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In patients with chronic obstructive pulmonary disease (COPD), pulmonary vascular dysfunction and destruction are observable before the onset of detectable emphysema, but it is unknown whether this is associated with central hypovolemia. We investigated if COPD patients have reduced pulmonary blood volume (PBV) evaluated by 82Rb-positron emission tomography(PET) at rest and during adenosine-induced hyperemia. This single-center retrospective cohort study assessed 6301 82Rb-PET myocardial perfusion imaging (MPI) examinations performed over a 6-year period. We compared 77 COPD patients with 44 healthy kidney donors (controls). Cardiac output (Q̇) and mean 82Rb bolus transit time (MBTT) were used to calculate PBV. Q̇ was similar at rest (COPD: 3649 ± 120 mL vs. control: 3891 ± 160 mL, p=0.368) but lower in COPD patients compared to controls during adenosine infusion (COPD: 5432 ± 124 mL vs. control: 6185 ± 161 mL, p < 0.050). MBTT was shorter in COPD patients compared to controls at rest (COPD: 8.7 ± 0.28 seconds vs. control: 11.4 ± 0.37 seconds, p < 0.001) and during adenosine infusion (COPD: 9.2 ± 0.28 seconds vs. control: 10.2 ± 0.37 seconds, p < 0.014). PBV was lower in COPD patients, even after adjustment for body surface area, sex, and age at rest (COPD: 530 (29) mL vs. 708 (38) mL, p < 0.001) and during adenosine infusion (COPD: 826 (29) mL vs. 1044 (38) mL, p<0.001). In conclusion, patients with COPD show evidence of central hypovolemia, but it remains to be determined whether this has any diagnostic or prognostic impact.

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.

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., 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.

Purpose: Ventilation Perfusion SPECT is important in the diagnostics of e.g. pulmonary embolism and chronic obstructive pulmonary disease. Classical and reverse mismatched defects can be identified by utilizing the ventilation-perfusion ratio. Unfortunately, this ratio is only linear in the ventilation, the scale is not symmetrical regarding classical and reversed mismatches and small perfusion values give rise to artifacts. The ventilation-perfusion (VQ) difference is developed as an alternative. Methods: For both VQ-ratio and VQ-difference a scaling factor for the perfusion is computed, so that voxels with matched ventilation and perfusion (on average) yield zero signal. The relative VQ-difference is calculated by scaling with the summed VQ-signal in each voxel. The scaled VQ-difference is calculated by scaling with the global maximum of this sum. Results: The relative and scaled differences have a scale from −1 (perfusion only) to + 1 (ventilation only). Image quality of relative VQ-difference and VQ-ratio images is hampered by artifacts from areas with both low perfusion and low ventilation. Ratio and differences have been investigated in ten patients and are shown for three patients (one without defects). Clinical thresholds for the difference images are derived resulting in color maps of relevant (reversed) mismatches with a (reciprocal) ratio larger than two. Conclusions: The relative ventilation-perfusion difference is a methodological improvement on the ventilation-perfusion ratio, because it has a symmetrical scale and is bound on a closed domain. A better diagnostic value is expected by utilizing the scaled difference, which represents functional difference instead of relative difference.

The combined single-breath measurement of the diffusing capacity of carbon monoxide (DL,CO) and nitric oxide (DL,NO) is a useful technique to measure pulmonary alveolar-capillary reserve in both healthy and patient populations. The measurement provides an estimate of the participant's ability to recruit and distend pulmonary capillaries. The method has recently been reported to exhibit a high test-retest reliability in healthy volunteers during exercise of light to moderate intensity. Of note, this technique permits up to 12 repeated maneuvers and only requires a single breath with a relatively short breath-hold time of 5 s. Representative data are provided showing the gradual changes in DL,NO and DL,CO from rest to exercise at increasing intensities of up to 60% of maximal workload. The measurement of diffusing capacity and evaluation of alveolar-capillary reserve is a useful tool to evaluate the lung's ability to respond to exercise both in the healthy population as well as in patient populations such as those with chronic lung disease.

