Sarcopenia does not impact the outcome of patients with Multiple Mieloma consolidated with autologous Hematopoietic Stem Cell Transplantation.

Sarcopenia has been associated with chronic diseases and cancer. Aim of this study was to evaluate sarcopenia in Multiple Myeloma patients undergoing autologous stem cell trans-plantation. In 68 eligible patients' measurement of skeletal muscle area (cm2) on computed tomography scans at the level of the L3 vertebra (L3-SMI) was performed. 37(54%) patients were categorized as sarcopenic: 26 males with L3-SMI values < 52.4 cm2/m2, and 11 women with L3-SMI values < 38.9 cm2/m2. The majority of sarcopenic patients included were older than 60 years (69%, p=0.0005), and with BMI <25 (75%; p=0.0000). A significant association was found between sarcopenia and Sorror score value > 1 (p=0.02). The Kaplan Meyer curve showed a median OS of 73.5 months for non-sarcopenic patients vs. 86.5 months for sarcopenic patients, suggesting that sarcopenia is not an independent prognostic factor in this cohort of patients.

Colonic Epithelial Permeability to Ions Is Restored after Vedolizumab Treatment and May Predict Clinical Response in Inflammatory Bowel Disease Patients.

Vedolizumab (VDZ) is used for treating inflammatory bowel disease (IBD) patients. A study investigating colonic epithelial barrier function ex vivo following VDZ is lacking. This work aims to evaluate ex vivo the colonic epithelial barrier function in IBD patients at baseline and during VDZ treatment, and to investigate the relationships between barrier function and clinical parameters. Colonic specimens were obtained from 23 IBD patients before, and at 24 and 52 weeks after VDZ treatment, and from 26 healthy volunteers (HV). Transepithelial electrical resistance (TEER, permeability to ions) and paracellular permeability were measured in Ussing chambers. IBD patients showed increased epithelial permeability to ions (TEER, 13.80 ± 1.04 Ω × cm2 vs. HV 20.70 ± 1.52 Ω × cm2, p < 0.001) without changes in paracellular permeability of a 4 kDa probe. VDZ increased TEER (18.09 ± 1.44 Ω × cm2, p < 0.001) after 52 weeks. A clinical response was observed in 58% and 25% of patients at week 24, and in 62% and 50% at week 52, in ulcerative colitis and Crohn's disease, respectively. Clinical and endoscopic scores were strongly associated with TEER. TEER < 14.65 Ω × cm2 predicted response to VDZ (OR 11; CI 2-59). VDZ reduces the increased permeability to ions observed in the colonic epithelium of IBD patients before treatment, in parallel to a clinical, histological (inflammatory infiltrate), and endoscopic improvement. A low TEER predicts clinical response to VDZ therapy.

Review Article title: Natural Compounds with Antimicrobial Activities in oral Candida infections during head and neck radiotherapy.

BACKGROUNDS: Oral colonization and infections are frequently observed in patients during and soon after radiation therapy (RT). Infective mucositis is a common side effect associated with cancer therapy, characterized by an inflammation of the oral mucous membranes with histological mucosal and submucosal changes. Ulcerative mucositis is responsible for significant pain, impairing the patient's nutritional intake and leading to local or systemic infections promoting mycosis due to several species of the genus Candida. According to international guidelines, treatment of candidiasis depends on the infection site and patient's condition. SUMMARY: Recently several studies have shown the protective role of natural compounds counteracting the activity of Candida biofilms. The aim of this review is to discuss the antimicrobial activities of natural compounds in fungal infections, especially Candida spp., during and soon after radiotherapy. Indeed new molecules are being discovered and assessed for their capacity to control Candida spp. growth and, probably in the future, will be used to treat oral candidiasis, overall, during radiotherapy. This review reports several preliminary data about preclinical and clinical evidence of their efficacy in the prevention and/or treatment of mucositis due to Radiotherapy with a brief description of the natural compounds with anti-Candida activities. KEY MESSAGES: The increase in the resistance to the available antifungal drugs related to Candida spp. infections increased as well as drug interactions, urging the development of innovative and more effective agents with antifungal action. Recent preclinical and clinical studies are identifying natural substances with anti-inflammatory and antifungal activity that could be tested in the prevention of candidiasis in patients undergoing radiotherapy. Further studies are needed to confirm these preliminary data.

