J. Pers. Med., Volume 12, Issue 7 (July 2022) – 174 articles

The prognostic value of CT-derived muscle quantity for overall survival (OS) in patients with non-small-cell lung cancer (NSCLC) is uncertain due to conflicting evidence. We hypothesize that increased muscle quantity is associated with better OS in patients with normal muscle radiodensity but not in patients with fatty degeneration of muscle tissue and low muscle radiodensity. We performed an observational cohort study in NSCLC patients treated with radiotherapy. A deep learning algorithm was used to measure muscle quantity as psoas muscle index (PMI) and psoas muscle radiodensity (PMD) on computed tomography. The potential interaction between PMI and PMD for OS was investigated using Cox proportional-hazards regression. Baseline adjustment variables were age, sex, histology, performance score and body mass index. We investigated non-linear effects of continuous variables and imputed missing values using multiple imputation. We included 2840 patients and observed 1975 deaths in 5903 patient years. The average age was 68.9 years (standard deviation 10.4, range 32 to 96) and 1692 patients (59.6%) were male. PMI was more positively associated with OS for higher values of PMD (hazard ratio for interaction 0.915; 95% confidence interval 0.861–0.972; p-value 0.004). We found evidence that high muscle quantity is associated with better OS when muscle radiodensity is higher, in a large cohort of NSCLC patients treated with radiotherapy. Future studies on the association between muscle status and OS should accommodate this interaction in their analysis for more accurate and more generalizable results. Full article

COVID-19 and chronic kidney disease (CKD) share similarity in sex bias and key genes in the disease pathway of sex difference. We investigated the sex difference of molecular pathways of four key players of these two diseases using an existing large set of whole genome expression profiles from the kidneys of female and male mouse models. Our data show that there is little to no correlation at the whole genome expression level between female and male mice among these four genes. There are considerable sex differences among genes in upstream regulation, Ace2 complex interaction, and downstream pathways. Snap25 and Plcb4 may play important roles in the regulation of the expression level of Adam17, Tmprss2, and Cd146 in females. In males, Adh4 is a candidate gene for the regulation of Adam17, while Asl, Auts2, and Rabger1 are candidates for Tmprss2. Within the Ace2 complex, Cd146 directly influences the expression level of Adam17 and Ace2 in the female, while in the male Adam potentially has a stronger influence on Ace2 than that of Tmprss2. Among the top 100 most related genes, only one or two genes from four key genes and 11 from the control B-Actin were found to be the same between sexes. Among the top 10 sets of genes in the downstream pathway of Ace2, only two sets are the same between the sexes. We concluded that these known key genes and novel genes in CKD may play significant roles in the sex difference in the CKD and COVID-19 disease pathways. Full article

Background: In chronic obstructive pulmonary disease (COPD), inhaled corticosteroids (ICSs) are recommended for use by patients with frequent exacerbations and blood eosinophilia. However, ICSs are often inappropriately prescribed and overused. COPD studies have reported an increased risk of tuberculosis among ICS users. This study aimed to compare the risk of tuberculosis according to the different ICS components. Methods: This study was conducted using a nationwide, population-based cohort. Patients newly diagnosed with COPD between 2005 and 2018, and treated with either fluticasone propionate or budesonide, were selected. The patients were followed up until the development of tuberculosis. Results: After propensity score matching, 16,514 fluticasone propionate and 16,514 budesonide users were identified. The incidence rate of tuberculosis per 100,000 person-years was 274.73 for fluticasone propionate and 214.18 for budesonide. The hazard ratio of tuberculosis in fluticasone propionate compared with budesonide was 1.28 (95% confidence interval 1.05–1.60). The risk of tuberculosis for fluticasone propionate increased with higher ICS cumulative doses: 1.01 (0.69–1.48), 1.16 (0.74–1.81), 1.25 (0.79–1.97), and 1.82 (1.27–2.62) from the lowest to highest quartiles, respectively. Conclusion: Fluticasone propionate is associated with a higher risk of tuberculosis than budesonide. ICS components can differently affect the risk of tuberculosis in patients with COPD. Full article

Background: In recent years, physical exercise has been investigated for its potential as a therapeutic tool in patients with end-stage renal disease (ESRD) undergoing hemodialysis maintenance treatment (HD). It has been shown that regular practice of moderate-intensity exercise can improve certain aspects of immune function and exert anti-inflammatory effects, having been associated with low levels of pro-inflammatory cytokines and high levels of anti-inflammatory cytokines. Purpose: The aim of this review is to examine the studies carried out in this population that analyzed the effect of intradialytic exercise on the inflammatory state and evaluate which exercise modality is most effective. Methods: The search was carried out in the MEDLINE, CINAHL Web of Science and Cochrane Central Register of Controlled Trials databases from inception to June 2022. The PEDro scale was used to assess methodological quality, and the Cochrane Risk of Bias Tool and MINORS were used to evaluate the risk of bias. The quality of evidence was assessed with GRADE scale. The outcome measures were systemic inflammation biomarkers. Results: Mixed results were found in terms of improving inflammation biomarkers, such as CRP, IL-6 or TNFα, after exercise. Aerobic exercise seems to improve systemic inflammation when performed at medium intensity while resistance training produced better outcomes when performed at high intensity. However, some studies reported no differences after exercise and these results should be taken with caution. Conclusions: The low quality of the evidence suggests that aerobic and resistance exercise during HD treatment improves systemic inflammation biomarkers in patients with ESRD. In any case, interventions that increase physical activity in patients with ESRD are of vital importance as sedentary behaviors are associated with mortality. More studies are needed to affirm solid conclusions and to make intervention parameters, such as modality, dose, intensity or duration, sufficiently clear. Full article

