Editor’s Choice Articles

Background: Although it is clear that stroke is a time-dependent and age-associated disease, we still need more evidence regarding the efficacy and outcomes in elderly patients who were excluded from the first trials of mechanical thrombectomy. The aim of this study is to highlight patient characteristics, the timing of medical attention and therapy, successful recanalization, and functional outcomes in patients over 80 y/o who underwent mechanical thrombectomy at the Ospedale Maggiore della Carità di Novara (Hub) since endovascular stroke treatment was first started here. Methods: all 122 consecutive patients over 80 y/o at admission who underwent mechanical thrombectomy between 2017 and 2022 at our Hub center were retrospectively included in our database. A good functional outcome in these elderly patients was considered as the 90 days modified Rankin Scale (mRS) ≤ 3 and/or a decrease in functional status as ∆mRS ≤ 1 in order to interpret the results for patients with intact intellect and basal mRS > 3. Successful recanalization as a score of TICI ≥ 2b (Thrombolysis in Cerebral Infarction) was analyzed as a secondary outcome. Results: Good functional outcome (mRS ≤ 3 and/or ∆mRS ≤ 1) was observed in 45.90% (56/122). The rate of successful recanalization (TICI ≥ 2b) was 65.57% (80/122). Conclusion: Our data confirm that a good outcome in the elderly age group has a correlation with age; being younger, with a milder NIHSS (National Institutes of Health Stroke Scale) at the onset and with a lower pre-morbid mRS is statistically associated with a better outcome. However, age should not be a criterion to exclude older patients from mechanical thrombectomy. Decision-making should take into consideration the pre-morbid mRS and the severity of the stroke on the NIHSS scale, especially in the age group over 85 y/o. Full article

Background: Sepsis/septic shock is a life-threatening and time-dependent condition that requires timely management to reduce mortality. This review aims to update physicians with regard to the main pillars of treatment for this insidious condition. Methods: PubMed, Scopus, and EMBASE were searched from inception with special attention paid to November 2021–January 2023. Results: The management of sepsis/septic shock is challenging and involves different pathophysiological aspects, encompassing empirical antimicrobial treatment (which is promptly administered after microbial tests), fluid (crystalloids) replacement (to be established according to fluid tolerance and fluid responsiveness), and vasoactive agents (e.g., norepinephrine (NE)), which are employed to maintain mean arterial pressure above 65 mmHg and reduce the risk of fluid overload. In cases of refractory shock, vasopressin (rather than epinephrine) should be combined with NE to reach an acceptable level of pressure control. If mechanical ventilation is indicated, the tidal volume should be reduced from 10 to 6 mL/kg. Heparin is administered to prevent venous thromboembolism, and glycemic control is recommended. The efficacy of other treatments (e.g., proton-pump inhibitors, sodium bicarbonate, etc.) is largely debated, and such treatments might be used on a case-to-case basis. Conclusions: The management of sepsis/septic shock has significantly progressed in the last few years. Improving knowledge of the main therapeutic cornerstones of this challenging condition is crucial to achieve better patient outcomes. Full article

Background: Recent advances in biologics have provided new insights into the clinical course of asthma, including disease modification, clinical remission (CR), and deep remission (DR). However, the extent to which biologics achieve CR and DR in severe asthma patients is poorly understood. Methods: To assess the achievement rate and predictors of CR and DR using long-term biologics, we retrospectively evaluated 54 severe asthma patients recently started on biologics. “CR” denotes the achievement of all three criteria: (1) absence of asthma symptoms, (2) no asthma exacerbations, and (3) no use of oral corticosteroids. DR denoted CR plus (4) normalized pulmonary function and (5) suppressed type 2 inflammation. Results: CR and DR achievement rates were 68.5% and 31.5%, respectively. Compared with the non-deep remission group, the DR group had higher adult-onset asthma rates (94.1% vs. 70.3%, p = 0.078), shorter asthma duration (5 vs. 19 years, p = 0.006), and higher FEV₁ (91.5% vs. 71.5%, p < 0.001). There were no significant differences in the Asthma Control Questionnaire scores, exacerbation frequency, or type 2 inflammation at baseline between groups. Asthma duration combined with FEV₁ can stratify the achievement rates of CR and DR. Conclusions: the early introduction of biologics in severe asthma patients may help achieve CR and DR. Full article

Background: Temporomandibular disorders (TMDs) are a series of disorders that affect the muscles and joint. Symptoms include joint pain, muscle pain, and limitation of mouth opening. One of several multifactorial diseases, temporomandibular dysfunction has mostly been linked to five etiological factors: occlusion, trauma, severe pain stimuli, parafunctional activities, and psychological elements, including stress, anxiety, and depression. The position of the human body as it is displayed in space is referred to as posture. Several nerve pathways regulate posture, and through ligaments, TMD and posture affect each other. The purpose of this study is to evaluate the possible correlation between posture and TMD through a meta-analysis of the literature; Methods: A literature search was performed on PubMed, Lilacs, and Web of science, and articles published from 2000 to 31 December 2022 were considered, according to the keywords entered. The term “temporomandibular disorders” has been combined with “posture”, using the Boolean connector AND; Results: At the end of the research, 896 studies were identified from the search conducted on the 3 engines. Only three were chosen to draw up the present systematic study summarizing the article’s main findings. The meta-analysis showed through forest plot analysis a correlation between posture and TMD Conclusions: This literature meta-analysis showed a correlation between posture and TMD. Nerve pathways probably regulate both body posture and mandibular posture. Further clinical studies will be needed to confirm this hypothesis and to indicate the main conclusions or interpretations. 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

