Favipiravir for the treatment of COVID-19 pneumonia: Can we predict the response to treatment?

INTRODUCTION: Early experience with favipiravir in the treatment of COVID-19 is promising, but no clinical data have been published in medical journals. This study aimed to review the experience with favipiravir treatment for COVID-19 pneumonia and to examine whether there are any predictors of treatment response. METHODOLOGY: Fifty-six patients with severe or progressive pneumonia associated with COVID-19 who were treated with favipiravir monotherapy for at least five days were included in this retrospective study. Treatment response was defined as clinical recovery without any need for admission into the intensive care unit and/or anti-cytokine therapy. The demographic, clinical, laboratory and radiographic features of the patients were compared between favipiravir-responders and non-responders. RESULTS: Of the 56 patients, 34 patients (60.7%) responded to treatment and recovered. There was no difference in the demographic, clinical, and radiographic findings between the responders and non-responders. The inflammatory biomarkers were also similar except for the CRP levels on the day favipiravir was started [74 (36-111) vs. 118.5 (46.5-203) mg/L, respectively, p = 0.043]. There was also a significant difference in the median time to defervescence [1 (1-2) vs. 3.5 (1.75-9.25) days, respectively]. Of clinical interest, 27 (79.4%) and 31 (91.2%) of the responders became afebrile within two and four days, respectively. The response rate was lower in patients who presented severe pneumonia associated with respiratory failure. CONCLUSIONS: Patients with non-severe pneumonia at admission and whose fever resolved within two days of treatment are more likely to improve with favipiravir.

COVID-19-Related Stigma and Mental Health of Children and Adolescents During Pandemic.

This cross-sectional study aimed to evaluate depression and anxiety symptoms of the children/grandchildren of COVID-19 patients, children/grandchildren of healthcare workers who have not infected COVID-19, and children/grandchildren of the control group. Parent and children's perception about COVID-19-related stigma is also investigated and compared between groups. The perception about COVID-19-related stigma between different age and gender groups among children also investigated and compared. The mental health of the 71 participants aged 6-18 years was evaluated via a telemedicine-based semi-structured interview between March and April 2020. Children's Depression Inventory (CDI), the Screen for Child Anxiety-Related Emotional Disorders (SCARED), and COVID-19-Related Stigma Form were administered to the participants. A significant negative correlation was found between age and separation anxiety disorder (p = .005) and a significant positive correlation was found between age and generalized anxiety disorder (p = .035) in the SCARED-Child report. Generalized anxiety disorder was found to be higher in females compared to males. A significant difference was found between the groups of parents in the COVID-19-Related Stigma Form. Patients infected with COVID-19, healthcare workers, and the control group have different perceptions about COVID-19-related stigma. The age of the children have an impact on stigma perceptions. Anxiety symptoms of children affected by age and gender. Future studies are recommended to determine the other factors associated with perceptions about COVID-19-related stigma among children and parents.

The Efficacy of Hydroxychloroquine and Azithromycin Combination Therapy on Hospital Mortality in COVID 19 Pneumonia Patients.

BACKGROUND/AIM: Effective therapeutic approaches for SARS-CoV-2 pandemic are urgently needed. Hydroxychloroquine (HCQ) alone or in combination with azithromycin has been used in several countries, without any clear evidence. This study aimed to determine the effectiveness and safety of hydroxychloroquine as compared to hydroxychloroquine and azithromycin combination in patients with COVID-19 pneumonia. MATERIALS AND METHODS: This retrospective study evaluated all patients admitted to two university hospitals between 18 March and 20 May 2020 with the diagnosis of COVID-19 pneumonia. Out of 496 patients, 370 met the eligibility criteria and were included in the final analysis. The primary outcome was in-hospital mortality. Secondary outcomes were time to recovery, presence of severe acute respiratory infection (SARI), the requirement for oxygen therapy, and/or mechanical ventilation, length of hospital stay, and adverse events. RESULTS: A total of 222 patients received hydroxychloroquine and 148 were treated with HCQ and azithromycin combination. The in-hospital mortality rates were similar in the two groups (10.8% vs. 6.8%, respectively, p=0.186). Additionally, the needs for oxygen therapy, invasive mechanic ventilation (IMV) and intensive care unit (ICU) admission were not different. The rate of the requirement of non-invasive mechanic ventilation (NIV) was higher in patients receiving HCQ plus azithromycin (10.1% vs. 4.5%, p=0.035). Time to recovery was 3.5 days in HCQ and 5.0 days in HCQ plus azithromycin group (p<0.001). The median length of hospital stay was longer in patients with the combination therapy (7.0 vs. 5.5 days, p<0.001). Amongst all patients, only 3 patients developed electrocardiographic changes needing discontinuation of therapy. LIMITATIONS: Observational design of the study is the main limitation. CONCLUSIONS: The present findings suggest that adding azithromycin to HCQ is not associated with any improvement in clinical outcome and mortality in patients with COVID-19 pneumonia and supports the current knowledge not to include azithromycin in the initial treatment of COVID-19.

