What do We Know about Cryptic Aspergillosis?

Cryptic Aspergillus species are increasingly recognized as pathogens involved in human disease. They are ubiquitarian fungi with high tenacity in their environment and can express various resistance mechanisms, often due to exposure to antifungal agents employed in agriculture and farming. The identification of such species is increasing thanks to molecular techniques, and a better description of this type of pathogen is granted. Nevertheless, the number of species and their importance in the clinical setting still need to be well studied. Furthermore, their cross-sectional involvement in animal disease, plants, and human activities requires a multidisciplinary approach involving experts from various fields. This comprehensive review aims to provide a sharp vision of the cryptic Aspergillus species, from the importance of correct identification to the better management of the infections caused by these pathogens. The review also accentuates the importance of the One Health approach for this kind of microorganism, given the interconnection between environmental exposure and aspergillosis, embracing transversely the multidisciplinary process for managing the cryptic Aspergillus species. The paper advocates the need for improving knowledge in this little-known species, given the burden of economic and health implications related to the diffusion of these bugs.

New score to predict COVID-19 progression in vaccine and early treatment era: the COVID-19 Sardinian Progression Score (CSPS).

BACKGROUND: Several scores aimed at predicting COVID-19 progression have been proposed. As the variables vaccination and early SARS-CoV-2 treatment were systematically excluded from the prognostic scores, the present study's objective was to develop a new model adapted to the current epidemiological scenario. METHODS: We included all patients evaluated by the Infectious Disease Unit in Sassari, with SARS-CoV-2 infection and without signs of respiratory failure at the first evaluation (P/F > 300). Disease progression was defined by the prescription of supplemental oxygen. In addition, variables related to demographics, vaccines, comorbidities, symptoms, CT scans, blood tests, and therapies were collected. Multivariate logistic regression modelling was performed to determine factors associated with progression; any variable with significant univariate test or clinical relevance was selected as a candidate for multivariate analysis. Hosmer-Lemeshow (HL) goodness of fit statistic was calculated. Odds ratio values were used to derive an integer score for developing an easy-to-use progression risk score. The discrimination performance of the risk index was determined using the AUC, and the best cut-off point, according to the Youden index, sensitivity, specificity, predictive value, and likelihood ratio, was chosen. RESULTS: 1145 patients [median (IQR) age 74 (62-83) years; 53.5% males] were enrolled; 336 (29.3%) had disease progression. Patients with a clinical progression were older and showed more comorbidities; furthermore, they were less vaccinated and exposed to preventive therapy. In the multivariate logistic regression analysis, age ≥ 60 years, COPD, dementia, haematological tumours, heart failure, exposure to no or one vaccine dose, fever, dyspnoea, GGO, consolidation, ferritin, De Ritis ≥ 1.2, LDH, and no exposure to early anti-SARS-CoV-2 treatment were associated with disease progression. The final risk score ranged from 0 to 45. The ROC curve analysis showed an AUC of 0.92 (95% CI 0.90-0.93) with a 93.7% specificity and 72.9% sensitivity. Low risk was defined when the cut-off value was less than 23. Three risk levels were identified: low (0-23 points), medium (24-35), and high (≥ 36). CONCLUSIONS: The proportion of patients with progression increases with high scores: the assessment of the risk could be helpful for clinicians to plan appropriate therapeutic strategies.

Is the 4C Score Still a Valid Item to Predict In-Hospital Mortality in People with SARS-CoV-2 Infections in the Omicron Variant Era?

