J. Clin. Med., Volume 11, Issue 10 (May-2 2022) – 273 articles

(1) Background: Our goal was to develop a risk prediction model for mortality in patients with moderate and severe aortic stenosis (AS). (2) Methods: All patients aged 40–95 years, with echocardiographic evidence of moderate and severe AS at a single institution, were studied over a median of 2.8 (1.5–4.8) years, between 2013–2018. Patient characteristics and mortality were compared using Chi-squares, t-tests, and Kaplan–Meier (KM) curves, as appropriate. The risk calculation for mortality was derived using the Cox proportional hazards model. A risk score was calculated for each parameter, and the total sum of scores predicted the individualized risks of 1-and 5-year mortality. (3) Results: A total of 1991 patients with severe and 2212 with moderate AS were included. Severe AS patients were older, had a lower ejection fraction %, were more likely to be Caucasian, and had lower rates of obesity and smoking, but had higher rates of cardiac comorbidities and AVR (49.3% vs. 2.8%, p < 0.0001). The unadjusted overall mortality was 41.7% vs. 41%, p = 0.6530, and was not different using KM curves (log rank, p = 0.0853). The models included only patients with complete follow-up (3966 in the 1-year, and 816 in the 5-year model) and included 13 variables related to patient characteristics, degree of AS, and AVR. The C-statistic was 0.75 and 0.72 for the 1-year and the 5-year models, respectively. (4) Conclusions: Patients with moderate and severe AS experience high morbidity and mortality. The usage of a risk prediction model may provide guidance for clinical decision making in complex patients. Full article

Background: Non-contact charge density (CD) mapping allows a global visualization of left atrium (LA) activation and of activation patterns during atrial fibrillation (AF). The aim of this study was to analyze, with CD mapping, the changes in persistent AF induced by pulmonary vein isolation (PVI) and LA posterior wall isolation (LAPWI). Methods: Patients undergoing PVI + LAPWI using the Arctic Front Advance PRO^TM cryoballoon system were included in the study. CD maps were created during AF at baseline, after PVI and after LAPWI. Three distinct activation patterns were identified in the CD maps: localized irregular activation (LIA), localized rotational activation (LRA) and focal centrifugal activation (FCA). LA maps were divided into the following regions: anterior, septal, lateral, roof, posterior, inferior. Results: Eleven patients were included, with a total of 33 maps and 198 AF regions analyzed. Global and regional AF cycle lengths significantly increased after PVI and LAPWI. Baseline analysis demonstrated higher LIA, LRA and FCA numbers in the posterior and anterior regions. After PVI, there was no change in LIA, LRA and FCA occurrence. After PVI + LAPWI, a significant decrease in LRA was observed with no difference in LIA and FCA occurrence. In the regional analysis, there was a significant reduction in the LIA number in the inferior region, in the LRA number in the roof and posterior regions and in the FCA number in the lateral region. Conclusions: A global reduction in the LRA number was observed only after PVI + LAPWI; it was driven by a reduction in rotational activity in the roof and posterior regions. Full article

The present study was designed to evaluate the relaxation effect of Rubus occidentalis (RO) and ellagic acid (EA) on rabbit penile corpus cavernosum smooth muscle (PCCSM). Rabbit PCCSM was treated with ROE or EA after preincubation with nitric oxide synthase (NOS), guanylate cyclase (GC), adenylyl cyclase (AC) or protein kinase A (PKA) blocker. Cyclic nucleotides in the perfusate were analyzed using radioimmunoassay (RIA). Subsequently, perfused PCCSMs were subjected to analysis to evaluate the expression level of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS). The interaction of ROE or EA with phosphodiesterase (PDE) 5 and PDE4 inhibitors, such as udenafil (UDE) and rolipram (ROL), were also evaluated. Both ROE and EA relaxed the PCCSM in a concentration-dependent manner. Coincubation of ROE or EA with NOS, GC, AC, or PKA blocker significantly decreased the ROE- and EA-induced relaxation. Pretreatment of ROE and EA significantly upregulated the cyclic guanosine monophosphate (cGMP), cyclic adenosine 3′,5′-monophosphate (cAMP), and eNOS levels in the perfused PCCSM. Furthermore, the treatment of ROE and EA markedly increased the UDE- and ROL-induced relaxation of the PCCSM. In conclusion, ROE and EA induced PCCSM relaxation by activating the nitric oxide (NO)-cGMp and cAMp signaling pathways and may have a synergistic action to improve erectile function. Full article

