Resorbable membrane design: In vitro characterization of silver doped-hydroxyapatite-reinforced XG/PEI semi-IPN composite.

In this study, the production and characterization of silver-doped hydroxyapatite (AgHA) reinforced Xanthan gum (XG) and Polyethyleneimine (PEI) reinforced semi-interpenetrating polymer network (IPN) biocomposite, known to be used as bone cover material for therapeutic purposes in bone tissue, were performed. XG/PEI IPN films containing 2AgHA nanoparticles were produced by simultaneous condensation and ionic gelation. Characteristics of 2AgHA-XG/PEI nanocomposite film were evaluated by structural, morphological (SEM, XRD, FT-IR, TGA, TM, and Raman) and biological activity analysis (degradation, MTT, genotoxicity, and antimicrobial activity) techniques. In the physicochemical characterization, it was determined that 2AgHA nanoparticles were homogeneously dispersed in the XG/PEI-IPN membrane at high concentration and the thermal and mechanical stability of the formed film were high. The nanocomposites showed high antibacterial activity against Acinetobacter Baumannii (A.Baumannii), Staphylococcus aureus (S.aureus), and Streptococcus mutans (S.mutans). L929 exhibited good biocompatibility for fibroblast cells and was determined to support the formation of MCC cells. It was shown that a resorbable 2AgHA-XG/PEI composite material was obtained with a high degradation rate and 64% loss of mass at the end of the 7th day. Physico-chemically developed biocompatible and biodegradable XG-2AgHA/PEI nanocomposite semi-IPN films possessed an important potential for the treatment of defects in bone tissue as an easily applicable bone cover. Besides, it was noted that 2AgHA-XG/PEI biocomposite could increase cell viability, especially in dental-bone treatments for coating, filling, and occlusion.

Boron nitride decorated poly(vinyl alcohol)/poly(acrylic acid) composite nanofibers: A promising material for biomedical applications.

In this study, polyvinyl alcohol (PVA) and polyacrylic acid (PAA) nanofibers loaded with boron nitride nanoparticles (mBN) were fabricated by using electrospinning and crosslinked by heat treatment. The physical, chemical, and mechanical properties, hydrophilic behavior, and degradability of composite nanofibers were evaluated. The mechanical properties such as elastic modulus, elongation percentage at the break, and mechanical strength of PVA/PAA nanofibers improved with mBN loading. The thermal conductivity of composite nanofibers reached 0.12 W/m·K at mBN content of 1.0 wt% due to the continuous heat conduction pathways of mBN. In the meantime, while there was no cytotoxicity recorded for both L929 and HUVEC cell lines for all composite nanofibers, the antimicrobial efficiency improved with the incorporation of mBN compared with PVA/PAA and recorded as 68.8% and 75.1% for Escherichia coli and Staphylococcus aureus, respectively. On this basis, the present work proposes a promising biomaterial for biomedical applications such as dual drug delivery, particularly including both hydrophobic and hydrophilic drugs or wound dressing.

Perioperative Tracking of Intravenous Iron in Patients Undergoing On-Pump Cardiac Surgery: A Prospective, Single-Center Pilot Trial.

