Abnormal quantitative pupillary light responses following COVID-19.

PURPOSE: To characterize alterations in pupillary light reflex responses in subjects following coronavirus disease 2019 (COVID-19), especially those with long-COVID. METHODS: Thirty-five subjects with previous COVID-19 and 30 healthy control participants were enrolled in this cross-sectional comparative study. An infrared dynamic pupillometry system (MonPack One; Metrovision, France) was used to quantify pupillary light responses. The National Institute for Health and Care Excellence (NICE) long-COVID questionnaire was used to identify persisting symptoms at least 4 weeks after acute COVID-19. RESULTS: The median time after the diagnosis of acute COVID-19 was 4.0 (2.0-5.0) months. There was an increase in the latency of pupil contraction (P = 0.001) and a reduction in the duration of pupil contraction (P = 0.039) in post-COVID-19 subjects compared to healthy controls. No significant differences were observed in the initial pupil diameter, amplitude and velocity of pupil contraction or latency, velocity and duration of pupil dilation. Long-COVID was present in 25/35 (71%) subjects and their duration of pupil contraction was reduced compared to subjects without long-COVID (P = 0.009). The NICE long-COVID questionnaire total score (ρ = - 0.507; P = 0.002) and neurological score (ρ = - 0.412; P = 0.014) correlated with the duration of pupil contraction and the total score correlated with the latency of dilation (ρ = - 0.352; P = 0.038). CONCLUSION: Dynamic pupillometry reveals significant alterations in contractile pupillary light responses, indicative of parasympathetic dysfunction after COVID-19.

Extended-spectrum of KRAS and NRAS mutations in lung cancer tissue specimens obtained with bronchoscopy.

Background: Mutations in the RAS genes, HRAS, KRAS, and NRAS, are the most common modifications in many types of human tumors and are found in approximately 30% of all human cancers. These mutations are usually found in codons 12, 13, or 61. Methods: The aim of this study is to evaluate mutations in codons 59, 117, and 146 of KRAS and NRAS genes in addition to codons 12,13, and 61 of KRAS gene in lung cancer tissue specimens obtained with bronchoscopy. KRAS and NRAS mutation analyses with pyrosequencing were performed on DNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue samples of 64 patients histopathologically diagnosed as lung cancer after bronchoscopic biopsy. Results: In all, 20 patients (31.2%) had mutations in KRAS gene (8/27 squamous cell carcinoma, 8/11 adenocarcinoma, 3/16 small cell carcinoma, and 1/1 pleomorphic carcinoma). The most common mutation in codon 12 was in c.35G>T (G12V). When the mutation rate of adenocarcinoma (72.7%) and squamous cell carcinoma (22.9%) patients was compared with each other, a statistically significant difference was observed (P = 0.008). There were no mutations in codons 59, 117, or 146 of KRAS and NRAS genes in patients with lung cancer. Conclusion: In this study, we firstly examined mutations in codons 59, 117, and 146 of KRAS and NRAS genes in addition to codons 12, 13, and 61 of KRAS gene in Turkish lung cancer patients both in non-small cell lung cancer and small cell lung cancer. Although no mutation was detected in codons 59, 117, and 146 of KRAS and NRAS genes, the frequency of KRAS gene mutation was higher than the rate of mutation in both Asian and Western countries, and multicenter studies including more cases should be performed to further explore our results.

Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID.

