Lung Cancer Screening: Use of Low-Dose Computed Tomography

IntroductionThe prognosis of lung cancer (LC) correlates directly with the stage of the disease at the time of diagnosis.Material and methodsWe performed low-dose CT (LDCT) in asymptomatic individuals ≥50 years old, smokers or former smokers of ≥10 pack-years, with no history of cancer. We followed an evaluation algorithm, according to the size and morphology of the nodules. The appropriate treatment for the LC diagnosis was given and patients were followed up for 5 years.ResultsWe studied 4951 individuals (65.4% males) with an average age of 56.89±5.26 years; 550 presented nodules. Of the 3891 nodules detected, 692 (19.57%) were considered positive, and 38 tumors (36 LC) were identified. In the annual follow-up, nodules were found in 224 subjects, 288 (7.91%) of which were positive (13 LC). In 80%, the study was performed with LDCT, and biopsy was indicated in 5.8% (baseline) and in 7.6% (annual) of the positive nodules. Prevalence was 0.89 and incidence was 0.1%. The sensitivity, specificity, PPV and NPV in the baseline study were 92.31, 89.54, 6.55 and 99.93%, respectively, and in the annual study, they were 76.92, 95.7, 4.52 and 99.94%, respectively. A total of 52 tumors were detected (49 LC), 25 (52.08%) in stage I. The 5-year overall survival rate for LC was 58.5% and cancer-specific survival was 67.1% (75.8% in surgical patients).ConclusionLDCT integrated into an elaborate nodule detection and evaluation program is a useful tool for diagnosing early-stage LC.     

6-Year Risk of Developing Lung Cancer in Spain: Analysis by Autonomous Communities

IntroductionLung cancer screening with low-dose computed tomography (LDCT) has been proposed as a strategy to reduce lung cancer mortality. Since LDCT has side effects there is a need to carefully select the target population for screening programmes. Because in Spain health competences are transferred to the seventeen Autonomous Communities (ACs), the present paper aims to identify individuals at high risk of developing lung cancer in the different ACs.MethodsWe used the 2011–2012 data of the Spanish National Interview Health Survey (n = 21,006) to estimate the proportion of individuals at high risk of developing lung cancer using a 6-year prediction model (PLCO_m2012). This proportion was then extrapolated into absolute figures for the Spanish population, using the population census data of 2018 from the National Institute of Statistics.ResultsThe proportion of individuals aged 50–74 with a risk of lung cancer ≥2% was 9.5% (15.9% in men, 3.5% in women). This proportion ranged from 6.6% in Región de Murcia to 12.7% in Andalucía and 13.0% in Extremadura. When extrapolated to the Spanish population, it was estimated that a total of 1,341,483 individuals may have a 6-year risk of lung cancer ≥2%.ConclusionsThe present study is the first one that evaluated the number of individuals at high risk of developing lung cancer in the different Spanish ACs using a prediction model and selecting people with a 6-year risk ≥2%. Further studies should assess the cost and effectiveness associated to the implementation of a lung cancer screening programme to such population.     

Relationship Among Radiological Measurements of Anterior Mediastinal Fat and Outcomes of Lung Transplantation in Fibrotic Patients

