Editor’s Choice Articles

Growing evidence has shown that high levels of lipoprotein (a) (Lp(a)) and chronic inflammation may be responsible for the residual risk of cardiovascular events in patients managed with an optimal evidence-based approach. Clinical studies have demonstrated a correlation between higher Lp(a) levels and several atherosclerotic diseases including ischemic heart disease, stroke, and degenerative calcific aortic stenosis. The threshold value of Lp(a) serum concentrations associated with a significantly increased cardiovascular risk is >125 nmol/L (50 mg/dL). Current available lipid-lowering drugs have modest-to-no impact on Lp(a) levels. Chronic inflammation is a further condition potentially implicated in residual cardiovascular risk. Consistent evidence has shown an increased risk of cardiovascular events in patients with high sensitivity C reactive protein (>2 mg/dL), an inflammation biomarker. A number of anti-inflammatory drugs have been investigated in patients with or at risk of cardiovascular disease. Of these, canakinumab and colchicine have been found to be associated with cardiovascular risk reduction. Ongoing research aimed at improving risk stratification on the basis of Lp(a) and vessel inflammation assessment may help refine patient management. Furthermore, the identification of these conditions as cardiovascular risk factors has led to increased investigation into diagnostic and therapeutic strategies targeting them in order to reduce atherosclerotic cardiovascular disease burden. Full article

Chondrosarcomas are a diverse group of malignant cartilaginous matrix-producing neoplasms. Conventional chondrosarcomas are a continuum of disease based on the biologic activity of the tumor. The tumors range from the relatively biologically benign low-grade tumors or intermediate atypical cartilaginous tumors (ACTs), to malignant, aggressive high-grade tumors. The clinical presentation, radiographic and pathologic findings, treatments and outcomes vary significantly based on the histologic grade of the tumor. Chondrosarcomas present a diagnostic dilemma, particularly in the differentiation between high- and intermediate-grade tumors and that of low-grade tumors from benign enchondromas. A multidisciplinary team at a tertiary sarcoma centre allows for optimal care of these patients. Full article

In recent years, we have witnessed a growing drug resistance among bacteria, which is associated with the use and availability of an increasing number of broad-spectrum antimicrobial agents, as well as with their irrational and excessive use. The present study aims to analyze changes in the drug resistance of Gram-negative Enterobacterales: Escherichia coli and Klebsiella pneumoniae, isolated from infections in a multi-profile hospital over five years (from 2017 to 2021). Among the practical outcomes of the evaluation of these data will be the possibility of determining changes in susceptibility to the antibiotics used in the hospital. In turn, this will help propose new therapeutic options, especially for empirical therapy that is necessary in severe infections. The analysis of the use of individual groups of antibiotics allowed for identification of the causes of the increasing resistance of Gram-negative bacilli. The highest number of infections whose etiological agent was K. pneumoniae ESBL(+) and E. coli ESBL(+) was observed in 2018. In the analyzed five-year period, the number of multi-resistant (MDR) K. pneumoniae strains increased successively, which seems to be related to the growing use, especially in the pandemic period, of broad-spectrum antibiotics, mainly penicillins with inhibitors, third-generation cephalosporins, and carbapenems. Full article

Noise-induced hearing loss (NIHL) is the second most common cause of sensorineural hearing loss, after age-related hearing loss, and affects approximately 5% of the world’s population. NIHL is associated with substantial physical, mental, social, and economic impacts at the patient and societal levels. Stress and social isolation in patients’ workplace and personal lives contribute to quality-of-life decrements which may often go undetected. The pathophysiology of NIHL is multifactorial and complex, encompassing genetic and environmental factors with substantial occupational contributions. The diagnosis and screening of NIHL are conducted by reviewing a patient’s history of noise exposure, audiograms, speech-in-noise test results, and measurements of distortion product otoacoustic emissions and auditory brainstem response. Essential aspects of decreasing the burden of NIHL are prevention and early detection, such as implementation of educational and screening programs in routine primary care and specialty clinics. Additionally, current research on the pharmacological treatment of NIHL includes anti-inflammatory, antioxidant, anti-excitatory, and anti-apoptotic agents. Although there have been substantial advances in understanding the pathophysiology of NIHL, there remain low levels of evidence for effective pharmacotherapeutic interventions. Future directions should include personalized prevention and targeted treatment strategies based on a holistic view of an individual’s occupation, genetics, and pathology. Full article

Multimorbidity, the coexistence of multiple health conditions in an individual, has emerged as one of the greatest challenges facing health services, and this crisis is partly driven by the aging population. Aging is associated with increased aortic stiffness (AoStiff), which in turn is linked with several morbidities frequently affecting and having disastrous consequences for the elderly. These include hypertension, ischemic heart disease, heart failure, atrial fibrillation, chronic kidney disease, anemia, ischemic stroke, and dementia. Two or more of these disorders (multimorbidity) often coexist in the same elderly patient and the specific multimorbidity pattern depends on several factors including sex, ethnicity, common morbidity routes, morbidity interactions, and genomics. Regular exercise, salt restriction, statins in patients at high atherosclerotic risk, and stringent blood pressure control are interventions that delay progression of AoStiff and most likely decrease multimorbidity in the elderly. Full article

Robot-assisted surgical systems (RASS) have revolutionised the management of many urological conditions over the last two decades with robot-assisted radical prostatectomy (RARP) now being considered by many to be the preferred surgical approach. Intuitive Surgical has dominated the market during this time period with successive iterations of the da Vinci model. The expiration of patents has opened the RASS market and several new contenders have become available or are currently in development. This comprehensive narrative review aims to explore the merits of each robotic system as well as the evidence and barriers to their use. The newly developed RASS have increased the versality of robotic surgical systems to a wider range of settings through advancement in technology. The increased competition may result in an overall reduction in cost, broadening the accessibility of RASS. Learning curves and training remain a barrier to their use, but the situation appears to be improving through dedicated training programmes. Outcomes for RARP have been well investigated and tend to support improved early functional outcomes. Overall, the rapid developments in the field of robot-assisted surgery indicate the beginning of a promising new era to further enhance urological surgery. Full article

Postoperative intraabdominal adhesions can occur after more than 90% of gynecologic surgeries. They not only cause chronic pelvic pain and small bowel obstruction, but are also one of the main reasons for infertility. Adhesions are not only a burden for the affected patients, but are also a burden for the healthcare system, since the treatment of adhesion-associated complications costs a considerable amount of money. The gold standard for the diagnosis of adhesions is by laparoscopy, although other methods, such as transvaginal hydro-laparoscopy, are being discussed as better alternatives. Ideally, adhesions are avoided inherently, by operating carefully and by using microsurgical principles. If this is not possible, gel barriers have been shown to be successful in reducing postoperative adhesions. Full article

