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Following the onset of the new COVID-19 pandemic, particular attention is paid to the long-term outcomes, especially concerning patients affected by the SARS-CoV-2 virus leading to interstitial pneumonia. The aim of this research is to evaluate the possible evolution over time of interstitial pneumonia into post-inflammatory fibrosing interstitial disease. This research included 42 patients admitted to the COVID ward for SARS-CoV-2 interstitial pneumonia, 10 patients with mild pneumonia and respiratory failure who were treated with O2 only, 32 patients with severe pneumonia in which O2 and non-invasive ventilation were used for respiratory assistance, and 4 patients treated with invasive mechanical ventilation. At 70±30 days, 6, 12, 24, and 36 months after discharge, the cohort of patients carried out the evaluation of inflammation indices, high-resolution computed tomography (CT) chest scans, and functional respiratory tests. The comparative analysis showed that 83.3% of patients had residual parenchymal lung disease at 36-month follow-up, with a significantly higher rate in those with severe pneumonia and more extensive disease on initial CT. Regarding the pulmonary involvement model, patients presented ground-glass opacity or peripheral parenchymal bands, or a combination of them, peri- and intralobular interstitial thickening, which may be representative of fibrotic interstitial lung disease. There is a correlation between the severity of pneumonia, the inflammatory state, the need to increase respiratory support, and the quantity and persistence of CT-related lesions. Reductions in respiratory functions and exercise capacity were observed, the latter more pronounced in patients (24%) who had contracted severe pneumonia and required ventilatory support.Pulmonary outcomes from SARS-CoV-2 respiratory infections show a wide range of radiological findings, from complete recovery to stable outcomes of thickening and distortion of the interstitial architecture. From a functional point of view, there is an impairment of the alveolar-capillary diffusion capacity and, in cases who had contracted severe pneumonia, desaturation and reduced exercise tolerance in 24% of cases at a 36-month follow-up.

Respiratory alkalosis is one of the four basic disturbances to the acid-base equilibrium. Persistent primary respiratory alkalosis during non-invasive mechanical ventilation in patients with hypoxemic respiratory failure could be a risk factor for NIV failure. A 69-year-old man with acute hypoxemic respiratory failure caused by severe COVID-19 pneumonia demonstrated progressive worsening of gas exchange and clinical conditions. Despite a positive response to noninvasive mechanical ventilation, a therapeutic increase in respiratory support was required.

Introduction: Cisplatin, nab-paclitaxel, capecitabine, and gemcitabine (PAXG) regimen activity was assessed in a single institution phase II trial (PACT-19) on pancreatic ductal adenocarcinoma (PDAC). The PACT-31 study explored the external validity of PACT-19 results., Materials and Methods: Patients aged ≥18 and ≤75 years with KPS ≥70, and PDAC diagnosis receiving PAXG in the participating institutions were eligible and categorized as follows: A) PACT-19; B) PACT-31-HSR; C) PACT-31-non-HSR. With a sample of 175 patients, assuming a target 1-year overall survival of 60 % for metastatic and of 80 % for non-metastatic patients, the trial will be considered successful with the 1-year OS falling into the 95 % CI., Results: Data from 68 PACT-19 and 168 PACT-31 patients were retrieved. After 124 events, 1yOS was 52.5 % (95 %CI: 44.6-60.4 %) for metastatic and 80.5 % (95 %CI: 71.9-89.1 %) for non-metastatic patients. Survival overlapped between PACT-19 and PACT-31-HSR (median 17.6 and 17.4 months, p = 0.21) and was significantly shorter in PACT-31-non-HSR (median 11.3 months; p = 0.03). Differences of dose-intensity, use of maintenance therapy, and treatment after progression between PACT-31-HSR and non-HSR were evidenced., Discussion: PACT-19 results have external validity. The outcome difference between HSR and non-HSR centers endorses the need of creating a hub-and-spoke network aimed at sharing the expertise on rare-diseases., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to comprehensively evaluate the prognostic value of T1 histo-anatomic substaging (T1a/T1b) for high grade (HG) non-muscle invasive bladder cancer (NMIBC) over a large single-centre cohort., Materials and Methods: Patients with primary HG T1 NMIBC were identified from our Institutional database, between 2011 and 2022. Data from diagnosis to repeated transurethral resection of bladder tumour (RE-TURBT), bacillus Calmette-Guérin (BCG) treatment and follow-up were collected. Patients were stratified based on histo-anatomic landmark into T1a (invasion above the Muscularis Mucosa-MM) and T1b (into/beyond MM). Kaplan-Meier curves and multivariate Cox regression analyses were used to assess the impact of histo-anatomic substaging on recurrence-free survival (RFS), cancer-specific survival (CSS), and progression-free survival (PFS)., Results: Substaging was feasible in 88% of cases. The median (IQR) follow-up was 40 (17-72) months. T1b patients had larger initial tumours (> 3 cm: 43.2% vs. 26.1%, p < 0.001), while upstaging to muscle-invasive bladder cancer (MIBC) at RE-TURBT was more frequent in T1b than in T1a (5.9% vs. 1.5%, p = 0.02). T1b patients without BCG induction had worse RFS and PFS (all p ≤ 0.02) compared to T1a, while no differences were observed in patients who received complete BCG induction. At Multivariate analysis, completing at least a BCG induction course was associated with better outcomes across all endpoints., Conclusions: Invasion of the MM in primary T1 NMIBC is associated with a higher risk of upstaging to MIBC. Patients who received full BCG induction had similar outcomes regardless of substaging, whereas T1b patients without BCG induction experienced higher recurrence and progression rates., Competing Interests: Declarations. IRB approval: Patients were retrospectively enrolled after this study was approved by IRB of Policlinico Riuniti of Foggia on 15th of March 2022 (Approval Code 31/CE/2022). An institutional review board waiver for informed consent was obtained prior to conducting this study, in accordance with institutional regulations when dealing with de-identified previously collected data. Conflict of interest: None of the authors have any relevant disclosures, and none of the authors have any financial or non-financial interests that may be relevant to the submitted work., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Monoclonal gammopathy of renal significance (MGRS) refers to a group of renal disorders caused by a monoclonal immunoglobulin (MIg), secreted by a non-malignant B-cell clone. Unlike overt multiple myeloma or B-cell proliferation, MGRS does not meet those diagnostic criteria. However, it is associated with significant morbidity, due to severe renal, and sometimes systemic, lesions induced by the MIg. Early recognition is crucial, as chemotherapy to suppress MIg secretion often improves outcomes. The spectrum of renal diseases in MGRS is broad, including both well-known conditions like AL amyloidosis and newly described lesions. Kidney biopsy is essential to determine the specific lesion associated with MGRS and assess its severity. Diagnosis involves integrating morphologic alterations using techniques such as light microscopy, immunofluorescence (IF), electron microscopy, and, in some cases, IF staining for Ig isotypes, immunoelectron microscopy, and proteomic analysis. Additionally, a complete hematologic evaluation, including serum and urine protein electrophoresis, immunofixation, and a serum-free light-chain assay, is necessary., Competing Interests: The authors declare no conflicts of interest.

