Cell free DNA as a new prognostic biomarker for COVID-19, A prospective cohort study.

Predicting the need of hospitalization and intensive care in COVID-19 patients has been challenging with current diagnostic tests since the beginning of the pandemic. We aimed to test cell free DNA (cfDNA) as a novel biomarker for COVID-19 disease severity and mortality. cfDNA concentration was quantified by RT-PCR based test. One hundred and sixty-eight patients(85 outpatients, 61 inpatients,22 ICU) included the study. Mean initial plasma cfDNA levels were significantly different (p < 0.01) in outpatients (1.190,66 ng/ml), inpatients (8.258,10 ng/ml) and ICU patients (84.806,87 ng/ml). ROC analysis showed with 95 % specificity that patients with initial cfDNA concentrations ≥6.389 ng/ml need to be hospitalized and those ≥26.104 ng/ml require ICU referral. cfDNA concentration was correlated with neutrophil/lymphocyte ratio, lymphocyte level, CRP, AST, LDH, CK, fibrinogen, ferritin and D-dimer. Plasma cfDNA levels on admission, well correlating with disease severity and mortality in COVID-19 that found as a useful biomarker.

Effect of prone positioning on end-expiratory lung volume, strain and oxygenation change over time in COVID-19 acute respiratory distress syndrome: A prospective physiological study.

Background: Prone position (PP) is a recommended intervention in severe classical acute respiratory distress syndrome (ARDS). Changes in lung resting volume, respiratory mechanics and gas exchange during a 16-h cycle of PP in COVID-19 ARDS has not been yet elucidated. Methods: Patients with severe COVID-19 ARDS were enrolled between May and September 2021 in a prospective cohort study in a University Teaching Hospital. Lung resting volume was quantitatively assessed by multiple breath nitrogen wash-in/wash-out technique to measure the end-expiratory lung volume (EELV). Timepoints included the following: Baseline, Supine Position (S1); start of PP (P0), and every 4-h (P4; P8; P12) until the end of PP (P16); and Supine Position (S2). Respiratory mechanics and gas exchange were assessed at each timepoint. Measurements and main results: 40 mechanically ventilated patients were included. EELV/predicted body weight (PBW) increased significantly over time. The highest increase was observed at P4. The highest absolute EELV/PBW values were observed at the end of the PP (P16 vs S1; median 33.5 ml/kg [InterQuartileRange, 28.2-38.7] vs 23.4 ml/kg [18.5-26.4], p < 0.001). Strain decreased immediately after PP and remained stable between P4 and P16. PaO2/FiO2 increased during PP reaching the highest level at P12 (P12 vs S1; 163 [138-217] vs 81 [65-97], p < 0.001). EELV/PBW, strain and PaO2/FiO2 decreased at S2 although EELV/PBW and PaO2/FiO2 were still significantly higher as compared to S1. Both absolute values over time and changes of strain and PaO2/FiO2 at P16 and S2 versus S1 were strongly associated with EELV/PBW levels. Conclusion: In severe COVID-19 ARDS, EELV steadily increased over a 16-h cycle of PP peaking at P16. Strain gradually decreased, and oxygenation improved over time. Changes in strain and oxygenation at the end of PP and back to SP were strongly associated with changes in EELV/PBW. Whether the change in EELV and oxygenation during PP may play a role on outcomes in COVID-ARDS deserves further investigation. Clinical trial registration: [www.ClinicalTrials.gov], identifier [NCT04818164].

Air leaks in COVID-19 pneumonia.

The novel coronavirus infection 2019 (COVID-19), which was first identified in Wuhan, China in December 2019 and caused a pandemic, is mostly survived with mild symptoms, while invasive and non-invasive mechanical ventilation support is required in some patients. Pneumothorax, pneumomediastinum, and subcutaneous emphysema may develop in COVID-19 patients. In this study, cases of pneumothorax, pneumomediastinum, and subcutaneous emphysema in patients who were followed in the intensive care unit with the diagnosis of COVID-19 were evaluated. In conclusion, although rare, these complications can be fatal and increase the severity of the disease, which already has a high mortality rate in the intensive care unit. Early detection and management of these complications can reduce morbidity and mortality.

Incidence, Risk Factors, and Prognosis of Bloodstream Infections in COVID-19 Patients in Intensive Care: A Single-Center Observational Study.