Clinical Outcome of PCR-Negative COVID-19 Patients: A Retrospective Study.

OBJECTIVE: To evaluate the clinical features and outcomes of patients who were admitted with a diagnosis of coronavirus disease 2019 (COVID-19) but who were not confirmed with polymerase chain reaction (PCR) positivity. MATERIAL AND METHODS: This is a retrospective analysis of all patients admitted to two tertiary care centers between March 15 and May 15, 2020, with a diagnosis of COVID-19. From a common database prepared for COVID-19, we retrieved the relevant data and compared the clinical findings and outcomes of PCR-positive patients with those of PCR-negative cases who had been diagnosed on the basis of typical clinical and radiographic findings. RESULTS: A total of 349 patients were included in the analysis, of which 126 (36.1%) were PCR-negative. PCR-negative patients were younger (54.6 ± 20.8 vs. 60.8 ± 18.9 years, P = .009) but were similar to PCR-positive patients in terms of demographics, comorbidities, and presenting symptoms. They had higher lymphocyte counts (1519 ± 868 vs. 1331 ± 737/mm3, P = .02) and less frequently presented with bilateral radiographic findings (68.3% vs. 79.4%, P = .046) than PCR-positive patients. Besides, they had less severe disease and better clinical outcomes regarding admission to the intensive care unit (9.6% vs. 20.6%, P = .023), oxygen therapy (21.4% vs. 43.5%, P < .001), ventilatory support (3.2% vs. 11.2%, P = .03) and length of hospital stay (5.0 ± 5.0 vs. 9.7 ± 5.9 days, P < .001). CONCLUSION: This study confirms that about one-third of the COVID-19 patients are PCR-negative and diagnosed based on clinical and radiographic findings. These patients have a more favorable clinical course, shorter hospital stays, and are less frequently admitted to the intensive care unit.

Communication: The Follow-Up of Biomarkers Better Predicts the Poor Outcome in COVID-19 Patients.

OBJECTIVE: To investigate the course of biomarkers on admission and follow-up in order to identify early predictors for poor outcome in COVID-19 patients. METHODS: In this study, 132 COVID-19 patients were classified as good outcome (n=62) and poor outcome (n=70) groups. Laboratory parameters were evaluated on admission and within 5-7 days after hospitalization. RESULTS: Baseline levels of neutrophil-lymphocyte ratio, CRP, procalcitonin, ferritin, D-dimer and LDH were higher (p<0.01); lymphocyte count was lower in the poor outcome patients. During follow-up there was a larger decrease in lymphocyte count and more prominent increases in other biomarkers (p<0.001). In ROC analysis, the AUCs strongly indicated the poor outcome on days 5-7 of the hospitalization. CONCLUSIONS: This study suggests that the follow-up measurements of the biomarkers better predict the poor outcome in COVID-19 pneumonia.

[Pneumococcal infections and protection with vaccination in adult chronic lung diseases]. / Eriskin kronik akciger hastaliklarinda pnömokok infeksiyonu ve asi ile korunma.

