Editor’s Choice Articles

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an acquired disease with significant morbidity that affects both children and adults. Post-exertional malaise is a cardinal symptom of ME/CFS and impacts a patient’s functional capacity (FC). The absence of effective tools to assess FC has significant consequences for timely diagnosis, clinical follow-up, assessments for patient disability benefits, and research studies. In interventional studies, the inability to assess FC can result in an incomplete assessment of the potential benefit of the intervention, leading to beneficial treatment outcomes being missed. Methods: Using extensive, repeated patient feedback, we have developed a new questionnaire, FUNCAP, to accurately assess FC in ME/CFS patients. The questionnaire consists of eight domains divided by activity types: A. personal hygiene/basic functions, B. walking/movement, C. being upright, D. activities in the home, E. communication, F. activities outside the home, G. reactions to light and sound, and H. concentration. Results: Through five rounds of anonymous web-based surveys and a further test–retest validation round, two versions of the questionnaire were developed: a longer version comprising 55 questions (FUNCAP55), developed for improved diagnostic and disability benefit/insurance FC assessments; and a shorter version (FUNCAP27) for clinical patient follow-up and potential use in research. Good reliability and validity and negligible floor and ceiling effects were found, with comparable findings in all aspects in both a large Norwegian (n = 1263) and a separate English-language international sample (n = 1387) demonstrating the validity and reliability of FUNCAP. Conclusions: Our findings support the utility of FUNCAP as an effective, reliable and valid tool for assessing FC in ME/CFS patients. Full article

Background: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an emerging technique for delivering chemotherapy directly to the peritoneum via a pressurized aerosol. Its growing attention stems from its effectiveness in treating peritoneal carcinomatosis (PC) originating from various primary tumors, with gastric cancer (GC) being among the most prevalent. This study aimed to systematically investigate PIPAC’s therapeutic role in gastric cancer peritoneal metastasis (GCPM). Methods: The systematic review and meta-analysis followed the PRISMA 2020 guidelines, searching Pubmed, Web of Science, and SCOPUS databases. The meta-analysis of relative risks and mean differences compared patients undergoing one or two PIPAC sessions with those completing three or more, assessing various outcomes. Results: Eighteen studies underwent qualitative analysis, and four underwent quantitative analysis. Patients with three or more PIPAC procedures had shorter hospital stays (MD = −1.2; 95%CI (−1.9; −0.5); p < 0.001), higher rates of histopathological response (RR = 1.77, 95%CI 1.08; 2.90; p = 0.023), and significantly improved overall survival (MD = 6.0; 95%CI 4.2; 7.8; p < 0.001). Other outcomes showed no significant differences. Conclusions: PIPAC demonstrated efficacy in carefully selected patients, enhancing histopathologic response rates and overall survival without prolonging hospital stays. This study underscores the necessity for randomized controlled trials and precise selection criteria to refine PIPAC’s implementation in clinical practice. Full article

Background/Objectives: Population aging is rapidly increasing, and the importance of preventive medicine has been stressed. Health checkups, diet, and exercise are of paramount importance. This study aimed to evaluate the effectiveness of a personalized dual-task intervention that combined exercise with cognitive tasks in improving physical and cognitive functions among independently living older individuals. Methods: Participants aged >65 years who were mostly independent in their activities of daily living were divided into two groups. The group receiving the 20 min robot-assisted session was compared with the group receiving traditional functional restoration training. This randomized trial assessed the impact of this intervention on the 30 s chair stand test score and Montreal Cognitive Assessment—Japanese version score of the participants. Results: Both scores significantly improved in the intervention group, indicating enhanced lower-limb function and cognitive capabilities. Conclusions: These findings suggest that integrating cognitive tasks with physical exercise can stand as an effective strategy to improve overall well-being in older people, offering valuable insights for designing comprehensive preventive health programs tailored to this demographic. Full article

Primary percutaneous coronary intervention (pPCI) has revolutionized the prognosis of ST-segment elevation myocardial infarction (STEMI) and is the gold standard treatment. As a result of its success, the number of pPCI centres has expanded worldwide. Despite decades of advancements, clinical outcomes in STEMI patients have plateaued. Out-of-hospital cardiac arrest and cardiogenic shock remain a major cause of high in-hospital mortality, whilst the growing burden of heart failure in long-term STEMI survivors presents a growing problem. Many elements aiming to optimize STEMI treatment are still subject to debate or lack sufficient evidence. This review provides an overview of the most contentious current issues in pPCI in STEMI patients, with an emphasis on unresolved questions and persistent challenges. Full article

Diagnostic and therapeutic decision-making in pregnancy with suspected pulmonary embolism (PE) is challenging. European and other international professional societies have proposed various recommendations that are ambiguous, probably due to the unavailability of randomized controlled trials. In the following sections, we discuss the supporting diagnostic steps and treatments. We suggest a standardized diagnostic work-up in pregnant patients presenting with symptoms of PE to make evidence-based diagnostic and therapeutic decisions. We strongly recommend that clinical decisions on treatment in pregnant patients with intermediate- or high-risk pulmonary embolism should include a multidisciplinary team approach involving emergency physicians, pulmonologists, angiologist, cardiologists, thoracic and/or cardiovascular surgeons, radiologists, and obstetricians to choose a tailored management option including an interventional treatment. It is important to be aware of the differences among guidelines and to assess each case individually, considering the specific views of the different specialties. This review summarizes key concepts of the diagnostics and acute management of pregnant women with suspected PE that are supportive for the clinician on duty. Full article

The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that mimics the physiological state of fasting. The potential therapeutic effects in many chronic conditions have led to the gaining popularity of the KD. The KD has been demonstrated to alleviate inflammation and oxidative stress, modulate the gut microbiota community, and improve metabolic health markers. The modification of these factors has been a potential therapeutic target in serious mental illness (SMI): bipolar disorder, major depressive disorder, and schizophrenia. The number of clinical trials assessing the effect of the KD on SMI is still limited. Preliminary research, predominantly case studies, suggests potential therapeutic effects, including weight gain reduction, improved carbohydrate and lipid metabolism, decrease in disease-related symptoms, increased energy and quality of life, and, in some cases, changes in pharmacotherapy (reduction in number or dosage of medication). However, these findings necessitate further investigation through larger-scale clinical trials. Initiation of the KD should occur in a hospital setting and with strict care of a physician and dietitian due to potential side effects of the diet and the possibility of exacerbating adverse effects of pharmacotherapy. An increasing number of ongoing studies examining the KD’s effect on mental disorders highlights its potential role in the adjunctive treatment of SMI. Full article

Over the last two decades, the invasiveness of thoracic surgery has decreased along with technological advances and better diagnostic tools, whereas the patient’s comorbidities and frailty patterns have increased, as well as the number of early cancer stages that could benefit from curative resection. Poor aerobic fitness, nutritional defects, sarcopenia and “toxic” behaviors such as sedentary behavior, smoking and alcohol consumption are modifiable risk factors for major postoperative complications. The process of enhancing patients’ physiological reserve in anticipation for surgery is referred to as prehabilitation. Components of prehabilitation programs include optimization of medical treatment, prescription of structured exercise program, correction of nutritional deficits and patient’s education to adopt healthier behaviors. All patients may benefit from prehabilitation, which is part of the enhanced recovery after surgery (ERAS) programs. Faster functional recovery is expected in low-risk patients, whereas better clinical outcome and shorter hospital stay have been demonstrated in higher risk and physically unfit patients. Full article

