A range of 30-62% of functioning multiciliated airway cells is sufficient to maintain ciliary airway clearance.

BACKGROUND: Primary ciliary dyskinesia is a genetic disorder caused by aberrant motile cilia function that results in defective ciliary airway clearance and subsequently leads to recurrent airway infections and bronchiectasis. We aimed to determine: how many functional multiciliated airway cells are sufficient to maintain ciliary airway clearance? METHODS: To answer this question we exploited the molecular defects of the X-linked recessive primary ciliary dyskinesia variant caused by pathogenic variants in DNAAF6 (PIH1D3), characterised by immotile cilia in affected males. We carefully analysed the clinical phenotype and molecular defect (using immunofluorescence and transmission electron microscopy) and performed in vitro studies (particle tracking in air-liquid interface cultures) and in vivo studies (radiolabelled tracer studies) to assess ciliary clearance of respiratory cells from female individuals with heterozygous and male individuals with hemizygous pathogenic DNAAF6 variants. RESULTS: Primary ciliary dyskinesia male individuals with hemizygous pathogenic DNAAF6 variants displayed exclusively immotile cilia, absence of ciliary clearance and severe primary ciliary dyskinesia symptoms. Owing to random or skewed X-chromosome inactivation in six female carriers with heterozygous pathogenic DNAAF6 variants, 54.3±10% (range 38-70%) of multiciliated cells were defective. Nevertheless, in vitro and in vivo assessment of the ciliary airway clearance was normal or slightly abnormal. Consistently, heterozygous female individuals showed no or only mild respiratory symptoms. CONCLUSIONS: Our findings indicate that having 30-62% of multiciliated respiratory cells functioning can generate either normal or slightly reduced ciliary clearance. Because heterozygous female carriers displayed either no or subtle respiratory symptoms, complete correction of 30% of cells by precision medicine could improve ciliary airway clearance in individuals with primary ciliary dyskinesia, as well as clinical symptoms.

Prognostic value of pulmonary diffusing capacity for carbon monoxide and ventilation-perfusion SPECT findings in pulmonary arterial hypertension.

Reduced pulmonary diffusing capacity for carbon monoxide (DLCO) can be observed in pulmonary arterial hypertension (PAH) and associates with increased mortality. However, the prognostic value of DLCO when corrected for haemoglobin (DLCOc), an independent modifier of DLCO, remains understudied. Additionally, the prognostic role of ventilation (V)-perfusion (Q) emission computed tomography (V/Q SPECT) findings in patients with PAH, which may concurrently be performed to rule out chronic thromboembolic pulmonary hypertension, is uncertain. A retrospective cohort study was conducted on 152 patients with PAH referred to a tertiary hospital for evaluation from January 2011 to January 2020. Lung function tests, clinical data and V/Q SPECT were ascertained. Cox regression analysis was performed to evaluate the association between DLCOc, DLCO and V/Q SPECT defects at referral with all-cause mortality. In equally adjusted Cox regression analysis, each percentage increase in DLCOc % predicted (%pred) (hazard ratio (HR) 0.97; 95% CI: 0.94-0.99) and DLCO%pred (HR 0.97; 95% CI: 0.94-0.99) was similarly associated with all-cause mortality. There was no detectable difference in area under the curve for prediction of all-cause mortality by DLCOc%pred and DLCO%pred (C-index 0.71 and 0.72, respectively, P = 0.85 for difference). None of the defects noted on V/Q SPECT were significantly associated with mortality, but mismatched defects were associated with lower values of DLCOc%pred and DLCO%pred. DLCOc%pred and DLCO%pred perform equally as prognostic markers in PAH, supporting the use of either metric when available for prognostic stratification.

Pulmonary diffusing capacity for carbon monoxide and nitric oxide after COVID-19: A prospective cohort study (the SECURe study).