Purpose: To propose a classification of the glistening in intraocular lenses (IOL) using swept-source optical coherence tomography (SS-OCT) by means of a simple, objective and reproducible method that allows the quantification of the presence and severity of glistening. Methods: A cross-sectional study on a sample of 150 eyes of 150 patients who underwent cataract surgery in at least 600 days before the exam and attended a routine examination. Each subject was examined by SS-OCT after pupil dilation, identifying the presence of glistening or hyperreflective foci (HRF) in the central area of the IOL. The degree of glistening was classified into four categories: 0: ≤5 HRF; 1: 6 to 15 HRF; 2: 16 to 30 HRF; and 3: >30 HRF. The intra and interobserver reproducibility (intraclass correlation coefficient, ICC) in the quantification and classification of the glistening were calculated. The correlation between the horizontal and vertical scan of the IOL was also assessed. Results: Glistening was present in the IOL in 42.7% of the patients. The mean number of HRF or glistening microvacuoles was 10.4 ± 26.2 (range 0 to 239). In total, 63.3% of the IOLs had a grade 0, 20% grade a 1, 6.7% grade a 2 and 10% a grade 3. The intraobserver and interobserver reproducibility were very high, both for the absolute quantification of the glistening (ICC ≥ 0.994) and for the severity scale (ICC ≥ 0.967). There was an excellent correlation in the quantification of the IOL glistening between the horizontal and vertical scans (R ≥ 0.834; p < 0.001). Conclusions: The use of SS-OCT makes it possible to identify, quantify and classify IOL glistening in a simple, objective and reproducible way. This technique could provide relevant information for the study of the glistening on IOLs. 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

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

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

The immediate aim of this study was to comparatively examine the bacterial respiratory microbiome of patients in a stable state and during an exacerbation of asthma–COPD (chronic obstructive pulmonary disease) overlap (ACO). This prospective observational study took place in Jordan between 1 September 2021 and 30 April 2022. Sputum samples from patients with recognized ACO were acquired within 48 h of the exacerbation onset and again at 3 weeks following the exacerbation. The next-generation sequencing Illumina MiSeq was employed and uncovered significantly high bacterial diversity in the sputa. The results showed a significant decrease in the taxonomic richness in the sputum samples collected during the exacerbation episodes compared with those collected from patients in a stable state (p = 0.008), with an increase in the taxonomic evenness (p < 0.005). This change in the composition of the airway bacterial community suggests that the replacement of a significant portion of the airway microbiome with certain microorganisms may play a role in the decrease in microbial diversity observed during an ACO exacerbation. Greater knowledge of this link could allow for a more focused administration of antibiotics, especially during exacerbations, improving clinical efficacy and patient outcomes. 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

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

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

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

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

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, typically characterized by anovulation, infertility, obesity, insulin resistance, and polycystic ovaries. Lifestyle or diet, environmental pollutants, genetics, gut dysbiosis, neuroendocrine alterations, and obesity are among the risk factors that predispose females to PCOS. These factors might contribute to upsurging metabolic syndrome by causing hyperinsulinemia, oxidative stress, hyperandrogenism, impaired folliculogenesis, and irregular menstrual cycles. Dysbiosis of gut microbiota may play a pathogenic role in the development of PCOS. The restoration of gut microbiota by probiotics, prebiotics, or a fecal microbiota transplant (FMT) might serve as an innovative, efficient, and noninvasive way to prevent and mitigate PCOS. This review deliberates on the variety of risk factors potentially involved in the etiology, prevalence, and modulation of PCOS, in addition to plausible therapeutic interventions, including miRNA therapy and the eubiosis of gut microbiota, that may help treat and manage PCOS. 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