Introduction: In the context of the current opioid crisis, non-pharmacologic approaches to pain management have been considered important alternatives to the use of opioids or analgesics. Advancements in nano and quantum technology have led to the development of several nanotransporters, including nanoparticles, micelles, quantum dots, liposomes, nanofibers, and nano-scaffolds. These modes of nanotransporters have led to the development of new drug formulations. In pain medicine, new liposome formulations led to the development of DepoFoam™ introduced by Pacira Pharmaceutical, Inc. (Parsippany, NJ, USA). This formulation is the base of DepoDur™, which comprises a combination of liposomes and extended-release morphine, and Exparel™, which comprises a combination of liposomes and extended-release bupivacaine. In 2021, Heron Therapeutics (San Diego, CA, USA) created Zynrelef™, a mixture of bupivacaine and meloxicam. Advancements in nanotechnology have led to the development of devices/patches containing millions of nanocapacitors. Data suggest that these nanotechnology-based devices/patches reduce acute and chronic pain. Methods: Google and PubMed searches were conducted to identify studies, case reports, and reviews of medical nanotechnology applications with a special focus on acute and chronic pain. This search was based on the use of keywords like nanotechnology, nano and quantum technology, nanoparticles, micelles, quantum dots, liposomes, nanofibers, nano-scaffolds, acute and chronic pain, and analgesics. This review focuses on the role of nanotechnology in acute and chronic pain. Results: (1) Nanotechnology-based transporters. DepoDur™, administered epidurally in 15, 20, or 25 mg single doses, has been demonstrated to produce significant analgesia lasting up to 48 h. Exparel™ is infiltrated at the surgical site at the recommended dose of 106 mg for bunionectomy, 266 mg for hemorrhoidectomy, 133 mg for shoulder surgery, and 266 mg for total knee arthroplasty (TKA). Exparel™ is also approved for peripheral nerve blocks, including interscalene, sciatic at the popliteal fossa, and adductor canal blocks. The injection of Exparel™ is usually preceded by an injection of plain bupivacaine to initiate analgesia before bupivacaine is released in enough quantity from the depofoarm to be pharmacodynamically effective. Finally, Zynrelef™ is applied at the surgical site during closure. It was initially approved for open inguinal hernia, abdominal surgery requiring a small-to-medium incision, foot surgery, and TKA. (2) Nanotechnology-based devices/patches. Two studies support the use of nanocapacitor-based devices/patches for the management of acute and chronic pain. A randomized study conducted on patients undergoing unilateral primary total knee (TKA) and total hip arthroplasty (THA) provided insight into the potential value of nanocapacitor-based technology for the control of postoperative acute pain. The results were based on 2 studies, one observational and one randomized. The observational study was conducted in 128 patients experiencing chronic pain for at least one year. This study suggested that compared to baseline, the application of a nanocapacitor-based Kailo™ pain relief patch on the pain site for 30 days led to a time-dependent decrease in pain and analgesic use and an increase in well-being. The randomized study compared the effects of standard of care treatment to those of the same standard of care approach plus the use of two nanocapacitor-based device/patches (NeuroCuple™ device) placed in the recovery room and kept in place for three days. The study demonstrated that the use of the two NeuroCuple™ devices was associated with a 41% reduction in pain at rest and a 52% decrease in the number of opioid refills requested by patients over the first 30 days after discharge from the hospital. Discussion: For the management of pain, the use of nano-based technology has led to the development of nano transporters, especially focus on the use of liposome and nanocapacitors. The use of liposome led to the development of DepoDur™, bupivacaine Exparel™ and a mixture of bupivacaine and meloxicam (Zynrelef™) and more recently lidocaine liposome formulation. In these cases, the technology is used to prolong the duration of action of drugs included in the preparation. Another indication of nanotechnology is the development of nanocapacitor device or patches. Although, data obtained with the use of nanocapacitors are still limited, evidence suggests that the use of nanocapacitors devices/patches may be interesting for the treatment of both acute and chronic pain, since the studies conducted with the NeuroCuple™ device and the based Kailo™ pain relief patch were not placebo-controlled, it is clear that additional placebo studies are required to confirm these preliminary results. Therefore, the development of a placebo devices/patches is necessary. Conclusions: Increasing evidence supports the concept that nanotechnology may represent a valuable tool as a drug transporter including liposomes and as a nanocapacitor-based device/patch to reduce or even eliminate the use of opioids in surgical patients. However, more studies are required to confirm this concept, especially with the use of nanotechnology incorporated in devices/patches. Full article

Although cardiopulmonary resuscitation (CPR) includes lifesaving maneuvers, it might be associated with a wide spectrum of iatrogenic injuries. Among these, acute lung injury (ALI) is frequent and yields significant challenges to post-cardiac arrest recovery. Understanding the relationship between CPR and ALI is determinant for refining resuscitation techniques and improving patient outcomes. This review aims to analyze the existing literature on ALI following CPR, emphasizing prevalence, clinical implications, and contributing factors. The review seeks to elucidate the pathogenesis of ALI in the context of CPR, assess the efficacy of CPR techniques and ventilation strategies, and explore their impact on post-cardiac arrest outcomes. CPR-related injuries, ranging from skeletal fractures to severe internal organ damage, underscore the complexity of managing post-cardiac arrest patients. Chest compression, particularly when prolonged and vigorous, i.e., mechanical compression, appears to be a crucial factor contributing to ALI, with the concept of cardiopulmonary resuscitation-associated lung edema (CRALE) gaining prominence. Ventilation strategies during CPR and post-cardiac arrest syndrome also play pivotal roles in ALI development. The recognition of CPR-related lung injuries, especially CRALE and ALI, highlights the need for research on optimizing CPR techniques and tailoring ventilation strategies during and after resuscitation. Full article

Acute kidney injury (AKI) is a complex and life-threatening condition with multifactorial etiologies, ranging from ischemic injury to nephrotoxic exposures. Management is founded on treating the underlying cause of AKI, but supportive care—via fluid management, vasopressor therapy, kidney replacement therapy (KRT), and more—is also crucial. Blood pressure targets are often higher in AKI, and these can be achieved with fluids and vasopressors, some of which may be more kidney-protective than others. Initiation of KRT is controversial, and studies have not consistently demonstrated any benefit to early start dialysis. There are no targeted pharmacotherapies for AKI itself, but some do exist for complications of AKI; additionally, medications become a key aspect of AKI management because changes in renal function and dialysis support can lead to issues with both toxicities and underdosing. This review will cover existing literature on these and other aspects of AKI treatment. Additionally, this review aims to identify gaps and challenges and to offer recommendations for future research and clinical practice. Full article

Acute coronary syndrome (ACS) remains a major challenge in clinical practice, requiring rapid and effective antithrombotic treatment to mitigate adverse ischemic events while minimizing the risk of bleeding. In recent years, results from several clinical trials addressing this issue through various approaches have substantially improved the treatment landscape for patients presenting with ACS. The emergence of new, potent P2Y₁₂ inhibitors has significantly enhanced thrombotic risk reduction and different strategies for de-escalating and shortening dual antiplatelet therapy (DAPT) have demonstrated promising outcomes in reducing bleeding rates. Furthermore, data from ongoing trials focusing on novel therapeutic agents and investigating alternative treatment strategies to optimize outcomes for ACS patients are expected in the next few years. In this review, we summarize the current knowledge and emphasize the critical role of individualized treatment approaches tailored to patient-specific risk factors and individual clinical scenarios. Full article

Background: We aimed to determine whether patients with postural orthostatic tachycardia syndrome (POTS) have sexual dysfunction compared to age-matched healthy controls. Methods: Utilizing online COMPASS-31 to evaluate dysautonomia symptom severity, Beck’s Depression Inventory Second Edition (BDII), Female Sexual Function (FSF), and International Index of Erection Function (IIEF) questionnaires, we compared sexual function scores in patients with POTS to scores obtained from sex- and age-matched healthy controls via a cross-sectional case–control study. Results: A total of 160 women with POTS, mean age 30.2 ± 7.9 (range 21–50 years), had lower FSF scores than 62 healthy age-matched female controls. IIEF scores in 29 male patients with POTS with a mean age of 30.1 ± 6.0 (range 21–47) were significantly lower than in 27 healthy age-matched male controls. Female POTS patients had significantly lower scores in the sub-domains of desire, arousal, and satisfaction, while male POTS patients had significantly lower scores in erectile and orgasmic function, desire, and satisfaction than healthy controls. Predictive factors of sexual dysfunction were depression in women and age in men. The severity of autonomic symptoms correlated with sexual dysfunction in women, but this effect disappeared after controlling for depression. Conclusions: Compared to healthy controls, women and men with POTS have significant sexual dysfunction, which needs to be considered in the diagnostic and therapeutic approaches as part of comprehensive patient care. Full article

