Association between ACE (rs4343 and rs1799752), AGTR1 (rs5186), and PAI-1 (rs2227631) polymorphisms in the host and the severity of Covid-19 infection.

OBJECTIVE: It is necessary to identify appropriate clinical, biochemical, epidemiological and genetic biomarkers to elucidate the underlying mechanisms of the coronavirus disease-2019 (COVID-19) disease. The study focused on not only the link between disease severity (non-intense unit care (non-ICU) versus intensive unit care (ICU) and genetic susceptibility in COVID-19 patients but also the connection between comorbidity and genetic susceptibility affecting the severity of COVID-19. SUBJECT AND METHODS: One hundred and sixty-two COVID-19 patients treated in the non-ICU and ICU in Kayseri City Hospital were included. All volunteers underwent a physical examination and biochemical evaluation. Angiotensin-converting enzyme (ACE p.T776T G > A(rs4343) and g.16471_16472delinsALU (also referred to as I/D polymorphism; rs1799752), angiotensin II receptor type-1 (AGTR1) c.*86A > C (also referred to as A1166C; rs5186), and plasminogen activator inhibitor-1 (PAI-1-844 G > A (rs2227631) polymorphisms were analysed as well. RESULTS: To have ACE "ID" genotype did not change the severity of the disease (OR: 0.92, 95% CI: 0.41-2.1, p = 0.84), but decreased the mortality risk 2.9-fold (OR: 2.9, 95% CI: 1.1-7.0, p = 0.03). In PAI-1-844 G > A, having the "AA" genotype in the "A" recessive model increased the risk of the diabetes mellitus (DM) 2.3-fold (OR: 2.3 95%, CI: 1.16-4.66, p = 0.018). In the "G" recessive model, to have the GG genotype increased the risk of chronic kidney disease (CKD) 4.8-fold (OR:4.8, 95% CI: 1.5-15.5, p = 0.008). "GG" genotype in the DM group had a higher fibrinogen level compared to those with the "AG" genotype (AG:4847.2 mg/L (1704.3) versus GG:6444.67 mg/L (1861.62) p = 0.019) and "AA" genotype in the CKD group had lower platelet levels and those with "GG" had higher platelet levels (AA:149 µL (18-159) versus GG: 228 µL (146-357) p = 0.022). CONCLUSION: This study was shown that genetic predispositions that causes comorbidities were also likely to affect the prognosis of COVID-19.

Melatonin as a radioprotective agent against flattening filter and flattening filter-free beam in radiotherapy-induced lung tissue damage.

BACKGROUND: Radiotherapy is a widely used treatment method in oncology, applied by delivering high-energy particles or waves to the tumor tissue. Although tumor cells are targeted with radiotherapy, it can cause acute or long-term damage to healthy tissues. Therefore, the preservation of healthy tissues has been an important subject of various scientific researches. Melatonin has been shown to have a radioprotective effect on many tissues and organs such as liver, parotid gland, brain, and testicles. This study aimed to evaluate the protective effect of melatonin against the radiation at various doses and rates administered to the lung tissue of healthy mice. METHODS: This study was a randomized case-control study conducted with 80 rats comprising 10 groups with eight animals per group. Of the 10 groups, first is the control group, which is not given any melatonin, and second is the group that does not receive RT, which is given only melatonin, and the other eight groups are RT groups, four with melatonin and four without melatonin. RESULTS: There was no statistical difference in terms of histopathological findings in the lung tissue between the second group, which did not receive radiotherapy and received only melatonin, and the control group. Lung damage due to radiotherapy was statistically significantly higher in the groups that did not receive melatonin compared to the groups that received melatonin. CONCLUSIONS: This study revealed that melatonin has a protective effect against the cytotoxic damage of RT in rats receiving RT.

Deciphering the host genetic factors conferring susceptibility to severe COVID-19 using exome sequencing.

