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Dorota Zarębska-Michaluk,1 Jerzy Jaroszewicz,2 Magdalena Rogalska,3 Diana Martonik,3 Paweł Pabjan,1 Aleksandra Berkan-Kawińska,4 Beata Bolewska,5 Barbara Oczko-Grzesik,2 Dorota Kozielewicz,6 Magdalena Tudrujek-Zdunek,7 Justyna Kowalska,8 Anna Moniuszko-Malinowska,9 Krzysztof Kłos,10 Marta Rorat,11,12 Piotr Leszczyński,13,14 Anna Piekarska,4 Joanna Polańska,15 Robert Flisiak3 1Department of Infectious Diseases, Jan Kochanowski University, Kielce, 25-369, Poland; 2Department of Infectious Diseases and Hepatology, Medical University of Silesia, Katowice, 40-055, Poland; 3Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, 15-089, Poland; 4Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łódź, 90-549, Poland; 5Department of Infectious Diseases, University of Medical Sciences, Poznań, 61-701, Poland; 6Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Toruń, 87-100, Poland; 7Department of Infectious Diseases and Hepatology, Medical University of Lublin, Lublin, 20-059, Poland; 8Department of Adults’ Infectious Diseases, Medical University of Warsaw, Warsaw, 02-091, Poland; 9Department of Infectious Diseases and Neuroinfections, Medical University of Białystok, Białystok, 15-089, Poland; 10Department of Infectious Diseases and Allergology, Military Institute of Medicine, Warsaw, 04-141, Poland; 11Department of Forensic Medicine, Wrocław Medical University, Wrocław, 50-367, Poland; 12First Infectious Diseases Ward, Gromkowski Regional Specialist Hospital in Wrocław, Wrocław, 51-149, Poland; 13Department of Rheumatology, Rehabilitation and Internal Medicine, Poznan University of Medical Sciences, Poznań, 61-701, Poland; 14Department of Rheumatology and Osteoporosis, Szpital im. J. Strusia w Poznaniu, Poznań, 61-285, Poland; 15Silesian University of Technology, Gliwice, 44-100, PolandCorrespondence: Dorota Zarębska-MichalukDepartment of Infectious Diseases, Jan Kochanowski University in Kielce, Ul. Radiowa 7, Kielce, 25-317, PolandTel +48 662441465Fax +48 41 3682262Email dorota1010@tlen.plPurpose: The pathogenesis of coronavirus disease 2019 (COVID-19) is complicated, and in addition to antiviral therapy and combating coagulopathy, treatment should also include inhibition of the proinflammatory cytokines overproduction. The purpose of this study is to compare the effectiveness of tocilizumab (TCZ) and dexamethasone (DEX) administered alone or in combination in patients with severe COVID-19.Patients and Methods: Patients were selected from the SARSTer database, containing 3330 individuals with COVID-19 treated between 1 March 2020 and 10 March 2021. The current study included adult patients with baseline oxygen saturation (SpO2) ≤ 90%, requiring regular or non-invasive high-flow oxygen supplementation.Results: Among included 460 patients, 59 were treated with TCZ, 125 with TCZ and DEX, 169 with DEX, and 107 did not receive TCZ nor DEX. The groups were balanced regarding demographics, coexisting diseases, baseline SpO2, and comedications with remdesivir or low-molecular-weight heparin. The death rate of 6.8% was significantly lower in patients receiving TCZ alone than each arm (19.6%– 23.1%), particularly in patients with interleukin-6 concentration exceeding 100pg/mL (5% vs 22.9%– 51.7%, respectively). Analysis of clinical improvement demonstrated doubled, significantly higher rate after 21 and 28 days in patients treated with TCZ alone (60% and 75%, respectively) compared to DEX (27.6% and 37.9%, respectively). The need for mechanical ventilation was similar in all arms.Conclusion: In patients with severe course of COVID-19, particularly those developing cytokine storm, administration of TCZ provides a significantly better effect than DEX regarding survival, clinical improvement, and hospital discharge rate. The combination of TCZ and DEX does not improve therapy effectiveness in patients with severe COVID-19 compared to the administration of TCZ alone.Keywords: SARS-CoV-2, COVID-19, tocilizumab, dexamethasone, cytokine storm

In the article the costs of alternative roofing techniques in the life cycle of the building were calculated. The calculations were made in accordance with ISO 15686-5 standard “Buildings and constructed assets – Service life planning – Part 5: Life-cycle costing”, using normative durability periods and minimum period of annual consumption of individual building elements to determine the durability of building components. The normative periods are valid in Poland in relation to the valuation of buildings. Probabilistic costs in the life cycle of ceramic, metal and bituminous coatings were analysed. The probability density distributions were assumed: beta for pricing factors and normal for the interest rate. Calculations were carried out for the periods of 100 years of operation of coverings, taking into account the costs of replacement and utilization. As a result of the calculations, the life cycle costs of alternative coatings with probabilities from 5 to 95% were obtained.

