Background: Severe calcification of the ascending aorta increases the peri-operative risk for neurological complications in patients with severe aortic stenosis. Transcatheter aortic valve implantation (TAVI) seems to be an optimal treatment option in these patients. However, the impact of the extent of aortic calcification on procedural and neurological outcomes during TAVI is unclear. Methods: Data from 3010 patients with severe native aortic valve stenosis treated with ACURATE neo/neo2 from May 2012 to July 2022 were evaluated and matched by 2-to-1 nearest-neighbor matching to identify one patient with porcelain aorta (PA) (n = 492) compared with two patients without PA (n = 984). PA was additionally subdivided into circumferential (classic PA) (n = 89; 3.0%) and non-circumferential (partial PA) (n = 403; 13.4%) calcification. We compared outcomes according to VARC-3 criteria among patients with and without PA and identified predictors for occurrence of stroke in the overall population. Results: Technical success (88.5% vs. 87.4%, p = 0.589) and device success at 30 days (82.3% vs. 81.5%, p = 0.755) after transcatheter ACURATE neo/neo2 implantation according to VARC-3 definition was high and did not differ between non-calcified aortas or PA. The rate of in-hospital complications according to VARC-3-definitions was low in both groups. Rates of all stroke (3.2% (n = 31) vs. 2.6% (n = 13), p = 0.705) or transitory ischemic attacks (1.1% vs. 1.2%, p = 1.000) did not differ significantly. Thirty-day all-cause mortality did not differ (3.0% vs. 3.2%, RR 1.1; p = 0.775). Overall device migration/embolization (OR 5.0 $\left[2.10;11.87\right]$), severe bleeding (OR 1.79 $\left[1.11;2.89\right]$), and major structural cardiac complications (OR 3.37 $\left[1.32;8.57\right]$) were identified as independent predictors for in-hospital stroke in a multivariate analysis after implantation of ACURATE neo/neo2. Conclusion: A porcelain aorta does not increase the risk of neurological complications after transfemoral ACURATE neo/neo2 implantation. Based on these findings, transfemoral ACURATE neo/neo2 implantation is safe in these particularly vulnerable patients. Full article

A correlation between mental illness and systemic rheumatoid arthritis (RA) has been observed in several prior investigations. However, little is known about the causative relationship between them. The present study aimed to systematically investigate the potential association between genetically determined mental illness and RA. Two-sample bidirectional Mendelian randomization (MR) analysis was performed using publicly released genome-wide association studies (GWAS). We selected independent genetic variants associated with four mental illnesses (bipolar disorder, broad depression, major depression, and anxiety) as instrumental variables. The inverse variance weighted (IVW) method was used as the primary analysis to assess the causal relationship between mental illness and RA. Results of the IVW analysis suggested that genetic predisposition to bipolar disorder was associated with a decreased risk of RA (odds ratio [OR] = 0.825, 95% CI = 0.716 to 0.95, p = 0.007). Furthermore, we did not find a significant causal effect of RA on bipolar disorder in the reverse MR analysis (p > 0.05). In addition, our study found no evidence of a bidirectional causal relationship between genetically predicted broad depression, major depression, anxiety, and RA (p > 0.05). The genetically proxied bipolar disorder population has a lower RA risk, which may indicate that there is a hidden mechanism for inhibiting the pathogenesis of RA in bipolar disorder. However, results do not support a causal connection between depression, anxiety, and RA. Full article

(1) Background: Modern imaging methods and constantly developing technologies extend the range of diagnostic tools in medicine and in orthodontics. Thanks to them, scientists and doctors can use devices designed to diagnose 3D structures of the human body. The aim of the study was to assess the usefulness of digital orthodontic models as a diagnostic tool in the work of an orthodontist through a comparative analysis of the value of orthodontic measurements made on traditional plaster models and virtual models. (2) Methods: A total of 80 sets of models were made, including 40 sets of plaster models and 40 sets of digital models. A total of 48 diagnostic parameters were developed. They concerned dental parameters. (3) Results: Comparative analysis of crown height values on plaster and digital models showed statistically significant differences (p < 0.05) in 26 out of 48 dental parameters. (4) Conclusions: The differences between the measurements made with the software on the digital models and the measurements made with the traditional method of measurement using the digital caliper on the plaster models were small and clinically acceptable. Full article

