Low-Medium and High-Intensity Inspiratory Muscle Training in Critically Ill Patients: A Systematic Review and Meta-Analysis.

Background and objectives: Mechanical ventilation is often used in intensive care units to assist patients' breathing. This often leads to respiratory muscle weakness and diaphragmatic dysfunction, causing weaning difficulties. Inspiratory muscle training (IMT) has been found to be beneficial in increasing inspiratory muscle strength and facilitating weaning. Over the years, different protocols and devices have been used. Materials and Methods: The aim of this systematic review and meta-analysis was to investigate the effectiveness of low-medium (LM-IMT) and high-intensity (H-IMT) threshold inspiratory muscle training in critically ill patients. A systematic literature search was performed for randomized controlled trials (RCTs) in the electronic databases Google Scholar, PubMed, Scopus, and Science Direct. The search involved screening for studies examining the effectiveness of two different intensities of threshold IMT in critically ill patients published the last 10 years. The Physiotherapy Evidence Database (PEDro) scale was chosen as the tool to assess the quality of studies. A meta-analysis was performed where possible. Results: Fourteen studies were included in the systematic review, with five of them having high methodological quality. Conclusions: When examining LM-IMT and H-IMT though, neither was able to reach statistically significant improvement in their maximal inspiratory pressure (MIP), while LM-IMT reached it in terms of weaning duration. Additionally, no statistical difference was noticed in the duration of mechanical ventilation. The application of IMT is recommended to ICU patients in order to prevent diaphragmatic dysfunction and facilitate weaning from mechanical ventilation. Therefore, further research as well as additional RCTs regarding different protocols are needed to enhance its effectiveness.

Unfractionated heparin reduces hepcidin levels in critically ill patients.

A strong anti-hepcidin activity has been observed in heparins. Mean hepcidin levels were significantly reduced compared to baseline, following the first day of unfractionated heparin administration in critically patients. Heparin displayed a strong independent negative association with hepcidin. These results may lead to future treatment methods of forms of anaemia characterised by hepcidin excess, common among the critically ill.

Variation of endothelium-related hemostatic factors during sepsis.

OBJECTIVE: The thrombomodulin/protein C and VWF/ADAMTS-13 pathways are disturbed in sepsis and have been implicated in the coagulation disorders that characterize the septic syndrome. We aimed to assess the variation of these endothelial parameters during sepsis and their putative association with outcome, in critically ill, septic patients. METHODS: We monitored 34 septic patients, 23 of whom improved (group A) while 11 deteriorated (group B). We assessed ADAMTS-13 levels, VWF activity, soluble thrombomodulin, and protein C activity upon admission to the ICU (time point 0) and at the time of a change in the clinical condition (remission or deterioration, time point 1). RESULTS: In group A, thrombomodulin and VWF increased at time point 1 compared to time point 0 (P = 0.011, P = 0.028, respectively). In group B, protein C and ADAMTS-13 significantly decreased (P = 0.023, P = 0.026, respectively), while VWF, VWF/ADAMTS-13 ratio, and the thrombomodulin/protein C ratio increased (P = 0.02, P = 0.002, P = 0.01, respectively). Protein C (> or ≤17%) and ADAMTS-13 percentage difference (> or ≤22%) were independently associated with sepsis outcome among the endothelial variables tested. CONCLUSIONS: An ongoing endothelial/hemostatic disorder was established during sepsis, observed even at clinical improvement. Among the variables tested, protein C and ADAMTS-13 change were associated with outcome.

Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: A Promising Medication for Chronic Obstructive Pulmonary Disease?

Chronic obstructive pulmonary disease (COPD) is a complex disorder that primarily affects the lungs and is characterized not only by local pulmonary, but also by systemic inflammation which promotes the development of extrapulmonary and cardiovascular co-morbidities. Angiotensin converting enzyme (ACE) inhibitors and ARBs (angiotensin receptor blockers) are widely used drugs in the treatment of cardiovascular diseases, with growing evidence suggesting potential benefits in COPD patients. The purpose of this review is to describe the correlation of renin-angiotensin system (RAS) with COPD pathophysiology and to present the latest data regarding the potential role of RAS blockers in COPD.

Muscle microcirculation alterations and relation to dipping status in newly diagnosed untreated patients with arterial hypertension-A pilot study.