The Persian Gulf hosts the second-largest population of Dugongs. The International Union for the Conservation of Nature (IUCN) lists them as Vulnerable to Extinction species. Incidental fishing, vessel strikes, environmental pollution, habitat degradation, and infectious diseases currently threaten these sirenians. While research focused on the abovementioned threats, little is known about pathogen infections, particularly waterborne parasites. The current study aimed to investigate the prevalence of the waterborne parasites, namely Blastocystis, Cryptosporidium, Dientamoeba fragilis, Giardia duodenalis, and Toxoplasma gondii in the Qatar Dugongs population. Hence, twenty-three tissues from stranded Dugongs' carcasses were collected postmortem and subjected to DNA extraction and parasite qPCR screening. Only Blastocystis and Cryptosporidium species were detected in different tissues across the tested animals harboring genotypes ST1 and Cryptosporidium hominis IbA9G3, respectively, with the first-time report of Blastocystis sp. within sirenian hosts. Continuous monitoring should be provided to shed lights about the contamination sources of these endangered species and clarify the zoonotic potential transmission routes between wildlife and humans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Systemic sclerosis is a rare rheumatic disease characterized by immune cell activation, tissue fibrosis, and endothelial dysfunction. Extracellular matrix synthesis disorder causes widespread fibrosis, primarily in skin and internal organs. Various factors such as TGFβ, VEGF, Galectin-3, and signaling pathways like Wnt/β-catenin are involved in pathophysiological processes. Treatment lacks a unified approach but combines diverse modalities tailored to disease subtype and progression. Current therapeutic strategies include biologics, JAK inhibitors, and IL-6 pathway modulators. Monoclonal antibodies and hypomethylating agents demonstrate potential in fibrosis inhibition. This review focuses on emerging therapeutic evidence regarding drugs targeting collagen, cytokines, and cell surface molecules in systemic sclerosis, aiming to provide insight into potential innovative treatment strategies., (© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sea turtles can host a wide range of parasitic taxa, some of which may lead to severe diseases, weakening and endangering their health. Assessing free-ranging sea turtles' responses to these potential pathogens using biomarkers can provide valuable insights into the cellular and molecular impacts of parasites. This information can serve as a crucial tool for conservation efforts. During rehabilitation, hematological, genotoxic and innate immune parameters were evaluated in 70 free-ranging sea turtles rescued along the Southern Adriatic coast (Eastern Mediterranean Sea) from 2021 to 2023, 24 of which were found to have parasitic infections. Hapalotrema mistroides, Sulcascaris sulcata and Neospirorchis sp. were identified by coprological and molecular techniques. Some significant differences for biomarkers were associated with these parasites. These findings highlight the importance of considering the infection status of free-ranging sea turtles when evaluating biomarker results, as major pathogens like parasites can influence certain parameters., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest and that they have no actual or potential competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A retrospective analysis was conducted to investigate how a bright luminal sign on high b-value diffusion-weighted imaging (DWI) could be considered as a new biomarker for identifying fibrotic strictures in Crohn's disease (CD). Fibrotic strictures, due to excessive deposition of extracellular matrix following chronic inflammatory processes, can be difficult to distinguish from inflammatory strictures using endoscopy. This study was performed on 65 patients with CD who underwent MRE, and among them 32 patients showed the bright luminal sign on high b-value DWI. DWI findings were compared to pre- and post-contrast MRE data. Luminal bright sign performance results were calculated using a confusion matrix, the relationship between categorical variables was assessed by the χ2 test of independence, and the Kruskal-Wallis test (ANOVA) was used for the assessment of statistical significance of differences between groups. The results indicated a high sensitivity (90%) and specificity (85%) of the bright luminal sign for fibro-stenotic CD and a significant correlation between DWI luminal brightness and markers such as the homogeneous enhancement pattern ( p < 0.001), increase in enhancement percentage from 70 s to 7 min after gadolinium injection ( p < 0.001), and submucosal fat penetration ( p = 0.05). These findings indicate that DWI hyperintensity can be considered as a good non-invasive indicator for the detection of severe intestinal fibrosis and may provide an efficient and accurate method for assessing fibrotic strictures. This new non-invasive biomarker could allow an early diagnosis of fibrotic stricture, delaying the onset of complications and subsequent surgery. Moreover, further evaluations through larger prospective trials with histopathological correlation are needed to confirm these results and completely determine the clinical benefits of DWI in treating CD.

Background: Lung cancer (LC) is the leading cause of cancer-related deaths. Although low-dose computed tomography (LD-CT) reduces mortality, its clinical use is limited by cost, radiation, and false positives. Therefore, there is an urgent need for non-invasive and cost-effective biomarkers. The Raf Kinase Inhibitor Protein (RKIP) plays a crucial role in cancer development and progression and may also contribute to regulating the tumor-immune system axis. This protein has recently been described in biological fluids. Therefore, we conducted a pilot case-control study to assess RKIP and phosphorylated RKIP (pRKIP) levels in the urine and blood of LC patients. Methods: A novel enzyme linked immunosorbent assay (ELISA) assay was used to measure RKIP and pRKIP levels in urine and blood samples of two cohorts of LC patients and healthy controls (HSs). Furthermore, the biomarkers levels were correlated with tumor characteristics. Results: Serum, but not urine, levels of RKIP were significantly elevated in LC patients, distinguishing them from low- and high-risk healthy subjects with 93% and 74% accuracy, respectively. The RKIP/pRKIP ratio (RpR score) showed an accuracy of 90% and 79% in distinguishing LC patients from HS and HR-HS, respectively. Additionally, the RpR score correlated better with dimension, stage, and lymph node involvement in the tumor group. Conclusions: The serum RKIP and pRKIP profile may be a promising novel biomarker for early-stage LC.

The task of preventing suicide in older adults is an important social burden as older adults aged above 65 are exposed to singular psychological aspects that increase suicide risks. Moreover, when an older adult corpse is found, the medico-legal inspection represents a fundamental tool to identify the exact cause of death, classifying or excluding it as suicide. In this scenario, this review aims to explore the neurobiological factors that could be related to suicidal behavior in older adults. A further goal of this review is the exploration of the medico-legal aspects surrounding older adult suicides, clarifying the importance of forensic investigation. Particularly, this review examines issues such as neurotransmitter imbalances, cognitive impairment, neuroinflammation, psychosocial factors related to geriatric suicide, and neurodegenerative diseases. Additionally, medico-legal aspects such as policy considerations, legal frameworks, mental health assessments, ethical implications and forensic investigation were explored. Considering the importance of this phenomenon, especially in western countries, a need has emerged for focused screening tools on suicidal behavior among older adults, in order to contain it. Therefore, this review makes an exhaustive appraisal of the literature giving insights into the delicate interplay between neurobiology as well as mental health in relation to older adult suicide within a medico-legal context. The comprehension of different aspects about this complex phenomenon is fundamental to propose new and more effective interventions, supporting tailored initiatives such as family support and improving healthcare, specifically towards vulnerable ageing societies to reduce older adult suicide risks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sessa, Polito, Li Rosi, Salerno, Esposito, Pisanelli, Ministeri, Messina, Carotenuto, Chieffi, Messina and Monda.)