The aim was to systematically synthesize the current research and influence of artificial intelligence (AI) models on temporomandibular joint (TMJ) osteoarthritis (OA) diagnosis using cone-beam computed tomography (CBCT) or panoramic radiography. Seven databases (PubMed, Embase, Scopus, Web of Science, LILACS, ProQuest, and SpringerLink) were searched for TMJ OA and AI articles. We used QUADAS-2 to assess the risk of bias, while with MI-CLAIM we checked the minimum information about clinical artificial intelligence modeling. Two hundred and three records were identified, out of which seven were included, amounting to 10,077 TMJ images. Three studies focused on the diagnosis of TMJ OA using panoramic radiography with various transfer learning models (ResNet model) on which the meta-analysis was performed. The pooled sensitivity was 0.76 (95% CI 0.35–0.95) and the specificity was 0.79 (95% CI 0.75–0.83). The other studies investigated the 3D shape of the condyle and disease classification observed on CBCT images, as well as the numerous radiomics features that can be combined with clinical and proteomic data to investigate the most effective models and promising features for the diagnosis of TMJ OA. The accuracy of the methods was nearly equivalent; it was higher when the indeterminate diagnosis was excluded or when fine-tuning was used. Full article

Introduction: Patent foramen ovale (PFO) is a potential source of cardiac embolism in cryptogenic ischemic stroke, but it may also be incidental. Right-to-left shunt (RLS) size may predict PFO-related stroke, but results have been controversial. In this cohort study of medically-managed PFO patients with cryptogenic stroke, we aimed to investigate the association of shunt size with recurrent stroke, mortality, newly detected atrial fibrillation (AF), and to identify predictors of recurrent stroke. Methods: Patients with cryptogenic stroke who screened positive for a RLS using a transcranial Doppler bubble study were included. Patients who underwent PFO closure were excluded. Subjects were divided into two groups: small (Spencer Grade 1, 2, or 3; n = 135) and large (Spencer Grade 4 or 5; n = 99) shunts. The primary outcome was risk of recurrent stroke, and the secondary outcomes were all-cause mortality and newly detected AF. Results: The study cohort included 234 cryptogenic stroke patients with medically-managed PFO. The mean age was 50.5 years, and 31.2% were female. The median period of follow-up was 348 (IQR 147-1096) days. The rate of recurrent ischemic stroke was higher in patients with large shunts than in those with small shunts (8.1% vs. 2.2%, p = 0.036). Multivariate analyses revealed that a large shunt was significantly associated with an increased risk of recurrent ischemic stroke [aOR 4.09 (95% CI 1.04–16.0), p = 0.043]. Conclusions: In our cohort of cryptogenic stroke patients with medically managed PFOs, those with large shunts were at a higher risk of recurrent stroke events, independently of RoPE score and left atrium diameter. Full article

Novel impedance-pH parameters, Mean Nocturnal Baseline Impedance (MNBI) and Post-Reflux Swallow-Induced Peristaltic Wave (PSPW) index, have been proposed to improve the gastro-esophageal reflux disease (GERD) diagnostic yield. This study aims to determine the integrity of the esophageal epithelial barrier and chemical clearance using these novel parameters and to correlate them with acid exposure time (AET) and acid clearance time (ACT) in obese patients who are candidates for bariatric surgery (BS). Twenty impedance-pHmetry tracings of patients prior to BS were reviewed. Nine (45%) patients with a conclusive diagnosis of GERD had significantly higher ACT, lower MNBI in the distal esophagus and lower PSPW indexes compared to obese patients without GERD. Moreover, 100% of obese patients with GERD had a pathological ACT compared to obese patients without GERD (p = 0.003). However, the percentage of pathological MNBI and PSPW index did not differ between obese patients with and without GERD. The PSPW index and MNBI of the distal channel significantly correlated with ACT and AET. Further studies are needed to assess the role of time-consuming novel parameters in the routine evaluation of morbidly obese patients candidates for BS. The value of acid clearance time is confirmed as a relevant impedance-pH parameter in these patients. Full article

There is insufficient evidence to confirm the efficacy of ustekinumab (UST) in promoting fistula closure in perianal fistulizing Crohn’s disease (CD) patients. We aimed to evaluate the efficacy of UST in a real-world setting. The data were retrospectively analyzed. Intestinal clinical and endoscopic changes were evaluated. Fistula radiological outcomes were determined using the Van Assche score. A total of 108 patients were included, 43.5% of whom had complex perianal fistulas. Intestinal clinical and endoscopic remission was achieved in 65.7% and 31.5% of patients, respectively. The fistula clinical remission and response rates were 40.7% and 63.0%, respectively, with a significant reduction in Perianal Crohn’s disease Activity Index [5.0(3.0, 8.0) vs. 7.5(5.0, 10.0), p < 0.001] and Crohn’s Anal Fistula Quality of Life [23.5(9.3, 38.8) vs. 49.0(32.3, 60.0), p < 0.001]. Radiological healing, partial response, no change, and deterioration were observed in 44.8%, 31.4%, 13.4%, and 10.4% of patients, respectively. The cut-off UST trough concentration for predicting fistula clinical remission was 2.11 μg/mL with an area under the curve of 0.795, a sensitivity of 93.3%, and a specificity of 67.6%. UST is efficacious in promoting radiological fistula closure in patients with perianal fistulizing CD. A UST trough concentration over 2.11 μg/mL was correlated with a higher likelihood of perianal fistula clinical remission. Full article