ObjectiveLung transplantation (LT) for pulmonary fibrosis is related to higher mortality than other transplant indications. We aim to assess whether the amount of anterior mediastinal fat (AMF) was associated to early and long-term outcomes in fibrotic patients undergoing LT.MethodsRetrospective analysis of 92 consecutive single lung transplants (SLT) for pulmonary fibrosis over a 10-year period. AMF dimensions were measured on preoperative CT-scan: anteroposterior axis (AP), transverse axis (T), and height (H). AMF volumes (V) were calculated by the formula: AP × T × H × 3.14/6.According to the radiological AMF dimensions, patients were distributed into two groups: low-AMF (V < 20 cm³) and high-AMF (V > 20 cm³), and early and long-term outcomes were compared by univariable and multivariable analyses.ResultsThere were 92 SLT: 73M/19F, 53 ± 11 [14–68] years old. 30-Day mortality (low-AMF vs. high-AMF): 5 (5.4%) vs. 15 (16.3%), p = 0.014. Patients developing primary graft dysfunction within 72 h post-transplant, and those dying within 30 days post-transplant presented higher AMF volumes: 21.1 ± 19.8 vs. 43.3 ± 24.7 cm³ (p = 0.03) and 24.4 ± 24.2 vs. 56.9 ± 63.6 cm³ (p < 0.01) respectively. Overall survival (low-AMF vs. high-AMF) (1, 3, and 5 years): 85%, 81%, 78% vs. 55%, 40%, 33% (p < 0.001).Factors predicting 30-day mortality were: BMI (HR = 0.77, p = 0.011), AMF volume (HR = 1.04, p = 0.018), CPB (HR = 1.42, p = 0.002), ischaemic time (HR = 1.01, p = 0.009).Factors predicting survival were: AMF volume (HR = 1.02, p < 0.001), CPB (HR = 3.17, p = 0.003), ischaemic time (HR = 1.01, p = 0.001).ConclusionPreoperative radiological assessment of mediastinal fat dimensions and volumes may be a useful tool to identify fibrotic patients at higher risk of mortality after single lung transplantation.     

Pilot Trial of Extended Hypothermic Lung Preservation to Analyze Ischemia-reperfusion Injury in Pigs

BackgroundIn lung transplantation (LT), the length of ischemia time is controversial as it was arbitrarily stablished. We ought to explore the impact of extended cold-ischemia time (CIT) on ischemia-reperfusion injury in an experimental model.MethodsExperimental, randomized pilot trial of parallel groups and final blind analysis using a swine model of LT. Donor animals (n = 8) were submitted to organ procurement. Lungs were subjected to 6 h (n = 4) or 12 h (n = 4) aerobic hypothermic preservation. The left lung was transplanted and re-perfused for 4 h. Lung biopsies were obtained at (i) the beginning of CIT, (ii) the end of CIT, (iii) 30 min after reperfusion, and (iv) 4 h after reperfusion. Lung-grafts were histologically assessed by microscopic lung injury score and wet-to-dry ratio. Inflammatory response was measured by determination of inflammatory cytokines. Caspase-3 activity was determined as apoptosis marker.ResultsWe observed no differences on lung injury score or wet-to-dry ratio any given time between lungs subjected to 6 h-CIT or 12h-CIT. IL-1β and IL6 showed an upward trend during reperfusion in both groups. TNF-α was peaked within 30 min of reperfusion. IFN-γ was hardly detected. Caspase-3 immunoexpression was graded semiquantitatively by the percentage of stained cells. Twenty percent of apoptotic cells were observed 30 min after reperfusion.ConclusionsWe observed that 6 and 12 h of CIT were equivalent in terms of microscopic lung injury, inflammatory profile and apoptosis in a LT swine model. The extent of lung injury measured by microscopic lung injury score, proinflammatory cytokines and caspase-3 determination was mild.     

Tuberculosis Following Lung Transplantation. A 27-Year Spanish Multicenter Experience. Incidence,Presentation, Prevention and Treatment with Rifampicin