Many patients exhibit persistently reduced pulmonary diffusing capacity after coronavirus disease 2019 (COVID-19). In this study, dual test gas diffusing capacity for carbon monoxide and nitric oxide (DL,CO,NO) metrics and their relationship to disease severity and physical performance were examined in patients who previously had COVID-19. An initial cohort of 148 patients diagnosed with COVID-19 of all severities between March 2020 and March 2021 had a DL,CO,NO measurement performed using the single-breath method at 5.7 months follow-up. All patients with at least one abnormal DL,CO,NO metric (n = 87) were revaluated at 12.5 months follow-up. The DL,CO,NO was used to provide the pulmonary diffusing capacity for nitric oxide (DL,NO), the pulmonary diffusing capacity for carbon monoxide (DL,CO,5s), the alveolar-capillary membrane diffusing capacity and the pulmonary capillary blood volume. At both 5.7 and 12.5 months, physical performance was assessed using a 30 s sit-to-stand test and the 6 min walk test. Approximately 60% of patients exhibited a severity-dependent decline in at least one DL,CO,NO metric at 5.7 months follow-up. At 12.5 months, both DL,NO and DL,CO,5s had returned towards normal but still remained abnormal in two-thirds of the patients. Concurrently, improvements in physical performance were observed, but with no apparent relationship to any DL,CO,NO metric. The severity-dependent decline in DL,NO and DL,CO observed at 5.7 months after COVID-19 appears to be reduced consistently at 12.5 months follow-up in the majority of patients, despite marked improvements in physical performance.

Predictors of reoperation after lung volume reduction surgery.

OBJECTIVES: Lung volume reduction surgery (LVRS) has proven an effective treatment for emphysema, by decreasing hyperinflation and improving lung function, activity level and reducing dyspnoea. However, postoperative air leak is an important complication, often leading to reoperation. Our aim was to analyse reoperations after LVRS and identify potential predictors. METHODS: Consecutive single-centre unilateral VATS LVRS performed from 2017 to 2022 were included. Typically, 3-5 minor resections were made using vascular magazines without buttressing. Data were obtained from an institutional database and analysed. Multivariable logistic regression was used to identify predictors of reoperation. Number and location of injuries were registered. RESULTS: In total, 191 patients were included, 25 were reoperated (13%). In 21 patients, the indication for reoperation was substantial air leak, 3 patients bleeding and 1 patient empyema. Length of stay (LOS) was 21 (11-33) vs. 5 days (3-11), respectively. Only 3 injuries were in the stapler line, 13 within < 2cm and 15 injuries were in another site. Multivariable logistic regression analysis showed that decreasing DLCO increased risk of reoperation, OR 1.1 (1.03, 1.18, P = 0.005). Resections in only one lobe, compared to resections in multiple lobes, were also a risk factor OR 3.10 (1.17, 9.32, P = 0.03). Patients undergoing reoperation had significantly increased 30-day mortality, OR 5.52 (1.03, 26.69, P = 0.02). CONCLUSIONS: Our incidence of reoperation after LVRS was 13% leading to prolonged LOS and increased 30-day mortality. Low DLCO and resections in a single lobe were significant predictors of reoperation. The air leak was usually not localized in the stapler line.

Brain imaging in children with neonatal cholestatic liver disease: A systematic review.

AIM: To determine if children with neonatal cholestatic liver disease had concurrent and later findings on brain imaging studies that could be attributed and the cholestasis to contribute to the understanding of the impaired neuropsychological development. METHODS: Ovid MEDLINE and EMBASE were searched on July 21, 2022, and updated on March 26, 2023. Studies with children under 18 years of age with neonatal cholestasis and a brain scan at the time of diagnosis or later in life were included. Excluded studies were non-English, non-human, reviews or conference abstracts. Data were extracted on demographics, brain imaging findings, treatment and outcome. The results were summarised by disease categories. Risk of bias was assessed using JBI critical appraisal tools. RESULTS: The search yielded 12 011 reports, of which 1261 underwent full text review and 89 were eligible for inclusion. Haemorrhage was the most common finding, especially in children with bile duct obstruction, including biliary atresia. Some findings were resolved after liver transplantation. CONCLUSION: Children with neonatal cholestasis had changes in brain imaging, which might play a role in impaired neuropsychological development, but longitudinal clinical research with structured assessment is needed to better qualify the aetiology of the impairment.

Pulmonary diffusing capacity to nitric oxide and carbon monoxide during exercise and in the supine position: a test-retest reliability study.