Assessment of core and support functions of the communicable disease surveillance system in the Kurdistan Region of Iraq.

Early detection and prompt response are crucial measures to prevent and control outbreaks. Public health agencies, therefore, designed the Communicable Disease Surveillance System (CDSS) to obtain essential data instantaneously to be used for appropriate action. However, a periodic evaluation of CDSS is indispensable to ensure the functionality of the system. For this reason, this study aims to assess the performance of the core and support functions of the CDSS in the Kurdistan Region of Iraq. A descriptive cross-sectional study was used. From a total of 291 health facilities HFs (Primary health care centers and Hospitals) in the Kurdistan region of Iraq that have surveillance activities, 74 HFs were selected using a random stratified sampling approach. The World Health Organization (WHO) generic questionnaire has been used to interview the surveillance staff, together with direct collection of the data. Our analysis shows a lack of surveillance guiding manual in the HFs. Even at the district level, where a surveillance manual existed, case definitions, thresholds, and control measures were still missing. To note, more than 93% of HFs had organized and comprehensive patients registers for the collection of their clinical and secondary data. Also, all HFs had functioning laboratories. The majority of them (almost 93%) were equipped to collect, process, and store blood, stool, and urine specimens. About 72% of these laboratories were also able to transport timely the specimens to more specialized laboratories. At all levels, data reporting to the higher level exceeded the recommended minimum rate of 80%. The reporting system at the district level was based on emails, while in the periphery on hand-delivered in paper-based formats (50%), telephone (22%), and social media (22%). Furthermore, our analysis highlights the lack of data analysis: only 3.8% of Primary Health Care Centers conduct simple data analysis regularly, while hospitals do not do any sort of analysis. Also, only a few HFs investigated an outbreak, though using system routine sources to capture these public health events. Our findings show a lack in epidemic preparedness (3%), in feedback (53%), in standard guidelines, training, supervision, and resource allocations in HFs (0%). Taken together, our data show the importance of strengthening the CDSS in the Kurdistan region of Iraq, by reinforcing the surveillance system with continuous feedback, supervision, well-trained and motivated staff, technical support, and coordination between researchers and physicians.

Endoscopic Mitral Valve Repair in a Patient With Persistent Left Superior Vena Cava Draining Into the Coronary Sinus - Cannulation Technique and Surgical Management.

Persistence of the left superior vena cava is often an incidental finding during cardiac surgical procedures. In minimally invasive valvular surgery, it may jeopardise venous drainage and myocardial protection. This How-To-Do-It paper describes the cannulation strategy in a case of minimally invasive mitral surgery in a patient with persistence of the left superior vena cava and absence of the anonymous vein detected with preoperative multimodality imaging.

The Results From Up-Front Esophageal Testing Predict Proton Pump Inhibitor Response in Patients With Chronic Cough.

INTRODUCTION: The clinical management of chronic cough patients is challenging, and their response to proton pump inhibitors (PPIs) is considered as unsatisfactory. Few data concerning the association between impedance-pH variables and PPI response in these patients are available. Mean nocturnal baseline impedance (MNBI) and postreflux swallow-induced peristaltic wave (PSPW) index increase the diagnostic yield of impedance-pH in gastroesophageal reflux disease. METHODS: Demographic, clinical, and endoscopy findings; impedance-pH; and high-resolution manometry tracings from consecutive patients assessed for cough were evaluated. Univariable and multivariable regression models were generated to evaluate the association between impedance-pH and high-resolution manometry findings, endoscopic and clinical characteristics, and PPI response. RESULTS: A total of 178 patients were included. Eighty-four of 178 cough patients (47.2%) displayed grade C-D erosive esophagitis or were characterized by a pathological acid exposure time (AET) and/or positive symptom association probability/symptom index. When also considering MNBI and PSPW, 135 of 178 patients (75.8%) were characterized by the evidence of reflux disease (P < 0.001). Eighty patients (44.9%) had cough responding to PPIs, whereas 98 (55.1%) were nonresponders (P = 0.071). At the receiver operating characteristic analysis, both PSPW index and MNBI were associated to PPI responsiveness. MNBI and PSPW index showed higher sensitivity in predicting PPI response compared with AET and symptom association probability/symptom index. The area under the curves of MNBI and PSPW index were significantly higher than that of AET (P < 0.01 for both comparisons). When patients were stratified according to AET and excluding those with erosive esophagitis, pathological MNBI or PSPW index, hiatal hernia, and hypomotility features were associated to PPI response in all groups. DISCUSSION: Our results demonstrate the usefulness of an up-front esophageal testing in discriminating reflux-related cough patients and predicting PPI response.