CYP2D6 and CYP2C19 are enzymes of essential significance for the pharmacokinetics of a multitude of commonly used antidepressants, antipsychotics, antiemetics, β-blockers, opioids, antiestrogen, antacids, etc. Polymorphisms in the respective genes are well established as resulting in functional differences, which in turn can impact safety and efficacy. Importantly, the prevalence of genetic CYP2D6 and CYP2C19 variability differs drastically between populations. Drawing on the limited information concerning genotype frequencies in Bulgaria, we here analyzed 742 Bulgarian psychiatric patients predominantly diagnosed with depression and/or anxiety. Specifically, we analyzed frequencies of CYPC19*2, *4 and *17, as well as of CYP2D6*2, *3, *4, *5, *6, *10 and *41. In total, 571 out of 742 patients (77%) carried at least one variant which impacts metabolizer status. Overall, 48.6% of the studied individuals were classified as non-normal metabolizers of CYP2D6 with most exhibiting reduced function (38.2% intermediate metabolizers and 6.6% poor metabolizers). In contrast, for CYP2C19, the majority of non-normal metabolizers showed increased functionality (28.9% rapid and 5.5% ultrarapid metabolizers), while reduced activity metabolizer status accounted for 25.6% (23.8% intermediate and 1.8% poor metabolizers). These results provide an important resource to assess the genetically encoded functional variability of CYP2D6 and CYP2C19 which may have significant implications for precision medicine in Bulgarian psychiatry practice. Full article

We investigated whether age at hypertension (HTN) onset was associated with the risk of atrial fibrillation (AF) in the general population. This prospective longitudinal community-based cohort study included 9892 participants without AF at baseline, who underwent biennial electrocardiography for a median duration of 11.5 years. The participants were divided into five groups, consisting of a normotensive group (Group-N) and four HTN groups based on HTN onset age: <45 years (Group-H1); 45–54 years (Group-H2); 55–64 years (Group-H3); and ≥65 years (Group-H4). A multivariate Cox proportional hazards model showed that the presence of HTN at baseline was associated with higher AF risk (hazard ratio [HR], 1.93; 95% confidence interval [CI] 1.32–2.80). The participants in Group-H1 had the highest risk of AF (HR 3.18; CI 1.74–5.82), and the risk of AF decreased as HTN onset age increased across the four HTN groups (p for trend = 0.014). The AF onset age was significantly younger in participants in Group-H1 than in Groups-H2–H4. Early-onset HTN was associated with an increased risk of AF, and younger onset of AF in the general population. Surveillance for AF should be considered at a younger age in individuals with HTN. Full article

Studies on older patients have established notable conceptual changes in the etiopathogenesis of acute coronary syndrome (ACS), but little is known about this disease in young patients (<45 years). Of special interest is thromboinflammation, key at onset, evolution and therapy of cardiovascular pathology. Therefore, we explored whether ACS at an early age is a thromboinflammatory disease by analyzing NETs and rs2431697 of miR-146a (a miRNA considered as a brake of TLR/NF-kB pathway), elements previously related to higher rates of recurrence in atrial fibrillation and sepsis. We included 359 ACS patients (<45 years) and classified them for specific analysis into G1 (collected during the hospitalization of the first event), G2 and G3 (retrospectively collected from patients with or without ACS recurrence, respectively). cfDNA and citH3–DNA were quantified, and rs2431697 was genotyped. Analysis in the overall cohort showed a moderate but significant correlation between cfDNA and citH3–DNA and Killip–Kimball score. In addition, patients with citH3–DNA > Q4 more frequently had a history of previous stroke (6.1% vs. 1.6%). In turn, rs2431697 did not confer increased risk for the onset of ACS, but T carriers had significantly higher levels of NET markers. By groups, we found that cfDNA levels were similarly higher in all patients, but citH3–DNA was especially higher in G1, suggesting that in plasma, this marker may be attenuated over time. Finally, patients from G2 with the worst markers (cfDNA and citH3–DNA > Q2 and T allele) had a two-fold increased risk of a new ischemic event at 2-year follow-up. In conclusion, our data confirm that ACS is younger onset with thromboinflammatory disease. In addition, these data consolidate rs2431697 as a silent proinflammatory factor predisposing to NETosis, and to a higher rate of adverse events in different cardiovascular diseases. Full article