Purpose: Prostatic urethral lift has been an effective ejaculation sparing treatment for benign prostatic hypertrophy. The aim of this study was to evaluate the effect on male semen parameters., Methods: Between July 2014 and January 2022, 20 young men with urinary symptoms of BPH, unresponsive to drug treatment and motivated to preserve ejaculation for eventual paternity, underwent UroLift. Semen analysis was performed before and 6 month after surgery with evaluation of pH, volume, sperm concentration, total motility, vitality and morphology according to WHO 2011. All underwent digital rectal examination, transrectal prostate ultrasound to measure prostate volume, PSA, uroflowmetry, cystoscopy and urodynamics test if necessary. Objective and subjective urinary function was scheduled at 1, 3, 6, 12 month than yearly with UFM, IPSS, IIEF-5, and MSHQ-EjD-SF., Results: At a mean follow-up of 36 month (range 12 to 63), no retroejaculation or changes in seminal parameters occurred. Mean age was 44.5 (range 36.5 to 48) years. Mean operative time was 15 (range 10 to 20) min and 2.5 (range 2 to 4) implants per patients were used. At 6 month there were no difference in terms of total sperm count, volume, pH, motility, vitality, morphology, liquefaction, leucocytes (p = 0.9; p = 0.8; p = 0.7; p = 1; p = 1; p = 1; p = 0,2; p = 0.5). At last, Q-max increased by 64.4% (p = 0.001), post-void residual volume decreased by 66.6% (p = 0.016), and IPSS decreased by 60% (p < 0.001). IIEF and MSHQ-EjD-SF were preserved (p = 0.14, p = 0.4)., Conclusions: UroLift appears safe technique to correct LUTS from BPH in young men desirous to preserve seminal analysis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite their critical roles in marine ecosystems, only few studies have addressed the gut microbiome (GM) of cetaceans in a comprehensive way. Being long-living apex predators with a carnivorous diet but evolved from herbivorous ancestors, cetaceans are an ideal model for studying GM-host evolutionary drivers of symbiosis and represent a valuable proxy of overall marine ecosystem health. Here, we investigated the GM of eight different cetacean species, including both Odontocetes (toothed whales) and Mysticetes (baleen whales), by means of 16S rRNA-targeted amplicon sequencing. We collected faecal samples from free-ranging cetaceans circulating within the Pelagos Sanctuary (North-western Mediterranean Sea) and we also included publicly available cetacean gut microbiome sequences. Overall, we show a clear GM trajectory related to host phylogeny and taxonomy (i.e., phylosymbiosis), with remarkable GM variations which may reflect adaptations to different diets between baleen and toothed whales. While most samples were found to be infected by protozoan parasites of potential anthropic origin, we report that this phenomenon did not lead to severe GM dysbiosis. This study underlines the importance of both host phylogeny and diet in shaping the GM of cetaceans, highlighting the role of neutral processes as well as environmental factors in the establishment of this GM-host symbiosis. Furthermore, the presence of potentially human-derived protozoan parasites in faeces of free-ranging cetaceans emphasizes the importance of these animals as bioindicators of anthropic impact on marine ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

An expansion of poly-alanine up to +13 residues in the C-terminus of the transcription factor PHOX2B underlies the onset of congenital central hypoventilation syndrome (CCHS). Recent studies demonstrated that the alanine tract expansion influences PHOX2B folding and activity. Therefore, structural information on PHOX2B is an important target for obtaining clues to elucidate the insurgence of the alanine expansion-related syndrome and also for defining a viable therapy. Here we report by NMR spectroscopy the structural characterization of the homeodomain (HD) of PHOX2B and HD + C-terminus PHOX2B protein, free and in the presence of the target DNA. The obtained structural data are then exploited to obtain a structural model of the PHOX2B-DNA interaction. In addition, the variant +7Ala, responsible for one of the most frequent forms of the syndrome, was analysed, showing different conformational proprieties in solution and a strong propensity to aggregation. Our data suggest that the elongated poly-alanine tract would be related to disease onset through a loss-of-function mechanism. Overall, this study paves the way for the future rational design of therapeutic drugs, suggesting as a possible therapeutic route the use of specific anti-aggregating molecules capable of preventing variant aggregation and possibly restoring the DNA-binding activity of PHOX2B., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Background: Among elderly inpatients, malnutrition is one of the most important predictive factors affecting length of stay (LOS), mortality, and risk of re-hospitalization., Methods: We conducted an observational, retrospective study on a cohort of 2206 acutely inpatients. Serum albumin and lymphocytes were evaluated. Instant Nutritional Assessment (INA) and the Prognostic Nutritional Index (PNI) were calculated to predict in-hospital mortality, LOS, and risk of rehospitalization., Results: An inverse relationship between LOS, serum albumin, and PNI were found. Deceased patients had lower albumin levels, lower PNI values, and third- and fourth-degree INA scores. An accurate predictor of mortality was PNI (AUC = 0.785) after ROC curve analysis; both lower PNI values (HR = 3.56) and third- and fourth-degree INA scores (HR = 3.12) could be independent risk factors for mortality during hospitalization after Cox regression analysis. Moreover, among 309 subjects with a lower PNI value or third- and fourth-class INA, hospitalization was re-hospitalization., Conclusions: PNI and INA are two simple and quick-to-calculate tools that can help in classifying the condition of hospitalized elderly patients also based on their nutritional status, or in assessing their mortality risk. A poor nutritional status at the time of discharge may represent an important risk factor for rehospitalization in the following thirty days. This study confirms the importance of evaluating nutritional status at the time of hospitalization, especially in older patients. This study also confirms the importance for adequate training of doctors and nurses regarding the importance of maintaining a good nutritional status as an integral part of the therapeutic process of hospitalization in acute departments.

