Congenital aniridia is a rare autosomal dominant congenital ocular disorder. Genetic studies suggest that heterozygous mutations in the developmental regulator PAX6 gene or the related regulatory regions leading to haploinsufficiency are the main cause of congenital aniridia. In this study, the clinical characteristics and pathogenic mutation of a four-generation Chinese family with congenital aniridia were investigated. All members recruited in this study underwent comprehensive ophthalmic examinations. Targeted gene capture sequencing and Sanger sequencing were performed to screen and confirm the candidate pathogenicity gene and its mutation. A multiple alignment of homologous sequences covering the identified mutation from different species was investigated, and the mutant protein structure was predicted using Swiss-Model. Additionally, the prediction of pathogenicity was analyzed using the ACMG Guidelines. Thirteen patients in this pedigree were diagnosed with congenital aniridia. A novel heterozygous frameshift mutation (c.391_398dupATACCAAG, p.Ser133Argfs*8) in exon 7 of the PAX6 gene was identified in all affected individuals in the family. This study demonstrates that this frameshift mutation of the PAX6 gene might be the causative genetic defect of congenital aniridia in this family. This mutation is predicted to cause the premature truncation of the PAX6 protein, leading to the functional haploinsufficiency of PAX6, which may be the major molecular mechanism underlying the aniridia phenotype. To the best of our knowledge, this is the first report of a novel pathogenic PAX6 gene variant c.391_398dupATACCAAG(p.Ser133Argfs*8) identified in a Chinese family with congenital aniridia. Full article

The aim of this 4-year observational study is to analyze the outcomes of stroke patients treated with direct mechanical thrombectomy (dMT) compared to bridging therapy (BT) (intravenous thrombolysis [IVT] + BT) based on 3-month outcomes, in real clinical practice in the "Stroke Belt" of Southern Europe. In total, 300 patients were included (41.3% dMT and 58.6% BT). The frequency of direct referral to the stroke center was similar in the dMT and BT group, whereas the time from onset to groin was longer in the BT group (median 210 [IQR 160–303] vs. 399 [IQR 225–675], p = 0.001). Successful recanalization (TICI 2b-3) and hemorrhagic transformation were similar in both groups. The BT group more frequently showed excellent outcomes at 3 months (32.4% vs. 15.4%, p = 0.004). Multivariate analysis showed that BT was independently associated with excellent outcomes (OR 2.7. 95% CI,1.2–5.9, p = 0.02) and lower mortality (OR 0.36. 95% CI 0.16–0.82, p = 015). Conclusions: Compared with dMT, BT was associated with excellent functional outcomes and lower 3-month mortality in this real-world clinical practice study conducted in a region belonging to the “Stroke Belt” of Southern Europe. Given the disparity of results on the benefit of BT in the current evidence, it is of vital importance to analyze the convenience of its use in each health area. Full article

Potocki–Lupski Syndrome (PTLS) is a rare condition associated with a duplication of 17p11.2 that may underlie a wide range of congenital abnormalities and heterogeneous behavioral phenotypes. Along with developmental delay and intellectual disability, autism-specific traits are often reported to be the most common among patients with PTLS. To contribute to the discussion of the role of autism spectrum disorder (ASD) in the PTLS phenotype, we present a case of a female adolescent with a de novo dup(17) (p11.2p11.2) without ASD features, focusing on in-depth clinical, behavioral, and electrophysiological (EEG) evaluations. Among EEG features, we found the atypical peak–slow wave patterns and a unique saw-like sharp wave of 13 Hz that was not previously described in any other patient. The power spectral density of the resting state EEG was typical in our patient with only the values of non-linear EEG dynamics: Hjorth complexity and fractal dimension were drastically attenuated compared with the patient’s neurotypical peers. Here we also summarize results from previously published reports of PTLS that point to the approximately 21% occurrence of ASD in PTLS that might be biased, taking into account methodological limitations. More consistent among PTLS patients were intellectual disability and speech and language disorders. Full article

We examine the significance of the predictive potential of EPI cystatin C (EPI CysC) in combination with NTproBNP, sodium, and potassium in the evaluation of renal function in patients with cardiorenal syndrome using standard mathematical classification models from the domain of artificial intelligence. The criterion for the inclusion of subjects with combined impairment of heart and kidney function in the study was the presence of newly discovered or previously diagnosed clinically manifest cardiovascular disease and acute or chronic kidney disease in different stages of evolution. In this paper, five standard classifiers from the field of machine learning were used for the analysis of the obtained data: ensemble of neural networks (MLP), ensemble of k-nearest neighbors (k-NN) and naive Bayes classifier, decision tree, and a classifier based on logistic regression. The results showed that in MLP, k-NN, and naive Bayes, EPI CysC had the highest predictive potential. Thus, our approach with utility classifiers recognizes the essence of the disorder in patients with cardiorenal syndrome and facilitates the planning of further treatment. Full article