OBJECTIVE: The importance of abnormalities observed in the microcirculation of patients with arterial hypertension (AH) is being increasingly recognized. The authors aimed to evaluate skeletal muscle microcirculation in untreated, newly diagnosed hypertensive patients with NIRS, a noninvasive method that evaluates microcirculation. METHODS: We evaluated 34 subjects, 17 patients with AH (13 males, 49±13 years, BMI: 26±2 kg/m2 ) and 17 healthy controls (12 males, 49±15 years, BMI: 25±3 kg/m2 ). The thenar muscle StO2 (%) was measured by NIRS before, during and after 3-minutes vascular occlusion to calculate OCR (%/min), EF (%/min), and RHT (minute). The dipping status of hypertensive patients was assessed. RESULTS: The RHT differed between AH patients and healthy subjects (2.6±0.3 vs 2.1±0.3 minutes, P<.001). Dippers had higher EF than nondippers (939±280 vs 710±164%/min, P=.05). CONCLUSIONS: The study suggests an impaired muscle microcirculation in newly diagnosed, untreated AH patients.

Microcirculatory alterations during continuous renal replacement therapy in ICU: A novel view on the 'dialysis trauma' concept.

OBJECTIVE: The purpose of this study was to evaluate microcirculation over 24 h renal replacement therapy (CRRT) in critically ill patients. METHODS: We conducted a single-center, prospective, observational study, measuring microcirculation parameters, monitored by near infrared spectroscopy (NIRS) before hemodiafiltration onset (H0), and at six (H6) and 24 h (H24) during CRRT in critically ill patients. Serum Cystatin C (sCysC) and soluble (s)E-selectin levels were measured at the same time points. Twenty-eight patients [19 men (68%)] were included in the study. RESULTS: Tissue oxygen saturation (StO2, %) [76.5 ± 12.5 (H0) vs 75 ± 11 (H6) vs 70 ± 16 (H24), p = 0.04], reperfusion rate, indicating endothelial function (EF, %/sec) [2.25 ± 1.44 (H0) vs 2.1 ± 1.8 (H6) vs 1.6 ± 1.4 (H24), p = 0.02] and sCysC (mg/L) [2.7 ± 0.8 (H0) vs 2.2 ± 0.6 (H6) vs 1.8 ± 0.8 (H24), p < 0.0001] significantly decreased within the 24 h CRRT. Change of EF positively correlated with changes of sCysC within 24 h CRRT (r = 0.464, p = 0.013) while in patients with diabetes the change of StO2 correlated with dose (r = − 0.8, p = 0.01). No correlation existed between hemoglobin and temperature changes with the deteriorated microcirculation indices. sE-Selectin levels in serum were elevated; no difference was established over the 24 h CRRT period. A strong correlation existed between the sE-Selectin concentration change at H6 and H24 and the mean arterial pressure change in the same period (r = 0.77, p < 0.001). CONCLUSIONS: During the first 24 h of CRRT implementation in critically ill patients, deterioration of microcirculation parameters was noted. Microcirculatory alterations correlated with sCysC changes and with dose in patients with diabetes.

Thyroglobulin antibodies could be a potential predictive marker for papillary thyroid carcinoma.

BACKGROUND: Hashimoto thyroiditis (HT) is associated with an increased risk of developing papillary thyroid carcinoma (PTC). The relationship between thyroid autoimmunity and cancer remains controversial. The purpose of this study was to investigate whether the preoperative TgAb could be a potential predictor of PTC in patients with thyroid nodules and to assess whether there is an association of preoperative TgAb with lymph node metastases. METHODS: This retrospective, nonrandomised study included 854 patients who underwent standard total thyroidectomy. Benign thyroid nodules were diagnosed in 447 patients, and 407 presented with malignant nodules. The examined parameters included the clinical characteristics, preoperative TSH and TgAb levels, and the histopathological characteristics of the tumour. RESULTS: Tumour size >10 mm (p = 0.01), the presence of PTC (p < 0.001), elevated TSH levels (2.64 ± 1.28 µU/ml vs. 2.09 ± 0.98 µU/ml, p = 0.001), HT (p < 0.001), and lymph node metastasis (p = 0.005) were significantly associated with positive TgAb. Additionally, tumour size >10 mm (p < 0.001), preoperative TgAb positivity (p = 0.003), and elevated TSH levels (TSH > 3.4 µU/ml, p = 0.038) were independent risk factors for PTC based on the multivariate logistic regression analysis. CONCLUSIONS: This study showed that TgAb positivity was an independent risk factor for PTC. A positive correlation between TgAb and PTC in patients with indeterminate nodules was existed. Additionally, a positive correlation existed between TgAb and lymph node metastases in patients with PTC. Prospective studies with a larger number of patients and long-term follow-up are needed clarify the potential role of positive serum TgAb in the prediction of PTC.

