Spontaneous Evolution of COVID-19 Lung Sequelae: Results from a Double-Step Follow-Up.

BACKGROUND: Few studies have reported a double-step follow-up of patients after hospitalization for COVID-19. OBJECTIVES: We designed an observational double-step follow-up study with a clinical, functional, and radiological evaluation at 2 and 6 months after COVID-19. The primary outcome was to describe symptoms, spirometry, and 6-minute walking test (6MWT) at 2 and 6 months. Secondary outcomes were to identify if the lowest PaO2/FiO2 during hospitalization is related with functional and radiological evolution and to assess the correlation between radiological and functional abnormalities at 6 months. METHODS: Symptoms, spirometry, and 6MWT were assessed at 2 and 6 months; arterial blood gas, chest x-ray, and lung ultrasound were performed at 2 months; body plethysmography, diffusing capacity for carbon monoxide (DLCO), and CT scan were performed at 6 months. RESULTS: Sixty-four per cent and 42% of patients reported at least one symptom at 2 and 6 months, respectively. The most common 6-month functional alteration was DLCO impairment (57% of patients). An improvement of FEV1, FVC, and 6MWT was observed between 2 and 6 months (p < 0.001). Patients with PaO2/FiO2 <200 during hospitalization performed worse at 6MWT at 2 and 6 months (p < 0.05) and reported more extended radiological abnormalities at 6 months (p < 0.001) compared with patients with PaO2/FiO2>200. At 6 months, more extended radiological abnormalities were related with worse 6MWT, DLCO, and total lung capacity (p < 0.05). DISCUSSION: DLCO and 6MWT impairment seem to be the functional hallmark of COVID-19 and are related with the severity of acute pneumonia. At 6 months, radiological abnormalities were related to functional impairment.

Behavior Modeling for a Beacon-Based Indoor Location System.

In this work we performed a comparison between two different approaches to track a person in indoor environments using a locating system based on BLE technology with a smartphone and a smartwatch as monitoring devices. To do so, we provide the system architecture we designed and describe how the different elements of the proposed system interact with each other. Moreover, we have evaluated the system's performance by computing the mean percentage error in the detection of the indoor position. Finally, we present a novel location prediction system based on neural embeddings, and a soft-attention mechanism, which is able to predict user's next location with 67% accuracy.

Liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical long-term follow-up and pathogenic implications.

We report the longest follow-up of clinical and biochemical features of two previously reported adult mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients treated with liver transplantation (LT), adding information on a third, recently transplanted, patient. All three patients overcame the early post-operative period and tolerated immunosuppressive therapy. Plasma nucleoside levels dramatically decreased, with evidence of clinical improvement of ambulation and neuropathy. Conversely, other features of MNGIE, as gastrointestinal dysmotility, low weight, ophthalmoparesis, and leukoencephalopathy were essentially unchanged. A similar picture characterized two patients treated with allogenic hematopoietic stem cell transplantation (AHSCT). In conclusion, LT promptly and stably normalizes nucleoside imbalance in MNGIE, stabilizing or improving some clinical parameters with marginal periprocedural mortality rate as compared to AHSCT. Nevertheless, restoring thymidine phosphorylase (TP) activity, achieved by both LT and AHSCT, does not allow a full clinical recovery, probably due to consolidated cellular damage and/or incomplete enzymatic tissue replacement.

Effects of high-flow nasal cannula in patients with persistent hypercapnia after an acute COPD exacerbation: a prospective pilot study.