The COVID-19 pandemic remains a significant public health concern despite the new vaccines and therapeutics. The clinical course of acute SARS-CoV-2 infection is highly variable and influenced by several factors related to the virus and the host. Numerous genetic studies, including candidate gene, exome, and genome sequencing studies, genome-wide association studies, and other omics efforts, have proposed various Mendelian and non-Mendelian associations with COVID-19 course. In this study, we conducted whole-exome sequencing on 90 unvaccinated patients from Turkey with no known comorbidities associated with severe COVID-19. Of these patients, 30 had severe, 30 had moderate, and 30 had mild/asymptomatic disease. We identified rare variants in genes associated with SARS-CoV-2 susceptibility and pathogenesis, with an emphasis on genes related to the regulation of inflammation, and discussed these in the context of the clinical course of the patients. In addition, we compared the frequencies of common variants between each group. Even though no variant remained statistically significant after correction for multiple testing, we observed that certain previously associated genes and variants showed significant associations before correction. Our study contributes to the existing literature regarding the genetic susceptibility to SARS-CoV-2. Future studies would be beneficial characterizing the host genetic properties in different populations.

Evaluation of whole blood thiamine pyrophosphate concentrations in critically ill patients receiving chronic diuretic therapy prior to admission to Turkish intensive care units: A pragmatic, multicenter, prospective study.

BACKGROUND/OBJECTIVES: Thiamine plays a pivotal role in energy metabolism. The aim of the study was to determine serial whole blood TPP concentrations in critically ill patients receiving chronic diuretic treatment before ICU admission and to correlate TPP levels with clinically determined serum phosphorus concentrations. SUBJECTS/METHODS: This observational study was performed in 15 medical ICUs. Serial whole blood TPP concentrations were measured by HPLC at baseline and at days 2, 5 and 10 after ICU admission. RESULTS: A total of 221 participants were included. Of these, 18% demonstrated low TPP concentrations upon admission to the ICU, while 26% of participants demonstrated low levels at some point during the 10-day study period. Hypophosphatemia was detected in 30% of participants at some point during the 10-day period of observation. TPP levels were significantly and positively correlated with serum phosphorus levels at each time point (P < 0.05 for all). CONCLUSIONS: Our results show that 18% of these critically ill patients exhibited low whole blood TPP concentrations on ICU admission and 26% had low levels during the initial 10 ICU days, respectively. The modest correlation between TPP and phosphorus concentrations suggests a possible association due to a refeeding effect in ICU patients requiring chronic diuretic therapy.

Clinical and Serological Features of Eosinophilic and Vasculitic Phases of Eosinophilic Granulomatosis with Poliangiitis: a Case Series of 15 Patients.

OBJECTIVES: Eosinophilic granulomatosis with poliangiitis (EGPA) which was previously called Churg-Strauss Syndrome, is classified into eosinophilic and vasculitic phases. To characterize the eosinophilic and vasculitic phases of the disease in terms of clinical findings, serology, and treatment. MATERIALS AND METHODS: We included 15 EGPA patients in the study. The clinical, serological, and therapeutic characteristics and the treatment responses of the patients were recorded. RESULTS: Thirteen patients were classified as being in the eosinophilic phase and two were classified as being in the vasculitic phase of EGPA. Initial symptoms were worsening asthma in all patients (n=15; 100%). All patients had rhinosinusitis, and 66.6% had hypersensitivity to nonsteroidal anti-inflammatory drugs. The two patients in the vasculitic phase did not have nasal polyposis. Pulmonary and nervous system involvement were the most common symptoms. The erythrocyte sedimentation rates (ESRs) of the two patients in the vasculitic phase were 65 mm/h and 55 mm/h, while ESR was normal in eosinophilic-phase patients. Antineutrophil cytoplasmic antibodies (ANCA) was detected in one patient (6.6%) who was in the vasculitic phase (Case 15). The disease was under control with higher doses of methylprednisolone in the vasculitic phase (Case 14: 12 mg/day, Case 15: 10 mg/day) than in the eosinophilic phase. Relapse was detected in the two patients in the vasculitic phase. Oral corticosteroid was not discontinued in any case, and no mortality was reported. CONCLUSION: Patients with eosinophilic phase or vasculitic phase EGPA had similar clinical onset. However, higher ESR, ANCA positivity, and extrapulmonary organ involvement were only found in patients in the vasculitic phase. Corticosteroid responsiveness was very good in all patients in the eosinophilic phase, and the disease could be controlled with a very low maintenance dose of a corticosteroid.

