Microbial Symphony: Exploring the Role of the Gut in Osteoarthritis-Related Pain. A Narrative Review.

One of the most common musculoskeletal disorders, osteoarthritis (OA), causes worldwide disability, morbidity, and poor quality of life by degenerating articular cartilage, modifying subchondral bone, and inflaming synovial membranes. OA pathogenesis pathways must be understood to generate new preventative and disease-modifying therapies. In recent years, it has been acknowledged that gut microbiota (GM) can significantly contribute to the development of OA. Dysbiosis of GM can disrupt the "symphony" between the host and the GM, leading to a host immunological response that activates the "gut-joint" axis, ultimately worsening OA. This narrative review summarizes research supporting the "gut-joint axis" hypothesis, focusing on the interactions between GM and the immune system in its two main components, innate and adaptive immunity. Furthermore, the pathophysiological sequence of events that link GM imbalance to OA and OA-related pain is broken down and further investigated. We also suggest that diet and prebiotics, probiotics, nutraceuticals, exercise, and fecal microbiota transplantation could improve OA management and represent a new potential therapeutic tool in the light of the scarce panorama of disease-modifying osteoarthritis drugs (DMOADs). Future research is needed to elucidate these complex interactions, prioritizing how a particular change in GM, i.e., a rise or a drop of a specific bacterial strain, correlates with a certain OA subset to pinpoint the associated signaling pathway that leads to OA.

Gut Microbiota Modulation and Its Implications on Neuropathic Pain: A Comprehensive Literature Review.

Neuropathic pain (NP) is a chronic pain disorder arising from somatosensory nervous system impairment. Extensive evidence supports the notion that the gut microbiota (GM) is crucial in maintaining human health by performing vital tasks. At the same time, its disruption has been linked to the emergence and advancement of an expanding range of disorders, including NP, in which GM could play a role in its pathophysiology. The crosstalk between the nervous system and GM happens through immune mediators, metabolites, and nervous structures and involves both central and peripheral nervous systems. This literature review aims to thoroughly investigate the function of modulating GM in the treatment of NP. It will achieve this by integrating existing knowledge, identifying underlying mechanisms, and evaluating the possible clinical consequences of exploiting the gut-brain axis. We will cover the main therapeutic applications of the described GM-modulators, such as probiotics, faecal microbiota transplantation, dietary supplements and emotional support, to the main kinds of NP in which any evidence, even if only pre-clinical, has been unravelled in recent years. The explored NP areas include chemotherapy-induced peripheral neuropathy, diabetic neuropathy, trauma-induced neuropathic pain, trigeminal neuralgia, postherpetic neuralgia and low back pain.

The Benefits of Probiotics on Oral Health: Systematic Review of the Literature.

Aim: Probiotic microorganisms, commonly used to bolster gut health, might also have benefits for dental health, according to certain studies. Probiotics (PBs) are associated with reducing cariogenic pathogens and protecting against periodontal diseases, although the exact way they function in the mouth is not fully clear. Our study aimed to explore the use of PBs to improve oral health, focusing on issues such as cavities, gum disease, bad breath, mucositis, and periimplantitis. Materials and Methods: We utilized the Boolean keywords "Probiotics" AND "Oral health" to search the databases of PubMed, Scopus, and Web of Science. The search was restricted to English-language papers published from 1 January 2019 to 13 April 2023. Results: A total of 3460 articles were found through our computerized search. After removing duplicates, reviewing the papers, and determining their relevance, 12 were selected for inclusion. Conclusions: Assessing how bacteria in food or dietary supplements might alter the stable oral microbiota is a complex task. Although probiotic microorganisms have been found to have proven therapeutic benefits, their application in dental health is not yet solidly backed by evidence. Further research is necessary to thoroughly understand the long-term effects of probiotic bacteria on the oral environment, including their ability to colonize and form biofilms.

Low Back Pain and Radiofrequency Denervation of Facet Joint: Beyond Pain Control-A Video Recording.