Chordomas are rare primary malignant tumours of notochordal origin usually arising along the axial skeleton with particular predilection of the skull base and sacrococcygeal region. Albeit usually slow-growing, chordomas can be aggressive mostly depending on their invasive behaviour and according to different histotypes and molecular alterations, including TBXT duplication and SMARCB1 homozygous deletion. Partial or complete PTEN deficiency has also been observed. PTEN is a negative regulator of the Akt/mTOR pathway and hyperactivation of Akt/mTOR in cells lacking PTEN expression contributes to cell proliferation and invasiveness. This pathway is targeted by mTOR inhibitors and the availability of in vitro models of chordoma cells will aid in further investigating this issue. However, isolation and maintenance of chordoma cell lines are challenging and PTEN-deleted chordoma cell lines are exceedingly rare. Hereby, we established and characterized a novel human PTEN-deleted chordoma cell line (CH3) from a primary skull base chordoma. Cells exhibited morphological and molecular features of the parent tumour, including PTEN loss and expression of Brachyury and EMA. Moreover, we investigated the activation of the mTOR pathway and cell response to mTOR inhibitors. CH3 cells were sensitive to Rapamycin treatment suggesting that mTOR inhibitors may represent a valuable option for patients suffering from PTEN-deleted chordomas. Full article

Background: In patients with liver cirrhosis, transjugular intrahepatic portosystemic shunt (TIPS) is considered a standardized treatment of refractory ascites or variceal bleeding. TIPS thrombosis (TT) and/or portal vein thrombosis (PVT) are possible complications during/after TIPS placement. Previous studies suggested increased clotting activity in portal circulation (PORC). This pilot study aimed to evaluate alterations and differences of coagulation function in PORC and in peripheral circulation (PERC) via rotational thromboelastometry during TIPS. Methods: Blood samples were collected from cirrhotic patients (n = 13; median Model of End Stage Liver Disease, MELD Score: 12; median age: 60 years) undergoing TIPS (10/13 TIPSs were elective procedures due to refractory ascites) as follows: median cubital vein (MCV; PERC)—confluence of the three hepatic veins to the inferior cava vein (HV/ICV; PORC)—portal vein (PV; PORC)—TIPS (PORC). This research utilized four variables of the extrinsic test EXTEM, i.e., clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), and maximum lysis (ML). Results: EXTEM results [mean, M (range) ± standard deviation, SD (range)] showed no significant differences for CT [M (70–73) ± SD (9–13); p = 0.93] or CFT [M (137–155) ± SD (75–112); p = 0.97] or MCF [M (51–54) ± SD (9–10); p = 0.90] or ML [M (9–10) ± SD (4–5); p = 0.89] between the compartments, i.e., MCV vs. HV/ICV vs. PV vs. TIPS. Overall, we detected no differences in coagulation function between PERC and PORC. Conclusion: These results are in contrast to previous reports suggesting increased clotting activity in PORC vs. PERC in association with liver cirrhosis. Rotational thromboelastometry-based evaluation of coagulation function in PERC appears to reliably reflect coagulation function in PORC with respect to risk estimation for TT and/or PVT in cirrhotic patients undergoing TIPS. Full article

Background and Objectives: Parenteral prostacyclins are crucial in the pharmacological treatment of pulmonary arterial hypertension (PAH). Indeed, subcutaneous administration of treprostinil has been associated with considerable clinical and hemodynamic improvement, right-sided heart reverse remodeling, and long-term survival benefit. However, evidence on patient perceptions about handling a subcutaneous infusion pump for self-treatment administration and nurse views about training the patients are lacking. This study aimed to describe the perception of PAH patients and nurses regarding the use of the new portable I-Jet infusion pump for the self-administration of subcutaneous treprostinil, as well as its real-world training needs. Materials and Methods: The study is an open, observational, prospective, single-center, non-interventional study. Patients with PAH on stable therapy with subcutaneous treprostinil were invited to take part in the study at their start of use of the portable I-Jet infusion pump for the self-administration of treatment. Participants filled in a questionnaire to report their satisfaction with the use of the pump, as well as their compliance, confidence, convenience, preferences, technical issues, and perceptions of the training they received. Results: Thirteen patients completed the questionnaire after being on the pump for 2 months: 69% were females and the mean age was 51 years. The most frequent PAH etiologies were congenital heart disease (46.2%) and idiopathic PAH (38.4%). Most patients were either World Health Organization (WHO) functional class II (53.8%) or III (46.2%). Ten patients (76.9%) found the pump easy and convenient to live with. All patients declared themselves to be fully compliant and confident in using the pump (n = 13) at the end of the study follow-up. Ten patients (76.9%) would choose the new pump in the future. None of the patients made reference to technical issues that required additional hospital visits. Eight patients (61.6%) reported that learning how to use the I-Jet infusion pump was easy or very easy, and none considered that further training was needed. One trainer nurse was interviewed and confirmed the satisfaction of patients and the simplicity of usage and training. Conclusions: PAH patients were highly satisfied with the use of the new portable I-Jet infusion pump for self-administering subcutaneous treprostinil. Convenience and ease of use were valuable and commonly reported features. Moreover, the training requirement was simple. These preliminary findings support the routine use of the I-Jet infusion pump. Full article