The effect of CPAP therapy on insulin-like growth factor and cognitive functions in obstructive sleep apnea patients.

OBJECTIVES: Cognitive impairment is common among patients with obstructive sleep apnea syndrome (OSAS). In this study, we aimed to investigate the effect of continuous positive airway pressure (CPAP) therapy on serum insulin-like growth factor-1 (IGF-1) levels and cognitive functions in patients with OSAS. PATIENT/METHODS: Thirty-three patients with newly diagnosed OSAS and 17 healthy-control subjects enrolled in the study. All individuals completed the mini-mental state examination (MMSE) to evaluate cognitive function. Blood samples were taken at the end of the polysomnography in the morning and the same procedures were repeated 3 months after starting CPAP treatment. RESULTS: In the OSAS group, the baseline MMSE score was 23.5 ± 3.6, and serum IGF-1 level was 79.1 ± 36.1 ng/mL. Both values were significantly lower compared with the control group (mean MMSE score = 28.1 ± 1.4, P = 0.0001; mean serum IGF-1 level = 147.1 ± 49.1 ng/mL, P < 0.0001). Three months after CPAP treatment, OSAS patients showed a significant improvement in MMSE scores (26.5 ± 2.8, P = 0.0001) and serum IGF-1 level (129.1 ± 58.2, P = 0.0001). In contrast, baseline and third-month measurements for IGF-1 levels and MMSE scores were not significantly different in the control group. CONCLUSIONS: The results indicate that effective CPAP therapy in OSAS patients leads to significant improvement in cognitive functions and IGF-1 even in a short-term follow-up. Cognitive function assessment might be a part of evaluation in OSAS patients.

Correlation between pentraxin-3 and endothelial dysfunction in obstructive sleep apnea syndrome.

BACKGROUND AND AIM: Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for cardiovascular disease. Recent studies showed endothelial dysfunction and pentraxin-3 both of an early marker for development of cardiovascular disease. The aim of the study was to evaluate the relationship between severity of OSAS and endothelial dysfunction and inflammatory markers including pentraxin-3 and high-sensitivity C-reactive protein (hs-CRP). METHODS: This was a cross-sectional study in which patients who had undergone a polysomnographic study for diagnosis of OSAS were recruited. Included patients were grouped according to apnea-hypopnea index (AHI) as mild (AHI between 5 and 14.9) and moderate-severe OSAS (AHI ⩾ 15). Patients with AHI < 5 served as control group. Endothelial function was evaluated by flow-mediated dilatation (FMD). Serum pentraxin-3 and hs-CRP levels were measured. RESULTS: Eighty-three patients enrolled for the study. We found a significant increment in pentraxin-3 and hs-CRP levels and a significant decrement in FMD as the severity of OSAS increased. There was a negative correlation between FMD and AHI, pentraxin, and hs-CRP. CONCLUSION: OSAS patients have significantly elevated pentraxin-3 levels and endothelial dysfunction. Furthermore, both pentraxin-3 and endothelial dysfunction were independently associated with severity of OSAS defined by AHI.

Non-asbestos-related malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an uncommon tumor derived from mesothelial lining cells. MPM has been described as an insidious neoplasm because of its long latency period. The tumor is typically found in patients several decades after asbestos exposure. We herein describe a 26-year-old patient with MPM who presented with pleural effusion. The patient had not been exposed to asbestos or erionite. There are few case reports of non-asbestos-related MPM in young patients. We report this case to remind physicians to consider MPM in the differential diagnosis of pleural effusion in young patients without exposure to asbestos or erionitis.

Myocardial performance index for detection of subclinical abnormalities in patients with sarcoidosis.

