The Effects of Oral Atenolol or Enalapril Premedication on Blood Loss and Hypotensive Anesthesia in Orthognathic Surgery

Purpose

The aim of this study was to evaluate the effects of premedication with oral atenolol or enalapril, in combination with remifentanil under sevoflurane anesthesia, on intraoperative blood loss by achieving adequate deliberate hypotension (DH) during orthognathic surgery. Furthermore, we investigated the impact thereof on the amount of nitroglycerin (NTG) administered as an adjuvant agent.

Materials and Methods

Seventy-three patients undergoing orthognathic surgery were randomly allocated into one of three groups: an angiotensin converting enzyme inhibitor group (Group A, n=24) with enalapril 10 mg, a β blocker group (Group B, n=24) with atenolol 25 mg, or a control group (Group C, n=25) with placebo. All patients were premedicated orally 1 h before the induction of anesthesia. NTG was the only adjuvant agent used to achieve DH when mean arterial blood pressure (MAP) was not controlled, despite the administration of the maximum remifentanil dose (0.3 µg kg^-1min^-1) with sevoflurane.

Results

Seventy-two patients completed the study. Blood loss was significantly reduced in Group A, compared to Group C (adjusted p=0.045). Over the target range of MAP percentage during DH was significantly higher in Group C than in Groups A and B (adjusted p-values=0.007 and 0.006, respectively). The total amount of NTG administered was significantly less in Group A than Group C (adjusted p=0.015).

Conclusion

Premedication with enalapril (10 mg) combined with remifentanil under sevoflurane anesthesia attenuated blood loss and achieved satisfactory DH during orthognathic surgery. Furthermore, the amount of NTG was reduced during the surgery.     

Predicted EC50 and EC95 of Remifentanil for Smooth Removal of a Laryngeal Mask Airway Under Propofol Anesthesia

Purpose

The purpose of this study was to determine the effect-site concentration (Ce) of remifentanil in 50% of patients (EC₅₀) and 95% of patients (EC₉₅) for smooth laryngeal mask airway (LMA) removal in adults under propofol and remifentanil anesthesia.

Materials and Methods

Twenty-five patients of ASA physical status I-II and ages 18-60 years who were to undergo minor gynecological or orthopedic surgery were assessed in this study. Anesthesia was induced and maintained with propofol and remifentanil target-controlled infusion (TCI). Remifentanil was maintained at a predetermined Ce during the emergence period. The modified Dixon''s up-and-down method was used to determine the remifentanil concentration, starting from 1.0 ng/mL (step size of 0.2 ng/mL). Successful removal of the LMA was regarded as absence of coughing/gagging, clenched teeth, gross purposeful movements, breath holding, laryngospasm, or desaturation to SpO₂<90%.

Results

The mean±SD Ce of remifentanil for smooth LMA removal after propofol anesthesia was 0.83±0.16 ng/mL. Using isotonic regression with a bootstrapping approach, the estimated EC₅₀ and EC₉₅ of remifentanil Ce were 0.91 ng/mL [95% confidence interval (CI), 0.77-1.07 ng/mL] and 1.35 ng/mL (95% CI, 1.16-1.38 ng/mL), respectively.

Conclusion

Our results showed that remifentanil TCI at an established Ce is a reliable technique for achieving safe and smooth emergence without coughing, laryngospasm, or other airway reflexes.     

The Clinical Significance of the Right Para-Oesophageal Lymph Nodes in Papillary Thyroid Cancer

Purpose

Although guidelines indicate that routine dissection of the central lymph nodes in patients with thyroid carcinoma should include the right para-oesophageal lymph nodes (RPELNs), located between the right recurrent laryngeal nerve and the cervical oesophagus and posterior to the former, RPELN dissection is often omitted due to high risk of injuries to the recurrent laryngeal nerve and the right inferior parathyroid gland.

Materials and Methods

We retrospectively identified all patients diagnosed with papillary thyroid carcinoma who underwent total thyroidectomy with central lymph node dissection, including the RPELNs, between January 1, 2009 and December 31, 2013 at the Thyroid Cancer Center of Yonsei University College of Medicine, Seoul, Korea.

