Amantadine in unvaccinated patients with early, mild to moderate COVID-19: A randomized, placebo-controlled, double-blind trial.

BACKGROUND AND PURPOSE: Adamantanes were listed as an interesting option as an early intervention against COVID-19. We aimed to evaluate the effectiveness of amantadine in preventing the progression of COVID-19 and its neurological sequelae. METHODS: Unvaccinated patients with confirmed SARS-CoV-2 infection within 5 days were enrolled. Subjects were randomized (50:50) to amantadine (AMD; 100 mg twice daily) or placebo (PLB) for 14 days. The Ordinal Scale for Clinical Improvement of the World Health Organization (OSCI-WHO) was the primary measure. Secondary endpoints included assessment for fatigue; depression, disorders of smell and taste, and sleepiness on Days 1 and 15. RESULTS: We enrolled 99 patients (49 AMD and 50 PLB). Disease progression (OSCI-WHO = 4) was observed in 6% (AMD) and 8% (PLB) patients (p > 0.05) with further deterioration (OSCI-WHO〉4) in 0% (AMD) and 8% (PLB) patients (p > 0.05). Complete recovery on Day 15 was 60% higher in the AMD compared with the PLB group (p = 0.025). There was improvement in taste (AMD: p = 0.003; PLB: p = 0.0001) and smell (AMD: p = 0.005; PLB: p = 0.0004) but not in fatigue in both groups. Improvement was observed in the AMD (p = 0.010) but not in the PLB group (p = 0.058) when assessing depression as well as sleepiness (AMD: p = 0.0002; PLB: p = 0.341). There was one death in the PLB group (2.0%) and none in the AMD group (p > 0.05) until Day 210. Overall, the drug was well tolerated. CONCLUSION: The central effects of amantadine on the nervous system with reduction of sleepiness and depression might have had a supportive effect on faster recovery in early COVID-19 patients.

One Molecule, Many Faces: Repositioning Cardiovascular Agents for Advanced Wound Healing.

Chronic wound treatments pose a challenge for healthcare worldwide, particularly for the people in developed countries. Chronic wounds significantly impair quality of life, especially among the elderly. Current research is devoted to novel approaches to wound care by repositioning cardiovascular agents for topical wound treatment. The emerging field of medicinal products' repurposing, which involves redirecting existing pharmaceuticals to new therapeutic uses, is a promising strategy. Recent studies suggest that medicinal products such as sartans, beta-blockers, and statins have unexplored potential, exhibiting multifaceted pharmacological properties that extend beyond their primary indications. The purpose of this review is to analyze the current state of knowledge on the repositioning of cardiovascular agents' use and their molecular mechanisms in the context of wound healing.

Lymphogranuloma venereum: an emerging problem in Poland.

Lymphogranuloma venereum (LGV) is a sexually transmitted disease that increases in incidence, particularly in more developed countries worldwide. LGV is caused by Chlamydia trachomatis serovars/genovars L1-3, including their subvariants, and in Europe mostly affects men who have sex with men (MSM). It can be asymptomatic but has now emerged as a frequent cause of severe proctitis/proctocolitis, especially in MSM. LGV has often been misdiagnosed as C. trachomatis serovars/genovars D-K infection. It is essential with accurate diagnosis that ensures appropriate treatment and protects the patient from complications and sequelae as well as from the consequences of misdiagnosis, e.g. as inflammatory bowel disease or cancer. We present a systematic review of LGV and two new LGV cases diagnosed in Poland.

Optimization of Novel Human Acellular Dermal Dressing Sterilization for Routine Use in Clinical Practice.

