J. Clin. Med., Volume 11, Issue 6 (March-2 2022) – 284 articles

The association between Parkinson’s disease (PD) and mutations in genes involved in lysosomal and mitochondrial function has been previously reported. However, little is known about the involvement of other genes or cellular mechanisms. We aim to identify novel genetic associations to better understand the pathogenesis of PD. We performed WES in a cohort of 32 PD patients and 30 age-matched controls. We searched for rare variants in 1667 genes: PD-associated, related to lysosomal function and mitochondrial function and TFEB-regulated. When comparing the PD patient cohort with that of age matched controls, a statistically significant burden of rare variants in the previous group of genes were identified. In addition, the Z-score calculation, using the European population database (GnomAD), showed an over-representation of particular variants in 36 genes. Interestingly, 11 of these genes are implicated in mitochondrial function and 18 are TFEB-regulated genes. Our results suggest, for the first time, an involvement of TFEB-regulated genes in the genetic susceptibility to PD. This is remarkable as TFEB factor has been reported to be sequestered inside Lewy bodies, pointing to a role of TFEB in the pathogenesis of PD. Our data also reinforce the involvement of lysosomal and mitochondrial mechanisms in PD. Full article

Lymphoid neoplasms are a heterogeneous group of lymphoid neoplastic diseases with multiple presentations, and varying prognoses. They are especially frequent in older patients (OPs) and the atypism of this frail elderly population can make the diagnostic process even more difficult. Blood lymphocyte immunophenotyping (BLI) is essential in rapid noninvasive diagnosis orientation and guides complementary investigations. To our knowledge, BLI prescription has never been evaluated in OPs. We hypothesized that, when there is a suspicion of lymphoid neoplasm in the geriatric population, a BLI is performed in view of various clinical or biological abnormalities. This study aimed to: (1) describe the characteristics of hospitalized OPs having undergone BLI for suspected lymphoid neoplasm, (2) identify the causes leading to BLI prescription, and (3) identify the most profitable criteria for BLI prescription. This was a descriptive retrospective study on 151 OPs aged ≥75 years who underwent BLI over a 2-year period. Regarding BLI prescriptions, eight had lymphocytosis, constituting the “lymphocytosis group” (LG+), while the 143 others had BLI prescribed for reasons other than lymphocytosis (LG−), mainly general weakness and anemia. In the LG−, we compared OPs with positive and negative BLI results. The criteria found to be profitable for BLI prescription were lymphadenopathy, splenomegaly, lymphocytosis, and thrombocytopenia. BLI identified circulating lymphoid neoplasms (positive BLI) in 21/151 OPs, mainly marginal zone lymphoma and chronic lymphocytic leukemia. In polymorbid OPs, as per our study population, the diagnostic and therapeutic complexity explained in part the sole use of indirect and minimally invasive diagnostic techniques such as BLI. Full article

Interstitial lung diseases (ILD) or diffuse parenchymal lung diseases (DPLD) comprise a large number of disorders. Disease definition and classification allow advanced and personalized judgements on clinical disease, risks for genetic or environmental transmissions, and precision medicine treatments. Registers collect specific rare entities and use ontologies for a precise description of complex phenotypes. Here we present a brief history of ILD classification systems from adult and pediatric pneumology. We center on an etiologic classification, with four main categories: lung-only (native parenchymal) disorders, systemic disease-related disorders, exposure-related disorders, and vascular disorders. Splitting diseases into molecularly defined entities is key for precision medicine and the identification of novel entities. Lumping diseases targeted by similar diagnostic or therapeutic principles is key for clinical practice and register work, as our experience with the European children’s ILD register (chILD-EU) demonstrates. The etiologic classification favored combines pediatric and adult lung diseases in a single system and considers genomics and other -omics as central steps towards the solution of “idiopathic” lung diseases. Future tasks focus on a systems’ medicine approach integrating all data and bringing precision medicine closer to the patients. Full article

The aim of the review was to present the state of knowledge about the respiratory pathology in former premature neonates (children that were born preterm—before 37 weeks of gestation—and are examined and evaluated after 40 weeks corrected age) other than chronic lung disease, in order to provide reasons for a respiratory follow-up program for this category of patients. After a search of the current evidence, we found that premature infants are prone to long-term respiratory consequences due to several reasons: development of the lung outside of the uterus, leading to dysmaturation of the structures, pulmonary pathology due to immaturity, infectious agents or mechanical ventilation and deficient control of breathing. The medium- to long-term respiratory consequences of being born before term are represented by an increased risk of respiratory infections (especially viral) during the first years of life, a risk of recurrent wheezing and asthma and a decrease in pulmonary volumes and airway flows. Late preterm infants have risks of pulmonary long-term consequences similar to other former premature infants. Due to all the above risks, premature neonates should be followed in an organized fashion, being examined at regular time intervals from discharge from the maternity hospital until adulthood—this could lead to an early detection of the risks and preventive therapies in order to improve their prognosis and assure a normal and productive life. The difficulties related to establishing such programs are represented by the insufficient standardization of the data gathering forms, clinical examinations and lung function tests, but it is our belief that if more premature infants are followed, the experience will allow standards to be established in these fields and the methods of data gathering and evaluation to be unified. Full article