Chronic low back pain is often due to L5S1 instability resulting in facet joint syndrome. Patients suffering from low back pain may also have a gait pattern characterized by a reduced speed and a shorter, asymmetrical step in order to reduce pain. This case is of a patient with L5S1 instability that occurred after L1 to L5 lumbar stabilization who was treated with radiofrequency (RF) denervation of the medial branch of L5S1 bilaterally. RF ablation outcome was tested by comparing its impact on pain, function, quality of life, and on gait pattern, before and 1 month after the procedure. To objectify the impact of a good pain control on gait, a video recording was performed (see Video 1).

Relationship between oral lesions and severe SARS-CoV-2 infection in intensive care unit patients.

OBJECTIVE: Oral lesions received increased attention as likely new signs or secondary manifestations of COVID-19. Therefore, we clinically examined oral cavity of patients with COVID-19 and investigated oral lesions and patient comorbidities as possible risk factors of COVID-19 disease outcome. METHODS: From January to March 2022, a prospective study was conducted by recruiting all COVID-19 patients admitted to the Intensive Care Unit and Respiratory Intensive Care Unit of Maxi-Emergencies Hospital in Bari, Italy. RESULTS: From the enrolled 103 COVID-19 patients, 46.6% were females and 53.4% were males. Findings show that risk of presenting with severe COVID-19 disease was higher in patients who developed oral lesions related to COVID-19 than those with no oral lesions (RR = 7.998, p = .002). Next, patients with concomitant autoimmune diseases were at higher risk of a negative COVID-19 disease outcome than those without comorbidities (OR = 8.838, p = .026). CONCLUSIONS: COVID-19-related lesions of oral mucosa should not be ignored as they can be early and easily detectable signs of severe COVID-19 disease condition, thus, serving as a prevention measure for any potential unfortunate event. Findings of this study, without implying causation, offer a direction for future investigations that aim to confirm the presence of specific oral lesions in COVID-19 patients as signs of severe disease progression.

The central role of the gut in intensive care.

Critically ill patients undergo early impairment of their gut microbiota (GM) due to routine antibiotic therapies and other environmental factors leading to intestinal dysbiosis. The GM establishes connections with the rest of the human body along several axes representing critical inter-organ crosstalks that, once disrupted, play a major role in the pathophysiology of numerous diseases and their complications. Key players in this communication are GM metabolites such as short-chain fatty acids and bile acids, neurotransmitters, hormones, interleukins, and toxins. Intensivists juggle at the crossroad of multiple connections between the intestine and the rest of the body. Harnessing the GM in ICU could improve the management of several challenges, such as infections, traumatic brain injury, heart failure, kidney injury, and liver dysfunction. The study of molecular pathways affected by the GM in different clinical conditions is still at an early stage, and evidence in critically ill patients is lacking. This review aims to describe dysbiosis in critical illness and provide intensivists with a perspective on the potential as adjuvant strategies (e.g., nutrition, probiotics, prebiotics and synbiotics supplementation, adsorbent charcoal, beta-lactamase, and fecal microbiota transplantation) to modulate the GM in ICU patients and attempt to restore eubiosis.

Diagnosis of SARS-CoV-2 during the Pandemic by Multiplex RT-rPCR hCoV Test: Future Perspectives.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a significant threat to public health. However, among the Coronaviridae family members, there are other viruses that can also cause infections in humans. Among these, severe acute respiratory syndrome (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV) have posed significant threats to human health in the past. Other human pathogenic coronaviruses have been identified, and they are known to cause respiratory diseases with manifestations ranging from mild to severe. In this study, we evaluated the performance of a multiplex RT-rPCR specific to seven human pathogenic coronaviruses in mainly detecting SARS-CoV-2 directly from nasopharyngeal swabs obtained from suspected COVID-19 infected patients, while simultaneously detecting different human pathogenic coronaviruses in case these were also present. We tested 1195 clinical samples suspected of COVID-19 infection. The assay identified that 69% of the samples tested positive for SARS-CoV-2 (1195), which was confirmed using another SARS-CoV-2 RT-PCR kit available in our laboratory. None of these clinical samples were positive for SARS-CoV, MERS-CoV or HCoV. This means that during the endemic phase of COVID-19, infection with other human pathogenic coronaviruses, even the common cold coronavirus (HCoV), is very uncommon. Our study also confirmed that the multiplex RT-rPCR is a sensitive assay for detecting SARS-CoV-2 regardless of differences among the variants. This multiplex RT-rPCR is also time- and cost-saving and very easy to apply in the diagnostic laboratory due to its simple procedure and its stability in storage after preparation. These features make the assay a valuable approach in screening procedures for the rapid detection of SARS-CoV-2 and other human pathogenic coronaviruses that could affect public health.

