CoQ10 and vitamin A supplementation support voice rehabilitation. A double-blind, randomized, controlled, three-period cross-over pilot study

Objectives: To evaluate the effectiveness of an adjuvant therapy (CoQ10 in its watersoluble form and vitamin A) in supporting voice rehabilitation in a large group of patients with muscle tension dysphonia (MTD). Study Design: Twelve-week, double-blind, randomized, controlled, three-period crossover pilot study. The primary endpoint was the change in the Dysphonia Severity Index (DSI) over the 12-week study period. Secondary endpoints were the changes in the subcomponents of DSI, including MPT, F0-high, I-low, and jitter. Exploratory endpoints were the changes in the Shimmer and in Voice Handicap Index (VHI). Methods: Patients were randomly assigned in a 1:1 ratio to two counter-balanced arms. Group A (ADJ-PLA) patients were administered QTer 300 mg and Vit A acetate 500.000 Ul/g 1 mg twice daily for a 4-week intervention period, followed by a 4-week period of wash-out, and then were submitted to a last 4-week period of placebo. Patients in Group B (PLB-ADJ) were given the treatment period in reverse order. Both groups received a 45-min voice therapy in a group format once a day for 4 weeks during the first and the second active periods. The therapy was held during the wash-out period. Results: The analysis of main time effect indicated a trend toward recovery of vocal function regardless of group assignment. A significant time by group effect was found on DSI [F = 3.4 (2.5, 80.5), p = 0.03], F0-high [F = 4.5 (2.6, 82.9), p = 0.008] and Shimmer [F = 3.6 (1.5, 46.9), p = 0.048], under CoQ10 and Vit A treatment, with a small effect size. There was no significant time by group effect on the other study measures, namely MPT, I-low, VHI. Conclusions: A trend toward recovery of vocal function was observed in all the patients, likely due to voice rehabilitation. The improvement of DSI was greater under CoQ10 and Vitamin treatment, indicating a more pronounced improvement of vocal quality under adjuvant therapy. The study protocol was reviewed and approved by the Ethics Committee of Policlinico Umberto I Hospital, Rome, Italy Rif. 3069/13.02.2014

Pulmonary tuberculosis followed by sarcoidosis in an HIV-infected patient: a case report and a simplified diagnostic flowchart for diagnosis and treatment of sarcoidosis

The diagnosis of sarcoidosis in a patient living with HIV infection is an uncommon event and a challenge for clinicians. Clinical manifestations are variable and fluctuating depending to adherence to ARV therapy and to the level of CD4 count. We analyze here one chronic case in which sarcoidosis appeared clinically two years after pulmonary tuberculosis. The course of the disease was influenced and prolonged by frequent interruptions of antiretroviral therapy. Moreover the diagnosis and the decision to treat have been delayed by the need of exclusion of other pathologies, principally tuberculosis reactivation/reinfection, other mycobacterial diseases, hematologic malignancies. We propose a simplified flowchart for diagnosis and follow up of sarcoidosis, which may also be applied to patients with HIV infection. Diagnosis of latent tuberculosis infection (LTBI) may be difficult in these patients, because the immunological paradox of sarcoidosis. For this reason, following exclusion of active tuberculosis, we advise to submit all sarcoidosis patients to IPT (isoniazid preventive therapy), when immunosuppressive therapy is started

Management of patients with lymphoma and COVID-19: Narrative review and evidence-based practical recommendations

Patients with hematologic malignancies can be immunocompromized because of their disease, anti-cancer therapy, and concomitant immunosuppressive treatment. Furthermore, these patients are usually older than 60 years and have comorbidities. For all these reasons they are highly vulnerable to infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and have an increased risk of developing severe/critical Coronavirus disease 2019 (COVID-19) compared to the general population. Although COVID-19 vaccination has proven effective in reducing the incidence of severe/critical disease, vaccinated patients with lymphoma may not be protected as they often fail to develop a sufficient antiviral immune response. There is therefore an urgent need to address the management of patients with lymphoma and COVID-19 in the setting of the ongoing pandemic. Passive immunization with monoclonal antibodies against SARS-CoV-2 is a currently available complementary drug strategy to active vaccination for lymphoma patients, while monoclonal antibodies and antiviral drugs (remdesivir, ritonavir-boosted nirmatrelvir, and molnupiravir) have proven effective in preventing the progression to severe/critical COVID-19. In this narrative review we present the most recent data documenting the characteristics and outcomes of patients with concomitant lymphoma and COVID-19. Our ultimate goal is to provide practice-oriented guidance in the management of these vulnerable patients from diagnosis to treatment and follow-up of lymphoma. To this purpose, we will first provide an overview of the main data concerning prognostic factors and fatality rate of lymphoma patients who develop COVID-19; the outcomes of COVID-19 vaccination will also be addressed. We will then discuss current COVID-19 prophylaxis and treatment options for lymphoma patients. Finally, based on the literature and our multidisciplinary experience, we will summarize a set of indications on how to manage patients with lymphoma according to COVID-19 exposure, level of disease severity and former history of infection, as typically encountered in clinical practice