BACKGROUND: Preoperative intravenous iron administration is a frequently used patient blood management procedure. If the timeframe of intravenous iron administration before surgery is short, (1) the concentration of the intravenous iron compound might still be high in patients' plasma when undergoing surgery and (2) this iron in patients' plasma is at risk to be lost due to blood loss. The aim of the current study was, therefore, to track the iron compound ferric carboxymaltose (FCM) before, during, and after cardiac surgery requiring cardiopulmonary bypass, with an emphasis on intraoperative iron losses in shed blood and potential recovery through autologous cell salvage. METHODS: Concentrations of FCM were analyzed in patients' blood using a hyphenation of liquid chromatography and inductively coupled plasma-mass spectrometry to distinguish between pharmaceutical compound FCM and serum iron. In this prospective, single-center pilot trial, 13 anemic and 10 control patients were included. Anemic patients with hemoglobin levels ≤12/13 g/dL in women and men were treated with 500 milligrams (mg) intravenous FCM 12 to 96 hours before elective on-pump cardiac surgery. Patients' blood samples were collected before surgery and at days 0, 1, 3, and 7 after surgery. One sample each was taken of the cardiopulmonary bypass, the autologous red blood cell concentrate generated by cell salvage, and the cell salvage disposal bag. RESULTS: Patients who had received FCM <48 hours before surgery had higher FCM serum levels (median [Q1-Q3], 52.9 [13.0-91.6]) compared to ≥48 hours (2.1 [0.7-5.1] µg/mL, P = .008). Of 500-mg FCM administered <48 hours, 327.37 (257.96-402.48) mg were incorporated compared to administration ≥48 hours with 493.60 (487.78-496.70) mg. After surgery, patients' plasma FCM concentration in the FCM <48 hours group was decreased (-27.1 [-30 to -5.9] µg/mL). Little FCM was found in the cell salvage disposal bag (<48 hours, 4.2 [3.0-25.8] µg/mL, equivalent to 29.0 [19.0-40.7] mg total; equivalent to 5.8% or 1/17th of the 500 mg FCM initially administered), almost none in the autologous red blood cell concentrate (<48 hours, 0.1 [0.0-0.43] µg/mL). CONCLUSIONS: The data generate the hypotheses that nearly all FCM is incorporated into iron stores with administration ≥48 hours before surgery. When FCM is given <48 hours of surgery, the majority is incorporated into iron stores by the time of surgery, although a small amount may be lost during surgical bleeding with limited recovery by cell salvage.

Fabrication of mechanically advanced polydopamine decorated hydroxyapatite/polyvinyl alcohol bio-composite for biomedical applications: In-vitro physicochemical and biological evaluation.

In this study, polydopamine (PDA) coated hydroxyapatite (HA) reinforced polyvinyl alcohol (PVA) films were produced to be used in biomedical applications such as bone tissue regeneration. pDA is coated not only to prevent the agglomeration of HA when encountering interstitial fluids but also to strongly bind the PVA for the interaction between materials so that the mechanical performance becomes more stabilized. pDA was coated on the hydroxyapatite surface using a radical polymerization technique, and the reinforced PVA were produced with pDA-coated HA (pDA-HA/PVA) nanoparticles. Fundamental characteristic properties of pDA-HA/PVA nanocomposite films were examined by morphological/chemical (SEM-EDS), microstructural (XRD, Ft-IR, and Raman), thermodynamic (TGA and TM), mechanical performance (Vickers microhardness) and biological activity analysis (MTT, genotoxicity and antimicrobial efficacy investigations). Physicochemical analysis showed that all the samples studied exhibited homogeneous mineral distributions through the main structures. According to TGA, TMA and hardness tests, the new composite structure possessed higher mechanical properties than neat PVA. Further, pDA-HA/PVA nanocomposites exhibited high antibacterial capacities against Acinetobacter Baumannii (A.Baumannii), Staphylococcus aureus (S. aureus), and Streptococcus mutans (S.mutans). Moreover, the new nanocomposites were noted to present good biocompatibility for fibroblast (L929) cells and to support remarkably MCS cells. All in all, this comprehensive work shows that the thermo-mechanically improved pDA-HA/PVA films will increase the application fields of PVA in biomedical fields especially tooth-bone treatments for coating, filling, or occlusion purposes.

Is disposable continuous positive airway pressure system effective for the management of acute hypercapnic respiratory failure?