BACKGROUND/AIMS: Long COVID is characterised by a range of potentially debilitating symptoms which develop in at least 10% of people who have recovered from acute SARS-CoV-2 infection. This study has quantified corneal sub-basal nerve plexus morphology and dendritic cell (DC) density in patients with and without long COVID. METHODS: Forty subjects who had recovered from COVID-19 and 30 control participants were included in this cross-sectional comparative study undertaken at a university hospital. All patients underwent assessment with the National Institute for Health and Care Excellence (NICE) long COVID, Douleur Neuropathique 4 (DN4) and Fibromyalgia questionnaires, and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD), corneal nerve fibre length (CNFL), and total, mature and immature DC density. RESULTS: The mean time after the diagnosis of COVID-19 was 3.7±1.5 months. Patients with neurological symptoms 4 weeks after acute COVID-19 had a lower CNFD (p=0.032), CNBD (p=0.020), and CNFL (p=0.012), and increased DC density (p=0.046) compared with controls, while patients without neurological symptoms had comparable corneal nerve parameters, but increased DC density (p=0.003). There were significant correlations between the total score on the NICE long COVID questionnaire at 4 and 12 weeks with CNFD (ρ=-0.436; p=0.005, ρ=-0.387; p=0.038, respectively) and CNFL (ρ=-0.404; p=0.010, ρ=-0.412; p=0.026, respectively). CONCLUSION: Corneal confocal microscopy identifies corneal small nerve fibre loss and increased DCs in patients with long COVID, especially those with neurological symptoms. CCM could be used to objectively identify patients with long COVID.

Effect of Asbestos Exposure on the Frequency of EGFR Mutations and ALK/ROS1 Rearrangements in Patients With Lung Adenocarcinoma: A Multicentric Study.

OBJECTIVE: The aim of this study is to investigate the effect of asbestos exposure on cancer-driver mutations. METHODS: Between January 2014 and September 2018, epidermal growth factor receptor (EGFR), anaplastic lymphoma receptor tyrosine kinase (ALK), and c-ros oncogene 1 receptor tyrosine kinase gene (ROS1) alterations, demographic characteristics, asbestos exposure, and asbestos-related radiological findings of 1904 patients with lung adenocarcinoma were recorded. RESULTS: The frequencies of EGFR mutations, ALK, and ROS1 rearrangements were 14.5%, 3.7%, and 0.9%, respectively. The rates of EGFR mutations and ALK rearrangements were more frequent in asbestos exposed non-smokers (48.7% and 9%, respectively). EGFR mutation rate was correlated to female gender and not-smoking, ALK rearrangement rate was correlated to younger age, not-smoking, and a history of asbestos exposure. CONCLUSIONS: The higher rate of ALK rearrangements in asbestos-exposed lung adenocarcinoma cases shows that asbestos exposure may most likely cause genetic alterations that drive pulmonary adenocarcinogenesis.

Evaluation of Serum Resistin, Visfatin, and Chemerin Levels in Patients with Lung Cancer and Chronic Obstructive Pulmonary Disease.

OBJECTIVES: Cachexia is an important problem in lung cancer and chronic obstructive pulmonary disease (COPD). Some studies report an association between adipokines and cachexia. Our study aimed to investigate the association of three novel adipokines, resistin, visfatin, and chemerin, with lung cancer and COPD. MATERIALS AND METHODS: 30 patients with non-smallcell lung cancer, 30 patients with COPD, and 30 healthy volunteers were included in the study. Statistically significant weight loss was found in COPD and lung cancer groups compared with that in the control group (p<0.001). Among the biomarkers, only resistin levels were significantly higher in patients with cachexia than in patients without weight loss in all groups (p=0.006). Resistin level was significantly higher in patients with COPD (p=0.002). Visfatin level was significantly higher in the control group (p=0.001). We found that a higher biomass exposure resulted in a significant increase and decrease in resistin (p=0.007) and visfatin levels (p=0.001), respectively, in the patient groups. For all groups, no statistically significant relationship was found between chemerin levels and weight loss or other variables. RESULTS: No significant relationship was found between the biomarkers and lung cancer type, tumor stage, lymph node stage, and metastasis stage. There was no relationship between the biomarkers by tumor, node, and metastasis and COPD stages (p>0.05). We observed no findings strong enough to support the use of these molecules as markers of disease stage or cachexia. CONCLUSION: Resistin, visfatin, and chemerin cannot be used as potential biomarkers for lung cancer or COPD or for disease stage or cachexia.