Antispike Immunoglobulin-G (IgG) Titer Response of SARS-CoV-2 mRNA-Vaccine (BNT162b2): A Monitoring Study on Healthcare Workers.

The secretion of IgG SARS-CoV-2 antispike antibodies after vaccination with BNT162b2 and the protection represent the response of the human organism to the viral vector symptomatic infections. The aim of the present investigation was to evaluate the immune reaction in health workers of the Polyclinic of Bari to identify the relationship of antispike titers with blood type, sex, age, and comorbidities. This prospective observational study (RENAISSANCE) had as its primary endpoint the assessment of serologic response to BNT162b2 at three blood titers: the first at 60 days after the second dose (3 February 2021); the second titer at 75 days after the first titer; and the third titer at 130 days after the second titer. Out of 230 enrolled staff members, all responded excellently to the mRna Pfizer (BNT162b) vaccine. Only one patient, 40 days after the second dose (3 February 2021), was positive on the swab control performed on 15 March 2021, although completely asymptomatic, and was negative on the subsequent molecular swab performed on 30 March 2021. All the patients responded to the mRNA Pfizer (BNT162b) vaccine with an antispike IgG level above 500 BAU/mL at the first antispike protein essay (60 days after the second dose on 3 April 2021); at the second titer (75 days after the first titer on 20 June 2021), 4 (1.7% of 230 enrolled) patients showed an antispike IgG level under 500 BAU/mL; at the third titer (130 days after the second titer on 30 June 2021, which means 9 months after the second dose), 37 (16.1% of 230 enrolled) patients showed an antispike IgG level under 500 BAU/mL. The data analysis demonstrated that patients belonging to blood group 0, regardless of their rhesus factor, showed the strongest level of antibodies compared to the other groups. No dependency was found between low antibodies level and sex or age. Molecular swab controls were performed every 15th of the month continuously. However, the enrolled patients' activity was at high risk because they carried out medical activities such as dental and surgical as well with droplets of water vaporized by the effect of turbines, piezosurgery. The vaccination campaign among health workers of the Policlinico of the University of Bari "Aldo Moro" led to an excellent serological response and the complete absence of COVID-19 incident cases, so the antibody response was excellent. The COVID-19 vaccine booster shot should be administered after 9 months and not without prompt antispike titer detection to assess if any sign of waning immunity is present in that specific patient.

Effects of Resveratrol, Curcumin and Quercetin Supplementation on Bone Metabolism-A Systematic Review.

Phenolic compounds are natural phytochemicals that have recently reported numerous health benefits. Resveratrol, curcumin, and quercetin have recently received the most attention among these molecules due to their documented antioxidant effects. The review aims to investigate the effects of these molecules on bone metabolism and their role in several diseases such as osteopenia and osteoporosis, bone tumours, and periodontitis. The PubMed/Medline, Web of Science, Google Scholar, Scopus, Cochrane Library, and Embase electronic databases were searched for papers in line with the study topic. According to an English language restriction, the screening period was from January 2012 to 3 July 2022, with the following Boolean keywords: ("resveratrol" AND "bone"); ("curcumin" AND "bone"); ("quercetin" AND "bone"). A total of 36 papers were identified as relevant to the purpose of our investigation. The studies reported the positive effects of the investigated phenolic compounds on bone metabolism and their potential application as adjuvant treatments for osteoporosis, bone tumours, and periodontitis. Furthermore, their use on the titanium surfaces of orthopaedic prostheses could represent a possible application to improve the osteogenic processes and osseointegration. According to the study findings, resveratrol, curcumin, and quercetin are reported to have a wide variety of beneficial effects as supplement therapies. The investigated phenolic compounds seem to positively mediate bone metabolism and osteoclast-related pathologies.