Introduction: Asthma, along with inhaled steroids, was initially considered a risk factor for worse clinical outcomes in COVID-19. This was related to the higher morbidity observed in asthma patients during previous viral outbreaks. This retrospective study aimed at evaluating the prevalence of asthma among patients admitted due to SARS-CoV-2 infection as well as the impact of inhaled therapies on their outcomes. Furthermore, a comparison between patients with asthma, COPD and the general population was made. Methods: All COVID-19 inpatients were recruited between February and July 2020 from four large hospitals in Northwest Italy. Data concerning medical history, the Charlson Comorbidity Index (CCI) and the hospital stay, including length, drugs and COVID-19 complications (respiratory failure, lung involvement, and the need for respiratory support) were collected, as well as the type of discharge. Results: patients with asthma required high-flow oxygen therapy (33.3 vs. 14.3%, p = 0.001) and invasive mechanical ventilation (17.9 vs. 9.5%, p = 0.048) more frequently when compared to the general population, but no other difference was observed. Moreover, asthma patients were generally younger than patients with COPD (59.2 vs. 76.8 years, p < 0.001), they showed both a lower mortality rate (15.4 vs. 39.4%, p < 0.001) and a lower CCI (3.4 vs. 6.2, p < 0.001). Patients with asthma in regular therapy with ICS at home had significantly shorter hospital stay compared to those with no treatments (25.2 vs. 11.3 days, p = 0.024). Discussion: Our study showed that asthma is not associated with worse outcomes of COVID-19, despite the higher need for respiratory support compared with the general population, while the use of ICS allowed for a shorter hospital stay. In addition, the comparison of asthma with COPD patients confirmed the greater frailty of the latter, according to their multiple comorbidities. Full article

There is scarcity in the evidence addressing the indirect impact of the COVID-19 pandemic on the epidemiology of CVDs. In this study we aimed to examine possible changes in the incidence of CVDs in Korea during the COVID-19 pandemic. ICD-10 codes of six common CVDs (cerebral hemorrhage, cerebral infarction, myocardial infarction, ischemic heart disease, cardiac failure, and arrhythmia) were collected from clinical visits between January 2018 and March 2021 using the National Health Insurance service database, which stores data on all citizens of Korea (~50 million people). The number and distribution of monthly visits for CVDs were compared before and during the COVID-19 pandemic, and the differences were analyzed using the Mann–Whitney U test and Levene’s test. Our data showed similar incidences of cerebral hemorrhage and ischemic heart disease, a lower incidence of cerebral infarction, and higher incidences of myocardial infarction, cardiac failure, and arrhythmia during COVID-19. Despite statistical differences, the changes in incidences were not considered meaningful. The monthly incidences also remained similar throughout the year, without seasonal variations, both before and during the COVID-19 outbreak. This study found no significant changes in the incidences or monthly variation in CVDs due to the COVID-19 pandemic in Korea. Full article

Background: Many causes of resorption remain unclear and are thus identified as idiopathic. In such cases, management is difficult, especially when multiple teeth are involved. The aim of the present study was to assess the literature regarding the medical, clinical, and radiographic aspects of multiple idiopathic resorptions (MIR) and to examine the factors associated with the risk of extraction. Methods: The title and protocol were registered a priori in PROSPERO (CRD42020191564), and the study followed the PRISMA methodology. Four electronic databases were searched to include reviews and case reports on MIR in permanent dentition. Results: Among the 1035 articles identified, 31 case reports were included. The mean age of the patients was 32 years (SD = 16.4). MIR were consistently diagnosed after radiographic evaluation and were undetected during intra-oral examination in 62% of cases. The treatment involved extraction in 77% of cases. The risk of extraction increased in the presence of periodontal inflammation. Conclusions: MIR are aggressive forms of resorption requiring routine visits. MIR mostly involve extraction and lead to a challenging prosthetic rehabilitation due to severely damaged abutment teeth. However, the current knowledge on MIR remains fragmental and based on a limited number of case reports. Full article

In our clinic, the current preferred primary treatment regime for unilateral condylar hyperactivity is a proportional condylectomy in order to prevent secondary orthognathic surgery. Until recently, to determine the indicated size of reduction during surgery, we used a ‘panorex-free-hand’ method to measure the difference between left and right ramus heights. The problem encountered with this method was that our TMJ surgeons measured differences in the amount to resect during surgery. Other 2D and 3D method comparisons were unavailable. The aim of this study was to determine the most reproducible ramus height measuring method. Differences in left/right ramus height were measured in 32 patients using three methods: one 3D and two 2D. The inter- and intra-observer reliabilities were determined for each method. All methods showed excellent intra-observer reliability (ICC > 0.9). Excellent inter-observer reliability was also attained with the panorex-bisection method (ICC > 0.9), while the CBCT and panorex-free-hand gave good results (0.75 < ICC < 0.9). However, the lower boundary of the 95% CI (0.06–0.97) of the inter-observer reliability regarding the panorex-free-hand was poor. Therefore, we discourage the use of the panorex-free-hand method to measure ramus height differences in clinical practice. The panorex-bisection method was the most reproducible method. When planning a proportional condylectomy, we advise applying the panorex-bisection method or using an optimized 3D-measuring method. Full article