Iron plays a crucial role in various metabolic processes. However, the impact of 5-aminolevulinic acid (ALA) in combination with iron chelators on iron metabolism and the efficacy of ALA-photodynamic therapy (PDT) remain inadequately understood. This study aimed to examine the effect of thiosemicarbazone derivatives during ALA treatment on specific genes related to iron metabolism, with a particular emphasis on mitochondrial iron metabolism genes. In our study, we observed differences depending on the cell line studied. For the HCT116 and MCF-7 cell lines, in most cases, the decrease in the expression of selected targets correlated with the increase in protoporphyrin IX (PPIX) concentration and the observed photodynamic effect, aligning with existing literature data. The Hs683 cell line showed a different gene expression pattern, previously not described in the literature. In this study, we collected an extensive analysis of the gene variation occurring after the application of novel thiosemicarbazone derivatives and presented versatile and effective compounds with great potential for use in ALA-PDT.

(1) Background: Liver damage is an important component of acute COVID-19, and the advancement of preexisting liver disease is associated with a worse prognosis; (2) Methods: A nationwide retrospective study including 7444 patients aimed to evaluate levels of selected markers of liver damage and disease advancement and their association with mortality and mechanical ventilation (MV); (3) Results: Elevation of the following markers in multivariate models were associated with increased odds of mortality: Alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), fibrosis-4 score (FIB-4), AST-to-platelet ratio index (APRI), and decreased levels of platelet count (PLT). Elevated levels of AST, LDH, APRI, FIB-4, and the AST/ALT ratio and decreased levels of PLT were associated with increased odds of MV in multivariate models. The best predictive accuracy against mortality was achieved with FIB-4 with AUC = 0.733 (95% CI, 0.718-0.749) at the optimal cut-off point of 2.764, while against MV was achieved with LDH with AUC = 0.753 (95% CI, 0.727-0.778) at the optimal cut-off point of 449.5 IU/L. (4) Conclusions: Our study confirms that the advancement of liver damage contributes to a worse prognosis in COVID-19 patients. Markers for liver damage and the advancement of liver disease can provide predictive value in clinical practice among COVID-19 patients.

Purpose: We aimed to determine the surgical indications and postoperative outcomes among pediatric patients with lobar cerebral cavernous malformations (CCMs)., Methods: We retrospectively reviewed pediatric patients operated on for lobar CCM between March 2010 and August 2021. Indications for surgery included (1) intracranial hemorrhage, (2) symptomatic superficially located lesion, and (3) asymptomatic CCM in non-eloquent area in case of strong parental preferences. Patients presenting with seizures were assessed using Engel Epilepsy Surgery Outcome Scale., Results: Twenty-one patients were included. The predominant symptoms were seizures (57.1%), headaches (33.3%), and focal neurological deficits (23.8%). Patients were qualified for surgery due to symptomatic intracranial hemorrhage (47.6%), drug-resistant epilepsy (28.6%), and focal neurological deficits (9.5%). Three patients (14.3%) were asymptomatic. A gross total resection of CCM with the surrounding hemosiderin rim was achieved in all patients. The mean follow-up was 52 months. No patient experienced surgery-related complications. In all individuals with a preoperative first episode of seizures or focal neurological deficits, the symptoms subsided. All six patients with drug-resistant epilepsy improved to Engel classes I (67%) and II (33%)., Conclusion: Surgical removal of symptomatic lobar CCMs in properly selected candidates remains a safe option. Parental preferences may be considered a sole qualifying criterion for asymptomatic lobar CCM excision., (© 2024. The Author(s).)

The aim of this study was to obtain drinking yogurts enriched with ACTICOA cocoa powder (ACTICOA), its extract (EACTICOA) and pure phenolics, as well as their inclusion complexes with cyclodextrins and alginate-chitosan (A-Ch) capsules, and to evaluate the effects of these additives on the viability of lactic acid bacteria (LAB) and antioxidant properties of fresh yogurts and yogurts stored for 14 days at 4 °C. The application of cocoa phenolic compounds in free form and in the form of EACTICOA to yogurts resulted in the greatest increase in the concentration of phenolic compounds and a significant improvement in the antioxidant properties of the fortified products. The highest TPC was found in yogurts enriched with free quercetin (107.98 mg CE/g). Yogurt fortified with free gallic acid showed the highest ability to neutralize free radicals (EC50 = 2.74 mg/mg DPPH, EC50 = 5.40 mg/mg ABTS) and reduce ferric ions (183.48 µM Trolox/g). The enrichment of yogurts with the tested phenolic compounds preparations, especially in the form of encapsulates, did not affect the viability of LAB during storage.