BackgroundTuberculosis (TB) represents a diagnostic and therapeutic challenge for solid organ transplant recipients, particularly after lung transplant (LT). Our aim was to determine the impact of TB in LT patients in Spain, considering prevalence, clinical presentation, prevention and therapeutic management. In addition, differences in outcome between rifampicin (RIF) versus non-RIF containing regimens were analyzed.MethodsMulticenter, observational retrospective study, including all cases of TB diagnosed in recipients after LT, in five pulmonary transplant units in Spain, between January 1990 and December 2017.ResultsAmong 2962 LT recipients, 45 cases of TB were diagnosed, resulting in a prevalence of 1.52%. Most of them (88.89%) were diagnosed during the first year posttransplantation, 86.67% with pulmonary presentation. Screening for latent TB infection (LTBI) was done in 36 of the 45 patients and LTBI was detected pretransplant in 12 (33.33%). Less than half of the patients with disease (42.22%) received rifampicin (RIF). Lower probability of TB worsening was found in RIF-containing regimens (p = 0.049), as well as longer survival (p = 0.001). RIF use was not associated with an increased risk in rejection (p = 0.99), but doses of calcineurin inhibitors (CNI) had to be raised an average of 215%.ConclusionsRisk of TB after LT was lower in our series than previously reported. TB should be searched during the first year posttransplant in patients with TB risk factors. Pulmonary presentation was predominant. More sensitive algorithms for detecting LTBI before LT are crucial. It is reasonable to use RIF-containing regimens over non-RIF regimens based on the tendency toward better outcome in our series. RIF regimen requires close monitoring of CNI trough level for 2–3 weeks, until stability is achieved.     

Spanish Video-Assisted Thoracic Surgery Group: Method,Auditing, and Initial Results From a National Prospective Cohort of Patients Receiving Anatomical Lung Resections

IntroductionOur study sought to know the current implementation of video-assisted thoracoscopic surgery (VATS) for anatomical lung resections in Spain. We present our initial results and describe the auditing systems developed by the Spanish VATS Group (GEVATS).MethodsWe conducted a prospective multicentre cohort study that included patients receiving anatomical lung resections between 12/20/2016 and 03/20/2018. The main quality controls consisted of determining the recruitment rate of each centre and the accuracy of the perioperative data collected based on six key variables. The implications of a low recruitment rate were analysed for “90-day mortality” and “Grade IIIb-V complications”.ResultsThe series was composed of 3533 cases (1917 VATS; 54.3%) across 33 departments. The centres’ median recruitment rate was 99% (25–75th:76–100%), with an overall recruitment rate of 83% and a data accuracy of 98%. We were unable to demonstrate a significant association between the recruitment rate and the risk of morbidity/mortality, but a trend was found in the unadjusted analysis for those centres with recruitment rates lower than 80% (centres with 95–100% rates as reference): grade IIIb-V OR = 0.61 (p = 0.081), 90-day mortality OR = 0.46 (p = 0.051).ConclusionsMore than half of the anatomical lung resections in Spain are performed via VATS. According to our results, the centre's recruitment rate and its potential implications due to selection bias, should deserve further attention by the main voluntary multicentre studies of our speciality. The high representativeness as well as the reliability of the GEVATS data constitute a fundamental point of departure for this nationwide cohort.     

Mortalidad por cáncer de próstata en la rama española del European Randomized Study of Screening for Prostate Cancer (ERSPC). Resultados tras 15 años de seguimiento

ObjectiveTo address if prostate cancer (PCa) screening decreases PCa mortality in the asymptomatic population, within the setting of the Spanish arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC).Material and methodsFrom 1996 to 1999, 4,278 men aged 45–70 years were recruited and randomized to the screening arm (PSA every 4 years, prostate biopsy when PSA  ≥ 3 ng/ml) and control arm (no tests). Dates and causes of death were collected on an annual basis. A Kaplan-Meier analysis was used to calculate overall and cancer-specific survival.ResultsA total of 2,416 men were recruited in the screening arm and 1,862 in the control arm. Mean age was 57.8 years, median follow-up was 13.3 years. At the end of the follow-up period, 427 deaths (9 from PCa) were observed. Survival analysis did not show any difference between the study arms with respect to overall and cancer-specific survival (p = 0.939 and p = 0.544 respectively). Most relevant causes of death were malignant tumors (52.9%), cardiovascular disease (17.3%) and respiratory (8.9%). Only 2.1% of deaths (0.2% of all recruited men) were due to PCa (2.5% screening, 1.6% control).ConclusionsThe Spanish arm of ERSPC failed to reproduce the long-term results shown in the whole study. No differences in mortality (overall or cancer-specific) were observed after 15 years of follow-up. PCa mortality was infrequent (less than 1%). These results suggest limited yield of PCa screening in our setting.     