The variants question: What is the problem?

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China in early December 2019 has rapidly widespread worldwide. Over the course of the pandemic, due to the advance of whole-genome sequencing technologies, an unprecedented number of genomes have been generated, providing both invaluable insights into the ongoing evolution and epidemiology of the virus and allowing the identification of hundreds of circulating genetic variants during the pandemic. In recent months variants of SARS-CoV-2 that have an increased number of mutations on the Spike protein have brought concern all over the world. These have been called "variants of concerns" (VOCs), and/or "variants of interests" (VOIs) as it has been suggested that their genome mutations might impact transmission, immune control, and virulence. Tracking the spread of emerging SARS-CoV-2 variants is crucial to inform public health efforts and control the ongoing pandemic. In this review, a concise characterization of the SARS-CoV-2 mutational patterns of the main VOCs and VOIs circulating and cocirculating worldwide has been presented to determine the magnitude of the SARS-CoV-2 threat to better understand the virus genetic diversity and its potential impact on vaccination strategy.

Betacoronaviruses genome analysis reveals evolution toward specific codons usage: Implications for SARS-CoV-2 mitigation strategies.

Since the start of the coronavirus disease 2019 (COVID-19) pandemic, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly widespread worldwide becoming one of the major global public health issues of the last centuries. Currently, COVID-19 vaccine rollouts are finally upon us carrying the hope of herd immunity once a sufficient proportion of the population has been vaccinated or infected, as a new horizon. However, the emergence of SARS-CoV-2 variants brought concerns since, as the virus is exposed to environmental selection pressures, it can mutate and evolve, generating variants that may possess enhanced virulence. Codon usage analysis is a strategy to elucidate the evolutionary pressure of the viral genome suffered by different hosts, as possible cause of the emergence of new variants. Therefore, to get a better picture of the SARS-CoV-2 codon bias, we first identified the relative codon usage rate of all Betacoronaviruses lineages. Subsequently, we correlated putative cognate transfer ribonucleic acid (tRNAs) to reveal how those viruses adapt to hosts in relation to their preferred codon usage. Our analysis revealed seven preferred codons located in three different open reading frame which appear preferentially used by SARS-CoV-2. In addition, the tRNA adaptation analysis indicates a wide strategy of competition between the virus and mammalian as principal hosts highlighting the importance to reinforce the genomic monitoring to prompt identify any potential adaptation of the virus into new potential hosts which appear to be crucial to prevent and mitigate the pandemic.

Impairment of GH/IGF-1 Axis in the Liver of Patients with HCV-Related Chronic Hepatitis.

Resistance to the action of growth hormone (GH) frequently complicates liver cirrhosis, while, physiologically, the activation of GH receptor (GHR) determines phosphorylation of signal transducer and activator of transcription (STAT)-5 and the consequent induction of insulin-like growth factor-1 (IGF-1) expression. The suppressor of cytokine signaling (SOCS)-3 negatively regulates this intracellular cascade. We aimed to evaluate the hepatic expression of the GH/IGF-1 axis components in the liver of patients with HCV-related chronic hepatitis at different fibrosis stages. The expression of GH/IGF-1 axis components, such as GHR, IGF-1, STAT5-p, and SOCS-3, was assessed by immunohistochemistry at the lobular level in 61 patients with HCV-related hepatitis. At the hepatocyte level, IGF-1 and nuclear STAT5-p positivity scores showed negative correlations with fibrosis stage, while SOCS-3 score a positive one (p<0.05 for all). Furthermore, the reduction of hepatocyte score of IGF-1 expression was associated with the serological parameters of liver damage (p<0.05) and with the increase of the score of IGF-1 expression by hepatic stellate cells (p<0.05). IGF-1 expression by hepatocytes was reduced with fibrosis progression, probably due to the impairment of GHR intracellular cascade by the SOCS-3 activation already in pre-cirrhotic stages. The inverse correlation between IGF-1 expressed by hepatocytes and by hepatic stellate cells suggests that IGF-1 may exert specific functions in different hepatic cells.