Purpose: Since new evidence regarding the impact of Wendler glottoplasty (WG) on the voice in transgender women became available in the literature in recent years, we aimed to perform an updated systematic review and meta-analysis to determine the actual safety and efficacy of WG in the process of vocal feminization., Methods: PubMed, Embase, and Cochrane were searched for English-language articles published until July 4, 2023. Studies were found eligible if they evaluated the impact of WG on the acoustic-aerodynamic measures and quality of voice in transgender women., Results: Twenty-three studies were identified. After exclusion of three studies due to incomplete data, 20 studies including 656 patients were included in the meta-analysis. After WG, there was a significant increase of fundamental frequency, speaking fundamental frequency, and lower limit of the frequency range (p < 0.001). Concurrently, a significant reduction of frequency range and maximum phonation time was observed (p < 0.001). No significant differences were found between the pre- and postoperative values regarding the Grade, Roughness, Breathiness, Asthenia, and Strain scale score (p = 0.339). The overall score in the Trans Woman Voice Questionnaire (TWVQ) significantly improved after WG (p < 0.001)., Conclusions: WG is an effective voice feminization method in transgender women, associated with a high procedural success and low risk of postoperative complications. Significantly improved TWVQ score after surgery suggests its positive impact on the voice-related quality of life. Postoperative decrease of maximum phonation time and frequency range does not seem to significantly impact the effectiveness of voice production., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Syphilis is a sexually transmitted multisystemic disease known as "the great imitator" due to its variable presentations. Despite being preventable and curable, it still constitutes a major health problem. Hepatic manifestation of syphilis is usually mild cholestatic liver injury but in very rare cases can become fulminant. Moreover, syphilitic hepatitis, known for several decades, is considered rare but is probably under-diagnosed. Given the significant morbidity associated with a missed diagnosis, syphilitic hepatitis should be taken into account as an element of differential diagnosis in patients with unexplained elevation of liver enzymes., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Clinical and Experimental Hepatology.)

Introduction: Many transsexual women seek to feminise their voice through pitch elevation surgeries so that it becomes congruent with their gender identity. This study aims to determine the safety and effectiveness of Wendler glottoplasty (WG) in vocal feminisation through the assessment of acoustic and aerodynamic parameters of the voice, as well as voice-related quality of life (QoL) in male-to-female transsexuals., Material and Methods: We retrospectively reviewed the medical records of transsexual women who underwent WG for voice feminisation at our institution between 2016 and 2023. All acoustic and aerodynamic analyses, a voice self-assessment, and a videolaryngostroboscopic evaluation were performed in the immediate preoperative period and at the follow-up visit 6 weeks after the procedure., Results: A total of 11 patients with a mean age of 32.73 years were included. After WG, there was a significant fundamental frequency and speaking fundamental frequency increase of 109.64 Hz and 83.48 Hz, respectively (p < 0.001), representing an average rise by 9.71 semitones and 8.36 semitones (STs), respectively. No significant differences were found between the mean pre- and postoperative values of fundamental frequencies, frequency range, upper limit of the frequency range of spoken voice, and maximum phonation time. Contrarily, the mean lower limit of frequency range rose by 75.56 Hz (p < 0.001), representing an average increase of 10.56 STs. None of the assessed spirometric parameters changed significantly after WG (p > 0.05). The mean overall Voice Handicap Index (VHI) and Voice-Related Quality of Life (V-RQOL) scores significantly improved after the surgery, decreasing by 24.54 points (p = 0.008) and 11.5 points (p = 0.001), respectively. A significant improvement was observed in the functional and emotional domains of VHI. Additionally, significantly fewer patients considered the overall quality of their voice to be "poor" after WG., Conclusions: WG constitutes an effective method of surgical voice feminisation in male-to-female transsexuals with concurrent improvement in their voice-related QoL. Furthermore, it remains a safe procedure without persistent complications and negative influence on the acoustic-aerodynamic measures of the voice.