Early bilateral cochlear implants (CIs) may enhance attention to speech, and reduce cognitive load in noisy environments. However, it is sometimes difficult to measure speech perception and listening effort, especially in very young children. Behavioral measures cannot always be obtained in young/uncooperative children, whereas objective measures are either difficult to assess or do not reliably correlate with behavioral measures. Recent studies have thus explored pupillometry as a possible objective measure. Here, pupillometry is introduced to assess attention to speech and music in noise in very young children with bilateral CIs (N = 14, age: 17–47 months), and in the age-matched group of normally-hearing (NH) children (N = 14, age: 22–48 months). The results show that the response to speech was affected by the presence of background noise only in children with CIs, but not NH children. Conversely, the presence of background noise altered pupil response to music only in in NH children. We conclude that whereas speech and music may receive comparable attention in comparable listening conditions, in young children with CIs, controlling for background noise affects attention to speech and speech processing more than in NH children. Potential implementations of the results for rehabilitation procedures are discussed. Full article

Background: Adenomyosis is a common gynecological disorder traditionally viewed as “elusive”. Several excellent review papers have been published fairly recently on its pathogenesis, and several theories have been proposed. However, the falsifiability, explanatory power, and predictivity of these theories are often overlooked. Since adenomyosis can occur spontaneously in rodents and many other species, the animal models may help us unveil the pathogenesis of adenomyosis. This review critically tallies experimentally induced models published so far, with a particular focus on their relevance to epidemiological findings, their possible mechanisms of action, and their explanatory and predictive power. Methods: PubMed was exhaustively searched using the phrase “adenomyosis and animal model”, “adenomyosis and experimental model”, “adenomyosis and mouse”, and “adenomyosis and rat”, and the resultant papers were retrieved, carefully read, and the resultant information distilled. All the retrieved papers were then reviewed in a narrative manner. Results: Among all published animal models of adenomyosis, the mouse model of adenomyosis induced by endometrial–myometrial interface disruption (EMID) seems to satisfy the requirements of falsifiability and has the predictive capability and also Hill’s causality criteria. Other theories only partially satisfy Hill’s criteria of causality. In particular, animal models of adenomyosis induced by hyperestrogenism, hyperprolactinemia, or long-term exposure to progestogens without much epidemiological documentation and adenomyosis is usually not the exclusive uterine pathology consequent to those induction procedures. Regardless, uterine disruption appears to be a necessary but not sufficient condition for causing adenomyosis. Conclusions: EMID is, however, unlikely the sole cause for adenomyosis. Future studies, including animal studies, are warranted to understand how and why in utero and/or prenatal exposure to elevated levels of estrogen or estrogenic compounds increases the risk of developing adenomyosis in adulthood, to elucidate whether prolactin plays any role in its pathogenesis, and to identify sufficient condition(s) that cause adenomyosis. Full article

Objective: The aim of the systematic review and meta-analysis carried out was to evaluate the effects of changing the prosthetic platform on peri-implant tissue after 1 year of prosthetic loading. Material and methods: In November 2020, an electronic search was carried out in PubMed, EMBASE, Web of Science, and Scopus databases with the aim of obtaining all the randomized clinical trials that had been published in the preceding 10 years comparing the effects on the peri-implant tissue of implants with a prosthetic platform change and implants with a conventional platform for at least 1 year after prosthetic loading. Randomized model meta-analyses of the selected studies were performed to compare the results of the two implant groups in terms of vertical maintenance of bone level and increased probing depth. Results: Nine studies were included, summing up a total of 475 implants with prosthetic platform exchange and 462 implants with a conventional platform. Implants with prosthetic platform exchange had less peri-implant bone loss than implants with a conventional platform (mean difference of 0.255 mm, statistically significant) but suffered a greater increase in probing depth (mean difference of 0.082 mm, not statistically significant). However, the probing depth from One Study Remove revealed a statistically significant increase of 0.190 mm in the prosthetic platform exchange group compared to the conventional platform group. Conclusion: Implants with platform switching suffer less peri-implant bone loss after 1 year of loading than implants with a conventional platform. Further long-term studies are required to observe how these differences vary over time. Full article

