Perioperative Management of a Patient With Multiple Comorbidities Undergoing Lung Resection for Bronchopulmonary Carcinoid Complicated by SARS-CoV-2 Infection: A Case Report.

We report a case of a high-risk patient with multiple comorbidities who underwent right median lobectomy and lymph node resection due to a carcinoid tumor. The patient's course was complicated by a hospital-acquired severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and a postoperative chest hematoma requiring urgent thoracotomy. Multidisciplinary and timely management resulted in a favorable patient outcome.

Post-Operative Thoracic Epidural Analgesia and Incidence of Major Complications according to Specific Safety Standardized Documentation: A Large Retrospective Dual Center Experience.

(1) Background: Thoracic epidural analgesia is considered the gold standard in post-operative pain management following thoracic surgery. This study was designed to explore the safety of thoracic epidural analgesia and to quantify the incidence of its post-operative complications and side effects in patients undergoing thoracotomy for major surgery, such as resection of lung malignancies and lung transplantation. (2) Methods: This is a retrospective, dual-center observational study including patients that underwent major thoracic surgery including lung transplantation and received concurrent placement of thoracic epidural catheters for post-operative analgesia. An electronic system of referral and documentation of complications was used, and information was retrieved from our electronic critical care charting system. (3) Results: In total, 1145 patients were included in the study. None of the patients suffered any major complication, including hematoma, abscess, or permanent nerve damage. (4) Conclusions: the present study showed that in experienced centers, post-operative epidural analgesia in patients with thoracotomy is a safe technique, manifesting minimal, none-serious complications.

Cardiopulmonary Exercise Testing in Heart Failure With Preserved Ejection Fraction: Technique Principles, Current Evidence, and Future Perspectives.

Heart failure with preserved ejection fraction (HFpEF) is a multifactorial clinical syndrome involving a rather complex pathophysiologic substrate and quite a challenging diagnosis. Exercise intolerance is a major feature of HFpEF, and in many cases, diagnosis is suspected in subjects presenting with exertional dyspnea. Cardiopulmonary exercise testing (CPET) is a noninvasive, dynamic technique that provides an integrative evaluation of cardiovascular, pulmonary, hematopoietic, neuropsychological, and metabolic functions during maximal or submaximal exercise. The assessment is based on the principle that system failure typically occurs when the system is under stress, and thus, CPET is currently considered to be the gold standard for identifying exercise intolerance, allowing the differential diagnosis of underlying causes. CPET is used in observational studies and clinical trials in HFpEF; however, in most cases, only a few from a wide variety of CPET parameters are examined, while the technique is largely underused in everyday cardiology practice. This article discusses the basic principles and methodology of CPET and studies that utilized CPET in patients with HFpEF, in an effort to increase awareness of CPET capabilities among practicing cardiologists.

Effect of kidney transplantation on indices of cardiorespiratory fitness assessed with cardiopulmonary exercise testing: a systematic review and meta-analysis.

BACKGROUND: Patients with kidney failure often present with reduced cardiovascular reserve. Kidney transplantation (KT) is the optimal treatment for patients with end-stage kidney disease as it is associated with longer survival and improved quality of life compared to dialysis. METHODS: This is a systematic review and meta-analysis of studies using cardiopulmonary-exercise-testing to examine the cardiorespiratory fitness of patients with kidney failure before and after KT. The primary outcome was difference in pre- and post-transplantation values of peak oxygen uptake (VO2peak). Literature search involved three databases (PubMed-Web of Science-Scopus), manual search, and grey literature. RESULTS: From 379 records initially retrieved, six studies were included in final meta-analysis. A marginal, but not significant, improvement was observed in VO2peak after KT compared to pre-transplantation values (SMD: 0.32, 95%CI -0.02; 0.67). Oxygen consumption at anaerobic threshold was significantly improved after KT (WMD: 2.30 ml/kg/min, 95%CI 0.50; 4.09). Consistent results were shown between preemptive and after-dialysis-initiation transplantation and a trend for improvement in VO2peak was observed at least 3 months post-transplantation, but not earlier. CONCLUSION: Several major indices of cardiorespiratory fitness tend to improve after KT. This finding may represent another modifiable factor contributing to better survival rates of kidney transplant recipients compared to patients undergoing dialysis.