Aim of the Study: Metabolic-associated fatty liver disease (MAFLD) requires close monitoring due to its increased incidence and progression to fibrosis, cirrhosis and even hepatocellular carcinoma. The search for non-invasive markers to diagnose liver fibrosis is ongoing. The aim of our study was to evaluate the serum levels of growth differentiation factor-15 (GDF-15), thrombospondin-2 (TSP2), pentraxin 3 (PTX3) and angiopoietin-like protein 8 (ANGPTL8) in children with MAFLD., Material and Methods: Fifty-six overweight/obese children with suspected liver disease were included in this prospective study. MAFLD was diagnosed according to the latest consensus. Vibration-controlled transient elastography (TE) was performed to detect clinically significant liver fibrosis. Serum concentrations of GDF-15, TSP2, PTX3 and ANGPTL8 were measured by enzyme-linked immunosorbent assay (ELISA)., Results: Liver steatosis was diagnosed in abdominal ultrasound in 31 (55.36%) overweight/obese patients who were classified as the MAFLD group. Aspartate aminotransferase (AST)/platelet ratio (APRI) and liver stiffness measurement (LSM) values and TSP2 concentrations showed significantly higher values in patients in MAFLD than in the non-MAFLD group. TSP2 was significantly positively correlated with alanine transaminase (ALT), AST, γ-glutamyltransferase (GGT) and APRI in the study group. The receiver operating characteristics (ROC) analysis showed that the area under the curve (AUC) of LSM, APRI and serum TSP2 was significant for predicting MAFLD in obese children. In the multivariable regression model, LSM was the only significant parameter associated with the diagnosis of MAFLD in children., Conclusions: TSP2 may be a potential biomarker of hepatocyte injury in pediatric patients with MAFLD. None of the examined biomarkers were found to be effective non-invasive markers of liver fibrosis in children., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Clinical and Experimental Hepatology.)

This study aimed to compare the clinical picture of COVID-19 in the initial and later period of Omicron dominance and to identify populations still at risk. A retrospective comparison of the clinical data of 965 patients hospitalized during the early period of Omicron's dominance (EO, January-June 2022) with 897 patients from a later period (LO, July 2022-April 2023) from the SARSTer database was performed. Patients hospitalized during LO, compared to EO, were older, had a better clinical condition on admission, had a lower need for oxygen and mechanical ventilation, had less frequent lung involvement in imaging, and showed much faster clinical improvement. Moreover, the overall mortality during EO was 14%, higher than that in LO-9%. Despite the milder course of the disease, mortality exceeding 15% was similar in both groups among patients with lung involvement. The accumulation of risk factors such as an age of 60+, comorbidities, lung involvement, and oxygen saturation <90% resulted in a constant need for oxygen in 98% of patients, an 8% risk of mechanical ventilation, and a 30% mortality rate in the LO period. Multiple logistic regression revealed lower odds of death during the LO phase. Despite the milder course of infections caused by the currently dominant subvariants, COVID-19 prophylaxis is necessary in people over 60 years of age, especially those with comorbidities, and in the case of pneumonia and respiratory failure.

Air pollution may affect the clinical course of respiratory diseases, including COVID-19. This study aimed to evaluate the relationship between exposure of adult patients to mean 24 h levels of particulate matter sized <10 μm (PM 10 ) and <2.5 μm (PM 2.5 ) and benzo(a)pyrene (B(a)P) during a week before their hospitalization due to SARS-CoV-2 infection and symptomatology, hyperinflammation, coagulopathy, the clinical course of disease, and outcome. The analyses were conducted during two pandemic waves: (i) dominated by highly pathogenic Delta variant (n = 1440) and (ii) clinically less-severe Omicron (n = 785), while the analyzed associations were adjusted for patient's age, BMI, gender, and comorbidities. The exposure to mean 24 h B(a)P exceeding the limits was associated with increased odds of fever and fatigue as early COVID-19 symptoms, hyperinflammation due to serum C-reactive protein >200 mg/L and interleukin-6 >100 pg/mL, coagulopathy due to  d-dimer >2 mg/L and fatal outcome. Elevated PM 10 and PM 2. 5 levels were associated with higher odds of respiratory symptoms, procalcitonin >0.25 ng/mL and interleukin >100 pg/mL, lower oxygen saturation, need for oxygen support, and death. The significant relationships between exposure to air pollutants and the course and outcomes of COVID-19 were observed during both pandemic waves. Short-term exposure to elevated PM and B(a)P levels can be associated with a worse clinical course of COVID-19 in patients requiring hospitalization and, ultimately, contribute to the health burden caused by SARS-CoV-2 variants of higher and lower clinical significance., (© 2023 Wiley Periodicals LLC.)