This study aimed to demonstrate the potential role of dual-energy CT in assessing bone mineral density (BMD) using hydroxyapatite-fat material pairing in postmenopausal women. A retrospective study was conducted on 51 postmenopausal female patients who underwent DXA and DECT examinations for other clinical reasons. DECT images were acquired with spectral imaging using a 256-slice system. These images were processed and visualized using a HAP-fat material pair. Statistical analysis was performed using the Bland-Altman method to assess the agreement between DXA and DECT HAP-fat measurements. Mean BMD, vertebral, and femoral T-scores were obtained. For vertebral analysis, the Bland-Altman plot showed an inverse correlation (R 2 : -0.042; RMSE: 0.690) between T-scores and DECT HAP-fat values for measurements from L1 to L4, while a good linear correlation (R 2 : 0.341; RMSE: 0.589) was found for measurements at the femoral neck. In conclusion, we demonstrate the enhanced importance of BMD calculation through DECT, finding a statistically significant correlation only at the femoral neck where BMD results do not seem to be influenced by the overlap of the measurements on cortical and trabecular bone. This outcome could be beneficial in the future by reducing radiation exposure for patients already undergoing follow-up for chronic conditions.

Background: Gastrointestinal pathogens (GPs) contribute significantly to the burden of illness worldwide with diarrhoea being the most common among gastrointestinal symptoms (GSs). In the COVID-19 disease, diarrhoea, could be one of the initial presenting symptoms. However, no data on the potential correlation between diarrhoea-causing pathogens and SARS-CoV-2 infection are available. Therefore, we carried out a 2-years retrospective study aimed to evaluate the prevalence of "classic" GPs among SARS-CoV-2 infected and non-infected patients with diarrhoea in Italy., Methods: Results of SARS-CoV-2 research from nasopharyngeal and detection of GPs from stool swab samples by Allplex™ SARS-CoV-2 and GI Virus, Bacteria and Parasite Assay were analysed for all patients with diarrhoea referring to Policlinico Ospedaliero Universitario, Foggia, (Italy) from February 2022 to October 2023., Results: Out of the 833 involved patients, 81 (3.9%) were COVID-19 positive, while 752 (90.3%) were COVID-19 negative. Among COVID-19-positive patients, 37% (n = 30/81) were found positive for one or more GPs with a higher prevalence of protozoan parasites (18.5%) ( Blastocystis ST1-ST4 subtypes, Dientamoeba fragilis genotype I), followed by bacteria (7.4%) ( Campylobacter sp., Salmonella sp.). Viral pathogens were more frequent among COVID-19 negative patients (Adenovirus, Norovirus). Among GPs, Blastocystis ST3 subtype was the most prevalent registered in the 16% of patients (p = 0.0001)., Conclusions: Based on obtained results, a likely interaction between the classic GPs and SARS-CoV-2 infection can be speculated, driven by protozoan parasites. Moreover, these results also provide baseline data to understand more deeply Blastocystis sp. role in this scenario of dysbiosis, particularly in those cases of SARS-CoV-2 co-infection., Competing Interests: The authors declare that they have no conflict of interest and that they have no actual or potential competing financial interests., (© 2024 The Authors.)

Aims: Stereotactic arrhythmia radioablation (STAR) is a novel therapeutic approach for cardiac arrhythmias. The aim of this trial is to investigate the feasibility of STAR for the treatment of paroxysmal atrial fibrillation (AF) in elderly patients., Methods and Results: Inclusion criteria were age >70 years, symptomatic AF, antiarrhythmic drugs failure, or intolerance. All patients underwent to 4D cardiac computed tomography simulation. The clinical target volume was identified in the area around pulmonary veins (PV). Stereotactic arrhythmia radioablation was performed with a total dose of 25 Gy (single fraction) delivered in 3 min. Twenty patients were enrolled and 18 underwent STAR. One patient withdrew informed consent before treatment and one patient was excluded due to unfavourable oesophagus position. With a median follow-up (FU) of 16 months (range 12-23), no acute toxicity more than Grade 3 was reported. Five patients had a Grade 1 oesophagitis 24 h after STAR; eight patients had an asymptomatic Grade 1 pericardial effusion, and one patient had a torsade de pointes treated effectively by electrical cardioversion and subsequent cardiac implantable cardioverter-defibrillator implantation. Most patients had a significant reduction in AF episodes. Five patients, due to arrhythmias recurrences after STAR, performed electrophysiological study documenting successful PV isolation. Finally, a significant improvement of quality of life was documented (48 ± 15 at enrolment vs. 75 ± 15 at 12 months FU; P < 0.001)., Conclusion: The present phase II trial demonstrated the feasibility of STAR in paroxysmal AF elderly patients and its potential role in increasing the quality of life. Surely, more robust data are needed about safety and efficacy., Trial Registration: ClinicalTrials.gov: NCT04575662., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

High-grade serous ovarian cancer (HGSOC) patients carrying the BRCA1/2 mutation or deficient in the homologous recombination repair system (HRD) generally benefit from treatment with PARP inhibitors. Some international recommendations suggest that BRCA1/2 genetic testing should be offered for all newly diagnosed epithelial ovarian cancer, along with HRD assessment. Academic tests (ATs) are continuously under development, in order to break down the barriers patients encounter in accessing HRD testing. Two different methods for shallow whole-genome sequencing (sWGS) were compared to the reference assay, Myriad. All these three assays were performed on 20 retrospective HGSOC samples. Moreover, HRD results were correlated with the progression-free survival rate (PFS). Both sWGS chemistries showed good correlation with each other and a complete agreement, even when compared to the Myriad score. Our academic HRD assay categorized patients as HRD-Deficient, HRM-Mild and HRN-Negative. These three groups were matched with PFS, providing interesting findings in terms of HRD scoring and months of survival. Both our sWGS assays and the Myriad test correlated with the patient's response to treatments. Finally, our AT confirms its capability of determining HRD status, with the advantage of being faster, cheaper, and easier to carry out. Our results showed a prognostic value for the HRD score.

