Host-Microbiome Crosstalk in Chronic Wound Healing.

The pathogenesis of chronic wounds (CW) involves a multifaceted interplay of biochemical, immunological, hematological, and microbiological interactions. Biofilm development is a significant virulence trait which enhances microbial survival and pathogenicity and has various implications on the development and management of CW. Biofilms induce a prolonged suboptimal inflammation in the wound microenvironment, associated with delayed healing. The composition of wound fluid (WF) adds more complexity to the subject, with proven pro-inflammatory properties and an intricate crosstalk among cytokines, chemokines, microRNAs, proteases, growth factors, and ECM components. One approach to achieve information on the mechanisms of disease progression and therapeutic response is the use of multiple high-throughput 'OMIC' modalities (genomic, proteomic, lipidomic, metabolomic assays), facilitating the discovery of potential biomarkers for wound healing, which may represent a breakthrough in this field and a major help in addressing delayed wound healing. In this review article, we aim to summarize the current progress achieved in host-microbiome crosstalk in the spectrum of CW healing and highlight future innovative strategies to boost the host immune response against infections, focusing on the interaction between pathogens and their hosts (for instance, by harnessing microorganisms like probiotics), which may serve as the prospective advancement of vaccines and treatments against infections.

Nanocoatings for Chronic Wound Repair-Modulation of Microbial Colonization and Biofilm Formation.

Wound healing involves a complex interaction between immunity and other natural host processes, and to succeed it requires a well-defined cascade of events. Chronic wound infections can be mono- or polymicrobial but their major characteristic is their ability to develop a biofilm. A biofilm reduces the effectiveness of treatment and increases resistance. A biofilm is an ecosystem on its own, enabling the bacteria and the host to establish different social interactions, such as competition or cooperation. With an increasing incidence of chronic wounds and, implicitly, of chronic biofilm infections, there is a need for alternative therapeutic agents. Nanotechnology shows promising openings, either by the intrinsic antimicrobial properties of nanoparticles or their function as drug carriers. Nanoparticles and nanostructured coatings can be active at low concentrations toward a large variety of infectious agents; thus, they are unlikely to elicit emergence of resistance. Nanoparticles might contribute to the modulation of microbial colonization and biofilm formation in wounds. This comprehensive review comprises the pathogenesis of chronic wounds, the role of chronic wound colonization and infection in the healing process, the conventional and alternative topical therapeutic approaches designed to combat infection and stimulate healing, as well as revolutionizing therapies such as nanotechnology-based wound healing approaches.

Pathogenesis, Prophylaxis, and Treatment of Candida auris.

Candida auris poses a serious threat to infection control and patient care since it can produce invasive infections that have a high fatality rate, has been linked to outbreaks in hospital environments, and is typically resistant to several antifungal medications. Since its first description in 2009, six clades have been described. The emerging fungal pathogen possesses adhesins that allow it to adhere to host tissues and medical devices, can form biofilms, produces various hydrolytic enzymes, employs several strategies to evade host immune responses, and exhibits high genetic diversity, which may contribute to its ability to adapt to different environmental conditions and evade host defenses. C. auris is very resistant to various disinfectants and may be difficult to detect.

Navigating the Maze: Exploring Non-Oncological Complexities in Non-Small-Cell Lung Cancer.

Pulmonary oncological pathologies are an important public health problem and the association with other pulmonary lesions may pose difficulties in diagnosis and staging or require different treatment options. To address this complexity, we conducted a retrospective observational study at the Marius Nasta Institute of Pneumophthisiology, Bucharest, Romania. Our study focused on patients admitted in 2019 with non-small-cell lung carcinoma and associated pulmonary lesions identified through surgical resection specimens. Among the 314 included patients, multiple pulmonary nodules were observed on macroscopic examination, with 12% (N = 37) exhibiting nonmalignant etiologies upon microscopic examination. These findings underscore the challenge of preoperative staging. Patients with coexisting nonmalignant lesions were similar in age, smoking habits, and professional or environmental exposure by comparison with those who presented only malignant lesions. The presentation of coexisting malignant and nonmalignant lesions may pose difficulties in diagnosing and staging pulmonary cancer.

How Morphology Shapes Survival in Invasive Squamous Cell Carcinoma of the Lung.