The purpose of this article was to assess the effectiveness of ozone therapy as an adjunct to mechanical therapy in periodontitis patients. Thirty-two patients diagnosed with generalized periodontitis were selected, with a total of 655 teeth examined. Each patient’s mouth was divided into four quadrants (the split-mouth model) to be randomly treated with four sessions of gaseous ozone or air. The following clinical variables were recorded: the gingival index, the periodontal clinical attachment loss, the Miller’s mobility index and the clinical improvements, as assessed through the visual analog scale (VAS). In addition, the microorganisms were qualitatively compared. After four weeks of treatment, the teeth of the ozone-treated quadrants showed statistically significant reductions in the gingival index and an improvement in the clinical attachment (p < 0.0001). The same treatment also significantly improved mobility by between 70% and 86% compared to the control group (p < 0.0001). Statistically significant differences were also recorded for the VAS (p < 0.0001). In the qualitative study of the subgingival flora, significant differences were observed (p < 0.0001). The overall results of this trial support the view that ozone treatment is effective and well tolerated in cases of generalized chronic periodontitis. Full article

(1) Background: In patients hospitalized with COVID-19 pneumonia, especially moderate and severe forms, a cytokine storm may occur, characterized by the worsening of symptoms and the alteration of biological parameters on days 8–12 of the disease. The therapeutic options for cytokine storms are still controversial, requiring further clarification; (2) Methods: Our study included 344 patients with moderate and severe pneumonia admitted to the internal medicine department who developed a cytokine storm (diagnosed by clinical and biochemical criteria). In group A, 149 patients were treated with Remdesivir and Tocilizumab (together with other drugs, including corticosteroids, antibiotics and anticoagulants), and in group B, 195 patients received Remdesivir and Anakinra. Patients were monitored clinically and by laboratory tests, with the main biochemical parameters being CRP (C-reactive protein), LDH (lactic dehydrogenase) and ferritin; (3) Results: Patients were followed up from a clinical point of view and also by the measurement of CRP, LDH and ferritin at the beginning of therapy, on days three to four and on the tenth day. In both groups, we registered a clinical improvement and a decrease in the parameters of the cytokine storm. In group A, with the IL-6 antagonist Tocilizumab, the beneficial effect occurred faster; in group B, with the IL-1 antagonist Anakinra, the beneficial effect was slower. (4) Conclusions: The use of the immunomodulators, Tocilizumab and Anakinra, in the cytokine storm showed favorable effects, both clinical and biochemical. Full article

Primary hyperparathyroidism (pHPT) is a common endocrine disorder due to hyperfunctioning parathyroid glands. To date, the only curing therapy is surgical removal of the dysfunctional gland, making correct detection and localization crucial in order to perform a minimally invasive parathyroidectomy. ¹⁸F-Fluorocholine positron emission tomography/computed tomography (¹⁸F-FCH PET/CT) has shown promising results for the detection of pHPT, suggesting superiority over conventional imaging with ultrasounds or scintigraphy. A total of 33 patients with pHPT who had negative or equivocal findings in conventional imaging received ¹⁸F-FCH PET/CT preoperatively and were retrospectively included. A pathological hyperfunctional parathyroid gland was diagnosed in 24 cases (positive PET, 72.7%), 4 cases showed equivocal choline uptake (equivocal PET, 12.1%), and in 5 cases, no enhanced choline uptake was evident (negative PET, 15.2%). Twelve of the twenty-four detected adenoma patients underwent surgery, and in all cases, a pathological parathyroid adenoma was resected at the site detected by PET/CT. Two of the six patients without pathological choline uptake who received a parathyroidectomy revealed no evidence of parathyroid adenoma tissue in the histopathological evaluation. This retrospective study analyzes ¹⁸F-FCH PET/CT in a challenging patient cohort with pHPT and negative or equivocal conventional imaging results and supports the use of ¹⁸F-FCH for the diagnosis of hyperfunctional parathyroid tissue, especially in this patient setting, with a 100% true positive and true negative detection rate. Our study further demonstrates the importance of ¹⁸F-FCH PET/CT for successful surgical guidance. Full article

Different surgical techniques are available to adequately correct the primary cleft lip deformity; however, when compared, none of these techniques have proven superior with regard to achieving optimal aesthetic results. Thus, the aim of this retrospective study was to assess the nasolabial appearance in patients with unilateral cleft lip and palate (UCLP) at age five with reference to two techniques for primary cleft lip repair used in our service: Pfeifer’s wave-line procedure and Randall’s technique. A modified Asher–McDade Aesthetic Index was applied to appraise the nasolabial area by means of 2D photographs of non-syndromic five-year-old patients with a UCLP. In this context, three parameters were assessed: 1. nasal frontal view; 2. shape of the vermilion border and philtrum length; and 3. the nasolabial profile. Five professionals experienced in cleft care were asked to rate the photographs on two occasions. Overall, 53 patients were included in the final analysis, 28 of whom underwent lip repair according to Pfeifer; 25 were treated employing Randall’s technique. Statistically significant differences between the two techniques regarding philtrum length and vermilion border were found (p = 0.046). With reference to the other parameters assessed, no significant differences were determined. The results suggest that Randall’s cleft lip repair may allow for more accurate alignment of the vermilion border and more adequate correction of the cleft lip length discrepancy in comparison to Pfeifer’s wave-line technique. Full article