COVID-19 and liver injury: An ongoing challenge.

The new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019, in Wuhan, China. The virus was rapidly spread worldwide, causing coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is presented, usually, with typical respiratory symptoms (i.e., dyspnea, cough) and fever, extrapulmonary manifestations are also encountered. Liver injury is a common feature in patients with COVID-19 and ranges from mild and temporary elevation of liver enzymes to severe liver injury and, even, acute liver failure. The pathogenesis of liver damage is not clearly defined; multiple mechanisms contribute to liver disorder, including direct cytopathic viral effect, cytokine storm and immune-mediated hepatitis, hypoxic injury, and drug-induced liver toxicity. Patients with underlying chronic liver disease (i.e., cirrhosis, non-alcoholic fatty liver disease, alcohol-related liver disease, hepatocellular carcinoma, etc.) may have greater risk to develop both severe COVID-19 and further liver deterioration, and, as a consequence, certain issues should be considered during disease management. The aim of this review is to present the prevalence, clinical manifestation and pathophysiological mechanisms of liver injury in patients with SARS-CoV-2 infection. Moreover, we overview the association between chronic liver disease and SARS-CoV-2 infection and we briefly discuss the management of liver injury during COVID-19.

Persistent Sleep Quality Deterioration among Post-COVID-19 Patients: Results from a 6-Month Follow-Up Study.

Background: To date, evidence about sleep disturbances among post-COVID-19 patients is limited. This study aimed to evaluate sleep quality after hospitalization due to SARS-CoV-2 infection. Methods: In-person follow-up was conducted in patients with prior hospitalization due to COVID-19 1(Τ1), 3(Τ2), and 6 (Τ3) months after hospital discharge. Patients were asked to complete questionnaires concerning sleep quality: the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Athens Insomnia Scale (AIS), the Fatigue Severity Scale (FSS), and the Stop-BANG (S-B) questionnaire. Results: In total, 133 patients were enrolled (mean age: 56.0 ± 11.48 years, 59.4% males). The most frequently reported comorbidity was arterial hypertension (29.8% of patients), while 37.4% of patients had no comorbidities. The majority of participants exhibited poor sleep quality (global PSQI ≥ 5) at T1 (84.3%), T2 (75.7%), and T3 (77.4%). Insomnia was observed in 56.5%, 53.5%, and 39.2% of participants, respectively (AIS ≥ 6). An FSS score ≥ 4 was observed in 51.2%, 33.7%, and 29.1% of participants at T1, T2, T3, respectively. Elapsed time was found to be negatively and independently associated with the global PSQI, PSQI C5-Sleep disturbance, PSQI C7-Daytime dysfunctions, FSS, and AIS after adjustment for possible confounders. No significant difference was found between groups with good and poor sleep quality (based on the global PSQI) with respect to gender (p = 0.110), age (p = 0.528), BMI (p = 0.816), smoking status (p = 0.489), hypertension (p = 0.427), severity of disease (p = 0.224), the Charlson Comorbidity Index (p = 0.827), or the length of hospital stay (p = 0.162). Participants with excessive daytime sleepiness (EDS) and patients with severe fatigue (FSS ≥ 4) were significantly younger. Females presented a higher rate of insomnia symptoms (55.7% vs. 44.3%, p < 0.001). Conclusions: Several sleep disturbances were observed after hospital discharge for COVID-19 pneumonia at certain time points; However, the improvement over time was remarkable in most domains of the assessed questionnaires.

Effects of different exercise programs on the cardiorespiratory reserve in HFpEF patients: a systematic review and meta-analysis.