Immune tolerance at the feto-maternal interface is crucial for the growth of the semi-allograft fetus in the womb. The outcome of pregnancy is dependent on a fine balance between various immunological forces. For a long time, the potential role of the immune system in pregnancy disorders has remained enigmatic. Current evidence has revealed that natural killer (NK) cells are the predominant immune cell population in the uterine decidua. NK cells cooperate with T-cells to provide an optimal microenvironment for the growth of the developing fetus by producing cytokines, chemokines, and angiogenic factors. These factors support trophoblast migration and angiogenesis which regulates the process of placentation. NK cells differentiate between “self” and “non-self” through their surface receptors known as killer-cell immunoglobulin-like receptors (KIRs). They induce immune tolerance through communication via their KIR and fetal human leucocyte antigens (HLA). KIRs are surface receptors of NKs that comprise both activating and inhibiting receptors. Due to the wide diversity manifested by its genes, the KIR repertoire is different in each individual. Significant evidence has implicated KIRs in recurrent spontaneous abortion (RSA); however, maternal KIR gene diversity in RSA is still unclear. Research has shown that immunological aberrancies including activating KIRs, NK abnormalities, and T cell downregulation are risk factors for RSA. In this review, we discuss relevant data from experimental studies on NK cell abnormalities, KIR, and T-cells in the incidence of recurrent spontaneous abortion. 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 and Goal of Study: Spinal anesthesia for cesarean section is frequently associated with a high incidence of hypotension, which may bring about untoward effects for both the mother and fetus. Recently, norepinephrine has emerged as a promising alternative in maintaining blood pressure in the obstetric setting. Fluid administration is another technique still widely used to prevent maternal hypotension. The optimal fluid strategy to prevent maternal hypotension has not been elucidated yet. It has been recently suggested that the main strategy in the prevention and management of hypotension should be the combination of vasoconstrictive medications and fluid administration. The aim of this randomized study was to compare the incidence of maternal hypotension in parturients receiving either colloid preload or crystalloid co-load in the setting of prophylactic norepinephrine infusion during elective cesarean section under combined spinal–epidural anesthesia. Materials and Methods: After ethics committee approval, 102 parturients with full-term singleton pregnancies were randomly allocated to either 6% hydroxyethyl starch 130/0.4 5 mL/kg before the onset of spinal anesthesia (colloid preload group) or Ringer’s lactate solution 10 mL/kg concurrent with the subarachnoid injection (crystalloid co-load group). In both groups, norepinephrine 4 μg/min starting simultaneously with the administration of the subarachnoid solution was also administered. The primary outcome of the study was the incidence of maternal hypotension, defined as systolic arterial pressure (SAP) <80% of baseline. The incidence of severe hypotension (SAP < 80 mmHg), total dose of vasoconstrictive agents administered, as well as the acid–base status and Apgar score of the neonate and any incidence of maternal side effects were also recorded. Results: Data analysis was performed on 100 parturients: 51 in the colloid preload group and 49 in the crystalloid co-load group. No significant differences were demonstrated between the colloid preload group and the crystalloid co-load group in the incidence of hypotension (13.7% vs. 16.3%, p = 0.933) or the incidence of severe hypotension (0% vs. 4%, p = 0.238). The median (range) ephedrine dose was 0 (0–15) mg in the colloid preload group and 0 (0–10) mg in the crystalloid co-load group (p = 0.807). The incidence of bradycardia, reactive hypertension, requirement for modification of vasopressor infusion, time to the first occurrence of hypotension, and maternal hemodynamics did not differ between the two groups. There were no significant differences in other maternal side effects or neonatal outcomes between groups. Conclusions: The incidence of hypotension with a norepinephrine preventive infusion is low and comparable with both colloid preload and crystalloid co-load. Both fluid-loading techniques are appropriate in women undergoing cesarean delivery. It appears that the optimal regimen for prevention of maternal hypotension is a combined strategy of a prophylactic vasopressor such as norepinephrine and fluids. Full article

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. A diagnosis of PCOS is established when a patient exhibits two of three Rotterdam criteria: oligoovulation or anovulation, excess androgen activity, and polycystic ovarian morphology. The pathogenesis of PCOS, as it affects adolescents, is often discussed in terms of a “two-hit” theory. This refers to a stepwise process in which the first “hit” is an inborn congenitally programmed predisposition, while the second “hit” arises from a provocative factor such as insulin resistance. The dynamic physiological and anatomical changes which occur in puberty make for a challenging diagnosis in this group of patients. It is important to be mindful of the physiological particularities in adolescence which often mimic the symptoms of PCOS. In their first-year post-menarche, approximately 75% of menstruating adolescents report their cycle to last between 21–45 days. Recent studies have shown that regular menstrual cyclicity is only achieved within 2–3 years post-menarche. Anovulation, as a crucial diagnostic element for PCOS, features in about half of early-post-menarchal adolescents. Hirsutism and acne are the most common clinical manifestations of hyperandrogenism, and mild features are developed by most adolescents as a result of elevated androgen levels. Distinguishing between a pathological sign and normal features of maturation is often difficult. A polycystic ovarian morphology (PCOM) through ultrasound has been found in up to 40%, 35%, and 33.3% of patients when assessed at 2, 3, and 4 years, respectively, after menarche. PCOM in adolescence is not associated with future abnormalities in ovulatory rate or menstrual cycle duration. For this reason, international guidelines recommend against the use of pelvic ultrasound until 8 years post-menarche. The primary aim of management is focused mainly on improving hormonal and metabolic status, the prevention of future comorbid complications, and generally improving the overall quality of life in young women with PCOS. Considerable controversy surrounds the choice of optimal pharmacological treatment to address PCOS in adolescents. Reliable studies, which include this sub-section of the population, are very limited. There is a lack of robust and reliable trials in the literature addressing the use of combined oral contraceptives. Further work needs to be undertaken in order to provide safe and effective care to the adolescent population in this regard. 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