Frequency of sarcopenia and associated outcomes in patients with chronic obstructive pulmonary disease

Background/aim: We aimed to evaluate the prevalence of sarcopenia and associated outcomes in patients with chronic obstructive pulmonary disease (COPD). Materials and methods: This cross-sectional study was performed on 219 patients aged 50 years and over who were diagnosed with chronic obstructive pulmonary disease (COPD) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. The study included 196 (89.5%) male and 23 (10.5%) female patients. The mean age of the patients was 66.9 ± 10.1 years. To diagnose sarcopenia, muscle function was determined by a gait speed test. Muscle strength was assessed with a hand dynamometer and muscle mass was measured with a bioelectrical impedance analysis device. Pulmonary function tests and six-min walking tests were also performed. The modified Medical Research Council (mMRC) dyspnoea scale was used to evaluate all the participants. Our sample consisted of sarcopenic patients at different stages (17 presarcopenic patients (7.8%), 32 patients with sarcopenia (14.6%), 65 patients with severe sarcopenia (29.7%), and 105 nonsarcopenic patients (47.9%). Results: Sarcopenia was significantly associated with age, BODE (body mass index (BMI), airflow obstruction, dyspnoea, and exercise capacity) index, GOLD spirometric classification, mMRC dyspnoea scale score, BMI, and educational status. Sarcopenia in COPD patients was firmly related to the severity of the disease and its prognosis. The prevalence of sarcopenia increased in severe and very severe COPD cases. The dyspnoea score was higher, and exercise capacities were lower in sarcopenic patients. Conclusions: Sarcopenia in COPD patients was closely related to the severity of COPD and a negative prognosis. The frequency of sarcopenia increased in severe and very severe COPD cases. Dyspnoea scores were higher and exercise capacities were lower in patients with sarcopenia. In patients with COPD, a diagnosis of sarcopenia should be considered, and preventive measures should be taken before irreversible changes develop.

Simple educational kit for patients diagnosed with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis(IPF) is a chronic, progressive lung disease of unknown cause characterized by advanced fibrosis and poor prognosis.This devastating and life threatening disease greatly impacts patients and their family members. Little is known about the best way to educate IPF patients. For this purpose, I developed an educational kit using simple and inexpensive materials that can be easily found and to help visually explain IPF. This educational kit consists of three parts. Using this kit, a patient can have a clearer idea of IPF disease visually, tactilely and auditorily. In conclusion, in medical practice, the educational kit can provide clear, easily understandable and concise information for patients with IPF.

Serum S100A12 and S100B proteins are independent predictors of the presence and severity of obstructive sleep apnea

Background/aim: Obstructive sleep apnea (OSA) is associated with serious cardiometabolic risks. Early diagnosis and treatment compliance are important. For this purpose, research is being carried out on biomarkers associated with the pathogenesis of the disease. We aimed to investigate whether serum S100A12 and S100B proteins could be used as biochemical markers in OSA patients to determine disease presence and severity. Materials and methods: A total of 60 (16 women, 44 men) patients with OSA and 50 (20 women, 30 men) controls were enrolled in this cross-sectional study. Each subject included in the study underwent full-night polysomnography (PSG). The presence and severity of OSA was assessed with the apnea­hypopnea index (AHI). In the OSA group, 17 cases were mild, 18 were moderate, and 25 were severe.The serum levels of S100A12 and S100B were measured using the enzyme-linked immunosorbent assay (ELISA) technique. These protein levels were compared using Student's t-test in the patient and control groups. Spearman's rho correlation coefficients and corresponding P-values were calculated to determine the correlations between these protein levels and polysomnographic parameters. For evaluating the association between OSA and biomarkers, as well as possible confounding factors with S100A12 and S100B, we employed multiple linear regression analyses for the patients with OSA Results: Serum levels of S100A12 and S100B were higher in patients than those in controls (P = 0.01 and P = 0.005, respectively), and a significant correlation was determined between S100A12 and S100B values and AHI (P = 0.0001; P = 0.0001), sleep time with SpO2 < 90% (P = 0.032; P = 0.01), minimum SpO2 during sleep (P = 0.019; P = 0.007), and oxygen desaturation index (ODI) (P = 0.001; P = 0.0001). In the linear regression analysis, AHI was independently related with both S100A12 (P < 0.0001) and S100B (P = 0.011). Receiving operating curves (ROC) identified patients with OSA: AUC for S100A12 = 0.643; AUC for S100B = 0.655 (P < 0.05). Conclusion: Serum levels of S100B and S100A proteins have high diagnostic performance in OSA and are independent predictors of OSA presence and severity.