First epidemiological and phylogenetic analysis of Hepatitis B virus infection in migrants from Mali.

The armed conflict in Mali caused a migration crisis since 2012. Most Malian refugees were in Italy. In Sub-Saharan Africa, the seroprevalence of anti-HBV antibodies is particularly high. Genotype E is the most prevalent throughout a crescent covering area from Angola to Senegal, including Mali. We report 16 HBV positive individual from 136 Malian asylum seekers in order to investigate the genetic diversity of HBV in this population. Sequencing and phylogenetic analysis has been used. The HBV genotype E isolates from Mali did not cluster together but were intermixed, with the other African sequences. Only three supported clade were evidenced and closely related to sequences from Burkina Faso. The estimated evolutionary rate was 9.29 × 104 . The root of the tree dated back to February 2008 in (95% HPD: 2006-2011). From this ancestor six main statistically supported clusters (pp > 0.80) were identified. The most recent Clade dated back to May 2015. The BSP showed that the effective number of infections softly increased from 2011 to the 2015. Phylogenetic analysis helped in understanding how two on sixteen individuals, have been infected in Italy, and give an important improvement in prevention campaigns and monitoring of the viral infection in migrants. J. Med. Virol. 89:639-646, 2017. © 2016 Wiley Periodicals, Inc.

Hepatitis C virus genotype 3A in a population of injecting drug users in Montenegro: Bayesian and evolutionary analysis.

Few reports are available on HCV molecular epidemiology among IDUs in Eastern Europe, and none in Montenegro. The aim of this study was to investigate the HCV genotype distribution in Montenegro among IDUs and to perform Bayesian and evolutionary analysis of the most prevalent HCV genotype circulating in this population. Sixty-four HCV-positive IDUs in Montenegro were enrolled between 2013 and 2014, and the NS5B gene was sequenced. The Bayesian analysis showed that the most prevalent subtype was HCV-3a. Phylogenetic data showed that HCV-3a reached Montenegro in the late 1990s, causing an epidemic that exponentially grew between the 1995 and 2005. In the dated tree, four different entries, from 1990 (clade D), 1994 (clade A) to 1999 (clade B) and 2001 (clade C), were identified. In the NS5B protein model, the amino acids variations were located mainly in the palm domain, which contains most of the conserved structural elements of the active site. This study provides an analysis of the virus transmission pathway and the evolution of HCV genotype 3a among IDUs in Montenegro. These data could represent the basis for further strategies aimed to improve disease management and surveillance program development in high-risk populations.

Weak peristalsis with large breaks is associated with higher acid exposure and delayed reflux clearance in the supine position in GERD patients.

OBJECTIVES: Ineffective esophageal motility is frequently observed in gastroesophageal reflux disease (GERD) patients but its clinical relevance remains controversial. In healthy subjects and in patients with nonobstructive dysphagia, it has been demonstrated, by means of high-resolution manometry (HRM), that long breaks of esophageal peristalsis predict delayed bolus clearance. METHODS: HRM and 24-h multichannel impedance-pH (MI-pH) monitoring were performed in 40 GERD patients with no evidence of hiatal hernia. Total bolus clearing time (BCT) in upright and supine position and acid exposure time (AET) were calculated. RESULTS: Of the 40 patients, 23 showed a pathological AET and 15 erosive reflux disease (ERD). Patients with a pathological number of large breaks were characterized by a significantly lower BCT value in the supine position and higher AET. In all, 10/15 ERD patients (67%) and 5/25 nonerosive reflux disease patients (20%) were characterized by an abnormal number of small or large breaks (P<0.05). ERD patients were characterized by significantly higher AET and BCT in the supine position. CONCLUSIONS: GERD patients with a pathological number of large breaks, assessed by HRM, are characterized by a significantly prolonged reflux clearance in the supine position and higher AET. ERD patients display a higher number of esophageal breaks that might explain the development of erosions.