AIM: This study aimed to investigate the effectiveness of disposable continuous positive airway pressure (DCPAP) system in decreasing the partial pressure of carbon dioxide (PaCO2) levels in patients with acute hypercapnic respiratory failure (AHRF). MATERIAL AND METHODS: This retrospective observational study included patients treated in the emergency department (ED) with respiratory distress and PaCO2 > 45 mmHg. Patients were divided into two groups (DCPAP and non-DCPAP), depending on the treatment received to treat AHRF. The difference between the baseline PaCO2 levels in the first blood gas obtained from patients at the time of admission and the follow-up blood gas after treatment. Then, the calculated PaCO2 decrease was divided by the time elapsed to obtain the rate of decrease in PaCO2 levels in mmHg/min. The statistical analyses were performed using SPSS version 18.0 software. A p value of < 0.05 was considered statistically significant. RESULTS: A total of 61 patients were included in the study, 31 patients in the DCPAP group and 30 patients in the non-DCPAP group. The mean age of the patients was 74.03 ± 10.04, and the male/female was 23/38. The study demonstrated a statistically significant difference between the DCPAP and non-DCPAP groups in terms of PaCO2 decreasing rate, and it was found to be twice higher in the DCPAP group (0.11 ± 0.07 mmHg/min) than in the non-DCPAP group (0.05 ± 0.06 mmHg/min). CONCLUSION: The study demonstrated that the treatment of AHRF patients with a DCPAP provides a faster decrease in PaCO2 levels in hypercapnic patients compared to standard medical therapy alone.

Evolution of dynamics of physico-chemical and mechanical properties of hydroxyapatite with fluorine addition and degradation stability of new matrices.

This multidisciplinary study examined sensitively the change in the dynamics of main mechanical performance, stability of crystal structure, crystallinity quality, strength, corrosion resistance, biocompatibility, resistance to structural degradation/separations and mechanical durability features of hydroxyapatite (HAp) biomedical materials based on the fluorine addition and degradation process to guide future medical and dental treatment studies. In the study, the fluorine ions were used to be the dental coating, filling and supporting material for biologically or synthetically produced bone minerals. The general characteristic properties were investigated by means of standard spectroscopic, structural and mechanical analysis methods including RAMAN, SEM-EDS, TEM, Vickers micro-indentation hardness and density measurements. A time dependent release test was performed to evaluate possible fluorine ion release after the degradation process. It was found that the fundamental characteristic properties of HAp biomedical materials are noted to improve with the increase in the fluoride level up to 2% due much more stabilization of HAp crystal system. The combination of RAMAN spectra and powder XRD analyzes indicates that 2% addition level affects positively the formation velocity of characteristic HAP phase. Besides, fluorine doped HAp materials all exhibited the main characteristic peaks after degradation process. This is attributed to the fact that the fluorine ions enabled the hydroxyapatite to enhance the structural quality and stability towards the corrosion environment. However, in case of excess dopant level of 3% the degradation rates were obtained to increase due to higher contribution rate and especially electrostatic interactions. As for the surface morphology examinations, 2% fluorine added HAp with the highest density of 3.0879 g/cm3 was determined to present the superior crystallinity quality (smallest grain size, best smooth surface, honeycomb pattern, regular shaped particles and densest particle distributions through the specimen surface). Conversely, the excess fluorine triggered to increase seriously degree of micro/macro porosity in the surface morphology and microscopic structural problems in the crystal system. Thus, the HAp doped with 3% was the most affected material from the degradation process. Additionally, the fluorine ion values read after the release process were quite far from the value that could cause toxic effects. Lastly, the optimum fluorine addition provides the positive effects on the highest durability, stiffness and mechanical fracture strength properties as a consequence of differentiation in the surface residual compressive stress regions (lattice strain fields), amplification sites and active operable slip systems in the matrix. Hence, the crack propagations prefer to proceed in the transcrystalline regions rather than the intergranular parts. Similarly, it was found that Vickers micro-indentation hardness tests showed that the microhardness parameters increased after the degradation process. All in all, the fluorine addition level of 2% was noted to be good choice to improve the fundamental characteristic properties of hydroxyapatite biomedical materials for heavy-duty musculoskeletal, orthopedic implant, biological and therapeutic applications in medicine and dentistry application fields.

Suicidal ideation, post-traumatic stress disorder, and depression in traumatic spinal cord injury: What resilience tells us.