NEW FINDINGS: What is the central question in this study? How reliable is the combined measurement of the pulmonary diffusing capacity to carbon monoxide and nitric oxide (DLCO/NO ) during exercise and in the resting supine position, respectively? What is the main finding and its importance? The DLCO/NO technique is reliable with a very low day-to-day variability both during exercise and in the resting supine position, and may thus provide a useful physiological outcome that reflects the alveolar-capillary reserve in humans. ABSTRACT: DLCO/NO , the combined single-breath measurement of the diffusing capacity to carbon monoxide (DLCO ) and nitric oxide (DLNO ) measured either during exercise or in the resting supine position may be a useful physiological measure of alveolar-capillary reserve. In the present study, we investigated the between-day test-retest reliability of DLCO/NO -based metrics. Twenty healthy volunteers (10 males, 10 females; mean age 25 (SD 2) years) were randomized to repeated DLCO/NO measurements during upright rest followed by either exercise (n = 11) or resting in the supine position (n = 9). The measurements were repeated within 7 days. The smallest real difference (SRD), defined as the 95% confidence limit of the standard error of measurement (SEM), the coefficient of variance (CV), and intraclass correlation coefficients were used to assess test-retest reliability. SRD for DLNO was higher during upright rest (5.4 (95% CI: 4.1, 7.5) mmol/(min kPa)) than during exercise (2.7 (95% CI: 2.0, 3.9) mmol/(min kPa)) and in the supine position (3.0 (95% CI: 2.1, 4.8) mmol/(min kPa)). SRD for DLCOc was similar between conditions. CV values for DLNO were slightly lower than for DLCOc both during exercise (1.5 (95% CI: 1.2, 1.7) vs. 3.8 (95% CI: 3.2, 4.3)%) and in the supine position (2.2 (95% CI: 1.8, 2.5) vs. 4.8 (95% CI: 3.8, 5.4)%). DLNO increased by 12.3 (95% CI: 11.1, 13.4) and DLCOc by 3.3 (95% CI: 2.9, 3.7) mmol/(min kPa) from upright rest to exercise. The DLCO/NO technique provides reliable indices of alveolar-capillary reserve, both during exercise and in the supine position.

Pulmonary function is a strong predictor of 2-year overall survival and non-relapse mortality after allogenic hematopoietic cell transplantation.

OBJECTIVES: The purpose of the study was to assess the validity of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and of pulmonary comorbidity prior to HCT in terms of predicting non-relapse mortality (NRM) and overall survival (OS). METHODS: In this retrospective single-center study of 663 consecutive adult recipients of HCT, we stratified patients into groups by pulmonary comorbidity: low-risk, intermediate-risk, and high-risk. The predictive value of this pulmonary comorbidity score (PCS) was compared to HCT-CI. RESULTS: In univariate analysis, the HCT-CI and the PCS were associated with OS after transplantation when comparing patients in high-risk groups with patients in low-risk groups. Using the PCS, the hazard ratios (HRs) of the 2-year OS in the entire population and in the myeloablative conditioning (MAC) group were 1.98 (p < .001) and 3.27 (p < .001), respectively, whereas the HRs using the HCT-CI were 1.83 (p < .001) and 2.57 (p = .002). The 2-year NRM incidence in the three risk-groups in the entire population was significant using both indexes. In the MAC group, the 2-year NRM was significant using the PCS (p = .003), but not using the HCT-CI (p = .23). CONCLUSIONS: Our study suggest that pulmonary function alone is a strong predictor of 2-year OS and NRM after HCT.

Nordic 2023 guidelines for the diagnosis and treatment of lung neuroendocrine neoplasms.

Lung neuroendocrine neoplasms (NEN) are a heterogeneous population of neoplasms with different pathology, clinical behavior, and prognosis compared to the more common lung cancers. The diagnostic work-up and treatment of patients with lung- NEN has undergone major recent advances and new methods are currently being introduced into the clinic. These Nordic guidelines summarize and update the Nordic Neuroendocrine Tumor Group's current view on how to diagnose and treat lung NEN-patients and are meant to be useful in the daily practice for clinicians handling these patients. This review reflects our view of the current state of the art of diagnosis and treatment of patients with lung-NEN. Small cell lung carcinoma (SCLC) is not included in these guidelines.

Diagnostic accuracy of combined optical- and radio-guided SNB for neck staging of oral squamous cell carcinoma lesions in the anterior oral cavity.