HFpEF represents a heterogeneous syndrome with complex pathophysiological substrates and multiple clinical manifestations. Recently, much attention has been focused on cardiac rehabilitation programs for HFpEF patients, and several studies have examined the effects of exercise training on this specific population. This systematic review and meta-analysis included studies on adult patients with HFpEF and evaluated the impact of exercise on the cardiorespiratory fitness variables measured during CPET. The primary outcome was the difference in the change in the peak oxygen uptake (Δpeak VO2) between the groups. Literature search involved PubMed/MEDLINE, Cochrane/CENTRAL and Scopus databases. From an initial 5,143 literature records, we identified 18 studies fulfilling the inclusion criteria; 11 studies with 515 patients were finally included in the primary outcome analysis. Δpeak VO2 between baseline and study end was significantly higher in the groups of exercise training versus control (WMD 2.25 ml/kg/min, 95% CI 1.81-2.70). Exercise training resulted in greater change in the 6-minute walking test (6MWT) distance (WMD 2.25 m, 95% CI 1.81-2.70). Health-related quality of life (HRQoL) (WMD: -3.36, 95% CI -9.42 to 2.70, I2 = 14%, p = 0.33) and echocardiographic indices of diastolic function showed no differences between exercise and control groups at study end. In the subgroup analysis, no difference between resistance versus aerobic exercise was noted in Δpeak VO2, but high-intensity interval training showed a greater increase in peak VO2 versus aerobic exercise (WMD 1.62 ml/kg/min, 95% CI 0.96-2.29, I2 = 0%, p = 0.82). Exercise training in HFpEF results in significant improvements in peak VO2 and 6MWT distance as compared to those for controls. High-intensity interval training may offer greater enhancement of the exercise capacity of these patients than standard aerobic exercise.

Effects of oxygen supplementation in autonomic nervous system function during exercise in patients with idiopathic pulmonary fibrosis and exertional desaturation.

INTRODUCTION: Patients with idiopathic pulmonary fibrosis (IPF) have reduced exercise capacity and often present exertional dyspnea and desaturation. The role of autonomic nervous system (ANS) as a pathogenetic contributor to this dysfunction has not been evaluated. OBJECTIVE: To evaluate whether improvement of arterial oxygen saturation (SpO2 ) via oxygen supplementation results to ANS function improvement, during steady state submaximal exercise. METHODS: This is a secondary analysis of a single-blind, randomized, placebo-controlled, cross-over trial, including 12 IPF patients, with isolated exertional desaturation. Following a maximal cardiopulmonary test, participants underwent two submaximal steady state tests during which they received either supplementary oxygen or medical air. Continuous beat-to-beat blood pressure measurements were recorded (Finapres Medical Systems, Amsterdam, The Netherlands). Autonomic function was assessed non-invasively by heart rate variability (HRV); root mean square of successive differences (RMSSD) and standard-deviation-Poincare-plot (SD1) were used as indices of parasympathetic output. Entropy and detrended fluctuation analysis (DFA) were also used. RESULTS: During rest, oxygen supplementation did not significantly alter RMSSD and SD1. During exercise, subjects presented no significant alterations compared with baseline, in most HRV indices examined. There was no improvement of this behavior with O2 -supplementation. Approximate-entropy increased during exercise, with no differences between protocols. CONCLUSIONS: IPF patients presented an inadequate adaptive response of their ANS to exercise and recovery. Although oxygen supplementation significantly prolonged exercise duration and prevented the substantial exertional desaturation, the blunted vagal response to steady-state exercise in these patients was not improved, suggesting that acute oxygen supplementation does not sufficiently improve ANS dysfunction in these patients.