Gamma rays and electrons with kinetic energy up to 10 MeV are routinely used to sterilize biomaterials. To date, the effects of irradiation upon human acellular dermal matrices (hADMs) remain to be fully elucidated. The optimal irradiation dosage remains a critical parameter affecting the final product structure and, by extension, its therapeutic potential. ADM slides were prepared by various digestion methods. The influence of various doses of radiation sterilization using a high-energy electron beam on the structure of collagen, the formation of free radicals and immune responses to non-irradiated (native) and irradiated hADM was investigated. The study of the structure changes was carried out using the following methods: immunohistology, immunoblotting, and electron paramagnetic resonance (EPR) spectroscopy. It was shown that radiation sterilization did not change the architecture and three-dimensional structure of hADM; however, it significantly influenced the degradation of collagen fibers and induced the production of free radicals in a dose-dependent manner. More importantly, the observed effects did not disrupt the therapeutic potential of the new transplants. Therefore, radiation sterilization at a dose of 35kGy can ensure high sterility of the dressing while maintaining its therapeutic potential.

SAFETY AND EFFICACY OF INTRAVENOUS ADMINISTRATION OF IRON PREPARATIONS.

Iron deficiency is the main cause of anemia worldwide. Iron supplementation leads to a rise of transferrin saturation and ferritin concentration, resulting in an increased hemoglobin level and decrease of anemia symptoms. Oral iron administration is a treatment of choice in iron deficiency anemia. In patients with impaired iron absorption from the gastrointestinal tract, as well as in large deficits, or poor tolerance of oral formulations, it becomes necessary to apply iron intravenously. In this paper we present, on the basis of current publications, the characteristics of intravenous iron preparations nowadays available on the market, in various clinical situations, with particular focus on their benefits and risk related to the administration of high single iron doses.

Road safety in Poland: magnitude, causes and injuries.

Road accidents are a serious problem of the modern world. They are one of the main causes of injuries and are the third most frequent cause of death. Every year, about one million people, adults and children, die on the roads and several millions get injured. Mortality rate due to injuries from road accidents amounts to 2.2% of all deaths in the world. The research presents epidemiology of road accidents in the period 2004-2015 with particular emphasis on the key issues of road safety in Poland, related to the dangerous behaviour of road users (disregard toward traffic rules). Between years 2004 and 2015 on Polish roads took place more than 508000 accidents with 53155 fatalities and more then 572000 casualties. Despite the various measures which are taken to improve safety on Polish roads, the number of dead and wounded in the vehicle mishap is still large, and losses borne by society are high. To improve safety on Polish roads, it is necessary to continue multi- action plan to systematically progress in the level of road safety.

Corn Crisps Enriched in Omega-3 Fatty Acids Sensory Characteristic and its Changes During Storage.

Extruded cereal snacks are usually deficient in protein, mineral ingredients, valuable fatty acids. With the rise of health awareness among consumers, food manufacturers and scientists are pressed to take measures in order to develop new functional/health-beneficial foods. The aim of this work was to manufacture extruded crisps enriched with α-linolenic acid (obtained from linseed oil) and to observe whether storage of the product for the period of 6 months would cause its disqualification, primarily due to its sensory properties and secondarily due to its chemical properties. The research demonstrated that the addition of linseed oil to corn crisps at the amount of 5 % enables to obtain functional corn crisps containing over 2 g of ALA in a portion of 100 g even after 6 months of storage at room temperature. ALA-enriched crisps maintain the original sensory profile after 6 months of storage and their sensory profile is similar to the profile of crisps without the addition of linseed oil if they are packed in barrier packaging filled 100 % with argon. Therefore, they may be a healthier alternative to typical corn crisps.

A NEW APPROACH TO THE STUDY OF MUCOADHESIVENESS OF POLYMERIC MEMBRANES USING SILICONE DISCS.