Since the start of the SARS-CoV-2 pandemic, several scores have been proposed to identify infected individuals at a higher risk of progression and death. The most famous is the 4C score. However, it was developed in early 2020. Our study aimed to evaluate the accuracy of the 4C score during the wave in which the Omicron variant was prevalent. An observational study was conducted at an Italian University Hospital between 1 January and 31 July 2022. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of the 4C score to predict mortality. Overall, 1186 people were recruited, of which 160 (13.5%) died. According to the 4C score, 177 (11.6%) were classified as having a low risk of mortality, 302 (25.5%) were intermediate, 596 (50.3%) were high, and 151 (12.7%) were very high. The ROC curve of the 4C score showed an AUC (95% CI) value of 0.78 (0.74−0.82). At the criterion value of > 10, the sensitivity was 76.2% and the specificity was 62.67%. Similar to previous studies, the 4C mortality score performed well in our sample, and it is still a useful tool for clinicians to identify patients with a high risk of progression. However, clinicians must be aware that the mortality rate reported in the original studies was higher than that observed in our study.

Reduced risk of death in people with SARS-CoV-2 infection treated with remdesivir: a nested case-control study.

INTRODUCTION: Since the start of the SARS-CoV-2 pandemic, several treatment options have been proposed (e.g. steroids, heparin, antivirals and monoclonal antibodies). Remdesivir was the first antiviral approved for the treatment of COVID-19, even though controversial evidence exists concerning the efficacy. Therefore, we aimed to conduct a study to evaluate whether the use of remdesivir was associated with lower mortality in patients with COVID-19. METHODS: We conducted a nested case-control study of a retrospective cohort collecting medical records of people with SARS-CoV-2 infection admitted in the infectious Disease Unit of Sassari University Hospital (S.C. Clinica di Malattie Infettive, AOU di Sassari, Italy), or in the Infectious Disease Unit of Foggia (AOU "Ospedali Riuniti" Foggia), between 1 July 2020 and 10 November 2021. The outcome considered was death; thus, we matched death (cases) to survivors (controls) by sex and age (1:1). RESULTS: We included in the study 342 patients, with 171 deaths (cases) and 171 survivors (controls). Remdesivir was administered to 60 people in the control group and to 18 people in the case group (35.1% vs. 10.5%, p < .0001). In the multivariate analysis, treatment with remdesivir and heparin was associated with lower mortality (OR: 0.19 [95% CI :0.10-0.38], p <.0001; OR: 0.39 [95% CI: 0.21-0.74] p = .004, respectively). On the contrary, diabetes, oxygen therapy and CPAP/NIV were associated with higher mortality. CONCLUSION: Our study showed lower mortality in people with SARS-CoV-2 infection treated with remdesivir.

Safety and efficacy of molnupiravir in SARS-CoV-2-infected patients: A real-life experience.

Since the start of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, several treatments have been proposed to cure coronavirus disease 2019 (COVID-19) and prevent it. Molnupiravir is a ribonucleoside prodrug of N-hydroxycytidine with an in vitro and in vivo activity against SARS-CoV-2. We conducted a retrospective cohort study that included all people treated with molnupiravir between January 10, 2022, and March 31, 2022, at the University Hospital of Sassari. Molnupiravir was prescribed, according to the Italian Agency of Drug indications, to patients with recent symptom onset (≤5 days), no need for oxygen supplementation, and with a high risk of disease progression for the presence of chronic diseases. We included 192 people with a mean age of 70.4 ± 15.4 years, with 144 (75%) patients over 60 years. During the follow-up, 20 (10.4%) patients showed a disease progression. At the multivariate analysis, older age, having neurological disease, having dyspnea at the onset of the symptoms, and acquiring SARS-CoV-2 infection during hospital admission were associated with an increased risk of progression. In contrast, an early start of treatment was associated with a reduced risk of disease progression. Molnupiravir was also extremely safe since 13 (6.8%) adverse events were reported, with only one interruption. Our study shows that monlupiravir confirmed its efficacy and safety in a real-life cohort that included a high percentage of elderly people with a high comorbidity burden.

How Little Do We Know about HIV and STIs Prevention? Results from a Web-Based Survey among the General Population.