PURPOSE: The purpose was to investigate the diagnostic performance of bimodal optical and radio-guided sentinel node biopsy (SNB) for oral squamous cell carcinoma (OSCC) sub-sites in the anterior oral cavity. METHODS: Prospective study of 50 consecutive patients with cN0 OSCC scheduled for SNB was injected with the tracer complex Tc99m:ICG:Nacocoll. A near-infrared camera was applied for optical SN detection. Endpoints were modality for intraoperative SN detection and false omission rate at follow-up. RESULTS: In all patients, a SN could be detected. In 12/50 (24%) of cases, the SPECT/CT showed no focus in level 1, but intraoperatively a SN in level 1 was optically detected. In 22/50 cases (44%), an additional SN was identified only due to the optical imaging. At follow-up, the false omission rate was 0%. CONCLUSION: Optical imaging appears to be an effective tool to allow real-time SN identification comprising level 1 unaffected by possible interference of radiation site from the injection.

Therapeutic benefits of proning to improve pulmonary gas exchange in severe respiratory failure: focus on fundamentals of physiology.

NEW FINDINGS: What is the topic of this review? The use of proning for improving pulmonary gas exchange in critically ill patients. What advances does it highlight? Proning places the lung in its 'natural' posture, and thus optimises the ventilation-perfusion distribution, which enables lung protective ventilation and the alleviation of potentially life-threatening hypoxaemia in COVID-19 and other types of critical illness with respiratory failure. ABSTRACT: The survival benefit of proning patients with acute respiratory distress syndrome (ARDS) is well established and has recently been found to improve pulmonary gas exchange in patients with COVID-19-associated ARDS (CARDS). This review outlines the physiological implications of transitioning from supine to prone on alveolar ventilation-perfusion ( V ̇ A -- Q ̇ ${\dot V_{\rm{A}}}\hbox{--}\dot Q$ ) relationships during spontaneous breathing and during general anaesthesia in the healthy state, as well as during invasive mechanical ventilation in patients with ARDS and CARDS. Spontaneously breathing, awake healthy individuals maintain a small vertical (ventral-to-dorsal) V ̇ A / Q ̇ ${\dot V_{\rm{A}}}/\dot Q$ ratio gradient in the supine position, which is largely neutralised in the prone position, mainly through redistribution of perfusion. In anaesthetised and mechanically ventilated healthy individuals, a vertical V ̇ A / Q ̇ ${\dot V_{\rm{A}}}/\dot Q$ ratio gradient is present in both postures, but with better V ̇ A -- Q ̇ ${\dot V_{\rm{A}}}\hbox{--}\dot Q$ matching in the prone position. In ARDS and CARDS, the vertical V ̇ A / Q ̇ ${\dot V_{\rm{A}}}/\dot Q$ ratio gradient in the supine position becomes larger, with intrapulmonary shunting in gravitationally dependent lung regions due to compression atelectasis of the dorsal lung. This is counteracted by proning, mainly through a more homogeneous distribution of ventilation combined with a largely unaffected high perfusion dorsally, and a consequent substantial improvement in arterial oxygenation. The data regarding proning as a therapy in patients with CARDS is still limited and whether the associated improvement in arterial oxygenation translates to a survival benefit remains unknown. Proning is nonetheless an attractive and lung protective manoeuvre with the potential benefit of improving life-threatening hypoxaemia in patients with ARDS and CARDS.

Bone mass density following developmental exposures to perfluoroalkyl substances (PFAS): a longitudinal cohort study.