BACKGROUND AND OBJECTIVES: Squamous cell carcinoma (SQCC) represents a significant proportion of human malignancies affecting various anatomical sites, including the lung. Understanding the prognostic factors is crucial for establishing effective risk stratification in these patients, as multiple critical aspects significantly impact overall survival. MATERIALS AND METHODS: A retrospective study was conducted on 99 patients with operable lung SQCC treated at a tertiary center. The exclusion criteria included patients under 18, those with in situ or metastatic SQCC, and those who received neoadjuvant therapy. The surgical specimens were re-analyzed, and data were collected on multiple variables, including pTNM staging, tumor characteristics, and overall survival (OS). The Kaplan-Meier survival analysis and Cox regression models were used to identify significant prognostic factors. RESULTS: The Kaplan-Meier analysis showed a median survival of 36 months with a 65.65% mortality rate. Significant factors influencing survival included keratinization, histological grading, tumor size and stage, pleural invasion, tumor cell arrangement, tumor budding, spread through air space (STAS), and mitotic index. A multiple Cox regression highlighted the nonkeratinizing tumors, advanced pT stages, single-cell invasion, and high mitotic index as key predictors of poorer outcomes. The nonkeratinizing tumors showed higher mortality and shorter median survival rates compared to keratinizing tumors. The tumor staging, cell arrangement, and tumor budding significantly impacted the survival curves. CONCLUSIONS: The study underscores the importance of detailed histopathological evaluations in lung SQCC. The nonkeratinizing tumors, advanced pT stage, single-cell invasion, and high mitotic index were associated with higher hazard rates, emphasizing the need for a comprehensive grading system incorporating these factors to improve prognostic accuracy and guide treatment strategies.

Advances in Alpha Herpes Viruses Vaccines for Human.

Alpha herpes simplex viruses are an important public health problem affecting all age groups. It can produce from common cold sores and chicken pox to severe conditions like encephalitis or newborn mortality. Although all three subtypes of alpha herpes viruses have a similar structure, the produced pathology differs, and at the same time, the available prevention measures, such as vaccination. While there is an available and efficient vaccine for the varicella-zoster virus, for herpes simplex virus 1 and 2, after multiple approaches from trivalent subunit vaccine to next-generation live-attenuated virus vaccines and bioinformatic studies, there is still no vaccine available. Although there are multiple failed approaches in present studies, there are also a few promising attempts; for example, the trivalent vaccine containing herpes simplex virus type 2 (HSV-2) glycoproteins C, D, and E (gC2, gD2, gE2) produced in baculovirus was able to protect guinea pigs against vaginal infection and proved to cross-protect against HSV-1. Another promising vaccine is the multivalent DNA vaccine, SL-V20, tested in a mouse model, which lowered the clinical signs of infection and produced efficient viral eradication against vaginal HSV-2. Promising approaches have emerged after the COVID-19 pandemic, and a possible nucleoside-modified mRNA vaccine could be the next step. All the approaches until now have not led to a successful vaccine that could be easy to administer and, at the same time, offer antibodies for a long period.

The Bidirectional Relationship between Pulmonary Tuberculosis and Lung Cancer.

Lung cancer and pulmonary tuberculosis are two significant public health problems that continue to take millions of lives each year. They may have similar symptoms and, in some cases, are diagnosed simultaneously or may have a causal relationship. In tuberculosis disease, the chronic inflammation, different produced molecules, genomic changes, and fibrosis are believed to be important factors that may promote carcinogenesis. As a reverse reaction, the development of carcinogenesis and the treatment may induce the reactivation of latent tuberculosis infection. Moreover, the recently used checkpoint inhibitors are a debatable subject since they help treat lung cancer but may lead to the reactivation of pulmonary tuberculosis and checkpoint-induced pneumonitis. Pulmonary rehabilitation is an effective intervention in post-tuberculosis patients and lung cancer patients and should be recommended to improve outcomes in these pathologies.

Romania, a Harbour of HIV-1 Subtype F1: Where Are We after 33 Years of HIV-1 Infection?

Infection with the human immunodeficiency virus (HIV) has been a major public health concern worldwide for more than 30 years, including in Romania. The F1 HIV-1 subtype was exported from Angola to Romania most probably because of the two countries' close political connections. Patients infected with HIV-1 via re-used and improperly sterilized injection equipment and through transfusions of unscreened blood, also known as the "Romanian cohort", were the most common type of HIV-1 infection in Romania in the early 1990s, when the virus's presence was recognized. Recently, subtype B started to increase in our country, mostly diagnosed in people using intravenous drugs or in men having sex with men. The evolution of the HIV-1 infection in Romania has been unique, with a dominance of the subtype F1, making it different from other countries in Europe.

