Development and validation of the Italian version of the pain attitudes and beliefs scale-musculoskeletal (PABS-MSK) among physiotherapists working with patients with musculoskeletal chronic pain.

BACKGROUND: Due to their high prevalence, long-term disability, work absenteeism, and low productivity capacity they often lead to, nociplastic and chronic pain are a major public health and social concern. Although high-level literature recommends the Biopsychosocial model, the traditional Biomedical approach is still very diffuse in clinical practise. It is recognized that the beliefs and attitudes of clinicians have an impact on those of patients. The Exploratory Factor Analysis (EFA) was used to validate the Italian version of the PABS-MSK questionnaire. OBJECTIVES: The aim of this study was to translate the original PABS-MSK items into Italian and then assess the construct validity of the new Italian version of the PABS-MSK questionnaire, addressed to physiotherapists, to gain knowledge about physiotherapists' attitudes and beliefs toward the management of chronic musculoskeletal pain and to correlate them with individual characteristics. METHODS: An EFA was performed to validate the modified-Italian-PABS-MSK questionnaire. Furthermore, multivariable regression models were implemented to assess any statistically significant differences in the total score of the two dimensions for sociodemographic and occupational characteristics. RESULTS: The sample consisted of 563 subjects who are members of the order of physiotherapists. The Parallel Analysis suggested extracting two factors, and the EFA showed that the first scale (which we called Biopsychosocial) had higher factor loadings values, while two items (7 and 19) did not adequately represent the other scale (Biomedical). Moreover, the regression models showed that younger and freelance clinicians are more prone to adhere to the Biopsychosocial model. CONCLUSIONS: The modified-Italian-PABS-MSK questionnaire appears to measure two factors related to the Biopsychosocial and Biomedical beliefs of physiotherapists in the management of chronic musculoskeletal pain. The results suggest that professional training based on the evidence and recommendations of international guidelines is necessary to improve the adherence of physiotherapists to the Biopsychosocial model. However, additional studies are needed to further validate the scales, and assess the test-retest reliability, responsiveness, and construct validity.

Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants, genome-wide, may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ⩽0.01) within genes or regions. We also identified individual rare variants that are influential within genes and estimated the heritability of IPF on the basis of rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP heritability of IPF was estimated to be 32% (SE = 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or the development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.

Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial.

Long COVID, a condition characterized by symptom and/or sign persistence following an acute COVID-19 episode, is associated with reduced physical performance and endothelial dysfunction. Supplementation of l-arginine may improve endothelial and muscle function by stimulating nitric oxide synthesis. A single-blind randomized, placebo-controlled trial was conducted in adults aged between 20 and 60 years with persistent fatigue attending a post-acute COVID-19 outpatient clinic. Participants were randomized 1:1 to receive twice-daily orally either a combination of 1.66 g l-arginine plus 500 mg liposomal vitamin C or a placebo for 28 days. The primary outcome was the distance walked on the 6 min walk test. Secondary outcomes were handgrip strength, flow-mediated dilation, and fatigue persistence. Fifty participants were randomized to receive either l-arginine plus vitamin C or a placebo. Forty-six participants (median (interquartile range) age 51 (14), 30 [65%] women), 23 per group, received the intervention to which they were allocated and completed the study. At 28 days, l-arginine plus vitamin C increased the 6 min walk distance (+30 (40.5) m; placebo: +0 (75) m, p = 0.001) and induced a greater improvement in handgrip strength (+3.4 (7.5) kg) compared with the placebo (+1 (6.6) kg, p = 0.03). The flow-mediated dilation was greater in the active group than in the placebo (14.3% (7.3) vs. 9.4% (5.8), p = 0.03). At 28 days, fatigue was reported by two participants in the active group (8.7%) and 21 in the placebo group (80.1%; p < 0.0001). l-arginine plus vitamin C supplementation improved walking performance, muscle strength, endothelial function, and fatigue in adults with long COVID. This supplement may, therefore, be considered to restore physical performance and relieve persistent symptoms in this patient population.