Vaccinated and Convalescent Donor-Derived Severe Acute Respiratory Syndrome Coronavirus 2-Specific T Cells as Adoptive Immunotherapy for High-Risk Coronavirus Disease 2019 Patients.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an urgent need for the development of effective therapies for coronavirus disease 2019 (COVID-19). METHODS: We first tested SARS-CoV-2-specific T-cell (CοV-2-ST) immunity and expansion in unexposed donors, COVID-19-infected individuals (convalescent), asymptomatic polymerase chain reaction (PCR)-positive subjects, vaccinated individuals, non-intensive care unit (ICU) hospitalized patients, and ICU patients who either recovered and were discharged (ICU recovered) or had a prolonged stay and/or died (ICU critical). CoV-2-STs were generated from all types of donors and underwent phenotypic and functional assessment. RESULTS: We demonstrate causal relationship between the expansion of endogenous CoV-2-STs and the disease outcome; insufficient expansion of circulating CoV-2-STs identified hospitalized patients at high risk for an adverse outcome. CoV-2-STs with a similarly functional and non-alloreactive, albeit highly cytotoxic, profile against SARS-CoV-2 could be expanded from both convalescent and vaccinated donors generating clinical-scale, SARS-CoV-2-specific T-cell products with functional activity against both the unmutated virus and its B.1.1.7 and B.1.351 variants. In contrast, critical COVID-19 patient-originating CoV-2-STs failed to expand, recapitulating the in vivo failure of CoV-2-specific T-cell immunity to control the infection. CoV-2-STs generated from asymptomatic PCR-positive individuals presented only weak responses, whereas their counterparts originating from exposed to other seasonal coronaviruses subjects failed to kill the virus, thus disempowering the hypothesis of protective cross-immunity. CONCLUSIONS: Overall, we provide evidence on risk stratification of hospitalized COVID-19 patients and the feasibility of generating powerful CoV-2-ST products from both convalescent and vaccinated donors as an "off-the shelf" T-cell immunotherapy for high-risk patients.

Assessment of Exercise Intolerance in Patients with Pre-Dialysis CKD with Cardiopulmonary Function Testing: Translation to Everyday Practice.

BACKGROUND: Chronic kidney disease (CKD) is often characterized by increased prevalence of cardiovascular risk factors and increased incidence of cardiovascular events and death. Reduced cardiovascular reserve and exercise intolerance are common in patients with CKD and are associated with adverse outcomes. SUMMARY: The gold standard for identifying exercise limitation is cardiopulmonary exercise testing (CPET). CPET provides an integrative evaluation of cardiovascular, pulmonary, hematopoietic, neuropsychological, and metabolic function during maximal or submaximal exercise. It is useful in clinical setting for differentiation of the causes of exercise intolerance, risk stratification, and assessment of response to relevant treatments. A number of recent studies have used CPET in patients with pre-dialysis CKD, aiming to assess the cardiovascular reserve of these individuals, as well as the effect of interventions such as exercise training programs on their functional capacity. This review provides an in-depth description of CPET methodology and an overview of studies that utilized CPET technology to assess cardiovascular reserve in patients with pre-dialysis CKD. Key Messages: CPET can delineate multisystem changes and offer comprehensive phenotyping of factors determining overall cardiovascular risk. Potential clinical applications of CPET in CKD patients range from objective diagnosis of exercise intolerance to preoperative and long-term risk stratification and providing intermediate endpoints for clinical trials. Future studies should delineate the association of CPET indexes, with cardiovascular and respiratory alterations and hard outcomes in CKD patients, to enhance its diagnostic and prognostic utility in this population.

Vascular endothelial damage in COPD: current functional assessment methods and future perspectives.

Introduction: Cardiovascular disease is a major cause of death in chronic obstructive pulmonary disease (COPD), but the relationship between these two entities is not fully understood; smoking, inflammation, arterial stiffness and endothelial dysfunction are significant determinants. Endothelial dysfunction is not only associated with cardiovascular disease, but also with COPD severity.Areas covered: Several functional methods have been developed to evaluate endothelial function in healthy and diseased individuals; from the invasive angiography of epicardial coronary arteries and Venous-Occlusion-Plethysmography, to more modern, noninvasive approaches such as Flow-Mediated-Dilatation, Peripheral-Arterial-Tonometry and Near-Infrared-Spectroscopy, all these methods have boosted clinical research in this field. In this context, this narrative review, which included articles published in PubMed and Scopus up to 25-November-2020, summarizes available functional methods for endothelial damage assessment in COPD and discusses existing evidence on their associations with comorbidities and outcomes in this population.Expert opinion: Accumulated evidence suggests that endothelial dysfunction occurs in early stages of CΟPD and worsens with pulmonary obstruction severity and during acute exacerbations. Novel methods evaluating endothelial function offer a detailed, real-time assessment of different parameters related to vascular function and should be increasingly used to shed more light on the role of endothelial damage on cardiovascular and COPD progression.