Pneumococcal infections are an important cause of mortality and morbidity in Chronic Lung Diseases. However, exacerbations, which make the treatment of diseases very difficult, and corticosteroids used during treatment carry a great risk of pneumococcal infection and adversely affect the treatment. The most rational way to reduce the negative impact of pneumococcal infections on the clinical and economic burden of Chronic Lung Diseases is vaccination of the risky population. Although, vaccination recommendations are well defined, recommended by national and international guidelines and are paid by health authorities, in Turkey, vaccination rates in adults with chronic lung disease is far below the expected. Since physicians are considered to be the most important and reliable resource that can guide their patients in vaccination, applying pneumococcal vaccination routinely in all patients with chronic lung diagnosis and making it a part of daily practice will greatly contribute to reducing the clinical and economic burden of pneumococcal infections in these patients. In this review, the effects of pneumococcal diseases on chronic lung diseases, the risk and clinical burden of pneumococcal diseases in chronic lung diseases are discussed in the light of guidelines and current literature, and the importance of protection from pneumonia in these patients is emphasized. In addition to general information and efficacy data about pneumococcal vaccines available in our country, application methods and access routes to vaccines are also described.

Factors affecting TST level in patients undergoing dialysis: a multicenter study.

INTRODUCTION: The risk of TB is increased in patients with chronic kidney disease (CKD) when compared with individuals with normal renal function. We aimed to determine tuberculin skin test (TST) response and the factors which might affect the response in patients with CKD undergoing dialysis in this study. METHODS: The purified protein derivative solution was administered to the patients and the diameter of induration was measured. Additionally, the age, gender and smoking status of the patients were interrogated. Comorbidities were recorded both by patients' self-reports and data from the hospital files. The number of Bacille Calmette-Guerin (BCG) scars was recorded by checking both shoulders. FINDINGS: The study was conducted with a total of 371 patients (194 men and 177 women). The mean age was 60.09 ± 15.88, TST was 6.99 ± 6.9, duration of dialysis was 4.44 ± 4.5 (3.8-0.1,24). A total of 229 patients have comorbodities (61.7%, the most frequent was hypertension). Logistic regression model was performed. Gender, vitamin D treatment and high parathormone (PTH) levels remained in the final stage of the analysis and vitamin D intake and PTH levels were detected to be statistically significant (P = 0.002, 0.007, respectively). DISCUSSION: This study is the first study which showed a correlation between TST negativity and increased PTH levels and receiving vitamin D treatment. Starting from this point, it was concluded that PTH may suppress the immune system and especially cellular immunity.

Role of Toll-Like Receptors in Tuberculosis Infection.

BACKGROUND: One-third of the world's population is infected with Mycobacterium tuberculosis. Investigation of Toll-like receptors (TLRs) has revealed new information regarding the immunopathogenesis of this disease. Toll-like receptors can recognize various ligands with a lipoprotein structure in the bacilli. Toll-like receptor 2 and TLR-4 have been identified in association with tuberculosis infection. OBJECTIVES: The aim of our study was to investigate the relationship between TLR polymorphism and infection progress. METHODS: Twenty-nine patients with a radiologically, microbiologically, and clinically proven active tuberculosis diagnosis were included in this 25-month study. Toll-like receptor 2 and TLR-4 polymorphisms and allele distributions were compared between these 29 patients and 100 healthy control subjects. Peripheral blood samples were taken from all patients. Genotyping of TLR-2, TLR-4, and macrophage migration inhibitory factor was performed. The extraction step was completed with a Qiagen mini blood purification system kit (Qiagen, Ontario, Canada) using a peripheral blood sample. The genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: In total, 19 of the 29 patients with tuberculosis infection had a TLR-2 polymorphism, and 20 of the 100 healthy subjects had a TLR-2 polymorphism (P < 0.001). The TLR-4 polymorphism and interferon-γ allele distributions were not statistically correlated. CONCLUSIONS: Toll-like receptor 2 polymorphism is a risk factor for tuberculosis infection. The limiting factor in this study was the lack of investigation of the interferon-γ and tumor necrosis factor-α levels, which are important in the development of infection. Detection of lower levels of these cytokines in bronchoalveolar lavage specimens, especially among patients with TLR-2 defects, will provide new data that may support the results of this study.

