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Background: Although useful in the time-race against COVID-19, CPAP cannot provide oxygen over the physiological limits imposed by severe pulmonary impairments. In previous studies, we reported that the administration of the SLAB51 probiotics reduced risk of developing respiratory failure in severe COVID-19 patients through the activation of oxygen sparing mechanisms providing additional oxygen to organs critical for survival., Methods: This "real life" study is a retrospective analysis of SARS-CoV-2 infected patients with hypoxaemic acute respiratory failure secondary to COVID-19 pneumonia undergoing CPAP treatment. A group of patients managed with ad interim routinely used therapy (RUT) were compared to a second group treated with RUT associated with SLAB51 oral bacteriotherapy (OB)., Results: At baseline, patients receiving SLAB51 showed significantly lower blood oxygenation than controls. An opposite condition was observed after 3 days of treatment, despite the significantly reduced amount of oxygen received by patients taking SLAB51. At 7 days, a lower prevalence of COVID-19 patients needing CPAP in the group taking probiotics was observed. The administration of SLAB51 is a complementary approach for ameliorating oxygenation conditions at the systemic level., Conclusion: This study proves that probiotic administration results in an additional boost in alleviating hypoxic conditions, permitting to limit on the use of CPAP and its contraindications.

Background: We previously reported that severe COVID-19 patients had higher chances of survival and a reduced risk of developing respiratory failure when administered with the probiotic formulation SLAB51. This study aimed to investigate further bacteriotherapy mechanisms and how early they are activated., Methods: We performed an analysis on the blood oxygenation parameters collected in sixty-nine severe COVID-19 patients requiring non-invasive oxygen therapy and presenting a CT lung involvement ≥50%. Twenty-nine patients received low-molecular-weight heparin, azithromycin and Remdesivir. In addition, forty subjects received SLAB51. Blood gas analyses were performed before the beginning of treatments and at 24 h., Results: The patients receiving only standard therapy needed significantly increased oxygen amounts during the 24 h observation period. Furthermore, they presented lower blood levels of pO 2 , O 2 Hb and SaO 2 than the group also supplemented with oral bacteriotherapy. In vitro data suggest that SLAB51 can reduce nitric oxide synthesis in intestinal cells., Conclusions: SARS-CoV-2 infected patients may present lesions in the lungs compromising their gas exchange capability. The functionality of the organs essential for these patients' survival depends mainly on the levels of pO 2 , O 2 Hb and SaO 2 . SLAB51 contains enzymes that could reduce oxygen consumption in the intestine, making it available for the other organs.

Background: Gastrointestinal disorders are frequent in COVID-19 and SARS-CoV-2 has been hypothesized to impact on host microbial flora and gut inflammation, infecting intestinal epithelial cells. Since there are currently no coded therapies or guidelines for treatment of COVID-19, this study aimed to evaluate the possible role of a specific oral bacteriotherapy as complementary therapeutic strategy to avoid the progression of COVID-19. Methods: We provide a report of 70 patients positive for COVID-19, hospitalized between March 9th and April 4th, 2020. All the patients had fever, required non-invasive oxygen therapy and presented a CT lung involvement on imaging more than 50%. Forty-two patients received hydroxychloroquine, antibiotics, and tocilizumab, alone or in combination. A second group of 28 subjects received the same therapy added with oral bacteriotherapy, using a multistrain formulation. Results: The two cohorts of patients were comparable for age, sex, laboratory values, concomitant pathologies, and the modality of oxygen support. Within 72 h, nearly all patients treated with bacteriotherapy showed remission of diarrhea and other symptoms as compared to less than half of the not supplemented group. The estimated risk of developing respiratory failure was eight-fold lower in patients receiving oral bacteriotherapy. Both the prevalence of patients transferred to ICU and mortality were higher among the patients not treated with oral bacteriotherapy. Conclusions: A specific bacterial formulation showed a significant ameliorating impact on the clinical conditions of patients positive for SARS-CoV-2 infection. These results also stress the importance of the gut-lung axis in controlling the COVID-19 disease., (Copyright © 2020 d'Ettorre, Ceccarelli, Marazzato, Campagna, Pinacchio, Alessandri, Ruberto, Rossi, Celani, Scagnolari, Mastropietro, Trinchieri, Recchia, Mauro, Antonelli, Pugliese and Mastroianni.)