Predictive Value of Immune Cell Functional Assay for Non-Cytomegalovirus Infection in Lung Transplant Recipients: A Multicenter Prospective Observational Study

IntroductionImmune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients.MethodsA multicenter prospective observational study of 92 patients followed up from 6 to 12 months after transplantation was performed. Immune cell functional assay was carried out at 6, 8, 10, and 12 months.ResultsTwenty-three patients (25%) developed 29 non-CMV infections between 6 and 12 months post-transplant. At 6 months, the immune response was moderate (ATP 225–525 ng/mL) in 14 (15.2%) patients and low (ATP < 225 ng/mL) in 78 (84.8%); no patients had a strong response (ATP ≥ 525 ng/mL). Only 1 of 14 (7.1%) patients with a moderate response developed non-CMV infection in the following 6 months compared with 22 of 78 (28.2%) patients with low response, indicating sensitivity of 95.7%, specificity of 18.8%, positive predictive value (PPV) of 28.2%, and negative predictive value (NPV) of 92.9% (AUC 0.64; p = 0.043). Similar acute rejection rates were recorded in patients with mean ATP ≥ 225 vs. <225 ng/mL during the study period (7.1% vs. 9.1%, p = 0.81).ConclusionAlthough ImmuKnow® does not seem useful to predict non-CMV infection, it could identify patients with a very low risk and help us define a target for an optimal immunosuppression.     

The effect of aortic stenosis on elderly hip fracture outcomes: A case control study

IntroductionAortic stenosis (AS) is an established predictor of perioperative complications following both cardiac and non-cardiac surgery. The purpose of this study was to evaluate the risk of mortality and perioperative complications among surgically treated hip fractures in elderly patients with moderate or severe AS compared to those without AS (negative controls).Materials and methodsA retrospective case-controlled review (1:2) of elderly (≥65 years) surgically treated hip fractures from 2011 to 2015 with moderate/severe AS (according to American Heart Association criteria) was conducted. Postoperative complication rates, 30 days and 1 year mortality were reviewed.ResultsModerate/severe AS was identified in 65 hip fracture cases and compared to 129 negative controls. AS cases were significantly older with higher rates of coronary artery disease and atrial fibrillation (p < 0.05). Rates of any 30-day perioperative complication (74% vs. 37%, p < 0.001) and severe non-cardiac 30-day perioperative complication (52% vs. 26%, p = 0.002) were significantly higher among AS cases compared to controls. Kaplan Meier estimates of 30-day mortality (14.7% vs. 4.2%, p < 0.001) and 1-year mortality (46.8% vs. 14.1%, p < 0.001) were significantly higher in AS cases compared to controls. Multivariate analysis of severe 30-day postoperative complications identified moderate/severe AS (OR 4.02, p = 0.001), pulmonary disease (OR 7.36, p = 0.002) and renal disease (OR 3.27, p = 0.04) as independent predictors. Moderate/severe AS (OR 3.38, p = 0.03), atrial fibrillation (OR 3.73, p = 0.03) and renal disease (OR 4.44, p = 0.02) were independent predictors of 30-day mortality. Moderate/severe AS (OR 5.79, p < 0.001) and renal disease (OR 3.39, p = 0.02) were independent predictors of 1-year mortality.ConclusionAortic stenosis is associated with a significantly increased risk of perioperative complications, 30-day mortality and 1-year mortality in elderly patients undergoing surgical treatment of hip fractures.     

