The discovery of immune checkpoints (CTLA-4, PD-1, and PD-L1) and their impact on the prognosis of oncological diseases have paved the way for the development of revolutionary oncological treatments. ...These treatments do not combat tumors with drugs “against” cancer cells but rather support and enhance the ability of the immune system to respond directly to tumor growth by attacking the cancer cells with lymphocytes. It has now been widely demonstrated that the presence of an adequate immune response, essentially represented by the number of TILs (tumor-infiltrating lymphocytes) present in the tumor mass decisively influences the response to treatments and the prognosis of the disease. Therefore, immunotherapy is based on and cannot be carried out without the ability to increase the presence of lymphocytic cells at the tumor site, thereby limiting and nullifying certain tumor evasion mechanisms, particularly those expressed by the activity (under positive physiological conditions) of checkpoints that restrain the response against transformed cells. Immunotherapy has been in the experimental phase for decades, and its excellent results have made it a cornerstone of treatments for many oncological pathologies, especially when combined with chemotherapy and radiotherapy. Despite these successes, a significant number of patients (approximately 50%) do not respond to treatment or develop resistance early on. The microbiota, its composition, and our ability to modulate it can have a positive impact on oncological treatments, reducing side effects and increasing sensitivity and effectiveness. Numerous studies published in high-ranking journals confirm that a certain microbial balance, particularly the presence of bacteria capable of producing short-chain fatty acids (SCFAs), especially butyrate, is essential not only for reducing the side effects of chemoradiotherapy treatments but also for a better response to immune treatments and, therefore, a better prognosis. This opens up the possibility that favorable modulation of the microbiota could become an essential complementary treatment to standard oncological therapies. This brief review aims to highlight the key aspects of using precision probiotics, such as Clostridium butyricum, that produce butyrate to improve the response to immune checkpoint treatments and, thus, the prognosis of oncological diseases.
Intense physical exercise can be related to a significant incidence of gastrointestinal symptoms, with a prevalence documented in the literature above 80%, especially for more intense forms such as ...running. This is in an initial phase due to the distancing of the flow of blood from the digestive system to the skeletal muscle and thermoregulatory systems, and secondarily to sympathetic nervous activation and hormonal response with alteration of intestinal motility, transit, and nutrient absorption capacity. The sum of these effects results in a localized inflammatory process with disruption of the intestinal microbiota and, in the long term, systemic inflammation. The most frequent early symptoms include abdominal cramps, flatulence, the urge to defecate, rectal bleeding, diarrhea, nausea, vomiting, regurgitation, chest pain, heartburn, and belching. Promoting the stability of the microbiota can contribute to the maintenance of correct intestinal permeability and functionality, with better control of these symptoms. The literature documents various acute and chronic alterations of the microbiota following the practice of different types of activities. Several nutraceuticals can have functional effects on the control of inflammatory dynamics and the stability of the microbiota, exerting both nutraceutical and prebiotic effects. In particular, curcumin, green tea catechins, boswellia, berberine, and cranberry PACs can show functional characteristics in the management of these situations. This narrative review will describe its application potential.
Antibiotics are one of the greatest scientific achievements of modern medicine, but excessive use is creating challenges for the future of medicine. Antibiotic resistance (AR) is thought to cause ...changes in bowel habits and an increased risk of gastroenteritis, but it may also increase the risk of overweight, obesity, autoimmune and atopic diseases, and a low response to vaccines and cancer, likely mediated by antibiotic-induced gut dysbiosis. Probiotic add-on therapy could partially prevent antibiotic-induced gut dysbiosis, but their antibiotic sensitivity features likely limits this potential. The EFSA (European Food Safety Authority) guidelines consider the use of probiotics whose antibiotic-resistant profile could be transferable an important hazard. Recently, a strain of
(PRL2020) has shown to be resistant to amoxicillin and amoxicillin-clavulanate (AC) by applying the microdilution protocol according EFSA guidelines. After verifying that horizontal gene transfer is unlikely to take place, this feature suggests its concomitant use with these specific antibiotics. The results of our tests demonstrated that the strain PRL2020 is indeed endowed with amoxicillin- and AC-resistant properties and that it is also insensitive to ampicillin. In-depth analysis of the annotated genome sequence of
PRL2020 was employed to query the Comprehensive Antibiotic Resistance Database (CARD) using Resistance Gene Identifier (RGI) software (version 5.2.1). The similarity among the AR determinants found was studied through nucleotide sequence alignment, and it was possible to verify not only the absence of genes explaining these features in the flanking regions but also the presence of genetic sequences (
and
) putatively responsible for rifampicin and erythromycin resistance. Both features are not phenotypically expressed, and for these antibiotics, the strain is within the EFSA limits. Analysis of the flanking regions of these genes revealed possible mobile elements upstream and downstream only in the case of the
gene, but the features of the Insertion Sequences (IS) are described as not to cause horizontal transfer. Our findings on strain PRL2020 demonstrate that its AR profile is compatible with antibiotics when taken with the aim of reducing the risk of dysbiosis.