Background: A wide debate is ongoing regarding the role of cutaneous dysbiosis in the pathogenesis and evolution of difficult-to-treat chronic wounds. Nowadays, probiotic treatment considered as an useful tool to counteract dysbiosis but the evidence in regard to their therapeutic use in the setting of difficult-to-treat cutaneous ulcers is still poor., Aim: CLINICAL REPORT: An 83-year-old woman suffering a critical limb ischemia and an infected difficult-to-treat ulcerated cutaneous lesion of the right leg, was complementary treated with local application of a mixture of probiotic bacteria., Methods: Microbiological and metabolomic analysis were conducted on wound swabs obtained before and after bacteriotherapy., Results: During the treatment course, a progressive healing of the lesion was observed with microbiological resolution of the polymicrobial infection of the wound. Metabolomic analysis showed a significant difference in the local concentration of propionate, 2-hydroxyisovalerate, 2-oxoisocaproate, 2,3-butanediol, putrescine, thymine, and trimethylamine before and after bacteriotherapy., Conclusion: The microbiological and metabolomic results seem to confirm the usefulness of complementary probiotic treatment in difficult-to-treat infected wounds. Further investigations are needed to confirm these preliminary findings.

Background: Variability in probiotics manufacturing may affect their properties, with potential implications for their efficacy and safety. This is of particular concern with probiotic products destined for use in patients with serious medical conditions, including human immunodeficiency virus (HIV) infection. The purpose of the study was to carry out a series of experiments comparing the properties of the US-made probiotic formulation originally commercialized under the brand name VSL#3 ® , with those of the Italian-made formulation now commercialized under the same name. The US-made formulation has previously shown beneficial effects at the intestinal and neurological levels in HIV-infected subjects as well as in patients with inflammatory bowel diseases and hepatic encephalopathy., Methods: Eleven subjects receiving combined antiretroviral therapy for HIV-1 were treated for 6 months with the US-made VSL#3 formulation. At baseline and 6 months, T-cells were analyzed for phenotype and activation markers, and fecal samples were analyzed for bifidobacteria, lactobacilli, and their metabolites. The fecal metabolome was assessed using 1 H-NMR spectroscopy. Production of metabolites of interest by bacteria obtained from sachets of the two formulations was compared in vitro and their effects on a rat intestinal epithelial cell line (IEC-6) were assessed. Particular attention was paid to the metabolite 1,3-dihydroxyacetone (DHA)., Results: At 6 months, fecal samples showed a significant increase in the specific bacterial genera contained in the probiotic supplement. Immune activation was reduced as shown by a significant reduction in the percentage of CD4 + CD38 + HLA-DR + T-cells at 6 months. Fecal concentrations of DHA decreased significantly. In vitro , significant differences in the production and metabolism of DHA were found between bacteria from the US-made and Italian-made formulations: the US-made formulation was able to metabolize DHA whereas the bacteria in the Italian-made formulation were producing DHA. DHA reduced the viability of Streptococcus thermophilus , reduced IEC-6 cell viability in a dose-dependent manner, and also led to a lower rate of repair to scratched IEC-6 cell monolayer., Conclusion: Our data, in conjunction with previously published findings, confirm that the new Italian-made formulation of VSL#3 ® is different from the previous US-made VSL#3 and therefore its efficacy and safety in HIV-infected subjects is still unproven.