Jacob’s disease is a rare entity consisting of the formation of a pseudojoint between an abnormal coronoid process of the mandible and the inner surface of the zygomatic bone. First described by Jacob in 1899, its diagnosis and definition have never been entirely univocal. In this paper, we present three emblematic cases and an extensive review of the literature on Jacob’s disease. Given the variability observed in the presentation of the disease, we have developed a proposal for the classification, here reported. Full article

Machine learning (ML) is being increasingly employed in dental research and application. We aimed to systematically compile studies using ML in dentistry and assess their methodological quality, including the risk of bias and reporting standards. We evaluated studies employing ML in dentistry published from 1 January 2015 to 31 May 2021 on MEDLINE, IEEE Xplore, and arXiv. We assessed publication trends and the distribution of ML tasks (classification, object detection, semantic segmentation, instance segmentation, and generation) in different clinical fields. We appraised the risk of bias and adherence to reporting standards, using the QUADAS-2 and TRIPOD checklists, respectively. Out of 183 identified studies, 168 were included, focusing on various ML tasks and employing a broad range of ML models, input data, data sources, strategies to generate reference tests, and performance metrics. Classification tasks were most common. Forty-two different metrics were used to evaluate model performances, with accuracy, sensitivity, precision, and intersection-over-union being the most common. We observed considerable risk of bias and moderate adherence to reporting standards which hampers replication of results. A minimum (core) set of outcome and outcome metrics is necessary to facilitate comparisons across studies. Full article

Little is known about the distribution of etiology in obstructive sleep apnea (OSA) combined with chronic breathlessness. A significant portion of patients in this group have so-called “overlap syndrome (OVS)”, characterized by chronic obstructive pulmonary disease (COPD). OVS has more complications and a poorer prognosis compared to patients with either OSA or COPD alone, which makes it important to identify OVS early in OSA. The current study was a retrospective cross-sectional analysis of consecutive adult patients who were diagnosed with OSA (n = 1062), of whom 275 were hospitalized due to chronic breathlessness. Respiratory and cardiac diseases accounted for the vast majority of causes, followed by gastrointestinal and renal disorders. The final study population comprised 115 patients with OSA alone (n = 64) and OVS (n = 51), who had chronic breathlessness as the primary complaint, not secondary as one of many other complaints. Lymphocytes, CD4 counts, neutrophil-to-lymphocyte ratio (NLR), and PLR were differently expressed between the OSA-alone group and OVS group. The NLR, lymphocytes, and CD4 counts had a moderate diagnostic value for OVS in OSA patients, with AUCs of 0.708 (95% CI, 0.614–0.802), 0.719 (95% CI, 0.624–0.813), and 0.744 (95% CI, 0.653–0.834), respectively. The NLR had the highest AUC for predicting a 6-month re-admission of OVS, with a cut-off of 3.567 and a moderate prognostic value. The sensitivity and specificity were 0.8 and 0.732, respectively. In the animal model, the spleen hematoxylin- and eosin-stained, electron microscopy images showed germinal-center damage, chromatin activation, and mitochondrial swelling under the overlapping effect of intermittent hypoxia and cigarette smoke exposure. OSA with chronic breathlessness cannot be overstated. A significant proportion of patients with COPD in this group had poor lung function at initial diagnosis. The NLR is a useful biomarker to differentiate OVS among OSA patients combined with chronic breathlessness. Full article

Background: Small intestinal bacterial overgrowth (SIBO) is often found in patients with gut dysbiosis such as irritable bowel syndrome. Recently, the association of SIBO and inflammatory bowel disease (IBD) has been described in some cases. While clinical symptoms might be similar in IBD and SIBO, treatment is quite different for both diseases. Therefore, the differentiation between SIBO or a flare in IBD patients is key to optimizing treatment for these patients. Methods: We retrospectively investigated our patients with IBD receiving a glucose breath test for SIBO and correlated the results with the clinical symptoms (clinical remission or active disease). Results: 128 patients with the diagnosis “colitis” were analyzed in our cohort. Fifty-three (41.4%) patients had Crohn’s disease and 22 (17.2%) patients were suffering from ulcerative colitis. Seventy-four (57.8%) were female and 54 (42.2%) were male patients. A total of 18 (14.1%) patients had a positive testing for SIBO. Eleven (61.1%) cases were associated with CD patients and two (11.1%) with UC. IBD patients in clinical remission had a positive SIBO in six (19.4%) cases, while IBD patients with active disease were positive in nine (15.3%) cases. The proportion of positive SIBO in active IBD patients was higher; however, it did not reach significance. Older age was a risk factor for SIBO in patients with CD (p < 0.003). Conclusions: In our study, we could show that an increased amount of SIBO was found in IBD patients and was especially more frequent in patients with CD than in those with UC. In UC patients, SIBO rates were not different to patients with other gastrointestinal diseases investigated (e.g., infectious colitis, collagenous colitis, or irritable bowel syndrome). In active IBD, positive SIBO was detected more often numerically compared to quiescent disease; however, due to the low number of patients included, it was not significant. However, older age was a significant risk factor for SIBO in patients with CD. SIBO is of clinical relevance in the vulnerable patient cohort with IBD, and its real prevalence and impact needs to be investigated in further and larger clinical trials. Full article

