Familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] level are the most common inherited disorders of lipid metabolism. This study evaluated the impact of high Lp(a) level on accuracy Dutch Lipid Clinic Network (DLCN) criteria of heterozygous FH diagnosis. A group of 206 individuals not receiving lipid-lowering medication with low-density lipoprotein cholesterol (LDL-C) >4.9 mmol/L was chosen from the Russian FH Registry. LDL-C corrected for Lp(a)-cholesterol was calculated as LDL-C − 0.3 × Lp(a). DLCN criteria were applied before and after adjusting LDL-C concentration. Of the 206 patients with potential FH, a total of 34 subjects (17%) were reclassified to less severe FH diagnosis, 13 subjects of them (6%) were reclassified to “unlike” FH. In accordance with Receiver Operating Characteristic curve, Lp(a) level ≥40 mg/dL was associated with FH re-diagnosing with sensitivity of 63% and specificity of 78% (area under curve = 0.7, 95% CI 0.7–0.8, p < 0.001). The reclassification was mainly observed in FH patients with Lp(a) level above 40 mg/dL, i.e., 33 (51%) with reclassified DLCN criteria points and 22 (34%) with reclassified diagnosis, compared with 21 (15%) and 15 (11%), respectively, in patients with Lp(a) level less than 40 mg/dL. Thus, LDL-C corrected for Lp(a)-cholesterol should be considered in all FH patients with Lp(a) level above 40 mg/dL for recalculating points in accordance with DLCN criteria. Full article

Biliary tract diseases that are not adequately treated on index hospitalization are linked to worse outcomes, including high readmission rates. Delays in care for conditions such as choledocholithiasis, gallstone pancreatitis, and cholecystitis often occur due to multiple reasons, and this delay is under-appreciated as a source of morbidity and mortality. Our study is based on the latest Nationwide Readmissions Database review and evaluated the effects of postponing definitive management to a subsequent visit. The study shows a higher 30-day readmission rate in addition to increased mortality rate, intubation rate, vasopressor use in this patient population and significantly added financial burden. Full article

Background: The objective of this study was to characterize patients with hyponatremia at hospital admission into clusters using an unsupervised machine learning approach, and to evaluate the short- and long-term mortality risk among these distinct clusters. Methods: We performed consensus cluster analysis based on demographic information, principal diagnoses, comorbidities, and laboratory data among 11,099 hospitalized adult hyponatremia patients with an admission serum sodium below 135 mEq/L. The standardized mean difference was utilized to identify each cluster’s key features. We assessed the association of each hyponatremia cluster with hospital and one-year mortality using logistic and Cox proportional hazard analysis, respectively. Results: There were three distinct clusters of hyponatremia patients: 2033 (18%) in cluster 1, 3064 (28%) in cluster 2, and 6002 (54%) in cluster 3. Among these three distinct clusters, clusters 3 patients were the youngest, had lowest comorbidity burden, and highest kidney function. Cluster 1 patients were more likely to be admitted for genitourinary disease, and have diabetes and end-stage kidney disease. Cluster 1 patients had the lowest kidney function, serum bicarbonate, and hemoglobin, but highest serum potassium and prevalence of acute kidney injury. In contrast, cluster 2 patients were the oldest and were more likely to be admitted for respiratory disease, have coronary artery disease, congestive heart failure, stroke, and chronic obstructive pulmonary disease. Cluster 2 patients had lowest serum sodium and serum chloride, but highest serum bicarbonate. Cluster 1 patients had the highest hospital mortality and one-year mortality, followed by cluster 2 and cluster 3, respectively. Conclusion: We identified three clinically distinct phenotypes with differing mortality risks in a heterogeneous cohort of hospitalized hyponatremic patients using an unsupervised machine learning approach. Full article