Intact endobronchial hydatid cyst: an unexpected bronchoscopic challenge.

We describe a rare case of intact endobronchial hydatid cyst that posed a diagnostic challenge because of an unusual imaging manifestation (atelectasis) and unexpected bronchoscopic findings. Although the role of bronchoscopy in the management of pulmonary hydatid cyst is still controversial, 6 cases of complicated pulmonary hydatid cyst removed completely by suction through a fiberoptic bronchoscope have been reported so far. To the best of our knowledge, this is the first nonsurgically treated case of intact endobronchial hydatid cyst with an uneventful long-term follow-up.

Impact of Continuous Positive Airway Pressure Treatment on Leptin Levels in Patients with Obstructive Sleep Apnea Syndrome.

BACKGROUND: There is growing evidence that leptin regulation is altered in obstructive sleep apnea syndrome (OSAS). Several potential mechanisms have been purported to explain how sleep apnea may alter leptin levels. We investigated whether repeated apneas, hypoxia, or excessive daytime sleepiness influenced the levels of leptin in OSAS patients. We also evaluated whether a 3-month continuous positive airway pressure (CPAP) treatment affected leptin levels in patients. METHODS: Randomly selected 31 untreated, otherwise healthy male, overweight [body mass index (BMI) >25 kg/m(2)] obstructive sleep apnea syndrome (OSAS) patients [apnea-hypopnea index (AHI) ≥15] and 25 control (AHI <5) were included in this study. To confirm the diagnosis, all subjects underwent standard polysomnography. Serum samples were taken at 07:00-08:00 a.m. after overnight fasting. The OSAS patients that had regular CPAP treatment (n=26) were re-evaulated 3 months later. RESULTS: Leptin levels (50.5±17.5 grams/L in OSAS and 56.3±25.5 grams/L in controls) and lipid profiles (TC, TGs, HDL-C, and LDL-C) between patient and control groups did not differ (P>0.05). Leptin levels were not correlated with the AHI, oxygen saturation, or excessive daytime sleepiness. CPAP treatment did not significantly change the (BMI), waist and neck circumference, or leptin levels in OSAS patients. Furthermore, we found no correlation between the decrease in serum leptin levels and parameters that were improved by CPAP treatment. CONCLUSION: Leptin levels and lipid profile of overweight subjects with and without OSAS were not different, and our results suggest that OSAS-related parameters and CPAP treatment do not play a significant role in the serum leptin levels.

Inherited and acquired immunodeficiencies underlying tuberculosis in childhood.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey.

Bronchoscopic intratumoral injection of tranexamic acid to prevent excessive bleeding during multiple forceps biopsies of lesions with a high risk of bleeding: a prospective case series.