Strong ion gap and anion gap corrected for albumin and lactate in patients with sepsis in the intensive care unit.

INTRODUCTION: Metabolic acidosis is very common amongst critically ill sepsis patients partly due to the presence of unmeasured ions in serum. These ions can be detected by anion gap (AG) or strong ion gap (SIG) concentration values. The purpose of this study is to assess the correlation and potential agreement of the two methods in critically ill patients with sepsis. MATERIALS AND METHODS: The present is a retrospective study including septic patients admitted to the Intensive Care Unit from December 2014 to July 2016. The [SIG] and the [AG] corrected for albumin and lactate ([AGcl]) were calculated on admission and on sepsis remission or deterioration. The correlation of the two parameters was assessed in all patient groups using the Pearson correlation coefficient and linear regression analysis and the agreement with Bland-Altman plots. ROC survival curves were also generated for the patients in relation to the values of [AGcl], [SIG] and inorganic [SIG] ([SIGi]) on admission. RESULTS: There was a strong correlation linking [AGcl] and [SIG] values (r>0.9, P<0.05) in all patient groups. The results from all three linear regression equations were statistically significant as the models predicted the [AGcl] value from the [SIG] value with high accuracy. The mean difference of the two methods (i.e. [AGcl] - [SIG] in every patient separately) in septic patients on admission was 11.75 mEq/l with 95% limits of agreement [9.7-13.8]; in patients with sepsis deterioration, it was 11.8 mEq/l with 95% limits of agreement [9.8-13.7] and in patients with sepsis remission, it was 11.5 mEq/l with 95% limits of agreement [10.4-12.7]. ROC survival curves demonstrated a small area under the curve (AUC): [SIG] AUC: 0.479, 95% CI [0.351, 0.606], [SIGi] AUC: 0.581, 95% CI [0.457, 0.705], [AGcl] AUC: 0.529, 95% CI [0.401, 0.656]. CONCLUSION: [AGcl] and [SIG] demonstrate excellent correlation in septic patients, with a mean difference of about 12 mEq/l. Both parameters failed to demonstrate any predictive ability regarding patient mortality.

The Diagnostic Accuracy of Procalcitonin and Its Combination with Other Biomarkers for Candidemia in Critically Ill Patients.

Background: The aim of this study was to investigate the usefulness of serum procalcitonin (PCT), C-reactive protein (CRP), neutrophil to lymphocyte count ratio (NLR), and their combination, in distinguishing candidemia from bacteremia in intensive care unit (ICU) patients. Methods: This is a retrospective study in ICU patients with documented bloodstream infections (BSIs) and with both serum PCT and CRP measurements on the day of the positive blood sample. Illness severity was assessed by sequential organ failure assessment (SOFA) score on both admission and BSI day. Demographic, clinical, and laboratory data, including PCT and CRP levels and NLR on the day of the BSI, were recorded. Results: A total of 63 patients were included in the analysis, of whom 32 had bacteremia and 31 had candidemia. PCT, CRP, and NLR values were all significantly lower in candidemia compared with bacteremia (0.29 (0.14-0.69) vs. 1.73 (0.5-6.9) ng/mL, p < 0.001, 6.3 (2.4-11.8) vs. 19 (10.7-24.8) mg/dl, p < 0.001 and 6 (3.7-8.6) vs. 9.8 (5.3-16.3), p = 0.001, respectively). PCT was an independent risk factor for candidemia diagnosis (OR 0.153, 95%CI: 0.04-0.58, p = 0.006). A multivariable model consisting of the above three variables had better predictive ability (AUC-ROC = 0.88, p < 0.001), for candidemia diagnosis, as compared to that of PCT, CRP, and NLR, whose AUC-ROCs were all lower (0.81, p < 0.001, 0.78, p < 0.001, and 0.68, p = 0.015, respectively). Conclusions: A combination of routinely available laboratory tests, such as PCT, CRP, and NLR, could prove useful for the early identification of ICU patients with candidemia.