Background: Liver failure represents a life-threatening organ dysfunction with liver transplantation as the only proven curable therapy to date. Liver assist devices have been extensively researched to either bridge such patients to transplantation or promote spontaneous recovery. The aim of our study was to compare two such devices, the Molecular Adsorbent Recirculating System (MARS) and CytoSorb, in patients with liver failure. Methods: We retrospectively included 15 patients who underwent MARS during their intensive care unit stay and matched them to 15 patients who underwent hemoadsorption using CytoSorb. Clinical and paraclinical data obtained after each individual session, after the course of treatment, as well as at the end of the intensive care unit stay were compared between the two groups. Results: Single sessions of CytoSorb and MARS were both associated with a significant decrease in bilirubin (p = 0.04 and p = 0.04, respectively) and ammonia levels (p = 0.04 and p = 0.04, respectively), but only CytoSorb therapy was associated with a decrease in lactate dehydrogenase levels (p = 0.04) and in platelet count (p = 0.04). After the course of treatment, only CytoSorb was associated with a significant decrease in lactate (p = 0.01), bilirubin (p = 0.01), ammonia (p = 0.02), and lactate dehydrogenase levels (p = 0.01), while patients treated with MARS did not show any improvement in paraclinical liver tests. In addition, only CytoSorb treatment was associated with a significant improvement in the Model for End-Stage Liver Disease Score (p = 0.04). Conclusion: In conclusion, our results show a potential benefit of CytoSorb in rebalancing liver functional tests in patients with liver failure compared to MARS but the exact effects on patient outcome, including hospital length of stay and survival, should be further investigated in randomized control trials. Full article

Stress has been consistently linked to negative impacts on physical and mental health. More specifically, patients with chronic pain experience stress intolerance, which is an exacerbation or occurrence of symptoms in response to any type of stress. The pathophysiological mechanisms underlying this phenomenon remain unsolved. In this state-of-the-art paper, we summarised the role of the autonomic nervous system (ANS) and hypothalamus-pituitary-adrenal (HPA) axis, the two major stress response systems in stress intolerance. We provided insights into such mechanisms based on evidence from clinical studies in both patients with chronic pain, showing dysregulated stress systems, and healthy controls supported by preclinical studies, highlighting the link between these systems and symptoms of stress intolerance. Furthermore, we explored the possible regulating role for (epi)genetic mechanisms influencing the ANS and HPA axis. The link between stress and chronic pain has become an important area of research as it has the potential to inform the development of interventions to improve the quality of life for individuals living with chronic pain. As stress has become a prevalent concern in modern society, understanding the connection between stress, HPA axis, ANS, and chronic health conditions such as chronic pain is crucial to improve public health and well-being. Full article

The correct determination of volume status is a fundamental component of clinical evaluation as both hypovolaemia (with hypoperfusion) and hypervolaemia (with fluid overload) increase morbidity and mortality in critically ill patients. As inferior vena cava (IVC) accounts for two-thirds of systemic venous return, it has been proposed as a marker of volaemic status by indirect assessment of central venous pressure or fluid responsiveness. Although ultrasonographic evaluation of IVC is relatively easy to perform, correct interpretation of the results may not be that simple and multiple pitfalls hamper its wider application in the clinical setting. In the present review, the basic elements of the pathophysiology of IVC behaviour, potential applications and limitations of its evaluation are discussed. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease with severe itch. The eosinophil-to-lymphocyte ratio (ELR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) are reported to reflect itch or the severity of AD. We examined if these parameters may act as indicators for therapeutic effects of the Janus kinase 1 inhibitor upadacitinib for patients with AD in real-world clinical practice. Between August 2021 and September 2023, 65 Japanese patients (aged ≥ 12 years) with moderate to severe AD were treated with 15 mg/day of oral upadacitinib, plus twice daily topical corticosteroids. Before treatment, the baseline ELR, NLR, MLR, and PLR levels positively correlated with the eczema area and severity index (EASI), while the baseline NLR and PLR levels positively correlated with the peak pruritus-numerical rating scale (PP-NRS). After upadacitinib treatment, ELR and NLR remarkably decreased at week 4 and the reduced levels were maintained until week 24, in parallel with EASI and PP-NRS, while MLR and PLR transiently reduced at week 4, but returned to baseline levels after week 12. The percent reduction of ELR significantly correlated with the percent reductions of EASI and PP-NRS at weeks 4, 12, and 24 of upadacitinib treatment. ELR may act as an indicator for the improvement of clinical signs and itch by upadacitinib treatment in AD. Full article

Among the myeloproliferative diseases, myelofibrosis is a widely heterogeneous entity characterized by a highly variable prognosis. In this context, several prognostic models have been proposed to categorize these patients appropriately. Identifying who deserves more invasive treatments, such as bone marrow transplantation, is a critical clinical need. Age, complete blood count (above all, hemoglobin value), constitutional symptoms, driver mutations, and blast cells have always represented the milestones of the leading models still used worldwide (IPSS, DIPSS, MYSEC-PM). Recently, the advent of new diagnostic techniques (among all, next-generation sequencing) and the extensive use of JAK inhibitor drugs have allowed the development and validation of new models (MIPSS-70 and version 2.0, GIPSS, RR6), which are continuously updated. Finally, the new frontier of artificial intelligence promises to build models capable of drawing an overall survival perspective for each patient. This review aims to collect and summarize the existing standard prognostic models in myelofibrosis and examine the setting where each of these finds its best application. Full article

Valvular heart disease is a leading cause of cardiovascular morbidity and mortality and a major contributor of symptoms and functional disability. Knowledge of valvular heart disease epidemiology and a deep comprehension of the geographical and temporal trends are crucial for clinical advances and the formulation of effective health policy for primary and secondary prevention. This review mainly focuses on the epidemiology of primary (organic, related to the valve itself) valvular disease and its management, especially emphasizing the importance of heart valve centers in ensuring the best care of patients through a multidisciplinary team. Full article

Artificial intelligence (AI) and deep learning (DL)-based systems have gained wide interest in macular disorders, including diabetic macular edema (DME). This paper aims to validate an AI algorithm for identifying and quantifying different major optical coherence tomography (OCT) biomarkers in DME eyes by comparing the algorithm to human expert manual examination. Intraretinal (IRF) and subretinal fluid (SRF) detection and volumes, external limiting-membrane (ELM) and ellipsoid zone (EZ) integrity, and hyperreflective retina foci (HRF) quantification were analyzed. Three-hundred three DME eyes were included. The mean central subfield thickness was 386.5 ± 130.2 µm. IRF was present in all eyes and confirmed by AI software. The agreement (kappa value) (95% confidence interval) for SRF presence and ELM and EZ interruption were 0.831 (0.738–0.924), 0.934 (0.886–0.982), and 0.936 (0.894–0.977), respectively. The accuracy of the automatic quantification of IRF, SRF, ELM, and EZ ranged between 94.7% and 95.7%, while accuracy of quality parameters ranged between 99.0% (OCT layer segmentation) and 100.0% (fovea centering). The Intraclass Correlation Coefficient between clinical and automated HRF count was excellent (0.97). This AI algorithm provides a reliable and reproducible assessment of the most relevant OCT biomarkers in DME. It may allow clinicians to routinely identify and quantify these parameters, offering an objective way of diagnosing and following DME eyes. Full article

Ultrasound guided parasternal block is a regional anaesthesia technique targeting the anterior branches of intercostal nerves, which supply the anterior thoracic wall. The aim of this prospective study is to assess the efficacy of parasternal block to manage postoperative analgesia and reduce opioid consumption in patients undergoing cardiac surgery throughout sternotomy. A total of 126 consecutive patients were allocated to two different groups, receiving (Parasternal group) or not (Control group) preoperative ultrasound guided bilateral parasternal block with 20 mL of 0.5% ropivacaine per side. The following data were recorded: postoperative pain expressed by a 0–10 numeric rating scale (NRS), intraoperative fentanyl consumption, postoperative morphine consumption, time to extubation and perioperative pulmonary performance at incentive spirometry. Postoperative NRS was not significantly different between Parasternal and Control groups with a median (IQR) of 2 (0–4.5) vs. 3 (0–6) upon awakening (p = 0.07); 0 (0–3) vs. 2 (0–4) at 6 h (p = 0.46); 0 (0–2) vs. 0 (0–2) at 12 h (p = 0.57). Postoperative morphine consumption was similar among groups. However, intraoperative fentanyl consumption was significantly lower in the Parasternal group [406.3 ± 81.6 mcg vs. 864.3 ± 154.4, (p < 0.001)]. Parasternal group showed shorter times to extubation [(191 ± 58 min vs. 305 ± 72 min, (p)] and better performance at incentive spirometer with a median (IQR) of 2 raised balls (1–2) vs. 1 (1–2) after awakening (p = 0.04). Ultrasound guided parasternal block provided an optimal perioperative analgesia with a significant reduction in intraoperative opioid consumption, time to extubation and a better postoperative performance at spirometry when compared to the Control group. Full article