Results

Of 5556 patients, 148 were positive for RPELN metastasis; of the latter, 91 had primary tumours greater than 1 cm (p<0.001). Extrathyroidal extension by the primary tumour (81.8%; p<0.001), bilaterality, and multifocality were more common in patients with than without RPELN metastasis; however, there were no significant differences in age and sex between groups. A total of 95.9% of patients with RPELN metastasis had central node (except right para-oesophageal lymph node) metastasis, and the incidence of lateral neck node metastasis was significantly higher in patients with than without RPELN metastasis (63.5% vs. 14.3%, p<0.001). Forty-one patients underwent mediastinal dissection, with 11 patients confirmed as having mediastinal lymph node metastasis with RPELN metastasis on pathological examination.

Conclusion

RPELN metastasis is significantly associated with lateral neck and mediastinal lymph node metastasis.     

Changes in Echocardiographic Parameters According to the Rate of Residual Renal Function Decline in Incident Peritoneal Dialysis Patients

Residual renal function (RRF) is associated with left ventricular (LV) hypertrophy as well as all-cause and cardiovascular (CV) mortality in patients with end-stage renal disease. However, no studies have yet examined the serial changes in echocardiographic findings according to the rate of RRF decline in incident dialysis patients.A total of 81 patients who started peritoneal dialysis (PD) between 2005 and 2012 at Yonsei University Health System, Seoul, South Korea, and who underwent baseline and follow-up echocardiography within the first year of PD were recruited. Patients were dichotomized into “faster” and “slower” RRF decline groups according to the median values of RRF decline slope (−1.60 mL/min/y/1.73 m²).Baseline RRF and echocardiographic parameters were comparable between the 2 groups. During the first year of PD, there were no significant changes in LV end-diastolic volume index (LVEDVI), left atrial volume index (LAVI), or LV mass index (LVMI) in the “faster” RRT decline group, while these indices decreased in the “slower” RRT decline group. The rate of RRF decline was a significant determinant of 1-year changes in LVEDVI, LAVI, and LVMI. The linear mixed model further confirmed that there were significant differences in the changes in LVEDVI, LAVI, and LVMI between the 2 groups (P = 0.047, 0.048, and 0.001, respectively). During a mean follow-up duration of 31.9 months, 4 (4.9%) patients died. Compared with the “slower” RRF decline group, CV composite (20.29/100 vs 7.18/100 patient-years [PY], P = 0.098), technique failure (18.80/100 vs 4.19/100 PY, P = 0.006), and PD peritonitis (15.73/100 vs 4.95/100 PY, P = 0.064) developed more frequently in patients with “faster” RRF decline rate. On multivariate Cox regression analysis, patients with “faster” RRF decline rate showed 4.82-, 4.44-, and 7.37-fold higher risks, respectively, for each clinical outcome.Preservation of RRF is important for conserving cardiac performance, resulting in an improvement in clinical outcomes of incident PD patients.     

Procedural outcomes of repeated transradial coronary procedure.

We evaluated the changes in radial arterial diameter and the procedural outcomes of repeated transradial procedures through the same radial artery in 117 cases. No significant differences were found in the mean diameter of the radial artery between preprocedure and 1 day after procedure on initial and repeated procedures. However, the mean radial arterial diameter was significantly decreased from 2.63 +/- 0.35 to 2.51 +/- 0.29 mm during follow-up after the initial procedure (P = 0.01). There was no significant difference in the vascular access times of the initial and repeated procedures (2.9 +/- 3.1 vs. 3.3 +/- 3.6 min; P = 0.08), and procedural success of repeated procedure was similar to those of the initial procedure. However, the incidence of radial arterial occlusion was higher for repeated procedures (2.6% vs. 0%; P = 0.01). We conclude that the repeated use of the radial artery is feasible in most patients with a high procedural success rate and low vascular complications.     

Clinical Correlation Between Tumor Maximal Standardized Uptake Value in Metabolic Imaging and Metastatic Tumor Characteristics in Advanced Non-small Cell Lung Cancer