BACKGROUND: Persistent hypercapnia after COPD exacerbation is associated with excess mortality and early rehospitalization. High Flow Nasal cannula (HFNC), may be theoretically an alternative to long-term noninvasive ventilation (NIV), since physiological studies have shown a reduction in PaCO2 level after few hours of treatment. In this clinical study we assessed the acceptability of HFNC and its effectiveness in reducing the level of PaCO2 in patients recovering from an Acute Hypercapnic Respiratory Failure (AHRF) episode. We also hypothesized that the response in CO2 clearance is dependent on baseline level of hypercapnia. METHODS: Fifty COPD patients recovering from an acute exacerbation and with persistent hypercapnia, despite having attained a stable pH (i.e. pH > 7,35 and PaCO2 > 45 mmHg on 3 consecutive measurements), were enrolled and treated with HFNC for at least 8 h/day and during the nighttime RESULTS: HFNC was well tolerated with a global tolerance score of 4.0 ± 0.9. When patients were separated into groups with or without COPD/OSA overlap syndrome, the "pure" COPD patients showed a statistically significant response in terms of PaCO2 decrease (p = 0.044). In addition, the subset of patients with a lower pH at enrolment were those who responded best in terms of CO2 clearance (score test for trend of odds, p = 0.0038). CONCLUSIONS: HFNC is able to significantly decrease the level of PaCO2 after 72 h only in "pure" COPD patients, recovering from AHRF. No effects in terms of CO2 reduction were found in those with overlap syndrome. The present findings will help guide selection of the best target population and allow a sample size calculation for future long-term randomized control trials of HFNC vs NIV. TRIAL REGISTRATION: This study is registered with www. clinicaltrials.gov with identifier number NCT03759457.

Noninvasive ventilation and renal replacement therapy in do-not-intubate order critically ill patients: A brief report.

INTRODUCTION: Multiple organ failure has been considered a contraindication for noninvasive ventilation (NIV). MATERIALS AND METHODS: We described the outcome of Do-not-Intubate (DNI) patients with acute respiratory failure, treated with NIV and, subsequently, necessitating renal replacement therapy (RRT). RESULTS AND DISCUSSION: Seven patients admitted to our Respiratory Intensive Care Unit, developed Acute Kidney Injury (AKI) during NIV treatment and received RRT for 12.8 ± 8 days together with NIV. All the patients but one, discontinued renal support because they regained a satisfactory urinary output; nevertheless mortality rate was high (71%). CONCLUSION: Our data suggest that RRT could be feasible together with NIV. RRT was associated with an acute improvement in renal function but did not modify the mortality rate.

Intensive care unit patients with lower respiratory tract nosocomial infections: the ENIRRIs project.

The clinical course of intensive care unit (ICU) patients may be complicated by a large spectrum of lower respiratory tract infections (LRTI), defined by specific epidemiological, clinical and microbiological aspects. A European network for ICU-related respiratory infections (ENIRRIs), supported by the European Respiratory Society, has been recently established, with the aim at studying all respiratory tract infective episodes except community-acquired ones. A multicentre, observational study is in progress, enrolling more than 1000 patients fulfilling the clinical, biochemical and radiological findings consistent with a LRTI. This article describes the methodology of this study. A specific interest is the clinical impact of non-ICU-acquired nosocomial pneumonia requiring ICU admission, non-ventilator-associated LRTIs occurring in the ICU, and ventilator-associated tracheobronchitis. The clinical meaning of microbiologically negative infectious episodes and specific details on antibiotic administration modalities, dosages and duration are also highlighted. Recently released guidelines address many unresolved questions which might be answered by such large-scale observational investigations. In light of the paucity of data regarding such topics, new interesting information is expected to be obtained from our network research activities, contributing to optimisation of care for critically ill patients in the ICU.

Change in pulmonary mechanics and the effect on breathing pattern of high flow oxygen therapy in stable hypercapnic COPD.