OBJECTIVE: Identification of unmet psychiatric needs, protective and risk factors for suicide are crucial for people with traumatic spinal cord injury (SCI). In this study, we aimed to explore depression, post-traumatic stress disorder (PTSD) status (non-PTSD, partial-PTSD, full-PTSD), resilience, suicidal ideation (SI) and to examine predictors and clinical correlates of current SI in traumatic SCI. METHOD: Sixty-three individuals with traumatic SCI who were at least 3 months post-injury were included in the study. The participants were evaluated in terms of PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (PCL-5), depression, SI, and resilience using the PCL-5, the Patient Health Questionnaire-9, the Brief Resilience Scale, and sociodemographic measures. RESULTS: 33% of our sample (n = 21) had SI over the past two weeks. 71.4% of the patients with SI (n = 15) had depression. A total of 52.4% of the patients with SI (n = 11) were diagnosed with full PTSD. Resilience was found to be significantly lower in individuals with depression and individuals with SI. While depression predicted SI in traumatic SCI, resilience stands as a protective factor against SI. CONCLUSION: SI is quite common in individuals with traumatic SCI and is accompanied by substantial psychiatric comorbidities such as depression and PTSD. Along with depression and PTSD, resilience - which has protective and predictive values and is inversely associated with SI - constitutes a significant psychotherapeutic intervention and screening area.

Frequency of Direct Oral Anticoagulants Usage in Acute Pulmonary Thromboembolism Treatment in Turkey (TUPEDO).

Background: Direct oral anticoagulants (DOACs) have been used in acute pulmonary thromboembolism as an alternative to warfarin due to drug interactions, narrow therapeutic range, and necessary close International Normalized Ratio (INR) monitoring. Phase 3 study results have reported that these drugs are at least as effective as warfarin and beneficial in terms of bleeding; however, studies that present up-to-date life data are necessary. Aims: To evaluate the frequency of using DOACs, which are prescribed with a limited number of indications in our country, and real-life data results. Study Design: Cross-sectional study. Methods: This cross-sectional survey collected the clinical data (history, current treatment, treatment duration, etc.) of patients with pulmonary thromboembolism and who applied to the physician for follow-up between October 15, 2019, and March 15, 2020. The researchers kept the patient records sequentially. Results: Data from 836 patients with acute pulmonary thromboembolism from 25 centers were collected, and DOAC was used in 320 (38.5%) of them. The most preferred DOAC was rivaroxaban (n = 294, 91.9%). DOAC was mostly preferred because it could not provide an effective INR level with warfarin (n=133, 41.6%). Bleeding was observed in 13 (4%) patients. Conclusion: The use of direct oral anticoagulants is becoming almost as widespread as conventional therapy. Real-life data results are important for their contribution to clinical practice.

Ocular Complications of Intravesicular BCG Treatment for Bladder Carcinoma.

PURPOSE: To report genital and ocular Bacillus Calmette-Guérin (BCG) infection as a rare complication of intravesical BCG immunotherapy. METHODS: We report a patient with bladder carcinoma who developed penile and ocular BCG infection. Medical history, clinical features, imaging findings, histopathological evaluation, and response to treatment clinched the diagnosis. RESULT: Granulomatous inflammation was noted on histopathological evaluation of lung and cutaneous lesion of the penis. The left eye with choroidal tubercle and tractional retinal detachment involving fovea underwent pars plana vitrectomy. After silicone removal, best-corrected visual acuity was 20/100 and patient received anti-TB regimen for 12 months. At 1 year follow-up, the choroidal tuberculoma was found to have completely resolved and the ocular status was stable. CONCLUSIONS: Though there are other reported cases of BCG infection secondary to intravesical BCG instillation noted in the literature, penile granuloma accompanying with choroidal tubercle is an uncommon form among these complications.

Comparison of obstructive sleep apnea syndrome and keratoconus patients on elevation maps.

PURPOSE: This study aimed to compare the tomographic features of the cornea on elevation maps between obstructive sleep apnea syndrome (OSAS) and keratoconus (KC) patients and to investigate the presence of susceptibility to ectatic corneal diseases in OSAS patients. DESIGN: This is a comparative cross-sectional case-control study. METHODS: This study included 84 eyes of 42 patients diagnosed with severe OSAS using polysomnography (apnea/hypopnea index > 30), 84 eyes of 56 patients diagnosed with keratoconus, and 84 eyes of 42 healthy subjects as control group and evaluated in three groups. Elevation maps of all the groups were performed using Pentacam, and topometric, pachymetric, and deviation indices were recorded. RESULTS: The study included 252 eyes of 130 participants divided in three groups. Comparing all the tomographic keratometric values, a significant difference was found among the three groups. All keratometric values were found to be higher in the OSAS patients group compared to those in the control group. Also topometric indices and Belin-Ambrosio enhanced ectasia display (BAD) were observed to be higher as in subclinical keratoconus and statistically significant when compared to those in the control group. CONCLUSION: The study reveals the tomographic corneal characteristics and topometric and pachymetric indices of patients with severe OSAS at the time of diagnosis; these findings statistically significantly differ from the control group. In addition to the known association of floppy eyelid in OSAS patients, the suspicion of keratoconus should be kept in mind.