Background & Aims: Several risk scores have been proposed for risk-stratification of patients with upper gastrointestinal bleeding. ABC score was found more accurate predicting mortality than AIMS65. MAP(ASH) is a simple, pre-endoscopy score with a great ability to predict intervention and mortality. The aim of this study was to compare ABC and MAP(ASH) discriminative ability for the prediction of mortality and intervention in UGIB. As a secondary aim we compared both scores with Glasgow-Blatchford score and AIMS65. Methods: Our study included patients admitted to the emergency room of Virgen de las Nieves University Hospital with UGIB (2017–2020). Information regarding clinical, biochemical tests and procedures was collected. Main outcomes were in-hospital mortality and a composite endpoint for intervention. Results: MAP(ASH) and ABC had similar AUROCs for mortality (0.79 vs. 0.80). For intervention, MAP(ASH) (AUROC = 0.75) and ABC (AUROC = 0.72) were also similar. Regarding rebleeding, AUROCs of MAP(ASH) and ABC were 0.67 and 0.61 respectively. No statistically differences were found in these outcomes. With a low threshold for MAP(ASH) ≤ 2, ABC and MAP(ASH) classified a similar proportion of patients as being at low risk of death (42% vs. 45.2%), with virtually no mortality under these thresholds. Conclusions: MAP(ASH) and ABC were similar for the prediction of relevant outcomes for UGIB, such as intervention, rebleeding and in-hospital mortality, with an accurate selection of low-risk patients. MAP(ASH) has the advantage of being easier to calculate even without the aid of electronic tools. Full article

Hearing loss, the most common human sensory defect worldwide, is a major public health problem. About 70% of congenital forms and 25% of adult-onset forms of deafness are of genetic origin. In total, 136 deafness genes have already been identified and there are thought to be several hundred more awaiting identification. However, there is currently no cure for sensorineural deafness. In recent years, translational research studies have shown gene therapy to be effective against inherited inner ear diseases, and the application of this technology to humans is now within reach. We provide here a comprehensive and practical overview of current advances in gene therapy for inherited deafness, with and without an associated vestibular defect. We focus on the different gene therapy approaches, considering their prospects, including the viral vector used, and the delivery route. We also discuss the clinical application of the various strategies, their strengths, weaknesses, and the challenges to be overcome. 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

The hair cycle is composed of four primary phases: anagen, catagen, telogen, and exogen. Anagen is a highly mitotic phase characterized by the production of a hair shaft from the hair follicle, whereas catagen and telogen describe regression and the resting phase of the follicle, respectively, ultimately resulting in hair shedding. While 9% of hair follicles reside in telogen at any time, a variety of factors promote anagen to telogen transition, including inflammation, hormones, stress, nutritional deficiency, poor sleep quality, and cellular division inhibiting medication. Conversely, increased blood flow, direct stimulation of the hair follicle, and growth factors promote telogen to anagen transition and subsequent hair growth. This review seeks to comprehensively describe the hair cycle, anagen and telogen balance, factors that promote anagen to telogen transition and vice versa, and the clinical utility of a variety of lab testing and evaluations. Ultimately, a variety of factors impact the hair cycle, necessitating a holistic approach to hair loss. Full article

Acute heart failure (AHF) is the most frequent cause of unplanned hospital admission in patients of >65 years of age and it is associated with significantly increased morbidity, mortality, and healthcare costs. Different AHF classification criteria have been proposed, mainly reflecting the clinical heterogeneity of the syndrome. Regardless of the underlying mechanism, peripheral and/or pulmonary congestion is present in the vast majority of cases. Furthermore, a marked reduction in cardiac output with peripheral hypoperfusion may occur in most severe cases. Diagnosis is made on the basis of signs and symptoms, laboratory, and non-invasive tests. After exclusion of reversible causes, AHF therapeutic interventions mainly consist of intravenous (IV) diuretics and/or vasodilators, tailored according to the initial hemodynamic status with the addition of inotropes/vasopressors and mechanical circulatory support if needed. The aim of this review is to discuss current concepts on the diagnosis and management of AHF in order to guide daily clinical practice and to underline the unmet needs. Preventive strategies are also discussed. Full article