Background: The treatment options for basal ganglia intracerebral hemorrhage (ICH), either surgical or conservative, remain controversial. A previous study developed “A new modified ICH (MICH) score” that suggests which treatment option will be better for basal ganglia ICH. According to this scoring system, a MICH score of 0 or 1 indicates that conservative treatment is better than surgical treatment. The purpose of this study was to determine whether conservative treatment is still a better option for a basal ganglia hemorrhage in patients with MICH scores of 0 and 1, with initial poor motor grades. Methods: This retrospective study was comprised of 41 patients with a spontaneous basal ganglia hemorrhage. These patient groups had no previous brain lesions, their initial MICH score was 0 or 1, and the manual muscle test (MMT) of their hand was grade 2+ or lower in the initial evaluation. All patients were transferred to the Department of Rehabilitation Medicine and received rehabilitation treatment. Ten patients had an operative intervention, which was burr-hole aspiration or craniotomy with hematoma removal. The control group included 31 patients who underwent conservative treatment. Outcome evaluations used the Berg Balance Scale (BBS), Modified Barthel Index (MBI), and Brunnstrom recovery stage (BRS) which were evaluated at initial and regular follow-ups after 1, 3, and 6 months. We defined an improvement state if the BRS of their hand became 4 or more in 6 months, which means an escape from the synergic pattern. Results: Demographic characteristics showed no significant differences in age, sex, hemiplegic side, initial GCS score, presence of IVH and hydrocephalus, or distribution of MICH scores 0 and 1. There was only a significant difference in the distribution of hematoma volume between groups of less than 20 mL and groups from 21 to 50 mL (p = 0.049). There were no significant differences in MBI values in 1 month or improvement of BRS of their hand in 6 months between the two groups. Conclusions: Even in the group classified as predominantly conservative in basal ganglia hemorrhage patients, if the initial muscle strength is low, it is necessary to reconsider whether conservative treatment is superior to surgical treatment in terms of functional improvement. Full article

Background: To assess the performance of cochlear implant users, speech comprehension benefits are generally measured in controlled sound room environments of the laboratory. For field-based assessment of preference, questionnaires are generally used. Since questionnaires are typically administered at the end of an experimental period, they can be inaccurate due to retrospective recall. An alternative known as ecological momentary assessment (EMA) has begun to be used for clinical research. The objective of this study was to determine the feasibility of using EMA to obtain in-the-moment responses from cochlear implant users describing their technology preference in specific acoustic listening situations. Methods: Over a two-week period, eleven adult cochlear implant users compared two listening programs containing different sound processing technologies during everyday take-home use. Their task was to compare and vote for their preferred program. Results: A total of 205 votes were collected from acoustic environments that were classified into six listening scenes. The analysis yielded different patterns of voting among the subjects. Two subjects had a consistent preference for one sound processing technology across all acoustic scenes, three subjects changed their preference based on the acoustic scene, and six subjects had no conclusive preference for either technology. Conclusion: Results show that EMA is suitable for quantifying real-world self-reported preference, showing inter-subject variability in different listening environments. However, there is uncertainty that patients will not provide sufficient spontaneous feedback. One improvement for future research is a participant forced prompt to improve response rates. Full article

Severe acquired brain injury (SABI) is a major global public health problem and a source of disability. A major contributor to disability after SABI is limited access to multidisciplinary rehabilitation, despite evidence of sustained functional gains, improved quality of life, increased return to work, and reduced need for long-term care. Twelve patients with a diagnosis of SABI were enrolled and equally divided into two groups: experimental and control. Patients in both groups underwent intensive neurorehabilitation according to the severity of their disabilities (motor, psycho-cognitive, and sensory deficits). However, in the experimental group, the treatment was performed by using a humanoid robot. At baseline, the two groups differed significantly only in Severe Impairment Battery (SIB) scores. Results showed that the experimental treatment had a higher effect than the traditional one on quality of life and mood. In conclusion, this pilot study provides evidence of the possible effects of relational and cognitive stimulation in more severely brain-injured patients. Full article