The number of people suffering from diabetes, including type 1, is constantly increasing both in Poland and worldwide. Type 1 diabetes is a chronic disease characterized by uncertain prognosis and relapses, as well as permanent, irreversible, and progressive changes in health status. The ongoing disease results in dysfunction or disability, and the patient requires specialized supervision, care, and rehabilitation. However, the success of therapy does not depend solely on the perfection of treatment, but also on the patient’s readiness to change their lifestyle and cooperate with the therapeutic team. The patient’s constant alertness in making therapeutic decisions does not always lead to expected treatment results, and the risk of hypoglycemia associated with intensive insulin treatment depletes the patient’s motivation for treatment, leading over time to the development of ‘therapeutic burnout’ and psychiatric disorders. This narrative review is an attempt to summarize the knowledge and possible future solutions in diabetes type 1 in Poland as well as highlight the importance of comprehensive care, including psychological care, which appears fundamental in a chronic disease such as type 1 diabetes. Therefore, the aim of the study was to present generational changes and psychosocial problems of patients with type 1 diabetes and to identify urgent challenges in diabetic care. Attention should be paid to the deteriorating mental condition of the young generations, who, in the course of diabetes, are exposed to additional psychological and psychiatric health problems. The next generation of patients will require more psychological care, which is why the challenge of the future is to create psychodiabetology centers. Full article

Background: Impaired glucose regulation is suggested to be related to chronic low back pain (CLBP), although it is not clear how they interact with each other. Thus, the primary aim of this study was to investigate differences in postprandial glycemic responses (PPGRs) (the first sign of impaired glucose metabolism) to high- (sucrose) and low-glycemic index (GI) (isomaltulose) beverages in normoglycemic women with CLBP and healthy controls (HCs) and explore whether any group that showed greater PPGRs to high-GI beverage intake would benefit when the high-GI beverage was replaced with a low-GI beverage. Secondly, this study aimed to explore the association between PPGR and pain in patients with CLBP. Methods: This study was registered at clinicaltrials.org (NCT04459104) before the start of the study. In this study, 53 CLBP patients and 53 HCs were recruited. After 11–12 h of fasting, each participant randomly received isomaltulose or sucrose. Blood glucose levels were measured during the fasting state and 15, 30, 45, 60, 90, and 120 min after the beverage intake, and each participant underwent experimental pain measures. Results: Compared to the HCs, the CLBP group showed significantly higher PPGRs to sucrose (p < 0.021). Additionally, the CLBP group showed a significantly higher decrease in PPGR (p = 0.045) when comparing PPGR to sucrose with PPGR to isomaltulose. Correlation analysis revealed a positive association between self-reported pain sensitivity and PPGR to sucrose, while there was no association found between any experimental pain measures and glycemic responses. Conclusions: Overall, these findings suggest that normoglycemic CLBP patients might have a higher risk of developing impaired glucose tolerance than the HCs and might benefit more when high-GI foods are replaced with low-GI ones. Full article

Achieving guideline-recommended low-density lipoprotein cholesterol (LDL-C) targets remains a significant challenge in clinical practice. This review assesses the barriers to reaching LDL-C goals and explores the potential solutions to these issues. When aiming for the recommended LDL-C goal, strategies like “lower is better” and “strike early and strong” should be used. The evidence supports the safety and efficacy of intensive lipid-lowering therapy post-acute coronary syndrome (ACS), leading to improved long-term cardiovascular health and atherosclerotic plaque stabilization. Despite the availability of effective lipid-lowering therapies, such as high-intensity statins, ezetimibe, the combination of both, bempedoic acid, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a substantial proportion of patients do not meet their LDL-C targets. Contributing factors include systemic healthcare barriers, healthcare provider inertia, patient non-adherence, and statin intolerance. Statin intolerance, often rather statin reluctance, is a notable obstacle due to perceived or expected side effects, which can lead to discontinuation of therapy. In conclusion, while there are obstacles to achieving optimal LDL-C levels post-ACS, these can be overcome with a combination of patient-centric approaches, clinical vigilance, and the judicious use of available therapies. The safety and necessity of reaching lower LDL-C goals to improve outcomes in patients post-ACS are well-supported by current evidence. Full article

Background: Pulmonary hypertension (PH) patients are at higher risk of postoperative complications. We analyzed the association of PH with 30-day postoperative pulmonary complications (PPCs). Methods: A single-center propensity score overlap weighting (OW) retrospective cohort study was conducted on 164 patients with a mean pulmonary artery pressure (mPAP) of >20 mmHg within 24 months of undergoing elective inpatient abdominal surgery or endoscopic procedures under general anesthesia and a control cohort (N = 1981). The primary outcome was PPCs, and the secondary outcomes were PPC sub-composites, namely respiratory failure (RF), pneumonia (PNA), aspiration pneumonia/pneumonitis (ASP), pulmonary embolism (PE), length of stay (LOS), and 30-day mortality. Results: PPCs were higher in the PH cohort (29.9% vs. 11.2%, p < 0.001). When sub-composites were analyzed, higher rates of RF (19.3% vs. 6.6%, p < 0.001) and PNA (11.2% vs. 5.7%, p = 0.01) were observed. After OW, PH was still associated with greater PPCs (RR 1.66, 95% CI (1.05–2.71), p = 0.036) and increased LOS (median 8.0 days vs. 4.9 days) but not 30-day mortality. Sub-cohort analysis showed no difference in PPCs between pre- and post-capillary PH patients. Conclusions: After covariate balancing, PH was associated with a higher risk for PPCs and prolonged LOS. This elevated PPC risk should be considered during preoperative risk assessment. Full article

Background: Lung resection using video-assisted thoracoscopic surgery (VATS) improves surgical accuracy and postoperative recovery. Unfortunately, moderate-to-severe acute postoperative pain is still inherent to the procedure, and a technique of choice has not been established for the appropriate control of pain. In this study, we aimed to compare the efficacy and safety of intrathecal morphine (ITM) with that of intercostal levobupivacaine (ICL). Methods: We conducted a single-center, prospective, randomized, observer-blinded, controlled trial among 181 adult patients undergoing VATS (ISRCTN12771155). Participants were randomized to receive ITM or ICL. Primary outcomes were the intensity of pain, assessed by a numeric rating scale (NRS) over the first 48 h after surgery, and the amount of intravenous morphine used. Secondary outcomes included the incidence of adverse effects, length of hospital stay, mortality, and chronic post-surgical pain at 6 and 12 months after surgery. Results: There are no statistically significant differences between ITM and ICL groups in pain intensity and evolution at rest. In cough-related pain, differences in pain trajectories over time are observed. Upon admission to the PACU, cough-related pain was higher in the ITM group, but the trend reversed after 6 h. There are no significant differences in adverse effects. The rate of chronic pain was low and did not differ significantly between groups. Conclusions: ITM can be considered an adequate and satisfactory regional technique for the control of acute postoperative pain in VATS, compatible with the multimodal rehabilitation and early discharge protocols used in these types of surgeries. Full article

Background: Proton pump inhibitors (PPIs) are commonly prescribed long-acting drugs used to treat acid reflux, gastroesophageal reflux disease (GERD), and peptic ulcers. Recently, concerns have been raised about their safety, particularly due to the association between long-term PPI use and cancer development. Multiple comprehensive studies have consistently suggested a noteworthy link between prolonged PPI usage and an increased risk of developing gastric, esophageal, colorectal, and pancreatic cancers, yet the precise underlying mechanism remains elusive. Methods: First, we review the extensive body of research that investigates the intricate relationship between cancer and PPIs. Then, we predict PPI toxicity using the prodrug structures with the ProTox-II webserver. Finally, we predict the relative risk of cancer for each PPI, using PubMed citation counts of each drug and keywords related to cancer. Results: Our review indicates that prolonged PPI use (exceeding three months) is significantly associated with an elevated risk of cancer, while shorter-term usage (less than three months) appears to pose a comparatively lower risk. Our review encompasses various proposed mechanisms, such as pH and microbiome alterations, vitamin and mineral malabsorption, hypergastrinemia, and enterochromaffin-like cell proliferation, while ProTox-II also suggests aryl hydrocarbon receptor binding. Potentially, the PubMed citations count suggests that the PPIs omeprazole and lansoprazole are more associated with cancer than pantoprazole and esomeprazole. In comparison, the H2R blocker, famotidine, is potentially less associated with cancer than PPIs, and may serve as a safer alternative treatment for periods beyond 3 months. Conclusions: Despite the well-established cancer risk associated with PPIs, it is notable that these medications continue to be widely prescribed for periods longer than 3 months. Thus, it is of paramount importance for clinicians and patients to thoughtfully evaluate the potential risks and benefits of long-term PPI usage and explore alternative treatments before making informed decisions regarding their medical management. Full article