Spinal cord injury (SCI) is a debilitating condition that can significantly affect an individual’s life, causing paralysis, autonomic dysreflexia, and chronic pain. Transspinal stimulation (TSS) is a non-invasive form of neuromodulation that activates the underlying neural circuitries of the spinal cord. Application of TSS can be performed through multiple stimulation protocols, which may vary in the electrodes’ size or position as well as stimulation parameters, and which may influence the response of motor functions to the stimulation. Due to the novelty of TSS, it is beneficial to summarize the available evidence to identify the range of parameters that may provide the best outcomes for motor response. The PubMed and Google Scholar databases were searched for studies examining the effects of TSS on limb motor function. A literature search yielded 34 studies for analysis, in which electrode placement and stimulation parameters varied considerably. The stimulation protocols from each study and their impact on limb motor function were summarized. Electrode placement was variable based on the targeted limb. Studies for the upper limbs targeted the cervical enlargement with anatomical placement of the cathode over the cervical vertebral region. In lower-limb studies, the cathode(s) were placed over the thoracic and lumbar vertebral regions, to target the lumbar enlargement. The effects of carrier frequency were inconclusive across the studies. Multisite cathodal placements yielded favorable motor response results compared to single-site placement. This review briefly summarized the current mechanistic evidence of the effect of TSS on motor response after SCI. Our findings indicate that optimization of stimulation parameters will require future randomized controlled studies to independently assess the effects of different stimulation parameters under controlled circumstances. Full article

Background: The metabolic effects of polycystic ovary syndrome (PCOS) may increase the risk of non-alcoholic fatty liver disease (NAFLD). However, the burden of NAFLD in PCOS has not been unequivocally defined. This systematic review (SR), meta-analysis (MA) assessed NAFLD’s prevalence, and risk factors in patients with PCOS. Methods: A literature search was performed in MEDLINE, Scopus, and Scielo. First, we performed a MA of proportions to estimate the prevalence of NAFLD in PCOS. Second, we performed meta-analyses of precalculated adjusted odds ratios to examine NAFLD risk factors. Finally, we performed a meta-regression to model how the estimated prevalence changed with changes in prespecified variables. Results: We identified 817 articles from the database searches. Thirty-six were included. MA of proportions found a pooled NAFLD prevalence of 43% (95% CI, 35–52%) with high heterogeneity (I² = 97.2%). BMI, waist circumference, ALT values, HOMA-IR values, free androgen index levels, hyperandrogenism, and triglycerides were associated with significantly higher risk-adjusted odds of NAFLD among patients with PCOS. Meta-regression showed that rises in NAFLD prevalence were mediated through increases in metabolic syndrome prevalence and higher levels of HOMA-IR, free androgen index, and total testosterone. Conclusion: The prevalence of NAFLD (43%) among PCOS patients is high despite their average young age, with several metabolic and PCOS-specific factors influencing its occurrence. Screening programs may aid in detecting metabolic-associated fatty liver disease and prevent its consequences. Further work is required to establish the burden of liver-related outcomes once NAFLD has progressed in the PCOS population. Full article

Over the past 20 years, there has been a significant reduction in the incidence of adverse events associated with sedation outside of the operating room. Non-pharmacologic techniques are increasingly being used as peri-operative adjuncts to facilitate and promote anxiolysis, analgesia and sedation, and to reduce adverse events. This narrative review will briefly explore the emerging role of immersive reality in the peri-procedural care of surgical patients. Immersive virtual reality (VR) is intended to distract patients with the illusion of “being present” inside the computer-generated world, drawing attention away from their anxiety, pain, and discomfort. VR has been described for a variety of procedures that include colonoscopies, venipuncture, dental procedures, and burn wound care. As VR technology develops and the production costs decrease, the role and application of VR in clinical practice will expand. It is important for medical professionals to understand that VR is now available for prime-time use and to be aware of the growing body in the literature that supports VR. Full article

We aimed to review the current evidence on surgical and functional outcomes of Transperineal Laser Ablation for LUTS due to BPH. A comprehensive review of the English-language literature was performed using the MEDLINE and Web of Science databases until 1 August 2022, aiming to select studies evaluating TPLA for the treatment of LUTS due to BPH. Additional records were found from Google Scholar. Data were extracted and summarized in Tables. An appropriate form was used for qualitative data synthesis. Seven studies were included in the review, with all being single arm, non-comparative studies. In all studies, functional outcomes were evaluated with uroflowmetry parameters and validated questionnaires, showing a promising effectiveness at short- and mid-term follow-up. There is a lack of standardized pathways for preoperative assessment of patients suitable for TPLA, and even the technique itself has been reported with a few nuances. A good safety profile has been reported by all the authors. Although promising results have been reported by different groups, selection criteria for TPLA and few technical nuances regarding the procedure were found to be heterogeneous across the published series that should be standardized in the future. Further research is needed to confirm these findings. Full article

The aim of this meta-meta-analysis was to assess the current evidence regarding the effect of physical therapy (PT) interventions on pain and functional variables in temporomandibular disorders (TMD). We conducted an umbrella systematic review (SR) and four meta-meta-analyses (MMA) and created an evidence map to determine the effectiveness of PT on pain intensity and maximum mouth opening in patients with TMD. The quality of the included SR was assessed with the AMSTAR 2, and the risk of bias with ROBIS. Of the 31 SR included in the umbrella SR, only 10 were included in the MMA. The MMA showed moderate effects for manual therapy and therapeutic exercise, and large effects for low-level laser therapy on improving pain intensity and maximum mouth opening in patients with TMD, with a limited to moderate quality of evidence. The overlapping analyses showed only a slight overlap for all the MMA according to the corrected covered area (range from 0.07 to 0.2), 23.1% to 41.6%. This umbrella SR showed that manual therapy and exercise interventions, as well as low-level laser therapy interventions, are effective in the reduction in pain intensity and improvement of maximum mouth opening in TMD. This article presents a synthesis of the available evidence related to the various physical therapy interventions used in patients presenting with temporomandibular disorders. These results could help clinicians to select the optimal intervention for their patients and to reject those that are less useful. Full article