The prevalence of Blastocystis sp., its genetic diversity and the distribution of circulating subtypes (STs) were molecularly investigated in a cohort of autochthonous and immigrant patients with gastrointestinal symptoms hospitalized over the period February 2022-June 2023 at the Policlinico Ospedaliero-Universitario "Riuniti", Foggia, in Southern Italy. The population variables, including patient geographical origin, gender and age classes were reported. Out of the 927 investigated patients, 36 (3.9%) were positive for Blastocystis sp. A statistically significant association with African origin and age classes >18 years old was found. ST1 (allele 4), ST2 (alleles 9, 13), ST3 (alleles 34, 36) and ST4 (allele 92) were the subtypes detected with a different distribution between autochthonous and immigrant patients. Co-infections with enteric protozoa such as Giardia duodenalis and Dientamoeba fragilis, pathogenic bacteria as Clostridioides difficile, Campylobacter jejuni and Aeromonas sp. and viral infections such as Norovirus were found in 33% of cases. This is the first study of Blastocystis sp., its circulating subtypes and allele variability among patients with different geographical origin in an area of Southern Italy, in the Central Mediterranean, characterized by high immigrant pressure. These results provide baseline data to better investigate a potential interaction between Blastocystis sp. and other risk factors in patients with gastrointestinal symptoms., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest and that they have no actual or potential competing financial interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. Abdominal ultrasound (US) is by far the most widely used first-level exam for the diagnosis of HCC. We aimed to assess whether different ultrasound patterns were related to tumor prognosis., Methods: We retrospectively reviewed all patients with a new diagnosis of HCC (single nodule) and undergoing radiofrequency thermal ablation (RFTA) at our clinic between January 2009 and December 2021. Patients were classified according to four HCC ultrasound patterns: 1A, single capsulated nodule; 1B, well capsulated intra-node nodule; 1C, cluster consisting of capsulated nodules; and 2, non-capsulated nodule., Results: 149 patients were analysed; median follow-up time was 43 months. US patterns 1A (32.9%) and 1B (61.1%) were the most commonly seen. Median overall survival (OS) and recurrence-free survival (RFS) from RFTA were 54 months (95% CI, 42-66) and 22 months (95% CI, 12-32), respectively. Pattern 1A showed the best OS. Compared to pattern 1A, 1B was independently associated with worse OS (51 months (95% CI, 34-68) vs. 46 months (95% CI, 18-62)) and RFS (34 months (95% CI, 27-41) vs. 18 months (95% CI, 12-24)). Patterns 1C and 2 were associated with worse RFS compared to 1A, while no difference was seen for OS. Among baseline clinical variables, pattern 1B exhibited higher histological grade ( p = 0.048) and tumor dimension ( p = 0.034) compared to pattern 1A., Conclusions: Our findings demonstrate that different US patterns correlate with different survival outcomes and tumor behavior in patients with HCC. Prospective studies are needed to confirm these results.

Background: The increased vascular risk associated with varicella-zoster virus (VZV) reactivation is extensively established in the general population. This retrospective cohort study investigates whether this observation holds for People Living with HIV (PLWH), a group already confronting heightened cardiovascular risk., Methods: Among PLWH who initiated antiretroviral therapy (ART) at our center and have been under our care for >24 months since 1st January 2005, individuals with a history of herpes zoster (HZ) were identified, and their features were compared with those of PLWH with no history of HZ. The prevalence of ischemic events (deep venous thrombosis, stroke, and acute myocardial infarction) was calculated and compared using the chi-square test. An odds ratio (O.R.) and a 95% confidence interval (C.I.) for ischemic events following HZ were evaluated through univariate and multivariate logistic regression., Results: Overall, 45/581 PLWH reported HZ. Ischemic events followed HZ significantly more often than not (13% vs. 5%, p = 0.01). Positive serology for both VZV and HZ correlated with increased ischemic risk (O.R. 4.01, 95% C.I. 1.38-11.6, p = 0.01 and O.R. 3.14, 95% C.I. 1.12-7.68, p = 0.02, respectively), though chronic heart disease demonstrated stronger predictive value in multivariate analysis(O.R. 8.68, 95% C.I. 2.49-29.50, p = 0.001)., Conclusions: VZV potentially exacerbates vascular risk in PLWH, particularly in the presence of other predisposing factors. Further research is needed to confirm our data.

Background: Rhinitis is as an inflammation of the nasal mucosa, characterized by high prevalence, widespread morbidity, and a significant financial burden on health care systems. Nevertheless, it is often considered as no more than a mere annoyance. This point of view has progressively led to underestimate and trivialize the disease. Therefore, there are numerous, mostly overlapping classifications of rhinopaties, but clear and standardized guidelines for diagnosis and treatment are still lacking. In the context of Precision Medicine, the development of a classification system focused on the endotypes of rhinitis to be widely adopted appears of utmost importance, also by virtue of study of the nasal immunophlogosis that, thanks to nasal cytology (NC), has recently allowed to better define the different forms of rhinitis, giving a new nosological dignity to several rhinopaties., Aim: We aimed to summarize the current knowledge regarding rhinitis and to propose a systematic classification of rhinitis, based on both etiology and cytological findings., (© 2023. The Author(s).)

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with unknown etiology. To date, the identification of new diagnostic, prognostic and progression biomarkers of IPF turns out to be necessary. MicroRNA (miRNA) are small non-coding RNAs which negatively regulate gene expression at the post-transcriptional level in several biological and pathological processes. An aberrant regulation of gene expression by miRNA is often associated with various diseases, including IPF. As result, miRNAs have emerged as potential biomarkers with relevance to pulmonary fibrosis. Several reports suggested that miRNAs are secreted as microvesicles or exosome, and hance they are stable and can be readily detected in the circulation. In the contest of miRNAs as circulating biomarkers, different studies show their role in various types of interstitial lung diseases and suggest that these small molecules could be used as prognostic markers of the disease. Exosomes are small, lipid-bound vesicles able to carry various elements of the naïve cells such as proteins, lipids, mRNAs and miRNA to facilitate cell communication under normal and diseases condition. Exosomal miRNAs (exo-miRNA) have been studied in relation to many diseases. However, there is little or no knowledge regarding exo-miRNA in bronchoalveolar lavage (BAL) in IPF. Our study's aim is to evaluate the changes in the expression of two exo-miRNAs in BAL, respectively miR-21 and miR-92a, through highlighting the differences between IPF, progressive pulmonary fibrosis (PPF) and not-progressive pulmonary fibrosis (nPPF)., Methods: Exosomes were characterized by Western Blot and Multiplex Surface Marker Analysis. Exosomal miRNA expression was performed by qRT-PCR. ANOVA or Kruskal-Wallis test, based on data normality, was used to compare the differential expression between groups., Results: MiR-21 expression was significantly higher in the nPPF group than in both IPF and PPF. A result that could point above a possible role of miR-21, as a biomarker in the differential diagnosis between PPF and nPPF. MiR-92a, indeed, was down regulated in PPF compared to IPF and down regulated in PPF compared to nPPF., Conclusions: This study demonstrated the putative role of both miR-21 and miR-92a as possible biomarkers of pulmonary fibrosis progression. Moreover, the role of exo-miRNAs is examined as a possible future direction that could lead to new therapeutic strategies for the treatment of progressive and non-progressive pulmonary fibrosis., (© 2023. The Author(s).)