Background: The aim of this study was to evaluate the outcomes of patients with the multisystem inflammatory syndrome in children (MIS-C) according to phenotypes of disease and define the prognostic factors for the severe course. Methods: This cross-sectional study included 293 patients with MIS-C from seven pediatric rheumatology centers. A two-step cluster analysis was performed to define the spectrum of disease and their outcomes were compared between each group. Results: Four subgroups were identified as follows: cluster I, predominantly Kawasaki-like features (n = 100); cluster II, predominantly MAS-like features (n = 34); cluster III, predominantly LV dysfunction (n = 47); cluster IV, other presentations (n = 112). The duration of fever was longer in cluster II and the length of hospitalization was longer in both clusters II and III. Laboratory findings revealed lower lymphocyte and platelet counts and higher acute phase reactants (APRs) in cluster II, while patients in cluster IV showed less inflammation with lower APRs. The resolution of abnormal laboratory findings was longer in clusters II and III, while it was shortest in cluster IV. Seven patients died. Among them, four belonged to cluster II, while three were labeled as cluster III. Patients with severe course had higher levels of neutrophil–lymphocyte ratio, mean platelet volume, procalcitonin, ferritin, interleukin-6, fibrinogen, D-Dimer, BNP, and troponin-I, and lower levels of lymphocyte and platelet counts. Conclusion: As shown, MIS-C is not a single disease presenting with various clinical features and outcomes. Understanding the disease spectrum will provide individualized management. Full article

Tranexamic acid (TXA) is an antifibrinolytic pharmacological agent, but its use in gastrointestinal bleeding remains contentious. Moreover, studies on the timing of TXA administration are limited. We examined whether early TXA administration reduced the risk of mortality in patients with gastrointestinal bleeding in a Taiwanese population. We used the National Health Insurance Research Database to identify patients diagnosed with gastrointestinal bleeding with early and late TXA treatment. We defined early treatment as initial TXA treatment in an emergency department and late treatment as initial TXA treatment after hospitalization. Mortality within 52 weeks was the primary outcome. A multivariable analysis using a multiple Cox regression model was applied for data analysis. Propensity score matching (PSM) was performed to reduce the potential for bias caused by measured confounding variables. Of the 52,949 selected patients with gastrointestinal bleeding, 5127 were assigned to either an early or late TXA treatment group after PSM. The incidence of mortality was significantly decreased during the first and fourth weeks (adjusted HR (aHR): 0.65, 95% CI: 0.56–0.75). A Kaplan–Meier curve revealed a significant decrease in cumulative incidence of mortality in the early TXA treatment group (log-rank test: p < 0.0001). Multiple Cox regression analysis revealed significantly lower mortality in the early TXA treatment group compared with the late treatment group (aHR: 0.64, 95% CI: 0.57–0.73). Thromboembolic events were not significantly associated with early or late TXA treatment (aHR: 1.03, 95% CI: 0.94–1.12). A Kaplan–Meier curve also revealed no significant difference in either venous or arterial events (log-rank test: p = 0.3654 and 0.0975, respectively). In conclusion, early TXA treatment was associated with a reduced risk of mortality in patients with gastrointestinal bleeding compared with late treatment, without an increase in thromboembolic events. The risk of rebleeding and need for urgent endoscopic intervention require further randomized clinical trials. Full article

Immune checkpoint inhibitors (ICI) have demonstrated encouraging results in terms of durable clinical benefit and survival in several malignancies. Nevertheless, the search to identify an “ideal” biomarker for predicting response to ICI is still far from over. Radiomics is a new translational field of study aiming to extract, by dedicated software, several features from a given medical image, ranging from intensity distribution and spatial heterogeneity to higher-order statistical parameters. Based on these premises, our review aims to summarize the current status of radiomics as a potential predictor of clinical response following immunotherapy treatment. A comprehensive search of PubMed results was conducted. All studies published in English up to and including December 2021 were selected, comprising those that explored computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) for radiomic analyses in the setting of ICI. Several studies have demonstrated the potential applicability of radiomic features in the monitoring of the therapeutic response beyond the traditional morphologic and metabolic criteria, as well as in the prediction of survival or non-invasive assessment of the tumor microenvironment. Nevertheless, important limitations emerge from our review in terms of standardization in feature selection, data sharing, and methods, as well as in external validation. Additionally, there is still need for prospective clinical trials to confirm the potential significant role of radiomics during immunotherapy. Full article