Clinical factors and comorbidities affecting the cost of hospital-treated COPD.

PURPOSE: We aimed to assess the effects of comorbidities on COPD costs and to investigate the relationship between comorbidities and clinical variables. PATIENTS AND METHODS: All patients hospitalized with a diagnosis of COPD exacerbation between January 1, 2014, and December 31, 2014, at all state hospitals of Aydin province, a city located in the western part of Turkey, were included in this study. The costs examined in the study pertained to medications, laboratory tests, hospital stays, and other treatment-related factors, such as consumption of materials, doctor visits, and consultation fees. RESULTS: A total of 3,095 patients with 5,237 exacerbations (mean age, 71.9±10.5 years; 2,434 males and 661 females) were evaluated. For 880 of the patients (28.9%), or 3,852 of the exacerbations (73.1%), at least one comorbid disease was recorded. The mean cost of each exacerbation was $808.5±1,586, including $325.1±879.9 (40.7%) for hospital stays, $223.1±1,300.9 (27.6%) for medications, $46.3±49.6 (0.9%) for laboratory expenditures, and $214±1,068 (26.5%) for other treatment-related factors, such as consumption of materials, doctor visits, and consultation fees. The cost of each exacerbation was $1,014.9 in patients with at least one comorbidity, whereas it was $233.6 in patients without comorbidity (P<0.001). Age >65 years, female gender, hospitalization in an intensive care unit, invasive or noninvasive mechanical ventilation, and a long duration of hospitalization were all found to be significant factors in increasing total costs during the exacerbations requiring hospitalization (P<0.05 for all). CONCLUSION: Comorbidities have an important role in the total costs of acute exacerbations of COPD. Strategies for the prevention, diagnosis, and effective management of comorbidities would decrease the overall financial burden associated with acute exacerbations of COPD.

ERCC1 expression does not predict survival and treatment response in advanced stage non-small cell lung cancer cases treated with platinum based chemotherapy.

BACKGROUND: ERCC1 is considered as a promising molecular marker that may predict platinum based chemotherapy response in non small cell lung cancer patients. We therefore investigated whether its expression is indeed associated with clinical outcomes in advanced stage NSCLC patients. MATERIALS AND METHODS: Pretreatment tumor biopsy samples of 83 stage 3B and 4 non-small cell lung cancer patients treated with platinum based chemotherapy were retrospectively analyzed for immunohistochemical ERCC1 expression. None of the patients received curative surgery or radiotherapy. RESULTS: By calculating H- scores regarding the extent and intensity of immunohistochemical staining of tumor biopsy samples, ERCC1 expression was found to be positive in 50 patients (60.2%). ERCC1 positive and negative groups had no statistically significant differences regarding treatment response, progression free survival and overall survival (respectively p=0.161; p=0.412; p=0.823). CONCLUSIONS: In our study we found no association between ERCC1 expression and survival or treatment response. The study has some limitations, such as small sample size and retrospective analysis method. There is need of more knowledge for use of ERCC1 guided chemotherapy regimens in advanced stage NSCLC.

Can impairments of thyroid function test affect prognosis in patients with respiratory failure?