SARS-CoV-2 Infection Anxiety, Knowledge and Attitudes in University Degree Pregnant Women from Romania-A Cross-Sectional Observational Survey in the First Two Pandemic Years.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had a high economic cost, morbidity, and death toll. Due to high rates of mortality and morbidity from coronavirus disease 2019 (COVID-19), pregnant women were at particular risk during this pandemic. We designed and conducted a cross-sectional observational survey in Romanian pregnant women to evaluate the outcome of the SARS-CoV-2 pandemic along with the preventive measures taken by authorities. We applied a 43-item questionnaire. We included 147 women over 18 years old from Romania who were pregnant or gave birth between March 2020 and March 2022. All pregnancies were monitored, most of them by a gynecologist, and only 23% faced rescheduled pregnancy visits. The majority (84%) were screened through the TORCH panel, 95.91% felt anxious because of the pandemic, 87% followed SARS-CoV2 preventive recommendations, and 82% were not infected with the coronavirus. Additionally, 80% were vaccinated against COVID-19. They felt the consequences of the pandemic through anxiety, and their level of anxiety influenced their vaccination decisions, the TORCH testing and the method of giving birth despite the level of education. Fortunately, their pregnancies were monitored properly, and there were no consequences noticed for fetuses at birth.

Phenotypic and genotypic detection methods for antimicrobial resistance in ESKAPE pathogens (Review).

Antimicrobial resistance (AMR) represents a growing public health problem worldwide. Infections with such bacteria lead to longer hospitalization times, higher healthcare costs and greater morbidity and mortality. Thus, there is a greater need for rapid detection methods in order to limit their spread. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) are a series of epidemiologically-important microorganisms of great concern due to their high levels of resistance. This review aimed to update the background information on the ESKAPE pathogens as well as to provide a summary of the numerous phenotypic and molecular methods used to detect their AMR mechanisms. While they are usually linked to hospital acquired infections, AMR is also spreading in the veterinary and the environmental sectors. Yet, the epidemiological loop closes with patients which, when infected with such pathogens, often lack therapeutic options. Thus, it was aimed to give the article a One Health perspective.

Biochemical and Metabolical Pathways Associated with Microbiota-Derived Butyrate in Colorectal Cancer and Omega-3 Fatty Acids Implications: A Narrative Review.

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research progress on the effect of bacterial dysbiosis from a metabolic point of view, particularly on the biochemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with anti-inflammatory and anti-tumor properties in CRC. Increased daily intake of omega-3 polyunsaturated fatty acids (PUFAs) significantly increases the density of bacteria that are known to produce butyrate. Omega-3 PUFAs have been proposed as a treatment to prevent gut microbiota dysregulation and lower the risk or progression of CRC.

Temporo-spatial variations in resistance determinants and clonality of Acinetobacter baumannii and Pseudomonas aeruginosa strains from Romanian hospitals and wastewaters.

BACKGROUND: Romania is one of the European countries reporting very high antimicrobial resistance (AMR) rates and consumption of antimicrobials. We aimed to characterize the AMR profiles and clonality of 304 multi-drug resistant (MDR) Acinetobacter baumannii (Ab) and Pseudomonas aeruginosa (Pa) strains isolated during two consecutive years (2018 and 2019) from hospital settings, hospital collecting sewage tanks and the receiving wastewater treatment plants (WWTPs) located in the main geographical regions of Romania. METHODS: The strains were isolated on chromogenic media and identified by MALDI-TOF-MS. Antibiotic susceptibility testing and confirmation of ESBL- and CP- producing phenotypes and genotypes were performed. The genetic characterization also included horizontal gene transfer experiments, whole-genome sequencing (WGS), assembling, annotation and characterization. RESULTS: Both clinical and aquatic isolates exhibited high MDR rates, especially the Ab strains isolated from nosocomial infections and hospital effluents. The phenotypic resistance profiles and MDR rates have largely varied by sampling point and geographic location. The highest MDR rates in the aquatic isolates were recorded in Galați WWTP, followed by Bucharest. The Ab strains harbored mostly blaOXA-23, blaOXA-24, blaSHV, blaTEM and blaGES, while Pa strains blaIMP, blaVIM, blaNDM, blaVEB, blaGES and blaTEM, with high variations depending on the geographical zone and the sampling point. The WGS analysis revealed the presence of antibiotic resistance genes (ARGs) to other antibiotic classes, such as aminoglycosides, tetracyclines, sulphonamides, fosfomycin, phenicols, trimethoprim-sulfamethoxazole as well as class 1 integrons. The molecular analyses highlighted: (i) The presence of epidemic clones such as ST2 for Ab and ST233 and ST357 for Pa; (ii) The relatedness between clinical and hospital wastewater strains and (iii) The possible dissemination of clinical Ab belonging to ST2 (also proved in the conjugation assays for blaOXA-23 or blaOXA-72 genes), ST79 and ST492 and of Pa strains belonging to ST357, ST640 and ST621 in the wastewaters. CONCLUSION: Our study reveals the presence of CP-producing Ab and Pa in all sampling points and the clonal dissemination of clinical Ab ST2 strains in the wastewaters. The prevalent clones were correlated with the presence of class 1 integrons, suggesting that these isolates could be a significant reservoir of ARGs, being able to persist in the environment.