Validity and reliability of the Turkish version of the neurogenic bladder symptom score.

PURPOSE: The neurogenic bladder symptom score (NBSS) represents the effect of disease-specific symptoms on the quality of life in patients with neurogenic bladder (NB). The purpose of this study was to assess the psychometric properties of the Turkish version of the NBSS in spinal cord injury (SCI) and multiple sclerosis (MS) patients. METHODS: The cross cultural adaptation was achieved through forward and back translation of the items of the original version by an expert committee. Face and content validity were evaluated in a prepatient group. Internal consistency and test-retest reliability were used for reliability assessment in 102 patients. Validity was examined using Short Form-12 and King's Health Questionnaire. RESULTS: Eighty-four patients with SCI and 18 with MS were included in the study. Cronbach's alpha values for the total score and the incontinence, storage/voiding, and consequences domains were 0.90, 0.91, 0.81, and 0.63, respectively. The intraclass correlation coefficients were >0.80 for all subdomains and the overall score. The correlation analyses indicated that the Turkish version has good construct validity. CONCLUSIONS: Our results showed that the Turkish version of the NBSS has good reliability and validity in patients with SCI and MS and can be used to evaluate NB symptoms. CLINICAL TRIAL NUMBER: NCT03964077.Implications for rehabilitationThe Turkish version of the neurogenic bladder symptom score (NBSS) is a valid and reliable instrument to measure symptom specific quality of life (QOL) in both patients with spinal cord injury and multiple sclerosis.The Turkish version of the NBSS can be used in the Turkish population to measure neurogenic bladder related QOL for clinical and research purposes.

The boundaries between survival and nonsurvival at COVID-19: Experience of tertiary care pandemic hospital.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is an emerging, fast-spreading, highly mortal and worldwide infectious disease. The pulmonary system was defined as the main target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mortality concept of this disease presented with more severe and systemic disease. The present study investigated the relationship between the patient characteristics at the initial hospital administration and fatality in COVID-19 patients. METHODS: In this retrospective and comparative cohort study, all the 767 hospitalised COVID-19 patients, treated between 18 March and 15 May 2020 in the Covid Clinics of Gulhane Training and Research Hospital in Ankara, Turkey, were evaluated. RESULTS: The fatality rate was significantly increased in patients with any comorbid disease except asthma. The initial laboratory test results indicated highly significant differences according to the patient's outcome. A multifactor logistic regression analysis was performed to calculate the adjusted odds ratios for predicting patient outcomes. Being older than 60 years increased the death risk with an adjusted OR of 7.2 (95% CI: 2.23-23.51; P = .001). The presence of a cancer and the extended duration of intensive care unit treatment were other significant risk factors for nonsurvival. Azithromycin treatment was determined as significantly reduced the death ratio in these patients (P = .002). CONCLUSION: It was revealed that being older than 60 years, presence of a cancer and extended duration of ICU treatment were the major risk factors for predicting fatality rate in hospitalised COVID-19 patients.

Clinical presentation and course of the novel coronavirus disease 2019 in patients with various types of cancer: A retrospective case-control analysis of an experienced cancer center in Turkey.

