It is certain and established that overcrowding represents one of the main problems that has been affecting global health and the functioning of the healthcare system in the last decades, and this is especially true for the emergency department (ED). Since 1980, overcrowding has been identified as one of the main factors limiting correct, timely, and efficient hospital care. The more recent COVID-19 pandemic contributed to the accentuation of this phenomenon, which was already well known and of international interest. Considering what would appear to be a trivial definition of overcrowding, it may seem simple for the reader to hypothesize solutions for what seems to be one of the most avoidable problems affecting the hospital system. However, proposing solutions to overcrowding, as well as their implementation, cannot be separated from a correct and precise definition of the issue, which must consider the main causes and aggravating factors. In light of the need of finding solutions that can put an end to hospital overcrowding, this review aims, through a review of the literature, to summarize the triggering factors, as well as the possible solutions that can be proposed.

Exposure of cultured endothelium to environments with low concentrations of oxygen, in the range of those observed in pathophysiologic hypoxemic states in vivo, compromises cellular barrier and coagulant function. An atmosphere with PO2 approximately 14 mm Hg was not lethally toxic to endothelial cultures, but cells became larger and exhibited small intercellular gaps. At low oxygen concentrations, passage of macromolecular tracers through hypoxic endothelial monolayers was accelerated in a time- and dose-dependent manner, presumably by a paracellular pathway via the gaps. Cell surface coagulant properties of the endothelium were also perturbed. At PO2 approximately 14 mm Hg thrombomodulin antigen and functional activity on the cell surface were diminished by 80-90%, and Northern blots demonstrated suppression of thrombomodulin mRNA. The decrease in thrombomodulin was twice as great compared with the general decline in total protein synthesis in hypoxia. In addition, expression of a direct Factor X activator developed under hypoxic conditions; the activator was membrane-associated and expressed on the surface of intact cultures, Ca-dependent, inhibited by HgCl2 but not PMSF, and had Km approximately 25 micrograms/ml for the substrate at pH 7.4. Synthesis of the activator was blocked by inclusion of cycloheximide, but not warfarin, in the culture medium. These results demonstrate that endothelial function is perturbed in a selective manner in the presence of low concentrations of oxygen, providing insights into mechanisms which may contribute to vascular dysfunction in hypoxemic states.

Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation is implicated in the pathogenesis of several gastrointestinal and extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through the increasingly defined gut microbiota brain axis, opening the possibility for new microbiota-based therapeutic options. Although several studies have been conducted to unravel the possible relationship between Alzheimer’s Disease (AD) pathogenesis and progression, the diagnostic and therapeutic potential of approaches aiming at restoring gut microbiota eubiosis remain to be fully addressed. In this narrative review, we briefly summarize the role of gut microbiota homeostasis in brain health and disease, and we present evidence for its dysregulation in AD patients. Based on these observations, we then discuss how dysbiosis might be exploited as a new diagnostic tool in early and advanced disease stages, and we examine the potential of prebiotics, probiotics, fecal microbiota transplantation, and diets as complementary therapeutic interventions on disease pathogenesis and progression, thus offering new insights into the diagnosis and treatment of this devastating and progressive disease.

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease characterized by amyloid-β (Aβ) plaque deposition and neurofibrillary tangle accumulation in the brain. Although several studies have been conducted to unravel the complex and interconnected pathophysiology of AD, clinical trial failure rates have been high, and no disease-modifying therapies are presently available. Fluid biomarker discovery for AD is a rapidly expanding field of research aimed at anticipating disease diagnosis and following disease progression over time. Currently, Aβ_1–42, phosphorylated tau, and total tau levels in the cerebrospinal fluid are the best-studied fluid biomarkers for AD, but the need for novel, cheap, less-invasive, easily detectable, and more-accessible markers has recently led to the search for new blood-based molecules. However, despite considerable research activity, a comprehensive and up-to-date overview of the main blood-based biomarker candidates is still lacking. In this narrative review, we discuss the role of proteins, lipids, metabolites, oxidative-stress-related molecules, and cytokines as possible disease biomarkers. Furthermore, we highlight the potential of the emerging miRNAs and long non-coding RNAs (lncRNAs) as diagnostic tools, and we briefly present the role of vitamins and gut-microbiome-related molecules as novel candidates for AD detection and monitoring, thus offering new insights into the diagnosis and progression of this devastating disease.

High altitude can be a hostile environment and a paradigm of how environmental factors can determine illness when human biological adaptability is exceeded. This paper aims to provide a comprehensive review of high-altitude sickness, including its epidemiology, pathophysiology, and treatments. The first section of our work defines high altitude and considers the mechanisms of adaptation to it and the associated risk factors for low adaptability. The second section discusses the main high-altitude diseases, highlighting how environmental factors can lead to the loss of homeostasis, compromising important vital functions. Early recognition of clinical symptoms is important for the establishment of the correct therapy. The third section focuses on high-altitude pulmonary edema, which is one of the main high-altitude diseases. With a deeper understanding of the pathogenesis of high-altitude diseases, as well as a reasoned approach to environmental or physical factors, we examine the main high-altitude diseases. Such an approach is critical for the effective treatment of patients in a hostile environment, or treatment in the emergency room after exposure to extreme physical or environmental factors.

Roughly 3% of patients worldwide with a new diagnosis of type 2 diabetes mellitus (T2DM) already have an overt nephropathy at diagnosis and about 20–30% of the remaining ones develop a complication of this kind later in life. The early identification of kidney disease in diabetic patients is important as it slows its progression, which is important not only because this reduces the need for renal replacement therapy, but also because it decreases the high rate of mortality and morbidity associated with a reduction in kidney function. The increasing prevalence of type 2 diabetes and the consequent greater probability of finding different types of kidney diseases in diabetic patients frequently gives rise to overlapping diagnoses, a definition encompassing the differential diagnosis between diabetic and non-diabetic kidney disease. The issue is made more complex by the acknowledgement of the increasing frequency of presentations of what is termed “diabetic kidney disease” without relevant proteinuria, in particular in T2DM patients. Distinguishing between diabetes related and non-diabetes related forms of kidney disease in diabetic patients is not only a semantic question, as different diseases require different clinical management. However, while the urologic and macrovascular complications of diabetes, as well as overlapping parenchymal damage, can be diagnosed by means of imaging studies, often only a kidney biopsy will make a differential diagnosis possible. In fact, the coexistence of typical diabetic lesions, such as nodular glomerulopathy or glomerulosclerosis, with different glomerular, vascular and tubulo-interstitial alterations has been extensively described, and an analysis of the dominant histological pattern can contribute to determining what therapeutic approach should be adopted. However, due to the high frequency of kidney diseases, and to the fact that T2DM patients are often affected by multiple comorbidities, a kidney biopsy is not generally performed in T2DM patients. What follows is a review aiming to discuss the diagnostic work-up, on the base of clinical, laboratory and imaging criteria, and evaluate the present indications and alternatives to renal biopsy.