The reduction in skeletal muscle mass (SMM) is a common phenomenon in older adults. It is associated with several diseases, a reduction in physical fitness, longer periods of hospitalization and high rates of mortality. We aimed to identify the reliability of simple tools for screening for reduced SMM among older adult males in Lebanon. The Tanita MC-780MA bioimpedance analyzer (BIA) was used to assess body composition in a population of 102 community-dwelling elderly males with overweight or obesity, in order to be then categorized as with or without reduced SMM. Participants also performed the handgrip strength test and the 4 m gait speed test. Of the total sample of 102 participants (mean age 67.4 ± 6.96 years; BMI 30.8 6 ± 4.04 kg/m²), 32 (31.4%) met the criteria for reduced SMM. Partial correlation analysis showed that handgrip strength (ρ = 0.308, p = 0.002) and 4 m gait speed (ρ = 0.284, p = 0.004) were both associated with low SMM. Receiver operating characteristic (ROC) curve analysis identified discriminating cut-off points of 1.1 m/s for the 4 m gait speed test and 32.0 kg for the handgrip strength test. Our study showed that participants displayed a substantial prevalence of reduced SMM. Reduced 4 m gait speed and handgrip strength were associated with low SMM. Clear cut-off points for strength and functional tests for screening for this condition in Lebanese older men were identified. Full article

Bone marrow, besides the known functions of hematopoiesis, is an active organ of the immune system, functioning as a sanctuary for several mature immune cells. Moreover, evidence suggests that hematopoietic stem cells (the bone marrow’s functional unit) are capable of directly sensing and responding to an array of exogenous stimuli. This chronic immune stimulation is harmful to normal hematopoietic stem cells, while essential for the propagation of myeloid diseases, which show a dysregulated immune microenvironment. The bone marrow microenvironment in myelodysplastic syndromes (MDS) is characterized by chronic inflammatory activity and immune dysfunction, that drive excessive cellular death and through immune evasion assist in cancer cell expansion. Acute myeloid leukemia (AML) is another example of immune response failure, with features that augment immune evasion and suppression. In this review, we will outline some of the functions of the bone marrow with immunological significance and describe the alterations in the immune landscape of MDS and AML that drive disease progression. Full article

Alzheimer’s disease (AD) is an age-dependent, progressive disorder affecting millions of people. Currently, the therapeutics for AD only treat the symptoms. Although they have been used to discover new products of interest for this disease, mammalian models used to investigate the molecular determinants of this disease are often prohibitively expensive, time-consuming and very complex. On the other hand, cell cultures lack the organism complexity involved in AD. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for the investigation of the pathophysiology of human AD. Numerous models of both Tau- and Aβ-induced toxicity, the two prime components observed to correlate with AD pathology and the ease of performing RNA interference for any gene in the C. elegans genome, allow for the identification of multiple therapeutic targets. The effects of many natural products in main AD hallmarks using these models suggest promising health-promoting effects. However, the way in which they exert such effects is not entirely clear. One of the reasons is that various possible therapeutic targets have not been evaluated in many studies. The present review aims to explore shared therapeutical targets and the potential of each of them for AD treatment or prevention. Full article

Obstructive sleep apnea (OSA) is a serious, potentially life-threatening condition. Epidemiologic studies show that sleep apnea increases cardiovascular diseases risk factors including hypertension, obesity, and diabetes mellitus. OSA is also responsible for serious illnesses such as congestive heart failure, stroke, arrhythmias, and bronchial asthma. The aim of this systematic review is to evaluate evidence for the association between OSA and cardiovascular disease morbidities and identify risk factors for the conditions. In a review of 34 studies conducted in 28 countries with a sample of 37,599 people, several comorbidities were identified in patients with severe OSA—these were: heart disease, stroke, kidney disease, asthma, COPD, acute heart failure, chronic heart failure, hyperlipidemia, thyroid disease, cerebral infarct or embolism, myocardial infarction, and psychological comorbidities including stress and depression. Important risk factors contributing to OSA included: age > 35 years; BMI ≥ 25 kg/m²; alcoholism; higher Epworth sleepiness scale (ESS); mean apnea duration; oxygen desaturation index (ODI); and nocturnal oxygen desaturation (NOD). Severe OSA (AHI ≥ 30) was significantly associated with excessive daytime sleepiness and oxygen desaturation index. The risk of OSA and associated disease morbidities can be reduced by controlling overweight/obesity, alcoholism, smoking, hypertension, diabetes mellitus, and hyperlipidemia. Full article