Background/Objectives: This study examined the impact of spasticity-related unpleasant sensations (pain, heaviness, stiffness) on various domains of the International Classification of Functioning, Disability, and Health (ICF) and psychosocial well-being in individuals affected by stroke or traumatic brain injury (TBI). The primary aim is to explore how these sensations affect daily activities, participation, and overall quality of life, guided by the comprehensive framework of the ICF. Methods: Utilizing a secondary analysis of data from a cohort undergoing Botulinum toxin type-A treatment for spasticity post-stroke or TBI, we developed and administered an ad-hoc questionnaire focusing on ICF domains such as body function, activities and participation, and psychosocial aspects such as mood, relationship, social life, motivation, and sleep quality. Spearman rho correlation was applied to assess the relationship between unpleasant sensations and functional as well as psychosocial outcomes among 151 participants. Results: This study identified significant correlations between the severity of unpleasant sensations and limitations in daily functioning, particularly in activities of daily living and mobility. Furthermore, an impactful association was identified between increased unpleasant sensations and deterioration in psychosocial well-being, notably in mood and sleep quality. Conclusions: These findings advocate for a person-centered approach in spasticity management, emphasizing the integration of sensory impairment strategies into rehabilitation to enhance functional outcomes and quality of life. Such an approach aims to improve functional outcomes and enhance the quality of life for individuals experiencing spasticity post-stroke or TBI. Future directions include targeted interventions to alleviate these sensations, support better rehabilitation results and improve patient experiences. Full article

Background: The prevalence of neurological disorders is increasing worldwide. In recent decades, the conventional rehabilitation for people with neurological disorders has been often reinforced with the use of technological devices (robots and virtual reality). The aim of this systematic review was to identify the evidence on the economic cost of rehabilitation with robotic and virtual reality devices for people with neurological disorders through a review of the scientific publications over the last 15 years. Methods: A systematic review was conducted on partial economic evaluations (cost description, cost analysis, description of costs and results) and complete (cost minimization, cost-effectiveness, cost utility and cost benefit) studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The main data sources used were PubMed, Scopus and Web of Science (WOS). Studies published in English over the last 15 years were considered for inclusion in this review, regardless of the type of neurological disorder. The critical appraisal instrument from the Joanna Briggs Institute for economic evaluation and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) were used to analyse the methodological quality of all the included papers. Results: A total of 15 studies were included in this review. Ten papers were focused on robotics and five on virtual reality. Most of the studies were focused on people who experienced a stroke. The robotic device most frequently used in the papers included was InMotion^® (Bionik Co., Watertown, MA, USA), and for those focused on virtual reality, all papers included used semi-immersive virtual reality systems, with commercial video game consoles (Nintendo Wii^® (Nintendo Co., Ltd., Kyoto, Japan) and Kinect^® (Microsoft Inc., Redmond, WA, USA)) being used the most. The included studies mainly presented cost minimization outcomes and a general description of costs per intervention, and there were disparities in terms of population, setting, device, protocol and the economic cost outcomes evaluated. Overall, the methodological quality of the included studies was of a moderate level. Conclusions: There is controversy about using robotics in people with neurological disorders in a rehabilitation context in terms of cost minimization, cost-effectiveness, cost utility and cost benefits. Semi-immersive virtual reality devices could involve savings (mainly derived from the low prices of the systems analysed and transportation services if they are applied through telerehabilitation programmes) compared to in-clinic interventions. Full article

Background: The management of spinal deformities diagnosed before the age of 10 is critical due to the child’s development, skeletal system, and growth mechanism. Magnetically controlled growing rods (MCGRs) are a surgical treatment option for the growing spine. The aim of this study was to analyze the radiological findings of patients treated with MCGRs for early-onset scoliosis (EOS) of various etiologies. We hypothesized that the MCGRs could provide acceptable long-term radiographic results, such as an increase in the T1–T12 and T1–S1 height and significant overall deformity correction. Methods: We retrospectively reviewed 161 EOS patients with a combined total of 302 MCGRs inserted at five institutions between 2016 and 2022 with a mean follow-up of at least two years. The Cobb angle of the major curve (MC), thoracic kyphosis (TK), lumbar lordosis (LL), and T1–T12 and T1–S1 height measurements were assessed before, after, and during the follow-up. Results: Among the 90 female and 71 male patients, there were 51 neurological, 42 syndromic, 58 idiopathic, and ten congenital scoliosis etiologies. Of the patients, 73 were aged under six years old. The mean follow-up time was 32.8 months. The mean age at placement of the MCGRs was 7 years and that at the last follow-up after fusion surgery was 14.5 years. The mean MC before the initial surgery was 86.2°; following rod implantation, it was 46.9°, and at the last follow-up visit, it was 45.8°. The mean correction rate among the etiology subgroups was from 43% to 50% at follow-up. The mean TK was noted as 47.2° before MCGR implantation, 47.1° after MCGR placement, and 44.5° at the last follow-up visit. The mean T1–T12 height increased by 5.95 mm per year, with a mean T1–S1 height of 10.1 mm per year. Conclusions: MCGR treatment allowed for an average correction of the curvature by 50% during the period of lengthening, while controlling any deformity and growth of the spine, with a significant increase in the T1–T12 and T1–S1 values during the observation period. MCGR treatment in EOS carries a risk of complications. While congenital and syndromic EOS often have short and less flexible curves in those groups of patients, single rods can be as effective and safe. Definitive fusion results in the mean final coronal correction between the start of MCGR treatment and after undergoing PSF of approximately 70%. The mean T1–T12 spinal height increased by 75 mm, while the T1–S1 spinal height gained a mean of 97 mm. Full article

Background: Portal vein thrombosis (PVT) is a rare disease with an estimated incidence of 2 to 4 cases per 100,000 inhabitants. The most common predisposing conditions for PVT are chronic liver diseases (cirrhosis), primary or secondary hepatobiliary malignancy, major infectious or inflammatory abdominal disease, or myeloproliferative disorders. Methods: PVT can be classified on the basis of the anatomical site, the degree of venous occlusion, and the timing and type of presentation. The main differential diagnosis of PVT, both acute and chronic, is malignant portal vein invasion, most frequently by hepatocarcinoma, or constriction (typically by pancreatic cancer or cholangiocarcinoma). Results: The management of PVT is based on anticoagulation and the treatment of predisposing conditions. The aim of anticoagulation in acute thrombosis is to prevent the extension of the clot and enable the recanalization of the vein to avoid the development of complications, such as intestinal infarction and portal hypertension. Conclusions: The treatment with anticoagulant therapy favors the reduction of portal hypertension, and this allows for a decrease in the risk of bleeding, especially in patients with esophageal varices. The anticoagulant treatment is generally recommended for at least three to six months. Prosecution of anticoagulation is advised until recanalization or lifelong if the patient has an underlying permanent pro-coagulant condition that cannot be corrected or if there is thrombosis extending to the mesenteric veins. Full article

Background: The probability of spontaneous conversion (SCV) to sinus rhythm (SR) in patients presenting to the emergency department (ED) with hemodynamically stable, symptomatic atrial fibrillation (AF) is not well known. Objective: To develop and validate a score to determine the probability of SCV to SR in patients presenting to the ED with hemodynamically stable, symptomatic AF. Methods: This retrospective, observational study enrolled consecutive patients admitted with AF to the ED. Variables associated to SCV during a 6 h “wait-and-see” approach were used to develop and validate a score to determine the probability of SCV to SR in AF patients. The study was divided in two phases: (1) score development and (2) validation of the predictive score. Results: Out of 748 eligible patients, 446 patients were included in the derivation cohort, whereas 302 patients were included in the validation cohort. In the derivation cohort, based on multivariable logistic analysis, a probability score weight was developed including: previous SCV (3 points), AF-related symptom duration < 24 h (5 points), age ≥ 65 years (3 points) and female sex (2 points). The score allowed us to divide patients in three groups based on the probability of SCV to SR during the 6 h observation period. The probability prediction model showed an area under the curve (AUC) of 0.707 and 0.701 in the derivation and validation cohorts, respectively. Conclusions: The proposed score allowed us to predict SCV probability with good accuracy and may help physicians in tailoring AF management in an effective and timely manner. Full article