BACKGROUND: Environmental exposures to industrial chemicals, including perfluoroalkyl substances (PFAS), may play a role in bone development and future risk of osteoporosis. However, as prospective evidence is limited, the role of developmental PFAS exposures in bone density changes in childhood is unclear. The objective of this study was to estimate associations between serum-PFAS concentrations measured in infancy and early childhood and areal bone mineral density (aBMD) measured at age 9 years in a birth cohort of children from the Faroe Islands. METHODS: We prospectively measured concentrations of five PFAS in cord serum and serum collected at 18 months, 5 years and 9 years, and conducted whole-body DXA scans at the 9-year clinical visit. Our study included 366 mother-child pairs with DXA scans and at least one PFAS measurement. We estimated covariate-adjusted associations of individual PFAS concentrations with age-, sex- and height-adjusted aBMD z-scores using multivariable regression models and applied formal mediation analysis to estimate the possible impact of by several measures of body composition. We also evaluated whether associations were modified by child sex. RESULTS: We found PFAS exposures in childhood to be negatively associated with aBMD z-scores, with the strongest association seen for perfluorononanoic acid (PFNA) at age 5 years. A doubling in age-5 PFNA was associated with a 0.15 decrease in aBMD z-score (95% CI: - 0.26, - 0.039). The PFNA-aBMD association was significantly stronger in males than females, although effect modification by sex was not significant for other PFAS exposures. Results from the mediation analysis suggested that any potential associations between aBMD and 18-month PFAS concentrations may be mediated by total body fat and BMI, although most estimated total effects for PFAS exposures at age 18 months were non-significant. PFAS exposures at age 9 were not associated with age-9 aBMD z-scores. CONCLUSIONS: The PFAS-aBMD associations identified in this and previous studies suggest that bone may be a target tissue for PFAS. Pediatric bone density has been demonstrated to strongly track through young adulthood and possibly beyond; therefore, these prospective results may have important public health implications.

Influence of reduced diffusing capacity and FEV1 on outcome after cardiac surgery.

BACKGROUND: Impaired lung function is a well-known risk factor in cardiac surgery patients and reduced forced expiratory volume in 1 second (FEV1 ) is associated with increased mortality. However, there is limited knowledge regarding the influence of impaired diffusing capacity of the lungs for carbon monoxide (DLCO) in unselected cardiac surgery patients. The aim of this study was to investigate the association of impaired DLCO and/or reduced FEV1 on post-operative mortality and morbidity in cardiac surgery patients. METHODS: In a prospective cohort study, 390 patients scheduled for elective cardiac surgery underwent preoperative lung function test including spirometry and DLCO measurements. We defined reduced FEV1 as FEV1 below lower limit of normal (LLN) and impaired DLCO as DLCO <60% of predicted. RESULTS: Mortality within 1 year (90-570 days) was significantly higher in patients with impaired DLCO (12% vs 3%, P = .010) and with reduced FEV1 (9% vs 3%, P = .028). Mortality was higher in patients with impaired DLCO both in the presence and absence of FEV1  < LLN. In multivariate analysis, only impaired DLCO [OR: 3.3, 95% confidence interval (CI) 1.4-7.5; P = .005] and age (OR: 1.1 per year, 95% CI 1.0-1.2; P = .001) were independent predictors of the combined outcome of mortality and prolonged intensive care unit (ICU) stay. Impaired DLCO was also associated with post-operative respiratory complications. CONCLUSION: In patients undergoing elective cardiac surgery, preoperative impaired FEV1 and DLCO were associated with increased mortality and morbidity. In multivariate analysis, only DLCO and age were independent predictors of a combined outcome of mortality and prolonged ICU stay.

Recurrence and survival rates in node negative patients after sentinel node biopsy for early-stage vulva cancer - A nationwide study.

OBJECTIVE: The sentinel node (SN) procedure is adopted in selected patients with early-stage vulva cancer (VC) in Denmark. Due to the low incidence of VC, large population-based studies on the safety of SN outside multicenter clinical trials are lacking. The current study evaluated the risk of recurrence and survival in SN- negative VC patients. METHODS: Nationwide data was collected and registered prospectively in the Danish Gynecologic Cancer Database from January 2011 to July 2017. Patients with clinically stage IB-II unifocal vulva squamous cell carcinoma, tumor <4 cm and no clinically suspicious groin nodes or distant metastases, who underwent SN-procedure, were included. RESULTS: The SN-procedure was performed in 286 patients, of these 190 (66.4%) patients were SN-negative. Twenty-three of the 190 SN-negative patients (12.1%) had one or more recurrences during a median follow-up of 30 months (range 1-83). Four patients (2.1%) had an isolated groin recurrence identified from 5 to 17 months after primary surgery. Fourteen patients (7.4%) experienced a local recurrence in vulva, 1 patient (0.5%) had a recurrence in the vulva and the groin and 4 patients (2.1%) had distant recurrences. The 3-year overall (OS) and disease-specific survival (DSS) for SN-negative patients was 84% and 93%, respectively. The 3-year OS for patients with recurrent disease was 58%. CONCLUSIONS: This is the largest prospective nationwide study on SN-procedure in vulva cancer. The study confirms the safety of the SN-procedure in selected early-stage VC patients with a low isolated groin recurrence rate and a good DSS.