: We studied the effects of high flow oxygen therapy (HFOT) versus non-invasive ventilation (NIV) on inspiratory effort, as assessed by measuring transdiaphragmatic pressure, breathing pattern and gas exchange. Fourteen patients with hypercapnic COPD underwent five 30-min trials: HFOT at two flow rates, both with open and closed mouth, and NIV, applied in random order. After each trial standard oxygen therapy was reinstituted for 10 min. Compared with baseline, HFOT and NIV significantly improved breathing pattern, although to different extents, and reduced inspiratory effort; however, arterial carbon dioxide oxygen tension decreased but not significantly. These results indicate a possible role for HFOT in the long-term management of patients with stable hypercapnic COPD. TRIAL REGISTRATION NUMBER: NCT02363920.

Oronasal mask versus helmet in acute hypercapnic respiratory failure.

The choice of the interface for noninvasive ventilation (NIV) is a key factor in NIV success. We hypothesised that a new helmet specifically design to improve performance in hypercapnic patients would be clinically equivalent to a standard oronasal mask. In a multicentre, short-term, physiological, randomised trial in chronic obstructive pulmonary disease patients facing an acute hypercapnic respiratory failure episode, we compared the changes in arterial blood gases (ABGs) and tolerance score obtained using the helmet or mask, and, as secondary end-points, dyspnoea, vital signs, early NIV discontinuation and rate of intubation. 80 patients were randomly assigned to receive NIV either with the helmet (n=39) or mask (n=41), using an intensive care unit ventilator. Compared with baseline, in the first 6 h, NIV improved ABGs, dyspnoea and respiratory rate (p<0.05) in both groups. Changes in ABGs and discomfort were similar with the two groups, while dyspnoea decreased more (p<0.005) using the mask. The rate of intubation and the need for interface change during the whole period of NIV were very low and not different between groups. The new helmet may be a valid alternative to a mask in improving ABGs and achieving a good tolerance during an episode of acute hypercapnic respiratory failure.

Extracorporeal Co2 removal in hypercapnic patients at risk of noninvasive ventilation failure: a matched cohort study with historical control.

OBJECTIVES: To assess efficacy and safety of noninvasive ventilation-plus-extracorporeal Co2 removal in comparison to noninvasive ventilation-only to prevent endotracheal intubation patients with acute hypercapnic respiratory failure at risk of failing noninvasive ventilation. DESIGN: Matched cohort study with historical control. SETTING: Two academic Italian ICUs. PATIENTS: Patients treated with noninvasive ventilation for acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease (May 2011 to November 2013). INTERVENTIONS: Extracorporeal CO2 removal was added to noninvasive ventilation when noninvasive ventilation was at risk of failure (arterial pH ≤ 7.30 with arterial PCO2 > 20% of baseline, and respiratory rate ≥ 30 breaths/min or use of accessory muscles/paradoxical abdominal movements). The noninvasive ventilation-only group was created applying the genetic matching technique (GenMatch) on a dataset including patients enrolled in two previous studies. Exclusion criteria for both groups were mean arterial pressure less than 60 mm Hg, contraindications to anticoagulation, body weight greater than 120 kg, contraindication to continuation of active treatment, and failure to obtain consent. MEASUREMENTS AND MAIN RESULTS: Primary endpoint was the cumulative prevalence of endotracheal intubation. Twenty-five patients were included in the noninvasive ventilation-plus-extracorporeal CO2 removal group. The GenMatch identified 21 patients for the noninvasive ventilation-only group. Risk of being intubated was three times higher in patients treated with noninvasive ventilation-only than in patients treated with noninvasive ventilation-plus-extracorporeal CO2 removal (hazard ratio, 0.27; 95% CI, 0.07-0.98; p = 0.047). Intubation rate in noninvasive ventilation-plus-extracorporeal CO2 removal was 12% (95% CI, 2.5-31.2) and in noninvasive ventilation-only was 33% (95% CI, 14.6-57.0), but the difference was not statistically different (p = 0.1495). Thirteen patients (52%) experienced adverse events related to extracorporeal CO2 removal. Bleeding episodes were observed in three patients, and one patient experienced vein perforation. Malfunctioning of the system caused all other adverse events. CONCLUSIONS: These data provide the rationale for future randomized clinical trials that are required to validate extracorporeal CO2 removal in patients with hypercapnic respiratory failure and respiratory acidosis nonresponsive to noninvasive ventilation.