Background: To characterize humoral response after standard anti-SARS-CoV-2 vaccination in Rituximab-treated patients and to determine the optimal time point after last Rituximab treatment for appropriate immunization. Methods: Sixty-four patients who received Rituximab within the last seven years prior to the first anti-SARS-CoV-2 vaccination were recruited in a prospective observational study. Anti-S1 IgG, SARS-CoV-2 specific neutralization, and various SARS-CoV-2 target antibodies were determined. A live virus assay was used to assess neutralizing antibody activity against B.1.617.2 (delta). In Rituximab-treated patients, CD19⁺ peripheral B-cells were quantified using flow cytometry. Results: After second vaccination, all antibodies were significantly reduced compared to healthy controls. Neutralizing antibody activity against B.1.617.2 (delta) was detectable with a median (IQR) ID₅₀ of 0 (0–1:20) compared to 1:320 (1:160–1:320) in healthy controls (for all p < 0.001). Longer time period since last Rituximab administration correlated with higher anti-SARS-CoV-2 antibody levels and a stronger neutralization of B.1.617.2 (delta). With one exception, only patients with a CD19⁺ cell proportion ≥ 1% had detectable neutralizing antibodies. Conclusion: Our data indicate that a reconstitution of the B-cell population to >1% seems crucial in developing neutralizing antibodies against SARS-CoV-2. We suggest that anti-SARS-CoV-2 vaccination should be administered at least 8–12 months after the last Rituximab treatment for sufficient humoral responses. Full article

Daily-practice challenges in oncology have been intensified by the approval of immune checkpoint inhibitors (ICI). We aimed to outline current therapy policies and management of locally advanced unresectable stage III non-small-cell lung cancer (NSCLC) in different countries. One thoracic oncologist from each of the following countries—Belgium, Croatia, Greece, Israel, the Netherlands, Norway, Poland, Portugal, Romania, Slovenia, and Switzerland—participated in an electronic survey. Descriptive statistics were conducted with categorical variables reported as frequencies and continuous variables as median and interquartile range (IQR) (StataSE-v15). EBUS (endobronchial ultrasound bronchoscopy) was used either upfront or for N2 confirmation. Resectability is still a source of disagreement; thus, decisions vary within each multidisciplinary team. Overall, 66% of stage III patients [IQR 60–75] undergo chemoradiation therapy (CRT); concurrent CRT (cCRT) accounts for most cases (~70%). Performance status is universally used for cCRT eligibility. Induction chemotherapy is fairly weighted based on radiotherapy (RT) availability. Mean time to evaluation after RT completion is less than a month; ICI consolidation is started within six weeks. Durvamulab expenditures are reimbursed in all countries, yet some limiting criteria exist (PD-L1 ≥ 1%, cCRT). No clear guidance on therapies at Durvamulab progression exist; experts agree that it depends on progression timing. Given the high heterogeneity in real-world practices, standardized evidence-based decisions and healthcare provision in NSCLC are needed. Full article

Background: COVID-19 caused by the Severe Acute Respiratory Syndrome Coronavirus 2 placed the health systems around the entire world in a battle against the clock. While most of the existing studies aimed at forecasting the infections trends, our study focuses on vaccination trend(s). Material and methods: Based on these considerations, we used standard analyses and ARIMA modeling to predict possible scenarios in Romania, the second-lowest country regarding vaccinations from the entire European Union. Results: With approximately 16 million doses of vaccine against COVID-19 administered, 7,791,250 individuals had completed the vaccination scheme. From the total, 5,058,908 choose Pfizer–BioNTech, 399,327 Moderna, 419,037 AstraZeneca, and 1,913,978 Johnson & Johnson. With a cumulative 2147 local and 17,542 general adverse reactions, the most numerous were reported in recipients of Pfizer–BioNTech (1581 vs. 8451), followed by AstraZeneca (138 vs. 6033), Moderna (332 vs. 1936), and Johnson & Johnson (96 vs. 1122). On three distinct occasions have been reported >50,000 individuals who received the first or second dose of a vaccine and >30,000 of a booster dose in a single day. Due to high reactogenicity in case of AZD1222, and time of launching between the Pfizer–BioNTech and Moderna vaccine could be explained differences in terms doses administered. Furthermore, ARIMA(1,1,0), ARIMA(1,1,1), ARIMA(0,2,0), ARIMA(2,1,0), ARIMA(1,2,2), ARI-MA(2,2,2), ARIMA(0,2,2), ARIMA(2,2,2), ARIMA(1,1,2), ARIMA(2,2,2), ARIMA(2,1,1), ARIMA(2,2,1), and ARIMA (2,0,2) for all twelve months and in total fitted the best models. These were regarded according to the lowest MAPE, p-value (p < 0.05, p < 0.01, and p < 0.001) and through the Ljung–Box test (p < 0.05, p < 0.01, and p < 0.001) for autocorrelations. Conclusions: Statistical modeling and mathematical analyses are suitable not only for forecasting the infection trends but the course of a vaccination rate as well. Full article