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., 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. Graphical abstract: Key question: What characterizes reoperations after lung volume reduction surgeries? Key findings: Lung injuries were predominantly located away from the original surgical site. Take home message: Lung injuries remote from the stapler

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.

Following publication of the original article [1], the affiliation details for Philippe Grandjean were incorrectly given as ’2,7’ but should have been ’1,7’. This has been corrected in this correction article and the original article has been updated.

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.

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 (D LCO/NO ) during exercise and in the resting supine position, respectively? What is the main finding and its importance? The D LCO/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: D LCO/NO , the combined single-breath measurement of the diffusing capacity to carbon monoxide (D LCO ) and nitric oxide (D LNO ) 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 D LCO/NO -based metrics. Twenty healthy volunteers (10 males, 10 females; mean age 25 (SD 2) years) were randomized to repeated D LCO/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 D LNO 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 D LCOc was similar between conditions. CV values for D LNO were slightly lower than for D LCOc 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)%). D LNO increased by 12.3 (95% CI: 11.1, 13.4) and D LCOc by 3.3 (95% CI: 2.9, 3.7) mmol/(min kPa) f

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.

Background: Primary ciliary dyskinesia (PCD) is an inherited disorder in which dyskinetic cilia cause impaired mucociliary clearance of upper and lower airways. Airway ciliary movement can be indirectly tested in vivo after administration of a radiolabelled tracer to the lower airways for assessment of pulmonary mucociliary clearance or to the nose for assessing nasal mucociliary clearance (NMC). With this study, we investigated NMC as a quantifiable study outcome parameter in patients with PCD. Material and methods: This single centre proof-of-concept study on NMC velocity investigated patients with PCD across different genotypes and nasal nitric oxide (nasal NO) levels. Healthy controls were used for comparison. NMC was determined as velocity in mm·min−1 of a nasally applied 99mTc-albumin colloid tracer. Using a gamma camera, repeated dynamic series of images each lasting 30 s were acquired during a 10-minute period and digitally stored. Results: NMC velocity was investigated in seven patients with PCD (aged 9–31 years) and five adult healthy controls. Mean NMC velocity in healthy controls (8.5 mm·min−1) was significantly higher compared with people with PCD (0.00 mm·min−1, p<0.0001). NMC was completely absent in all included patients with PCD across different PCD genotypes and regardless of nasal NO values. The success rate of the test was 100% in both groups. Conclusion: NMC velocity discriminated highly significantly between patients with PCD and healthy controls. We suggest here a fast and feasible set up for NMC measurements that is easily applicable for any clinical trial involving PCD medication aimed for the nasal compartment, a step before or parallel to conducting clinical trials investigating whole-lung ciliary function in PCD., Background Primary ciliary dyskinesia (PCD) is an inherited disorder in which dyskinetic cilia cause impaired mucociliary clearance of upper and lower airways. Airway ciliary movement can be indirectly tested in vivo after administration of a radiolabelled tracer to the lower airways for assessment of pulmonary mucociliary clearance or to the nose for assessing nasal mucociliary clearance (NMC). With this study, we investigated NMC as a quantifiable study outcome parameter in patients with PCD. Material and methods This single centre proof-of-concept study on NMC velocity investigated patients with PCD across different genotypes and nasal nitric oxide (nasal NO) levels. Healthy controls were used for comparison. NMC was determined as velocity in mm·min−1 of a nasally applied99mTc-albumin colloid tracer. Using a gamma camera, repeated dynamic series of images each lasting 30 s were acquired during a 10-minute period and digitally stored. Results NMC velocity was investigated in seven patients with PCD (aged 9–31 years) and five adult healthy controls. Mean NMC velocity in healthy controls (8.5 mm·min−1) was significantly higher compared with people with PCD (0.00 mm·min−1, p<0.0001). NMC was completely absent in all included patients with PCD across different PCD genotypes and regardless of nasal NO values. The success rate of the test was 100% in both groups. Conclusion NMC velocity discriminated highly significantly between patients with PCD and healthy controls. We suggest here a fast and feasible set up for NMC measurements that is easily applicable for any clinical trial involving PCD medication aimed for the nasal compartment, a step before or parallel to conducting clinical trials investigating whole-lung ciliary function in PCD.