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and dose-limiting adverse side effect of treatment. CIPN affects the oncological prognosis of patients, as well as their quality of life. To date, no specific pharmacological therapy has demonstrated effectiveness in preventing CIPN. Accumulating preclinical evidence suggests that renin-angiotensin system (RAS) inhibitors may have neuroprotective effects. One hundred and twenty patients were included in this observational study and were followed from the beginning of their neurotoxic chemotherapy schedule until their final assessment, at least one month after its cessation. The National Cancer Institute’s common toxicity criteria 4.0 (NCI-CTC 4.0) were used to grade the severity of adverse events. Follow-ups also included electrochemical skin conductance and scales for pain, quality of life and disability. Among patients receiving a platinum-based regimen, the mean grade of sensory neuropathy (NCI-CTC 4.0) was significantly lower in the RAS inhibitor group after the end of their anticancer treatment schedule. Because of the observational design of the study, patients in the RAS inhibitor group cumulated comorbidities at risk of developing CIPN. Randomized controlled trials in platinum-based regimens would be worth conducting in the future to confirm the neuroprotective potential of RAS inhibitors during chemotherapy. Full article

Fascinatingly, the immune-privileged healthy eye has a small unique population of microbiota. The human microbiome project led to continuing interest in the ocular microbiome. Typically, ocular microflorae are commensals of low diversity that colonize the external and internal sites of the eye, without instigating any disorders. Ocular commensals modulate immunity and optimally regulate host defense against pathogenic invasion, both on the ocular surface and neuroretina. Yet, any alteration in this symbiotic relationship culminates in the perturbation of ocular homeostasis and shifts the equilibrium toward local or systemic inflammation and, in turn, impaired visual function. A compositional variation in the ocular microbiota is associated with surface disorders such as keratitis, blepharitis, and conjunctivitis. Nevertheless, innovative studies now implicate non-ocular microbial dysbiosis in glaucoma, age-related macular degeneration (AMD), uveitis, and diabetic retinopathy. Accordingly, prompt identification of the extra-ocular etiology and a methodical understanding of the mechanisms of invasion and host-microbial interaction is of paramount importance for preventative and therapeutic interventions for vision-threatening conditions. This review article aims to explore the current literature evidence to better comprehend the role of oral pathogens in the etiopathogenesis of ocular diseases, specifically AMD. Full article

In this study, we compare the efficacy and diagnostic concordance of the ICDAS, the radiographic criterion and the instrument known as the DIAGNOdent fluorescence laser pen on occlusal caries lesions using a histological section as the gold standard. Of 100 teeth that did not present cavitated occlusal lesions or occlusal fillings, 80 were chosen through a randomization program and examined by two previously trained and calibrated researchers. Subsequently, the teeth were sectioned with a diamond disk and observed under an optical microscope. The results were studied for caries with a limit established in enamel and caries with extension to dentin. The intra-examiner (0.821–0.933) and inter-examiner (0.817–0.924) reproducibility obtained for both ICDAS and DIAGNOdent for the diagnosis of borderline enamel caries was high. Similarly, intra-examiner (0.686–1.000) and inter-examiner (0.809–0.944) reproducibility for diagnosis of caries with dentin extension was also high for both methods. The sensitivity obtained was 0.76 (ICDAS), 0.87 (DIAGNOdent) and 0.58 (Rx), whereas the specificity obtained was 0.66 (ICDAS), 0.4 (DIAGNOdent) and 0.77 (Rx) for lesions limited to enamel. For lesions with extension to dentin, the sensitivity obtained was 0.73 (ICDAS), 0.82 (DIAGNOdent) and 0.09 (Rx), and the specificity obtained was 0.79 (ICDAS), 0.52 (DIAGNOdent) and 0.97 (Rx). Sensitivity increases in both cases by combining diagnostic methods. In conclusion, ICDAS and DIAGNOdent are better diagnostic methods than Rx for the detection of occlusal caries, and the combination of these methods helps to obtain a better diagnosis. Full article

Working memory (WM) impairments are common and debilitating symptoms of multiple sclerosis (MS), often emerging early in the disease. Predominantly, WM impairments are considered in a binary manner, with patients considered either impaired or not based on a single test. However, WM is comprised of different activated subcomponents depending upon the type of information (auditory, visual) and integration requirements. As such, unique WM impairment phenotypes occur. We aimed to determine the most frequent WM phenotypes in early MS, how they progress and which WM test(s) provide the best measure of WM impairment. A total of 88 participants (63 early relapsing–remitting MS: RRMS, 25 healthy controls) completed five WM tests (visual–spatial, auditory, episodic, executive) as well as the symbol digit modalities test as a measure of processing speed. RRMS patients were followed-up for two years. Factors affecting WM (age/gender/intelligence/mood) and MS factors (disease duration/disability) were also evaluated. Some 61.9% of RRMS patients were impaired on at least one WM subcomponent. The most subcomponents impaired were visual,–spatial and auditory WM. The most common WM phenotypes were; (1) visual–spatial sketchpad + episodic buffer + phonological loop + central executive, (2) visual–spatial sketchpad + central executive. The test of visual–spatial WM provided the best diagnostic accuracy for detecting WM impairment and progression. The SDMT did not achieve diagnostic accuracy greater than chance. Although this may be unsurprising, given that the SDMT is a measure of cognitive processing speed in MS, this does highlight the limitation of the SDMT as a general screening tool for cognitive impairment in early MS. Full article