Thyroid function test (TFT) impairments can be detected in extrathyroidal dysfunction, primarily in chronic obstructive pulmonary disease (COPD) with acute respiratory failure (RF). The aims of this study were to: (i) evaluate TFT impairments in patients with RF, (ii) compare TFT results to a control group without RF and (iii) assess the effects of thyroid dysfunction on clinical outcome and prognosis of RF. The TFT parameters were assessed in 65 patients (65.0 +/- 10.0 years, 49 males) with RF and compared to 18 patients (64.4 +/- 9.8 years, 13 males) with lung disease and no RF (p> 0.05). Arterial blood gas analysis, free T3 (FT3), free T4 (FT4) and TSH levels were all measured. The impairments of TFT were demonstrated in 34 (52.3%) patients with RF and 8 (44.4%) patients without RF (p> 0.05). The most common finding was a decrease in at least one of the TFT parameters in both groups (43.1% vs. 44.4%, respectively). In RF group, there was no significant association between TFT results and gender, age, diagnosis and co-morbid disease. However, need for invasive mechanical ventilation was higher both in patients with low FT3 and low FT4 when compared to those with normal TFT results (p= 0.001 and p= 0.003, respectively). In-hospital mortality rate was also higher both in the patients with low FT3 and low FT4 than the others (p= 0.006 and p= 0.01, respectively). We conclude that TFT impairments are not observed more frequently in patients with RF when compared to the patients without RF. However, low FT3 and FT4 levels increase the rates of invasive mechanical ventilation and mortality.

Exudative pleural effusion due to brucellosis in a patient with chronic obstructive pulmonary disease.

Pleural involvement is a rare presentation of brucellosis. We report a patient referred for the evaluation of fever, right-sided pleural effusion and hilar lymph node enlargement. The pleural fluid revealed exudative characteristics with the predominance of neutrophils. Brucella melitensis was isolated from bone marrow, pleural effusion and blood cultures. The diagnosis was also confirmed by demonstration of a high Brucella agglutinin titre. The patient was successfully treated with rifampicin and doxicycline for three months.

[Surgical results of large cell neuroendocrine carcinoma of the lung]. / Akcigerin büyük hücreli nöroendokrin karsinomunda cerrahi tedavi sonuçlari.

Large cell neuroendocrine carcinoma is rare in the group of primary lung cancers and its appropriate treatment and prognosis are controversial. In this report, patients diagnosed as large cell neuroendocrine carcinoma of the lung were presented and discussed in the light of pertaining literature. Between February 1997 and March 2005, eight patients, who were diagnosed as large cell neuroendocrine carcinoma postoperatively among the patients with a preoperative diagnosis of nonsmall cell lung cancer, were analyzed retrospectively, by means of treatment method, disease free survival and overall survival. All eight patients were male and their mean age and age range were 64 +/- 7.6 and 50-72, respectively. Four patients had lobectomy, two had pneumonectomy and two had limited resections. One patient received neoadjuvant chemotherapy and seven patients received adjuvant chemotherapy, radiotherapy, or chemoradiotherapy. Follow-up period was 19.7 +/- 12.5 (3-39) months and disease-free interval was 19 +/- 12.9 (3-39) months. Two patients died of recurrence 14 and 16 months postoperatively, whereas six of the cases are alive with disease-free. Large cell neuroendocrine carcinomas are aggressive tumors with poor prognosis but better prognosis is also revealed after surgery at early stages. Most of the series in the literature are small in number of patients, as in our report, and treatment strategies are tried to be formed according to these data.

Plasma and bronchoalveolar lavage fluid levels of endothelin-1 in patients with chronic obstructive pulmonary disease and pulmonary hypertension.

BACKGROUND: Secondary pulmonary hypertension (PH) and cor pulmonale are the major clinical cardiovascular complications affecting prognosis in patients with chronic obstructive pulmonary disease (COPD). It is also known that endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by the pulmonary vascular endothelium, and ET-1 may be implicated in the pathogenesis of PH. OBJECTIVES: The purpose of this study was to investigate the presence of ET-1 in patients with COPD and to assess the correlation of ET-1 levels in the plasma and bronchoalveolar lavage (BAL) fluid (BALF) in COPD patients with or without PH. METHODS: Twenty-two patients with COPD and 15 healthy controls were enrolled in the study. Peripheral venous blood samples were collected in all patients and controls. BAL was obtained in COPD patients, and ET-1 levels were measured by radioimmunoassay in all plasma and BALF samples. RESULTS: Plasma ET-1 levels were 2.46 +/- 0.55 and 1.70 +/- 0.42 pmol/dl in patients with COPD and controls, respectively (p < 0.0001). Sixteen of the 22 patients with COPD (73%) had PH established by echocardiography. The ET-1 level in these patients amounted to 2.59 +/- 0.50 pmol/dl, and it was 2.10 +/- 0.54 pmol/dl in 6 patients with COPD without PH. In COPD patients with and without PH, BALF ET-1 levels were 0.19 +/- 0.08 and 0.24 +/- 0.01 pmol/dl, respectively (p > 0.05). CONCLUSIONS: These results suggest that ET-1 is detectable in both the peripheral blood and BALF of COPD patients, but the levels do not statistically differ between patients with and without PH.