OBJECTIVE: Cancers have been reported to worsen the clinical course of coronavirus disease 2019 (COVID-19) infection. We aimed to demonstrate the real-life data on health outcomes in COVID-19-infected cancer patients. MATERIALS AND METHODS: We analyzed the data of 43 COVID-19-infected cancer patients in our COVID-19 clinics between March 25, 2020, and May 9, 2020, retrospectively. RESULTS: We determined that 1051 patients were followed up with COVID-19 infection and 43 (4%) of them were cancer patients. The mean age of the patients was 64.3 ± 12.3 years. Lung cancer is the most common cancer type among the patients (23.2%). Dyspnea (51.2%) was the most common symptom in the first admission. Typical ground-glass consolidation or patchy appearance with peribronchial thickening resembling bronchopneumonia on high-resolution computed tomography (HRCT) was present in 29 (67.4%) patients. COVID-19 was diagnosed in 14 (32.5%) patients based on reverse transcriptase-polymerase chain reaction analysis of nose-throat swab samples without any sign of lung involvement on HRCT. Total mortality of the COVID-19 infection was 46.5% (n = 20). Presence of heart disease (hazard ratio [HR]: 3.5; 95% confidence interval [CI]: 1.29-9.4), previous surgeries to the respiratory system (HR: 6.95; 95% CI: 1.29-27.7), and presence of dyspnea at admission (HR: 4; 95% CI: 1.31-12.3) were statistically significantly associated with death (P = 0.01, 0.02, and 0.01, respectively). CONCLUSION: Our practices supported that cancer patients were more affected by COVID-19 disease than the normal population. However, our findings can not be generalized due to being retrospective and single centered study, Also, we did not compare the findings with noncancer patients with COVID19 disease.

Relationship between chest computed tomography findings and clinical conditions of coronavirus disease (COVID-19): A multicentre experience.

AIMS: This study aimed to investigate the clinical and chest computed tomography (CT) features associated with clinical parameters for coronavirus disease (COVID-19) in the capital of Turkey, Ankara. MATERIALS AND METHODS: Epidemiological, clinical features, laboratory findings and radiological characteristics of 1563 hospitalised patients with COVID-19 in Ankara were collected, reviewed and analysed in this study. The risk factors associated with disease severity were investigated. RESULTS: Non-severe (1214; 77.7%) and severe cases (349; 22.3%) were enrolled in the study. Compared with the non-severe group, the severe group were significantly older and had more comorbidities (ie, hypertension, diabetes mellitus, cardiovascular disease and chronic kidney disease). Smoking was more common in the severe group. Severe patients had higher respiratory rates and higher incidences of cough and dyspnoea compared with non-severe patients. Compared with the non-severe patients, the severe patients had increased C-reactive protein (CRP), procalcitonin, neutrophil to lymphocyte ratio (NLR) and CRP/albumin ratio and decreased albumin. The occurrence rates of consolidation, subpleural sparing, crazy-paving pattern, cavity, halo sign, reversed halo sign, air bronchogram, pleural thickening, micronodule, subpleural curvilinear line and multilobar and bilateral involvement in the CT finding of the severe patients were significantly higher than those of the non-severe patients. CONCLUSIONS: Many factors are related to the severity of COVID-19, which can help clinicians judge the severity of the patient and evaluate the prognosis. This cohort study revealed that male sex, age (≥55 years), patients with any comorbidities, especially those with cardiovascular disease, dyspnoea, increased CRP, D-dimer and NLR, and decreased lymphocyte count and CT findings of consolidation and multilobar involvement were predictors of severe COVID-19.

Robotic integration enables autonomous operation of laboratory scale stirred tank bioreactors with model-driven process analysis.

Given its geometric similarity to large-scale production plants and the excellent possibilities for precise process control and monitoring, the classic stirred tank bioreactor (STR) still represents the gold standard for bioprocess development at a laboratory scale. However, compared to microbioreactor technologies, bioreactors often suffer from a low degree of process automation and deriving key performance indicators (KPIs) such as specific rates or yields often requires manual sampling and sample processing. A widely used parallelized STR setup was automated by connecting it to a liquid handling system and controlling it with a custom-made process control system. This allowed for the setup of a flexible modular platform enabling autonomous operation of the bioreactors without any operator present. Multiple unit operations like automated inoculation, sampling, sample processing and analysis, and decision making, for example for automated induction of protein production were implemented to achieve such functionality. The data gained during application studies was used for fitting of bioprocess models to derive relevant KPIs being in good agreement with literature. By combining the capabilities of STRs with the flexibility of liquid handling systems, this platform technology can be applied to a multitude of different bioprocess development pipelines at laboratory scale.