Background: Dapagliflozin has been shown to reduce morbidity and mortality in Heart Failure with reduced Ejection Fraction (HFrEF), but its impact on exercise capacity of non-diabetic HF outpatients is unknown. Methods: Adult non-diabetic HF patients with a left ventricular ejection fraction (LVEF) <50% were randomized 1:1 to receive dapagliflozin 10 mg or to continue with HF medication. Patients underwent an initial evaluation which was repeated after 6 months. The variation of several clinical parameters was compared, with the primary endpoint being the 6 month peak oxygen uptake (pVO₂) variation. Results: A total of 40 patients were included (mean age 61 ± 13 years, 82.5% male, mean LVEF 34 ± 5%), half being randomized to dapagliflozin, with no significant baseline differences between groups. The reported drug compliance was 100%, with no major safety events. No statistically significant difference in HF events was found (p = 0.609). There was a 24% reduction in the number of patients in New York Heart Association (NYHA) class III in the treatment group as opposed to a 15.8% increase in the control group (p = 0.004). Patients under dapagliflozin had a greater improvement in pVO₂ (3.1 vs. 0.1 mL/kg/min, p = 0.030) and a greater reduction in NT-proBNP levels (−217.6 vs. 650.3 pg/mL, p = 0.007). Conclusion: Dapagliflozin was associated with a significant improvement in cardiopulmonary fitness at 6 months follow-up in non-diabetic HFrEF patients. Full article

The determination of acylcarnitines (AC) in dried blood spots (DBS) by tandem mass spectrometry in newborn screening (NBS) programs has enabled medium-chain acyl-coA dehydrogenase deficiency (MCADD) to be identified in presymptomatic newborns. Nevertheless, different confirmatory tests must be performed to confirm the diagnosis. In this work, we have collected and analyzed the NBS results and confirmatory test results (plasma AC, molecular findings, and lymphocyte MCAD activity) of forty individuals, correlating them with clinical outcomes and treatment, with the aim of obtaining useful diagnostic information that could be applied in the follow-up of the patients. Our results led us to classify patients into two groups. The first group (14 cases) had high increased octanoylcarnitine (C8) levels, biallelic pathogenic variants, and severe impaired enzyme activity (<10% of the intra-assay control (IAC)); all of these cases received nutritional therapy and required carnitine supplementation during follow-up, representing the most severe form of the disease. The second group (16 patients) was a heterogeneous group presenting moderate increases in C8, biallelic likely pathogenic/pathogenic variants, and intermediate activity (<41% IAC). All of them are currently asymptomatic and could be considered as having a milder form of the disease. Finally, eight cases presented a normal–mild increase in plasma C8, with only one pathogenic variant detected, and high–intermediate residual activity (15–100%). Based on our results, we confirm that combined evaluation of acylcarnitine profiles, genetic findings, and residual enzyme activities proves useful in predicting the risk of future metabolic decompensation, in making decisions regarding future treatment or follow-up, and also in confirming the clinical effects of unknown clinical variants. Full article

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, affecting up to 14% of pregnant women. The population of patients with risk factors of GDM is increasing; thus, it is essential to improve management of this condition. One of the key factors affecting perinatal outcomes in GDM is glycaemic control. Until recently, glucose monitoring was only available with self-monitoring of blood glucose (SMBG). However, nowadays, there is a new method, continuous glucose monitoring (CGM), which has been shown to be safe in pregnancy. Since proper glycaemia assessment has been shown to affect perinatal outcomes, we decided to perform a systematic review to analyse the role of CGM in glycaemic control in GDM. We conducted a web search of the MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science databases according to the PRISMA guidelines. The web search was performed by two independent researchers and resulted in 14 articles included in the systematic review. The study protocol was registered in the PROSPERO database with registration number CRD42021289883. The main outcome of the systematic review was determining that, when compared, CGM played an important role in better glycaemic control than SMBG. Furthermore, glycaemic control with CGM improved qualification for insulin therapy. However, most of the articles did not reveal CGM’s role in improving neonatal outcomes. Therefore, more studies are needed to analyse the role of CGM in affecting perinatal outcomes in GDM. Full article