The role of Tc-99m sestamibi imaging in predicting clinical response to chemotherapy in lung cancer.

Multidrug resistance (MDR) is a major problem in lung cancer. Tc-99m methoxyisobutyl isonitrile (MIBI) has been demonstrated to be a non-invasive marker to diagnose MDRI related P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP) expression in various solid tumors. The aim of this study was to evaluate the relationship between the degree of Tc-99m MIBI uptake and its retention on delayed images and the response to chemotherapy in lung cancer. Twenty-three patients (1 woman and 22 men, age range 40-67 years) with lung cancer (9 small cell and 14 non-small cell) were examined with Tc-99m MIBI imaging before chemotherapy. After i.v. administration of 740 MBq Tc-99m MIBI, planar and SPECT imaging at 30 minutes and 2 hours was performed. Tumor to normal lung uptake ratio (T/N) and percent retention were measured. Response to chemotherapy was evaluated according to follow-up CT and grouped as complete responders (CR), partial responders (PR) and non-responders (NR). Clinical follow-up and CT evaluation revealed that 12 patients had partial remission, 4 patients had complete remission and 7 patients had no-remission after chemotherapy. Statistically, there was no significant correlation between early (30 min), delayed (2 hr) T/N ratios and percent retention of Tc-99m MIBI with chemotherapeutic response of the lung cancer among the three groups (p > 0.05). Results of the current study imply that Tc-99m MIBI uptake and the retention index may not correlate with chemotherapy response in lung cancer, so that the accuracy of this method needs to be verified in a larger series with additional investigation at the molecular level.

Technetium-99m-DTPA aerosol scintigraphy in amiodarone induced pulmonary toxicity in comparison with Ga-67 scintigraphy.

Amiodarone hydrochloride, which is used in life-threatening cardiac tachyarrhythmia, has been known to cause amiodarone induced pulmonary toxicity (AIPT) as a complication. In this study we aimed to investigate the clinical value of technetium-99m diethylene triamine penta-acetic acid (DTPA) aerosol lung scintigraphy in patients with AIPT in comparison with gallium-67 (Ga-67) scan. The study group included 26 cases, 7 patients with diagnosis of AIPT (Group A), 8 patients receiving amiodarone therapy but without AIPT (Group B) and 11 healthy subjects as a control group (Group C). All patients underwent Ga-67 and Tc-99m-DTPA aerosol scintigraphy in addition to various laboratory tests, Ga-67 scintigraphy was positive in 4 of 7 AIPT patients but quite normal in Group B. A positive correlation was found (r = 0.52, p < 0.05) between kep values determined by Tc-99m-DTPA aerosol scintigraphy and the cumulative dose of amiodarone. The mean kep values were 2.04% +/- 0.85%/min, 1.30% +/- 0.42%/min and 0.86% +/- 0.19%/min for groups A, B and C, respectively. The mean clearance rate of group A was significantly faster than that of normals (p < 0.0005) and group B (p = 0.028). In addition, there was a significant difference between groups B and C (p = 0.015). In conclusion, Ga-67 lung scintigraphy is a useful method for the detection of AIPT but Tc-99m-DTPA aerosol scintigraphy offers better results than Ga-67 scintigraphy. Early changes in Tc-99m-DTPA clearance may be observed in patients receiving amiodarone. The kep value in patients with AIPT is noticeably increased with respect to the control group. With its favorable physical properties, low cost, lower radiation burden and its ability to be used as an objective measure for the pulmonary clearance rate, Tc-99m-DTPA aerosol scintigraphy appears to be promising in patients receiving amiodarone therapy.