Exploring the Interplay between COVID-19 and Gut Health: The Potential Role of Prebiotics and Probiotics in Immune Support.

The COVID-19 pandemic has profoundly impacted global health, leading to extensive research focused on developing strategies to enhance outbreak response and mitigate the disease's severity. In the aftermath of the pandemic, attention has shifted towards understanding and addressing long-term health implications, particularly in individuals experiencing persistent symptoms, known as long COVID. Research into potential interventions to alleviate long COVID symptoms has intensified, with a focus on strategies to support immune function and mitigate inflammation. One area of interest is the gut microbiota, which plays a crucial role in regulating immune responses and maintaining overall health. Prebiotics and probiotics, known for their ability to modulate the gut microbiota, have emerged as potential therapeutic agents in bolstering immune function and reducing inflammation. This review delves into the intricate relationship between long COVID, the gut microbiota, and immune function, with a specific focus on the role of prebiotics and probiotics. We examine the immune response to long COVID, emphasizing the importance of inflammation and immune regulation in the persistence of symptoms. The potential of probiotics in modulating immune responses, including their mechanisms in combating viral infections such as COVID-19, is discussed in detail. Clinical evidence supporting the use of probiotics in managing long COVID symptoms is summarized, highlighting their role as adjunctive therapy in addressing various aspects of SARS-CoV-2 infection and its aftermath.

Phylogenetic analysis of Prevotella copri from fecal and mucosal microbiota of IBS and IBD patients.

Background: Prevotella copri is the most abundant member of the genus Prevotella that inhabits the human large intestines. Evidences correlated the increase in Prevotella abundance to inflammatory disorders, suggesting a pathobiont role. Objectives: The aim of this study was to investigate the phylogenetic dynamics of P. copri in patients with irritable bowel syndrome (IBS), inflammatory bowel diseases (IBDs) and in healthy volunteers (CTRL). Design: A phylogenetic approach was used to characterize 64 P. copri 16S rRNA sequences, selected from a metagenomic database of fecal and mucosal samples from 52 patients affected by IBD, 44 by IBS and 59 healthy. Methods: Phylogenetic reconstructions were carried out using the maximum likelihood (ML) and Bayesian methods. Results: Maximum likelihood phylogenetic tree applied onto reference and data sets, assigned all the reads to P. copri clade, in agreement with the taxonomic classification previously obtained. The longer mean genetic distances were observed for both the couples IBD and CTRL and IBD and IBS, respect to the distance between IBS and CTRL, for fecal samples. The intra-group mean genetic distance increased going from IBS to CTRLs to IBD, indicating elevated genetic variability within IBD of P. copri sequences. None clustering based on the tissue inflammation or on the disease status was evidenced, leading to infer that the variability seemed to not be influenced by concomitant diseases, disease phenotypes or tissue inflammation. Moreover, patients with IBS appeared colonized by different strains of P. copri. In IBS, a correlation between isolates and disease grading was observed. Conclusion: The characterization of P. copri phylogeny is relevant to better understand the interactions between microbiota and pathophysiology of IBD and IBS, especially for future development of therapies based on microbes (e.g. probiotics and synbiotics), to restore the microbiota in these bowel diseases.

Constipation-Predominant Irritable Bowel Syndrome (IBS-C): Effects of Different Nutritional Patterns on Intestinal Dysbiosis and Symptoms.