Recurrent clinical deterioration and repeat medical emergency team (MET) activation are common and associated with high in-hospital mortality. This study assessed the predictors for repeat MET activation in deteriorating patients admitted to a general ward. We retrospectively analyzed the data of 5512 consecutive deteriorating hospitalized adult patients who required MET activation in the general ward. The patients were divided into two groups according to repeat MET activation. Multivariate logistic regression analyses were used to identify the predictors for repeat MET activation. Hematological malignancies (odds ratio, 2.07; 95% confidence interval, 1.54–2.79) and chronic lung disease (1.49; 1.07–2.06) were associated with a high risk of repeat MET activation. Among the causes for MET activation, respiratory distress (1.76; 1.19–2.60) increased the risk of repeat MET activation. A low oxygen saturation-to-fraction of inspired oxygen ratio (0.97; 0.95–0.98), high-flow nasal cannula oxygenation (4.52; 3.56–5.74), airway suctioning (4.63; 3.59–5.98), noninvasive mechanical ventilation (1.52; 1.07–2.68), and vasopressor support (1.76; 1.22–2.54) at first MET activation increased the risk of repeat MET activation. The risk factors identified in this study may be useful to identify patients at risk of repeat MET activation at the first MET activation. This would allow the classification of high-risk patients and the application of aggressive interventions to improve outcomes. Full article

Recent studies have focused on the role of skin microbiota in the pathogenesis of atopic dermatitis (AD). Among the various clinical phenotypes of AD, scalp dermatitis is a commonly observed clinical feature of AD. However, little is known about the pathogenesis of scalp dermatitis in AD. Hence, the aim of this study was to identify the distinct microbiota associated with scalp dermatitis in patients with AD. Using scalp swab samples from 10 patients with AD and 10 healthy controls, this study characterized the scalp microbiota in patients with AD via V3–V4 regions of the 16S rRNA gene sequencing for bacterial identification, and ITS2 gene sequencing for fungal identification. Among bacterial genera, Staphylococcus was the most abundant in AD than in healthy controls, whereas Cutibacterium was the most abundant species in the healthy controls. The most predominant scalp fungal microbiota was Malassezia both in AD and healthy controls, while a higher diversity of non-Malassezia fungi was observed in AD than in healthy controls. The study findings indicate the dysbiosis of scalp microbiota in AD and highlight the potential biomarker role of specific microbiota in AD on the scalp dermatitis. Full article

Despite recent improvements in survival, metastatic castration-resistant prostate cancers (mCRPCs) remain lethal. Alterations in genes involved in the homologous recombination repair (HRR) pathway are associated with poor prognosis. Poly-ADP-ribose polymerase (PARP) inhibitors (PARPis) have demonstrated anti-tumoral effects by synthetic lethality in patients with mCRPCs harboring HRR gene alterations, in particular BRCA2. While both olaparib and rucaparib have obtained government approvals for use, the selection of eligible patients as well as the prescription of these treatments within the clinical urology community are challenging. This review proposes a brief review of the rationale and outcomes of PARPi treatment, then a pragmatic vision of PARPi use in terms of prescription and the selection of patients based on molecular screening, which can involve potential genetic counseling in the case of associated germinal alterations. Full article

Fatigue is a common symptom after traumatic brain injuries (TBI) and a crucial target of rehabilitation. The subjective and multifactorial nature of fatigue necessitates a biopsychosocial approach in understanding the mechanisms involved in its development. The aim of this study is to provide a comprehensive exploration of factors relevant to identification and rehabilitation of fatigue following TBI. Ninety-six patients with TBI and confirmed intracranial injuries were assessed on average 200 days post-injury with regard to injury-related factors, several patient-reported outcome measures (PROMS) of fatigue, neuropsychological measures, and PROMS of implicated biopsychosocial mechanisms. Factor analytic approaches yielded three underlying factors, termed Psychosocial Robustness, Somatic Vulnerability and Injury Severity. All three dimensions were significantly associated with fatigue in multiple regression analyses and explained 44.2% of variance in fatigue. Post hoc analyses examined univariate contributions of the associations between the factors and fatigue to illuminate the relative contributions of each biopsychosocial variable. Implications for clinical practice and future research are discussed. Full article

Long-duration atrial high-rate episodes (AHREs) monitored using cardiac implantable electronic devices (CIEDs) can predict long-term major adverse cardiovascular events (MACEs). This study aimed to compare the impact of long-duration AHRE on MACE development between patients with and without a history of atrial fibrillation (AF). This single-center observational study included 132 CIED-implanted patients with AHREs detected via remote monitoring. The population was dichotomized into groups: with (n = 69) and without (n = 63) AF. In each group, cumulative incidences of MACEs comprising all-cause deaths, heart failure hospitalizations, strokes, and acute coronary syndromes were compared between patients with AHRE durations of ≥24 h and <24 h. Multivariate analysis was performed to identify predictors of MACEs among patients without AF. MACE incidence was significantly higher in patients with AHRE ≥24 h than in those with <24 h in the group without AF (92% vs. 30%, p = 0.005). MACE incidence did not significantly differ between AHRE ≥24 h and <24 h in the group with AF (54% vs. 26%, p = 0.44). After a multivariate adjustment, AHRE duration of ≥24 h emerged as the only independent predictor of MACEs among patients without AF (p = 0.03). In conclusion, a long-duration AHRE was prognostic in patients without a history of AF but not in patients with a history of AHREs. Full article