Immunotherapy-Related Publications in Colorectal Cancer: A Bibliometric Analysis.

Patients with microsatellite-instability-high (MSI-H) or mismatched repair-deficient colorectal cancer (CRC) appear to be responsive to checkpoint inhibitors. This study aimed to assess research trends in CRC immunotherapy. Publication patterns of articles covering immunotherapies in CRC in the Web of Science Core Collection database were retrospectively examined using VOS viewer software (version 1.6.16) prior to 25 May 2021. Ultimately, 3977 records were identified that were published between 1975 and 2021, which received a total of 128,681 citations (an average of 32.36 citations per item), with a noticeable rise in 2014. The majority of articles were published in the US (35.8%), China (17.7%), and Germany (9.4%). Publications mainly originated from the Institut National de la Santé Et De La Recherche Medicale Inserm, followed by the University of Texas System and Harvard University; however, Johns Hopkins University received the most citations (18,666 for 69 publications). The Journal of Clinical Oncology issued the most publications (n = 146), while the most referenced item (7724 citations) was published in the New England Journal of Medicine in 2012. The most common keywords were associated with tumors (expression and microsatellite instability) or immune system components (t-cells/dendritic cells). The findings demonstrate the scientific community's interest in the MSI-H subtype of colorectal tumors and how immunotherapy may be employed more successfully to treat metastatic CRC.

Phenotypic and genotypic virulence features of staphylococcal strains isolated from difficult-to-treat skin and soft tissue infections.

Chronic infections represent an important burden on the healthcare system and have a significant impact on the patients' quality of life. While Staphylococcus spp. are commensal bacteria, they can become pathogenic, leading to various types of infections. In this study we aimed to characterize the virulence profiles of staphylococcal strains involved in difficult-to-treat skin and soft tissue infections, from both phenotypic and genotypic points of view. Phenotypic ability of the strains to secrete soluble virulence factors was assessed by a culturing dependent assay and their capacity to develop biofilms on inert substrate was screened by an adapted crystal violet microtiter method. We also tested the presence of several virulence genes by PCR. Most of the studied strains were isolated from purulent secretions of acne lesions and frequently secreted two or three soluble virulence factors. Most frequently secreted soluble virulence factors were caseinase (89%), lipase (71%) and lecithinase (67%). Almost half of the strains produced a well-represented biofilm. The molecular characterization showed the presence of the genes cna, hlg, clfA, and clfB. Staphylococcal strains that produce difficult-to-treat skin and soft tissue infections seem to be characterized by an enhanced ability to produce different soluble virulence factors and to develop biofilms in vitro. Further studies need to be developed in other Staphylococcus spp. infections in order to confirm this hypothesis.

A Romanian experience of syphilis in pregnancy and childbirth.

OBJECTIVE: to establish the incidence of syphilis in a group of childbearing women and their newborn babies in Romania and to identify the major risk factors of materno-fetal transmission in order for midwives to develop strategies to help prevent congenital syphilis. MATERIAL AND METHODS: a descriptive study of a group of 982 childbearing women who gave birth during a three-month period at an Obstetrics and Gynaecology Hospital in Romania. The women completed a questionnaire, which consisted of three sections: general data, general knowledge of syphilis and birth and pregnancy data. After admission to hospital, the women were investigated for syphilis using serological tests. RESULTS: there was a syphilis frequency of 0.91649% (n = 9) among the surveyed women. Among the nine infected women, two were not aware that they had a syphilis infection when initially admitted to hospital. The maternal profile with the highest risk of being diagnosed with syphilis was a young woman who had not had adequate prenatal care, who had elementary sex education and who lacked knowledge of personal health and hygiene. A significant percentage of the respondents, namely 11.9% (n = 117), were aged 15 to 20. CONCLUSIONS: in certain population groups, syphilis is still an important health care problem, especially in vulnerable individuals, such as childbearing women and newborns babies. More attention needs to be paid to primary prevention; the number of cases of congenital syphilis could be reduced by more involvement of midwifes and family doctors in antenatal care.