Background: Spreading data describe cardiovascular disease (CVD) as a growing cause of hospitalization in systemic sclerosis (SSc) patients. Although interstitial lung disease and pulmonary arterial hypertension (PAH) remain the principal causes of mortality, the presence of CVD has been shown to further increase mortality in SSc patients. Few and contrasting data are available on cardiovascular impairment, particularly of subclinical coronary arteries disease, in SSc patients. The aims of this study were: 1) to determine the demographic, clinical, and cardiovascular differences between the groups of SSc patients with and without subclinical coronary atherosclerosis (SCA) assessed by coronary calcium score; 2) to verify the performance of cardiovascular risk scores in SSc for detection of SCA major cardiovascular events (MCVE); 3) to evaluate the risk factors associated to MCVE in 5 years of follow-up in this study group of patients., Methods: Sixty-seven SSc patients were enrolled in this study. SCA was assessed using quantification of coronary calcium score by computerized tomography, reported as Agatson. Evaluation of common cardiovascular risk scores, carotid plaques by Doppler ultrasonography, the history of peripheral artery disease (PAD), lipid profiles, and clinical and laboratiristic characteristics of SSc were assessed at baseline visits for each patient. Factors associated with the presence of SCA were assessed by multivariate logistic analysis. A five years prospective study was performed for the evaluation of MCVE occurrence and its possible predictors., Results: The prevalence of SCA was 42% (Agatston scores of 266.04 ± 455.9 units) in our group of SSc patients. Patients with SCA were principally older (p = 0.0001) and had higher rates of CENP-B antibodies (57% vs 26%; p = 0.009), pulmonary arterial hypertension (PAH) (25% vs 3%; p = 0.008), dysphagia (86% vs 61%; p = 0.027), and users of statins (36% vs 8%; p = 0.004), carotid plaque (82% vs 13%; p = 0.0001), PAD (79% vs 18%; p = 0.0001), and metabolic syndrome (25% vs 0%; p = 0.002) than patients without SCA. Metabolic syndrome (OR: 8.2, p = 0.0001), presence of a PAD (OR: 5.98, p = 0.031), and carotid plaque (OR: 5.49, p = 0.010) were the main factors associated with SCA in SSc patients, by multivariate regression analysis. MCVE occurred in 7 patients. By multivariate COX regression analysis unique predictor of MCVE in 5 years of follow-up in our SSc patients was the presence of PAH (HR: 10.33, p = 0.009). Of note, the contemporary presence of PAH and SCA (defined as "not pure" pattern of PAH) was observed in 71% of patients with the occurrence of MCVE CONCLUSION: This study evidenced the high presence of the new "not pure" pattern of PAH, which could worsen the outcome in SSc in a medium-term (5 years) observation period. Furthermore, our data confirmed a higher cardiovascular impairment in SSc due to the presence of both SCA, mainly associated with typical cardiovascular risk factors, and PAH, life-threatening complications of SSc, that is the principal cause of the occurrence of MCVE in our SSc patients. A careful assessment of cardiovascular involvement in SSc and a more aggressive therapeutic strategy for preventing CAD and treating PAH should be highly suggested to reduce MCVE in SSc patients., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Purpose: The diagnosis of obstructive sleep apnea (OSA) is instrument, operator, and time-dependent and therefore requires long waiting times. In recent decades, technological development has produced useful devices to monitor the health status of the population, including sleep. Therefore, the aim of this study was to evaluate a wearable device (WD) in a group of individuals at high risk of OSA., Methods: The study was conducted on consecutive subjects with high risk of OSA assessed by sleep questionnaires and clinical evaluation. All subjects performed cardio-respiratory monitoring (CRM) and WD simultaneously on a single night, after which the parameters of the two sleep investigations were compared., Results: Of 20 individuals enrolled, 60% were men and mean age was 57.3 ± 10.7 years. The apnea-hypopnea index (AHI) for the CRM was 23.1 ± 19.6 events·h -1 while it was 10.3 ± 8.3 events·h -1 for the WD. Correlation analysis between the results of the two investigations showed r = 0.19 (p = 0.40) for AHI and r = 0.4076 (p = 0.07) for sO2%. The accuracy for different stages of OSA severity was 70% in OSA cases and 60% in moderate to severe cases with sensitivity and specificity varying a great deal., Conclusion: Small and low-cost devices may prove to be a valuable resource to reduce costs and waiting times for a sleep investigation in suspected OSA. However, diagnosis of sleep apnea requires valid and reliable instruments, so validation tests are necessary before a device can be commercialized., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Chronic rhinosinusitis with nasal polyps (CRSwNP) is defined as a Type 2 eosinophilic disease, while CRSsNP is considered a Type 1 neutrophilic disease. Since neutrophils are also activated in eosinophilic CRSwNP, the eosinophil-neutrophil dualism has been revaluated. Among the inflammatory cells infiltrating sinus-nasal tissues, the role of mast cells (MCs) is not already recognized, although Clinical-Cytological Grading, which defines the severity of CRSwNP, attributes to mixed eosinophil-MC forms of CRSwNP a greater risk of recurrence. We aimed to examine nasal polyps from both a cytological and histopathological point of view, to evaluate the presence and localization of MCs. Cytological and histological examination of 39 samples of nasal polyps were performed. Immunohistochemistry was used to evaluate the presence of Tryptase + CD117 + MCs, which were counted both in the epithelial layer and in the lamina propria. A statistically significant correlation was found between intraepithelial MCs and CRSwNP severity (p < 0.001) and between the total eosinophil count and the total mast cell count (p < 0.001). Cytological examination and immunohistochemistry were comparable in detecting the presence of intraepithelial MCs (p = 0.002). The histological cut-off of 6 intraepithelial MCs was identified to detect severe CRSwNP (p < 0.001). MCs have been shown to be located in the lamina propria of almost all eosinophilic nasal polyps without significantly affecting their severity. Intraepithelial MCs are associated with greater severity of CRSwNP. Histopathological criteria of the eosinophil-MC form of CRSwNP in addition to the eosinophilic one, should be defined to guarantee patients effective and tailored treatments., (© 2023. The Author(s).)

Anogenital warts (AWs) represent a therapeutic challenge, especially in infants, due to sensitive skin and frequent disease recurrence. Though the initial wait-and-see approach is often adopted in asymptomatic immunocompetent children, with spontaneous clearing in almost 90% of cases within two years, persistent or symptomatic lesions can be reasonably treated. However, few studies have been conducted on children. Consequently, most treatments on patients under age 12 are not approved by the Food and Drug Administration. Herein, we review possible therapies for pediatric use in AW and report an illustrative case of a two-year-old boy with atopic skin and symptomatic, persistent AWs who was successfully treated with topical podophyllotoxin, without adverse effects or recurrence. Among available therapies for AWs, topical therapies, such as immunomodulating-agents (topical imiquimod 5% and 3.75% cream, sinecatechins 15% ointment) and cytotoxic agents (podophyllotoxin and cidofovir) are considered manageable in children because of their low aggressiveness. In particular, podofillotoxin gel 5% and imiquimod 5% cream have been reported to be safe and efficacious in children. Currently, HPV vaccination is not recommended as a treatment for established HPV infection and AWs, yet a possible therapeutic role of HPV vaccination was recently suggested in the literature and deserves mention.