A Merkel-cell carcinoma metastatic to the tonsil: a case report and review of the literature.

Metastatic tumors to the palatine tonsils are extremely rare, with nearly 100 cases reported. Only 3 cases of Merkel cell carcinoma of the skin metastasizing to the palatine tonsil have been reported. We present the interesting case of a 61-year-old man with an enlargement of the left palatine tonsil that caused a moderate narrowing of the oropharynx. Three years previously he had been treated for Merkel cell carcinoma (MCC) on skin of his left shoulder. A tonsillectomy followed by palatoplasty was performed. Immunohistochemical staining demonstrated a pronounced reaction for cytokeratin 20, chromogranin, and CD56 histodiagnostic markers. Immunohistochemical studies are useful diagnostic tools in the establishment of the diagnosis of MCC. Treatment includes wide local surgical excision of the tumor, radiotherapy, and chemotherapy. Considering the aggressiveness of MCC, an early diagnosis is critical to enable the choice of adequate therapy at an early stage.

External auditory canal mass as the first manifestation of a bronchogenic carcinoma: report of a rare case.

OBJECTIVES: Metastatic tumors in the external auditory canal (EAC) are exceptionally rare. These metastases almost always occur in the latter stages of the disease process. Ten cases of metastatic tumors of the EAC have been reported in the literature. We report the first case of a metastatic bronchogenic adenocarcinoma that presented initially as an EAC mass. METHODS: We present a case report and a literature review. RESULTS: Although bronchogenic adenocarcinoma not uncommonly metastasizes to the temporal bone, metastasis to the EAC is extremely rare. We report the case of a 62-year-old woman who presented with a 6-week history of swelling in her right EAC and sudden onset of hearing loss. Physical examination revealed a small, polypoid, friable mass originating from the superior-posterior wall of the right EAC. Incision biopsy was performed, and the histopathologic examination of specimens revealed a moderately to poorly differentiated adenocarcinoma compatible with a bronchogenic origin. CONCLUSIONS: A patient with an aural mass presents a diagnostic dilemma. Metastatic tumors in the EAC are extremely rare, but they should be included in the differential diagnosis of a mass in this location.

Common Pathogenetic Pathways of Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are two cardinal manifestations of the metabolic syndrome, which is becoming a growing global pandemic and a health care burden. They constitute a pathogenetic duo, with complex interplay through interrelated, but still partly understood, pathophysiological pathways, which mainly involve lipid toxicity (expressed through increased hepatic de novo lipogenesis, hepatic and peripheral insulin resistance, upregulated lipolysis, lipoprotein abnormalities, hyperinsulinemia), impaired autophagy, mitochondrial dysfunction, endoplasmic reticulum stress, adipose tissue dysfunction with a consequent latent inflammatory state, inflammasome activation, genetic and epigenetic factors, altered gut microbiota and finally dietary factors. In this review, based on data from recent studies and focusing mainly on common molecular mechanisms, we will highlight the common pathophysiological grounds and the interplay between NAFLD and T2DM.

Incidence and peri-operative risk factors for development of acute kidney injury in patients after cardiac surgery: A prospective observational study.

BACKGROUND: Patients admitted to intensive care unit (ICU) after cardiac surgery develop acute kidney injury (AKI) immediately post-operation. We hypothesized that AKI occurs mainly due to perioperative risk factors and may affect outcome. AIM: To assess peri-operative risk factors for AKI post cardiac surgery and its relationship with clinical outcome. METHODS: This was an observational single center, tertiary care setting study, which enrolled 206 consecutive patients, admitted to ICU after cardiac surgery. Patients were followed-up until ICU discharge or death, in order to determine the incidence of AKI, perioperative risk factors for AKI and its association with outcome. Univariate and multivariate logistic regression analysis was performed to assess predictor variables for AKI development. RESULTS: After ICU admission, 55 patients (26.7%) developed AKI within 48 h. From the logistic regression analysis performed, high EuroScore II (OR: 1.18; 95%CI: 1.06-1.31, P = 0.003), white blood cells (WBC) pre-operatively (OR: 1.0; 95%CI: 1.0-1.0, P = 0.002) and history of chronic kidney disease (OR: 2.82; 95%CI: 1.195-6.65, P = 0.018) emerged as independent predictors of AKI among univariate predictors. AKI that developed AKI had longer duration of mechanical ventilation [1113 (777-2195) vs 714 (511-1020) min, P = 0.0001] and ICU length of stay [70 (28-129) vs 26 (21-51) h, P = 0.0001], higher rate of ICU-acquired weakness (16.4% vs 5.3%, P = 0.015), reintubation (10.9% vs 1.3%, P = 0.005), dialysis (7% vs 0%, P = 0.005), delirium (36.4% vs 23.8%, P = 0.001) and mortality (3.6% vs 0.7%, P = 0.046). CONCLUSION: Patients present frequently with AKI after cardiac surgery. EuroScore II, WBC count and chronic kidney disease are independent predictors of AKI development. The occurrence of AKI is associated with poor outcome.