Outcome of patients in laparoscopic training courses compared to standard patients

Background & aimCurrent Laparoscopic simulators have limited usefulness and patients have been used for training since the dawn of surgery. NUGITS (Northumbrian Upper Gastro Intestinal Team of Surgeons) Laparoscopic Skills courses utilise hands-on experience with simulators moving to live operating on volunteer patients. It is vital to know that the volunteer patient is not disadvantaged by greater surgical risk.MethodsThis was a case-controlled prospective comparison of patients undergoing both Laparoscopic Cholecystectomy (LC) [n = 51] and Laparoscopic Inguinal Hernia (LIH) [n = 62] during NUGITS training courses. They are compared with a matched (age, sex and ASA grade) control group LC (n = 51) and LIH (n = 62) operated on by consultants. The outcome measures were surgical peri-and post-operative complications, post-operative hospital stay, readmission and early recurrence of inguinal hernia (<6 months).ResultsIn the LC cohort, there was no significant difference in the length of hospital stay (p = 0.07) or readmission (p = 0.16) in both the groups. The mean operating time was higher in the trainee compared to the control group (p = 0.001). There was no difference in the post-operative morbidity or mortality in either group. In LIH cohort, the mean operating time was higher in the trainee compared with the control group. There was no significant difference in post-operative complications (p > 0.05) and early post-operative recurrence of hernia (p > 0.05).ConclusionThe post-operative outcomes of patients undergoing laparoscopic surgery during laparoscopic training courses are similar to consultant-operated patients. Thus, it is acceptable and safe to encourage patients to volunteer for laparoscopic training courses.     

Long Non-Coding RNA NANCI/NKX2-1 Duplex Impacts Prognosis in Stage I Non-Small-Cell Lung Cancer

BackgroundNANCI, an intergenic long non-coding RNA (lncRNA) is essential for buffering NKX2-1 expression during embryonic development and in adult tissue. We analyzed NANCI and NKX2-1 in human lung embryonic samples and adult lung tissues and evaluated their potential as prognostic markers in stage I non-small cell lung cancer (NSCLC).Methods and resultsNANCI and NKX2-1 expression was assessed by TaqMan assays in 18 human embryonic samples from 8 to 13 weeks, 59 non-tumoral (NT) lung tissue samples, and 98 stage I NSCLC tumor samples. NANCI and NKX2-1 expression in embryonic and NSCLC samples were downregulated in comparison to adult NT tissue. Patients with low expression of NANCI had shorter disease-free survival (DFS) and overall survival (OS) than those with high levels (47.6 vs 69.3 months, P = 0.032 and 57.7 vs 77.6 months, P = 0.021, respectively). When the expression levels of NANCI and NKX2-1 were evaluated in combination, four groups were identified (high NANCI/high NKX2-1, low NANCI/high NKX2-1, high NANCI/low NKX2-1 and low NANCI/low NKX2-1) with differential impact on DFS (P = 0.042) and OS (P = 0.024). Interestingly, the high NANCI/high NKX2-1 duplex group had longer DFS and OS than the other three groups (71.25 vs 46.3 months, P = 0.009 and 81.3 vs 56.1 months, P = 0.004, respectively). In the multivariate analysis, the high NANCI/high NKX2-1 duplex was identified as an independent prognostic factor for longer DFS (HR 0.346, 95% CI, 0.169–0.709; P = 0.004) and OS (HR 0.309, 95% CI, 0.121–0.786; P = 0.014).ConclusionsNANCI and the NANCI-NKX2-1 duplex impacts prognosis in stage I NSCLC patients.     

Long Non-coding RNA LINC-PINT and LINC00599 Polymorphisms are Associated With High-altitude Pulmonary Edema in Chinese