Background: The pathogenesis of hypercoagulability in COVID-19 patients is complex and not fully understood. Rotational thromboelastometry (ROTEM ® ) is a viscoelastic method that allows the definition of a patient's hemostatic profile. This study aimed to assess the relationship between ROTEM ® parameters, the profile of inflammatory cytokines, and clinical outcomes in COVID-19 patients. Methods: A total of 63 participants ( n = 29 symptomatic non-ICU COVID-19 patients, and n = 34 healthy controls) were prospectively included in the study. We assessed the relationship between the parameters of three ROTEM ® tests (NATEM ® , EXTEM ® , and FIBTEM ® ) and levels of CRP, interleukin-8, interleukin-1β, interleukin-6, interleukin-10, tumor necrosis factor, interleukin 12p70, and clinical outcomes. Results: ROTEM ® indicated hypercoagulability in COVID-19 patients in all the tests performed. The levels of all inflammatory cytokines were significantly higher in COVID-19 patients. NATEM more frequently detected hypercoagulability in COVID-19 patients compared to EXTEM. The strongest correlations with inflammatory biomarkers and CT severity score were with FIBTEM parameters. The elevated maximum clot elasticity (MCE) in FIBTEM was the strongest predictor of poor outcomes. Conclusions: Increased FIBTEM MCE may be associated with greater severity of COVID-19. Non-activated ROTEM (NATEM test) seems to be more valuable for detecting hypercoagulability in COVID-19 patients compared to the tissue factor activated test (EXTEM).

Introduction: Up to now, COVID‑19 caused more than 6 million deaths worldwide. So far, 5 variants of concerns have been identified, with Delta and Omicron being the subject of our analysis., Objectives: We aimed to compare baseline characteristics and outcomes of patients hospitalized during the Delta and Omicron predominance in Poland., Patients and Methods: The study population consisted of 2225 patients divided into 2 groups depending on the variant with which they were infected during the corresponding period of the pandemic., Results: During the Delta wave, the median age of patients was significantly lower (65 vs 73 years; P <0.001), and the cohort was significantly less burdened with comorbidities than during the Omicron surge. The Omicron‑infected patients presented significantly less often in an unstable symptomatic state with SpO2 equal to or below 90% on admission (49.9% for Delta vs 29.9% for Omicron; P <0.001). Regardless of the pandemic period, the 2 most common early symptoms of COVID‑19 were fever and cough. In‑hospital treatment consisted of antiviral drugs, more frequently used in the Omicron wave, and immunomodulatory drugs, more frequently used during the Delta wave. The risk of mechanical ventilation was significantly lower in the patients infected with the Omicron variant (7.2% for Delta vs 3.1% for Omicron; P <0.001). For the age group above 80 years old, the risk of death was significantly higher during the Delta wave than during the Omicron wave. The risk of death was significantly lower in the patients treated with antiviral drugs regardless of the pandemic wave., Conclusions: The Delta variant is associated with a more severe clinical course of the disease and a higher risk of death than the Omicron variant.

This study aimed to systematically review the literature to determine the efficacy and safety of transoral robotic surgery (TORS) in the management of submandibular gland (SMG) sialolithiasis. PubMed, Embase, and Cochrane were searched for English-language articles evaluating TORS in the management of SMG stones published up to 12 September 2022. Nine studies with a total of 99 patients were included. Eight patients underwent TORS followed by sialendoscopy (TS); 11 patients underwent sialendoscopy followed by TORS and sialendoscopy (STS); 4 patients underwent sialendoscopy followed by TORS only (ST); and 4 patients underwent TORS without sialendoscopy (T). The mean operative time amounted to 90.97 min. The mean procedure success rate reached 94.97%, with the highest for ST (100%) and T (100%), followed by the TS (95.04%) and STS (90.91%) variants. The mean follow-up time was 6.81 months. Transient lingual nerve injury occurred in 28 patients (28.3%) and was resolved in all of them within the mean of 1.25 months. No permanent lingual nerve injury was reported. TORS is a safe and effective management modality for hilar and intraparenchymal SMG sialoliths, with high procedural success in terms of successful sialolith removal, SMG preservation, and reduced risk of permanent postoperative lingual nerve damage.

Mast cells (MCs) are the immune cells distributed throughout nearly all tissues, mainly in the skin, near blood vessels and lymph vessels, nerves, lungs, and the intestines. Although MCs are essential to the healthy immune response, their overactivity and pathological states can lead to numerous health hazards. The side effect of mast cell activity is usually caused by degranulation. It can be triggered by immunological factors, such as immunoglobulins, lymphocytes, or antigen-antibody complexes, and non-immune factors, such as radiation and pathogens. An intensive reaction of mast cells can even lead to anaphylaxis, one of the most life-threatening allergic reactions. What is more, mast cells play a role in the tumor microenvironment by modulating various events of tumor biology, such as cell proliferation and survival, angiogenesis, invasiveness, and metastasis. The mechanisms of the mast cell actions are still poorly understood, making it difficult to develop therapies for their pathological condition. This review focuses on the possible therapies targeting mast cell degranulation, anaphylaxis, and MC-derived tumors.