Cardiovascular disease (CVD) is the leading cause of death worldwide. Management of cardiovascular risk factors, particularly hypertension and dyslipidemia, has been shown to reduce cardiovascular morbidity and mortality. However, current guidelines recommend adjusting the intensity of blood pressure- and lipid-lowering treatment according to the cardiovascular risk of the patient. Therefore, cardiovascular risk prediction is a sine qua non for optimizing cardiovascular prevention strategies, particularly in patients without established CVD or type 2 diabetes mellitus (T2DM). As a result, several cardiovascular risk prediction equations have been developed. Nevertheless, it is still unclear which is the optimal prediction risk equation. In the present review, we summarize the current knowledge regarding the accuracy of the most widely used cardiovascular risk prediction equations. Notably, most of these risk scores have not been validated in external cohorts or were shown to over- or underestimate risk in populations other than those in which they derive. Accordingly, country-specific risk scores, where available, should be preferred for cardiovascular risk stratification. Full article

Background: In order to evaluate the efficacy of intranasal mometasone furoate in patients with non-allergic rhinitis (NAR), a real-life, observational, prospective study is performed. Methods: Thirty-one patients (age 18–64 years) receive intranasal (mometasone furoate, 200 µg b.i.d. for 15 consecutive days per month for 6 consecutive months), plus isotonic nasal saline. The cytologic pattern of local inflammation, nasal airflow, through peak nasal inspiratory flow (PNIF), quality of life (QoL), through the rhinitis quality of life questionnaire (RQLQ), the sinonasal outcome test (SNOT-22), the short-form 36-item health survey (SF-36v2), and the combined symptom medication score (CSMS), and, finally, olfactory function, through Sniffin’ sticks-16 identification test (SSIT-16), are evaluated at baseline and after treatment. Results: NARNE is the most frequent cytological pattern (48% of the total sample). The therapeutic response shows improvement in olfactory function and QoL. Conclusions: The results of this study confirm that intranasal mometasone furoate is an effective treatment for patients with NAR. Full article

Consequences of a spinal cord injury (SCI) entail much more than damage to the spinal cord. The lives of people with SCI, along with those around them, experience profound long-lasting changes in nearly every life domain. SCI is a physical (biological) injury that is inextricably combined with various psychological and social consequences. The objective of this review is to present psychosocial challenges following SCI through the biopsychosocial model, beginning with acknowledgement of the larger societal effects of ableism and stigma before addressing the many unique psychosocial aspects of living with SCI. Included in this review are qualitative studies and systematic reviews on current psychosocial outcomes and consequences. This paper attempts to structure this information by dividing it into the following sections: relationships and family; changes in finances and employment; issues related to the person’s living situation; community reintegration; factors associated with mood and coping (e.g., depression, anxiety, substance use, and PTSD); self-harm behaviors (ranging from nonadherence to suicide); effects of traumatic brain injury; considerations regarding sexual health; aging with SCI; and concludes with a brief discussion about post-traumatic growth. Cultivating an understanding of the unique and interrelated psychosocial consequences of people living with SCI may help mitigate the psychosocial aftermath and serve as a reminder to providers to maintain a person-centered approach to care. Full article

The introduction of personalized medicine, through the increasing multi-omics characterization of disease, brings new challenges to disease modeling. The scope of this review was a broad evaluation of the relevance, validity, and predictive value of the current preclinical methodologies applied in stratified medicine approaches. Two case models were chosen: oncology and brain disorders. We conducted a scoping review, following the Joanna Briggs Institute guidelines, and searched PubMed, EMBASE, and relevant databases for reports describing preclinical models applied in personalized medicine approaches. A total of 1292 and 1516 records were identified from the oncology and brain disorders search, respectively. Quantitative and qualitative synthesis was performed on a final total of 63 oncology and 94 brain disorder studies. The complexity of personalized approaches highlights the need for more sophisticated biological systems to assess the integrated mechanisms of response. Despite the progress in developing innovative and complex preclinical model systems, the currently available methods need to be further developed and validated before their potential in personalized medicine endeavors can be realized. More importantly, we identified underlying gaps in preclinical research relating to the relevance of experimental models, quality assessment practices, reporting, regulation, and a gap between preclinical and clinical research. To achieve a broad implementation of predictive translational models in personalized medicine, these fundamental deficits must be addressed. Full article