BACKGROUND: Critically ill COVID-19 patients are prone to bloodstream infections (BSIs). AIM: To evaluate the incidence, risk factors, and prognosis of BSIs developing in COVID-19 patients in the intensive care unit (ICU). METHODS: Patients staying at least 48 h in ICU from 22 March 2020 to 25 May 2021 were included. Demographic, clinical, and laboratory data were analyzed. RESULTS: The median age of the sample (n = 470) was 66 years (IQR 56.0-76.0), and 64% were male. The three most common comorbidities were hypertension (49.8%), diabetes mellitus (32.8%), and coronary artery disease (25.7%). Further, 252 BSI episodes developed in 179 patients, and the BSI incidence rate was 50.2 (95% CI 44.3-56.7) per 1000 patient-days. The source of BSI is central venous catheter in 42.5% and lower respiratory tract in 38.9% of the episodes. Acinetobacter baumannii (40%) and carbapenem-resistant Klebsiella pneumoniae (21%) were the most common pathogens. CRP levels were lower in patients receiving tocilizumab. Multivariable analysis revealed that continuous renal replacement therapy, extracorporeal membrane oxygenation, and treatment with a combination of methylprednisolone and tocilizumab were independent risk factors for BSI. The estimated cumulative risk of developing first BSI episode was 50% after 6 days and 100% after 25 days. Of the 179 patients, 149 (83.2%) died, and a statistically significant difference (p < 0.001) was found in the survival distribution in favor of the group without BSI. CONCLUSION: BSI is a common complication in COVID-19 patients followed in the ICU, and it can lead to mortality. Failure in infection control measures, intensive immunosuppressive treatments, and invasive interventions are among the main factors leading to BSIs.

ACE2 and ANGII levels in patients with COVID-19 based on thoracic tomography findings and PCR test results.

INTRODUCTION: Reverse transcriptase polymerase chain reaction tests and thoracic tomography have been widely employed in the diagnosis of the disease, but doubts about their sensitivity still persist. Also there are controversial results about ACE2 and AngII levels according to the severity of disease. In this study, we aimed to analyze the ACE2 and AngII levels in patients with suspected COVID-19 based on polymerase chain reaction test results and thoracic tomography findings and to examine their relationship with disease severity. METHODOLOGY: Patients with suspected COVID-19 in the emergency department were divided into 4 groups according to thoracic tomography findings and PCR test results. The in-hospital mortality of patients was recorded. ACE2 and AngII levels in patients were analyzed according to groups and severity of the disease. RESULTS: ACE2 levels for the patients with suspected COVID-19 were significantly lower than in the control group, but AngII levels were higher (not statistically significant). The mean age and male sex ratio of patients who developed acute respiratory distress syndrome (ARDS) and died were significantly higher than those who survived. Whereas there was no difference in ACE2 levels in patients with severe diseases such as ARDS and mortality, their AngII levels were significantly lower. CONCLUSIONS: It can be suggested that decreased ACE2 levels combined with increased AngII levels are determinative at disease onset and in the development of lung damage. However, decreased AngII levels are more determinative in patients with severe diseases such as ARDS and mortality.

A pan-resistant Myroides odoratimimus catheter-related bacteremia in a COVID-19 patient and review of the literature.

Myroides spp. are opportunistic environmental Gram-negative bacteria. These affect mostly immunocompromised hosts and generally lead to soft tissue, and urinary tract infections. Bacteremia most commonly develop secondary to soft tissue or catheter related infections and may lead rarely to mortality. Myroides spp. are generally suscetible to fluoroquinolones, piperacillin/tazobactam, trimethoprim/sulfamethoxazole, carbapenems or tetracyclines however, pan-resistant isolates and multiple resistance genes have been reported in clinical isolates of Myroides spp. We report a pan-resistant Myroides odoratimimus bacteremia in a patient with severe COVID-19 ending with fatality and in this context a review of reported Myroides bacteremias are also described. In this study, a 64-year old male patient with history of coronary artery bypass was admitted to ICU with severe COVID-19 pneumonia accompanied by pneumomediastinum and pneumopericardium. Continous renal replacement therapy and extracorporeal membraneous-oxygenation were initiated due to acute renal failure and persistent hypercarbia/hypoxia, respectively. Within four weeks of hospitalization various episodes of bacteremia developed and multiple antibiotics were used. On the 5th week of follow-up, acute phase reactants increased and empirical broad spectrum antibiotics were initiated. Blood culture revealed Gram-negative rods. The patient became hypotensive and despite maximum medical care he was lost due to cardiac arrest. M. odoratimimus was identified by MALDI-TOF and the bacterium was pan-resistant. According to Center for Genomic Epidemiology results the strain was identified as M. odoratimimus PR63039 and the genome analysis revealed antibiotic resistance genes associated with resistance to beta-lactams (bla OXA-347, bla MUS-1, bla EBR-1), tetracyclines (tetX), sulfonamides (sul2), macrolides (ereD), (ermF).