The introduction of new test methods and the modification of existing ones are crucial for obtaining reliable results, which contributes to the development of innovative materials that may have clinical applications. Today, silicone is commonly used in medicine and the diversity of its applications are continually growing. The aim of this study is to evaluate the mucoadhesiveness of polymeric membranes by a method that modifies the existing test methods through the introduction of silicone discs. The matrices were designed for clinical application in the management of diseases within the oral cavity. The use of silicone discs allows reliable and reproducible results to be obtained, which allows us to make various tensometric measurements. In this study, different types of polymeric matrices were examined, as well as their crosslinking and the presence for the active pharmaceutical ingredient were compared to the pure dosage form. The lidocaine hydrochloride (Lid(HCl)) was used as a model active substance, due to its use in dentistry and clinical safety. The results were characterized by a high repeatability (RSD < 10.6%). The advantage of silicone material due to its mechanical strength, chemical and physical resistance, allowed a new test method using a texture analyzer to be proposed.

Long-term outcomes of the use of allogeneic, radiation-sterilised bone blocks in reconstruction of the atrophied alveolar ridge in the maxilla and mandible.

Increasingly dental surgeons face the challenge of reconstruction of the height and/or thickness of the alveolar ridge as more and more patients wish to have permanent restoration of their dental defects based on intraosseous implants. Evaluation of human allogeneic bone tissue grafts in reconstruction of atrophied alveolar ridge as a pre-implantation procedure. The material comprised 21 patients aged 19-63, treated between 2009 and 2012 by the same surgeon. Restoration of bone tissue defects was performed with allogeneic, frozen, radiation-sterilised, corticocancellous blocks. The study included 26 grafting procedures with 7 procedures consisting in reconstruction of the alveolar ridge in the mandible and 19 in the maxilla. In all the cases the atrophied alveolar ridge was successfully reconstructed, which allowed placement of intraosseous implants in compliance with the initial treatment plan. After the treatment was completed the patients reported for follow-up annually. The average time of follow-up amounted to 39 months (28-50 months). None of the implants was lost during the follow-up period. There was one case of gingival recession causing aesthetics deterioration of the prosthetic restoration. In three cases the connector became unscrewed partially, which was corrected at the same visit. Frozen, radiation-sterilised, allogeneic bone blocks constitute good and durable bone-replacement material allowing effective and long-lasting reconstruction of the atrophied alveolar ridge to support durable, implant-based, prosthetic restoration.

Global maxillary ridge augmentation with frozen radiation-sterilised bone blocks followed by implant placement: a case report.

Due to atrophy of the tissue within the alveolar ridge, implantation must sometimes be preceded by bone regeneration. The use of allogeneic material allows the surgeon to prepare grafts of any shape and amount; therefore it is a good alternative to autograft reconstruction in patients with extensive atrophy of the alveolar ridge. The patient with maxillary anodontia showed insufficient width of the ridge along its entire length, which prevented implantation. Therefore, alveolar ridge reconstruction was planned. Four frozen, radiation-sterilised bone blocks processed in the Tissue Bank in Warsaw were used for reconstruction of the alveolar ridge. The blocks were grafted to the area of molars, premolars and lateral incisors bilaterally. Three months after surgery a normal union of transplants with the recipient site was achieved. Six implants were embedded and following the 6-month integration period a permanent prosthetic restoration was successfully performed. During a 38-month follow-up none of the implants were lost and the aesthetic or functional condition of the prosthetic restoration did not deteriorate. Frozen allogeneic radiation-sterilised bone blocks constitute good, efficient and safe material used in reconstruction of the alveolar ridge in extensive bone atrophy. This is only one of possible grafting materials for reconstruction of extremely atrophic alveolar ridge.

Allogeneic materials in complications associated with pre-implantation restoration of maxillary and mandibular alveolar processes. A four case report.