BACKGROUND: Prevention campaigns have led to a significant decrease in new HIV diagnoses in Western Europe, while other sexual transmitted infections (STIs) have shown an opposite trend. Several educational programs are promoted among young students, whereas informational campaigns addressing the general population are scarce. We aimed to investigate the level of awareness regarding STIs among the general population. METHODS: We proposed a questionnaire regarding STIs and HIV to the general population in Italy. We assigned 1 point to correct, 0.5 point to partially correct, and 0 point to wrong answers. We collected data about age, sex, region of origin, level of education and whether they were health workers. RESULTS: Overall, 2183 people answered the questionnaire, of which 555 aged over 50 years old. Being male, older than 50 years old, retired or unemployed, not educated, and no regular use of condoms were associated with lower scores. Only 16% of participants knew the Undetectable = Untransmittable (U = U) campaign. Overall, 2131 (97.6%) people think more educational campaigns should be offered. Of interest, 80% said the questionnaire led them to learn more about HIV and STIs. CONCLUSION: Our study reveals several gaps in general population awareness about HIV and STIs, especially among people aged over 50 years old. Most participants stated that the questionnaire was a learning opportunity. These data suggest that improvement of knowledge could start from easy-to-dispose medium, such as surveys and questionnaires delivered through social media. Furthermore, particular attention should be paid to population segmentation and campaign tailoring to enhance interventions effectiveness. Our data reinforce the need for more informational and educational campaigns tailored to the specific segments of the population.

Impact of Early SARS-CoV-2 Antiviral Therapy on Disease Progression.

Since the start of the SARS-CoV-2 pandemic, several treatments have been proposed to prevent the progression of the disease. Currently, three antiviral (molnupiravir, nirmaltrevir/r, remdesivir) and two monoclonal antibodies (casirivimab/imdevimab and sotrovimab) are available in Italy. Therefore, we aimed to evaluate the presence of risk factors associated with disease progression. We conducted a retrospective cohort study, including all patients with a confirmed diagnosis of SARS-CoV-2 evaluated between 01/01/2022 ad 10/05/2022 by our Unit of Infectious Diseases in Sassari. We defined disease progression as the necessity of starting O2 therapy. According to AIFA (Italian Medicines Agency) indications, preventive treatment was prescribed in patients with recent symptoms onset (≤five days), no need for oxygen supplementation, and risk factors for disease progression. Subgroup differences in quantitative variables were evaluated using Student's t-test. Pearson chi-square or Fisher's exact tests were used to assess differences for qualitative variables. Multivariate logistic regression modelling was performed to determine factors associated with progression. A two-tailed p-value less than 0.05 was considered statistically significant. All statistical analyses were performed with STATA version 17 (StataCorp, College Station, TX, USA). We included 1145 people with SARS-CoV-2 diagnosis, of which 336 (29.3%) developed severe disease with oxygen supplementation. In multivariate logistic regression analysis, age, dementia, haematologic tumors, heart failure, dyspnoea or fever at first evaluation, having ground glass opacities or consolidation at the first CT scan, and bacteria coinfection were associated with an increased risk of disease progression. Vaccination (at least two doses) and early treatment with antiviral or monoclonal antibodies were associated with a lower risk of disease progression. In conclusion, our study showed that vaccination and early treatment with antiviral and/or monoclonal antibodies significantly reduce the risk of disease progression.

Failed vascularized fibular graft in treatment of osteonecrosis of the femoral head. A histopathological analysis.