(1) Background: Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related mortality worldwide. Up to 50% of patients with CRC develop metastatic CRC (mCRC). Surgical and systemic therapy advances can now offer significant survival advantages. Understanding the evolving treatment options is essential for decreasing mCRC mortality. We aim to summarize current evidence and guidelines regarding the management of mCRC to provide utility when making a treatment plan for the heterogenous spectrum of mCRC. (2) Methods: A comprehensive literature search of PubMed and current guidelines written by major cancer and surgical societies were reviewed. The references of the included studies were screened to identify additional studies that were incorporated as appropriate. (3) Results: The standard of care for mCRC primarily consists of surgical resection and systemic therapy. Complete resection of liver, lung, and peritoneal metastases is associated with better disease control and survival. Systemic therapy now includes chemotherapy, targeted therapy, and immunotherapy options that can be tailored by molecular profiling. Differences between colon and rectal metastasis management exist between major guidelines. (4) Conclusions: With the advances in surgical and systemic therapy, as well as a better understanding of tumor biology and the importance of molecular profiling, more patients can anticipate prolonged survival. We provide a summary of available evidence for the management of mCRC, highlighting the similarities and presenting the difference in available literature. Ultimately, a multidisciplinary evaluation of patients with mCRC is crucial to selecting the appropriate pathway. Full article

Although treatment with fixed or mobile appliances has become an important part of modern orthodontics, side effects such as white spot lesions (WSLs) have a negative impact on the aesthetic outcome of orthodontic treatment. The purpose of this article was to review current evidence on the diagnosis, risk assessment, prevention, management and post-orthodontic treatment of these lesions. Data collection was performed electronically, and the initial search using the keywords “white spot lesions”, “orthodontics”, “WSL”, “enamel” and “demineralization” in different combinations resulted in 1032 articles for the two electronic databases used. Ultimately, a total of 47 manuscripts were considered relevant to the aim of this research and included in this review. The results of the review indicate that WSLs remain a significant problem during orthodontic treatment. According to studies in the literature, the severity of WSLs correlates to the duration of treatment. Using toothpaste with more than 1000 ppm fluoride at home reduces the frequency of WSL separation and regular application of varnishes in the office reduces the frequency of the occurrence of WSLs only in the context of maintaining a strict hygiene regime. The old hypothesis that elastomeric ligatures retain more dental plaque than metal ones has been refuted. There are no differences in the appearance of WSLs between conventional brackets and self-ligating brackets. Clear aligner mobile devices develop fewer WSLs but are more extensive as opposed to conventional fixed devices, while lingual orthodontic appliances have a lower incidence of WSLs, and the most effective device for preventing these lesions is WIN, followed by Incognito. Full article

Objectives: Low-field MRI at 0.55 Tesla (T) with deep learning image reconstruction has recently become commercially available. The objective of this study was to evaluate the image quality and diagnostic reliability of knee MRI performed at 0.55T compared with 1.5T. Methods: A total of 20 volunteers (9 female, 11 male; mean age = 42 years) underwent knee MRI on a 0.55T system (MAGNETOM Free.Max, Siemens Healthcare, Erlangen, Germany; 12-channel Contour M Coil) and a 1.5T scanner (MAGNETOM Sola, Siemens Healthcare, Erlangen, Germany; 18-channel transmit/receive knee coil). Standard two-dimensional (2D) turbo spin echo (TSE), fat-suppressed (fs) proton density-weighted (PDw), T1w TSE, and T2w TSE sequences were acquired in approximately 15 min. In total, 2 radiologists blinded to the field strength subjectively assessed all MRI sequences (overall image quality, image noise, and diagnostic quality) using a 5-point Likert scale (1–5; 5 = best). Additionally, both radiologists evaluated the possible pathologies of menisci, ligaments, and cartilage. Contrast ratios (CRs) of different tissues (bone, cartilage, and menisci) were determined on coronal PDw fs TSE images. The statistical analysis included Cohen’s kappa and the Wilcoxon rank sum test. Results: The overall image quality of the 0.55T T2w, T1w, and PDw fs TSE sequences was diagnostic and rated similar for T1w (p > 0.05), but lower for PDw fs TSE and T2w TSE compared with 1.5T (p < 0.05). The diagnostic accordance of meniscal and cartilage pathologies at 0.55T was similar to 1.5T. The CRs of the tissues were not significantly different between 1.5T and 0.55T (p > 0.05). The inter-observer agreement of the subjective image quality was generally fair between both readers and almost perfect for the pathologies. Conclusions: Deep learning-reconstructed TSE imaging at 0.55T yielded diagnostic image quality for knee MRI compared with standard 1.5T MRI. The diagnostic performance of meniscal and cartilage pathologies was equal for 0.55T and 1.5T without a significant loss of diagnostic information. Full article

Chronic physical health conditions (CPHC) are on the rise in younger age groups and might have a negative impact on children and adolescents. In a representative sample of Austrian adolescents aged 10–18 years, internalizing, externalizing, and behavioral problems were assessed cross-sectionally using the Youth Self-Report and health-related quality of life (HrQoL) using the KIDSCREEN questionnaire. Sociodemographic variables, life events, and chronic illness specific parameters were considered as associated variables with mental health problems in individuals with CPHC. Of 3469 adolescents, 9.4% of girls and 7.1% of boys suffered from a chronic pediatric illness. Of these individuals, 31.7% and 11.9% had clinically relevant levels of internalizing and externalizing mental health problems, respectively, compared to 16.3% and 7.1% adolescents without a CPHC. Anxiety, depression, and social problems were twice as high in this population. Medication intake due to CPHC and any traumatic life-event were related to mental health problems. All HrQoL domains were deteriorated in adolescents with a double burden of mental and CPHC, whereas adolescents with a CPHC without mental health problems did not differ significantly from adolescents without a chronic illness. Targeted prevention programs for adolescents with a CPHC are urgently needed to prevent mental health problems in the long term. Full article