Background: Lens–iris diaphragm retropulsion syndrome (LIDRS) is common in vitrectomized or high myopic eyes during phacoemulsification. We evaluated the results of a modified technique for cataract treatment using phacoemulsification in vitrectomized eyes. Methods: In this retrospective study, we enrolled thirty-four vitrectomized eyes treated with modified phacoemulsification (Modified Group) and nineteen vitrectomized eyes treated with routine phacoemulsification (Control Group). The modified technique comprised irrigation with a balanced salt solution underneath the pupil before phacoemulsification instrument entry, lens implantation and stromal hydration to stabilize the anterior chamber and equilibrate the pressure between the anterior chamber and posterior cavity. Results: We compared the incidences of intra and postoperative complications and visual outcomes between modified and routine phacoemulsification. Pain, LIDRS and difficulty in stromal hydration were significantly more common in the Control Group than in the Modified Group (p < 0.05). There were no significant differences in the rates of posterior capsular rupture, iris trauma, lens dislocation, or posterior capsular opacification between the Modified and Control Groups (p > 0.05). However, there was no significant difference in visual acuity between the groups (p > 0.05). Complications such as loss of nuclear fragments into the vitreous cavity, cystoid macular edema, retina redetachment, suprachoroidal hemorrhage and vitreous hemorrhage did not occur either intra or postoperatively in any of our patients. Conclusions: Our modified technique prevents LIDRS and complications arising during cataract surgery in vitrectomized eyes. Aside from this, the results of modified and routine phacoemulsification are similar in vitrectomized eyes. Full article

The collection of family health history (FHH) is an essential component of clinical practice and an important piece of data for patient risk assessment. However, family history data have generally been limited to diseases and have not included medication history. Family history was a key component of early pharmacogenetic research, confirming the role of genes in drug response. With the substantial number of known pharmacogenes, many affecting response to commonly prescribed medications, and the availability of clinical pharmacogenetic (PGx) tests and guidelines for interpretation, the collection of family medication history can inform testing decisions. This paper explores the roots of family-based pharmacogenetic studies to confirm the role of genes in these complex phenotypes and the benefits and challenges of collecting family medication history as part of family health history intake. Full article

We evaluated the clinical features of patients admitted to the ED with acute vertigo, verifying symptoms after one month and one year to establish epidemiological factors and predictors of resolution. We reviewed 233 records of patients admitted to ED for acute vertigo (125 F and 85 M, mean age 56.12 years). We analyzed the correlation between time of resolution (at one month and one year) and symptoms duration (subjective and/or objective vertigo, instability, cervical pain, audiological, neurological, and neurovegetative symptoms), comorbidities, and therapies, the result of the clinical and instrumental vestibular examination. Resolution of acute vertigo occurred in 81.1%, while persistence of vertigo one year after ED access was reported in 18.8%. There were 135 patients who recovered in one month. The presence of instability, auditory and neurovegetative symptoms, and neck pain represents a significant factor for recovery within one year. Age over 65 and a history of hypertension are associated with a worst recovery. Patients with spontaneous Nystagmus or positive HIT showed a significant difference in symptoms recovery within one month and one year. Presence of positional Nystagmus represents a positive prognostic factor. Our findings emphasize the importance of clinical evaluation of the acute vertigo, helping the clinicians to define central or peripheral diagnosis and predict the resolution of vertigo. Full article

Background: This study aimed to compare the knotless internal brace technique and the knot-tying suture bridge technique via the medial approach in the treatment of calcific Achilles tendinopathy. Methods: The clinical data of 25 cases of calcific Achilles tendinopathy in which nonoperative treatments had failed were retrospectively collected. All the patients received Achilles tendon debridement and Haglund deformity excision through a medial approach, followed by repair using the knotless internal brace technique or the knot-tying suture bridge technique. Pain was evaluated by using the visual analog scale (VAS). The American Orthopedic Foot and Ankle Score (AOFAS) questionnaire was administered preoperatively and postoperatively. Results: The mean follow-up time was 2.6 (range 2–3.5) years. There were no wound complications and no Achilles tendon ruptures. At 1 year postoperatively, the internal brace group was superior to the suture bridge group in terms of the VAS scores (p = 0.003). However, no differences were noticed between the two groups in either the VAS or the AOFAS scores at 2 years postoperatively. Conclusions: The medial approach in combination with the suture bridge technique was effective in treating calcific Achilles tendinopathy. The knotless internal brace technique involved less pain compared to the knot-tying suture bridge technique only at the early postoperative stage. Full article