(1) Background: Exercise is recommended to improve physical fitness in patients recovering from acute type A aortic dissection (ATAAD). However, surgery corrects the diseased blood vessels and reduces the risk of ATAAD, but it does not redefine a safe exercise blood pressure (BP) threshold. This review aimed to discuss whether the safe threshold of exercise BP can be upregulated after ATAAD surgery to increase exercise intensity with additional benefits. (2) Data sources: The PubMed databases were searched with the keywords “type A acute aortic dissection surgery”, “exercise”, “BP”, “stress”, and variations of these terms. (3) Study selection: Data from clinical trials, guidelines, and recent reviews were selected for review. (4) Results: Regular exercise can be considered a cardioprotective intervention for aortic dissection patients by attenuating hemodynamic responses at rest and during exercise. Previous studies have mainly focused on moderate-intensity aerobic exercise. In practice, the exercise systolic BP of some patients was higher than 160 mm Hg without adverse events, which indicates that the training intensity may be underestimated for patients after ATAAD surgery. Limited studies suggest a light-to-moderate resistance training for selected patients because it may cause a greater increase in BP. (5) Conclusions: Moderate-intensity continuous aerobic exercise supplemented by low-intensity resistance training is appropriate for cardiac rehabilitation after ATAAD surgery. The BP increase based on the normal exercise BP response, corresponding to the moderate-intensity is relatively safe. For high-risk post-ATAAD patients, considering the overall volume of training, personalizing the exercise regimen to remain within “safe” BP limits, and avoiding excessive fluctuations in BP should be the primary considerations for exercise training. Full article

Postoperative bowel dysfunction poses difficulty to patients during their recovery from surgery, and reversal agents may affect bowel function. This study aimed to investigate and compare the effects of sugammadex and a neostigmine/glycopyrrolate combination on postoperative bowel movement in patients undergoing robotic thyroidectomy. The electronic medical records of 122 patients, who underwent robotic thyroidectomy between March 2018 and December 2020, were retrospectively reviewed. Demographic, clinical, and laboratory findings and the first gas-passing time after surgery were assessed. The number of patients with a first gas emission time over 24 h was significantly higher in the neostigmine group than in the sugammadex group (p = 0.008). Multivariate logistic regression analysis indicated that sugammadex was a prognostic factor for the first gas-passing time within 24 h (odds ratio = 4.60, 95% confidence interval 1.47–14.36, p = 0.005). Although postoperative bowel motility, based on the first gas emission time, was comparable, the number of patients with a first gas emission time within 24 h was significantly higher in the sugammadex group than in the neostigmine group. This shows that the use of sugammadex did not affect the delayed recovery of postoperative bowel motility after robotic thyroidectomy. Full article

Background: Performing functional magnetic resonance imaging (fMRI) examination is difficult when a child needs to stay awake and cooperate. Many techniques help to prepare them for the study but without modification of the examination protocol. The objective of this research was to prepare a gamified motor paradigm (“computer game”) that will improve the fMRI examination of young children. Methods: After preparing a dedicated application the fMRI examination was performed on 60 healthy children (10 girls and 10 boys in each age group of 4, 5, and 6 years old). Each child performed the gamified and a standard motor paradigm, both based on squeezing a rubber bulb. The effectiveness of squeezing were compared. Results: With the application of the gamified paradigm children completed significantly more active blocks (3.3 ± 1.4) than for the standard paradigm (2.2 ± 1.6) (p < 0.0001). In mixed-effects Poisson regression, age (IRR = 1.9; 95%CI: 1.5–2.5) and application of gamified paradigm (IRR = 5.6; 95%CI: 1.1–28.0) were significantly associated with more completed blocks. Conclusions: The gamified motor paradigm performed better than a standard paradigm in the fMRI examination of children between 4 and 6 years old. It allowed a significant increase in the number of completed active blocks and also better squeezing effectiveness in each block. Full article

In epidemiological studies, higher calcium intake has been associated with decreased colorectal cancer (CRC) incidence. However, whether circulating calcium concentrations are associated with CRC prognosis is largely unknown. In this retrospective cohort analysis, we identified 498 patients diagnosed with stage I–IV CRC between the years of 2000 and 2018 in whom calcium and albumin level measurements within 3 months of diagnosis had been taken. We used the Kaplan–Meier method for survival analysis. We used multivariate Cox proportional hazards regression to identify associations between corrected calcium levels and CRC survival outcomes. Corrected calcium levels in the highest tertile were associated with significantly lower progression-free survival rates (hazard ratio (HR) 1.85; 95% confidence interval (CI) 1.28–2.69; p = 0.001) and overall survival (HR 1.86; 95% CI 1.26–2.74, p = 0.002) in patients with stage IV or recurrent CRC, and significantly lower disease-free survival rates (HR 1.44; 95% confidence interval (CI) 1.02–2.03; p = 0.040) and overall survival rates (HR 1.72; 95% CI 1.18–2.50; p = 0.004) in patients with stage I–III disease. In conclusion, higher corrected calcium levels after the diagnosis of CRC were significantly associated with decreased survival rates. Prospective trials are necessary to confirm this association. Full article