Hypoglycemia is an often-observed acute complication in the management of children and adolescents with type 1 diabetes. It causes inappropriate glycemic outcomes and may impair the quality of life in the patients. Severe hypoglycemia with cognitive impairment, such as a convulsion and coma, is a lethal condition and is associated with later-onset cognitive impairment and brain-structural abnormalities, especially in young children. Therefore, reducing the frequency of hypoglycemia and minimizing the occurrence of severe hypoglycemia are critical issues in the management of children and adolescents with type 1 diabetes. Advanced diabetes technologies, including continuous glucose monitoring and sensor-augmented insulin pumps with low-glucose suspension systems, can reduce the frequency of hypoglycemia and the occurrence of severe hypoglycemia without aggravating glycemic control. The hybrid closed-loop system, an automated insulin delivery system, must be the most promising means to achieve appropriate glycemic control with preventing severe hypoglycemia. The use of these advanced diabetes technologies could improve glycemic outcomes and the quality of life in children and adolescents with type 1 diabetes. Full article

Background. The best format of exercise training (ET) in the setting of cardiac rehabilitation in patients with chronic heart failure (CHF) is still to be defined. Current guidelines recommend aerobic exercises, such as running and cycling, including some sessions per week of resistance exercise. Aim. The aim of this study was to address the effectiveness of a concurrent exercise training program utilizing a circuit of sequential endurance and resistance exercises on functional capacity and muscular strength in patients with CHF. Methods. Ninety-five consecutive male patients (age 63.1 ± 6 years) with CHF (EF < 40%) in NYHA functional class II/III, were randomly assigned on 1:1 basis to a 12-week aerobic continuous training (AT) or concurrent CT), aerobic + resistance, training (CT), three times a week, with each session lasting 80 min. We used high quality, specifically designed ergometers, connected with each other and governed by a central console, and managed by a single physiotherapist. Before and after training all patients performed a symptoms-limited exercise test on a treadmill and a 6-min walking test (6MWT). Patients in the CT group also performed resistance exercises of upper and lower body. Results. The 6MWT and exercise duration at ergometric test increased significantly in both AT and CT groups, with the increase being greater in CT group (p < 0.001; ES = 0.13; p < 0.01; ES = 0.07). Muscular strength increased significantly in the CT group, particularly in the lower body muscular districts (p < 0.001). Quality of life improved in both groups, with a significantly greater improvement in the CT group (p < 0.05). No side effects leading to discontinuation of training were observed. Conclusions. These findings indicate that concurrent, within-session training results in larger improvements in functional capacity, in addition to muscle performance, in patients with CHF, in comparison to single-mode aerobic training. Full article

(1) Background: Multiple Sclerosis (MS) is a chronic, progressive, immune-mediated disorder that affects the Central Nervous System and is the most common cause of non-traumatic neurological disability in young adults. The study aimed to assess the levels of stress, resilience, well-being, sleep quality, and fatigue in Israeli people with MS (PwMS), and to examine the associations between these factors and the sociodemographic and clinical characteristics. These factors had never before been studied in conjunction in PwMS, nor had they been systematically addressed in Israel, the unique geopolitical situation of which may pose unique challenges. (2) Methods: This was a survey-based, cross-sectional study conducted through an Internet platform. (3) Results: Israeli PwMS who participated in the study were experiencing relatively high levels of stress and low resilience, poor sleep quality, and severe fatigue. The analysis revealed significant associations between resilience and stress, well-being, and anxiety, as well as stress and well-being, resilience, sleep quality, fatigue, and Clinically Isolated Syndrome (CIS). (4) Conclusions: the Israeli PwMS who participated in the study were experiencing higher levels of stress, lower resilience and worse sleep quality than PwMS in other countries, as compared to results previously reported in literature. The findings of this study ought to serve as a call to action for the MS care providers in Israel and warrant further research into the possible causes of the phenomenon and strategies to address it. Full article

The burden of inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasing worldwide. The aim of the present study was to investigate the clinical characteristics and the changing in epidemiology of IBD in the Healthcare District Bra, an area of North-West Italy accounting for 57,615 inhabitants as of 31 December 2021. Clinical and demographic data were retrieved from administrative databases and the medical records of general practitioners (n = 39) at Verduno Hospital. Prevalence and incidence rates were calculated for the time span 2016–2021 and compared to the 2001–2006 period. IBD prevalence was 321.2 per 100,000 population in 2021 and, compared with 2006 (200 per 100,000 population), the prevalence has increased at a rate of +46%. Similarly, the average incidence has increased from the period 2001–2006 (6.7 per 100,000 population/year) to the period 2016–2021 (18.0 per 100,000 population/year) at a rate of +169%; such an increase was greater for CD than UC. In the 2016–2021 period, the mean age at diagnosis was 42.0 ± 17.4 years and 30.9% required at least one hospitalization, while 10.9% of patients underwent at least one surgery. In conclusion, the prevalence and incidence of IBD distinctly increased over a two decade period in the Healthcare District Bra paralleling the results of previous surveys from other Italian regions. These data warrant specific interventions to improve patients’ management and resources’ allocation. Full article