One-lung ventilation is also used in some thoracic or cardiac surgery, vascular surgery and oesophageal procedures. We conducted a search of the literature for relevant studies in PubMed, Web of Science, Embase, Scopus and Cochrane Library. The final literature search was performed on 10 December 2022. Primary outcomes included the quality of lung collapse. Secondary outcome measures included: the success of the first intubation attempt, malposition rate, time for device placement, lung collapse and adverse events occurrence. Twenty-five studies with 1636 patients were included. Excellent lung collapse among DLT and BB groups was 72.4% vs. 73.4%, respectively (OR = 1.20; 95%CI: 0.84 to 1.72; p = 0.31). The malposition rate was 25.3% vs. 31.9%, respectively (OR = 0.66; 95%CI: 0.49 to 0.88; p = 0.004). The use of DLT compared to BB was associated with a higher risk of hypoxemia (13.5% vs. 6.0%, respectively; OR = 2.27; 95%CI: 1.14 to 4.49; p = 0.02), hoarseness (25.2% vs. 13.0%; OR = 2.30; 95%CI: 1.39 to 3.82; p = 0.001), sore throat (40.3% vs. 23.3%; OR = 2.30; 95%CI: 1.68 to 3.14; p < 0.001), and bronchus/carina injuries (23.2% vs. 8.4%; OR = 3.45; 95%CI: 1.43 to 8.31; p = 0.006). The studies conducted so far on comparing DLT and BB are ambiguous. In the DLT compared to the BB group, the malposition rate was statistically significantly lower, and time to tube placement and lung collapse was shorter. However, the use of DLT compared to BB can be associated with a higher risk of hypoxemia, hoarseness, sore throat and bronchus/carina injuries. Multicenter randomized trials on larger groups of patients are needed to draw definitive conclusions regarding the superiority of any of these devices. Full article

Transperineal laser ablation (TPLA) of the prostate is a new minimally invasive treatment option in men with lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE). The aim of this systematic review was to investigate the efficacy and safety of TPLA in the management of BPE. The primary outcomes were the improvement in urodynamic parameters (maximum urinary flow (Q_max) and postvoiding residue (PVR)) and LUTS relief, assessed using the IPSS questionnaire. The secondary outcomes were the preservation of sexual and ejaculatory functions, assessed with the IEEF-5 and MSHQ-EjD questionnaires, respectively, and rates of postoperative complications. We reviewed the literature for prospective or retrospective studies evaluating the use of TPLA in the treatment of BPE. A comprehensive search in PubMed, Scopus, Web of Science, and ClinicalTrials.gov was performed for English language articles published between January 2000 and June 2022. Pooled analysis of the included studies with available follow-up data for the outcomes of interest was additionally performed. After screening 49 records, six full-text manuscripts were identified, including two retrospective and four prospective non-comparative studies. Overall, 297 patients were included. All the studies independently reported a statistically significant improvement, from baseline, in Q_max, PVR, and IPSS score at each timepoint. Three studies additionally demonstrated that TPLA did not affect sexual function, reporting no change in the IEEF-5 score, and a statistically significant improvement in MSHQ-EjD score at each timepoint. Low rates of complications were recorded in all the included studies. Pooled analysis showed a clinically meaningful improvement in both micturition and sexual outcomes mean values at 1, 3, 6, and 12 months of follow-up, compared with baseline. Transperineal laser ablation of the prostate for the treatment of BPE showed interesting results in pilot studies. However, higher level and comparative studies are needed to confirm its efficacy in relieving obstructive symptoms and preserving sexual function. Full article

Non-alcoholic fatty liver disease (NAFLD) is a serious health problem due to its high incidence and consequences. In view of the existing controversies, new therapeutic options for NAFLD are still being sought. Therefore, the aim of our review was to evaluate the recently published studies on the treatment of NAFLD patients. We searched for articles in the PubMed database using appropriate terms, including “non-alcoholic fatty liver disease”, “nonalcoholic fatty liver disease”, “NAFLD”, “diet”, “treatment”, “physical activity”, “supplementation”, “surgery”, “overture” and “guidelines”. One hundred forty-eight randomized clinical trials published from January 2020 to November 2022 were used for the final analysis. The results show significant benefits of NAFLD therapy associated with the use of not only the Mediterranean but also other types of diet (including low-calorie ketogenic, high-protein, anti-inflammatory and whole-grain diets), as well as enrichment with selected food products or supplements. Significant benefits in this group of patients are also associated with moderate aerobic physical training. The available therapeutic options indicate, above all, the usefulness of drugs related to weight reduction, as well as the reduction in insulin resistance or lipids level and drugs with anti-inflammatory or antioxidant properties. The usefulness of therapy with dulaglutide and the combination of tofogliflozin with pioglitazone should be emphasized. Based on the results of the latest research, the authors of this article suggest a revision of the therapeutic recommendations for NAFLD patients. Full article

Sleep disturbances are widely prevalent following a traumatic brain injury (TBI) and have the potential to contribute to numerous post-traumatic physiological, psychological, and cognitive difficulties developing chronically, including chronic pain. An important pathophysiological mechanism involved in the recovery of TBI is neuroinflammation, which leads to many downstream consequences. While neuroinflammation is a process that can be both beneficial and detrimental to individuals’ recovery after sustaining a TBI, recent evidence suggests that neuroinflammation may worsen outcomes in traumatically injured patients, as well as exacerbate the deleterious consequences of sleep disturbances. Additionally, a bidirectional relationship between neuroinflammation and sleep has been described, where neuroinflammation plays a role in sleep regulation and, in turn, poor sleep promotes neuroinflammation. Given the complexity of this interplay, this review aims to clarify the role of neuroinflammation in the relationship between sleep and TBI, with an emphasis on long-term outcomes such as pain, mood disorders, cognitive dysfunctions, and elevated risk of Alzheimer’s disease and dementia. In addition, some management strategies and novel treatment targeting sleep and neuroinflammation will be discussed in order to establish an effective approach to mitigate long-term outcomes after TBI. Full article

Preimplantation genetic testing for aneuploidies (PGT-A) is arguably the most effective embryo selection strategy. Nevertheless, it requires greater workload, costs, and expertise. Therefore, a quest towards user-friendly, non-invasive strategies is ongoing. Although insufficient to replace PGT-A, embryo morphological evaluation is significantly associated with embryonic competence, but scarcely reproducible. Recently, artificial intelligence-powered analyses have been proposed to objectify and automate image evaluations. iDAScore v1.0 is a deep-learning model based on a 3D convolutional neural network trained on time-lapse videos from implanted and non-implanted blastocysts. It is a decision support system for ranking blastocysts without manual input. This retrospective, pre-clinical, external validation included 3604 blastocysts and 808 euploid transfers from 1232 cycles. All blastocysts were retrospectively assessed through the iDAScore v1.0; therefore, it did not influence embryologists’ decision-making process. iDAScore v1.0 was significantly associated with embryo morphology and competence, although AUCs for euploidy and live-birth prediction were 0.60 and 0.66, respectively, which is rather comparable to embryologists’ performance. Nevertheless, iDAScore v1.0 is objective and reproducible, while embryologists’ evaluations are not. In a retrospective simulation, iDAScore v1.0 would have ranked euploid blastocysts as top quality in 63% of cases with one or more euploid and aneuploid blastocysts, and it would have questioned embryologists’ ranking in 48% of cases with two or more euploid blastocysts and one or more live birth. Therefore, iDAScore v1.0 may objectify embryologists’ evaluations, but randomized controlled trials are required to assess its clinical value. Full article

Chronic low back pain (cLBP) is a public and occupational health problem that is a major professional, economic and social burden. We aimed to provide a critical overview of current international recommendations regarding the management of non-specific cLBP. We conducted a narrative review of international guidelines for the diagnosis and conservative treatment of people with non-specific cLBP. Our literature search yielded five reviews of guidelines published between 2018 and 2021. In these five reviews, we identified eight international guidelines that fulfilled our selection criteria. We added the 2021 French guidelines into our analysis. Regarding diagnosis, most international guidelines recommend searching for so-called yellow, blue and black flags, in order to stratify the risk of chronicity and/or persistent disability. The relevance of clinical examination and imaging are under debate. Regarding management, most international guidelines recommend non-pharmacological treatments, including exercise therapy, physical activity, physiotherapy and education; however, multidisciplinary rehabilitation, in selected cases, is the core treatment recommended for people with non-specific cLBP. Oral, topical or injected pharmacological treatments are under debate, and may be offered to selected and well-phenotyped patients. The diagnosis of people with cLBP may lack precision. All guidelines recommend multimodal management. In clinical practice, the management of individuals with non-specific cLBP should combine non-pharmacological and pharmacological treatments. Future research should focus on improving tailorization. Full article