Exertional Desaturation in Idiopathic Pulmonary Fibrosis: The Role of Oxygen Supplementation in Modifying Cerebral-Skeletal Muscle Oxygenation and Systemic Hemodynamics.

BACKGROUND: In patients with idiopathic pulmonary fibrosis (IPF) with isolated exertional desaturation, there are limited data regarding the effectiveness of oxygen supplementation during exercise training; the underlying mechanisms that contribute to these responses are unknown. OBJECTIVES: To examine in these IPF patients the effects of oxygen supplementation during submaximal exercise (vs. medical air) on cerebral/skeletal muscle oxygenation and systemic hemodynamics. METHODS: In this randomized, cross-over, placebo-controlled trial, IPF patients (n = 13; 63.4 ± 9.6 years) without resting hypoxemia but a significant desaturation during maximal cardiopulmonary exercise testing underwent 2 steady-state exercise trials (65% peak-work-load), breathing either oxygen-enriched or medical air. Cerebral/skeletal muscle oxygenation (near-infrared spectroscopy) and beat-by-beat hemodynamics (photoplethysmography) were monitored. RESULTS: In the air protocol, from the initial minutes of submaximal exercise, patients exhibited a marked decline in cerebral oxygenated hemoglobin (O2Hb) and an abrupt rise in deoxygenated hemoglobin (HHb). Oxygen supplementation alleviated desaturation, lessened dyspnea, and prolonged exercise duration (p < 0.01). Oxygen supplementation during exercise (i) attenuated cerebral deoxygenation (cerebral-HHb: 0.7 ± 1.9 vs. 2.5 ± 1.5 µmol/L, O2 and air protocol; p = 0.009) and prevented cerebral-Hbdifference decline (2.1 ± 2.7 vs. -1.7 ± 2.0 µmol/L; p = 0.001), (ii) lessened the decline in muscle O2-saturation index, and (iii) at isotime exercise, it resulted in lower muscle-HHb (p = 0.05) and less leg fatigue (p < 0.05). No differences between protocols were observed in exercise cardiac output and vascular resistance. CONCLUSIONS: IPF patients with isolated exertional hypoxemia exhibit an inability to increase/maintain cerebral oxygenation during submaximal exercise. Correcting desaturation with O2 supplementation prevented the decline in brain oxygenation, improved muscle oxygenation, and lessened dyspnea, suggesting an efficacy of acute oxygen supplementation during exercise training in protecting brain hypoxia in these IPF patients.

Serum Copeptin, NLPR3, and suPAR Levels among Patients with Autosomal-Dominant Polycystic Kidney Disease with and without Impaired Renal Function.