Portal hypertension is the consequence of cirrhosis and results from increased sinusoidal vascular resistance and hepatic blood inflow. Etiological therapies represent the first intervention to prevent a significant increase in portal pressure due to chronic liver damage. However, other superimposed pathophysiological drivers may worsen liver disease, including inflammation, bacterial translocation, endothelial dysfunction, and hyperactivation of hemostasis. These mechanisms can be targeted by a specific class of drugs already used in clinical practice. Albumin, rifaximin, statins, aspirin, and anticoagulants have been tested in cirrhosis and were a topic of discussion in the last Baveno consensus as non-etiological therapies. Based on the pathogenesis of portal hypertension in cirrhosis, our review summarizes the main mechanisms targeted by these drugs as well as the clinical evidence that considers them a valid complementary option to manage patients with cirrhosis and portal hypertension. Full article

It is known that valproate inhibits platelet functions; however, the exact mechanisms are not clearly identified. We studied 12 healthy adult volunteers (1 female, 11 male; age range 31.7 ± 7.8 years) before and after valproate 500 mg and compared the results to levetiracetam 1000 mg as a control substance and placebo. The study had a crossover and double-blind design. A blood sample was taken before and 90 min after medication intake, because the times to maximum serum concentration (T_max) are 1.5 h for levetiracetam and 1 to 3 h for valproate. We analysed changes in platelet, erythrocyte, and leukocyte cell count and in platelet functions (CD62 expression (P selectin), thrombin binding, and fibrinogen binding). We found no significant differences in all cell counts before and after different study drugs. After valproate intake, but not after placebo or levetiracetam intake, the fibrinogen binding significantly decreased and the CD62 expression significantly increased resulting in decreased platelet aggregation. Our data suggest that the platelet dysfunctions reported for valproate result from decreased fibrinogen binding and from increased CD62 expression. This phenomenon might be one reason for the increased bleeding risk under valproate and cannot be observed for levetiracetam. Full article

The usefulness of minimally invasive posterior fixation without debridement and autogenous bone grafting remains unknown. This multicenter case series aimed to determine the clinical outcomes and limitations of this method for thoracolumbar pyogenic spondylitis. Patients with thoracolumbar pyogenic spondylitis treated with minimally invasive posterior fixation alone were retrospectively evaluated at nine affiliated hospitals since April 2016. The study included 31 patients (23 men and 8 women; mean age, 73.3 years). The clinical course of the patients and requirement of additional anterior surgery constituted the study outcomes. The postoperative numerical rating scale score for lower back pain was significantly smaller than the preoperative score (5.8 vs. 3.6, p = 0.0055). The preoperative local kyphosis angle was 6.7°, which was corrected to 0.1° after surgery and 3.7° at the final follow-up visit. Owing to failed infection control, three patients (9.6%) required additional anterior debridement and autogenous bone grafting. Thus, in this multicenter case series, a large proportion of patients with thoracolumbar pyogenic spondylitis could be treated with minimally invasive posterior fixation alone, thereby indicating it as a treatment option for pyogenic spondylitis. Full article

The aim was to identify patient- and disease-related characteristics predicting moderate-to-high disease activity in recent-onset psoriatic arthritis (PsA). We performed a multicenter observational prospective study (2-year follow-up, regular annual visits) in patients aged ≥18 years who fulfilled the CASPAR criteria and had less than 2 years since the onset of symptoms. The moderate-to-high activity of PsA was defined as DAPSA > 14. We trained a logistic regression model and random forest–type and XGBoost machine learning algorithms to analyze the association between the outcome measure and the variables selected in the bivariate analysis. The sample comprised 158 patients. At the first follow-up visit, 20.8% of the patients who attended the clinic had a moderate-to-severe disease. This percentage rose to 21.2% on the second visit. The variables predicting moderate-high activity were the PsAID score, tender joint count, level of physical activity, and sex. The mean values of the measures of validity of the machine learning algorithms were all high, especially sensitivity (98%; 95% CI: 86.89–100.00). PsAID was the most important variable in the prediction algorithms, reinforcing the convenience of its inclusion in daily clinical practice. Strategies that focus on the needs of women with PsA should be considered. Full article