In humans, the gut microbiota (GM) are known to play a significant role in the metabolism of nutrients and drugs, immunomodulation, and pathogen defense by inhabiting the gastrointestinal tract (GIT). The role of the GM in the gut–brain axis (GBA) has been documented for different regulatory mechanisms and associated pathways and it shows different behaviors with individualized bacteria. In addition, the GM are known as susceptibility factor for neurological disorders in the central nervous system (CNS), regulating disease progression and being amenable to intervention. Bidirectional transmission between the brain and the GM occurs in the GBA, implying that it performs a significant role in neurocrine, endocrine, and immune-mediated signaling pathways. The GM regulates multiple neurological disorders by supplementing them with prebiotics, probiotics, postbiotics, synbiotics, fecal transplantations, and/or antibiotics. A well-balanced diet is critically important for establishing healthy GM, which can alter the enteric nervous system (ENS) and regulate multiple neurological disorders. Here, we have discussed the function of the GM in the GBA from the gut to the brain and the brain to the gut, the pathways associated with neurology that interacts with the GM, and the various neurological disorders associated with the GM. Furthermore, we have highlighted the recent advances and future prospects of the GBA, which may require addressing research concerns about GM and associated neurological disorders. Full article

This umbrella review aimed to systematically identify the peri-operative risk factors associated with post-operative cognitive dysfunction (POCD) using meta-analyses of observational studies. To date, no review has synthesised nor assessed the strength of the available evidence examining risk factors for POCD. Database searches from journal inception to December 2022 consisted of systematic reviews with meta-analyses that included observational studies examining pre-, intra- and post-operative risk factors for POCD. A total of 330 papers were initially screened. Eleven meta-analyses were included in this umbrella review, which consisted of 73 risk factors in a total population of 67,622 participants. Most pertained to pre-operative risk factors (74%) that were predominantly examined using prospective designs and in cardiac-related surgeries (71%). Overall, 31 of the 73 factors (42%) were associated with a higher risk of POCD. However, there was no convincing (class I) or highly suggestive (class II) evidence for associations between risk factors and POCD, and suggestive evidence (class III) was limited to two risk factors (pre-operative age and pre-operative diabetes). Given that the overall strength of the evidence is limited, further large-scale studies that examine risk factors across various surgery types are recommended. Full article

Due to the key role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used in the clinical treatment of autoimmune disorders. Currently, five anti-TNF-α drugs have been approved: infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. Anti-TNF-α biosimilars are also available for clinical use. Here, we will review the historical development as well as the present and potential future applications of anti-TNF-α therapies, which have led to major improvements for patients with several autoimmune diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn’s disease (CD), ulcerative colitis (UC), psoriasis (PS) and chronic endogenous uveitis. Other therapeutic areas are under evaluation, including viral infections, e.g., COVID-19, as well as chronic neuropsychiatric disorders and certain forms of cancer. The search for biomarkers able to predict responsiveness to anti-TNF-α drugs is also discussed. Full article

Triple-negative breast cancer (TNBC) accounts for 15–20% of all breast cancers and is characterized by an aggressive nature and a high rate of recurrence despite neoadjuvant and adjuvant chemotherapy. Although novel agents are constantly being introduced for the treatment of breast cancer, conventional cytotoxic chemotherapy based on anthracyclines and taxanes is the mainstay treatment option for TNBC. Based on CTNeoBC pooled analysis data, the achievement of pathologic CR (pCR) in TNBC is directly linked to improved survival outcomes. Therefore, the treatment paradigm for early TNBC has shifted to neoadjuvant treatment, and the escalation of neoadjuvant chemotherapy to improve the pCR rate and the addition of post-neoadjuvant chemotherapy to control the residual disease have been investigated. In this article, we review the current treatment landscape for early TNBC, from standard cytotoxic chemotherapy to recent data on immune checkpoint inhibitors, capecitabine, and olaparib. Full article

Invasive fungal infections (IFIs) are one of the most important infectious complications after liver transplantation, determining morbidity and mortality. Antimycotic prophylaxis may impede IFI, but a consensus on indication, agent, or duration is still missing. Therefore, this study aimed to investigate the incidence of IFIs under targeted echinocandin antimycotic prophylaxis in adult high-risk liver transplant recipients. We retrospectively reviewed all patients undergoing a deceased donor liver transplantation at the Medical University of Innsbruck in the period from 2017 to 2020. Of 299 patients, 224 met the inclusion criteria. We defined patients as being at high risk for IFI if they had two or more prespecified risk factors and these patients received prophylaxis. In total, 85% (190/224) of the patients were correctly classified according to the developed algorithm, being able to predict an IFI with a sensitivity of 89%. Although 83% (90/109) so defined high-risk recipients received echinocandin prophylaxis, 21% (23/109) still developed an IFI. The multivariate analysis identified the age of the recipient (hazard ratio—HR = 0.97, p = 0.027), split liver transplantation (HR = 5.18, p = 0.014), massive intraoperative blood transfusion (HR = 24.08, p = 0.004), donor-derived infection (HR = 9.70, p < 0.001), and relaparotomy (HR = 4.62, p = 0.003) as variables with increased hazard ratios for an IFI within 90 days. The fungal colonization at baseline, high-urgency transplantation, posttransplant dialysis, bile leak, and early transplantation showed significance only in a univariate model. Notably, 57% (12/21) of the invasive Candida infections were caused by a non-albicans species, entailing a markedly reduced one-year survival. The attributable 90-day mortality rate of an IFI after a liver transplant was 53% (9/17). None of the patients with invasive aspergillosis survived. Despite targeted echinocandin prophylaxis, there is still a notable risk for IFI. Consequently, the prophylactic use of echinocandins must be critically questioned regarding the high rate of breakthrough infections, the increased occurrence of fluconazole-resistant pathogens, and the higher mortality rate in non-albicans Candida species. Adherence to the internal prophylaxis algorithms is of immense importance, bearing in mind the high IFI rates in case algorithms are not followed. Full article

Prostate cancer is the most commonly diagnosed cancer in men worldwide, making up 21% of all cancer cases. With 345,000 deaths per year owing to the disease, there is an urgent need to optimize prostate cancer care. This systematic review collated and synthesized findings of completed Phase III clinical trials administering immunotherapy; a current clinical trial index (2022) of all ongoing Phase I–III clinical trial records was also formulated. A total of four Phase III clinical trials with 3588 participants were included administering DCVAC, ipilimumab, personalized peptide vaccine, and the PROSTVAC vaccine. In this original research article, promising results were seen for ipilimumab intervention, with improved overall survival trends. A total of 68 ongoing trial records pooling in 7923 participants were included, spanning completion until June 2028. Immunotherapy is an emerging option for patients with prostate cancer, with immune checkpoint inhibitors and adjuvant therapies forming a large part of the emerging landscape. With various ongoing trials, the characteristics and premises of the prospective findings will be key in improving outcomes in the future. Full article