Circulating microvesicles across a population with various degree of cardiovascular burden are associated with systolic blood pressure.

Circulating microvesicles (MVs) have been studied in heterogeneous, divergent, and rather small patient populations with cardiovascular risk . Therefore, we measured endothelial (EMVs), platelet (PMVs) and erythrocyte (RMVs) MVs in patients with divergent cardiovascular risk. We then compared them to coronary artery disease (CAD) and healthy subjects and identified independent MVs' predictors. We enrolled consecutive patients from our Cardiology, Hypertension, Diabetic, Rheumatic, and Nephrology Outpatient Units with MVs measurements. Central blood pressure (BP) was measured by either applanation tonometry or Mobil-O-graph device, while MVs by a standardized flow cytometry protocol. We studied 369 participants with increased cardiovascular risk: 63 with high cardiovascular risk (47 diabetes mellitus type II/DM and 16 end-stage renal disease/ESRD), 92 with chronic inflammatory disorders and 73 with untreated essential hypertension/UEH. We further included 53 subjects with CAD and 87 otherwise healthy individuals. All MVs were lower in patients with increased cardiovascular risk compared to CAD, showing predictive value with high sensitivity and specificity. Furthermore, PMVs and EMVs were increased in patients with cardiovascular risk compared to healthy individuals. DM and ESRD patients had increased EMVs versus UEH and chronic inflammatory disorders. In the whole study population, RMVs were associated only with history of essential hypertension. In multivariate analysis, systolic BP predicted PMVs. Aage, systolic BP, and DM predicted EMVs. In a large population of patients with divergent cardiovascular risk, MVs are independently associated with systolic blood pressure.

Papillary thyroid microcarcinoma: clinicopathological characteristics and implications for treatment in 276 patients.

BACKGROUND: There is debate concerning the clinical significance of papillary thyroid microcarcinoma (PTMC), and therefore, the rise in the incidence of PTMC creates management dilemmas. The purpose of this study was to analyse the clinicopathological characteristics of PTMC in an island region that has a high prevalence of goitre and to determine risk factors for the worst prognosis. MATERIALS AND METHODS: Data from 1874 patients who underwent a total thyroidectomy between January 2002 and December 2008 were reviewed retrospectively. A total of 276 patients who were diagnosed with PTMC in a final pathology report were included in the study. A PTMC was defined as a papillary thyroid carcinoma with a diameter ≤ 10 mm. Clinicopathological features were evaluated by both univariate and multivariate analyses. RESULTS: Of the 276 patients with PTMC, 219 patients (79·3%) were incidentally diagnosed. Two hundred and two patients had carcinomas of ≤ 5 mm, and 74 patients presented with carcinomas that ranged in size from 0·6 to 1·0 cm. Lymph node metastasis was diagnosed in 3·5% of patients with tumours ≤ 5 mm, and 21·6% of patients presented tumours > 5 mm. Upon multivariate analysis, clinically suspected diagnosis, a tumour size > 5 mm and an age over 45 years at diagnosis were independent risk factors for capsule invasion, while tumour multifocality, bilaterality, size of tumour > 5 mm and thyroid capsule invasion were independent risk factors for lymph node metastasis at diagnosis. CONCLUSIONS: Patients presenting multifocal, bilateral PTMC with a maximum diameter > 5 mm and thyroid capsule invasion may have an increased risk of lymph node metastasis. These factors should be considered in the follow-up for these patients.

Plexiform (multinodular) schwannoma of soft palate. Report of a case.