Atherosclerosis is a generalized and progressive disease. Ageing is a key risk factor for atherosclerosis progression that is associated with the increased incidence of ischemic events in supplied organs, including stroke, coronary events, limb ischemia, or renal failure. Cardiovascular disease is the leading cause of death and major disability in adults ≥ 75 years of age. Atherosclerotic occlusive disease affects everyday activity and quality of life, and it is associated with reduced life expectancy. Although there is evidence on coronary artery disease management in the elderly, there is insufficient data on the management in older patients presented with atherosclerotic lesions outside the coronary territory. Despite this, trials and observational studies systematically exclude older patients, particularly those with severe comorbidities, physical or cognitive dysfunctions, frailty, or residence in a nursing home. This results in serious critical gaps in knowledge and a lack of guidance on the appropriate medical treatment and referral for endovascular or surgical interventions. Therefore, we attempted to gather data on the prevalence, risk factors, and management strategies in patients with extra-coronary atherosclerotic lesions. Full article

Background: This meta-analysis aims to evaluate the proportion of people with TMDs in different studies, considering factors such as geographical region, patient age, and sample size. Methods: The search yielded 6984 articles on the incidence of TMDs. Finally, 74 studies with 172,239 subjects and 35,259 with TMDs were selected for final analysis. Analyses were performed using the R statistical language. Results: The incidence of TMDs in the world population was 34%. The age group 18–60 years is the most exposed to TMDs. From the data presented, we observed that for each continent, the female group was 9% to 56% larger than the male group. The highest female-to-male ratio (F:M) was reported in South America (1.56), whereas the lowest F:M ratio was reported in Europe (1.09), suggesting an almost equal distribution of males and females. Conclusions: This suggests that geographical location may play a role in the results of the studies. The prevalence of TMDs was significantly higher in South America (47%) compared to Asia (33%) and Europe (29%). Larger epidemiological studies of TMDs in African and Australian populations are recommended. In conclusion, both visual and statistical assessments suggest that the results of our meta-analysis are robust and unlikely to be significantly affected by publication bias. This suggests that geographical location may play a role in the prevalence of TMDs. Full article

Although mitral valve prolapse (MVP) is the most prevalent valvular abnormality in Western countries and generally carries a good prognosis, a small subset of patients is exposed to a significant risk of malignant ventricular arrhythmias (VAs) and sudden cardiac death (SCD), the so-called arrhythmic MVP (AMVP) syndrome. Recent work has emphasized phenotypical risk features of severe AMVP and clarified its pathophysiology. However, the appropriate assessment and risk stratification of patients with suspected AMVP remains a clinical conundrum, with the possibility of both overestimating and underestimating the risk of malignant VAs, with the inappropriate use of advanced imaging and invasive electrophysiology study on one hand, and the catastrophic occurrence of SCD on the other. Furthermore, the sports eligibility assessment of athletes with AMVP remains ill defined, especially in the grey zone of intermediate arrhythmic risk. The definition, epidemiology, pathophysiology, risk stratification, and treatment of AMVP are covered in the present review. Considering recent guidelines and expert consensus statements, we propose a comprehensive pathway to facilitate appropriate counseling concerning the practice of competitive/leisure-time sports, envisioning shared decision making and the multidisciplinary “sports heart team” evaluation of borderline cases. Our final aim is to encourage an active lifestyle without compromising patients’ safety. Full article

(1) Background: Atrial fibrillation (AF) is a major risk factor for stroke and is often underdiagnosed, despite being present in 13–26% of ischemic stroke patients. Recently, a significant number of machine learning (ML)-based models have been proposed for AF prediction and detection for primary and secondary stroke prevention. However, clinical translation of these technological innovations to close the AF care gap has been scant. Herein, we sought to systematically examine studies, employing ML models to predict incident AF in a population without prior AF or to detect paroxysmal AF in stroke cohorts to identify key reasons for the lack of translation into the clinical workflow. We conclude with a set of recommendations to improve the clinical translatability of ML-based models for AF. (2) Methods: MEDLINE, Embase, Web of Science, Clinicaltrials.gov, and ICTRP databases were searched for relevant articles from the inception of the databases up to September 2022 to identify peer-reviewed articles in English that used ML methods to predict incident AF or detect AF after stroke and reported adequate performance metrics. The search yielded 2815 articles, of which 16 studies using ML models to predict incident AF and three studies focusing on ML models to detect AF post-stroke were included. (3) Conclusions: This study highlights that (1) many models utilized only a limited subset of variables available from patients’ health records; (2) only 37% of models were externally validated, and stratified analysis was often lacking; (3) 0% of models and 53% of datasets were explicitly made available, limiting reproducibility and transparency; and (4) data pre-processing did not include bias mitigation and sufficient details, leading to potential selection bias. Low generalizability, high false alarm rate, and lack of interpretability were identified as additional factors to be addressed before ML models can be widely deployed in the clinical care setting. Given these limitations, our recommendations to improve the uptake of ML models for better AF outcomes include improving generalizability, reducing potential systemic biases, and investing in external validation studies whilst developing a transparent modeling pipeline to ensure reproducibility. Full article

(1) Background: The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) is a tool designed to measure disability in accordance with the International Classification of Functioning, Disability and Health. Measuring disability is becoming increasingly important due to its high prevalence, which continues to rise. Rehabilitation interventions can reduce disability and enhance functioning. (2) Objective: The present study aims to assess the impact of rehabilitation interventions on reducing disability, as measured by the WHODAS 2.0 questionnaire. It also seeks to identify which specific rehabilitation interventions are more effective and to explore other disability assessment questionnaires. (3) Methods: Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology, we conducted a systematic review, with the protocol registered with the identifier CRD42023495309, focused on “WHODAS” and “rehabilitation” using PubMed and Web of Science electronic databases. (4) Results: We identified 18 articles from various regions encompassing patients with various health conditions, related to stroke, the cardiovascular system (cardiovascular disease, chronic heart failure), the pulmonary system (chronic obstructive pulmonary disease), the neurologic system (Parkinson’s disease, cerebral palsy, neurodegenerative disease), the musculoskeletal system (orthopaedic surgery), cancer, and chronic pain, and among frail elderly. These patients have received a wide range of rehabilitation interventions: from conventional therapy to virtual reality, robot-assisted arm training, exergaming, and telerehabilitation. (5) Discussion and Conclusions: A wide range of rehabilitation techniques can effectively improve disability with various comorbidities, offering numerous benefits. The WHODAS 2.0 questionnaire proves to be an efficient and reliable tool for measuring disability, and scores have a tendency to decrease after rehabilitation. Full article

Anti-amyloid immunotherapies have recently emerged as treatments for Alzheimer’s disease. While these therapies have demonstrated efficacy in clearing amyloid-β and slowing cognitive decline, they have also been associated with amyloid-related imaging abnormalities (ARIA) which include both edema (ARIA-E) and hemorrhage (ARIA-H). Given that ARIA have been associated with significant morbidity in cases of antithrombotic or thrombolytic therapy, an understanding of mechanisms of and risk factors for ARIA is of critical importance for stroke care. We discuss the latest data regarding mechanisms of ARIA, including the role of underlying cerebral amyloid angiopathy, and implications for ischemic stroke prevention and management. Full article