Today, in the era of precision medicine, the determination of genomic instability or other potentially targetable mutations, along with BRCA 1 and BRCA 2, is a crucial component of the diagnosis and treatment management of advanced ovarian cancer. Advanced technologies such as next-generation sequencing (NGS) have enabled comprehensive genomic profiling (CGP) analysis to become more feasible for routine use in daily clinical work. Here, we present the results for the first two years of an analysis of patients with advanced ovarian cancer on a national level. The aim was to establish the position of CGP in the daily clinical practice of treating ovarian cancer. We performed a multicenter, retrospective, cross-sectional analysis on the total population of Croatian patients who were newly diagnosed with locally advanced or metastatic ovarian cancer or whose initial disease had progressed from 1 January 2020 to 1 December 2021, and whose tumors underwent CGP analysis. All 86 patients (100%) analyzed with CGP had at least one genomic alteration (GA). The median LOH was 14.6 (IQR 6.8–21.7), with 35 patients (41%) having an LOH ≥ 16. We found BRCA-positive status in 22 patients (26%). Conventional testing, which detects only BRCA mutations, would have opted for therapy with PARP inhibitors in 22 (26%) of our patients. However, CGP revealed the need for PARP inhibitors in 35 patients (41%). The results identified a significantly higher number of women who would achieve a possible benefit from targeted therapy. Hence, we believe that CGP should be a backbone diagnostic tool in the management of ovarian cancer. Full article

Although erythropoietin-stimulating agents are effective in treating anemia in patients with end-stage kidney disease (ESKD) undergoing hemodialysis, some ESKD patients, especially those with inflammation, continue to suffer from anemia. Statin, an inhibitor of hydroxymethylglutaryl-CoA (HMG-CoA) reductase with lipid-lowering effects, may have a pleiotropic effect in reducing inflammation, and thus increase hemoglobin (Hb) level. We searched the PubMed, Embase, and Cochrane databases for relevant studies. The population of interest comprised advanced chronic kidney disease (CKD) patients and ESKD patients receiving hemodialysis with statin treatment. The included study designs were randomized control trial/cohort study/pre-post observational study, and outcomes of interest were Hb, erythropoietin resistance index (ERI) and ferritin. PRISMA 2020 guidelines were followed, and risk of bias (RoB) was assessed using the RoB 2.0 tool in randomized controlled trials, and the Newcastle-Ottawa scale (NOS) in cohort studies. We eventually included ten studies (5258 participants), comprising three randomized controlled trials and seven cohort studies. Overall, Hb increased by 0.84 g/dL (95% confidence interval [CI]: −0.02 to 1.70) in all groups using statins, including single-arm cohorts, and by 0.72 g/dL (95% CI: −0.02 to 1.46) in studies with placebo control. Hb levels were higher in the study group than in the control group, with a mean difference of 0.18 g/dL (95% CI: 0.04–0.32) at baseline and 1.0 g/dL (95% CI: 0.13–1.87) at the endpoint. Ferritin increased by 9.97 ng/mL (95% CI: −5.36 to 25.29) in the study group and decreased by 34.01 ng/mL (95% CI: −148.16 to 80.14) in the control group; ferritin fluctuation was higher in the control group. In conclusion, statin may improve renal anemia in ESKD patients receiving hemodialysis and regular erythropoietin-stimulating agents. Future studies with more rigorous methodology and larger sample size study should be performed to confirm this beneficial effect. Full article

Background: We investigated how the non-medical switching (NMS) between Etanercept (ETN)/originator and SB4/biosimilar affects treatment efficacy in a rheumatic disease (RD) cohort, evaluating some laboratory parameters as loss of efficacy predictors after NMS. Methods: We enrolled 124 patients with RD (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis): 79 switchers from ETN/originator to SB4 and 45 naïve patients receiving SB4 (first biological treatment). At baseline, 6 (T1), and 12 months (T2), clinical and laboratory parameters were evaluated. Results: In naïve patients, TNF-α significantly increased at T1 in responders (NR) and non-responders (NNR). TNF-α was lower in NNR than in NR at T1 and T2. In NR and NNR, drug levels (DL) increased between T1 and T2. However, DLs were lower in NNR than in NR at T1 and T2. TNF-α was higher in switcher responders (SR) than in non-responders (SNR) at T1 and T2. In SNR, DLs were higher at baseline than in SR, but they decreased significantly at T1 and T2. Conclusions: We observed a decrease in DL and TNF-α levels after NMS in SNR. Moreover, in naïve patients, DL and TNF-α levels were higher in NR than in NNR. Monitoring DL and TNF-α levels may represent a future precision medicine approach to predict loss of efficacy after NMS. Full article