There are numerous types of bone replacement materials used to regenerate atrophic alveolar processes before the elective intraosseous implantation. Properties of these materials differ one from another, therefore the choice of material should be thoroughly analysed as well as its type and texture in regard of intraoral conditions and the objective to be achieved. The study involved reconstruction of atrophic alveolar processes with allogeneic bone following unsuccessful use of synthetic and animal materials. The procedure of bone regeneration was performed with frozen bone block (case 1) and allogeneic bone granulate (cases 2, 3, 4) radiation-sterilised with 35 kGy prepared by the Tissue Bank. In all of the presented cases after 3-month implant reorganisation optimal width of the process was obtained, which allowed implant embedment (case 1) or correct implant submergence in the osseous tissue, when implantation took place at the same time (case 2, 3, 4). Allogeneic bone material both, in the form of a block as well as granulate, seems to be an adequate alternative for other materials used in order to widen the bone of the alveolar process, particularly in difficult, complicated cases, where the first regeneration procedure was not successful.

Safety and efficacy of bone wax in patients on oral anticoagulant therapy.

Cardiovascular conditions, apart from neoplastic diseases, remain the major cause of death in developed countries; therefore, the number of patients receiving oral anticoagulants is constantly increasing. Anticoagulant therapy considerably reduced mortality in patients with history of myocardial infarction among others. Although many interventions may be performed without withdrawal of the anticoagulant and tooth extraction was qualified as a procedure of low hemorrhage risk, a majority of dentists refer the patient to a cardiologist several days before the elective tooth extraction to withdraw anticoagulants. The aim of the study was to evaluate the efficacy and safety of bone wax used to stop bleeding after dental procedures in a group of patients on chronic anticoagulant therapy and find an answer to a question, whether it is justified to temporarily withdraw anticoagulants for this type of procedures. The study involved 176 patients on chronic anticoagulant therapy undergoing tooth extraction (154 subjects) or surgical extraction of a retained tooth (48 subjects). After the procedure, in each case the alveolus was filled with bone wax to stop bleeding. In all patients involved in the study bleeding from the alveolus was successfully stopped during the procedure. None of the subjects reported increased bleeding from the operational site after coming back home. Bone wax is a good, efficient, and safe material to block bleeding from the alveolus following tooth extractions, also in patients on chronic anticoagulant therapy. The study demonstrated that withdrawal or adjustment of anticoagulant therapy is not necessary before an elective tooth extraction.

[Clinical usefulness of diagnostic methods for human papilloma virus dependent lesions]. / Przydatnosc kliniczna metod wykorzystywanych w diagnostyce zmian wywolanych zakazeniem wirusem brodawczaka ludzkiego.

Persistent infection of Human Papilloma Virus (HPV) is confirmed necessary factor for development of cervical cancer and anogenital neoplasia. DNA HPV is detected in 96% of cervical cancer, 40% of vulvar and vaginal cancer, 90% of anal cancer and 26% of oral cavity cancer cases in general population. The most common high-risk HPV types observed in anogenital intraepithelial neoplasia or anogenital cancer are HPV 16, 18 and 45. Numerous diagnostic methods of detection of HPV infection and lesions causes by persistent HPV infection are widely used. Epidemiological data reveals correlation of incidence and mortality reduction due to cervical cancer and consequent prosecution and improvement of screening programmes based on morphological assessment of exfoliative smears. In last decade some limitations of conventional smear method were pointed out and a new diagnostic techniques were introduced: liquid-based cytology and HPV DNA testing. Combination of cytological examination and HPV DNA testing seems to be optimal solution to be introduced in large population because of combining high sensitivity of molecular test with high specificity of cytological smear.

Are Current Educational and Therapeutic Programs, Directed at Rare Disease Transplant Candidates and Recipients, Sufficient to Support Them on the Path From Diagnosis to Life After Allogenic Transplantation?-Recommendations for Member State Policymakers.