(1) Background: Spatial cognition (SC) is one of the earliest cognitive domains to be impaired in the course of Alzheimer’s disease (AD), resulting in spatial disorientation and becoming lost even in familiar surroundings as later dementia symptoms. To date, few studies have identified initial alterations of spatial navigation (SN) in the premorbid AD phase by real-world paradigms, and none have adopted an innovative technological apparatus to better detect gait alterations as well as physiological aspects correlated to spatial disorientation (SD). The present study aimed at exploring initial SN defects in patients with prodromal AD via a naturalistic task by using a sensory garment. (2) Methods: 20 community-dwelling patients with Mild Cognitive Impairment (MCI) due to AD and 20 age/education controls were assessed on their sequential egocentric and allocentric navigation abilities by using a modified version of the Detour Navigation Test (DNT-mv). (3) Results: When compared to controls, patients with MCI due to AD exhibited higher wrong turns (WT) and moments of hesitation (MsH) in the DNT-mv, reflecting difficulties both in sequential egocentric and allocentric navigation, depending on hippocampal deterioration. Moreover, they reported more complaints about their SN competencies and lower long-term visuospatial memory abilities than controls. Remarkably, WTs and MsH manifested in the allocentric naturalistic task of the DNT-mv were associated with autonomic nervous system alteration pertaining to cardiac functioning in the whole sample. (4) Conclusions: Naturalistic navigation tests of hippocampal function using a continuous non-invasive monitoring device can provide early markers of spatial disorientation in patients with MCI due to AD. Future studies should develop cognitive remediation techniques able to enhance SC residual abilities in patients at high risk of conversion into dementia and ecological paradigms to be replicated on a large scale. Full article

Background: In Italy, data on long-term survivors after liver transplantation are lacking. Materials and Methods: We conducted a hybrid design study on a cohort of 359 adult recipients who received transplants between 1996 and 2002 to identify predictors of survival and the prevalence of co-morbidities among long-term survivors. Results: The actuarial (95% CI) patient survival was 96% (94.6–98.3%), 69% (64.2–73.6%), 55% (49.8–59.9%), 42.8% (37.6–47.8%), and 34% (29.2–38.9%) at 1, 5, 10, 15, and 20 years, respectively. The leading causes of death were hepatitis C virus recurrence (24.6%), extrahepatic malignancies (16.9%), infection (14.4%), and hepatocellular carcinoma recurrence (14.4%). The factors associated with the survival probability were younger donor and recipient ages (p = 0.001 and 0.004, respectively), female recipient sex (p < 0.001), absence of HCV (p < 0.01), absence of HCC (p = 0.001), and absence of diabetes mellitus at one year (p < 0.01). At the latest follow-up, the leading comorbidities were hypertension (53.6%), obesity (18.7%), diabetes mellitus (17.1%), hyperlipidemia (14.7%), chronic kidney dysfunction (14.7%), and extrahepatic malignancies (13.8%), with 73.9% of patients having more than one complication. Conclusions: Aging with a liver graft is associated with an increased risk of complications and requires ongoing care to reduce the long-term attrition rate resulting from chronic immunosuppression. Full article

(1) Background: Spinal cord injury (SCI) represents a major health challenge, often leading to significant and permanent sensorimotor and autonomic dysfunctions. This study reviews the evolving role of epidural spinal cord stimulation (eSCS) in treating chronic SCI, focusing on its efficacy and safety. The objective was to analyze how eSCS contributes to the recovery of neurological functions in SCI patients. (2) Methods: We utilized the PRISMA guidelines and performed a comprehensive search across MEDLINE/PubMed, Embase, Web of Science, and IEEE Xplore databases up until September 2023. We identified studies relevant to eSCS in SCI and extracted assessments of locomotor, cardiovascular, pulmonary, and genitourinary functions. (3) Results: A total of 64 studies encompassing 306 patients were identified. Studies investigated various stimulation devices, parameters, and rehabilitation methods. Results indicated significant improvements in motor function: 44% of patients achieved assisted or independent stepping or standing; 87% showed enhanced muscle activity; 65% experienced faster walking speeds; and 80% improved in overground walking. Additionally, eSCS led to better autonomic function, evidenced by improvements in bladder and sexual functions, airway pressures, and bowel movements. Notable adverse effects included device migration, infections, and post-implant autonomic dysreflexia, although these were infrequent. (4) Conclusion: Epidural spinal cord stimulation is emerging as an effective and generally safe treatment for chronic SCI, particularly when combined with intensive physical rehabilitation. Future research on standardized stimulation parameters and well-defined therapy regimens will optimize benefits for specific patient populations. Full article

Background: To investigate the prevalence of sleep disorders in patients with multiple sclerosis (PwMS) in comparison to healthy controls (HCs), we aim to explore the correlation between sleep disorders and fatigue, bladder dysfunction, mood disorders in PwMS. Methods: This study involved 175 PwMS and 115 HCs. We conducted a self-administered survey using questionnaires (the authors’ questionnaire, the Athens Insomnia Scale (AIS), the Epworth Sleepiness Scale (ESS), the Modified Fatigue Impact Scale (MFIS), the Fatigue Severity Scale (FSS), the Hospital Anxiety and Depression Scale (HADS), and the Numerical Rating Scale (NRS). The neurological disability was determined using Expanded Disability Status Scale. Logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Results: According to AIS, insomnia was found in 20.6% of PwMS compared to 9.6% of HCs (p < 0.001). Comparing female and male PwMS, we observed that insomnia was more prevalent among female PwMS (25.95% vs. 4.55%, respectively, p < 0.05). Excessive daytime sleepiness was more prevalent in female PwMS (p < 0.05). Female PwMS were more fatigue based on the FSS and the MFIS (p < 0.05). Bladder disorders were observed in 39.43% of PwMS and were significantly linked to MS (p < 0.001). Sleep disturbances were associated with anxiety disorders (OR = 0.22, 95% CI 0.12–0.32 p < 0.001), bladder dysfunction (OR = 0.52 95% CI 0.16–0.87 p < 0.05), and female gender (OR = 0.49, 95% CI 0.037–0.94 p < 0.05). Conclusions: Insomnia is prevalent among PwMS. Our study revealed independent predictors of sleep disturbances among PwMS: female gender, bladder disorders, and anxiety. Full article

Bone strength is determined not only by bone quantity [bone mineral density (BMD)] but also by bone quality, including matrix composition, collagen fiber arrangement, microarchitecture, geometry, mineralization, and bone turnover, among others. These aspects influence elasticity, the load-bearing and repair capacity of bone, and microcrack propagation and are thus key to fractures and their avoidance. In chronic kidney disease (CKD)-associated osteoporosis, factors traditionally associated with a lower bone mass (advanced age or hypogonadism) often coexist with non-traditional factors specific to CKD (uremic toxins or renal osteodystrophy, among others), which will have an impact on bone quality. The gold standard for measuring BMD is dual-energy X-ray absorptiometry, which is widely accepted in the general population and is also capable of predicting fracture risk in CKD. Nevertheless, a significant number of fractures occur in the absence of densitometric World Health Organization (WHO) criteria for osteoporosis, suggesting that methods that also evaluate bone quality need to be considered in order to achieve a comprehensive assessment of fracture risk. The techniques for measuring bone quality are limited by their high cost or invasive nature, which has prevented their implementation in clinical practice. A bone biopsy, high-resolution peripheral quantitative computed tomography, and impact microindentation are some of the methods established to assess bone quality. Herein, we review the current evidence in the literature with the aim of exploring the factors that affect both bone quality and bone quantity in CKD and describing available techniques to assess them. Full article

Background: Early-stage tongue cancer has a good prognosis in general; however, high-risk patients with late cervical lymph node and distant metastases have a poor prognosis. Elective neck dissection and postoperative chemoradiotherapy are considered for these patients, although no clear criteria have been identified for their evaluation. Methods: This retrospective observational study aimed to determine the predictive factors for late cervical lymph node and distant metastases in 102 patients with cT1-2N0 tongue cancer. The data regarding the demographic characteristics, as well as the depth of invasion, tumor budding, histological grade, and tumor–stromal ratio, among other things, were extracted from medical records. Results: We found that the potential lymph node metastasis rate was 27.5%. The significant clinical predictors of late cervical lymph node metastasis were the tumor thickness and endophytic growth pattern and the significant histopathological factors were poorly and moderately differentiated tumors and ≥3 tumor buds. In addition, the prognostic factors for distant metastasis included ≥4 lymph node metastases, ≥7 tumor budding, and moderate and poor tumor differentiation. Conclusions: The usefulness of tumor budding as a predictor of metastasis for tongue cancer was suggested. The findings of this study can help establish the criteria for evaluating the metastasis risk and prognosis of patients with tongue cancers. Full article