Background: The treatment of children and adolescents with disabilities (CA-Dis) and psycho-emotional disorders (CA-Psy) places special demands on dentists. Aim: To explore German dentists’ (with key expertise in paediatric dentistry) perception of their competence and comfort levels in dealing with these patients, and implications for access to care. Methods: Online questionnaire surveying demographic information and self-assessment of training, knowledge, and comfort in dealing with CA-Dis and CA-Psy among 1725 members of the German Society of Paediatric Dentistry (DGKiZ). Results: Ninety-two participants (11 male, 81 female) completed the questionnaire: 17.4% (n = 16) treated CA-Dis once or more a day; CA-Psy were rarely treated on a daily basis (7.6%; n = 7). In regard to CA-Dis, 62% (n = 57) rated their level of expertise as “good” or “very good”; for CA-Psy this was 40.2% (n = 37). Overall, 76.1% (n = 70), respectively, 88.0% (n = 81) of the respondents felt they had been inadequately prepared to treat CA-Dis or CA-Psy. Although the physical burden of treating CA-Psy was rated as “not at all stressful” or only “slightly stressful” by 45.7% of the participants, 31.5% rated the psychological distress as “very stressful” or “extremely stressful”. The better their self-assessed expertise in treating CA-Dis was, the lower their own psychological distress was rated (r = −0.34). Training on this topic seems to have an impact on the perceived burden of treating such patients. Conclusions: A core curriculum in special care dentistry needs to be embedded in the German dental curriculum. The results permit the development of health programs for workplace health management in dentistry. Full article

The rapid antigen test (RAT) has been adopted as a screening tool for SARS-CoV-2 infection in many emergency departments (EDs). We aimed to investigate the diagnostic value of the accuracy of the SARS-CoV-2 RAT as a screening tool in the ED. This retrospective observational study included patients who underwent both RAT and RT–PCR and visited the ED from 1 December 2021 to 15 March 2022. RAT and RT–PCR were performed by appropriately trained physicians. We performed detailed analyses using the E gene cyclic threshold (Ct) values of RT–PCR. Out of a total of 1875 patients, 348 (18.6%) had positive and 1527 (81.4%) had negative RT–PCR results. The overall sensitivity, specificity, positive predictive value, and negative predictive value of the RAT were 67.8%, 99.9%, 99.6%, and 93.2%, respectively. The E gene Ct value was significantly lower in the RAT-positive patients than in the RAT-negative patients (18.5 vs. 25.3, p < 0.001). When the E gene Ct cutoff was 30.0, 25.0, 20.0, and 15.0, the sensitivity of the RAT was 71.9%, 80.3%, 93.0%, and 97.8%, respectively. The sensitivity of the RAT could be considered high in patients with a high viral load, and the RAT could be used as a screening tool in the ED. Full article

Performing GI endoscopy under sedoanalgesia improves the quality-indices of the examination, in particular for cecal intubation and adenoma detection rates during colonoscopy. The implementation of procedural sedoanalgesia in GI endoscopy is also strongly recommended by the guidelines of the major international scientific societies. Nevertheless, there are regional barriers that prevent the widespread adoption of this good practice. A retrospective monocentric analytic study was performed on a cohort of 529 patients who underwent EGDS/Colonoscopy in sedoanalgesia, with personalized dosage of Fentanyl and Midazolam. ASA class, age and weight were collected for each patient. The vital parameters were recorded during, pre- and post-procedure. The rates of cecal intubation and of procedure-related complications were entered. The VAS scale was used to evaluate the efficacy of sedoanalgesia, and the Aldrete score was used for patient discharge criteria. No clinically significant differences were found between vital signs pre- and post-procedure. Both anesthesia and endoscopic-related complications occurring were few and successfully managed. At the end of examination, both the mean Aldrete score (89.56), and the VAS score (<4 in 99.1%) were suitable for discharge. For the colonoscopies, the cumulative adenoma detection rate (25%) and the cecal intubation rate in the general group (98%) and in the colorectal cancer screening group (100%) were satisfying. Pain control management is an ethical and medical issue aimed at increasing both patient compliance and the quality of the procedures. The findings of this work underscore that in selected patients personalized sedoanalgesia in GI endoscopy can be safely managed by gastroenterologists. Full article

Background: To investigate the effects of the COVID-19 lockdowns on the vasculopathic population. Methods: The Divisions of Vascular Surgery of the southern Italian peninsula joined this multicenter retrospective study. Each received a 13-point questionnaire investigating the hospitalization rate of vascular patients in the first 11 months of the COVID-19 pandemic and in the preceding 11 months. Results: 27 out of 29 Centers were enrolled. April-December 2020 (7092 patients) vs. 2019 (9161 patients): post-EVAR surveillance, hospitalization for Rutherford category 3 peripheral arterial disease, and asymptomatic carotid stenosis revascularization significantly decreased (1484 (16.2%) vs. 1014 (14.3%), p = 0.0009; 1401 (15.29%) vs. 959 (13.52%), p = 0.0006; and 1558 (17.01%) vs. 934 (13.17%), p < 0.0001, respectively), while admissions for revascularization or major amputations for chronic limb-threatening ischemia and urgent revascularization for symptomatic carotid stenosis significantly increased (1204 (16.98%) vs. 1245 (13.59%), p < 0.0001; 355 (5.01%) vs. 358 (3.91%), p = 0.0007; and 153 (2.16%) vs. 140 (1.53%), p = 0.0009, respectively). Conclusions: The suspension of elective procedures during the COVID-19 pandemic caused a significant reduction in post-EVAR surveillance, and in the hospitalization of asymptomatic carotid stenosis revascularization and Rutherford 3 peripheral arterial disease. Consequentially, we observed a significant increase in admissions for urgent revascularization for symptomatic carotid stenosis, as well as for revascularization or major amputations for chronic limb-threatening ischemia. Full article