PURPOSE: vascularized fibular grafting has been used to treat osteonecrosis of the femoral head in younger patients. Although the results described in the literature are promising, the failure rate is still significant, especially in steroid users. This study was undertaken to learn more, on a histopathological level, about the mechanism of vascularized fibular graft failure. METHODS: fifteen femoral heads removed at conversion to total hip arthroplasty were analyzed. The case load comprised 10 men and 5 women. They ranged in age from 28 to 39 years and had a median age of 35 years. The interval between the vascularized fibular implant procedure and the conversion to total hip arthroplasty ranged from 22 months to 30 months; the median interval was 26 months. All the patients were steroid users. The heads were sectioned and axial and coronal sections were taken and stained using the WHO method (hematoxylin, phloxine, saffron and Alcian green). A quantitative and qualitative analysis of graft-host interaction at the head (zone 1), neck (zone 2) and epiphysis (zone 3) was performed. RESULTS: all the specimens showed recognizable collapse of the articular surface over the area of necrosis. Thirteen femoral heads showed the presence of an osteochondral flap attached only at the margins of the area of avascular necrosis, and 10 of these 13 femoral heads also showed loss of the articulating surface with an ulcer crater corresponding to the exposed area of avascular necrosis. CONCLUSIONS: vascularized fibular graft failure seems to be related to a negative effect of creeping substitution: the revascularization becomes a negative force as it supports unbalanced bone resorption, which, as is well known, is enhanced by corticosteroids. CLINICAL RELEVANCE: creeping substitution is an undermining force in the repair and revascularization of the necrotic area in the femoral head.

Soft tissue balancing in total knee arthroplasty.

A good outcome in total knee arthroplasty depends on many factors: joint alignment, range of motion, patellar tracking and ligament stability. A correct soft tissue balance keeps the joint aligned in flexion and extension, and therefore constitutes the most important factor for durability of the implant. Indeed, incorrect soft tissue balancing is the primary cause of early implant failure necessitating revision surgery. Soft tissue releases, serving to correct imbalances, are performed until the flexion and extension gaps appear symmetrical and balanced. A knee is considered perfectly balanced when the flexion and extension gaps are perfectly rectangular and all the measurements are absolutely equal.

Arthroscopic management of calcific tendinopathy of the shoulder--do we need to remove all the deposit?

Results of arthroscopic management of chronic, recalcitrant calcific tendinopathy of the shoulder in 28 patients were evaluated. Twenty-six patients (average age, 44 years) were ultimately enrolled in the study. Postoperative radiographs were performed to determine the amount of calcium deposit removal. Radiographic examination 2 months after surgery was performed to evaluate further deposit changes. The Constant score showed a statistically significant improvement in all patients. Better results were obtained when complete removal of the calcifications was achieved. On radiographic examination, performed two months after surgery, no calcification deposit increased in size and no translucent deposit changed into a dense deposit. Most of the dense deposits, partially removed, changed into translucent deposits. In this series, we found arthroscopic management was effective in treating calcific tendinopathy.

Compression neuropathy of the motor fibers of the median nerve at wrist level.

Selective electrophysiological involvement of median motor fibers is rare in carpal tunnel syndrome. We report a patient with compression neuropathy of the median nerve who presented with isolated motor signs and symptoms without macroscopic evidence of compressive pathologies.

Para-articular osteochondroma of the knee.

We report a case of para-articular chondroma located in the infrapatellar fat pad of the knee of a 42-year-old woman with a history of anterior knee pain and restricted range of motion. On clinical examination, a solid palpable mass in the infrapatellar region was detected. Radiography and computed tomography of the knee revealed the presence of 3 different "popcorn"-like gross calcifications within Hoffa's fat pad. Magnetic resonance imaging showed areas of signal intensity in Hoffa's fat pad that were consistent with calcific nodules surrounded by chondral tissue. During arthroscopy, a dense extrasynovial mass was discerned within Hoffa's fat pad. The mass was entirely removed through an open approach medial to the patellar tendon. Resection specimens consisted of 3 well-circumscribed nodules of 5 x 2.5 x 1.5, 2 x 2 x 1, and 1.5 x 2 x 1 cm, respectively. Grossly, these nodules were surrounded by adipose tissue and presented a thin fibrous membrane. Histologic examination showed that the nodules were composed of cartilaginous tissue surrounded by fibrous connective and adipose tissue with multifocal endochondral ossification. The precise pathogenetic mechanism of these tumors remains unknown, but cartilaginous metaplasia of articular and para-articular connective tissue seems to be the primary cause. Patients with these lesions are currently treated with the use of marginal resection or excision.