The application of thoracic ultrasound examination has not long been developed because ultrasound’s interaction with the lung does not generate an anatomical image but an artifactual one. Subsequently, the evaluation of pulmonary artifacts and their correlation to specific diseases allowed the development of ultrasound semantics. Currently, pneumonia still represents one of the main causes of hospitalization and mortality. Several studies in the literature have demonstrated the ultrasound features of pneumonia. Although ultrasound cannot be considered the diagnostic gold standard for the study of all lung diseases, it has experienced an extraordinary development and growth of interest due to the SARS-CoV-2 pandemic. This review aims to provide essential information on the application of lung ultrasound to the study of infectious pneumonia and to discuss the differential diagnosis. Full article

Over the last decade, the management of acute respiratory distress syndrome (ARDS) has made considerable progress both regarding supportive and pharmacologic therapies. Lung protective mechanical ventilation is the cornerstone of ARDS management. Current recommendations on mechanical ventilation in ARDS include the use of low tidal volume (V_T) 4–6 mL/kg of predicted body weight, plateau pressure (P_PLAT) < 30 cmH₂O, and driving pressure (∆P) < 14 cmH₂O. Moreover, positive end-expiratory pressure should be individualized. Recently, variables such as mechanical power and transpulmonary pressure seem promising for limiting ventilator-induced lung injury and optimizing ventilator settings. Rescue therapies such as recruitment maneuvers, vasodilators, prone positioning, extracorporeal membrane oxygenation, and extracorporeal carbon dioxide removal have been considered for patients with severe ARDS. Regarding pharmacotherapies, despite more than 50 years of research, no effective treatment has yet been found. However, the identification of ARDS sub-phenotypes has revealed that some pharmacologic therapies that have failed to provide benefits when considering all patients with ARDS can show beneficial effects when these patients were stratified into specific sub-populations; for example, those with hyperinflammation/hypoinflammation. The aim of this narrative review is to provide an overview on current advances in the management of ARDS from mechanical ventilation to pharmacological treatments, including personalized therapy. Full article

Recent technological advances in the field of artificial intelligence hold promise in addressing medical challenges in breast cancer care, such as early diagnosis, cancer subtype determination and molecular profiling, prediction of lymph node metastases, and prognostication of treatment response and probability of recurrence. Radiomics is a quantitative approach to medical imaging, which aims to enhance the existing data available to clinicians by means of advanced mathematical analysis using artificial intelligence. Various published studies from different fields in imaging have highlighted the potential of radiomics to enhance clinical decision making. In this review, we describe the evolution of AI in breast imaging and its frontiers, focusing on handcrafted and deep learning radiomics. We present a typical workflow of a radiomics analysis and a practical “how-to” guide. Finally, we summarize the methodology and implementation of radiomics in breast cancer, based on the most recent scientific literature to help researchers and clinicians gain fundamental knowledge of this emerging technology. Alongside this, we discuss the current limitations of radiomics and challenges of integration into clinical practice with conceptual consistency, data curation, technical reproducibility, adequate accuracy, and clinical translation. The incorporation of radiomics with clinical, histopathological, and genomic information will enable physicians to move forward to a higher level of personalized management of patients with breast cancer. Full article

Coronary artery disease (CAD) in women occurs later than in men. Underlying atherosclerosis, a chronic process of lipoprotein deposition in arterial walls with a prominent inflammatory component, is influenced by several risk factors. In women, commonly used inflammatory markers are generally found to be related to the occurrence of acute coronary syndrome (ACS), as well as the development of other diseases that influence CAD. New inflammatory markers derived from total blood count—systemic inflammatory response index (SII), systemic inflammatory reaction index (SIRI), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR)—were analyzed in the group of 244 elderly, postmenopausal women with the diagnosis of ACS or stable CAD. SII, SIRI, MLR, and NLR were significantly higher in women with ACS compared to those with stable CAD (p < 0.05 for all)—the highest values were observed in women with NSTEMI. MLR from new inflammatory markers, HDL, and history of MI turned out to be significant factors associated with ACS. These results suggest that MLR as representative of blood count-derived inflammatory markers may be considered as additional CVD risk factors in women with suspected ACS. Full article

Background: Point Of Care Ultra-Sound (POCUS) is an operator dependent modality. POCUS examinations usually include ‘Eyeballing’ the inspected anatomical structure without conducting accurate measurements due to complexity and insufficient time. Automatic real time measuring tools can make accurate measurements fast and simple and dramatically increase examination reliability while saving the operator much time and effort. In this study we aim to assess three automatic tools which are integrated into the Venue™ device by GE: the automatic ejection fraction, velocity time integral, and inferior vena cava tools in comparison to the gold standard—an examination by a POCUS expert. Methods: A separate study was conducted for each of the three automatic tools. In each study, cardiac views were acquired by a POCUS expert. Relevant measurements were taken by both an auto tool and a POCUS expert who was blinded to the auto tool’s measurement. The agreement between the POCUS expert and the auto tool was measured for both the measurements and the image quality using a Cohen’s Kappa test. Results: All three tools have shown good agreement with the POCUS expert for high quality views: auto LVEF (0.498; p < 0.001), auto IVC (0.536; p = 0.009), and the auto VTI (0.655; p = 0.024). Auto VTI has also shown a good agreement for medium quality clips (0.914; p < 0.001). Image quality agreement was significant for the auto EF and auto IVC tools. Conclusions: The Venue™ show a high agreement with a POCUS expert for high quality views. This shows that auto tools can provide reliable real time assistance in performing accurate measurements, but do not reduce the need of a good image acquisition technique. Full article

Gastric cancer (GC) is one of the most clinically challenging cancers worldwide. Over the past few years, new molecular-targeted agents and immunotherapy have markedly improved GC prognosis. Human epidermal growth factor receptor 2 (HER2) expression is a key biomarker in first-line chemotherapy for unresectable advanced GC. Further, the addition of trastuzumab to cytotoxic chemotherapy has extended the overall survival of patients with HER2-positive advanced GC. In HER2-negative GC, the combination of nivolumab, an immune checkpoint inhibitor, and a cytotoxic agent has been demonstrated to prolong the overall survival of GC patients. Ramucirumab and trifluridine/tipiracil, which are second- and third-line treatments for GC, and trastuzumab deruxtecan, an antibody–drug conjugate for HER2-positive GC, have been introduced in clinics. New promising molecular-targeted agents are also being developed, and combination therapy comprising immunotherapy and molecular-targeted agents is expected. As the number of available drugs increases, it is important to understand the target biomarkers and drug characteristics and select the optimal therapy for each patient. For resectable disease, differences in the extent of standard lymphadenectomy between Eastern and Western countries have led to different standard treatments: perioperative (neoadjuvant) and adjuvant therapy. This review aimed to summarize recent advances in chemotherapy for advanced GC. Full article

Delirium is characterized by an acutely altered mental status accompanied by reductions in cognitive function and attention. Delirium in septic patients, termed sepsis-associated delirium (SAD), differs in several specific aspects from the other types of delirium that are typically encountered in intensive care units. Since sepsis and delirium are both closely associated with increased morbidity and mortality, it is important to not only prevent but also promptly diagnose and treat SAD. We herein reviewed the etiology, pathogenesis, risk factors, prevention, diagnosis, treatment, and prognosis of SAD, including coronavirus disease 2019 (COVID-19)-related delirium. Delirium by itself not only worsens long-term prognosis, but it is also regarded as an important factor affecting the outcome of post-intensive care syndrome. In COVID-19 patients, the difficulties associated with adequately implementing the ABCDEF bundle (Assess, prevent, and manage pain; Both spontaneous awakening and breathing trials: Choice of analgesia and sedation; Delirium assess, prevent, and manage; Early mobility and exercise; Family engagement/empowerment) and the need for social isolation are issues that require the development of conventional care for SAD. Full article