BACKGROUND: The pathophysiology of renal disease progression in autosomal-dominant polycystic kidney disease (ADPKD) involves not only cystogenesis but also endothelial dysfunction, leading to the activation of inflammatory and fibrotic pathways. This study evaluated the levels of biomarkers related to osmoregulation, immune system activation, and tubular injury in ADPKD patients with impaired or preserved renal function. METHODS: This study included 26 ADPKD patients with modestly impaired renal function (estimated glomerular filtration rate [eGFR] 45-70 mL/min/1.73 m2; Group A), 26 age- and sex-matched ADPKD patients with relatively preserved renal function (eGFR >70 mL/min/1.73 m2; Group B), and 26 age- and sex-matched controls (Group C). Serum levels of copeptin, the inflammasome nucleotide-binding and oligomerization domain-like receptors pyrin domain-containing protein 3 (NLRP3), and soluble urokinase-type plasminogen activator receptor (suPAR) were measured with ELISA techniques. RESULTS: Patients in Group A had higher levels of copeptin (median [interquartile range]: 50.44 [334.85] pg/mL), NLRP3 (5.86 [3.89] ng/mL), and suPAR (390.05 [476.53] pg/mL) compared to patients in Group B (32.38 [58.33], p = 0.042; 2.42 [1.96], p < 0.001; and 313.78 [178.85], p = 0.035, respectively) and Group C (6.75 [6.43]; 1.09 [0.56]; and 198.30 [28.53], respectively; p < 0.001 for all comparisons). Levels of all studied markers were also significantly higher in Group B patients compared to controls (p < 0.001), despite having similar eGFR. In patients with ADPKD, all studied biomarkers were correlated positively with asymmetric-dimethylarginine (ADMA) and endocan levels, and negatively with eGFR. ADMA and endocan levels were the only parameters independently associated with increased copeptin levels. CONCLUSIONS: This study showed that ADPKD patients with impaired and preserved renal function had higher copeptin, NLRP3, and suPAR levels than controls. Such findings support that cystogenesis and inflammation are associated with endothelial dysfunction, even in the early stages of ADKPD.

Longitudinal changes in exercise capacity among adult cystic fibrosis patients.

INTRODUCTION: Longitudinal data regarding changes in exercise capacity among adult cystic fibrosis (CF) patients are currently scarce. The aim of this brief report was to assess changes in exercise capacity among adult CF patients with stable and mild-to-moderate disease eight years after their initial evaluation. MATERIAL AND METHODS: Maximum cardiopulmonary exercise testing (CPET) was utilized. Other assessments included Doppler echocardiography, the 6-minute walking test, spirometry, and lung volume evaluation. RESULTS: Eleven (6 male, 5 female) patients completed both evaluations (initial and after eight years). During follow-up, indices of ventilatory impairment (such as ventilatory reserve; p=0.019, and ventilatory equivalent for carbon dioxide; p = 0.047) deterio-rated significantly following a decline in respiratory function measurements. Peak oxygen uptake (VO2), both as an absolute (26.6 ± 8.46 vs 23.89 ± 6.16 mL/kg/min; p = 0.098) and as a % of predicted value (71.21 ± 16.54 vs 70.60 ± 15.45; p = 0.872), did not deteriorate. This is also true for oxygen pulse (p = 0.743), left heart ejection fraction (p = 0.574), and pulmonary artery systolic pressure (p = 0.441). However, the anaerobic threshold, both as an absolute (p = 0.009) and as a % of predicted value (p = 0.047), was significantly lower during follow-up. CONCLUSION: In adult CF patients with stable, mild-to-moderate disease, a peak VO2 may be preserved for several years. However, even in these patients, deconditioning is present.

Nicotine treatment and smoking cessation in the era of COVID-19 pandemic: an interesting alliance.

In the era of this pandemic, the role of medicinal nicotine in the prevention and treatment of #COVID19 disease should be evaluated in placebo-controlled trials, while smoking cessation should be further promoted as a general public health measure https://bit.ly/3fpsBdq.

Hyponatremia accompanying volatile hypertension caused by baroreflex failure after neck surgery: case report and literature review.

: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of euvolemic hyponatremia, and many disorders have been associated with it. Baroreflex failure is a rare disorder characterized by extreme blood pressure (BP) fluctuations, most frequently caused by neck or head trauma and irradiation. We report a case of a 48-year-old patient referred to our department for asymptomatic hyponatremia and volatile hypertension. His past medical history included nasopharyngeal carcinoma treated with surgery and bilateral neck radiation. Following the diagnostic algorithm for hyponatremia, the diagnosis of SIADH was made. Ambulatory BP monitoring revealed highly variable BP; extensive autonomic nervous system function testing suggested baroreflex-cardiovagal failure. We propose the hypothesis that not only labile hypertension because of baroreflex failure but also hyponatremia can develop as a late consequence of neck trauma and irradiation.