Forward head posture (FHP) is a common postural displacement that is significantly associated with neck pain, with higher risks of having neck pain in female and older populations. This study investigated the effect of two different forward head posture (FHP) interventions in elderly participants with poor posture and non-specific neck pain. Sixty-six elderly participants with a craniovertebral angle (CVA) < 50° were randomized into either a Chiropractic Biophyics^® (CBP^®) or a standardized exercise based FHP correction group (Standard Group). Both groups were treated for 18 sessions over a 6-week period. A 3-month post-treatment follow-up was also assessed with no further interventions. The CBP group received a mirror image^® exercise and a Denneroll™ cervical traction orthotic (DCTO); the standard group performed a protocol of commonly used stretching and strengthening exercises for the neck. Both groups received 30 min of their respective interventions per session. The primary outcome was the CVA, with secondary outcomes including pain intensity, Berg balance score (BBS), head repositioning accuracy (HRA), and cervical range of motion (CROM). After 18 sessions (6 weeks later), the CBP group had statistically significant improvement in the CVA (p < 0.001), whereas the standard group did not. In contrast, both groups showed improved functional measurements on the BBS and HRA as well as improved pain intensity. However, at the 3-month follow-up (with no further treatment), there were statistically significant differences favoring the CBP group for all outcomes (p < 0.001). The differences in the between group outcomes at the 3-month follow-up indicated that the improved outcomes were maintained in the CBP group, while the standard group experienced regression of the initially improved outcomes at 6 weeks. It is suggested that the improvement in the postural CVA (in the CBP group but not in the standard group) is the driver of superior and maintained pain and functional outcomes. Full article

Technology is rapidly evolving in the modern world, and the accompanying developments due to its influence are shaping each and every aspect of our life, with the field of orthodontics being no exception. This systematic review and meta-analysis aimed to examine such trends in orthodontics and hypothesize which ones would emerge and continue in the near future. After a thorough search of online journals using keywords such as “3D printing,” “Aligners,” “Artificial intelligence,” “Future trends,” “Orthodontics,” and “Teleorthodontics” across databases of PubMed-MEDLINE, Web of Science, Cochrane, and Scopus, a total of 634 papers were initially recovered. Technological advancements in 3D printing, Computer-aided design and Computer-aided manufacturing (CAD/CAM), biopolymers and Teleorthodontics were the most important categories of development seen across the 17 studies that we selected for our review. All the investigations selected for this systematic review depicted aspects of orthodontics that were influenced by rapid technological changes and could potentially become mainstream in the coming times. However, caution was sought to be observed in the usage/adoption of some of these trends, with social media usage amongst both patients as well as orthodontists being a prime example of this. Full article

Background: Indocyanine green (ICG) imaging has been increasingly used for intraoperative guidance in colorectal surgery over the past decade. The aim of this study was to review and organize, according to different type of use, all available literature on ICG guided colorectal surgery and highlight areas in need of further research and discuss future perspectives. Methods: PubMed, Scopus, and Google Scholar databases were searched systematically through November 2022 for all available studies on fluorescence-guided surgery in colorectal surgery. Results: Available studies described ICG use in colorectal surgery for perfusion assessment, ureteral and urethral assessment, lymphatic mapping, and hepatic and peritoneal metastases assessment. Although the level of evidence is low, results are promising, especially in the role of ICG in reducing anastomotic leaks. Conclusions: ICG imaging is a safe and relatively cheap imaging modality in colorectal surgery, especially for perfusion assessment. Work is underway regarding its use in lymphatic mapping, ureter identification, and the assessment of intraperitoneal metastatic disease. Full article

Melatonin modulates the circadian rhythm and has been studied as a preventive measure against the development of delirium in hospitalized patients. Such an effect may be more evident in patients admitted to the ICU, but findings from the literature are conflicting. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We assessed whether melatonin or ramelteon (melatonin agonist) reduce delirium incidence as compared to a placebo in ICU patients. Secondary outcomes were ICU length of stay, duration of mechanical ventilation (MV) and mortality. Estimates are presented as risk ratio (RR) or mean differences (MD) with 95% confidence interval (CI). Nine RCTs were included, six of them reporting delirium incidence. Neither melatonin nor ramelteon reduced delirium incidence (RR 0.76 (0.54, 1.07), p = 0.12; I² = 64%), although a sensitivity analysis conducted adding other four studies showed a reduction in the risk of delirium (RR = 0.67 (95%CI 0.48, 0.92), p = 0.01; I² = 67). Among the secondary outcomes, we found a trend towards a reduction in the duration of MV (MD −2.80 (−6.06, 0.47), p = 0.09; I² = 94%) but no differences in ICU-LOS (MD −0.26 (95%CI −0.89, 0.37), p = 0.42; I² = 75%) and mortality (RR = 0.85 (95%CI 0.63, 1.15), p = 0.30; I² = 0%). Melatonin and ramelteon do not seem to reduce delirium incidence in ICU patients but evidence is weak. More studies are needed to confirm this finding. Full article