Does Bronchoscopic Lung Volume Reduction Reduce Mortality in Patients with Severe Emphysema?

ABSTRACT       Objective: To compare the 12-month mortality for patients with severe emphysema who underwent either endobronchial valve (EBV) or coil treatments with those managed with standard of care (SoC). Bronchoscopic lung volume reduction (BLVR) is a useful treatment option in patients with chronic obstructive pulmonary disease (COPD), who have severe emphysema. STUDY DESIGN: A case-control study. PLACE AND DURATION OF STUDY: Department of Pulmonology, Yedikule Pulmonary Diseases and Thoracic Surgery Education and Research Hospital, Turkey, between January 2018 and January 2019. METHODOLOGY: Medical data of patients diagnosed with severe/very severe emphysema between January 2010 and January 2017 were evaluated. One hundred and forty-eight patients with advanced COPD-emphysema phenotype, who met the BLVR treatment criteria, were evaluated. One hundred and twenty-four patients with 12-month follow-up data, 73 patients treated with BLVR, 43 cases of EBV, 30 cases of coil treatment, and 51 patients managed with standard of care (SoC) were analysed for this study. RESULTS: A total of 20 (16.1%) patients died at the end of 12th month and 4 (3.2%) in the early period. At the end of the 12th month, mortality was found in 7 patients (9.6%) in the BLVR group (3 underwent EBV and 4 received coil treatment, respectively), and 13 (25.5%) patients in the SoC group. There was no statistically significant difference in mortality between groups in the early period, but it was lower in the BLVR group at the end of 12th month. CONCLUSION: BLVR treatment significantly decreases mortality compared to SoC in patients with advanced emphysema. Key Words: Emphysema, Mortality, Endobronchial valve, Coil, Bronchoscopic lung volume reduction.

CENP-A Nucleosome is a Sensitive Allosteric Scaffold for DNA and Chromatin Factors.

Centromeric loci of chromosomes are defined by nucleosomes containing the histone H3 variant CENP-A, which bind their DNA termini more permissively than their canonical counterpart, a feature that is critical for the mitotic fidelity. A recent cryo-EM study demonstrated that the DNA termini of CENP-A nucleosomes, reconstituted with the Widom 601 DNA sequence, are asymmetrically flexible, meaning one terminus is more clearly resolved than the other. However, an earlier work claimed that both ends could be resolved in the presence of two stabilizing single chain variable fragment (scFv) antibodies per nucleosome, and thus are likely permanently bound to the histone octamer. This suggests that the binding of scFv antibodies to the histone octamer surface would be associated with CENP-A nucleosome conformational changes, including stable binding of the DNA termini. Here, we present computational evidence that allows to explain at atomistic level the structural rearrangements of CENP-A nucleosomes resulting from the antibody binding. The antibodies, while they only bind the octamer façades, are capable of altering the dynamics of the nucleosomal core, and indirectly also the surrounding DNA. This effect has more drastic implications for the structure and the dynamics of the CENP-A nucleosome in comparison to its canonical counterpart. Furthermore, we find evidence that the antibodies bind the left and the right octamer façades at different affinities, another manifestation of the DNA sequence. We speculate that the cells could use induction of similar allosteric effects to control centromere function.

The effectiveness of early anticoagulant treatment in Covid-19 patients.