BackgroundHigh-altitude pulmonary edema (HAPE) is a kind of non-cardiogenic edema with high incidence and life-threatening. This study was designed to explore the association of LINC-PINT and LINC00599 polymorphisms with HAPE susceptibility.MethodsThis study included 244 HAPE patients and 243 age-, sex-matched healthy controls from the Chinese population. The genotypes of polymorphisms were detected using the Agena MassARRAY. The relationship between polymorphisms and HAPE risk was evaluated using a χ² test with an odds ratio (OR) and 95% confidence intervals (CIs) in multiple genetic models.ResultsWe observe a significant association between the rs157928 and decreased HAPE risk in genotype model (OR = 0.65, 95% CI = 0.43–0.98, p = 0.038). The subgroup analysis results indicated that rs2272026 was associated with a decreased risk of HAPE in younger patients with age ≤32 (codominant model: p = 0.006; recessive model: p = 0.005 additive model: p = 0.018; and allele model: p = 0.012; rs72625676, codominant model: p = 0.038; recessive model: p = 0.037). Among patients older than 32 years, there was a significantly increased risk of HAPE associated with the rs2272026 and rs1962430 (rs2272026: genotype model: p = 0.049; recessive model: p = 0.029; rs1962430: genotype model: p = 0.024; recessive model: p = 0.020). Nevertheless, rs157928 had relationship with significantly reducing the risk of HAPE in the genotype model (p = 0.018).ConclusionOur study suggests that LINC-PINT and LINC00599 polymorphisms are associated with HAPE susceptibility in Chinese population.     

Has the COVID-19 pandemic changed the clinical picture and tumour stage at the time of presentation of patients with colorectal cancer? A retrospective cohort study

IntroductionTreatment of patients with Coronavirus Disease 2019 (COVID-19) has affected the management of patients with colorectal cancer (CRC). The aim of this study was to compare the diagnosis delay, symptoms, and stage of patients with CRC during the pandemic with a control cohort.Material and methodsPatients referred to the CRC multidisciplinary team between September 2019 and January 2020 (cohort 1, control group) were compared with those who presented between September 2020 and March 2021 (cohort 2, pandemic group).Results389 patients were included, 169 in cohort 1 and 220 in cohort 2. No differences were observed in the main characteristics of the patients. CRC screening and anaemia were the most common causes leading to the diagnosis of the tumour in cohort 1 and 2, respectively (p < 0.001). Diagnostic and therapeutic delay was longer in cohort 2 [6.4 (95% CI 5.8–6.9) vs. 4.8 (95% CI 4.3–5.3) months, p < 0.001]. More patients required non-elective treatment in the pandemic cohort (15.5% vs. 9.5%, p = 0.080). The tumour stage was more advanced in patients in cohort 2 [positive nodes in 52.3% vs. 36.7% (p = 0.002), and metastatic disease in 23.6% vs. 16.6% (p = 0.087)].ConclusionCRC patients in the pandemic cohort had a longer diagnostic and therapeutic delay and less patients were diagnosed because of CRC screening. In addition, patients with CRC during the pandemic needed non-elective treatment more frequently than patients in the control cohort, and their tumour stage tended to be more advanced.     

Endovascular Repair of the Thoracic Aorta: Predictors of 30-Day Mortality in Patients on the New Zealand Thoracic Aortic Stent Database (NZ TAS)

ObjectivesTo evaluate data in the New Zealand Thoracic Aortic Stent database to try and identify a scoring system that could predict 30-day mortality in patients undergoing stenting of the descending thoracic aorta (TEVAR).DesignRetrospective analysis of the New Zealand thoracic aortic stent database between December 2001 and August 2007.Materials and methodsThe 30-day mortality of the 122 patients is 7.38% (n = 9). Risk factors were recorded based on the Society of Thoracic Surgeons (STS) risk score. Glasgow aneurysm score was calculated and the pathology being treated analysed. Univariate analyisis was carried out.ResultsThe mortality of three pathology groups was compared. 30-day mortality was 2.04% (n = 1) in the elective aneurysm group, 17.95% (n = 7) in the complicated Stanford type B dissection group, and 0% (n = 0) in the trauma group. Thirty-day mortality is significantly higher in the dissection group compared with the elective aneurysm (p = 0.02) and trauma (p = 0.03) groups. The most frequent risk factors in the dissection group of patients were peripheral vascular disease, smoking and hypertension. Although percentage mortality is higher with increasing GAS, the results are not statistically significant (p = 0.34). No independent risk factors were identified from the STS risk score data.ConclusionNo specific risk score system seems to be able to predict mortality in TEVAR patients.     