Determinants of Survival in Malignant Pleural Mesothelioma: A Surveillance, Epidemiology, and End Results (SEER) Study of 14,228 Patients

INTRODUCTION: Left untreated, malignant pleural mesothelioma (MPM) is associated with uniformly poor prognosis. Better survival has been reported with surgery-based multimodality therapy, but to date, no trial has demonstrated survival benefit of surgery over other therapies. We evaluated whether cancer-directed surgery influenced survival independently from other predictors in a large population-based dataset. METHODS: The SEER database was explored from 1973 to 2009 to identify all cases of pathologically-proven MPM. Age, sex, race, year of diagnosis, histology stage, cancer-directed surgery, radiation, and vital status were analyzed. The association between prognostic factors and survival was estimated using Cox regression and propensity matched analysis. RESULTS: There were 14,228 patients with pathologic diagnosis of MPM. On multivariable analysis, female gender, younger age, early stage, and treatment with surgery were independent predictors of longer survival. In comparison to no treatment, surgery alone was associated with significant improvement in survival [adjusted hazard ratio (adj HR) 0.64 (0.61-0.67)], but not radiation [adj HR 1.15 (1.08-1.23)]. Surgery and radiation combined had similar survival as surgery alone [adj HR 0.69 (0.64-0.76)]. Results were similar when cases diagnosed between 1973 and 1999 were compared to cases diagnosed between 2000 and 2009. CONCLUSIONS: Despite developments in surgical and radiation techniques, the prognosis for MPM patients has not improved over the past 4 decades. Cancer-directed surgery is independently associated with better survival, suggesting that multimodal surgery-based therapy can benefit these patients. Further research in adjuvant treatment is necessary to improve prognosis in this challenging disease

Consensus document on controversial issues in the diagnosis and treatment of prosthetic joint infections.

BACKGROUND: Joint replacement surgery has been on the increase in recent decades and prosthesis infection remains the most critical complication. Many aspects of the primary prevention and clinical management of such prosthesis infections still need to be clarified. CONTROVERSIAL ISSUES: The aim of this GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) working group - a panel of multidisciplinary experts - was to define recommendations for the following controversial issues: (1) Is a conservative surgical approach for the management of prosthetic joint infections effective? (2) Is the one-stage or the two-stage revision for the management of prosthetic joint infections more effective? (3) What is the most effective treatment for the management of prosthetic joint infections due to methicillin-resistant staphylococci? Results are presented and discussed in detail. METHODS: A systematic literature search using the MEDLINE database for the period 1988 to 2008 of randomized controlled trials and/or non-randomized studies was performed. A matrix was created to extract evidence from original studies using the CONSORT method to evaluate randomized clinical trials and the Newcastle-Ottawa Quality Assessment Scale for case-control studies, longitudinal cohorts, and retrospective studies. The GRADE method for grading quality of evidence and strength of recommendation was applied

Assessment of vocal cord nodules: A case study in speech processing by using Hilbert-Huang Transform

Vocal cord nodules represent a pathological condition for which the growth of unnatural masses on vocal folds affects the patients. Among other effects, changes in the vocal cords' overall mass and stiffness alter their vibratory behaviour, thus changing the vocal emission generated by them. This causes dysphonia, i.e. abnormalities in the patients' voice, which can be analysed and inspected via audio signals. However, the evaluation of voice condition through speech processing is not a trivial task, as standard methods based on the Fourier Transform, fail to fit the non-stationary nature of vocal signals. In this study, four audio tracks, provided by a volunteer patient, whose vocal fold nodules have been surgically removed, were analysed using a relatively new technique: the Hilbert-Huang Transform (HHT) via Empirical Mode Decomposition (EMD); specifically, by using the CEEMDAN (Complete Ensemble EMD with Adaptive Noise) algorithm. This method has been applied here to speech signals, which were recorded before removal surgery and during convalescence, to investigate specific trends. Possibilities offered by the HHT are exposed, but also some limitations of decomposing the signals into so-called intrinsic mode functions (IMFs) are highlighted. The results of these preliminary studies are intended to be a basis for the development of new viable alternatives to the softwares currently used for the analysis and evaluation of pathological voice