Rapid and Effective Vitamin D Supplementation May Present Better Clinical Outcomes in COVID-19 (SARS-CoV-2) Patients by Altering Serum INOS1, IL1B, IFNg, Cathelicidin-LL37, and ICAM1.

BACKGROUND: We aimed to establish an acute treatment protocol to increase serum vitamin D, evaluate the effectiveness of vitamin D3 supplementation, and reveal the potential mechanisms in COVID-19. METHODS: We retrospectively analyzed the data of 867 COVID-19 cases. Then, a prospective study was conducted, including 23 healthy individuals and 210 cases. A total of 163 cases had vitamin D supplementation, and 95 were followed for 14 days. Clinical outcomes, routine blood biomarkers, serum levels of vitamin D metabolism, and action mechanism-related parameters were evaluated. RESULTS: Our treatment protocol increased the serum 25OHD levels significantly to above 30 ng/mL within two weeks. COVID-19 cases (no comorbidities, no vitamin D treatment, 25OHD <30 ng/mL) had 1.9-fold increased risk of having hospitalization longer than 8 days compared with the cases with comorbidities and vitamin D treatment. Having vitamin D treatment decreased the mortality rate by 2.14 times. The correlation analysis of specific serum biomarkers with 25OHD indicated that the vitamin D action in COVID-19 might involve regulation of INOS1, IL1B, IFNg, cathelicidin-LL37, and ICAM1. CONCLUSIONS: Vitamin D treatment shortened hospital stay and decreased mortality in COVID-19 cases, even in the existence of comorbidities. Vitamin D supplementation is effective on various target parameters; therefore, it is essential for COVID-19 treatment.

Role of plasma angiotensin II and angiotensin-converting enzyme 2 levels on prognosis and mortality in hypertensive patients with COVID-19.

Introduction: SARS-CoV-2 requires angiotensin-converting enzyme 2 (ACE2) to enter the cell. In our study, we aimed to investigate the role of angiotensin-converting enzyme 2 and angiotensin II plasma levels on prognosis and mortality in patients with isolated hypertension, patients with chronic diseases in addition to hypertension and patients with COVID-19 without comorbidities, in accordance with the use of renin-angiotensin-aldosterone system inhibitor. Materials & methods: In the study, patients diagnosed with COVID-19 were divided into three groups. Angiotensin II and ACE2 levels were compared by comorbidities, antihypertensive drugs used, intensive care hospitalization and termination of patients. The relationship between angiotensin II and ACE2 levels and service and intensive care times was investigated. Findings: A total of 218 patients were enrolled in our study, including 68 patients diagnosed with COVID-19 without comorbidities, 33 patients diagnosed with isolated hypertension and 117 patients with other chronic diseases in addition to hypertension. There was no statistically significant difference between the comorbid disease groups between angiotensin II and ACE2 levels of the patients enrolled in the study. The rate of patients admitted to the intensive care unit was 17.9%, and the mortality rate was 11.5%. Results: In our study, we did not obtain significant findings regarding angiotensin II and ACE2 levels on presentation that can be used in prognosis and mortality of COVID-19 patients and development of future treatment methods.

Tocilizumab in COVID-19: The Cerrahpasa-PREDICT score.