Tumor de Buschke ­ Löwenstein: Presentación de un Caso y Revisión Bibliográfica / Buschke ­ Löwenstein Tumor: A Case Report and Review of the Literature

Introducción: El tumor de Buschke ­ Lowenstein (TBL) es enfermedad de transmisión sexual causada por el virus del papiloma humano (VPH), descrita como una forma intermedia entre un condiloma acuminado y un carcinoma de células escamosas. Afecta principalmente al área genital y anorrectal, posee capacidad de transformación maligna y una alta tasa de recurrencia. La cirugía es el tratamiento de primera línea. Caso clínico: Presentamos el caso de un paciente masculino de 27 años con lesiones verrucosas de crecimiento progresivo en el área inguinal y genital. Mediante la correlación clínico-patológica se llegó al diagnóstico de TBL. Tras discusión en comité multidisciplinario se declaró irresecable y se resolvió tratamiento con radioterapia, además vacunación terapéutica contra el VPH, tanto sistémica como intralesional. Conclusión: El TBL es localmente agresivo y de difícil tratamiento, por lo que la prevención contra el VPH es fundamental. La vacunación terapéutica en conjunto con la radioterapia ofreció mejoría clínica.

Introduction: Buschke-Lowenstein tumor (BLT) is a sexually transmitted disease caused by the human papillomavirus (HPV), described as an intermediate form between condyloma acuminata and squamous cell carcinoma. It mainly affects the genital and anorectal areas and has the capacity for malignant transformation and a high recurrence rate. Surgery is the first-line treatment. Clinical case: We present the case of a 27-year-old male patient with warty lesions of progressive growth in the inguinal and genital areas. Through the clinical-pathological correlation, the diagnosis of BLT was reached. After discussion in a multidisciplinary committee, it was declared unresectable, and treatment with radiotherapy was resolved, in addition to therapeutic vaccination against HPV, both systemic and intralesional. Conclusion: BLT is locally aggressive and challenging to treat, so prevention against HPV is essential. Therapeutic vaccination in conjunction with radiotherapy offered clinical improvement.

Ventilatory Support in Patients with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the novel coronavirus disease 2019 (COVID-19) pandemic, which spread throughout the world. Acute hypoxemic respiratory failure is the most dangerous complication of COVID-19 pneumonia. To date, no specific therapeutic drugs or vaccines have been proven efficacious. Ventilatory support is still a significant challenge for physicians facing COVID-19. The mechanisms underlying hypoxemia in those patients are not fully understood, but a new physiopathology model has been proposed. Oxygen therapy should be delivered to patients with mild to moderate hypoxemia. More severe patients could benefit from other treatments (high-flow nasal cannula, noninvasive ventilation or intubation, and invasive ventilation). Given the rapid evolution of COVID-19, there has been a paucity of the high-quality data that typically inform clinical practice guidelines from professional societies, and a worldwide consensus is still lacking. This chapter aims to illustrate the potentials of ventilatory support as therapeutic options for adult and pediatric patients affected by COVID-19 pneumonia.

Pan-Echinocandin-Resistant Candida glabrata Bloodstream Infection Complicating COVID-19: A Fatal Case Report.

Coinfections with bacteria or fungi may be a frequent complication of COVID-19, but coinfections with Candida species in COVID-19 patients remain rare. We report the 53-day clinical course of a complicated type-2 diabetes patient diagnosed with COVID-19, who developed bloodstream infections initially due to methicillin-resistant Staphylococcus aureus, secondly due to multidrug-resistant Gram-negative bacteria, and lastly due to a possibly fatal Candida glabrata. The development of FKS-associated pan-echinocandin resistance in the C. glabrata isolated from the patient after 13 days of caspofungin treatment aggravated the situation. The patient died of septic shock shortly before the prospect of receiving potentially effective antifungal therapy. This case emphasizes the importance of early diagnosis and monitoring for antimicrobial drug-resistant coinfections to reduce their unfavorable outcomes in COVID-19 patients.

Clinical Decision-Making in Hypersensitivity Pneumonitis: Diagnosis and Management.

This review provides an updated approach to the diagnosis and management of hypersensitivity pneumonitis (HP). The importance of using a multidisciplinary discussion to increase diagnostic and treatment confidence is emphasized. The role of Bayesian reasoning is highlighted throughout, underscoring the importance of hypothesis generation (differential diagnosis) and diagnostic test interpretation based on the probability of HP. Probability estimates of diagnostic certainty (i.e., a confident versus a working diagnosis) and treatment thresholds are carefully examined.Therapeutically, beyond antigen avoidance and newly available antifibrotic therapy for patients with a progressive fibrosing phenotype; the role, timing, and expected response to anti-inflammatory therapy in individual patients are unanswered questions. Since the evidence and validation of testing generally performed during the diagnostic work-up and longitudinal monitoring of HP is feeble at best, the viewpoints discussed are not intended to resolve current controversies but rather to provide a conceptual framework for evaluating discordant information when evaluating and caring for patients with HP.