Consensus document on controversial issues for the treatment of hospital-associated pneumonia

Background: Hospital-associated pneumonia (HAP) remains an important cause of morbidity and mortality despite advances in antimicrobial therapy. Many aspects of the treatment of HAP caused by multi-resistant Gram-positive microorganisms have been extensively studied, but controversial issues remain. Controversial issues: The aim of this GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) working group – a panel of multidisciplinary experts – was to define recommendations for some controversial issues using an evidence-based and analytical approach. The controversial issues were: (1) Is combination antibiotic therapy or monotherapy more effective in the treatment of HAP? (2) What role do pharmacokinetic/pharmacodynamic antibiotic features have as a guide in the selection of treatment for HAP? (3) Is a de-escalation approach for the management of HAP effective? An analysis of the studies published up until April 2009 is presented and discussed in detail. Methods: A systematic literature search using PubMed, MEDLINE, and EMBASE databases and the Cochrane Library was performed. A matrix was created to extract evidence from original studies using the CONSORT method to evaluate randomized clinical trials and the Newcastle–Ottawa Quality Assessment Scale for case–control studies, longitudinal cohorts, and retrospective studies. The GRADE method for grading quality of evidence was applied. 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserve

The unbalanced p53/SIRT1 axis may impact lymphocyte homeostasis in COVID-19 patients

BACKGROUND/OBJECTIVES: A dysregulated inflammatory profile plays an important role in coronavirus disease-2019 (COVID-19) pathogenesis. Moreover, the depletion of lymphocytes is typically associated with an unfavourable disease course. We studied the role and impact of p53 and deacetylase Sirtuin 1 (SIRT1) on lymph-monocyte homeostasis and their possible effect on T and B cell signalling. METHODS: Gene expression analysis and flow cytometry were performed on peripheral blood mononuclear cells (PBMC) of 35 COVID-19 patients and 10 healthy donors (HD). Inflammatory cytokines, the frequency of Annexin+ cells among CD3+ T cells and CD19+ B cell subsets were quantified. RESULTS: PBMC from COVID-19 patients had a higher p53 expression, and higher concentrations of plasma proinflammatory cytokines (IL1β, TNF-α, IL8, and IL6) than HD. Deacetylase Sirtuin 1 (SIRT1) expression was significantly decreased in COVID-19 patients and was negatively correlated with p53 (p = 0.003 and r = -0.48). A lower expression of IL-7R and B Cell linker (BLNK), key genes for lymphocyte homeostasis and function, was observed in COVID-19 than in HD. The reduction of IgK and IgL chains was seen in lymphopenic COVID-19 patients. A significant increase in both apoptotic B and T cells were observed. Inflammatory cytokines correlated positively with p53 (IL-1β: r = 0.5 and p = 0.05; IL-8: r = 0.5 and p = 0.05) and negatively with SIRT1 (IL1-β: r = -0.5 and p = 0.04; TNF-α: r = -0.4 and p = 0.04). CONCLUSIONS: Collectively, our data indicate that the inflammatory environment, the dysregulated p53/SIRT1 axis and low expression of IL7R and BLNK may impact cell survival, B cell signalling and antibody production in COVID-19 patients. Further studies are required to define the functional impact of low BLNK/IL7R expression during severe acute respiratory syndrome coronavirus-2 infection

Consensus document on controversial issues in the treatment of complicated skin and skin-structure infections

Summary Background Complicated skin and skin-structure infections (cSSSI), including surgical site infections (SSI), cellulitis, and abscesses, have been extensively studied, but controversial issues still exist. Controversial issues The aim of this GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) working group – a panel of multidisciplinary experts – was to define recommendations for the following controversial issues: (1) What is the efficacy of topical negative pressure wound treatment as compared to standard of care in the treatment of severe surgical site infections, i.e., deep infections, caused by Gram-positive microorganisms? (2) Which are the most effective antibiotic therapies in the treatment of cSSSI, including SSI, due to methicillin-resistant staphylococci? Results are presented and discussed. Methods A systematic literature search using the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and www.clinicaltrials.gov databases of randomized controlled trials and/or non-randomized studies was performed. A matrix was created to extract evidence from original studies using the CONSORT method to evaluate randomized clinical trials and the Newcastle–Ottawa Quality Assessment Scale for case–control studies, longitudinal cohorts, and retrospective studies. The GRADE method was used for grading quality of evidence. An analysis of the studies published between 1990 and 2008 is presented and discussed in detail