial with blinding of participants, health care staff, and the research team. Patients aged between 18 and 80 years undergoing nonemergency isolated coronary artery bypass graft or aortic valve replacement surgery with cardiopulmonary bypass at the Bristol Heart Institute are being invited to participate. Participants are randomly assigned in a 1:1 ratio to either cardioplegia supplementation with propofol (intervention) or cardioplegia supplementation with intralipid (placebo) using a secure, concealed, Internet-based randomization system. Randomization is stratified by operation type and minimized by diabetes mellitus status. Biomarkers of cardiac injury and metabolism are being assessed to investigate any cardioprotection conferred. The primary outcome is myocardial injury, studied by measuring myocardial troponin T. The trial is designed to test hypotheses about the superiority of the intervention within each surgical stratum. The sample size of 96 participants has been chosen to achieve 80% power to detect standardized differences of 0.5 at a significance level of 5% (2-tailed) assuming equal numbers in each surgical stratum. RESULTS: A total of 96 patients have been successfully recruited over a 2-year period. Results are to be published in late 2014. CONCLUSIONS: Designing a practicable method for delivering a potentially protective dose of propofol to the heart during cardiac surgery was challenging. If our approach confirms the potential of propofol to reduce damage during cardiac surgery, we plan to design a larger multicenter trial to detect differences in clinical outcomes. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 84968882; http://www.controlled-trials.com/ISRCTN84968882/ProMPT (Archived by WebCite at http://www.webcitation.org/6Qi8A51BS).

Bronchoscopic lung volume reduction in patients with severe emphysema: anesthetic management.

Bronchoscopic lung volume reduction is a novel approach to the treatment of severe emphysema. Its objective is to achieve the same improvements in lung function and exercise tolerance as lung volume reduction surgery while avoiding the surgical morbidity and mortality. We describe the anesthetic experience in a series of seven patients who underwent a total of eight procedures (one patient underwent a second procedure on the contralateral side). The technique used was one of total IV anesthesia using remifentanil and propofol, with a ventilatory strategy aimed at avoiding gas trapping and dynamic hyperinflation. To achieve this pressure, limited ventilation with a prolonged expiratory phase was provided by a Draeger Evita 2 ventilator. This technique resulted in intraoperative hypercapnia (Paco(2) 6.75 kPa) compared with baseline values (median Paco(2) 5.1 kPa; P < 0.05), but 2 h postoperatively the arterial partial pressure of CO(2) was returning to baseline (median Paco(2) 5.6 kPa; P < 0.01 compared with intraoperative data). There were no deaths or admissions to the intensive care unit after the procedure. One patient developed a pneumothorax that required drainage, three patients had acute exacerbations of chronic obstructive pulmonary disease, and one patient developed a cough that resolved spontaneously. Total hospital stay did not exceed 5 days for any of these patients.

Bronchoscopic volume reduction with valve implants in patients with severe emphysema.

Eight patients with severe emphysema entered a pilot study of unilateral volume reduction by endobronchial valve insertion. Five patients had emphysema judged too severe for volume reduction surgery and three refused the operation. After valve insertions, the median forced expiratory volume in 1 s (FEV1) increased from 0.79 L (range 0.61-1.07) to 1.06 L (0.75-1.22) (difference 34%, p=0.028) and the median diffusing capacity (TL(CO)) increased from 3.05 mL/min/mm Hg (2.35-4.71) to 3.92 mL/min/mm Hg (2.89-5.40) (difference 29%, p=0.017). CT scans showed a substantial reduction in regional volume in four of the eight patients. Two patients developed a transient pneumothorax (one requiring drainage) but we recorded no other important adverse effects during follow-up. Lung-volume reduction can be achieved with unilateral bronchoscopically placed valve implants in patients with severe emphysema with acceptable short-term safety and worthwhile functional benefits.