Cardiovascular disease (CVD) constitutes a real pandemic of the 21st century. According to data from the Centers for Disease Control and Prevention, one person dies every 34 min due to some form of CVD in the United States. Apart from the extremely high morbidity and mortality accompanying CVD, the economic burden seems to be unbearable even for developed countries in the Western World. The role of inflammation in the development and progression of CVD appears to be crucial, while, various inflammatory pathways, such as the Nod-like receptor protein 3 (NLRP3) inflammasome-interleukin (IL)-1/IL-6 pathway of the innate immunity, have attracted scientific interest during the last decade, as a potential treatment target in primary and/or secondary prevention of CVD. Whereas there is a significant amount of evidence, stemming mainly from observational studies, concerning the cardiovascular safety of IL-1 and IL-6 antagonists in patients with rheumatic diseases, evidence from relevant randomized controlled trials (RCTs) is rather scarce and conflicting, especially for patients without underlying rheumatic disease. In this review, we summarize and critically present the currently available evidence, both from RCTs and observational studies, concerning the place that IL-1 and IL-6 antagonists may hold in the treatment of CVD. Full article

Although defined by the presence of airflow obstruction and respiratory symptoms, patients with chronic obstructive pulmonary disease (COPD) are characterized by multimorbidity. Numerous co-occurring conditions and systemic manifestations contribute to the clinical presentation and progression of COPD; however, underlying mechanisms for multimorbidity are currently not fully elucidated. Vitamin A and vitamin D have been related to COPD pathogenesis. Another fat-soluble vitamin, vitamin K, has been put forward to exert protective roles in COPD. Vitamin K is an unequivocal cofactor for the carboxylation of coagulation factors, but also for extra-hepatic proteins including the soft tissue calcification inhibitor matrix Gla-protein and the bone protein osteocalcin. Additionally, vitamin K has been shown to have anti-oxidant and anti-ferroptosis properties. In this review, we discuss the potential role of vitamin K in the systemic manifestations of COPD. We will elaborate on the effect of vitamin K on prevalent co-occurring chronic conditions in COPD including cardiovascular disorders, chronic kidney disease, osteoporosis, and sarcopenia. Finally, we link these conditions to COPD with vitamin K as a connecting factor and provide recommendations for future clinical studies. Full article

(1) Background: Inflammatory processes in the thoracolumbar fascia (TLF) lead to thickening, compaction, and fibrosis and are thought to contribute to the development of nonspecific low back pain (nLBP). The blood flow (BF) of fascial tissue may play a critical role in this process, as it may promote hypoxia-induced inflammation. The primary objective of the study was to examine the immediate effects of a set of myofascial release (MFR) techniques on the BF of lumbar myofascial tissue. The secondary objectives were to evaluate the influence of TLF morphology (TLFM), physical activity (PA), and body mass index (BMI) on these parameters and their correlations with each other. (2) Methods: This study was a single-blind, randomized, placebo-controlled trial. Thirty pain-free subjects (40.5 ± 14.1 years) were randomly assigned to two groups treated with MFR or a placebo intervention. Correlations between PA, BMI, and TLFM were calculated at baseline. The effects of MFR and TLFM on BF (measured with white light and laser Doppler spectroscopy) were determined. (3) Results: The MFR group had a significant increase in BF after treatment (31.6%) and at follow-up (48.7%) compared with the placebo group. BF was significantly different between disorganized and organized TLFM (p < 0.0001). There were strong correlations between PA (r = −0.648), PA (d = 0.681), BMI (r = −0.798), and TLFM. (4) Conclusions: Impaired blood flow could lead to hypoxia-induced inflammation, possibly resulting in pain and impaired proprioceptive function, thereby likely contributing to the development of nLBP. Fascial restrictions of blood vessels and free nerve endings, which are likely associated with TLFM, could be positively affected by the intervention in this study. Full article

Iterations in stent technologies, advances in pharmacotherapy, and awareness of the implications of implantation techniques have markedly reduced the risk of stent failure, both in the form of stent thrombosis (ST) and in-stent restenosis (ISR). However, given the number of percutaneous coronary interventions (PCI) performed worldwide every year, ST and ISR, albeit occurring at a fairly low rate, represent a public health problem even with contemporary DES platforms. The understanding of mechanisms and risk factors for these two PCI complications has been of fundamental importance for the parallel evolution of stent technologies. Risk factors associated with ST and ISR are usually divided into patient-, lesion-, device- and procedure-related. A number of studies have shown how certain risk factors are related to early (1 month) versus late/very late ST (between 1 month and 1 year and >1 year, respectively). However, more research is required to conclusively show the role of time-dependence of risk factors also in the incidence of ISR (early [1 year] or late [>1 year]). A thorough risk assessment is required due to the complex etiology of ST and ISR. The most effective strategy to treat ST and ISR is still to prevent them; hence, it is crucial to identify patient-, lesion-, device- and procedure-related predictors. Full article

Gingivitis and periodontitis are chronic inflammatory diseases that affect the supporting tissues of the teeth. Although induced by the presence of bacterial biofilms, other factor, such as tobacco smoking, drugs, and various systemic diseases, are known to influence their pathogenesis. Diabetes mellitus and periodontal diseases correspond to inflammatory diseases that have pathogenic mechanisms in common, with the involvement of pro-inflammatory mediators. A bidirectional relationship between type 2 diabetes and periodontitis has been documented in several studies. Significantly less studies have focused on the association between periodontal disease and type 1 diabetes. The aim of the study is to analyze the association between periodontal status and type 1 diabetes mellitus. The “Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines” was used and registered at PROSPERO. The search strategy included electronic databases from 2012 to 2021 and was performed by two independent reviewers. According to our results, we found one article about the risk of periodontal diseases in type 1 diabetes mellitus subjects; four about glycemic control; two about oral hygiene; and eight about pro-inflammatory cytokines. Most of the studies confirm the association between type 1 diabetes mellitus and periodontal diseases. The prevalence and severity of PD was higher in DM1 patients when compared to healthy subjects. Full article

Many studies have recently used several deep learning methods for detecting skin cancer. However, hyperspectral imaging (HSI) is a noninvasive optics system that can obtain wavelength information on the location of skin cancer lesions and requires further investigation. Hyperspectral technology can capture hundreds of narrow bands of the electromagnetic spectrum both within and outside the visible wavelength range as well as bands that enhance the distinction of image features. The dataset from the ISIC library was used in this study to detect and classify skin cancer on the basis of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and seborrheic keratosis (SK). The dataset was divided into training and test sets, and you only look once (YOLO) version 5 was applied to train the model. The model performance was judged according to the generated confusion matrix and five indicating parameters, including precision, recall, specificity, accuracy, and the F1-score of the trained model. Two models, namely, hyperspectral narrowband image (HSI-NBI) and RGB classification, were built and then compared in this study to understand the performance of HSI with the RGB model. Experimental results showed that the HSI model can learn the SCC feature better than the original RGB image because the feature is more prominent or the model is not captured in other categories. The recall rate of the RGB and HSI models were 0.722 to 0.794, respectively, thereby indicating an overall increase of 7.5% when using the HSI model. Full article