Introduction. Long-term non-progressors (LTNPs) are HIV-infected individuals (HIV⁺) whose viral replication is controlled. However, these individuals experience complications associated with HIV, among them, bone remodeling impairment. This study aims to perform a comprehensive bone health assessment and its association with the inflammatory status of HIV⁺ LTNPs. A cross-sectional study was conducted comparing bone strength components (bone mineral density and bone tissue quality) between age-, sex-, and comorbidities-matched groups of HIV⁺ LTNPs, HIV⁺ progressors, and HIV-negative individuals. A panel of bone turnover and inflammatory biomarkers was measured in fasting plasma using ELISA. Bone tissue quality was assessed by bone microindentation, a technique that directly measures the bone resistance to fracture and yields a dimensionless quantifiable parameter called bone material strength (BMSi). Thirty patients were included: ten LTNPs, ten HIV⁺ progressors, and ten HIV-negative individuals. LTNPs showed an abnormal pattern of immune activation that was represented by significantly lower levels of anti-inflammatory cytokine IL-10 (p = 0.03), pro-inflammatory cytokine IL-8 (p = 0.01), and TNF-α (p < 0.001) with respect to the other groups. Regarding bone health, LTNPs presented lower BMSi, and thus, worse bone tissue quality than HIV-negative individuals (83 (78–85) vs. 90 (89–93), respectively; p = 0.003), and also lower BMSi than HIV⁺ progressors (83 (78–85) vs. 86 (85–89), respectively; p = 0.022). A trend was found of lower BMSi in HIV⁺ progressors with respect to the HIV-negative individuals (86 (85–89) vs. 90 (89–93), respectively; p = 0.083). No differences were detected in bone mineral density between groups. In conclusion, LTNPs showed a different inflammatory profile, along with worse bone tissue quality, when compared to HIV⁺ progressors and HIV-negative individuals. This may contribute to increasing evidence that HIV infection itself has a deleterious effect on bone tissue, likely through a persistent altered inflammation status. Full article

Background: The COVID-19 pandemic increased the complexity of the clinical management and pharmacological treatment of patients presenting with an Acute Coronary Syndrome (ACS). Aim: to explore the incidence and prognostic impact of in-hospital bleeding in patients presenting with ACS before and during the COVID-19 pandemic. Methods: We evaluated in-hospital Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding among 2851 patients with ACS from 17 Italian centers during the first wave of the COVID-19 pandemic (i.e., March–April 2020) and in the same period in the previous two years. Results: The incidence of in-hospital TIMI major and minor bleeding was similar before and during the COVID-19 pandemic. TIMI major or minor bleeding was associated with a significant threefold increase in all-cause mortality, with a similar prognostic impact before and during the COVID-19 pandemic. Conclusions: the incidence and clinical impact of in-hospital bleeding in ACS patients was similar before and during the COVID-19 pandemic. We confirmed a significant and sizable negative prognostic impact of in-hospital bleeding in ACS patients. Full article

Prostate cancer (PCa) is one of the most common cancers among men, and its incidence has been rising through the years. Several risk factors have been associated with this disease and unhealthy lifestyles and inflammation were appointed as major contributors for PCa development, progression, and severity. Despite the advantages associated with the currently used diagnostic tools [prostate-specific antigen(PSA) serum levels and digital rectal examination (DRE)], the development of effective approaches for PCa diagnosis is still necessary. Finding lifestyle-associated proteins that may predict the development of PCa seems to be a promising strategy to improve PCa diagnosis. In this context, several biomarkers have been identified, including circulating biomarkers (CRP, insulin, C-peptide, TNFα-R2, adiponectin, IL-6, total PSA, free PSA, and p2PSA), urine biomarkers (PCA3, guanidine, phenylacetylglycine, and glycine), proteins expressed in exosomes (afamin, vitamin D-binding protein, and filamin A), and miRNAs expressed in prostate tissue (miRNA-21, miRNA-101, and miRNA-182). In conclusion, exploring the impact of lifestyle and inflammation on PCa development and progression may open doors to the identification of new biomarkers. The discovery of new PCa diagnostic biomarkers should contribute to reduce overdiagnosis and overtreatment. Full article

The aim of this cross-sectional study was to assess the influence of simvastatin treatment in children with familial hypercholesterolemia (FH) on parameters of cellular immunity. Twenty-six children with FH were included, of which thirteen were treated with 10 mg simvastatin for at least 26 weeks, and thirteen were age- and sex-matched with a low-cholesterol diet only. Total WBC count and lipid profile were measured. Flow cytometry was used to identify lymphocyte subsets and determine the expression of adhesion molecules (AM) and toll-like receptors (TLRs) on leukocytes. No differences were found in the basic values of peripheral blood count and subpopulations of lymphocytes between groups. The percentage of granulocytes with the expression of AM was higher in those treated with statins. The TLR-2 expression on granulocytes and monocytes showed higher values, whereas the TLR-4 expression was lower on lymphocytes and granulocytes in simvastatin-treated children. Treatment with simvastatin in children with FH is not associated with alterations in the amounts of granulocytes and monocytes. There is no association between statin treatment and the pattern of peripheral blood lymphocyte subpopulations. The role of AM and TLRs needs further investigation, given the effect of statins on the innate immunity may be important for their efficacy and safety during growth. Full article