Purpose: While Ruptured Arteriovenous Malformation Grading Scale (RAGS) has recently been validated in children, the literature lacks validation on adults exclusively. Therefore, we aimed to determine the validity of RAGS on the external multicenter adult cohort and compare its accuracy with other scales., Methods: A retrospective analysis was performed in five neurosurgical departments to extract patients who presented with the first episode of acute brain arteriovenous malformation (bAVM) rupture between 2012 and 2019. Standard logistic regression and area under the receiver operating curve (AUROC) calculations were performed to determine the value of the following scales: intracerebral hemorrhage (ICH), AVM-associated ICH (AVICH), Spetzler-Martin (SM), Supplemented SM (Supp-SM), Hunt and Hess (HH), Glasgow Coma Scale (GCS), World Federation of Neurological Surgeons (WFNS), and RAGS to predict change in categorical and dichotomized modified Rankin Scale (mRS) across three follow-up periods: within the 6 months, 6 months to 1 year, and above 1 year., Results: Sixty-one individuals with a mean age of 43.6 years were included. The RAGS outperformed other grading scales during all follow-up time frames. It showed AUROC of 0.78, 0.74, and 0.71 at the first 6 months, between 6 and 12 months, and after 12 months of follow-up, respectively, when categorized mRS was applied, while corresponding values were 0.79, 0.76, and 0.73 for dichotomized mRS, respectively., Conclusion: The RAGS constitutes a reliable scale predicting clinical outcomes following bAVM rupture among adults. Furthermore, the RAGS proved its generalizability across medical centers with varying treatment preferences., (© 2022. The Author(s).)

In clinical trials, adenovirus vectors (AdVs) are commonly used platforms for human gene delivery therapy. High genome capacity and flexibility in gene organization make HAdVs suitable for cloning. Recent advancements in molecular techniques have influenced the development of genetically engineered adenovirus vectors showing therapeutic potential. Increased molecular understanding of the benefits and limitations of HAdVs in preclinical research and clinical studies is a crucial point in the engineering of refined oncolytic vectors. This review presents HAdV species (A-G) used in oncotherapy. We describe the adenovirus genome organizations and modifications, the possibilities oncolytic viruses offer, and their current limitations. Ongoing and ended clinical trials based on oncolytic adenoviruses are presented. This review provides a broad overview of the current knowledge of oncolytic therapy. HAdV-based strategies targeting tumors by employing variable immune modifiers or delivering immune stimulatory factors are of great promise in the field of immune oncologyy This approach can change the face of the fight against cancer, supplying the medical tools to defeat tumors more selectively and safely.

Continuous evaluation of real-world treatment effectiveness of COVID-19 medicines is required due to the ongoing evolution of SARS-CoV-2 and the possible emergence of resistance. Therefore, this study aimed to analyze, in a retrospective manner, the outcomes in patients hospitalized with COVID-19 during the pandemic waves dominated by Delta and Omicron variants and treated with remdesivir (RDV) ( n = 762) in comparison to a demographically and clinically matched group not treated with any antivirals ( n = 1060). A logistic regression analysis revealed that RDV treatment was associated with a significantly lower risk of death during both Delta wave (OR = 0.42, 95%CI: 0.29-0.60; p < 0.0001) and Omicron-dominated period (OR = 0.56, 95%CI: 0.35-0.92; p = 0.02). Moreover, RDV-treated groups were characterized by a lower percentage of patients requiring mechanical ventilation, but the difference was not statistically significant. This study is the first real-world evidence that RDV remains effective during the dominance of more pathogenic SARS-CoV-2 variants and those that cause a milder course of the disease, and continues to be an essential element of COVID-19 therapy.