Postpartum depression (PPD) is defined as the onset of major depressive disorder in mothers, occurring during pregnancy or within 4 weeks post-delivery. With 7% of pregnancy-related death in the United States owing to mental health conditions, including PPD, and a global prevalence of 12%, PPD is a growing public health concern. In 2019, the Food and Drug Administration (FDA) approved brexanolone, an exogenous analog of allopregnanolone, as the first ever drug to be specifically indicated for treating patients with PPD. This approval was preceded by an open-label study and three randomized placebo-controlled trials, each assessing the safety, tolerability, and efficacy of brexanolone, using mean Hamilton Rating Scale for Depression (HAM-D) score reduction as the primary outcome. In each randomized controlled trial, the drug was administered as an intravenous infusion given over 60 h. Enrolled participants were followed up on days 7 and 30 to evaluate the sustained effect. A statistically significant reduction in mean HAM-D score compared to placebo was observed in all three studies, supporting brexanolone’s use in treating moderate-to-severe PPD. Therefore, this article attempts to briefly review the pharmacology of brexanolone, evaluate the latest available clinical data and outcomes concerning its use, reevaluate its position as a ‘breakthrough’ in managing PPD, and review the cost-related barriers to its worldwide standardized use. Full article

Throughout the history of biological/medicine sciences, there has been opposing strategies to find solutions to complex human disease problems. Both empirical and deductive approaches have led to major insights and concepts that have led to practical preventive and therapeutic benefits for the human population. The classic definitions of “science” (to know) has been paired with the classic definition of technology (to do). One knew more as the technology developed, and that development was often based on science. In other words, one could do more if science could improve the technology. In turn, this made possible to know more science with improved technology. However, with the development of new technologies of today in biology and medicine, major advances have been made, such as the information from the Human Genome Project, genetic engineering techniques and the use of bioinformatic uses of sophisticated computer analyses. This has led to the renewed idea that Precision Medicine, while raising some serious ethical concerns, also raises the expectation of improved potential of risk predictions for prevention and treatment of various genetically and environmentally influenced human diseases. This new field Artificial Intelligence, as a major handmaiden to Precision Medicine, is significantly altering the fundamental means of biological discovery. However, can today’s fundamental premise of “Artificial Intelligence”, based on identifying DNA, as the primary nexus of human health and disease, provide the practical solutions to complex human diseases that involve the interaction of those genes with the broad spectrum of “environmental factors”? Will it be “precise” enough to provide practical solutions for prevention and treatments of diseases? In this “Commentary”, with the example of human carcinogenesis, it will be challenged that, without the integration of mechanistic and hypothesis-driven approaches with the “unbiased” empirical analyses of large numbers of data, the Artificial Intelligence approach with fall short. Full article

Vaccines are actually the most effective strategy to control the COVID-19 spread and reduce mortality, but adverse reactions can occur. Skin involvement with novel messenger RNA coronavirus vaccines seems frequent but is not completely characterized. A real-world experience in the recent vaccination campaign among health care workers in Sardinia (Italy) is reported. In over a total of 1577 persons vaccinated, 9 cases of skin adverse reactions were observed (0.5%). All reactions have been reported to the Italian Pharmacovigilance Authority. Eight occurred in women (mean age 46 years), and five were physicians and four nurses. All patients had a significant allergology history but not for the known vaccine excipients. After dose one, no injection site reactions were observed, but widespread pruritus (n = 3), mild facial erythema (n = 1), and maculopapular rash (n = 3) occurred in the following 24–48 h in three patients. These three patients were excluded from the second dose. Of the remaining six patients, one developed mild anaphylaxis within the observation period at the vaccination hub and five delayed facial erythematous edema and maculopapular lesions, requiring antihistamines and short-course corticosteroid treatment. Spontaneous reporting is paramount to adjourning vaccination guidance and preventive measures in order to contribute to the development of a safe vaccine strategy. Dermatologist’ expertise might provide better characterization, treatment, and screening of individuals at high risk of skin adverse reactions. Full article