Acute pancreatitis (AP) is a leading gastrointestinal disease that causes hospitalization. Initial management in the first 72 h after the diagnosis of AP is pivotal, which can influence the clinical outcomes of the disease. Initial management, including assessment of disease severity, fluid resuscitation, pain control, nutritional support, antibiotic use, and endoscopic retrograde cholangiopancreatography (ERCP) in gallstone pancreatitis, plays a fundamental role in AP treatment. Recent updates for fluid resuscitation, including treatment goals, the type, rate, volume, and duration, have triggered a paradigm shift from aggressive hydration with normal saline to goal-directed and non-aggressive hydration with lactated Ringer’s solution. Evidence of the clinical benefit of early enteral feeding is becoming definitive. The routine use of prophylactic antibiotics is generally limited, and the procalcitonin-based algorithm of antibiotic use has recently been investigated to distinguish between inflammation and infection in patients with AP. Although urgent ERCP (within 24 h) should be performed for patients with gallstone pancreatitis and cholangitis, urgent ERCP is not indicated in patients without cholangitis. The management approach for patients with local complications of AP, particularly those with infected necrotizing pancreatitis, is discussed in detail, including indications, timing, anatomical considerations, and selection of intervention methods. Furthermore, convalescent treatment, including cholecystectomy in gallstone pancreatitis, lipid-lowering medications in hypertriglyceridemia-induced AP, and alcohol intervention in alcoholic pancreatitis, is also important for improving the prognosis and preventing recurrence in patients with AP. This review focuses on recent updates on the initial and convalescent management strategies for AP. Full article

This review addresses the complexities of type 1 diabetes (T1D) and its associated complications, with a particular focus on diabetic retinopathy (DR). This review outlines the progression from non-proliferative to proliferative diabetic retinopathy and diabetic macular edema, highlighting the role of dysglycemia in the pathogenesis of these conditions. A significant portion of this review is devoted to technological advances in diabetes management, particularly the use of hybrid closed-loop systems (HCLSs) and to the potential of open-source HCLSs, which could be easily adapted to different patients’ needs using big data analytics and machine learning. Personalized HCLS algorithms that integrate factors such as patient lifestyle, dietary habits, and hormonal variations are highlighted as critical to reducing the incidence of diabetes-related complications and improving patient outcomes. Full article

Uterus transplantation (UTx) is currently the only available treatment for absolute uterine factor infertility. More than 90 uterus transplantations have been performed worldwide, mostly from living donors. Living-donor (LD) UTx is a challenging surgical procedure since it poses ethical issues, and it is a high-risk and invasive surgery with higher hysterectomy-related risks compared to conventional hysterectomy. A total of 59 living-donor hysterectomies have been reported in the literature, including 35 performed with a laparotomic approach, 20 with a robotic approach and 4 with a laparoscopic approach. The mean donor age was 45.6 ± 9.1 years, and 22 were unrelated with the recipients, 34 were emotionally related (27 mothers, 5 sisters, 2 mother’s sisters). The mean recipient age was 28.8 ± 4.5 years. Mayer–Rokitansky–Küster–Hauser syndrome was the most common indication for uterus transplant. Robotic living-donor hysterectomy had the longest operative time but resulted in a lower blood loss and postoperative stay compared to laparotomic and laparoscopic approaches. Twenty-nine births from LD-UTx have been reported, four after robotic living-donor hysterectomy and twenty-five after a laparotomic procedure. UTx is now an effective treatment for women with UFI. While living-donor UTx in some cases may be considered an experimental procedure, it offers the extraordinary possibility to give women the opportunity to have a pregnancy. Many efforts should be made to reduce the potential risks for donors, including the use of mini-invasive techniques, and the efficacy of UTx in the recipients, giving the potential harm of immunosuppression in a recipient of a non-life-saving organ. Full article

Lipoprotein(Lp)(a) is a variant of low-density lipoprotein (LDL), bound to apolipoprotein B100, whose levels are associated with a significant increase in the risk of atherosclerosis-related cardiovascular events, but also to aortic stenosis and atrial fibrillation. Since plasma levels of Lp(a) are commonly considered resistant to lifestyle changes, we critically reviewed the available evidence on the effect of weight loss, dietary supplements, and physical activity on this risk factor. In our review, we observed that relevant body weight loss, a relatively high intake of saturated fatty acids, the consumption of red wine, and intense physical exercise seems to be associated with significantly lower plasma Lp(a) levels. On the contrary, foods rich in trans-unsaturated fatty acids are associated with increased Lp(a) levels. With regard to dietary supplements, coenzyme Q10, L-Carnitine, and flaxseed exert a mild but significant lowering effect on plasma Lp(a). Full article

Syncope is a highly prevalent clinical condition characterized by a rapid, complete, and brief loss of consciousness, followed by full recovery caused by cerebral hypoperfusion. This symptom carries significance, as its potential underlying causes may involve the heart, blood pressure, or brain, leading to a spectrum of consequences, from sudden death to compromised quality of life. Various factors contribute to syncope, and adhering to a precise diagnostic pathway can enhance diagnostic accuracy and treatment effectiveness. A standardized initial assessment, risk stratification, and appropriate test identification facilitate determining the underlying cause in the majority of cases. New technologies, including artificial intelligence and smart devices, may have the potential to reshape syncope management into a proactive, personalized, and data-centric model, ultimately enhancing patient outcomes and quality of life. This review addresses key aspects of syncope management, including pathogenesis, current diagnostic testing options, treatments, and considerations in the geriatric population. Full article

Spinal injuries, including cervical and thoracolumbar fractures, continue to be a major public health concern. Recent advancements in machine learning and deep learning technologies offer exciting prospects for improving both diagnostic and prognostic approaches in spinal injury care. This narrative review systematically explores the practical utility of these computational methods, with a focus on their application in imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI), as well as in structured clinical data. Of the 39 studies included, 34 were focused on diagnostic applications, chiefly using deep learning to carry out tasks like vertebral fracture identification, differentiation between benign and malignant fractures, and AO fracture classification. The remaining five were prognostic, using machine learning to analyze parameters for predicting outcomes such as vertebral collapse and future fracture risk. This review highlights the potential benefit of machine learning and deep learning in spinal injury care, especially their roles in enhancing diagnostic capabilities, detailed fracture characterization, risk assessments, and individualized treatment planning. Full article

Introduction: Interest in 3D printing for orthopedic surgery has been increasing since its progressive adoption in most of the hospitals around the world. The aim of the study is to describe all the current applications of 3D printing in patients undergoing hip surgery of any type at the present time. Materials and Methods: We conducted a systematic narrative review of publications indexed in MedLine through the search engine PubMed, with the following parameters: 3D printing AND (orthopedics OR traumatology) NOT tissue engineering NOT scaffold NOT in vitro and deadline 31 July 2023. After reading the abstracts of the articles, papers were selected according to the following criteria: full text in English or Spanish and content related to hip surgery. Those publications involving experimental studies (in vitro or with anatomical specimens) or 3D printing outside of hospital facilities as well as 3D-printed commercial implants were excluded. Results are presented as a reference guide classified by disease, including the used software and the steps required for the development of the idea. Results: We found a total of 27 indications for in-house 3D printing for hip surgery, which are described in the article. Conclusions: There are many surgical applications of 3D printing in hip surgery, most of them based on CT images. Most of the publications lack evidence, and further randomized studies should be encouraged to assess the advantages of these indications. Full article

Endometriosis has a prevalence of 10% worldwide in premenopausal women. Probably, endometriosis begins early in the life of young girls, and it is commonly diagnosed later in life. The prevalence of deep infiltrating endometriosis (DIE) in adolescence is currently unknown due to diagnostic limits and underestimation of clinical symptoms. Dysmenorrhea is a common symptom in adolescents affected by DIE, often accompanied by dyspareunia and chronic acyclic pelvic pain. Ultrasonography—either performed transabdominal, transvaginal or transrectal—should be considered the first-line imaging technique despite the potential for missed diagnosis due to early-stage disease. Magnetic resonance imaging should be preferred in the case of virgo patients or when ultrasonographic exam is not accepted. Diagnostic laparoscopy is deemed acceptable in the case of suspected DIE not responding to conventional hormonal therapy. An early medical and/or surgical treatment may reduce disease progression with an immediate improvement in quality of life and fertility, but at the same time, painful symptoms may persist or even recur due to the surgery itself. The aim of this narrative review is to report the prevalence of DIE in adolescents, describe the pathogenetic theories and discuss the management in adolescent women, including the challenging road to diagnosis and the treatment alternatives. Full article