Introduction: HIV infection is characterized by a persistent immune activation associated to a compromised gut barrier immunity and alterations in the profile of the fecal flora linked with the progression of inflammatory symptoms. The effects of high concentration multistrain probiotic (Vivomixx®, Viale del Policlinico 155, Rome, Italy in EU; Visbiome®, Dupont, Madison, Wisconsin in USA) on several aspects of intestinal immunity in ART-experienced HIV-1 patients was evaluated., Methods: A sub-study of a longitudinal pilot study was performed in HIV-1 patients who received the probiotic supplement twice a day for 6 months (T6). T-cell activation and CD4+ and CD8+ T-cell subsets expressing IFNγ (Th1, Tc1) or IL-17A (Th17, Tc17) were stained by cytoflorimetric analysis. Histological and immunohistochemical analyses were performed on intestinal biopsies while enterocytes apoptosis index was determined by TUNEL assay., Results: A reduction in the frequencies of CD4 + and CD8 + T-cell subsets, expressing CD38 + , HLA-DR + , or both, and an increase in the percentage of Th17 cell subsets, especially those with central or effector memory phenotype, was recorded in the peripheral blood and in gut-associated lymphoid tissue (GALT) after probiotic intervention. Conversely, Tc1 and Tc17 levels remained substantially unchanged at T6, while Th1 cell subsets increase in the GALT. Probiotic supplementation was also associated to a recovery of the integrity of the gut epithelial barrier, a reduction of both intraepithelial lymphocytes density and enterocyte apoptosis and, an improvement of mitochondrial morphology sustained in part by a modulation of heat shock protein 60., Conclusions: These findings highlight the potential beneficial effects of probiotic supplementation for the reconstitution of physical and immunological integrity of the mucosal intestinal barrier in ART-treated HIV-1-positive patients., (© 2017 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.)

Background: The prevention of oral mucositis (OM) in the management of hematological malignancies continues to represent an unmet clinical need. Addressing this issue has major clinical implications as OM can also greatly impair patient's quality of life., Objectives: To review currently available measures and investigational agents to prevent OM in hematological patients., Methods: we searched for OM and related issues using Medline; the abstract books of the most important hematological and oncological meetings were also reviewed., Results/conclusions: Many agents targeting different mechanisms of mucosal damage have been applied in order to prevent OM; most of them have failed or its efficacy has not been fully demonstrated. Palifermin is the first pharmaceutical/biological agent approved for the prevention of OM; its use is currently restricted to patients who have received radiotherapy-containing conditioning regimens prior to autologous hematopoietic stem cell transplantation. No clear benefit by this agent has been demonstrated outside of this specific setting and its application should be limited to clinical trials. Other interventions, such as other growth factors and non mitogenic measures are under investigation or in development and their application in the hematological setting is expected in the short term.

Lactococcus garvieae is a human opportunistic pathogen with low virulence, but it is a well-known pathogen in aquaculture. A total of 21 human infections have been reported in the literature, mostly endocarditis. Automated methods can wrongly identify this microorganism as Enterococcus spp with a non-standard phenotype, leading to an underestimation of the incidence of this infection. The route of infection could be the ingestion of raw fish, grilled fish or fresh dairy products. We describe the first case of L. garvieae mitral valve endocarditis in Italy, in a patient with mitral valve repair with autologous pericardium, mechanic prosthetic aortic valve and colonic diverticulosis.

Breast tuberculosis is a rare disease in highly endemic countries, and it is even rarer in Western countries, where only occasionally the local population is affected. The rarity of the disease and particularly the lack of a typical clinical-radiological presentation may cause tuberculosis to be mistaken for breast cancer or a pyogenic abscess. The authors present a case of breast tuberculosis in a 27-year-old nulliparous woman, an Italian citizen of the Caucasian race, who has never resided in a tuberculosis endemic area. She presented with painful retroareolar and para-areolar swelling in the right breast associated with cutaneous hyperemia (without fistulization), resistant to antibiotic therapy. Histopathological examination revealed features of mastitis with epithelioid histiocytes and Langhans giant cells and was characterized by the presence of caseous necrosis which suggested tuberculous inflammation. Ziehl-Neelsen staining showed the presence of acid fast bacilli. In countries where tuberculosis is non-endemic, breast tuberculosis should always be included in the differential diagnosis in cases of inflammatory breast lesions resistant to the usual antibiotic therapies. Early recognition may prevent both clinical progression and surgical excision, as breast tuberculosis usually regresses as a response to appropriate anti-tuberculosis therapy.