Plexiform schwannoma is a rare benign neoplasm of the neural sheath characterized by a multinodular plexiform growth pattern. Only 5% of schwannomas have a plexiform or multinodular growth pattern. Schwannoma apparently derives from the Schwann cells. Extracranially, 25% of all schwannomas are located in the head and neck region, but only 1% show an intraoral origin. The intraoral lesions show a predilection for the tongue, followed by the palate, buccal mucosa, lip and gingival. Microscopic examination is necessary to confirm the diagnosis. Characteristic histological signs are the palisading of the spindle-shaped Schwann cells around the central acellular area, so called Verocay bodies. We report a case of a 21-year-old woman with a smooth mass of the soft palate that was gradually increasing. Surgical excision of the mass was done and the histopathology and immunohistochemistry study of the excised lesion revealed a multinodular plexiform schwannoma of the soft palate. The patient is under regular clinical control, with no signs of recurrence after 17 months. Plexiform schwannomas of the soft palate are mentioned very rarely in the English literature. This rare benign tumor is worthy of recognition because it can be misdiagnosed as plexiform neurofibroma.

Thromboinflammation in Sepsis and Heparin: A Review of Literature and Pathophysiology.

BACKGROUND/AIM: Thromboinflammation is the pathophysiologic mechanism in which coagulation and inflammation interact and complement each other. It is observed in a number of degenerative diseases, one of them being sepsis. Quiescent endothelial cells exert antithrombotic and anti-inflammatory actions that are reduced during sepsis. The concomitant effect of the subsequent dysregulation of coagulation and complement actuation is platelet activation and aggregation, and leukocyte recruitment, with detrimental effects on the vascular endothelium. Tissue factor and α-thrombin are major sentinels in the pathogenesis of this process. This literature review aimed to cover the basic principles of the mechanisms implicated in thromboinflammation occurring during sepsis and also investigates the role of heparin as a possible therapeutic agent, since it exhibits both anticoagulant and anti-inflammatory functions. MATERIALS AND METHODS: PubMed, SCOPUS and ScienceDirect databases were used for search of literature from inception to April 2022. To be included in our review, studies had to refer to the pathophysiologic mechanisms leading to coincident coagulation and inflammation, or to the administration of heparin either for treatment or prophylaxis, both in the context of sepsis. RESULTS: A total of 276 articles were drawn from the initial literature search. 124 were duplicated and out of the remaining 152 articles, 29 met our inclusion criteria and were reviewed. CONCLUSION: Clinical trials among sepsis patients have indicated that the thromboinflammatory process is more complex than believed, as adverse bleeding events continue to occur despite the use of anticoagulants with different pharmacodynamics. However, heparin has a pleiotropic effect that might provide protection against sepsis and related complications and merits further research.

A Novel Non-invasive Index of Cardiopulmonary Reserve for the Prediction of Failure of Weaning From Mechanical Ventilation.

PURPOSE: To develop an easy-to-implement prediction index of weaning failure for ICU patients. Materials and methods: We developed a prediction index modifying respiratory exchange ratio (RER), Mod-RER, a parameter measured during the cardiopulmonary exercise test (CPET) based on respiratory quotient. The Mod-RER index is the ratio of partial pressure of CO2 in central venous blood over the difference of partial pressure of O2 in arterial and central venous blood (Mod-RER=PcvCO2/PaO2-PcvO2, where PcvCO2 = partial pressure of CO2 in central venous blood, PaO2 = partial pressure of O2 in arterial blood, and PcvO2 = partial pressure of O2 in central venous blood). We prospectively tested its predictive value, compared to other indices of weaning outcome, in an observational study of difficult-to-wean ICU patients. RESULTS: Mod-RER index increased significantly only in failed trials and receiver operating characteristic (ROC) analysis for prediction of outcome based on Mod-RER index change had an area under the curve (AUC) 0.80 (p<0.001). Mod-RER change exhibited the highest sensitivity (84.6%) and specificity (78.1%) among the tested indices, with the optimal cut-off of 19.3%. Comparison of AUCs did not reach statistical significance (p=0.106). CONCLUSIONS: We conclude that Mod-RER index is an accurate, easy-to-use prediction tool of weaning failure, useful in decision making of timely extubation of ICU patients, especially in the demanding era of the coronavirus disease 2019 (COVID-19) pandemic.