This study aimed to elucidate whether the maximal standardized uptake value (SUVmax) of primary tumors in metabolic imaging correlated with pathological or metastatic characteristics and whether it was prognostic in stage IV nonsmall cell lung cancer (NSCLC).We retrospectively reviewed the medical records of 412 eligible patients between June 2007 and January 2013. All enrolled patients fulfilled the following criteria: they were newly diagnosed with stage IV NSCLC without any previous treatment and had undergone a systemic evaluation, including 18(F)-Fluoro-2-deoxyglucose positron emission tomography/computed tomography, to assess synchronous metastatic sites. Patient and tumor characteristics were analyzed, and clinical correlations between SUVmax and metastatic features were investigated.The median age of the study population was 65 years (range, 30–94), and 259 (62.9%) patients were male. The median SUVmax was statistically higher in males, in tumors with squamous cell histology, and in poorly differentiated tumors. Multivariate logistic regression analysis revealed that SUVmax ≥ 11.4 (top 30 percentiles) were significantly correlated with positive lymph node status (odds ratio [OR] 3.473), abdomen/pelvis metastasis (OR 1.949), and the absence of bone metastasis (OR 0.399) in the subgroup of nonsquamous NSCLC (n = 343). In Kaplan–Meier survival analysis, overall survival was significantly lower among cohorts with high SUVmax (≥11.4) than with low SUVmax (<11.4) (P < 0.001, median 7.4 months vs 12.1 months).The tumors with different SUVmax have distinctive metastatic and biological features in stage IV NSCLC. The underlying mechanisms of this unique metabolic biology need to be resolved in future studies.     

Vitamin D Deficiency Is an Independent Risk Factor for Urinary Tract Infections After Renal Transplants

Vitamin D deficiency is frequently found in patients with renal transplants (RTxs). Because vitamin D plays indispensable roles in the immune system, there may be an association between vitamin D deficiency and infection in these patients, but this has not been fully elucidated. Therefore, this study investigated the impact of pre-RTx vitamin D deficiency on urinary tract infection (UTI) development after RTx.We measured 25-hydroxyvitamin D3 (25(OH)D3) levels in 410 patients 2 weeks before they underwent RTx. Vitamin D deficiency was defined as 25(OH)D3 <10 ng/mL. The primary outcome was UTI occurrence after RTx. Cox proportional hazard analysis determined whether vitamin D deficiency was independently associated with UTI.The mean 25(OH)D3 level was 12.8 ± 6.9 ng/mL, and 171 patients (41.7%) were vitamin D deficient. During a median follow-up duration of 7.3 years, the UTI incidence was significantly higher in vitamin D-deficient patients (52 patients, 30.4%) compared with vitamin D-nondeficient patients (40 patients, 16.7%) (P = 0.001). Moreover, multivariate Cox proportional hazard analysis showed that vitamin D deficiency was an independent predictor of UTI after RTx (hazard ratio 1.81, 95% confidence interval 1.11–2.97, P = 0.02).Vitamin D deficiency was an independent risk factor for UTI after RTx; hence, determining 25(OH)D3 levels might help to predict infectious complications after RTx.     

TRPC6 channel translocation into phagosomal membrane augments phagosomal function