Total hip arthroplasty (THA) is one of the most common surgical procedures in orthopedics; however, it is subjected to different kinds of failures, one of them being dislocation. Many different prosthetic designs have been developed to overcome this problem, such as dual mobility coupling. The main purpose of this article is to determine whether there are differences regarding the revision surgery of unstable THA comparing the risk of failure between dual mobility cup (DMC) implants, standard implants, and among different head sizes. A registry-based population study has been conducted by analyzing data collected by the Emilia Romagna Registry of Orthopedic Prosthetic Implants (RIPO), including a total of 253 implants failed for dislocation and instability that were operated on by cup revision surgery between 2000 and 2019. The selected population has been divided into two groups based on the insert type: standard and DMC. The age at revision surgery was significantly lower in the standard cup group with respect to DMC (p = 0.014 t-test), with an average age of 71.2 years (33–96 years range) for the standard cups and 74.8 years (48–92 years range) for the DMC group. The cumulative survival of DMC implants was 82.0% at 5-years, decreasing to 77.5% at a 10-year follow-up, which is not significantly different from standard cups (p = 0.676, Log-Rank test). DMC implants showed a significantly lower risk of re-revision for dislocation compared to standard cups (p = 0.049). Femoral heads ≥36 mm had a higher overall survival compared to smaller femoral heads (p = 0.030). This study demonstrated that DMC or femoral heads ≥36 mm are a valid choice to manage THA instability and to reduce the revision rate for dislocation at a mid-term follow-up; in those selected and targeted patients, these options should be taken into consideration because they are associated with better outcomes. Full article

With the progression of diabetic retinopathy (DR) from the non-proliferative (NPDR) to proliferative (PDR) stage, the possibility of vision impairment increases significantly. Therefore, it is clinically important to detect the progression to PDR stage for proper intervention. We propose a segmentation-assisted DR classification methodology, that builds on (and improves) current methods by using a fully convolutional network (FCN) to segment retinal neovascularizations (NV) in retinal images prior to image classification. This study utilizes the Kaggle EyePacs dataset, containing retinal photographs from patients with varying degrees of DR (mild, moderate, severe NPDR and PDR. Two graders annotated the NV (a board-certified ophthalmologist and a trained medical student). Segmentation was performed by training an FCN to locate neovascularization on 669 retinal fundus photographs labeled with PDR status according to NV presence. The trained segmentation model was used to locate probable NV in images from the classification dataset. Finally, a CNN was trained to classify the combined images and probability maps into categories of PDR. The mean accuracy of segmentation-assisted classification was 87.71% on the test set (SD = 7.71%). Segmentation-assisted classification of PDR achieved accuracy that was 7.74% better than classification alone. Our study shows that segmentation assistance improves identification of the most severe stage of diabetic retinopathy and has the potential to improve deep learning performance in other imaging problems with limited data availability. Full article

Sinonasal ameloblastoma (SNA) is considered to be a subtype of ameloblastoma. It differs from gnathic ameloblastoma in terms of clinicopathologic features, management and prognosis. Thus, the objective of the present review was to study the complications, survival, recurrence rate and outcomes following the management of SNA. The electronic search process was conducted on PubMed-Medline, Embase, and Scopus. Google Scholar was used to search grey literature. Quality assessment of the case reports (CR) and case series (CS) was done based on CARE guidelines. The initial search resulted in 2111 articles. 15 studies (13 CR and 2 CS) were found to meet the eligibility criteria. The majority of the studies described histological features of SNA, which were consistent with ameloblastomas of gnathic origin. There were no SNA-related deaths reported in the included studies. Five studies described endoscopic surgeries to remove SNAs, and three SNAs were treated with post-surgery radiotherapy. Data from included studies suggest that sinonasal ameloblastomas are histologically similar to gnathic ameloblastomas, but their clinical presentation is different. They may cause complete or partial obstruction of the nasal cavity and the sinus. They appear to affect an older demographic, and their resection may be accompanied by the excision of a large portion of the maxilla, necessitating maxillofacial prosthetic rehabilitation. Full article

Transcatheter aortic valve implantation (TAVI) has risen over the past 20 years as a safe and effective alternative to surgical aortic valve replacement for treatment of severe aortic stenosis, and is now a well-established and recommended treatment option in suitable patients irrespective of predicted risk of mortality after surgery. Studies of numerous devices, either newly developed or reiterations of previous prostheses, have been accruing. We hereby review TAVI devices, with a focus on commercially available options, and aim to present a guide for prosthesis tailoring according to patient-related anatomical and clinical factors that may favor particular designs. Full article