Background Pulmonary radioaerosol mucociliary clearance (PRMC) is a reliable method for assessing in vivo whole lung mucociliary clearance and has been used at the Danish PCD Centre as a supplementary diagnostic test for primary ciliary dyskinesia (PCD) for more than two decades. This study aimed to investigate genotype-specific differences in PRMC measures and evaluate its potential as an outcome parameter. Material and methods The study was based on a retrospective analysis of PRMC tests performed over a 24-year period (1999–2022) in individuals referred for PCD work-up and included patients with genetically confirmed PCD and non-PCD controls. Patients inhaled nebulised technetium-albumin-colloid before static and dynamic imaging was obtained. Three parameters were evaluated: 1-h lung retention (LR1), tracheobronchial velocity (TBV) and cough clearance. Results The study included 69 patients from the Danish PCD cohort, representing 26 different PCD genotypes. Mucociliary clearance by PRMC was consistently absent in most PCD patients, regardless of genotype. However, a single patient with a CCDC103 mutation, preserved ciliary function and normal nasal nitric oxide levels exhibited normal LR1 and low TBV values. Voluntary cough significantly improved clearance, with a median improvement of 11% (interquartile range 4–24%). Conclusion Absent mucociliary clearance by PRMC should be expected in PCD regardless of genotype but residual ciliary function could result in measurable PRMC. This indicates a potential for PRMC to detect improvements in ciliary function if this can be restored. Addressing involuntary cough and peripheral deposition of radioaerosol is important if PRMC is to be used as an outcome measure in future clinical PCD trials., Background Pulmonary radioaerosol mucociliary clearance (PRMC) is a reliable method for assessing in vivo whole lung mucociliary clearance and has been used at the Danish PCD Centre as a supplementary diagnostic test for primary ciliary dyskinesia (PCD) for more than two decades. This study aimed to investigate genotype-specific differences in PRMC measures and evaluate its potential as an outcome parameter. Material and methods The study was based on a retrospective analysis of PRMC tests performed over a 24-year period (1999–2022) in individuals referred for PCD work-up and included patients with genetically confirmed PCD and non-PCD controls. Patients inhaled nebulised technetium-albumin-colloid before static and dynamic imaging was obtained. Three parameters were evaluated: 1-h lung retention (LR1), tracheobronchial velocity (TBV) and cough clearance. Results The study included 69 patients from the Danish PCD cohort, representing 26 different PCD genotypes. Mucociliary clearance by PRMC was consistently absent in most PCD patients, regardless of genotype. However, a single patient with a CCDC103 mutation, preserved ciliary function and normal nasal nitric oxide levels exhibited normal LR1 and low TBV values. Voluntary cough significantly improved clearance, with a median improvement of 11% (interquartile range 4–24%). Conclusion Absent mucociliary clearance by PRMC should be expected in PCD regardless of genotype but residual ciliary function could result in measurable PRMC. This indicates a potential for PRMC to detect improvements in ciliary function if this can be restored. Addressing involuntary cough and peripheral deposition of radioaerosol is important if PRMC is to be used as an outcome measure in future clinical PCD trials.