Physical maltreatment is one of the most common forms of child abuse. Cutaneous injuries often raise the suspicion of child maltreatment. Nevertheless, among health professionals there is still ...uncertainty in the evaluation of such injuries. In the literature, there are few indications about the most important factors that allow the differentiation of physical abuse findings from signs/lesions that are caused by “folk medicine practices” with similar presentations. We report the case of two brothers who were brought to the Emergency Department of a pediatric hospital by their father because each of them showed one painful, circular and red-purple bruise on their back. Suspecting child abuse, the emergency physicians reported the case to a multidisciplinary unit (dedicated to child abuse). After a careful physical examination, psychological interviews, as well as the evaluation of their medical history, the operators pointed out that the lesions were the result of cupping practices (a form of folk medicine). This case highlights the need for a multidisciplinary approach and demonstrates the importance of a careful evaluation of the cultural background of the family.
Recent investigations have highlighted, both experimentally and clinically, that probiotic strains equipped with arabinofuranosidase, in particular abfA and abfB, favor regular intestinal motility, ...thus counteracting constipation. By analyzing the gene expression and the proliferative response in the presence of arabinan of the probiotic B. longum W11, a strain previously validated as an anti-constipation probiotic, we have speculated that its response mechanism to arabinan can effectively explain its clinical action. Our approach could be used in the future to select probiotics endowed with arabinofuranosidase-related anti-constipation effects.
The outbreak of SARS-CoV-2 disease (COVID-19) is currently, March 2020, affecting more than 100,000 people worldwide and, according to the WHO (World Health Organization), a pandemic is shortly ...expected. The virus infects the lower respiratory tract and causes severe pneumonia and mortality in approximately 10% and 3-5%, respectively, of cases, mainly among the elderly and/or people affected by other diseases. AHCC is an α-glucan-based standardized mushroom extract that has been extensively investigated as an immunostimulant both in animals and/or in humans affected by West Nile virus, influenza virus, avian influenza virus, hepatitis C virus, papillomavirus, herpes virus, hepatitis B virus and HIV by promoting a regulated and protective immune response. Although the efficacy of AHCC has not yet been specifically evaluated with respect to SARS-CoV-2 disease, its action in promoting a protective response to a wide range of viral infections, and the current absence of effective vaccines, could support its use in the prevention of diseases provoked by human pathogenic coronavirus, including COVID-19.
Abstract
Background: The outcome of bloodstream infections (BSIs) is strongly related to microbiological diagnosis. Several factors may reduce blood culture (BC) diagnostic yield in pediatric BSIs, ...making the application of molecular methods quite promising. Methods: Multiplex real-time polymerase chain reaction (PCR) tests (the LightCycler Septifast Test MGRADE by Roche Diagnostics - LC-SF) performed in the tertiary centre of Regina Margherita Children's Hospital (Turin, Italy) over a 3-year period were retrospectively evaluated. Results of the LC-SF test were compared with those of BC (Automated Bact/Alert 3D, Biomerieux) collected at a close time point. Results: 545 LC-SF tests were collected from 289 patients (183 males, median age 6.8 years, interquartile range (IQR) = 2.7-13.1); 163 had congenital or acquired immunodeficiency. In 515 cases (94.5%) the LC-SF test was performed with ongoing empirical antimicrobial therapy. Etiological definition was achieved in 111 BSI cases (20.4%). Both LC-SF and BC identified the responsible pathogen in 39 episodes. The LC-SF test alone gave a positive result in 29 septic episodes; BC alone permitted the etiological diagnosis in 43 episodes, but isolates were not included in the LC-SF master list in 10 cases. A 26% increase in bacterial identification chances due to the LC-SF test was documented. Cohen's kappa test indicated a moderate strength of agreement (0.49) between LC-SF tests and BCs closely collected. Conclusions: BC remains the gold standard for the etiological diagnosis of BSIs, but PCR methods proved to be a valuable adjunctive diagnostic tool in pediatric BSIs, especially in children receiving empirical chemotherapy.
A constant surveillance of susceptibility to antimalarials allows to optimize prevention and treatment of malaria in nonendemic countries. In vitro susceptibility of imported
Plasmodium falciparum ...isolates to chloroquine, quinine, mefloquine, halofantrin, pyronaridine, and amodiaquine was analyzed by WHO Micro-test Mark III; IC
50 and IC
90 were calculated by WHO Log-probit. Sixty-seven tests were performed. All the infections were acquired in Africa: 14.9% in East Africa and 85.1% in West Africa (WA). IC
50 and IC
90 (μmol/L) were chloroquine: 0.129 and 0.648; amodiaquine: 1.134 and 5.445; mefloquine: 0.38 and 0.868; quinine: 0.193 and 0.478; halofantrin: 3.27 and 25.35; pyronaridine: 11.504 and 51.996. Higher IC
50 and IC
90 were observed in East Africa versus West Africa strains. All strains were susceptible to quinine and mefloquine; chloroquine resistance, 14%; amodiaquine resistance, 33%, with cross-resistance to chloroquine (
r = 0.93;
P < .0001); halofantrin resistance, 3.6%, no cross-resistance with chloroquine; low susceptibility to pyronaridine (66.7%), with cross-resistance with chloroquine (
r = 0.38,
P < 0.05). Lower levels of chloroquine resistance were observed in 2000–2003 as compared with prior data; thus, the reemergence of chloroquine susceptibility in Africa may be hypothesized.