Complex regional pain syndrome (CRPS) can result in a devastating condition. For a small number of patients, there is a non-response to any existing multimodal therapies and they ultimately request amputation. Such a drastic and final decision is not easy to take for both the patient and the surgeon and requires careful and interdisciplinary assessments and considerations. Furthermore, new surgical procedures, such as targeted muscle reinnervation (TMR) and hybrid prosthetic fitting, and multidisciplinary board advice should be included when considering amputation. In order to help other therapeutic teams in decision making for such rare but more than demanding cases, we aimed to propose an advanced algorithm for amputation indications in CRPS patients combining all these new factors. This algorithm consists of extensive pre-operative psychiatric assessment, diagnostic hybrid prosthetic fitting including fMRI analyses, multidisciplinary board advice as well as targeted muscle reinnervation and amputation procedures with final prosthetic fitting and rehabilitation. By involving multiple disciplines, this algorithm should provide optimized and individualized patient treatment on the one hand and a reliable base for decision making for therapists on the other. Full article

Physiological Closed-Loop Controlled systems continue to take a growing part in clinical practice, offering possibilities of providing more accurate, goal-directed care while reducing clinicians’ cognitive and task load. These systems also provide a standardized approach for the clinical management of the patient, leading to a reduction in care variability across multiple dimensions. For fluid management and administration, the advantages of closed-loop technology are clear, especially in conditions that require precise care to improve outcomes, such as peri-operative care, trauma, and acute burn care. Controller design varies from simplistic to complex designs, based on detailed physiological models and adaptive properties that account for inter-patient and intra-patient variability; their maturity level ranges from theoretical models tested in silico to commercially available, FDA-approved products. This comprehensive scoping review was conducted in order to assess the current technological landscape of this field, describe the systems currently available or under development, and suggest further advancements that may unfold in the coming years. Ten distinct systems were identified and discussed. Full article

Background: Clinician-reported outcome measures (ClinROMs) are frequently used in clinical trials and daily practice to evaluate the disease status and evolution of skin disorders. The minimal important difference (MID) represents the smallest difference that decreases the disease impact enough to make a treatment change worthwhile for patients. As no clear guidance exists on the preferred method to calculate MIDs for ClinROMs, we evaluated how the published values for different skin disorders should be interpreted. Methods: A systematic search was performed for MIDs of ClinROMs that focus on skin disorders and/or symptoms. The results of the questions in the credibility instrument for MIDs of Devji et al., 2020 were analyzed to gain insights into the meaning of these MIDs. Results: 29 MIDs were identified. The most common skin diseases were atopic dermatitis/eczema, followed by bullous disorders and psoriasis. A minimal important difference from the patients’ perspective was determined in 31% of the cases. However, in 41.4% of the cases, it concerned a substantial rather than a minimal difference in disease severity rated by physicians. Over half (55.1%) of the studies contained an inadequate number of patients (n < 150). MID values increased substantially in patients with severe compared to mild disease. Conclusions: MIDs of ClinROMs for skin disorders should be carefully interpreted due to the substantial differences in methodology between the studies. There is an urgent need for a consensus method to report reliable MIDs. Otherwise, this lack of uniformity could not only affect the design and conclusion of clinical trials but also skew treatment decisions. Full article

Nonalcoholic fatty liver disease (NAFLD) is considered a highly prevalent disease associated with various co-morbidities that lead to socioeconomic burden. Despite large-scale investigation, no pharmacological treatment has been approved specifically for NAFLD to date. Lifestyle modifications and diet are regarded as highly beneficial for the management of NAFLD, albeit with poor compliance, thus rendering pharmacological treatment highly important. Based on the current failure to discover a “magic bullet” to treat all patients with NAFLD and considering the multifaceted pathophysiology of the disease, combination therapies may be considered to be a rational alternative approach. In this regard, several drug categories have been considered, including, but not limited to, lipid-lowering, anti-hypertensive, glucose-lowering, anti-obesity, anti-oxidant, anti-inflammatory and anti-fibrotic medications. The aim of this review is, in addition to summarizing some of the multiple factors contributing to the pathophysiology of NAFLD, to focus on the efficacy of pharmacological combinations on the management of NAFLD. This may provide evidence for a more personalized treatment of patients with NAFLD in the future. Full article