Chronic kidney disease (CKD) is a global health problem. In patients with CKD, exercise endurance is decreased, especially as renal dysfunction advances. This is due to the combined effects of protein-energy wasting, uremic acidosis, and inflammatory cachexia, which lead to sarcopenia and are aggravated by a sedentary lifestyle, resulting in a progressive downward spiral of deconditioning. Renal rehabilitation (RR) is a coordinated, multifaceted intervention designed to optimize a patient’s physical, psychological, and social functioning, as well as to stabilize, slow, or even reverse the progression of renal deterioration, improving exercise tolerance and preventing the onset and worsening of heart failure, thereby reducing morbidity and mortality. This review focused on the history and benefits of RR in patients with CKD. Based on current evidence, RR is an effective, feasible, and safe secondary prevention strategy in CKD. RR is a promising model for a new field of rehabilitation. Therefore, efforts to increase RR implementation rates are urgently needed. Full article

The dietary restriction of salt intake and the adhesion to Mediterranean dietary patterns are among the most recommended lifestyle modifications for the prevention of cardiovascular diseases. A large amount of evidence supports these recommendations; indeed, several studies show that a higher adherence to Mediterranean dietary patterns is associated with a reduced risk of cardiovascular disease. Likewise, findings from observational and clinical studies suggest a causal role of excess salt intake in blood pressure increase, cardiovascular organ damage, and the incidence of cardiovascular diseases. In this context, it is also conceivable that the beneficial effects of these two dietary patterns overlap because Mediterranean dietary patterns are typically characterized by a large consumption of plant-based foods with low sodium content. However, there is little data on this issue, and heterogeneous results are available on the relationship between adherence to salt restriction and to Mediterranean dietary patterns. Thus, this short review focuses on the epidemiological and clinical evidence of the relationship between the adherence to Mediterranean dietary patterns and dietary salt restriction in the context of cardiovascular risk. Full article

Endometriosis, a systemic ailment, profoundly affects various aspects of life, often eluding detection for over a decade. This leads to enduring issues such as chronic pain, infertility, emotional strain, and potential organ dysfunction. The prolonged absence of diagnosis can contribute to unexplained obstetric challenges and fertility issues, necessitating costly and emotionally taxing treatments. While biopsy remains the gold standard for diagnosis, emerging noninvasive screening methods are gaining prominence. These tests can indicate endometriosis in cases of unexplained infertility, offering valuable insights to patients and physicians managing both obstetric and non-obstetric conditions. In a retrospective cross-sectional study involving 215 patients aged 25 to 45 with unexplained infertility, diagnostic laparoscopy was performed after unsuccessful reproductive technology attempts. Pathology results revealed tissue abnormalities in 98.6% of patients, with 90.7% showing endometriosis, confirmed by the presence of endometrial-like glands and stroma. The study underscores the potential role of endometriosis in unexplained infertility cases. Although the study acknowledges selection bias, a higher than previously reported prevalence suggests evaluating endometriosis in patients who have not responded to previous reproductive interventions may be justified. Early detection holds significance due to associations with ovarian cancer, prolonged fertility drug use, pregnancy complications, and elevated post-delivery stroke risk. Full article

Background: Neutrophil-to-lymphocyte ratio (NLR), platelets-to-lymphocyte ratio (PLR) and C-reactive protein-to-albumin ratio (CAR) are believed to be potential inflammatory markers that are closely related to the prognosis and course of cardiovascular diseases. The main goal of this study was the evaluation of NLR, PLR and CAR as factors reflecting the clinical picture and the prognosis of elderly chronic heart failure (CHF) patients. Methods: In 150 elderly patients with newly diagnosed CHF, the NLR, PLR and CAR were correlated with cardiac, laboratory and nutritional parameters. Results: Systemic inflammatory ratios were correlated with selected patient’s parameters. CAR was associated with an unfavorable clinical picture of CHF—a reduced EF (p = 0.007), an elevated PASP (p = 0.014), an increased LVESD in both males and females (p = 0.032 and 0.024, respectively) and a decreased TAPSE (p = 0.023). CAR allowed us to distinguish between NYHA I–III and NYHA IV classes with AUC of 0.830. By analyzing the five-year mortality rate in patients with different CAR values, the greater death rate was recorded for patients with high CAR values—one-year death rate (40.3% vs. 17.2%) and five-year death rate (80% vs. 58.3%) (p = 0.002). Both NLR and PLR correlated only with selected parameters. Conclusion: An analysis of inflammatory markers, mainly CAR, allows the management of CHF, because its value can reflect the cardiac and nutritional status of patients with a prognostic value. NLR and PLR can serve as supplementary examinations for CAR evaluation. Full article

Limitations of pharmaceutical drugs and biologics for chronic diseases (e.g., medication non-adherence, adverse effects, toxicity, or inadequate efficacy) can be mitigated by mobile medical apps, known as digital therapeutics (DTx). Authorization of adjunct DTx by the US Food and Drug Administration and draft guidelines on “prescription drug use-related software” illustrate opportunities to create drug + digital combination therapies, ultimately leading towards drug–device combination products (DTx has a status of medical devices). Digital interventions (mobile, web-based, virtual reality, and video game applications) demonstrate clinically meaningful benefits for people living with Alzheimer’s disease, dementia, rheumatoid arthritis, cancer, chronic pain, epilepsy, depression, and anxiety. In the respective animal disease models, preclinical studies on environmental enrichment and other non-pharmacological modalities (physical activity, social interactions, learning, and music) as surrogates for DTx “active ingredients” also show improved outcomes. In this narrative review, we discuss how drug + digital combination therapies can impact translational research, drug discovery and development, generic drug repurposing, and gene therapies. Market-driven incentives to create drug–device combination products are illustrated by Humira^® (adalimumab) facing a “patent-cliff” competition with cheaper and more effective biosimilars seamlessly integrated with DTx. In conclusion, pharma and biotech companies, patients, and healthcare professionals will benefit from accelerating integration of digital interventions with pharmacotherapies. Full article

Cardiac magnetic resonance (CMR) imaging has witnessed substantial progress with the advent of parametric mapping techniques, most notably T1 and T2 mapping. These advanced techniques provide valuable insights into a wide range of cardiac conditions, including ischemic heart disease, cardiomyopathies, inflammatory cardiomyopathies, heart valve disease, and athlete’s heart. Mapping could be the first sign of myocardial injury and oftentimes precedes symptoms, changes in ejection fraction, and irreversible myocardial remodeling. The ability of parametric mapping to offer a quantitative assessment of myocardial tissue properties addresses the limitations of conventional CMR methods, which often rely on qualitative or semiquantitative data. However, challenges persist, especially in terms of standardization and reference value establishment, hindering the wider clinical adoption of parametric mapping. Future developments should prioritize the standardization of techniques to enhance their clinical applicability, ultimately optimizing patient care pathways and outcomes. In this review, we endeavor to provide insights into the potential contributions of CMR mapping techniques in enhancing the diagnostic processes across a range of cardiac conditions. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating, and multi-faceted illness. Heterogenous onset and clinical presentation with additional comorbidities make it difficult to diagnose, characterize, and successfully treat. Current treatment guidelines focus on symptom management, but with no clear target or causative mechanism, remission rates are low, and fewer than 5% of patients return to their pre-morbid activity levels. Therefore, there is an urgent need to undertake robust clinical trials to identify effective treatments. This review synthesizes insights from clinical trials exploring pharmacological interventions and dietary supplements targeting immunological, metabolic, gastrointestinal, neurological, and neuroendocrine dysfunction in ME/CFS patients which require further exploration. Additionally, the trialling of alternative interventions in ME/CFS based on reported efficacy in the treatment of illnesses with overlapping symptomology is also discussed. Finally, we provide important considerations and make recommendations, focusing on outcome measures, to ensure the execution of future high-quality clinical trials to establish clinical efficacy of evidence-based interventions that are needed for adoption in clinical practice. Full article