The early endoscopic identification, resection, and treatment of precancerous adenoma and early-stage cancer has been shown to reduce not only the prevalence of colorectal cancer but also its mortality rate. Recent advances in endoscopic devices and imaging technology have dramatically improved our ability to detect colorectal lesions and predict their pathological diagnosis. In addition to this, rapid advances in artificial intelligence (AI) technology mean that AI-related research and development is now progressing in the diagnostic imaging field, particularly colonoscopy, and AIs (i.e., devices that mimic cognitive abilities, such as learning and problem-solving) already approved as medical devices are now being introduced into everyday clinical practice. Today, there is an increasing expectation that sophisticated AIs will be able to provide high-level diagnostic performance irrespective of the level of skill of the endoscopist. In this paper, we review colonoscopy-related AI research and the AIs that have already been approved and discuss the future prospects of this technology. Full article

Emotional dysregulation (ED) is common in attention-deficit/hyperactivity disorder (ADHD). Nonetheless, research on ADHD in children with autism spectrum disorder (ASD) and ADHD is still ongoing. Several studies suggest that methylphenidate (MPH) may be effective for ED in ADHD, while there is not enough evidence about its use in ASD with comorbid ADHD. This naturalistic study aims to investigate the effectiveness of immediate- and extended-release MPH in the treatment of ED in 70 children and adolescents (6–18 years), with a diagnosis of ADHD (n = 41) and of ASD with comorbid ADHD (n = 29), using the Child Behavior Checklist—Attention/Aggressive/Anxious (CBCL-AAA). Their parents completed the CBCL twice—first during the summer medication-free period, that is, at least one month after drug interruption; and again after three months of treatment restart. Results demonstrate that MPH is associated with a statistically significant reduction in ED in ADHD and ASD, without substantial adverse events, supporting the use of psychostimulants for the treatment of ED in these neurodevelopmental disorders. Full article

Mitral valve disease, and in particular mitral regurgitation, is a common clinical entity. Until recently, surgical repair and replacement were the only therapeutic options available, leaving many patients untreated mostly due to excessive surgical risk. Over the last number of years, huge strides have been made regarding percutaneous, catheter-based solutions for mitral valve disease. Transcatheter repair procedures have most commonly been used, and in recent years there has been exponential growth in the number of devices available for transcatheter mitral valve replacement. Furthermore, the evolution of these devices has resulted in both smaller delivery systems and a shift towards transeptal access, negating the need for surgical incisions. In line with these advancements, and clinical trials demonstrating promising outcomes in carefully selected cases, recent guidelines have strengthened their recommendations for these devices. It is appropriate, therefore, to now review the current transcatheter repair and replacement devices available and the evidence for their use. Full article

This study aimed to explore the safety and efficacy of neoadjuvant SCRT and tegafur–uracil/leucovorin plus oxaliplatin (TEGAFOX) for LARC in comparison to those of the modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX-6) regimen. We retrospectively evaluated 15 and 22 patients with LARC who underwent SCRT, followed by consolidation chemotherapy with TEGAFOX and mFOLFOX-6 before surgery, respectively, between January 2015 and December 2019. The primary endpoint was the tumor response rate. The secondary endpoints were compliance, toxicity, complications, overall survival (OS), and disease-free survival (DFS). The dose reduction rate was lower in the TEGAFOX group (0 vs. 9.1% (n = 2)). No grade III-IV toxicities occurred in the TEGAFOX group. Two and four patients in the TEGAFOX and mFOLFOX-6 groups, respectively, achieved clinical complete responses. The pathologic complete response rate was lower in the TEGAFOX group (7.7% vs. 17.6%). Overall, 11 (73.3%) and 17 (81.0%) patients had a neoadjuvant rectal (NAR) score of <16 in the TEGAFOX and mFOLFOX-6 groups, respectively. All patients in this study received sphincter-preservation surgery. One patient in each group developed Clavien–Dindo grade III complications. There were no significant between-group differences in the 3-year OS (81.8% vs. 84.8%, p = 0.884) and 3-year DFS (72% vs. 71.6%, p = 0.824) rates. TEGAFOX, as consolidation chemotherapy after SCRT, achieves good tumor downstaging and patient compliance in LARC. The toxicity, complications, and surgical outcomes are similar to those of mFOLFOX-6. Thus, TEGAFOX can be considered a chemotherapy option for rectal cancer treatment. Full article