Scientific research has widely examined the therapeutic and health benefits of being in contact with natural environments. Nature walk have been proposed as a cost-effective and inclusive method for successfully exploiting nature for the promotion of health and well-being. Depression and anxiety symptoms have been shown to benefit from nature walk. Despite recent empirical findings published in the scientific literature, a summary quantitative work on the effect of nature walk on depression and anxiety does not yet exist. The present systematic review and meta-analysis quantitatively analyze and qualitatively discuss the studies published on the effect of nature walk on depression and anxiety published during the past decade. A database search as well as snowballing methods were used to retrieve eligible articles. The research question and literature search were based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Based on screening and retrieval processes, seven studies met the eligibility criteria and were then included in the quantitative meta-analysis. Risk of bias (RoB) analysis was used to evaluate the quality of the included studies using the Newcastle–Ottawa Scale. After a qualitative evaluation of the studies, data from six experiments were included in the meta-analysis. The meta-analysis show that nature walk effectively improve mental health. The findings were confirmed for the experiments reporting the quantitative data within groups (pre- and post-test) and between groups (experimental vs. control group). Full article

The role of hepatitis B core-related antigen (HBcrAg) level in defining clinical phase and predicting prognosis of chronic hepatitis B (CHB) has not been fully studied. CHB patients who had undergone liver biopsy in Korea University Medical Center were included. Patients with liver cirrhosis were excluded. The associations of HBcrAg level with CHB phase, and nucleos(t)ide analogue (NA)-induced hepatitis B e antigen (HBeAg) seroconversion were analyzed. In total, 387 patients (median follow-up of 82.4 months) were included. The CHB phases of patients were defined histologically as immune-tolerant (IT, n = 32, 8.3%), HBeAg-positive and immune-active (PIA, n = 211, 54.5%), HBeAg-negative and immune-active (n = 125, 32.3%), and inactive (n = 19, 4.9%), respectively. In HBeAg-positive patients, the mean HBV DNA levels were comparable between the two groups (p = 0.990). However, the mean HBsAg (7.4 log IU/mL and 6.9 log IU/mL, p = 0.002) and HBcrAg levels (8.2 log U/mL vs. 7.6 log U/mL, p < 0.001) of IT patients were significantly higher than that of PIA patients. In multivariate analysis, younger age (odds ratio [OR] 0.949, p = 0.025), lower alanine aminotransferase (OR 0.988, p = 0.002) and higher HBcrAg level (OR = 2.745 p = 0.022) were independent predictors of the IT phase. Of the patients in the PIA phase, 194 received NA after liver biopsy, and 61 (31.4%) had achieved HBeAg seroconversion after antiviral therapy. In Cox regression analysis, the higher HBcrAg level was the only independent predictor of the NA-induced HBeAg seroconversion (hazard ratio 1.285, p = 0.028). The HBcrAg level is useful for predicting clinical phase of CHB and NA-induced HBeAg seroconversion in HBeAg-positive patients. Full article

During the normal aging process, a series of events occur, such as a decrease in telomere length and a decrease in various cognitive functions, such as attention, memory, or perceptual-motor speed. Several studies have attempted to establish a correlation between both variables; however, there is considerable controversy in the scientific literature. The aim of our study was to establish a correlation between the scores obtained in the following different cognitive tests: the Mini-Mental State Examination, the Benton Visual Retention Test, the Trail Making Test, the Rey Auditory Verbal Learning Test, the Stroop Test, and the measurement of telomere length. The sample consisted of a total of 41 physically active, healthy women, with a mean age of 71.21 (±4.32) and of 33 physically inactive, healthy women, with a mean age of 72.70 (±4.13). Our results indicate that there is no correlation between the scores obtained by the women in either group and their telomere length. Therefore, it is not possible to conclude that telomere length can be correlated with cognitive performance. Full article

Whether the COVID-19 pandemic may have modified the clinical planning and course in bronchiectasis patients remains to be fully elucidated. We hypothesized that the COVID-19 pandemic may have influenced the management and clinical outcomes of bronchiectasis patients who were followed up for 12 months. In bronchiectasis patients (n = 30, 23 females, 66 years), lung function testing, disease severity [FEV₁, age, colonization, radiological extension, dyspnea (FACED), exacerbation (EFACED)] and dyspnea scores, exacerbation numbers and hospitalizations, body composition, sputum microbiology, and blood analytical biomarkers were determined at baseline and after a one-year follow-up. Compared to baseline (n = 27, three patients dropped out), in bronchiectasis patients, a significant increase in FACED and EFACED scores, number of exacerbations, and erythrocyte sedimentation rate (ESR) was observed, while FEV₁, ceruloplasmin, IgE, IgG, IgG aspergillus, IgM, and IgA significantly decreased. Patients presenting colonization by Pseudomonas aeruginosa (PA) remained unchanged (27%) during follow-up. In bronchiectasis patients, FEV₁ declined only after a one-year follow-up along with increased exacerbation numbers and disease severity scores, but not hospitalizations. However, a significant decrease in acute phase-reactants and immunoglobulins was observed at the one-year follow-up compared to baseline. Despite the relatively small cohort, the reported findings suggest that lung function impairment may not rely entirely on the patients’ inflammatory status. Full article