Effectiveness of SARS-CoV-2 Vaccines for Short- and Long-Term Immunity: A General Overview for the Pandemic Contrast.

BACKGROUND: The recent COVID-19 pandemic produced a significant increase in cases and an emergency state was induced worldwide. The current knowledge about the COVID-19 disease concerning diagnoses, patient tracking, the treatment protocol, and vaccines provides a consistent contribution for the primary prevention of the viral infection and decreasing the severity of the SARS-CoV-2 disease. The aim of the present investigation was to produce a general overview about the current findings for the COVID-19 disease, SARS-CoV-2 interaction mechanisms with the host, therapies and vaccines' immunization findings. METHODS: A literature overview was produced in order to evaluate the state-of-art in SARS-CoV-2 diagnoses, prognoses, therapies, and prevention. RESULTS: Concerning to the interaction mechanisms with the host, the virus binds to target with its Spike proteins on its surface and uses it as an anchor. The Spike protein targets the ACE2 cell receptor and enters into the cells by using a special enzyme (TMPRSS2). Once the virion is quietly accommodated, it releases its RNA. Proteins and RNA are used in the Golgi apparatus to produce more viruses that are released. Concerning the therapies, different protocols have been developed in observance of the disease severity and comorbidity with a consistent reduction in the mortality rate. Currently, different vaccines are currently in phase IV but a remarkable difference in efficiency has been detected concerning the more recent SARS-CoV-2 variants. CONCLUSIONS: Among the many questions in this pandemic state, the one that recurs most is knowing why some people become more seriously ill than others who instead contract the infection as if it was a trivial flu. More studies are necessary to investigate the efficiency of the treatment protocols and vaccines for the more recent detected SARS-CoV-2 variant.

Oralbiotica/Oralbiotics: The Impact of Oral Microbiota on Dental Health and Demineralization: A Systematic Review of the Literature.

The oral microbiota plays a vital role in the human microbiome and oral health. Imbalances between microbes and their hosts can lead to oral and systemic disorders such as diabetes or cardiovascular disease. The purpose of this review is to investigate the literature evidence of oral microbiota dysbiosis on oral health and discuss current knowledge and emerging mechanisms governing oral polymicrobial synergy and dysbiosis; both have enhanced our understanding of pathogenic mechanisms and aided the design of innovative therapeutic approaches as ORALBIOTICA for oral diseases such as demineralization. PubMed, Web of Science, Google Scholar, Scopus, Cochrane Library, EMBEDDED, Dentistry & Oral Sciences Source via EBSCO, APA PsycINFO, APA PsyArticles, and DRUGS@FDA were searched for publications that matched our topic from January 2017 to 22 April 2022, with an English language constraint using the following Boolean keywords: ("microbio*" and "demineralization*") AND ("oral microbiota" and "demineralization"). Twenty-two studies were included for qualitative analysis. As seen by the studies included in this review, the balance of the microbiota is unstable and influenced by oral hygiene, the presence of orthodontic devices in the oral cavity and poor eating habits that can modify its composition and behavior in both positive and negative ways, increasing the development of demineralization, caries processes, and periodontal disease. Under conditions of dysbiosis, favored by an acidic environment, the reproduction of specific bacterial strains increases, favoring cariogenic ones such as Bifidobacterium dentium, Bifidobacterium longum, and S. mutans, than S. salivarius and A. viscosus, and increasing of Firmicutes strains to the disadvantage of Bacteroidetes. Microbial balance can be restored by using probiotics and prebiotics to manage and treat oral diseases, as evidenced by mouthwashes or dietary modifications that can influence microbiota balance and prevent or slow disease progression.