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 as

Background: Long-term follow-up studies of COVID-19 olfactory and gustatory disorders (OGDs) are scarce. OGD, parosmia, and dysgeusia affect health-related quality of life (HRQoL) and the ability to detect potential hazards. Methods: In this study, 29 patients reporting OGD 1 month after severe-to-critical COVID-19 were tested at 3–6 months and retested at 12 months in case of hyposmia/anosmia. We used Sniffin Sticks Threshold, Discrimination, and Identification (TDI) test, Sniffin Sticks Identification Test (SIT16), Brief Smell Identification Test (BSIT), taste strips, and HRQoL. The patients were part of the prospective SECURe cohort. Results: Overall, 28% OD (TDI), 12% GD, 24% parosmia, and 24% dysgeusia (questionnaire) at 3–6 months (n = 29) and 28% OD (TDI), 38% parosmia, and 25% dysgeusia (questionnaire) at 12 months (n = 8) were observed. OGD decreased HRQoL: For 13%, it had a negative effect on daily life and, for 17%, it affected nutrition, 17% reported decreased mood, and 87–90% felt unable to navigate everyday life using their sense of smell and taste. A comparison of SIT16 and BSIT to TDI found sensitivity/specificity values of 75%/100% and 88%/86%. Conclusions: This is the first study to examine TDI, SIT16, BSIT, taste strips, and HRQoL up to 1 year after severe-to-critical COVID-19. The patients suffering from prolonged OGD, parosmia, and dysgeusia experienced severely decreasing HRQoL. We recommend including ear–nose–throat specialists in multidisciplinary post-COVID clinics.

A large proportion of patients exhibit persistently reduced pulmonary diffusion capacity after COVID-19. It is unknown whether this is due to a post-COVID restrictive lung disease and/or pulmonary vascular disease. The aim of the current study was to investigate the association between initial COVID-19 severity and haemoglobin-corrected diffusion capacity to carbon monoxide (DLco) reduction at follow-up. Furthermore, to analyse if DLco reduction could be linked to pulmonary fibrosis (PF) and/or thromboembolic disease within the first months after the illness, a total of 67 patients diagnosed with COVID-19 from March to December 2020 were included across three severity groups: 12 not admitted to hospital (Group I), 40 admitted to hospital without intensive care unit (ICU) admission (Group II), and 15 admitted to hospital with ICU admission (Group III). At first follow-up, 5 months post SARS-CoV-2 positive testing/4 months after discharge, lung function testing, including DLco, high-resolution CT chest scan (HRCT) and ventilation-perfusion (VQ) single photon emission computed tomography (SPECT)/CT were conducted. DLco was reduced in 42% of the patients; the prevalence and extent depended on the clinical severity group and was typically observed as part of a restrictive pattern with reduced total lung capacity. Reduced DLco was associated with the extent of ground-glass opacification and signs of PF on HRCT, but not with mismatched perfusion defects on VQ SPECT/CT. The severity-dependent decline in DLco observed early after COVID-19 appears to be caused by restrictive and not pulmonary vascular disease.

No effective therapy exists for the most common long-term side effect of radiation therapy for head and neck cancer (HNC)-xerostomia. The objective was to evaluate safety and provide proof of concept for efficacy of allogeneic adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) injected into the major salivary glands of irradiated patients. This open-label, first-in-human, phase 1b, and single-center trial was conducted with repeated measurements days 0, 1, 5, and 30 and 4 months. Eligible patients with objective and subjective signs of radiation-induced salivary gland damage after treatment of oropharyngeal squamous cell carcinoma stages I-II (UICC 8) were enrolled. Twenty-five million cryopreserved AT-MSCs were injected into each submandibular and 50 million AT-MSCs into each parotid gland. Data were collected on adverse events, unstimulated and stimulated whole saliva (UWS and SWS) flow rates and saliva composition, patient-reported outcomes (EORTC QLQ-H&N35 and Xerostomia Questionnaire [XQ]), blood samples and salivary gland scintigraphy. Data were analyzed using repeated measures linear mixed models. Ten patients (7 men, 3 women, 59.5 years [range: 45-70]) were treated in 4 glands. No treatment-related serious adverse events occurred. During 4 months, UWS flow rate increased from 0.13 mL/minute at baseline to 0.18 mL/minute with a change of 0.06 (P = .0009) mL/minute. SWS flow rate increased from 0.66 mL/minute at baseline to 0.75 mL/minute with a change of 0.09 (P = .017) mL/minute. XQ summary score decreased by 22.6 units (P = .0004), EORTC QLQ-H&N35 dry mouth domains decreased by 26.7 (P = .0013), sticky saliva 23.3 (P = .0015), and swallowing 10.0 (P = .0016). Our trial suggests treatment of the major salivary glands with allogenic AT-MSCs is safe, warranting confirmation in larger trials.