BACKGROUND: Significant bleeding may occur following endobronchial forceps biopsy or brushing of necrotic or hypervascular tumors in the airways. In some cases, methods such as endobronchial instillation of iced saline lavage and epinephrine may fail to control bleeding. The present study evaluated the efficacy and safety of a new bronchoscopic technique using intratumoral injection of tranexamic acid (IIT) for control of bleeding during forceps biopsy in patients with endobronchial tumors with a high risk of bleeding. METHODS: The study was a prospective case series carried out in a single center. Bronchoscopic IIT was performed in those patients who had endoscopically visible tumoral lesions with persistent active bleeding following the first attempt at bronchoscopic sampling. Tranexamic acid (TEA) was injected through a 22-gauge Wang cytology needle into the lesion in nominal doses of 250-500 mg. After 2-3 minutes, multiple forceps biopsy specimens were obtained from the lesion. RESULTS: Of the 57 consecutive patients included in the study, 20 patients (35.1%) underwent bronchoscopic IIT. The first attempt in 18 patients was endobronchial forceps biopsy (EBB), and because of a high risk of bleeding, the first attempt for the remaining two patients, who were on continuous dual antiplatelet therapy (aspirin and clopidogrel), employed endobronchial needle aspiration (EBNA) as a precautionary measure. Following IIT, subsequent specimens were obtained using EBB in all patients. Multiple forceps biopsy specimens (3-10) were obtained from the lesions (8 necrotic and 12 hypervascular) without incurring active bleeding. The following histopathologic diagnoses were made: squamous cell carcinoma (n = 14), adenocarcinoma (n = 2), small-cell lung cancer (n = 3), and malignant mesenchymal tumor (n = 1). No side effects of TEA were observed. CONCLUSIONS: Bronchoscopic IIT is a useful and safe technique for controlling significant bleeding from a forceps biopsy procedure and can be considered as a pre-biopsy injection for lesions with a high risk of bleeding. TRIAL REGISTRATION: ISRCTN23323895.

[MicroRNAs and lung cancer]. / MikroRNA'lar ve akciger kanseri.

MicroRNAs (miRNAs) are a class of non-coding RNAs that hybridize to mRNAs and induce either translation repression or mRNA cleavage. Patterns of altered miRNA expression in cancer may work as molecular biomarkers for tumor diagnosis, prognosis of disease-specific outcomes, and prediction of therapeutic responses. In addition, miRNAs can serve as specific targets for gene therapies. This review summarizes the current knowledge of miRNAs and their roles in lung cancer.

The first case report of a metastatic myxoid liposarcoma invading the left atrial cavity and pulmonary vein.

Myxoid liposarcoma (MLS) is the most commonly encountered liposarcoma subgroup, accounting for about 50% of all cases. Metastatic MLS of the heart is extremely rare. Herein we describe for the first time metastasis of MLS to the left atrium and left upper pulmonary vein in a 54-year-old woman who was admitted with shortness of breath and cough persisting for 2 weeks. The patient reported that a total surgical excision of MLS of the left thigh followed by radiotherapy was performed 4 years ago. An emergency operation was performed due to rapidly progressive worsening of clinical condition and echocardiographic determination of left atrial mass protruding into the left ventricle and obstructing the mitral inflow throughout the diastole. The mass could not be totally excised because it was tightly adhered to the surrounding tissue. Postoperative magnetic resonance imaging (MRI) showed a 5 × 3 cm residual tumor deforming the posterior wall of the left atrium entirely and extending into the left upper pulmonary vein. Histopathological examination was consistent with MLS. In conclusion, considering probable cardiac metastasis in patients presenting with respiratory symptoms with medical history of soft tissue sarcomas would be life saving. The case is discussed, and a review of the literature in relation to the metastatic involvement of the heart by MLS is presented.

Bronchoscopic intratumoral injection of tranexamic acid: a new technique for control of biopsy-induced bleeding.

In order to achieve an optimal diagnostic yield in patients with endoscopically visible tumors multiple biopsies are needed. However, some centrally located necrotic endobronchial tumors and other vascular-appearing tumors are prone to bleed significantly after the first biopsy, which poses a distressed and complicated management problem for a bronchoscopist. In the present case study, a new technique, using intratumoral injection of tranexamic acid to control significant bleeding during bronchoscopic biopsy, is described. Although this study is limited to two cases, it has been suggested that good control of biopsy-induced bleeding can be attained using this technique.