We present a case of Rhodococcus equi primary retroperitoneal abscesses without pulmonary involvement in an immunocompromised patient with severe nephrotic syndrome. No risk factors for exposure to R. equi were present. The infection was successfully treated with long-term combination antibiotic treatment including linezolid and tigecycline., (Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

AIM.: The lactic bacteria are Gram-positive microorganisms with coccus or stick shape, which share a number of physiological and biochemical properties. Several experimental evidences suggest the possibility of using lactic acid bacterial as a preventive or therapeutic potential approaches, alternative or complementary to prevention or treatment protocols currently followed in several pathological conditions. Lactobacillus brevis is able, through the arginine-deiminase activity, to subtract the substrate (arginine) to nitric oxide synthase, and to inhibit in vitro generation of nitric oxide from rat's peritoneal macrophages. These data led us to study the in vivo L. brevis anti-inflammatory effect choosing as experimental model the gingivitis. MATERIALS AND METHODS.: In our study were examined 21 subjects, 16 males and 5 females, aged between 5 and 12 years, with marginal gingivitis problems who have been given chewing gum containing the principle to test in measure of three per day. RESULTS.: At the time T1, after treatment, 18 patients no longer showed inflammation; 2 of them had a slight inflammation and only 1 patient still showed a moderate inflammation. CONCLUSIONS.: From our research, as confirmed by clinical and laboratory investigation, results an effective anti-inflammatory action of arginine-deiminase system that some bacteria possessing.

Carnitine and its congeners may regulate the immune networks, and their influence on functions of immune cells predominantly or exclusively relies on carnitine-dependent energy production from fatty acids. A reduced pool of carnitines has been demonstrated in either serum or tissues, or both, from patients with a wide spectrum of disorders characterized by unregulated or impaired immune responses ranging from sepsis syndrome to systemic sclerosis, infection with human immunodeficiency virus, and chronic fatigue syndrome. Furthermore, experimental studies have consistently reported that the deranged immune responses and the less efficient inflammation towards infectious organisms associated with aging may be enhanced or modulated by treatment with carnitines. There is also evidence that carnitine deprivation could adversely affect the course of the sepsis syndrome, at least in experimental models, and preliminary studies suggest that carnitine deficiency is ultimately implicated in the pathophysiology of endotoxin-mediated multiple organ failure. Several data indicate that carnitine deficiency is a contributing factor to the progression of infection with human immunodeficiency virus, and carnitine therapy in those patients could counteract the unregulated process of lymphocyte apoptosis and improve CD4 counts. Some case reports have suggested the use of carnitine for the treatment of the severe lactic acidosis that complicates in some patients the use of reverse transcriptase inhibitors.

Inflammatory bowel disease, such as ulcerative colitis and Crohn's disease, results from an interaction between susceptibility genes, the host's bacterial environment, gut barrier defects, and immunological factors. New management approaches have been evolved from advances in our understanding of the pathobiology of this common gut disorder In particular, the therapeutic manipulation of the bacterial microenvironment in the gut seems to offer an innovative tool for the treatment of those patients. Since the gut is a highly sensitizing organ that contributes to the systemic immune response, potent treatments need to be developed to reduce gut inflammation in this disorder. Recent studies have demonstrated that probiotic lactobacilli, and also immunostimulatory DNA sequences from those same bacteria have an important anti-inflammatory potential in this context. Future research should better define among patients with inflammatory bowel disease the various clinical phenotypes with the greatest potential of response to probiotic treatment. Identification of the genes leading to the disease and a rather better understanding of the underlying immunoregulatory abnormalities will be crucial steps to define the different profiles of interaction between endogenous digestive bacterial flora and the immune system in each individual patient. Such advances will probably lead to targeting of effective treatments, including bacteriotherapy with probiotic lactobacilli, to subsets of patients with inflammatory bowel disease.