For many rare disease (RD) patients, allogenic transplantation represents an effective therapy, improving overall survival rates and quality of life (QoL). Globally, ∼1% of liver transplants are performed for RDs and rare indications. However, patients and carers report unmet needs on their pathway toward treatment-in education and therapeutic measures, oftentimes shouldering expertise-building responsibility themselves. These issues are exacerbated in child patients. Estimates indicate that 6% to 8% of Poland's population (2.3-3 million persons) are burdened by RDs and potentially face such issues. This work aims to identify shortcomings of Polish policy in the field of educational and therapeutic measures for RD transplant candidates and recipients. Based on solutions introduced by pioneers, recommendations are formulated regarding priority actions. An analysis of national, transnational, and individual-center programs, directed at patients during their path from diagnosis to life post-transplant, was conducted. The investigation uncovered measure gaps not addressed by the National Plan for Rare Diseases-in fields of patient and stakeholder education (pre- and post-transplant), psychological care provision, specialized center creation, integration of data scattered among registries with the national insurer's database, and artificial intelligence (AI) tool implementation to support both early diagnostic efforts and tailoring of patient treatment. Programs directed at RD transplant candidates and recipients must aim to ensure that a satisfactory psychosomatic condition of the patient is maintained before and following the procedure, therefore lending credence to success. This necessitates early diagnosis schemes, and personalized medicine, multidisciplinary approaches to the individual, achievable only through big data system creation and AI introduction.

Comparison of Long-Term Outcomes of Surgical Treatment of Human Papillomavirus-Dependent Neoplastic Lesions in Patients With Chronic Immunosuppression After Allogenic Organ Transplantation and Patients With Primary or Acquired Immunodeficiency-A One-Center Experience.

Immunodeficiency predisposes to severe manifestations of human papillomavirus (HPV) infection, including extensive, recalcitrant anogenital lesions and their progression towards carcinomas. This holds for primary and acquired immunodeficiencies, and post-transplant immunosuppressive therapy. About 50% to 90% of patients receiving chronic immunosuppression after allogenic transplantation develop HPV-associated lesions within 4 to 5 years, comprising 10% to 15% of patients presenting with (pre)cancerous HPV-dependent anogenital lesions. Immunodeficiency is one of the highest risk factors associated with severe clinical manifestations of HPV-associated cancers. The primary objective of this work is to compare the long-term therapeutic effectiveness of surgical intervention for HPV-dependent lesions in transplant recipients undergoing chronic immunosuppression and patients burdened with primary or acquired immunodeficiencies. Two groups of 30 patients (selected for most extensive presentations of HPV-dependent neoplastic anogenital lesions), who underwent surgical treatment of these lesions were followed up for 3 to 5 years. The first group comprised patients who qualified and underwent kidney or liver transplantation (10 for a rare disease indication) and are under chronic immunosuppressive regimens. The second group comprised patients burdened by primary or acquired immunodeficiency (15 each). The recurrence rate in the follow-up period was the primary compared parameter. The recurrence rate was higher in the second group, amounting to >15%. For the first group a <5% recurrence rate was observed for recipients without rare disease indications, compared to <15% for recipients with such indications. The importance of rapid surgical intervention and the need for postoperative monitoring for recurrence is highlighted. Chronic immunosuppression demonstrates high relative safety and efficacy in terms of HPV-dependent anogenital lesion recurrence.

Evaluation of safety and efficacy of radiation-sterilized bone allografts in reconstructive oral surgery.

Bone grafting allows reconstruction of the atrophied or destroyed alveolar process. In orthopaedics and traumatology allogeneic grafting has been used to restore defects of osseous tissue for over 60 years. In order to improve safety of the graft recipient, sterilized allogeneic grafts have been use. The aim of the study was to assess the direct and long-term outcomes following augmentation of atrophied alveolar processes with the use of radiation-sterilized allogeneic bone grafts. Sixty-eight patients were surgically treated between 2004 and 2011: 29 underwent open sinus floor elevation, post-extraction alveoli augmentation was performed in 16 subjects and 23 underwent reconstruction of the atrophied alveolar process. Augmentation of bone defects used bone granulate in 63 patients and bone blocks stabilized with titanium screws in 5 patients. PRF membranes collected from the patient's blood were also used in all the procedures. In each of the cases optimal dimensions of the alveolar process were obtained allowing embedment of BIOMET 3I dental implant/-s. In all the patients the defects were successfully restored with implant-supported prostheses. Radiation-sterilized allogeneic bone grafts proved to be safe and effective for the patients and manageable for the surgeon constituting a good alternative to autogeneic material.