The clinical introduction of molecular imaging for the management of oropharyngeal squamous cell carcinoma (OPSCC) relies on the identification of relevant cancer-specific biomarkers. The application of three membrane-bound receptors, namely urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and EGFR have been previously explored for targeted imaging and therapeutic strategies in a broad range of solid cancers. The present study aimed to investigate the expression patterns of uPAR, EGFR and TF by immunohistochemistry (IHC) to evaluate their potential for targeted imaging and prognostic value in OPSCC. In a retrospective cohort of 93 patients with primary OPSCC, who were balanced into the 45 human papillomavirus (HPV)-positive and 48 HPV-negative groups, the IHC-determined expression profiles of uPAR, TF and EGFR in large biopsy or tumor resection specimens were analyzed. Using the follow-up data, overall survival (OS) and recurrence-free survival were measured. Specifically, associations between survival outcome, biomarker expression and clinicopathological factors were examined using Cox proportional hazards model and log-rank test following Kaplan-Meier statistics. After comparing the expression pattern of biomarkers within the tumor compartment with that in the adjacent normal tissues, uPAR and TF exhibited a highly tumor-specific expression pattern, whereas EGFR showed a homogeneous expression within the tumor compartment as well as a consistent expression in the normal mucosal epithelium and salivary gland tissues. The positive expression rate of uPAR, TF and EGFR in the tumors was 98.9, 76.3 and 98.9%, respectively. No statistically significant association between biomarker expression and survival outcome could be detected. Higher uPAR expression levels had a trend towards reduced OS according to results from univariate analysis (P=0.07; hazard ratio=2.01; 95% CI=0.92-4.37). Taken together, these results suggest that uPAR, TF and EGFR

The presence of malnutrition is increasingly becoming a postdischarge problem in surgical patients. We aimed to investigate whether oral nutritional supplements combined with resistance training could minimize skeletal muscle atrophy in surgical patients after discharge. This randomized controlled study was conducted at the Department of Surgery, National Hospital of Faroe Islands from 2018 to 2020. A total of 45 patients aged 37–74 years participated and were allocated to one of three groups: diet (DI; n = 13), exercise and diet (EX + DI; n = 16), or control (CON; n = 16). The intervention period lasted 8 weeks. The intervention groups received individual dietary counselling and a protein-rich oral nutritional supplement twice a day containing 22 g of protein/day. Patients in the EX + DI group were assigned to resistance training sessions. Patients in the CON group received standard care. The primary outcome was change in lean body mass (LBM). Secondary outcomes were change in body weight, handgrip strength, quality of life, surgery-related side effects, energy and protein intake, length of stay and one-year mortality. To estimate within-group changes, linear mixed models including group–time interactions as fixed effects and patients as random effects were fitted. Within-group change in LBM was 233, 813 and 78 g in the DI, EX + DI and CON groups, respectively, with no significant between-group difference (p > 0.05). Pain score declined more (p = 0.04) in the EX + DI group compared with the CON group. Body weight, handgrip strength, quality of life and surgery-related side effects did not differ between groups. At the end of study, mean cumulative weight change in the DI and EX + DI groups was 0.4% and 1.6%, respectively, whereas the CON group experienced a weight loss of −0.6%. No significant difference in primary outcome between groups was noted. However, our results indicate some benefits from exercise and nutrition for m

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 ((Formula presented.)) 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) (Formula presented.) 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 (Formula presented.) ratio gradient is present in both postures, but with better (Formula presented.) matching in the prone position. In ARDS and CARDS, the vertical (Formula presented.) 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