Objective: The Chicago Chiari Outcome Scale (CCOS) serves as a standardized clinical outcome evaluation tool among patients with Chiari malformation type I (CM-I). While the reliability of this scale has been proven for pediatric patients, the literature lacks CCOS validation when used solely in adults. Therefore, this study aimed to determine the validity of the CCOS in an external cohort of adult patients., Methods: The authors retrospectively analyzed the medical records of symptomatic patients with CM-I who underwent posterior fossa decompression between 2010 and 2018 in six neurosurgical departments. Each patient was clinically assessed at the latest available follow-up. Gestalt outcome was determined as improved, unchanged, or worsened compared with the preoperative clinical state. Additionally, the CCOS score was calculated for each patient based on the detailed clinical data. To verify the ability of the CCOS to determine clinical improvement, the area under the receiver operating characteristic (AUROC) curve was evaluated. A logistic regression analysis using all four components of the CCOS (pain symptoms, nonpain symptoms, functionality, and complications) was performed to establish predictors of the improved outcome., Results: Seventy-five individuals with a mean age of 42 ± 15.32 years were included in the study. The mean follow-up duration was 52 ± 33.83 months. Considering gestalt outcome evaluation, 41 patients (54.7%) were classified as improved, 24 (32%) as unchanged, and 10 (13.3%) as worsened. All patients with a CCOS score of 14 or higher improved, while all those with a CCOS score of 8 or lower worsened. The AUROC was 0.986, suggesting almost perfect accuracy of the CCOS in delineating clinical improvement. A CCOS score of 13 showed high sensitivity (0.93) and specificity (0.97) for identifying patients with clinical improvement. Additionally, a meaningful correlation was found between higher CCOS scores in each component and better outcomes. Patient stratification by total CCOS score showed that those categorized as improved, unchanged, and worsened scored prevalently between 13 and 16 points, 10 and 12 points, and 4 and 9 points, respectively., Conclusions: In this adult cohort, the CCOS was found to be almost perfectly accurate in reflecting postoperative clinical improvement. Moreover, all four CCOS components (pain symptoms, nonpain symptoms, functionality, and complications) significantly correlated with patient clinical outcomes.

The COVID-19 pandemic proceeds in waves, with variable characteristics of the clinical picture resulting from the evolution of the SARS-CoV-2 virus. This study aimed to compare the epidemiological characteristics, symptomatology, and outcomes of the disease in patients hospitalized for COVID-19 during periods of different variants dominance. Comparing the periods of dominance of variants preceding the Delta variant, the Delta period was characterized by a higher share of hospitalized females, less frequent comorbidities among patients, and a different age distribution. The lowest need for oxygen therapy and mechanical ventilation was observed under Omicron dominance. The triad of classic COVID-19 symptoms, cough, fever, dyspnoea, and fatigue, were most prevalent during the Delta period, and significantly less common under the Omicron dominance. During the Omicron period, nearly twice as many patients as in the previous periods could be discharged from the hospital within 7 days; the overall 28-day mortality was significantly lower compared to that of the Delta period. It also did not differ between periods that were dominated by the BA.1 and BA.2 subvariants. The study indicates that the Omicron SARS-CoV-2 variant that dominated between January and June 2022 caused a disease which resembled the common cold, and was caused by seasonal alpha and beta-coronaviruses with a low pathogenicity for humans. However, one should note that this effect may not only have been related to biological features of the Omicron lineage, but may additionally have been driven by the increased levels of immunization through natural infections and vaccinations, for which we could not account for due to a lack of sufficient data.

Recently, contrast-enhanced ultrasound (CEUS) has become a promising tool in distinguishing benign from malignant parotid gland tumors. However, its usefulness in differentiating various benign parotid tumors has not been determined so far. This study aimed to systematically review the literature to determine the utility of CEUS in the preoperative differentiation between pleomorphic adenomas (PAs) and Warthin's tumors (WTs) of the parotid gland. PubMed, Embase, and Cochrane were searched for English-language articles published until 21 July 2022. Fifteen studies were included. On CEUS examination, a significantly greater percentage of PAs displayed heterogeneous enhancement texture compared to WTs. Contrarily, the enhanced lesion size, the enhancement margin, and the presence of the enhancement rim did not differ significantly between the entities. Significantly longer normalized mean transit time (nMTT) and time to peak (TTP) were observed in PAs. Contrarily, the mean values of area under the curve (AUC) and time from peak to one half (TPH) were significantly higher for WTs. Due to the considerable overlap among the qualitative CEUS characteristics of PAs and WTs, the reproducible, investigator-independent quantitative CEUS measurements have a greater potential to distinguish PAs from WTs, which might influence the selection of an appropriate management strategy.

Patients with systemic autoimmune rheumatic disease (SARD) have increased susceptibility to viral infections, including SARS-CoV-2. The aim of this study was to analyse the SARD patient population with COVID-19 (coronavirus disease 2019) in terms of baseline characteristics, severity, course and outcomes of the disease compared with the non-SARD group, and to identify factors associated with prognosis, including remdesivir therapy efficacy. Retrospective study comprised 8220 COVID-19 cases from the SARSTer database, including 185 with SARD. Length of hospitalisation, duration of oxygen therapy, mortality and the need for HFNO (high-flow nasal oxygen) and/or NIV (noninvasive ventilation) were significantly higher in the SARD versus non-SARD group. There was no difference in clinical features on admission to hospital. Patients with SARD were older and more likely to have cardiovascular, pulmonary and chronic kidney diseases. Age, the presence of cardiovascular disease, more severe conditions on admission and higher inflammatory marker values were found to be risk factors for death in the SARD group. In patients with SARD treated with remdesivir, there was a trend towards improved mortality but without statistical significance. Length of hospitalisation, 28-day mortality and the need for HFNO and/or NIV were higher in the SARD group. These patients often had other chronic diseases and were older.