Cholangiocarcinoma (CCA) is a rare malignancy of the gastrointestinal tract, with aggressive behavior, and portends a poor prognosis. Traditionally, it is classified according to its site of involvement as intrahepatic, perihilar, and distal cholangiocarcinoma. A host of genetic and epigenetic factors have been involved in its pathogenesis. Chemotherapy has remained the standard first-line treatment over the last decade, with a disappointing median overall survival of 11 months for locally advanced and metastatic CCA. The advent of immunotherapy has revolutionized the treatment of many pancreaticobiliary malignancies, offering durable responses with a safe therapeutic profile. To date, there have been no significant advances in the management of CCA. Novel immunotherapeutic methods, such as cancer vaccines, adoptive cell therapy, and combinations of immune checkpoint inhibitors with other agents, are currently under investigation and may improve prognosis with overall survival. Efforts to find robust biomarkers for response to treatment along with multiple clinical trials are also ongoing in this regard. In this review, we present an overview of the current advances and the future perspectives of immunotherapy in the management of CCA.

Purpose: Radical cystectomy (RC) is the standard treatment for high-risk non muscle-invasive bladder cancer (NMIBC) failing first BCG treatment. A second BCG course is an option for those patients who refuse RC or are not eligible for it, but its success rate is quite low. Aim of the present study was to determine whether the addition of intravesical electromotive drug administration of mytomicin-C (EMDA-MMC) improved the efficacy of second BCG course., Methods: Patients with high-risk NMIBC having failed first BCG treatment and having refused RC were offered a second BCG induction course either alone (group A) or combined with EMDA-MMC (group B). Recurrence-free survival (RFS), progression-free survival (PFS) and cancer-specific survival (CSS) were tested., Results: Of the 80 evaluable patients, 44 were in group A and 36 in group B; median follow-up was 38 months. RFS was significantly worse in group A whereas there was no difference in PFS and CSS between the two groups. Stratifying by disease stage, Ta patients receiving combined treatment had statistically better RFS and PFS survival than those receiving BCG only; this difference did not apply to T1 patients. Multivariable analysis confirmed that combined treatment was a significant predictor of recurrence and was close to predict progression. No tested variable was predictive of recurrence or progression in T1 tumours. Among those who underwent RC, CSS was 61.5% in those who had progression and 100% in those who remained with NMIBC., Conclusion: Combined treatment improved RFS and PFS only in patients with Ta disease., (© 2023. The Author(s).)

Soft tissue sarcomas (STS) are a heterogeneous group of solid tumors. There are many histologic subtypes. The prognosis after treatment may be estimated by the analysis of the type of tumor, grade, depth, size at diagnosis, and age of the patient. These type of sarcomas most commonly metastasize to the lungs and may have a relatively high rate of local recurrence, depending on the histologic type and surgical margins. Patients with recurrence have a poorer prognosis. The surveillance of patients with STS is therefore extremely important. This review analyzes the role of MR imaging and US in detecting local recurrence., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Type 2 diabetes mellitus (T2DM) is a risk factor that plays a major role in the onset of heart failure (HF) both directly, by impairing cardiac function, and indirectly, through associated diseases such as hypertension, coronary disease, renal dysfunction, obesity, and other metabolic disorders. In a population of HF patients, the presence of T2DM ranged from 20 to 40%, according to the population studied, risk factor characteristics, geographic area, and age, and it is associated with a worse prognosis. Finally, patients with HF, when compared with those without HF, show an increased risk for the onset of T2DM due to several mechanisms that predispose the HF patient to insulin resistance. Despite the epidemiological data confirmed the relationship between T2DM and HF, the exact prevalence of HF in T2DM comes from interventional trials rather than from observational registries aimed to prospectively evaluate the risk of HF occurrence in T2DM population. This review is focused on the vicious cycle linking HF and T2DM, from epidemiological data to prognostic implications., (© 2022. The Author(s).)