Background: Diabetic peripheral neuropathy (DPN) is the most frequent chronic complication and is that which generates the highest disability and mortality in diabetes mellitus (DM). As it is currently the only microvascular complication of DM without a specific treatment, prevention is essential. The aim of this study was to determine the most effective preventive strategy to avoid or delay the appearance and/or development of DPN in patients with DM. Methods: A systematic search was carried out in the main health science databases (PubMed, Scopus, CINAHL, PEDro and The Cochrane Library) from 1 January 2010 to 31 August 2020. The study selection was conducted by two independent reviewers and data extraction was performed by the author. The eligibility criteria included randomized clinical trials (RCTs) and cohort studies from RCTs. Results: Eleven studies were selected that included 23,595 participants with DM. The interventions evaluated were intensive or standard glycemic control, the use of drugs to achieve glycemic control, and the promotion of a healthy lifestyle and exercise. Intensive glucose control achieved a significant reduction in the development of DPN in TIDM patients, and lifestyle modifications and exercise achieved it moderately in TIIDM patients. Conclusions: The main preventive strategy for DPN is intensive glycemic control with a target HbA1c < 6% in patients with TIDM and standard control of 7.0–7.9 in patients with TIIDM, incorporating lifestyle modifications. Full article

Epidural catheterization has become an indispensable part of modern pain therapy, for example, in obstetrics. Learning how to master this skill is an important competency. Videos are among the information sources with the highest information content for learning such skills. The present study aims to analyze videos regarding epidural catheter placement provided on the YouTube platform based on a validated checklist. An expert workshop selected crucial items for learning epidural catheterization in obstetrics. Items were identified and optimized in a five-step testing process. Using this checklist, videos from YouTube were evaluated by eleven health care professionals. Sixteen videos were identified and analyzed. Concerning the catheterization-specific part of the checklist, only two videos showed satisfactory quality. In the didactic part, eleven out of 21 items reached a mean score >50% of the points. Regarding interrater reliability, the catheterization-specific checklist was shown to be substantial (Fleiss’ kappa = 0.610), and the didactic part was shown to be fair (Fleiss’ kappa = 0.401). Overall, standard monitoring and appropriate aseptic technique were followed in only 42% and 49% for the procedure. There was a significant correlation between the runtime and the content quality (p < 0.001). No correlation could be found in terms of platform rating parameters. The video quality varied highly in terms of the requirements of this practical skill. The majority appear unsuitable for self-study due to serious errors and deficiencies regarding patient safety. However, there is no quality control on free platforms. Accordingly, it is difficult to identify suitable videos for educational purposes. Full article

This study investigated whether changes in work schedule are associated with health behavior changes. We used data from the Korea Labor and Income Panel Survey from 2005 to 2019. A generalized estimating equation model was used to assess the association between changes of work schedules (day–day, day–shift, shift–day, and shift–shift) and health behaviors. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated after adjusting for general and socioeconomic characteristics. Fixed daytime work was observed for 25,716 person-years, and fixed shift work was observed for 2370 person-years out of the total 4046 participants during a 14 year period. Workers who changed their work schedule from fixed daytime to shift work and from shift to fixed daytime work contributed to 670 and 739 person-years, respectively. Considering continuous fixed daytime workers as a reference group, continuous exposure to shift work (aOR 1.11, CI 1.01–1.26) and changes from fixed daytime to shift work (aOR 1.18, CI 1.05–1.44) were significantly associated with an increased risk of changing either smoking or drinking behavior to unhealthy patterns. The results of our study suggest that workers who work irregular shift times, in contrast to those with more standard, regular work schedules, are at a higher risk of changing smoking and/or drinking behavior to unhealthy patterns. Full article