Cavernous Sinus Involvement and Near Miss Mediastinitis following Mandibular Tooth Infection Treated during the COVID-19 Pandemic: Clinical Diagnosis and Treatment.

Odontogenic infections represent a frequent condition that in some cases, if not treated promptly, can spread quickly to the rest of the body and turn into life-threatening infections. In this work, the case is reported of a 59-year-old woman, diabetic and overweight, who presented to the Odontostomatology and Otolaryngology Section of the Policlinic of Bari with mandibular tooth infection that had developed into a deep neck space infection leading to the involvement of cavernous sinuses and near mediastinum. The diagnosis, the surgical drainage of the phlegmon and removal of infection foci, appropriate control of the airways, and a correct antibiotic therapy made it possible to avoid a potentially fatal condition. Prompt management and early diagnosis of deep space neck infections, such as phlegmon and/or necrotizing fasciitis, with the auxilium of CT scans and tools such as LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis), NLR (Neutrophil-to-Lymphocyte Ratio), and LRINECxNLR scores (Laboratory Risk Indicator for Necrotizing Fasciitis and Neutrophil to Lymphocyte Ratio), are advised to evade delays and complications that could potentially worsen the patient's outcome.

COVID-19 Variants in Critically Ill Patients: A Comparison of the Delta and Omicron Variant Profiles.

BACKGROUND: Coronavirus disease is a pandemic that has disrupted many human lives, threatening people's physical and mental health. Each pandemic wave struck in different ways, infectiveness-wise and mortality-wise. This investigation focuses on critically ill patients affected by the last two variants, Delta and Omicron, and aims to analyse if any difference exists between the two groups. METHODS: intensive care unit (ICU) COVID-19 consecutive admissions between 1 October 2021 and 31 March 2022 were recorded daily, and data concerning the patients' demographics, variants, main comorbidities, ICU parameters on admission, and the outcome were analysed by a univariate procedure and by a multivariate analysis. RESULTS: 65 patients were enrolled, 31 (47.69%) belonging to the Omicron versus 34 (52.31%) to the Delta group. The mortality rate was 52.94% for the Omicron group versus 41.9% for the Delta group. A univariate analysis showed that the Omicron variant was associated with total comorbidities number, Charlson Comorbidity Index (CCI), pre-existing pulmonary disease, vaccination status, and acute kidney injury (AKI). In stepwise multivariate analysis, the total number of comorbidities was positively associated with the Omicron group, while pulmonary embolism was negatively correlated with the Omicron group. CONCLUSION: Omicron appears to have lost some of the hallmarks of the Delta variant, such as endothelialitis and more limited cellular tropism when it comes to the patients in the ICU. Further studies are encouraged to explore different therapeutic approaches to treat critical patients with COVID-19.

Benefits and Implications of Resveratrol Supplementation on Microbiota Modulations: A Systematic Review of the Literature.

Resveratrol is a polyphenol that has been shown to possess many applications in different fields of medicine. This systematic review has drawn attention to the axis between resveratrol and human microbiota, which plays a key role in maintaining an adequate immune response that can lead to different diseases when compromised. Resveratrol can also be an asset in new technologies, such as gene therapy. PubMed, Cochrane Library, Scopus, Web of Science, and Google Scholar were searched to find papers that matched our topic dating from 1 January 2017 up to 18 January 2022, with English-language restriction using the following Boolean keywords: ("resveratrol" AND "microbio*"). Eighteen studies were included as relevant papers matching the purpose of our investigation. Immune response, prevention of thrombotic complications, microbiota, gene therapy, and bone regeneration were retrieved as the main topics. The analyzed studies mostly involved resveratrol supplementation and its effects on human microbiota by trials in vitro, in vivo, and ex vivo. The beneficial activity of resveratrol is evident by analyzing the changes in the host's genetic expression and the gastrointestinal microbial community with its administration. The possibility of identifying individual microbial families may allow to tailor therapeutic plans with targeted polyphenolic diets when associated with microbial dysbiosis, such as inflammatory diseases of the gastrointestinal tract, degenerative diseases, tumors, obesity, diabetes, bone tissue regeneration, and metabolic syndrome.