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by abdominal pain associated with defecation or a change in bowel habits. The pathogenesis of IBS is not completely clear, but it is known to be multifactorial and complex. Endogenous and exogenous factors such as abnormal GI motility, low-grade inflammation, increased epithelial permeability and visceral hypersensitivity, but diet and psychosocial aspects are also recognized as important actors. Furthermore, the interaction between diet and gut microbiota has gained interest as a potential contributor to the pathophysiology of IBS. To date, there is no specific diet for IBS with constipation (IBS-C); however, many studies show that fiber intake, especially soluble fiber such as inulin, could have a positive effect on symptoms. This review aims to evaluate the effects of some nutritional components such as fibers but also functional foods, prebiotics, probiotics and symbiotics on symptoms and microbiota in IBS-C subjects.

Protective Effect of Procyanidin-Rich Grape Seed Extract against Gram-Negative Virulence Factors.

Biofilm formation and lipopolysaccharide (LPS) are implicated in the pathogenesis of gastrointestinal (GI) diseases caused by Gram-negative bacteria. Grape seeds, wine industry by-products, have antioxidant and antimicrobial activity. In the present study, the protective effect of procyanidin-rich grape seed extract (prGSE), from unfermented pomace of Vitis vinifera L. cv Bellone, on bacterial LPS-induced oxidative stress and epithelial barrier integrity damage has been studied in a model of Caco-2 cells. The prGSE was characterized at the molecular level using HPLC and NMR. The in vitro activity of prGSE against formation of biofilm of Salmonella enterica subsp. enterica serovar Typhimurium and Escherichia coli was investigated. In vivo, prGSE activity using infected Galleria mellonella larvae has been evaluated. The results show that the prGSE, if administered with LPS, can significantly reduce the LPS-induced permeability alteration. Moreover, the ability of the extract to prevent Reactive Oxygen Species (ROS) production induced by the LPS treatment of Caco-2 cells was demonstrated. prGSE inhibited the biofilm formation of E. coli and S. Typhimurium. In terms of in vivo activity, an increase in survival of infected G. mellonella larvae after treatment with prGSE was demonstrated. In conclusion, grape seed extracts could be used to reduce GI damage caused by bacterial endotoxin and biofilms of Gram-negative bacteria.

HCl-induced and ATP-dependent upregulation of TRPV1 receptor expression and cytokine production by human esophageal epithelial cells.

The pathogenesis of gastroesophageal reflux disease (GERD) remains elusive, but recent evidence suggests that early secretion of inflammatory cytokines and chemokines by the mucosa leads to influx of immune cells followed by tissue damage. We previously showed that exposure of esophageal mucosa to HCl causes ATP release, resulting in activation of acetyl-CoA:1-O-alkyl-sn-glycero-3-phosphocholine acetyltransferase (lyso-PAF AT), the enzyme responsible for the production of platelet-activating factor (PAF). In addition, HCl causes release of IL-8 from the esophageal mucosa. We demonstrate that esophageal epithelial cells secrete proinflammatory mediators in response to HCl and that this response is mediated by ATP. Monolayers of the human esophageal epithelial cell line HET-1A were exposed to acidified cell culture medium (pH 5) for 12 min, a total of seven times over 48 h, to simulate the recurrent acid exposure clinically occurring in GERD. HCl upregulated mRNA and protein expression for the acid-sensing transient receptor potential cation channel, subfamily vanilloid member 1 (TRPV1), lyso-PAF AT, IL-8, eotaxin-1, -2, and -3, macrophage inflammatory protein-1α, and monocyte chemoattractant protein-1. The chemokine profile secreted by HET-1A cells in response to repeated HCl exposure parallels similar findings in erosive esophagitis patients. In HET-1A cells, the TRPV1 agonist capsaicin reproduced these findings for mRNA of the inflammatory mediators lyso-PAF AT, IL-8, and eotaxin-1. These effects were blocked by the TRPV1 antagonists iodoresiniferatoxin and JNJ-17203212. These effects were imitated by direct application of ATP and blocked by the nonselective ATP antagonist suramin. We conclude that HCl/TRPV-induced ATP release upregulated secretion of various chemoattractants by esophageal epithelial cells. These chemoattractants are selective for leukocyte subsets involved in acute inflammatory responses and allergic inflammation. The data support the validity of HET-1A cells as a model of the response of the human esophageal mucosa in GERD.