Overview of current lung imaging in acute respiratory distress syndrome.

Imaging plays a key role in the diagnosis and follow-up of acute respiratory distress syndrome (ARDS). Chest radiography, bedside lung ultrasonography and computed tomography scans can provide useful information for the management of patients and detection of prognostic factors. However, imaging findings are not specific and several possible differential diagnoses should be taken into account. Herein we will review the role of radiological techniques in ARDS, highlight the plain radiological and computed tomography findings according to the pathological stage of the disease (exudative, inflammatory and fibroproliferative), and summarise the main points for the differential diagnosis with cardiogenic oedema, which is still challenging in the acute stage.

Saber-sheath trachea as a marker of severe airflow obstruction in chronic obstructive pulmonary disease.

PURPOSE: Saber-sheath trachea is a specific radiographic parameter for chronic obstructive pulmonary disease (COPD), which consists of marked coronal narrowing associated with sagittal widening (tracheal index <2/3-0.67). The aim of this study was to investigate the correlation between saber-sheath trachea and clinical-radiological findings in a group of patients with COPD of varying severity. MATERIALS AND METHODS: We evaluated the chest radiographs of 71 patients with COPD distributed as follows: GOLD class I, 8/71 (11.3 %); class II, 34/71 (47.9 %); class III, 16/71(22.5 %); class IV, 13/71 (18.3 %). In 52/71 (73.2 %) patients we also evaluated chest computed tomography (CT) scans. We analyzed the prevalence of saber-sheath trachea and its correlation with the Tiffenau index, GOLD stage and radiological signs of COPD. Moreover, we evaluated the sensitivity, specificity and accuracy of chest radiography as compared to CT taken as the gold standard, and the correlation between the radiographic and CT tracheal index. RESULTS: Saber-sheath trachea was found in 18/71 (25.4 %) patients, with a greater prevalence in patients with lower Tiffenau Index (p = 0.02), GOLD stages III-IV and visual severity score 3 (severe) on chest CT. Saber-sheath trachea was not found to be related to other radiological signs of COPD. The sensitivity, specificity and accuracy values of radiography were 72.2, 97.0 and 88.5 %, with perfect concordance between the radiographic and CT tracheal index (p < 0.00001). CONCLUSION: Saber-sheath trachea is linked to the functional severity of airway obstruction, but not to other radiological signs of COPD. Thus, evaluation of the trachea at chest radiography is strongly recommended.

Influence of the admission pattern on the outcome of patients admitted to a respiratory intensive care unit: does a step-down admission differ from a step-up one?

BACKGROUND: The outcomes of patients admitted to a respiratory ICU (RICU) have been evaluated in the past, but no study has considered the influence of location prior to RICU admission. METHODS: We analyzed prospectively collected data from 326 consecutive patients admitted to a 7-bed RICU. The primary end points were survival and severity of morbidity-related complications, evaluated according to the patient's location prior to RICU admission. Three admission pathways were considered: step-down for patients transferred from the ICUs of our hospital; step-up for patients coming from our respiratory wards or other medical wards; and directly for patients coming from the emergency department. The secondary end point was the potential influence of several risk factors for morbidity and mortality. RESULTS: Of the 326 subjects, 92 (28%) died. Overall, subjects admitted in a step-up process had a significantly higher mortality (P < .001) than subjects in the other groups. The mortality rate was 64% for subjects admitted from respiratory ward, 43% for those from medical wards, and 18% for subjects from both ICU and emergency department (respiratory ward vs medical ward P = .04, respiratory ward vs emergency department P < .001, respiratory ward vs ICU P < .001, medical ward vs emergency department P < .001, and medical ward vs ICU P < .001). Subjects admitted from a respiratory ward had a lower albumin level, and Simplified Acute Physiology Score II was significantly higher in subjects following a step-up admission. About 30% of the subjects admitted from a respiratory ward received noninvasive ventilation as a "ceiling treatment." The highest odds ratios related to survival were subject location prior to RICU admission and female sex. Lack of use of noninvasive ventilation, younger age, female sex, higher albumin level, lower Simplified Acute Physiology Score II, higher Barthel score, and absence of chronic heart failure were also statistically associated with a lower risk of death. CONCLUSIONS: The pathway of admission to a RICU is a determinant of outcome. Patients following a step-up pattern are more likely to die. Other major determinants of survival are age, nutritional status and female sex.