BACKGROUND: Cytokine release syndrome (CRS), characterized by overproduction of proinflammatory cytokines in the course of severe coronavirus disease 2019 (COVID-19), has been suggested as the major cause of mortality. Tocilizumab, a recombinant humanized monoclonal antibody against human IL-6 receptor, poses a therapeutic option for the treatment of CRS leading to severe acute respiratory syndrome in coronavirus-2 (SARS-CoV-2) infection. METHODS: We performed a single-center retrospective study to reveal the outcome of COVID-19 patients on tocilizumab and proposed "the Cerrahpasa-PREDICT score", a new clinical scoring system using clinical and laboratory parameters that would help predicting the 28-day mortality of COVID-19 patients receiving tocilizumab. RESULTS: Eighty-seven patients (median age: 59 years) were included of whom 75.8% were male. Tocilizumab use significantly improved clinical and laboratory parameters. The 28-day mortality rate on tocilizumab was 16.1%. The Cerrahpasa-PREDICT score, consisting of platelet counts, procalcitonin, D-dimer levels, SO2R and the time from symptom onset to tocilizumab administration had a positive predictive value of 94.5% and negative predictive value of 92.9% for anticipating 28-day mortality. CONCLUSIONS: Severe COVID-19 should closely be monitored for the signs of hyperinflammation. We showed that administration of tocilizumab early in the course of the disease (prior to ICU admission) resulted in a favorable outcome. Close monitoring usually aids identifying patients who would benefit from tocilizumab. In this regard, the Cerrahpasa-PREDICT score might serve as a practical tool for estimating the 28-day mortality in COVID-19 patients who received tocilizumab and would facilitate timely recognition of fatal cases to be evaluated for other therapeutic options.

Change in species distribution and antifungal susceptibility of candidemias in an intensive care unit of a university hospital (10-year experience).

Candidemia is a nosocomial infection mostly found in critically ill patients. Our objectives were to evaluate the change in distribution and resistance profile of Candida spp. isolated from candidemic patients in our intensive care unit over two 5-year periods spanning 15 years and to evaluate the risk factors. Records from the microbiology laboratory were obtained, from January 2004 to December 2008 and from January 2013 to December 2017, retrospectively. Antifungal susceptibility was performed by E-test and evaluated according to EUCAST breakpoints. A total of 210 candidemia cases occurred; 238 Candida spp. were isolated in 197 patients (58.8% male; mean age, 59.2 ± 19.6 years). The most predominant risk factor was central venous catheter use. Species distribution rates were 32%, 28%, 17%, and 11% for C. albicans (n = 76), C. parapsilosis (n = 67), C. glabrata (n = 40), and C. tropicalis (n = 27), respectively. Resistance rate to anidulafungin was high in C. parapsilosis over both periods and increased to 73% in the second period. Fluconazole showed a remarkable decrease for susceptibility in C. parapsilosis (94 to 49%). The prevalence of MDR C. parapsilosis (6%/33%) and C. glabrata (0%/44%) increased in the second period. We observed a predominance of non-albicans Candida spp., with C. parapsilosis being the most frequent and C. glabrata infections presenting with the highest mortality. High level of echinocandin resistance in C. parapsilosis and increasing prevalences of MDR C. parapsilosis and C. glabrata seem emerging challenges in our institution.

Sedation Practices and Preferences of Turkish Intensive Care Physicians: A National Survey.

OBJECTIVE: Sedation is one of the most common practices applied in the intensive care units (ICUs), and the management of sedation, analgesia and delirium is a quality measure in the ICUs. Several guidelines on sedation had been published, and many surveys investigated the practices of sedation in the ICUs, but knowledge on the sedation practices in Turkey is lacking. The aim of the present study was to provide baseline knowledge on the sedation practices and preferences of Turkish intensive care physicians and to establish some points to be improved. METHODS: An electronic survey form consisting of 34 questions was generated and posted to email addresses. The survey included questions about demographics and practices on sedation, analgesia, neuromuscular blockage and delirium. RESULTS: Of 1700 email addresses, 429 (25.0%) were returned. Sedation was practised by 98.0% of the respondents, and mechanical ventilation was indicated as the primary indication (94.0%) for sedation. The presence of a written sedation protocol was 37.0%. For drug choices for sedation, midazolam was the most preferred agent (90.0%). With regard to pain questions, the most commonly used evaluation tool was Visual Analogue Scale (69.0%), and the most preferred drug was tramadol. Nearly half of the participants routinely evaluated delirium and used the confusion assessment method in the ICU. CONCLUSION: The results of this survey have indicated some areas to be improved, and a national guideline should be prepared taking pain, agitation and delirium in focus. ClinicalTrials.gov ID: NCT03488069.