Cervical spinal cord injury (SCI) causing tetraplegia is extremely disabling. In such circumstances, restoration of upper extremity (UE) function is considered the highest priority. The advent of early nerve transfer (NT) procedures, in addition to more traditional tendon transfers (TT), warranted in-depth consideration given the time-limited nature of NT procedures. Potential surgery candidates may not yet have come to terms with the permanence of their disability. A mixed methods convergent design was utilized for concurrent analysis of the Aotearoa/New Zealand upper limb registry data from the clinical assessments of all individuals considering UE surgery, regardless of their final decision. The International Classification of Functioning, Disability and Health (ICF) taxonomy guided data interpretation during the three-phased study series. It was the integration of the findings using the Stewart Model of care drawn from palliative health that enabled the interpretation of higher order messages. It is clear the clinical assessment and selection processes in use require reconsideration given the complexities individuals face following onset of SCI. We draw attention to the higher order cognitive demands placed on individuals, the requirement for SCI peer involvement in decision making and the need for acknowledgment of interdependence as a relational construct when living with tetraplegia. Full article

Cleft lip and cleft palate (CLCP) patients often have a retrusive maxilla and a severe skeletal Class III malocclusion, which can result in velopharyngeal insufficiency (VPI). The aim of this study was to evaluate the changes in the volume of the 3D airway in CLCP children after maxilla distraction using the transcutaneous maxillary distraction osteogenesis (TMDO) method. 15 children with bilateral or unilateral CLCP were included in the study. 3D CBCT images were taken before and after distraction and were segmented and reconstructed to create a 3D airway model. The airway was divided into three regions: the upper, oropharyngeal, and hypopharyngeal airway. Pearson correlation tests were used to assess correlations between volume changes and corresponding skeletal and dental landmark movements (Point N, ANS, A, B, Pog, U1, and L1). The results showed that the ANS point advanced 9.85 ± 3.60 mm, and the A point advanced 14.22 ± 4.57 mm. The total airway volume change increased by 2535.06 ± 2791.80 mm³. However, there was no significant correlation between the A/ANS/U1 and the three different airway regions. Only B/Pog/L1 showed a positive correlation with these airway regions, with a high correlation between B/Pog/L1 and the hypopharyngeal airway region. TMDO can result in greater anterior advancement of the maxilla and an increase in airway volume, but the changes in bony landmarks did not show a strong positive correlation with the increase in airway volume as expected. Further investigation is needed to analyze the influence of surrounding soft tissue on the changes in airway volume. Full article

Background: Autoimmune hepatitis (AIH) is a rare entity; in addition, single-nucleotide polymorphisms (SNPs) may impact its course and outcome. We investigated liver-related SNPs regarding its activity, as well as in relation to its stage and treatment response in a Central European AIH cohort. Methods: A total of 113 AIH patients (i.e., 30 male/83 female, median 57.9 years) were identified. In 81, genotyping of PNPLA3-rs738409, MBOAT7-rs626238, TM6SF2-rs58542926, and HSD17B13-rs72613567:TA, as well as both biochemical and clinical data at baseline and follow-up, were available. Results: The median time of follow-up was 2.8 years; five patients died and one underwent liver transplantation. The PNPLA3-G/G homozygosity was linked to a worse treatment response when compared to wildtype [wt] (ALT 1.7 vs. 0.6 × ULN, p < 0.001). The MBOAT7-C/C homozygosity was linked to non-response vs. wt and heterozygosity (p = 0.022). Male gender was associated with non-response (OR 14.5, p = 0.012) and a higher prevalence of PNPLA3 (G/G vs. C/G vs. wt 41.9/40.0/15.0% males, p = 0.03). The MBOAT7 wt was linked to less histological fibrosis (p = 0.008), while no effects for other SNPs were noted. A polygenic risk score was utilized comprising all the SNPs and correlated with the treatment response (p = 0.04). Conclusions: Our data suggest that genetic risk variants impact the treatment response of AIH in a gene-dosage-dependent manner. Furthermore, MBOAT7 and PNPLA3 mediated most of the observed effects, the latter explaining, in part, the predisposition of male subjects to worse treatment responses. Full article