(18)F-FDG PET/CT for the assessment of disease extension and activity in patients with sarcoidosis: results of a preliminary prospective study.

PURPOSE: This study aimed to prospectively investigate F-FDG PET/CT role for the assessment of sarcoidosis activity and extension in comparison with thoracic high-resolution CT (HRCT) and to evaluate the potential clinical impact of PET/CT findings. Secondary aim was to investigate the changes in cardiac FDG uptake related to the specific preparation before PET/CT. METHODS: We prospectively enrolled biopsy proven sarcoidosis patients consecutively referred for F-FDG PET/CT since January 2010. PET/CT was performed after a fat meal followed by 12-hour fasting and compared with thoracic HRCT results obtained in supine position and clinical follow-up. The impact on the clinical management was recorded.Patterns of cardiac FDG uptake of the study group were compared with a historical population in which PET/CT was performed following standard preparation. RESULTS: A total of 28 patients were enrolled, and 35 PET/CT scans were reviewed. On a scan basis, PET/CT was concordant with HRCT in 16 (45.7%), detecting active disease in 10/16 and no signs of activity in 4/16. PET/CT data had a direct impact on management in 4/16.In 19 (54.3%) discordant scans, PET/CT finding was positive in 14 and negative in 5. PET/CT findings influenced the clinical management in 18/19 cases.Considering all scans, PET/CT information influenced the clinical management of 22 (63%) of 35.Our data suggest that cardiac FDG uptake may vary regardless of the preparation before PET/CT. CONCLUSIONS: F-FDG PET/CT was useful to assess sarcoidosis activity and extension and provided valuable information for the clinical management in a single-step examination. Additional data are needed to better ascertain the optimal patient preparation before image acquisition to improve sensitivity of heart lesions.

Idiopathic pulmonary fibrosis and polymorphisms of the folate pathway genes.

OBJECTIVES: This study aims to determine the possible association between folate pathway gene polymorphisms and idiopathic pulmonary fibrosis. This represents the first study carried out on folate pathway gene polymorphisms as possible risk factors in this kind of pathology. The premise is that several polymorphisms mapping on genes responsible for folate uptake are associated with the risk of numerous diseases occurring between pregnancy and old age, and that too little is currently known about idiopathic pulmonary fibrosis. DESIGN AND METHODS: We genotyped 9 single nucleotide polymorphisms and 1 polymorphic insertion in 7 essential genes belonging to the folate pathway in 32 Italian idiopathic pulmonary fibrosis patients and 81 control subjects. This was done by PCR and restriction analysis. RESULTS: Allelic and genotypic association tests indicated that for all the analysed polymorphisms there were no significant differences between patients and controls. Nevertheless, the haplotype association analysis revealed a significant association between idiopathic pulmonary fibrosis and transcobalamin II gene polymorphisms: specifically the haplotype 776G (rs1801198)-c.1026-394G (rs7286680)-444C (rs10418) (OR=2.84; 95% C.I. 1.36-5.93, P value=0.004). CONCLUSIONS: This small-scale preliminary study would suggest the importance of further research focusing on the role of folate in the onset of idiopathic pulmonary fibrosis.

Different tracheotomy tube diameters influence diaphragmatic effort and indices of weanability in difficult to wean patients.