Background: The real-world effectiveness of molnupiravir (MOL) during the dominance of Omicron SARS-CoV-2 lineage is urgently needed since the available data relate to the period of circulation of other viral variants. Therefore, this study assessed the efficacy of MOL in patients hospitalized for COVID-19 in a real-world clinical practice during the wave of Omicron infections., Methods: Among 11,822 patients hospitalized after 1 March 2020 and included in the SARSTer national database, 590 were treated between 1 January and 30 April 2022, a period of dominance of the Omicron SARS-CoV-2 variant. MOL was administered to 203 patients, whereas 387 did not receive any antiviral regimen. Both groups were similar in terms of sex, BMI and age allowing for direct comparisons., Results: Patients who did not receive antiviral therapy significantly more often required the use of Dexamethasone and Baricitinib. Treatment with MOL resulted in a statistically significant reduction in mortality during the 28-day follow-up (9.9 vs. 16.3%), which was particularly evident in the population of patients over 80 years of age treated in the first 5 days of the disease (14.6 vs. 35.2%). MOL therapy did not affect the frequency of the need for mechanical ventilation, but patients treated with MOL required oxygen supplementation less frequently than those without antivirals (31.7 vs. 49.2%). The time of hospitalization did not differ between groups., Conclusions: The use of molnupiravir in patients hospitalized for COVID-19 during the dominance of Omicron variant reduced mortality. This effect is particularly evident in patients over 80 years of age., (© 2022. The Author(s).)

Data on the use of remdesivir, the first antiviral agent against SARS-CoV-2, are limited in oncologic patients. We aimed to analyze contributing factors for mortality in patients with malignancies in the real-world CSOVID-19 study. In total, 222 patients with active oncological disorders were selected from a nationwide COVID-19 study of 4890 subjects. The main endpoint of the current study was the 28-day in-hospital mortality. Approximately half of the patients were male, and the majority had multimorbidity (69.8%), with a median age of 70 years. Baseline SpO2 < 85% was observed in 25%. Overall, 59 (26.6%) patients died before day 28 of hospitalization: 29% due to hematological, and 20% due to other forms of cancers. The only factor increasing the odds of death in the multivariable model was eGFR < 60 mL/min/m2 (4.621, p = 0.02), whereas SpO2 decreased the odds of death at baseline (0.479 per 5%, p = 0.002) and the use of remdesivir (0.425, p = 0.03). This study shows that patients with COVID-19 and malignancy benefit from early remdesivir therapy, resulting in a decrease in early mortality by 80%. The prognosis was worsened by low glomerular filtration rate and low peripheral oxygen saturation at baseline underlying the role of kidney protection and early hospitalization.

Purpose: The aim of the study was to assess the coagulation and inflammatory markers connected with severe course of COVID-19 and no clinical improvement., Material and Methods: The study population included 2590 adult patients, diagnosed with COVID-19, selected from the SARSTer national database - an ongoing project led by the Polish Association of Epidemiologists and Infectiologists and supported by the Medical Research Agency. Clinical and laboratory parameters, such as C-reactive protein (CRP), white blood cells (WBCs), neutrophil and lymphocyte count, procalcitonin, ferritin, interleukin-6 (IL-6), D-dimer concentration and platelet (PLT) count were analyzed before and after treatment (remdesivir, tocilizumab, dexamethasone, anticoagulants)., Results: Significant differences between patients with mild and severe course of the disease were observed in all examined parameters before treatment (p ​< ​0.05). After treatment only ferritin concentration did not differ significantly. In patients with pulmonary embolism, CRP concentration, neutrophil count, D-dimer and IL-6 concentration were significantly higher than in patients without embolism (p ​< ​0.05). The significant differences between the groups with and without fatal outcome were observed within all analyzed parameters. Significant differences in all examined parameters before treatment were observed between patients with and without clinical improvement (p ​< ​0.05). Multivariate logistic regression showed that no clinical improvement was associated with: IL-6>100 ​pg/ml (OR-2.14), D-dimer concentration over 1000 ​ng/ml (OR-1.62) and PLT count below 150,000/μl (OR-1.57)., Conclusions: Severe course of the disease is associated with lower PLT and lymphocyte count, higher D-dimer, CRP, neutrophil count and IL-6 concentration. The best predictors of no clinical improvement in COVID-19 are: IL-6>100 ​pg/ml, D-dimer>1000 ​ng/ml and PLT<150,000/μl., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)