OBJECTIVES: Coronavirus disease 2019 (Covid-19) is an emerging, fast-spreading and worldwide infectious disease that would be deteriorated with the precipitation of systemic or local thrombosis. The aim of current study was evaluating the effects of early anticoagulant treatment in hospitalized Covid-19 patients. METHOD: The present retrospective and comparative cohort study investigated 413 hospitalized Covid-19 patients treated with or without Low Molecular Weight Heparin (LMWH) (n = 187 and 226, respectively) in the Covid Clinics of Gulhane Education and Research Hospital in Ankara, Turkey, between March 18 and May 03, 2020. The treatment groups were consisted of the patients evaluated before and after The Covid-19 Treatment Guide update on April 12, 2020 that included the anticoagulant treatment thereafter. RESULTS: The mean age of all 413 patients (204 male and 209 female) at disease onset was 50.6 ± 16.7 years. The LMWH-treated patients had significantly higher coagulation markers such as d-dimer and platelet count than LMWH-untreated patients (p values < 0.05). The inflammatory markers, ferritin, interleukin-6 and procalcitonin were significantly increased in LMWH-untreated patients (p values < 0.05). The presence of any comorbidity was significantly more common in LMWH-treated patients compared to LMWH-untreated group (39.6% vs 19.9%, respectively; p < 0.001). Hypertension and diabetes mellitus were the most frequent comorbidities in both groups. The number of intensive care unit (ICU) transfer and longer length of hospital stay were more commonly observed in LMWH-untreated patients (p values <0.05). CONCLUSIONS: Early anticoagulant treatment with relatively higher doses of LMWH may improve the clinical outcome of Covid-19 patients and shorten the length of hospital stay.

Real life results of coil treatment for bronchoscopic lung volume reduction in emphysema.

INTRODUCTION: The lung volume reduction coil treatment is a minimally invasive bronchoscopic treatment option for emphysema patients who suffer from severe hyperinflation. Previous studies have reported successful outcomes in selected cases using coil for bronchoscopic lung volume reduction (BLVR). Our aim is to determine the changes in respiratory function tests, perception of dyspnea and exercise capacities after 12 months in patients treated with endobronchial coil. MATERIALS AND METHODS: The data of patients with severe emphysema and treated with coils between 2014-2017 were evaluated retrospectively. Dynamic and static lung volume capacities at baseline and 12 months, modified Medical Research Council (mMRC) questionnaire and six-minute walk test (6-MWT) results were recorded. RESULT: BLVR was performed in thirty patients (one female, twenty-nine males). Five patients were treated bilaterally and twentyfive unilaterally. One patient died after 7 days and 4 patients died during follow-up. Five patients were lost to follow-up. A total of twenty patients with available data were included in the study. A statistically significant difference was found in mMRC results in pre-treatment and 12-month evaluations. There was no significant difference in FEV1, TLC and RV values at the end of 12 months. There was an increase of 18.9 meters (± 83.5 m) between the baseline and 12 months in 6-MWT. 45% of the patients improved their walking distance over 26 meters which is known as minimal clinically important difference (MCID). CONCLUSIONS: Although no significant changes were observed in pulmonary function tests and lung volumes, the increase in exercise capacity and decreased perception of dyspnea indicate the efficacy of endobronchial coil.

The impact of co-existing comorbid diseases on long-term mortality in bronchoscopic lung volume reduction.

Aim Emphysema is a lung disease in which alveolar capillary units are destroyed supporting tissue lost. Bronchoscopic lung volume reduction (BLVR) is a novel treatment for emphysema. Several comorbidities have been reported to coexist in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate comorbidities of patients with severe emphysema who underwent BLVR and association of these comorbidities with mortality. Methods Between January 2011 and December 2017 the records of severe emphysema patients who underwent endobronchial valve (EBV) or lung volume reduction coil (LVRC) placement were reviewed retrospectively. Results There were 37 patients who received EBV therapy and 29 received LVRC therapy. There were no significant differences in the demographic and clinical characteristics between two groups before the treatment. There were seven deaths (10.6%) over the period of twelve months following the BLVR treatment. All deaths occurred in patients with at least one comorbid condition. Mortality was increased in the presence of comorbidities (14.3% vs 0%, respectively; p=0.099), and it was significantly increased in the presence of multiple comorbidities (18.5% vs 0%; p=0.059). The mortality rate was higher (37.5% vs 10.5%) in the LVRC comparing to the EBV treatment group in the presence of multiple comorbid conditions, albeit not reaching statistical significance (p=0.099). Conclusion The presence of more than one comorbidity in patients who underwent the LVRC treatment are associated with significant increase of mortality. For patients with severe emphysema who have more than one comorbidity, EBV is a better choice than LVRC.