OBJECTIVE: To determine the effects of different tracheotomy tube sizes on diaphragm effort and weanability indices. METHODS: Ten tracheotomized and difficult to wean subjects were randomized to 2 T-piece trials, with different tracheotomy tube diameters: inner diameters 8 mm and 6.5 mm. Diaphragm pressure-time product per min. (PTP(di/min)), lung compliance and resistance (C(L) and R(L)), breathing pattern, tension-time index of the diaphragm (TT(di)), and the ratio of breathing frequency to tidal volume (f/V(T)) were recorded. In an in vitro model, the flow-pressure relationship was measured using the 2 tracheotomy tubes and 2 endotracheal tubes of the same diameter. RESULTS: The use of a smaller diameter resulted in an increase of PTP(di) (337.63 ± 194.35 cm H(2)O · s/min vs 263.28 ± 156.23 cm H(2)O · s/min for 6.5 mm and 8 mm, respectively, P = .004) and R(L) (16.74 ± 8.10 cm H(2)O · s/min vs 11.72 ± 7.88 cm H(2)O · s/min, respectively, P = .008). Both weanability indices were also significantly higher using the smaller tube: f/V(T) 93.32 ± 20.91 vs 77.06 ± 19.26 for 6.5 mm and 8 mm, respectively, P < .02; TT(di) 0.09 ± 0.052 vs 0.08 ± 0.04, respectively, P < .02. In vitro measurements confirmed that the resistances were higher with the smaller diameter and similar between the tracheotomy tubes and the endotracheal tubes of the same diameters. CONCLUSIONS: In tracheotomized difficult to wean subjects the decrease of the tracheotomy tube size was associated with an increased PTP(di), f/V(T), and TT(di), that were otherwise normal, using a higher diameter. The in vitro study showed that the resistances increased similarly for tracheotomy tube and endotracheal tube, decreasing the diameter and increasing the flows.

Noninvasive mechanical ventilation.

PURPOSE OF REVIEW: A critical review of the most recent literature regarding use and clinical indications of noninvasive mechanical ventilation (NIV). RECENT FINDINGS: According to several randomized controlled trials, NIV has gained acceptance as the preferred ventilatory modality to treat acute respiratory failure (ARF) due to chronic obstructive pulmonary disease exacerbations, cardiogenic pulmonary edema, respiratory failure in immunocompromised patients, and to decrease the intubation length and to improve weaning results in patients recovering from a hypercapnic respiratory failure. Observational studies suggest that NIV may also be used to treat other conditions like severe pneumonia (including H1N1 virus), severe asthma attack, cystic fibrosis, obesity hypoventilation, and to improve the respiratory outcome in postsurgical patients. SUMMARY: NIV has radically changed the management of ARF. Recently the possible applications of NIV have increased, both in the hospital and extrahospital setting. NIV is no longer confined to the ICU, but has crossed over into the regular ward, Emergency Department and 'out-of-hospital' environment. Current research is focusing on improving the quality and safety of the devices and establishing new ventilatory modes in order to extend even further the indications to NIV as well as its rate of success.

Inspiratory muscle training in difficult to wean patients: work it harder, make it better, do it faster, makes us stronger.

Weaning from prolonged mechanical ventilation is a complex, time-consuming process that involves the loss of force/generating capacity of the inspiratory muscle. In their study 'Inspiratory muscle strength training improves the outcome in failure to wean patients: a randomized trial', Martin and colleagues showed that the use of an inspiratory muscle strength program increased the maximal inspiratory pressure and improved weaning success compared to a control group. The study was performed mainly in post-surgical patients, however, and the results, therefore, may not be generalizable to other subsets of patients, such as those with chronic obstructive pulmonary disease or congestive heart failure. Indeed, the study applied so-called 'strength training' and not 'endurance training', which may be more appropriate in certain circumstances.