Lobar Quantification by Ventilation/Perfusion SPECT/CT in Patients with Severe Emphysema Undergoing Lung Volume Reduction with Endobronchial Valves.

BACKGROUND: Endoscopic lung volume reduction (ELVR) therapy using one-way valves is used to treat chronic obstructive pulmonary disease patients with severe heterogeneous emphysema. A successful treatment results in atelectasis of the treated pulmonary lobe with subsequent reduction of ventilation (V) and perfusion (Q). OBJECTIVE: We evaluated the effects of ELVR on the targeted lobe using a new 3-dimensional ventilation and perfusion (V/Q) single-photon emission computed tomography (SPECT)/computed tomography (CT) analysis, which allows for simultaneous semi-automatic lobar pulmonary quantification of volume, ventilation and perfusion, on the first consecutive patients treated with ELVR at Rigshospitalet, Denmark. V/Q planar scintigraphy and V/Q SPECT/CT and lung function measurements were performed before and 6 months after intervention. RESULTS: We included 24 subjects (60 years, range 46-74 years; 37.5% men) with a baseline FEV1 of 25% predicted and RV of 257% predicted. V/Q SPECT/CT-assessed volume of the targeted lobe decreased by a mean of -395 mL and a relative mean of -26.8%, whilst ventilation and perfusion decreased by a relative mean of -37.1 and -25.7%. There was a significant increase in the same parameters of the non-targeted lobe(s) on the ipsilateral side. None of these changes were found in the analysis of planar V/Q imaging. The total lung volume decreased on average by -420 mL. Six months after ELVR, FEV1 had increased by 22%. Significant correlations were found between changes in FEV1 and changes in the volume of the treated lobe (SPECT/CT). CONCLUSION: Semi-automatic SPECT/CT analysis can quantify volume, ventilation and perfusion changes in pulmonary lobes and may be used in the assessment of patient eligibility for ELVR, identifying target lobes, and evaluation of the regional effects of treatment.

Reference equations for pulmonary diffusing capacity of carbon monoxide and nitric oxide in adult Caucasians.

The aim of this study was to determine reference equations for the combined measurement of diffusing capacity of the lung for carbon monoxide (CO) and nitric oxide (NO) (DLCONO). In addition, we wanted to appeal for consensus regarding methodology of the measurement including calculation of diffusing capacity of the alveolo-capillary membrane (Dm) and pulmonary capillary volume (Vc).DLCONO was measured in 282 healthy individuals aged 18-97 years using the single-breath technique and a breath-hold time of 5 s (true apnoea period). The following values were used: 1) specific conductance of nitric oxide (θNO)=4.5 mLNO·mLblood-1·min-1·mmHg-1; 2) ratio of diffusing capacity of the membrane for NO and CO (DmNO/DmCO)=1.97; and 3) 1/red cell CO conductance (1/θCO)=(1.30+0.0041·mean capillary oxygen pressure)·(14.6/Hb concentration in g·dL-1).Reference equations were established for the outcomes of DLCONO, including DLCO and DLNO and the calculated values Dm and Vc Independent variables were age, sex, height and age squared.By providing new reference equations and by appealing for consensus regarding the methodology, we hope to provide a basis for future studies and clinical use of this novel and interesting method.

Osteogenic impact of football training in 55- to 70-year-old women and men with prediabetes.