COVID-19 Infection in Children and Infants: Current Status on Therapies and Vaccines.

Since the beginning in December 2019, the SARS-CoV-2 outbreak appeared to affect mostly the adult population, sparing the vast majority of children who only showed mild symptoms. The purpose of this investigation is to assess the status on the mechanisms that give children and infants this variation in epidemiology compared to the adult population and its impact on therapies and vaccines that are aimed towards them. A literature review, including in vitro studies, reviews, published guidelines and clinical trials was performed. Clinical trials concerned topics that allowed a descriptive synthesis to be produced. Four underlying mechanisms were found that may play a key role in providing COVID-19 protection in babies. No guidelines are available yet for therapy due to insufficient data; support therapy remains the most used. Only two vaccines are approved by the World Health Organization to be used in children from 12 years of age, and there are currently no efficacy or safety data for children below the age of 12 years. The COVID-19 clinical frame infection is milder in children and adolescents. This section of the population can act as vectors and reservoirs and play a key role in the transmission of the infection; therefore, vaccines are paramount. More evidence is required to guide safely the vaccination campaign.

Perioperative goal-directed therapy and postoperative complications in different kind of surgical procedures: an updated meta-analysis.

BACKGROUND: Goal-directed therapy (GDT) aims to assure tissue perfusion, by optimizing doses and timing of fluids, inotropes, and vasopressors, through monitoring of cardiac output and other basic hemodynamic parameters. Several meta-analyses confirm that GDT can reduce postoperative complications. However, all recent evidences focused on high-risk patients and on major abdominal surgery. OBJECTIVES: The aim of the present meta-analysis is to investigate the effect of GDT on postoperative complications (defined as number of patients with a least one postoperative complication) in different kind of surgical procedures. DATA SOURCES: Randomized controlled trials (RCTs) on perioperative GDT in adult surgical patients were included. The primary outcome measure was complications, defined as number of patients with at least one postoperative complication. A subgroup-analysis was performed considering the kind of surgery: major abdominal (including also major vascular), only vascular, only orthopedic surgery. and so on. STUDY APPRAISAL AND SYNTHESIS METHODS: Meta-analytic techniques (analysis software RevMan, version 5.3.5, Cochrane Collaboration, Oxford, England, UK) were used to combine studies using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In 52 RCTs, 6325 patients were enrolled. Of these, 3162 were randomized to perioperative GDT and 3153 were randomized to control. In the overall population, 2836 patients developed at least one complication: 1278 (40%) were randomized to perioperative GDT, and 1558 (49%) were randomized to control. Pooled OR was 0.60 and 95% CI was 0.49-0.72. The sensitivity analysis confirmed the main result. The analysis enrolling major abdominal patients showed a significant result (OR 0.72, 95% CI 0.59-0.87, p = 0.0007, 31 RCTs, 4203 patients), both in high- and low-risk patients. A significant effect was observed in those RCTs enrolling exclusively orthopedic procedures (OR 0.53, 95% CI 0.35-0.80, p = 0.002, 7 RCTs, 650 patients. Also neurosurgical procedures seemed to benefit from GDT (OR 0.40, 95% CI 0.21-0.78, p = 0.008, 2 RCTs, 208 patients). In both major abdominal and orthopedic surgery, a strategy adopting fluids and inotropes yielded significant results. The total volume of fluid was not significantly different between the GDT and the control group. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The present meta-analysis, within the limits of the existing data, the clinical and statistical heterogeneity, suggests that GDT can reduce postoperative complication rate. Moreover, the beneficial effect of GDT on postoperative morbidity is significant on major abdominal, orthopedic and neurosurgical procedures. Several well-designed RCTs are needed to further explore the effect of GDT in different kind of surgeries.