To evaluate the prenatal course and perinatal outcome of fetuses with bronchopulmonary sequestration (BPS) managed expectantly or using minimally invasive methods. This was a retrospective study of 29 fetuses with suspected BPS managed between 2010 and 2021 in three fetal medicine centers in Poland. Medline was searched to identify cases of BPS managed expectantly or through minimally-invasive methods. In 16 fetuses with BPS, there was no evidence of cardiac compromise. These fetuses were managed expectantly. Thirteen hydropic fetuses with BPS qualified for intrauterine intervention: a thoraco-amniotic shunt (TAS) was inserted in five fetuses, laser coagulation of the feeding vessel was performed in seven cases, and one fetus had combined treatment. In the combined data from the previous and the current study of various percutaneous interventions for BPS associated with hydrops, the survival rate was 91.2% (31/34) for TAS, 98.1% (53/54) for laser coagulation, and 75% (3/4) for intratumor injection of sclerosant. After taking into account cases with available data, the rate of preterm birth before 37 weeks in the group treated with laser coagulation was 14.3% (7/49) compared to 84.6% (22/26) in the group treated with TAS. The need for postnatal sequestrectomy was lower in the group of fetuses treated with laser coagulation 23.5% (12/51) in comparison to fetuses treated with TAS 84% (21/26). In fetuses with BPS without hydrops, progression of the lesion’s volume, leading to cardiac compromise, is unlikely. In hydropic fetuses with BPS, intrauterine therapy using minimally invasive methods prevents fetal demise. Both, the rate of preterm birth and the need for postnatal surgery is significantly lower in the group treated with laser coagulation compared to the group treated with TAS. Full article

We aimed to evaluate the effects of the coronavirus disease (COVID-19) pandemic on the Ophthalmology Department. This study was based on data collected between January 2019 and November 2021. We divided patients scheduled for eye care during pre-COVID-19 (January–December 2019), early COVID-19 (January–December 2020), and late COVID-19 (January–November 2021) periods. Changes in the outpatient cancellation rate in each department were analyzed and compared in the pre-, early, and late periods. The basic information of cancellation and reason for not visiting the clinic were also analyzed. Overall, 121,042 patients were scheduled to visit the Sanggye Paik Hospital Ophthalmology Department. The overall cancellation rate was 19.13% during pre-COVID-19, 24.13% during early COVID-19, and 17.34% during late COVID-19. The reasons for not visiting the clinic included hospital, patient, and contact factors; hospitalization in other departments and hospitals; and death. The Strabismus/Pediatric Ophthalmology Department showed the highest cancellation rate of 24.21% over three years. There were no significant differences in the causes of hospital visits by period. The COVID-19 pandemic has caused an overall decrease in the number of ophthalmic outpatients. However, after about a year, the number of outpatients in these departments recovered to the level before the COVID-19 outbreak. Full article

Patients with adolescent idiopathic scoliosis (AIS) more frequently suffer dysfunctions of dento-skeletal complex. To our knowledge, no study has ever evaluated the temporomandibular joint disorders (TMD) of AIS patients at least 23 years after the completion of Milwaukee brace treatment. We aimed to provide a complex assessment of TMD and AIS patients treated with a Milwaukee brace, in a minimum 23-year follow-up, using radiological, clinical, and socio-demographical data, and to adapt the TMD Disability Index Questionnaire (TMDQ) and Fonseca’s questionnaire (FQ) to Polish conditions. In total, 42 healthy females and 30 AIS patients with a minimum of 23 years after a completed Milwaukee brace treatment were asked to complete the Polish version of (TMDQ-PL) and (FQ-PL). AIS patients present higher TMD levels than healthy controls. Significant differences exist between TMDQ-PL and FQ-PL (both in total scores and particular sub-sections), and AIS patients. Clinical and radiological factors affected the TMDQ-PL and FQ-PL results. Adult patients with scoliosis treated conservatively present limitations in everyday activities connected with the temporomandibular joint (TMJ). The variety of curve-related factors in a long-term follow-up of wearing the Milwaukee brace influence TMJ. Full article

Background: There is a need for reliable risk assessment tools to better predict peri-implantitis occurrence. This study compared the long-term prognosis value of two models of risk assessment scoring in predicting peri-implantitis. Methods: Seventy-three patients with treated periodontitis representing 232 implants and attending long-term implant maintenance were evaluated. The Periodontal Risk Assessment (PRA) score, which combines only periodontal risk factors/indicators, and the Implant Risk Assessment (IRA) score, which combines both periodontal and implant risk factors/indicators, were calculated during implant maintenance. Peri-implantitis was defined by the presence of probing depth ≥6 mm with bleeding on probing/suppuration and bone level ≥3 mm. Analyses were performed at the patient level. Results: The mean implant follow-up was 6.5 years. Peri-implantitis incidence was 17.8%, and high-risk PRA and IRA percentages were 36.9% and 27.3%, respectively. High-risk PRA and IRA were significantly associated with peri-implantitis incidence, with hazard ratio (HR) = 4.8 and 3.65, respectively. Risk factors/indicators considered separately showed reduced associations with peri-implantitis. Conclusions: The PRA score combining periodontal parameters and IRA score combining both periodontal and implant parameters have comparable value in predicting peri-implantitis. These scores could allow practicians to intercept the risk of peri-implantitis and to manage follow-up modalities in patients with treated periodontitis. Full article