Defects in the innate immune system in the lung with attendant bacterial infections contribute to lung tissue damage, respiratory insufficiency, and ultimately death in the pathogenesis of cystic fibrosis (CF). Professional phagocytes, including alveolar macrophages (AMs), have specialized pathways that ensure efficient killing of pathogens in phagosomes. Phagosomal acidification facilitates the optimal functioning of degradative enzymes, ultimately contributing to bacterial killing. Generation of low organellar pH is primarily driven by the V-ATPases, proton pumps that use cytoplasmic ATP to load H⁺ into the organelle. Critical to phagosomal acidification are various channels derived from the plasma membrane, including the anion channel cystic fibrosis transmembrane conductance regulator, which shunt the transmembrane potential generated by movement of protons. Here we show that the transient receptor potential canonical-6 (TRPC6) calcium-permeable channel in the AM also functions to shunt the transmembrane potential generated by proton pumping and is capable of restoring microbicidal function to compromised AMs in CF and enhancement of function in non-CF cells. TRPC6 channel activity is enhanced via translocation to the cell surface (and then ultimately to the phagosome during phagocytosis) in response to G-protein signaling activated by the small molecule (R)-roscovitine and its derivatives. These data show that enhancing vesicular insertion of the TRPC6 channel to the plasma membrane may represent a general mechanism for restoring phagosome activity in conditions, where it is lost or impaired.Chronic infection and inflammation in the airways in cystic fibrosis (CF), as well as chronic obstructive pulmonary disease (COPD), tuberculosis, and asthma are now among the most common chronic diseases. Pulmonary infection associated with these diseases has historically been treated with antibiotics that kill bacteria but also select for development of resistance in the pathogen in the chronically infected lung (1, 2). One solution to antimicrobial drug resistance is to target the host rather than the pathogen. This strategy necessitates finding alternative targets or signaling strategies amplifying or restoring bactericidal capacity in the cells charged with the task of resolving chronic infection.Mononuclear phagocytes orchestrate the innate immune response in the lung through the combinatorial interplay between the phagocytic uptake and killing of bacterial invaders, clearance of apoptotic cells, antigen presentation, and secretion of vesicle-bound signaling molecules to recruit help in the resolution of infection. Ionic fluxes across the phagosomal membrane that encloses the pathogen produce a hostile acidic environment developed through the action of a V-ATPase proton translocation. However, a positive intraphagosomal membrane potential generated by proton translocation minimizes the proton content of the phagosome. An influx of Cl⁻ via Cl⁻ channels reduces the membrane potential generated by the proton pump, thereby, allowing maximal acidification of the phagolysosomal compartment, which in turn maximizes the activation of lysosomal degradative enzymes, generation of hypochlorous acid, and consequent bacterial killing (3, 4). We have previously demonstrated that murine alveolar macrophages (AMs) use the anion channel cystic fibrosis transmembrane conductance regulator (CFTR) as a Cl⁻ permeation pathway in the phagosomal membrane. In CF, loss of functional CFTR in the AM alkalinizes the phagosomal lumen and allows antimicrobial-resistant bacterial pathogens to survive macrophage surveillance.Not all tissue macrophages use CFTR as a charge compensation pathway in phagolysosomal acidification (4). In fact, recent data suggest that multiple V-ATPase charge-shunt pathways can exist in diverse macrophage lineages (5) via lysosomal recruitment and membrane insertion upon particle uptake. This observation led us to search for possible alternative charge-shunt pathways in pulmonary macrophages and how they might be activated or targeted to the maturing phagosome. Could a pharmacological tool circumvent the defect in CF AMs and activate alternative pathways to rescue both organellar acidification and bactericidal activity in cells expressing mutations in CFTR? Such a tool might activate parallel charge-shunt pathways used in peritoneal macrophages for maximum acidification, thereby allowing them to clear bacteria independently of CFTR expression as well as amplify the microbicidal response in the presence of functional CFTR. The transport proteins and channels active in peritoneal macrophage bacterial clearance have not been described but may involve a K⁺/H⁺ exchanger important in promoting excitatory synaptic vesicle filling (6) or a cation channel moving positive charge out of the phagolysosomal compartment, as has been suggested for macrophage cell lines (7).We began our investigations pursuing a novel pharmacological strategy to identify compounds that would resolve bacterial infection in the CF lung without the use of antimicrobials. We picked a cellular defect in CF because of the availability of animal models and extended our observations to non-CF human pulmonary cells. We designed screening assays of phagosome function, which could be used in a clinical setting as both diagnostic and investigational tools. We interrogated host function by studying surface receptor-mediated mechanisms that might provide parallel signaling pathways in subcellular organellar function in the resolution of disease.We report that a series of small molecules first identified in chemotherapeutics, (R)-roscovitine [2-(R)-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine] and its derivatives, restore microbicidal function to compromised AMs in CF and enhance function in non-CF cells. The compounds use a G protein-mediated signaling pathway, which results in the mobilization of transient receptor potential canonical-6 (TRPC6) calcium-permeable, nonselective cation channels to the plasma membrane and subsequently to the phagosomal membrane. Members of the TRP channel family have been implicated in a number of critical phagocytic functions, including particle uptake, migration, and reactive oxygen species (ROS) production (5, 8–11). Numerous studies (12–15) have suggested TRP channels as potential targets for the development of therapies in pulmonary inflammation because of their abundant and diverse cellular expression throughout the respiratory tree. Although TRPC6 channels have been previously identified in lung macrophages and shown to be up-regulated in COPD, their precise role in the pathophysiology of the disease is yet to be determined (16). Perhaps more relevant to our study, a TRPC6-mediated Ca²⁺ influx is increased in human CF airway epithelial cells, possibly because of a functional association between CFTR and TRPC6 that is lost in CF (17), with unknown consequences. To our knowledge, this study is the first to associate TRPC6 channels a specific drug-targeting strategy for the resolution chronic pulmonary infection.