Current Diagnosis and Management of Hypersensitivity Pneumonitis.

Hypersensitivity Pneumonitis (HP) one of the most common interstitial lung diseases (ILDs) is characterized by exposure to an inhaled inciting antigen that leads to a host immunologic reaction determining interstitial inflammation and architectural distortion. The underlying pathogenetic mechanisms are unclear. The absence of international shared diagnostic guidelines and the lack of a "gold-standard" test for HP combined with the presence of several clinical and radiologic overlapping features makes it particularly challenging to differentiate HP from other ILDs, also in expert contests. Radiology is playing a more crucial role in this process; recently the headcheese sign was recognized as a more specific for chronic-HP than the extensive mosaic attenuation. Several classification proposals and diagnostic models have been advanced by different groups, with no prospective validation. Therapeutic options for HP have been limited to antigen avoidance and immunosuppressant drugs over the last decades. Several questions about this condition remain unanswered and there is a need for more studies.

Interstitial lung abnormalities a risk factor for rheumatoid arthritis interstitial lung disease progression: what's new.

ILA/ILD extension and subpleural ILA localisation are risk factors for disease progression in RA subjects. A semiquantitative method to assess ILA/ILD extent and to measure the fibrotic burden is feasible to accurately determine ILA progression. https://bit.ly/3mmMJk2.

Interstitial Pneumonia with Autoimmune Features and Undifferentiated Connective Tissue Disease.

In 2015, a multidisciplinary task force comprising pulmonologists, rheumatologists, pathologists, and radiologists representing the European Respiratory Society and American Thoracic Society published a diagnostic classification schema for individuals with interstitial lung disease and autoimmune features who did not meet criteria for a defined connective tissue disease. The term interstitial pneumonia with autoimmune features (IPAF) was applied. Classification criteria are often nonspecific, but up to 90% of subjects with IPAF have serological evidence for autoimmunity (particularly (+) antinuclear antibodies). Distinguishing patients with IPAF from idiopathic pulmonary disorders may be difficult. The natural history and appropriate management of IPAF have not been clarified, as data are largely limited to retrospective studies. In this review, we discuss the salient clinical, serologic, histologic, and radiographic features of IPAF and discuss an approach to management.

Investigational drugs for idiopathic pulmonary fibrosis.

INTRODUCTION: IPF is a specific form of chronic fibrosing interstitial pneumonia of unknown cause, characterized by progressive worsening in lung function and an unfavorable prognosis. Current concepts on IPF pathogenesis are based on a dysregulated wound healing response, leading to an over production of extracellular matrix. Based on recent research however, several other mechanisms are now proposed as potential targets for novel therapeutic strategies. Areas covered: This review analyzes the current investigational strategies targeting extracellular matrix deposition, tyrosine-kinase antagonism, immune and autoimmune response, and cell-based therapy. A description of the pathogenic rationale implied in each novel therapeutic approach is summarized. Expert opinion: New IPF drugs are being evaluated in the context of phase 1 and 2 clinical trials. Nevertheless, many drugs that have shown efficacy in preclinical studies, failed to exhibit the same positive effect when translated to humans. A possible explanation for these failures might be related to the known limitations of animal models of the disease. The recent development of 3D systems composed of cells from individual patients that recreate an ex-vivo model of IPF, could lead to significant improvements in disease pathogenesis and treatment. New drugs could be tested on more genuine models and clinicians could tailor therapy based on patient's response.

New treatment directions for IPF: current status of ongoing and upcoming clinical trials.

INTRODUCTION: The main objective of this review is to explore the wide and expanding field of new clinical trials in IPF. Recent trials have confirmed the efficacy of the approved drugs pirfenidone and nintedanib; nonetheless, the discovery of new biological pathways has opened new horizons in this field. Areas covered: New strategies against matrix deposition are under study and so is for the role of immunity and autoimmunity. Recent advances in the use of stem cells are opening new possibilities for the recovery of damaged lung tissues. The role of microbioma is under investigation in order to evaluate the use of antibiotics in IPF treatment. Analysing all the new and the upcoming clinical trials, we are trying to offer a comprehensive view of the emerging new frontiers in the treatment of IPF. Expert commentary: The key points for the ongoing and upcoming clinical trials will be to avoid previous mistakes and to choose carefully both study populations and efficacy endpoints. The exciting possibility to enrol patients with progressive lung fibrosis, both idiopathic and not, could be a next step forward. How the existing therapies will fit in a futurist scenario of personalized medicine is still a challenge.