AIM: The aim of this study was to evaluate ventricular functions in patients with sarcoidosis without an obvious heart disease by using tissue Doppler-derived left and right ventricular myocardial performance index (MPI). METHODS: The study population included 45 patient with sarcoidosis (29 men, 16 women; mean age, 44±10 years, mean disease duration, 4.2±2.7 years) and 45 healthy control subjects (31 men, 14 women; mean age, 41±8 years). Cardiac functions were determined using echocardiography, consisting of standard two-dimensional and conventional Doppler and tissue Doppler imaging (TDI). Myocardial tissue Doppler velocities [peak systolic (Sa), early diastolic (Ea), and late diastolic velocities (Aa)] were recorded using spectral pulsed Doppler from the LV free wall, septum, and RV free wall from the apical four chamber view. MPI was also calculated by TDI. RESULTS: The conventional echocardiographic parameters and tissue Doppler measurements were similar between the patients and controls. Left ventricular MPI (0.490±0.092 vs. 0.396±0.088, P=0.010) and right ventricular MPI (0.482±0.132 vs. 0.368±0.090, P=0.006) were significantly higher in patients with sarcoidosis than the control subjects. There was a correlation between the disease duration and right and left ventricular MPI (r=0.418, P=0.005; r=0.366, P=0.013, respectively). There was also a correlation between the systolic pulmonary arterial pressure and right ventricular MPI but not left ventricular MPI (r=0.370, P=0.012; r=0.248, P=0.109, respectively). In receiver operating characteristics curve analysis, the cutoff value of left ventricular MPI >0.46 had 92% sensitivity and 64% specificity in predicting left ventricular diastolic dysfunction. CONCLUSIONS: We have demonstrated that tissue Doppler-derived myocardial left and right ventricular MPI were impaired in sarcoidosis patients, although systolic function parameters were comparable in the patients and controls, showed a subclinic impaired ventricular functions in patients with sarcoidosis.

Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is an infection often occurring in neutropenic patients and has high mortality rates. In recent years, it has been reported that the incidence of IPA has also increased in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study is to investigate the clinical and demographic characteristics and treatment responses of IPA in patients with COPD. METHODS: Seventy-one patients with a positive culture of Aspergillus from lower respiratory tract samples were examined retrospectively. Eleven (15.4%) of these patients, affected with grade 3 or 4 COPD, had IPA. RESULTS: Aspergillus hyphae were detected in lung biopsy in three (27.3%) out of 11 patients and defined as proven IPA; a pathological sample was not taken in the other eight (72.7%) patients, and these were defined as probable IPA. Aspergillus isolates were identified as six cases of Aspergillusfumigatus and three of Aspergillusniger in nine patients, while two isolates were not identified at species level. While five patients required intensive care unit admission, four of them received mechanical ventilation. The most common finding on chest X-ray and computed tomography (CT) (respectively 63.6%, 72.7%) was infiltration. Amphotericin B was the initial drug of choice in all patients and five patients were discharged with oral voriconazole after amphotericin B therapy. Six patients (54.5%) died before treatment was completed. CONCLUSIONS: IPA should be taken into account in the differential diagnosis particularly in patients with severe and very severe COPD presenting with dyspnea exacerbation, poor clinical status, and a new pulmonary infiltrate under treatment with broad-spectrum antibiotics and steroids.

A Rare Cause of Diffuse Parenchymal Lung Disease together with Granulomatous Reaction: Pulmonary Amyloidosis.

Amyloidosis is a heterogeneous group of disorder associated with the deposition of protein in an abnormal fibrillar form. Primary Sjögren's syndrome (PSS) is a systemic inflammatory disorder that commonly affects the exocrine glands. The reported frequency of pulmonary involvement in PSS varies widely, ranging from 9% to 75%. Pulmonary involvement occurs in light-chain (AL) amyloidosis and is uncommon in the reactive (AA) and hereditary forms. Herein we present a case of PSS associated diffuse multinodular amyloidosis in the lung. We followed up the patient without treatment for three years. There are only minimal lung symptoms related to lung infiltration. In conclusion, pulmonary involvement in SS is an extremely rare clinical manifestation and usually has a good survival rate without treatment.