The effects of football training on bone health were examined in 55- to 70-year-old sedentary women and men with prediabetes. Patients (n = 50) with prediabetes (age; 61 ± 9 years, BMI 29.7 ± 0.6 kg/m2 , body fat content; 37 ± 1%, VO2max ; 22.7 ± 0.8 mL/min/kg and mean arterial pressure; 104 ± 3 mm Hg) were randomized into a football training group (FTG; n = 27, 14 women) and a control group (CON; n = 23, 11 women). At baseline, 73% and 24% were diagnosed with femur osteopenia and osteoporosis, respectively. FTG performed football training twice weekly 30-60-minute sessions in 16 weeks, and both FTG and CON received professional dietary advice. Pre- and post-intervention whole-body and regional bone mineral content (BMC) and density (BMD) were determined with DXA-scans, and venous blood samples were drawn and analyzed for plasma bone turnover markers. Change scores were greater (P < 0.05) in FTG compared to CON in leg BMD (0.023 ± 0.005 vs -0.004 ± 0.001 g/cm2 ) and in leg BMC (32 ± 8 vs -4 ± 6 g). Between-group changes in favor of FTG (P < 0.05) also occurred in the femur neck BMD (3.2%) and femur shaft BMD (2.5%). Whole-body BMC and BMD were unchanged in both groups during the intervention. In FTG, resting plasma osteocalcin, P1NP, and CTX-1 rose (P < 0.05) by 23 ± 8, 52 ± 9 and 38 ± 7%, with greater change scores (P < 0.05) than in CON. Finally, P1NP (formation)/CTX-1 (resorption) ratio increased (P < 0.05) in FTG (127 ± 15 vs 150 ± 11) from pre- to post-intervention, with no change in CON (124 ± 12 and 123 ± 12). In conclusion, football training provides a powerful osteogenic stimulus and improves bone health in 55- to 70-year-old women and men diagnosed with prediabetes.

Urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and epidermal growth factor receptor (EGFR): tumor expression patterns and prognostic value in oral cancer.

BACKGROUND: Tumor-specific biomarkers are a prerequisite for the development of targeted imaging and therapy in oral squamous cell carcinoma (OSCC). urokinase-type Plasminogen Activator Receptor (uPAR), Tissue Factor (TF) and Epidermal Growth Factor Receptor (EGFR) are three biomarkers that exhibit enhanced expression in many types of cancers, and have been investigated as potential biomarkers for targeted strategies and prognostication. The aim of the study was to investigate the expression patterns of uPAR, TF and EGFR and their potential prognostic value in OSCC. METHODS: Immunohistochemical expression of uPAR, TF and EGFR in tumor resection specimens from 191 patients with primary OSCC was analyzed. Overall (OS) and disease-free survival (DFS) was calculated. Associations between biomarker expression, clinicopathological factors and patient survival was analyzed using the Cox proportional hazards model for univariate and multivariate analysis, log rank and Kaplan-Meier statistics. RESULTS: uPAR and TF exhibited a highly tumor-specific expression pattern while EGFR also showed expression in normal tissues outside the tumor compartment. The overall positive expression rate of uPAR, TF and EGFR was 95%, 58% and 98%, respectively. High uPAR expression across the entire cohort was negatively associated with OS (p = 0.031, HR = 1.595 (95%CI 1.044-2.439)) in univariate analysis. The 5-year OS for high and low uPAR expression was 39% and 56%, respectively. The expression of TF and EGFR was not associated with survival outcome. CONCLUSIONS: This study may suggest that uPAR and TF could potentially be attractive targets for molecular imaging and therapy in OSCC due to high positive expression rates and tumor-specific expression patterns. High uPAR expression was significantly associated with a reduced survival. uPAR seems to be a prognostic biomarker in oral cancer.

Pulmonary thromboembolism as a complication of lung transplantation.

Post-transplantation mortality after lung transplantation (LTX) is higher than for other solid organ transplantations. Thoracic surgery is associated with increased risk of thromboembolic complications, and as LTX recipients lack the collateral bronchial circulation, pulmonary thromboembolism (PTE) may represent a pertinent yet largely underdiagnosed cause of post-transplantation respiratory failure. In this systematic review, we sought to elucidate the occurrence and predilection site of PTE after LTX, and its potential impact on LTX-associated mortality. Based on twelve original articles identified by a systematic search strategy in PubMed, we found that PTE was reported in 4% of LTX recipients, and 38% of these events occurred within the first 30 days after the LTX procedure. In single-lung transplantation (SLTX) recipients, 12% were diagnosed with PTE, with 92% of these affecting the allograft. Of LTX patients diagnosed with PTE, 11% died within 1 year after LTX and 75% of these deaths occurred within the first 30 days. Our findings suggest that PTE is a potentially underdiagnosed cause of early post-LTX respiratory failure. This should be confirmed in larger studies with systematic follow-up diagnostic imaging.