Backgroud: Biofilm formation has been recently recognised as one of the most important etiopathological mechanisms underlying chronic rhinosinusitis (CRS) and its recalcitrance. In this context, nasal cytology (NC) has become an integral part of diagnostic work up of patients suffering from sino-nasal diseases, since it is an easy-to-apply, reproducible and non-invasive diagnostic tool that allows to assess both the nasal inflammatory infiltrate and the presence of biofilms on nasal mucosal surface, further orienting the therapeutic choices in case of infectious diseases for eradicating infections and biofilms. Nevertheless, biofilms are typically resistant to common antibiotic treatments and may trigger or maintain chronic inflammation. Hence, the importance of correctly detecting the presence of biofilm and identifying new effective treatments., Purpose: The aim of this brief review is to better clarify the role of biofilm in the pathogenesis and recurrence of sino-nasal disorders and to highlight the role of nasal cytology (NC) in the rhino-allergologic diagnostic path and in the evaluation of the effectiveness of new treatments., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction and Importance: Metastatic localization of melanoma often affects the gastrointestinal tract, with reference to the small intestine., Case Presentation: In this work we present the clinical course of a patient affected by a surgically treated melanoma of the right conjunctiva, suddenly manifesting abdominal symptomatology. The abdominal computed tomography scan (CT scan) show evidence of free air into the peritoneal cavity, cholecystitis and brain lesions highly suspicious for metastases. Patient underwent emergency surgery, consisting of ileo-cecal resection, cholecystectomy, with the construction of an ileostomy. The histological examination diagnosed multiple ileal and gallbladder localizations of pigmented epithelial melanoma, and localization., Clinical Discussion: The treatment of conjunctival melanoma consists in surgical removal. Distant metastases frequently affect the gastrointestinal tract, leading to the necessity to assess patients with abdominal symptoms, in order to avoid emergency scenarios such as the one reported in our study., Conclusions: Intra-abdominal metastases from melanoma are an event that should not be underestimated, because if detected in time, they can be treated with surgery resulting in a clear improvement in the prognosis. Late diagnosis of intestinal metastases can cause an acute abdomen scenario frequently caused by intestinal obstruction or gastrointestinal bleeding., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Recently, the use of barbed pharyngoplasty (BP) has become widespread in snoring and obstructive sleep apnoea (OSA) palatal surgery, but there are no studies regarding the short- and long-term complications resulting from these different techniques. This systematic review aimed to report the complications and side effects of different BP techniques., Methods: An electronic search was performed on PubMed/MEDLINE, Google Scholar, and Ovid databases. The PRISMA statement was followed. Databases were searched from inception through September 2, 2021., Results: We included 14 prospective clinical studies consisting of 769 patients aged 23 to 81 years. The associated intra-operative complications of BP were as follows: partial thread extrusion (2.9%), self-limited bleeding (2.9%), broken needle (1.0%), and suture rupture (1.0%). Short-term complications were as follows: thread/knot extrusion (12.4%), dysphagia (5.6%), bleeding (1.5%), velopharyngeal insufficiency (1.5%), anterior pharyngoplasty dehiscence (1.2%), tonsillar haemorrhage (1.0%), excessive postnasal discharge (1.0%), barbed suture failure (0.5%), acute infection (0.2%), mucosal granulomas (0.2%), chipped tooth caused by mouth gag displacement (0.2%), and fibrous scar (0.2%). Long-term complications were as follows: foreign body sensation (7.8%), sticky mucus in throat (5.9%), dysphagia (3.6%), rhinolalia (3.1%), throat phlegm (1.1%), nose regurgitation (0.8%), dry throat (0.6%), and throat lump (0.3%)., Conclusion: BP is a safe technique free of significant side effects and major complications. However, in this review, patients undergoing BP were very heterogeneous in terms of characteristics of patients chosen and severity of diseases, surgical technique used (myoresective vs non-myoresective), time of follow-up, and mono level vs multilevel surgery. More studies on a larger scale with long-term follow-up are needed to confirm these promising results., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Detailed knowledge of anatomy helps to understand pathologic processes. This article focuses on the anatomy and functionality of the knee, with emphasis on recently studied concepts and anatomic features that have an association with the development of pathology. The most common anatomic variants posing a challenge for diagnosis and other common findings in asymptomatic patients are reviewed. Good understanding of the different surgical procedures helps in providing as much information as possible to guarantee a positive outcome, improving prognosis. We review what are the commonly expected postsurgical appearances and the most common postsurgical complications., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The anatomy of the ankle and foot is complex, allowing for a wide range of functionality. The movements of the joints represent a complex dynamic interaction. A solid understanding of the characteristics and actions of the anatomic elements helps explain the mechanisms and patterns of injury. This article reviews the anatomy, with special focus on concepts that are the object of recent study and the features that favor the development of symptoms. Good understanding of the surgical procedures helps in providing information to guarantee a favorable outcome. We review the commonly expected postsurgical appearances and the most common postsurgical complications., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Detailed knowledge of anatomy helps to understand pathologic processes. This article focuses on the anatomy and functionality of the hip, with emphasis on recently studied concepts and anatomic features that have an association with the development of symptoms. The most common anatomic variants posing a challenge for diagnosis and other common findings in asymptomatic patients are reviewed. Good understanding of the different surgical procedures helps in providing as much information as possible to guarantee a favorable outcome, improving prognosis. We review what are the commonly expected postsurgical appearances and the most common postsurgical complications., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Recently, new non-invasive electrical stimulation devices have been developed with the aim to increase the tongue muscle tone for patients with obstructive sleep apnoea (OSA) and snorers. The aim of this study was to provide a review of the first results found in the literature regarding the efficacy of non-invasive electric stimulation devices for the treatment of primary snoring and OSA., Material and Methods: An electronic search was performed on PubMed/MEDLINE, Google Scholar, and Ovid databases. The PRISMA statement was followed. Databases were searched from inception through September, 2021., Results: Four studies met the criteria for inclusion in this review, for a total of 265 patients. Two devices were included in this review, Apone-Stim 400 Muscle Stimulator and eXciteOSA. All studies suggested that these new devices are effective in improving snoring by approximately 50% after device training, without major complications. However data regarding OSA improvement are conflicting., Conclusions: Intraoral non-invasive electrical stimulation devices can be considered a valid option to current therapies for snoring. Further studies are needed to support these interesting new devices for treatment of OSA., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In January 2020, the World Health Organization (WHO) issued a Public Health Emergency of International Concern, declaring the COVID-19 outbreak a pandemic in March 2020. Stringent measures decreased consumption of some drugs, moving the illicit market to alternative substances, such as New Psychoactive Substances (NPS). A systematic literature search was performed, using scientific databases such as PubMed, Scopus, Web of Science and institutional and government websites, to identify reported intoxications and fatalities from NPS during the COVID-19 pandemic. The search terms were: COVID-19, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019, intox*, fatal*, new psychoactive substance, novel psychoactive substance, smart drugs, new psychoactive substance, novel synthetic opioid, synthetic opioid, synthetic cathinone, bath salts, legal highs, nitazene, bath salt, legal high, synthetic cannabinoid, phenethylamine, phencyclidine, piperazine, novel benzodiazepine, benzodiazepine analogue, designer benzodiazepines, tryptamine and psychostimulant. From January 2020 to March 2022, 215 NPS exposures were reported in Europe, UK, Japan and USA. Single NPS class intoxications accounted for 25, while mixed NPS class intoxications represented only 3 cases. A total of 130 NPS single class fatalities and 56 fatalities involving mixed NPS classes were published during the pandemic. Synthetic opioids were the NPS class most abused, followed by synthetic cathinones and synthetic cannabinoids. Notably, designer benzodiazepines were frequently found in combination with fentalogues. Considering the stress to communities and healthcare systems generated by the pandemic, NPS-related information may be underestimated. However, we could not define the exact impacts of COVID-19 on processing of toxicological data, autopsy and death investigations.

(1) Background: Previous studies showed left ventricular (LV) and left atrial (LA) improvement and reverse remodeling after therapy with Sacubitril/Valsartan (S/V) in patients affected by heart failure with reduced ejection fraction (HFrEF). Therefore, we sought to investigate predictors of LA structural and functional reverse remodeling (LARR) in this setting of patients after therapy with S/V, focusing on left atrial strain parameters, such as peak atrial longitudinal strain (PALS). (2) Methods: Patients with HFrEF underwent clinical and echocardiographic evaluation at baseline and after six months of therapy with S/V. Measures of LA structure (LA volume index, LAVi) and function (LA emptying fraction (LAEF), PALS, LA conduit strain and peak atrial contraction strain (PACS) were also analyzed. Patients were divided in two groups, those with a LARR (relative reduction in LAVi > 15%, LARR+) and those without (LARR-). (3) Results: A total of 47 consecutive patients (66 ± 8 years, 85% male, mean LVEF 28 ± 6%) were enrolled in the study and followed up. A significant increase of LAEF (46 ± 13 vs. 37 ± 11%, p < 0.001) and a significant reduction of LAVi (42 ± 15 vs. 45 ± 15 mL/m 2 , p = 0.008) were found after 6 months of S/V therapy; 47% of the population showed LA reverse remodeling. LA strain parameters, PALS (19 ± 8 vs. 15 ± 7 %, p < 0.001) and LA conduit (-9.7 ± 5.2% vs. -7.6 ± 4.1%, p = 0.007) significantly improved after 6 months of S/V therapy. At multivariable stepwise regression analysis, changes in LV End Diastolic Volume (LVEDV) and PALS were significantly proportional to changes in LAVi values. (4) Conclusions: Six months of treatment with S/V in patients with HFrEF was associated with an improvement in LA functional reverse remodeling in a real-world scenario. LARR was not significantly correlated to baseline echocardiographic variables, but was proportional to changes in LV volumes and LA strain parameters. Finally, after S/V therapy, a strict connection between LA and LV reverse remodeling and between LA anatomical and functional reverse remodeling seems to be outlined.