Telemedicine gives a safe and effective way of providing healthcare. During the COVID-19 pandemic, it was possible to offer teleconsultations in primary care (Primary Care Teleconsultation-PCT). The study aimed to present an analysis of the PCTs served in the years 2020–2021 in the field of primary care in Poland to determine how the COVID-19 pandemic contributed to the development of telemedicine in primary care in Poland. The database, containing a list of medical services provided remotely obtained from the National Health Fund, was analyzed. Economic and tax indicators obtained from the Ministry of Finance were also analyzed. Personal Income Tax (PIT) value was used as an indicator of household wealth, and the Corporate Income Tax (CIT) was used as an indicator of economic activity in individual counties for 2019. Along with the COVID-19 pandemic, patients as healthcare beneficiaries can take advantage of previously unserved telemedicine services as part of primary care. The data analysis showed that, along with the introduced recommendations and restrictions in connection with the pandemic, the number of teleconsultations in 2021 increased compared to 2020. In response to the pandemic, an educational campaign targeted older patients. These indicate the most significant percentage of PCTs among patients aged 70 and older. The study shows that the awareness barrier in implementing services for the elderly population decreased significantly. There was a clear correlation between the increase in PCTs and patient age. Full article

Kinematic alignment (KA) total knee arthroplasty (TKA) has gained popularity in the past decade, but outcomes of KA-TKA in the valgus knee have never been specifically evaluated. In this retrospective single institution study, we analyzed patient reported outcomes and radiographic measurements at minimum 2 years following KA-TKA for valgus knees (n = 51) and compared the results to KA-TKA performed for non-valgus knees (n = 275). The same approach, technique, and implants were used in both groups without the need to release soft tissues or use constrained implants. Surgery duration was similar between groups (p = 0.353). Lateral distal femoral angle was lower in the valgus group postoperatively (p = 0.036). In both groups significant improvement was seen in relieving pain and improving function, while average scores were superior in the non-valgus group for visual analog score (p = 0.005), oxford knee score (p = 0.013), and knee injury and osteoarthritis outcome score (p = 0.009). However, these differences did not translate to statistically significant differences in minimal clinical important difference achievement rates. In conclusion, KA-TKA is efficient in relieving pain and improving function, as reported in subjective questionnaires, and holds advantage in patients with valgus alignment by avoiding soft tissue releases and use of constrained implants. Future studies should examine whether bone loss occurs in the lateral distal femur. Full article

Background: As the world population continues to age, interest in muscle strength loss in older people is increasing. This study aimed to confirm the association between present teeth and muscle strength in older people in Korea. Methods: Using data extracted from the 2014–2019 Korea National Health and Nutrition Examination Survey, we analyzed 5136 older people aged 65–79 years. The present teeth were based on 20 teeth, which is the criteria for comfortable mastication. The association of the risk of low muscle strength according to the present teeth was assessed using multiple logistic regression analysis, and the association was confirmed by dividing into subgroups according to sex. Results: The prevalence of low muscle strength was 17.87% among all participants. Multiple logistic regression analysis confirmed the association between low muscle strength and present teeth; a significant association was found even in the model in which all covariates were adjusted (odds ratios (OR) = 1.35; 95% confidence interval (CI): 1.13–1.61). Subgroup analysis revealed a significant association between present teeth and low muscle strength even in the model in which both covariates were adjusted for sex (Men, OR = 1.41; 95% CI: 1.02–1.95; Women, OR = 1.31; 95% CI: 1.06–1.6). Conclusion: An association between present teeth and low muscle strength was confirmed in older people in Korea. These results indicate that the importance of oral hygiene management should be emphasized to prevent muscle strength loss in older people. Full article

Allergic asthma is the most common asthma phenotype and is characterized by IgE sensitization to airborne allergens and subsequent typical asthmatic symptoms after exposure. A form of type 2 (T2) airway inflammation underlies allergic asthma. It usually arises in childhood and is accompanied by multimorbidity presenting with the occurrence of other atopic diseases, such as atopic dermatitis and allergic rhinitis. Diagnosis of the allergic endotype is based on in vivo (skin prick tests) and/or in vitro (allergen-specific IgE levels, component-resolved diagnosis (CRD)) documentation of allergic sensitization. Biomarkers identifying patients with allergic asthma include total immunoglobulin E (IgE) levels, fractional exhaled nitric oxide (FeNO) and serum eosinophil counts. The treatment of allergic asthma is a complex procedure and requires a patient-tailored approach. Besides environmental control involving allergen avoidance measurements and cornerstone pharmacological interventions based on inhaled drugs, allergen-specific immunotherapy (AIT) and biologics are now at the forefront when it comes to personalized management of asthma. The current review aims to shed light on the distinct phenotype of allergic asthma, ranging over its current definition, clinical characteristics, pathophysiology and biomarkers, as well as its treatment options in the era of precision medicine. Full article