Analysis of effect of non-steroidal anti-inflammatory drugs on teeth and oral tissues during orthodontic treatment. Report based on literature review.

In view of high availability and diversity of non-steroidal anti-inflammatory drugs (NSAIDs) on Polish market it is important for orthodontists to be aware of NSAID effect on the range of orthodontic tooth movement as well as the risk of root resorption in the moved teeth and other adverse effects, which might occur within oral cavity. The disadvantages of NSAID non-selective inhibition of COX include common oral inflammatory conditions, gingival bleeding, and disturbances of salivary secretion. Both, the selective and non-selective COX inhibitors, meloxicam excluded, used to alleviate the pain of orthodontic tooth movement, impede the movement of teeth. Paracetamol, explicitly indicated by most authors as the safest NSAID, seems to be the drug of choice in view of no influence on the range of tooth movement, the risk of root resorption or other adverse effects within oral cavity.

Clinical aspects of fungal infections in diabetes.

Diabetes mellitus is one of the main risk factors of fungal infections of oral cavity, lower part of gastrointestinal tract, skin, foot, urogenital system and blood. Mycosis is a serious diagnostic and therapeutic problem and cause of mortality in diabetes. Fungal infections are also an important problem among hemodialysis patients with diabetes or diabetic patients after pancreas or kidney transplantation This work briefly describes the etiology, symptoms, diagnosis and ways of prophylaxis and treatment of mycosis in diabetic population. There is also emphasized the great connection between effective treatment of mycosis and glycemic control.

Insulin replacement therapy in patients with type 1 diabetes by isolated pancreatic islet transplantation.

Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia which causes micro- and macrovascular complications. A significant increase in diabetes morbidity rate has been observed. It is estimated that in year 2030 there will be 552 million diabetics worldwide. Type 1 diabetes requires lifelong treatment with insulin. The only available treatment of diabetes restoring physiological glucose metabolism is transplantation of pancreatic beta cells in form of pancreas or isolated pancreatic islets transplantation. The treatment restores normoglycemia and reduces chances of complications of diabetes. Over the past 10 years there has been significant progress in the development of the islet transplantation procedure. Constant improvement of the method, in particular the development of islets isolation and sourcing techniques, shows promise. According to the Collaborative Islet Transplant Registry in 1999-2009, there have been performed 1,072 allotransplantations. This paper summarizes the indications and contraindications for the procedure, the transplantation process, as well as the surgical procedure and immunosuppressive treatment. The review presents problems related to pancreatic islet cells transplantation and standard scheme of immunosuppressive treatment, requiring a solution.

POLCOVID: a multicenter multiclass chest X-ray database (Poland, 2020-2021).

The outbreak of the SARS-CoV-2 pandemic has put healthcare systems worldwide to their limits, resulting in increased waiting time for diagnosis and required medical assistance. With chest radiographs (CXR) being one of the most common COVID-19 diagnosis methods, many artificial intelligence tools for image-based COVID-19 detection have been developed, often trained on a small number of images from COVID-19-positive patients. Thus, the need for high-quality and well-annotated CXR image databases increased. This paper introduces POLCOVID dataset, containing chest X-ray (CXR) images of patients with COVID-19 or other-type pneumonia, and healthy individuals gathered from 15 Polish hospitals. The original radiographs are accompanied by the preprocessed images limited to the lung area and the corresponding lung masks obtained with the segmentation model. Moreover, the manually created lung masks are provided for a part of POLCOVID dataset and the other four publicly available CXR image collections. POLCOVID dataset can help in pneumonia or COVID-19 diagnosis, while the set of matched images and lung masks may serve for the development of lung segmentation solutions.