Implementation of an Integrated Care Model for Frequent-Exacerbator COPD Patients: A Controlled Prospective Study

IntroductionFrequent-exacerbator COPD (fe-COPD) associated with frequent hospital admissions have high morbidity, mortality and use of health resources. These patients should be managed in personalized integrated care models (ICM). Accordingly, we aimed to evaluate the long-term effectiveness of a fe-COPD ICM on emergency room (ER) visits, hospital admissions, days of hospitalization, mortality and improvement of health status.MethodsProspective-controlled study with analysis of a cohort of fe-COPD patients assigned to ICM and followed-up for maximally 7 years that were compared to a parallel cohort who received standard care. All patients had a confirmed diagnosis of COPD with a history of ≥2 hospital admissions due to exacerbations in the year before enrollment. The change in CAT score and mMRC dyspnea scale, hospital admissions, ER visits, days of hospitalization, and mortality were analyzed.Results141 patients included in the ICM were compared to 132 patients who received standard care. The ICM reduced hospitalizations by 38.2% and ER visits by 69.7%, with reduction of hospitalizations for COPD exacerbation, ER visits and days of hospitalization (p < 0.05) compared to standard care. Further, health status improved among the ICM group after 1 year of follow-up (p = 0.001), effect sustained over 3 years. However, mortality was not different between groups (p = 0.117). Last follow-up CAT score > 17 was the strongest independent risk factor for mortality and hospitalization among ICM patients.ConclusionsAn ICM for fe-COPD patients effectively decreases ER and hospital admissions and improves health status, but not mortality.     

Core Microbiota in Central Lung Cancer With Streptococcal Enrichment as a Possible Diagnostic Marker

BackgroundDysbiosis in lung cancer has been underexplored. The aim of this study was to define the bacterial and fungal microbiota of the bronchi in central lung cancer and to compare it with that of the oral and intestinal compartments.MethodsTwenty-five patients with central lung cancer and sixteen controls without antimicrobial intake during the previous month were recruited. Bacterial and fungal distribution was determined by massive sequencing of bronchial biopsies and saliva and faecal samples. Complex computational analysis was performed to define the core lung microbiota.ResultsAffected and contralateral bronchi of patients have almost identical microbiota dominated by Streptococcus, whereas Pseudomonas was the dominant genera in controls. Oral and pulmonary ecosystems were significantly more similar in patients, probably due to microaspirations. Streptococcal abundance in the bronchi differentiated patients from controls according to a ROC curve analysis (90.9% sensitivity, 83.3% specificity, AUC = 0.897). The saliva of patients characteristically showed a greater abundance of Streptococcus, Rothia, Gemella and Lactobacillus. The mycobiome of controls (Candida) was significantly different from that of patients (Malassezia). Cancer patients’ bronchial mycobiome was similar to their saliva, but different from their contralateral bronchi.ConclusionsThe central lung cancer microbiome shows high levels of Streptococcus, and differs significantly in its composition from that of control subjects. Changes are not restricted to tumour tissue, and seem to be the consequence of microaspirations from the oral cavity. These findings could be useful in the screening and even diagnosis of this disease.     

iDXA,Prodigy, and DPXL Dual-Energy X-ray Absorptiometry Whole-Body Scans: A Cross-Calibration Study