Edema laringotraqueal a causa de una lesión térmica: Complicación tras una tiroidectomía en niños / Laryngotracheal edema due to thermal injury: A complication after thyroidectomy in children

La insuficiencia respiratoria posoperatoria es una complicación grave de la tiroidectomia, y su origen puede ser multifactorial, especialmente en los niños. Presentamos el caso de dos hermanos sometidos a una tiroidectomia que luego tuvieron dificultad respiratoria. Para la disección de la tiroides se emplearon un bisturí armónico y el sistema de sellado vascular bipolar electrotérmico. Ambos pacientes presentaron problemas para respirar tempranamente en el posoperatorio. El hermano mayor tuvo dificultad respiratoria leve durante 24 horas, que se resolvió espontáneamente. Se extubó a la hermana menor, pero tuvo estridor grave acompañado de tiraje intercostal y retracción abdominal. Se la volvió a intubar y se la trasladó a la UCI, donde se la conectó a un respirador. Permaneció en la UCI durante 14 días debido a múltiples intentos fallidos de extubación. Es probable que los síntomas fueran más graves en la niña pequeña debido a que la pared de la tráquea era más blanda y los cartílagos, más débiles. Es necesario considerar las posibles complicaciones respiratorias posoperatorias a causa de una lesión térmica o una técnica quirúrgica inadecuada tras una tiroidectomía.

Postoperative respiratory insufficiency is a serious complication of total thyroidectomies which can be multifactorial, especially in children. We report two siblings who had undergone thyroidectomy with subsequent respiratory distress. Electrothermal bipolar and harmonic scalpel were used during thyroid dissections. Both patients had early postoperative respiratory problems. The older one suffered from mild respiratory distress for 24 hours and then he spontaneously recovered. The younger one was extubated but then she had serious stridor accompanied with abdominal and intercostal retractions. She was re-intubated and admitted to ICU for mechanical ventilatory support, where she stayed for 14 days due to multiple failed extubation attempts. The symptoms were more severe in the younger child probably due to softer tracheal wall and weaker tracheal cartilages. We should keep in mind the probable postoperative respiratory complications due to thermal injury or inappropriate surgical technique after thyroid surgeries.

Laryngotracheal edema due to thermal injury: A complication after thyroidectomy in children. / Edema laringotraqueal a causa de una lesión térmica: Complicación tras una tiroidectomía en niños.

Postoperative respiratory insufficiency is a serious complication of total thyroidectomies which can be multifactorial, especially in children. We report two siblings who had undergone thyroidectomy with subsequent respiratory distress. Electrothermal bipolar and harmonic scalpel were used during thyroid dissections. Both patients had early postoperative respiratory problems. The older one suffered from mild respiratory distress for 24 hours and then he spontaneously recovered. The younger one was extubated but then she had serious stridor accompanied with abdominal and intercostal retractions. She was re-intubated and admitted to ICU for mechanical ventilatory support, where she stayed for 14 days due to multiple failed extubation attempts. The symptoms were more severe in the younger child probably due to softer tracheal wall and weaker tracheal cartilages. We should keep in mind the probable postoperative respiratory complications due to thermal injury or inappropriate surgical technique after thyroid surgeries.

La insuficiencia respiratoria posoperatoria es una complicación grave de la tiroidectomía, y su origen puede ser multifactorial, especialmente en los niños. Presentamos el caso de dos hermanos sometidos a una tiroidectomía que luego tuvieron dificultad respiratoria. Para la disección de la tiroides se emplearon un bisturí armónico y el sistema de sellado vascular bipolar electrotérmico. Ambos pacientes presentaron problemas para respirar tempranamente en el posoperatorio. El hermano mayor tuvo dificultad respiratoria leve durante 24 horas, que se resolvió espontáneamente. Se extubó a la hermana menor, pero tuvo estridor grave acompañado de tiraje intercostal y retracción abdominal. Se la volvió a intubar y se la trasladó a la UCI, donde se la conectó a un respirador. Permaneció en la UCI durante 14 días debido a múltiples intentos fallidos de extubación. Es probable que los síntomas fueran más graves en la niña pequeña debido a que la pared de la tráquea era más blanda y los cartílagos, más débiles. Es necesario considerar las posibles complicaciones respiratorias posoperatorias a causa de una lesión térmica o una técnica quirúrgica inadecuada tras una tiroidectomía

Chediak-Higashi syndrome in the intensive care unit.

Chediak-Higashi Syndrome is a rare autosomal recessive disease characterized by recurrent infections, giant cytoplasmic granules and oculocutaneous albinism. We describe the clinical and laboratory findings of a patient with Chediak-Higashi syndrome who was diagnosed and treated in the intensive care unit because of bleeding tendency after surgery.