Tinnitus is a common symptom reported in otolaryngologic practice. Although the pathophysiology of tinnitus has not been fully understood, clinical studies suggest that psychological symptoms of depression, anxiety, and somatization are increased in tinnitus patients. However, patients seeking medical treatment for tinnitus may be especially vulnerable. Population-based studies reporting on the association between tinnitus and psychological distress are still lacking. The aim of this study was to investigate the correlation of tinnitus with depression, anxiety, or somatization in a large population-based cohort. The Gutenberg Health Study is a population-based cohort study. Participants were asked about the occurrence of tinnitus (yes/no) and how much they were bothered by it. In addition, they completed the PHQ-9, GAD-7, and SSS-8 questionnaires to assess depressive symptoms, anxiety, and somatic symptom disorders. A total of 8539 participants were included in the study cohort. Tinnitus prevalence was 28.0% (2387). The prevalence of depression/anxiety/somatic symptom disorders was significantly higher among participants with tinnitus than among participants without tinnitus (7.9%/5.4%/40.4% participants with tinnitus vs. 4.6%/3.3%/26.9% participants without tinnitus, p-value < 0.0001). Logistic regression results showed that participants with tinnitus were more likely to suffer from depression (OR = 2.033, 95% CI [1.584; 2.601], p-value < 0.0001), anxiety (OR = 1.841, 95% CI [1.228; 2.728], p-value = 0.0027), or somatic symptom disorders (OR = 2.057, 95% CI [1.799; 2.352], p-value < 0.0001). Symptoms of depression, anxiety, and somatic symptom disorders were increased in participants with tinnitus. This must be taken into account when treating these patients. Full article

Thyroid hormones are required for the physiological growth and maintenance of hair follicles. We aim to study the thyroid profile of patients with alopecia. This is a narrative review. PubMed literature was searched from 2013 to 2022. We followed different types of alopecia: alopecia areata (AA), androgenic alopecia in males and females, telogen effluvium (TE), frontal fibrosing alopecia (FFA), lichen planopilaris, and alopecia neoplastica (AN). AA shares a common autoimmune background with autoimmune thyroid diseases, either sporadic or belonging to autoimmune polyglandular syndromes. Some data suggested that AA is more severe if thyroid anomalies are confirmed, including subclinical dysfunction or positive antithyroid antibodies with normal hormone values. However, routine thyroid screening for patients with AA, if the patients are asymptomatic from a thyroid point of view and they have negative personal and family history of autoimmunity, remains controversial. TE, apart from the autoimmune type, associates thyroid anomalies of a hormonal assay (between 5.7% and 17%). FFA, mostly a postmenopausal entity (however, not exclusive), associates a higher prevalence of thyroid conditions (up to 50%) than the general population. However, these might have an age-dependent pattern, thus the association may be incidental since there are a limited number of studies. Overall, alopecia remains a very challenging condition for patients and physicians; a multidisciplinary team is required to improve the outcome and quality of life. The common autoimmune background is suggestive of some types of alopecia and thyroid disorders, yet, the underlying mechanisms are still a matter of debate. AA, TE, FFA, LPP, and, potentially, female pattern hair loss have been found to be connected with thyroid entities, thus a state of awareness from a dual perspective, of trichology and endocrinology, is helpful. Full article

Direct and indirect links between brain regions and cardiac function have been reported. We performed a systematic literature review to summarize current knowledge regarding the associations of heart rate variability (HRV) and brain region morphology, activity and connectivity involved in autonomic control at rest in healthy subjects. Both positive and negative correlations of cortical thickness and gray matter volumes of brain structures with HRV were observed. The strongest were found for a cluster located within the cingulate cortex. A decline in HRV, as well as cortical thickness with increasing age, especially in the orbitofrontal cortex were noted. When associations of region-specific brain activity with HRV were examined, HRV correlated most strongly with activity in the insula, cingulate cortex, frontal and prefrontal cortices, hippocampus, thalamus, striatum and amygdala. Furthermore, significant correlations, largely positive, between HRV and brain region connectivity (in the amygdala, cingulate cortex and prefrontal cortex) were observed. Notably, right-sided neural structures may be preferentially involved in heart rate and HRV control. However, the evidence for left hemispheric control of cardiac vagal function has also been reported. Our findings provide support for the premise that the brain and the heart are interconnected by both structural and functional networks and indicate complex multi-level interactions. Further studies of brain–heart associations promise to yield insights into their relationship to health and disease. Full article

We performed a retrospective and observational study of patients with psoriasis. The aim of this study was to define the laboratory indicators reflecting the treatment response to tumor necrosis factor (TNF)-α inhibitors and the predictors for the treatment response. From January 2010 to June 2022, 28, 15 and 12 patients with psoriasis were treated with infliximab (IFX), adalimumab (ADA) and certolizumab pegol (CZP), respectively. The values of C-reactive protein (CRP), platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio and monocyte to lymphocyte ratio decreased in parallel with psoriasis area and severity index (PASI) at weeks 12 and 52 of treatment. The percentage reduction of the CRP was correlated with that of the PASI at week 52 in all patients and subgroups treated with IFX. The percentage reduction of the PLR was correlated with that of the PASI at week 52 in all patients. Linear multivariate regression analyses revealed that the presence of scalp lesions was associated with a high percentage reduction of the PASI at week 52 in the ADA subgroup. The CRP and PLR might act as biomarkers reflecting the treatment response to TNF-α inhibitors in patients with psoriasis. The presence of scalp lesions might be a predictive factor for a high treatment response to ADA in patients with psoriasis. Full article

Triple negative breast cancer (TNBC) is a highly heterogeneous disease with a poor prognosis and a paucity of therapeutic options. In recent years, immunotherapy has emerged as a new treatment option for patients with TNBC. However, this therapeutic evolution is paralleled by a growing need for biomarkers which allow for a better selection of patients who are most likely to benefit from this immune checkpoint inhibitor (ICI)-based regimen. These biomarkers will not only facilitate a better optimization of treatment strategies, but they will also avoid unnecessary side effects in non-responders, and limit the increasing financial toxicity linked to the use of these agents. Huge efforts have been deployed to identify predictive biomarkers for the ICI, but until now, the fruits of this labor remained largely unsatisfactory. Among clinically validated biomarkers, only programmed death-ligand 1 protein (PD-L1) expression has been prospectively assessed in TNBC trials. In addition to this, microsatellite instability and a high tumor mutational burden are approved as tumor agnostic biomarkers, but only a small percentage of TNBC fits this category. Furthermore, TNBC should no longer be approached as a single biological entity, but rather as a complex disease with different molecular, clinicopathological, and tumor microenvironment subgroups. This review provides an overview of the validated and evolving predictive biomarkers for a response to ICI in TNBC. Full article

Machine learning (ML) is being increasingly employed in dental research and application. We aimed to systematically compile studies using ML in dentistry and assess their methodological quality, including the risk of bias and reporting standards. We evaluated studies employing ML in dentistry published from 1 January 2015 to 31 May 2021 on MEDLINE, IEEE Xplore, and arXiv. We assessed publication trends and the distribution of ML tasks (classification, object detection, semantic segmentation, instance segmentation, and generation) in different clinical fields. We appraised the risk of bias and adherence to reporting standards, using the QUADAS-2 and TRIPOD checklists, respectively. Out of 183 identified studies, 168 were included, focusing on various ML tasks and employing a broad range of ML models, input data, data sources, strategies to generate reference tests, and performance metrics. Classification tasks were most common. Forty-two different metrics were used to evaluate model performances, with accuracy, sensitivity, precision, and intersection-over-union being the most common. We observed considerable risk of bias and moderate adherence to reporting standards which hampers replication of results. A minimum (core) set of outcome and outcome metrics is necessary to facilitate comparisons across studies. Full article