PurposeTotal body fat, lean, and bone mineral content (BMC) in addition to regional fat and lean mass values for arms, legs, and trunk were compared across a pencil-beam (Lunar DPXL) and 2 fan-beam (GE Lunar Prodigy and GE Lunar iDXA) dual-energy X-ray absorptiometry (DXA) systems.MethodsSubjects were a multiethnic sample of 99 healthy adult males (47%) and females (mean ± SD: age, 46.3 ± 16.9 yr; weight, 73.4 ± 16.6 kg; height, 167.6 ± 9.7 cm; body mass index, 26.0 ± 5.2 kg/m²) who had whole-body scans performed within a 3-h period on the 3 systems. Repeated measures ANOVA was used to test the null hypothesis that the mean values for the 3 systems were equal. Translation equations between the methods were derived using regression techniques.ResultsBone mineral content (BMC): For both genders, total BMC by iDXA was lower (p ≤ 0.004) than the other systems. Lean: for males, iDXA was lower (p ≤ 0.03) than the other systems for total, trunk, and arms. For females, DPXL estimated higher (p < 0.001) lean mass compared with the other systems for total, trunk, and arms, but iDXA estimated greater legs lean mass. For both genders, all DPXL mean values were greater than Prodigy mean values (p < 0.001).Fat: in females, all the 3 systems were different from each other for total, trunk, and legs (p ≤ 0.04). For arms, DPXL and iDXA were higher than Prodigy (p < 0.0004). For males, DPXL was less (p < 0.001) for total body, trunk, and legs compared with the other 2 systems and greater than Prodigy only for arms (p < 0.0007). These data were used to derive translation equations between systems. For several measurements, the differences between systems were related to gender.ConclusionFor estimation of BMC and body composition, there was high agreement between all DXA systems (R² = 0.85–0.99). Even so, cross-calibration equations should be used to examine data across systems to avoid erroneous conclusions.     

The impact of serum albumin and serum protein levels on POSSUM score of patients with proximal femur fractures

BackgroundPOSSUM was developed to predict risk-adjusted mortality and morbidity rates for surgical procedures. We evaluated the impact of serum albumin and serum protein levels on POSSUM scores.MethodsMedical files of 2269 patients operated for proximal femur fractures were reviewed. Preoperative serum albumin levels were available for 387 patients (mean 35.1 g/l, range 22–49) and serum protein levels for 279 patients (mean 61.6 g/l, range 40–86).ResultsSerum albumin and protein levels were inversely associated with mortality in multivariate models (albumin, OR = 0.89, p = 0.009; protein, OR = 0.92, p = 0.009) and in composite outcome models as well (albumin, OR = 0.955, p = 0.219, protein, OR = 0.94, p = 0.014). The area under the curve (AUC) for POSSUM prediction of mortality (n = 1770) was 0.632 (95% CI: 0.580–0.684, p < 0.001). The AUC for a model including serum protein levels was 0.742 (95% CI: 0.649–0.834, p < 0.001). Hospitalisation time was longer for patients with lower serum proteins levels (p = 0.045), with an inverse correlation (Pearson correlation −0.164, p = 0.011).ConclusionsLower preoperative serum albumin and serum protein levels were associated with increased risk for mortality, increased hospitalisation time and poorer outcomes in patients operated for proximal femoral fractures. Including those values to POSSUM scores would increase their predictive power.     

Pharmacokinetics and safety of tobramycin administered by the PARI eFlow® rapid nebulizer in cystic fibrosis

BackgroundNebulization times have been identified as an issue in patient compliance with tobramycin solution for inhalation (TSI) therapy in cystic fibrosis (CF).MethodsIn this randomized, open-label, multicentre, two-period, crossover study, patients (n = 25) with CF and chronic pulmonary pseudomonal infection received TSI for 15 days via eFlow rapid or LC PLUS nebulizer. Nebulization times and sputum/serum tobramycin concentrations were determined, and safety evaluated.ResultsNebulization times were significantly shorter for eFlow rapid versus LC PLUS on Day 1 (least squares mean estimate of the difference − 10.5 min, 95% confidence intervals [CI] − 12.6, − 8.3, p < 0.0001) and Day 15 (difference − 7.7 min, 95% CI − 9.0, − 6.5, p < 0.0001). Broadly comparable sputum/systemic exposure to tobramycin was observed and the incidence of adverse events was similar for both nebulizers.ConclusionUse of the eFlow rapid nebulizer reduced TSI nebulization time. The systemic exposure to tobramycin appeared to be broadly similar in this exploratory study.