Timed rolling and rising tests in Duchenne muscular dystrophy ambulant boys: a feasibility study.

BACKGROUND: Functional activities are extensively used in motor assessments of patients with Duchenne muscular dystrophy. The role of timed items has been reported as an early prognostic factor for disease progression. However, there are two functional activities that are not widely assessed in clinical practice among Duchenne muscular dystrophy patients: rolling and bed rising. This study aimed to investigate whether the 360-degree roll (roll) and supine to sit-to-edge (bed rise) measurements are feasible tools reflecting the functional status of ambulatory DMD children by establishing possible correlations between validated measures: the Vignos Scale (VS), timed rise from floor and the 6-Minute Walk Test (6MWT). METHODS: A total of 32 ambulant boys with DMD were assessed using timed items, the 6MWT and VS. RESULTS: The roll and bed rise are correlated with each other. The 6MWT, the floor rise and VS are correlated with the roll and with the bed rise. CONCLUSIONS: Findings offer preliminary empirical evidence addressing feasibility and safety of roll and bed rise measurements. There is a potential clinical utility of these tests in assessing functional status of DMD ambulant patients.

Organisation of paediatric echocardiography laboratories and governance of echocardiography services and training in Europe: current status, disparities, and potential solutions. A survey from the Association for European Paediatric and Congenital Cardiology (AEPC) imaging working group.

BACKGROUND: There is limited data on the organisation of paediatric echocardiography laboratories in Europe. METHODS: A structured and approved questionnaire was circulated across all 95 Association for European Paediatric and Congenital Cardiology affiliated centres. The aims were to evaluate: (1) facilities in paediatric echocardiography laboratories across Europe, (2) accredited laboratories, (3) medical/paramedical staff employed, (4) time for echocardiographic studies and reporting, and (5) training, teaching, quality improvement, and research programs. RESULTS: Respondents from forty-three centres (45%) in 22 countries completed the survey. Thirty-six centres (84%) have a dedicated paediatric echocardiography laboratory, only five (12%) of which reported they were European Association of Cardiovascular Imaging accredited. The median number of echocardiography rooms was three (range 1-12), and echocardiography machines was four (range 1-12). Only half of all the centres have dedicated imaging physiologists and/or nursing staff, while the majority (79%) have specialist imaging cardiologist(s). The median (range) duration of time for a new examination was 45 (20-60) minutes, and for repeat examination was 20 (5-30) minutes. More than half of respondents (58%) have dedicated time for reporting. An organised training program was present in most centres (78%), 44% undertake quality assurance, and 79% perform research. Guidelines for performing echocardiography were available in 32 centres (74%). CONCLUSION: Facilities, staffing levels, study times, standards in teaching/training, and quality assurance vary widely across paediatric echocardiography laboratories in Europe. Greater support and investment to facilitate improvements in staffing levels, equipment, and governance would potentially improve European paediatric echocardiography laboratories.

Generation of human induced pluripotent stem cell line derived from Becker muscular dystrophy patient with CRISPR/Cas9-mediated correction of DMD gene mutation.

Becker muscular dystrophy (BMD) is an X-linked recessive disorder caused by in-frame deletions in the dystrophin gene (DMD), leading to progressive muscle degeneration and weakness. We generated a human induced pluripotent stem cell (hiPSC) line from a BMD patient. BMD hiPSCs were then engineered by CRISPR/Cas9-mediated knock-in of missing exons 3-9 of DMD gene. Obtained hiPSC line may be a valuable tool for investigating the mechanisms underlying BMD pathogenesis.

Evaluation of PHASES Score for Predicting Rupture of Intracranial Aneurysms: Significance of Aneurysm Size.

BACKGROUND: Recent data have identified that certain risk factors for rupture differ between small and larger intracranial aneurysms (IAs). Such differing risk factors make up 5 out of the 6 predictor variables used in the PHASES score, which raises the question on whether IA size has a significant effect on the score's performance. METHODS: Patients who were diagnosed with an IA incidentally or due to a subarachnoid hemorrhage between 2015 and 2023 were selected for potential inclusion. The median IA size of the cohort was chosen as the cutoff point to categorize small and large (6 mm). The PHASES score was calculated for all patients, and a receiver operating characteristic curve analysis was performed to evaluate the classification accuracy of PHASES in predicting rupture for small and large IAs. RESULTS: A total of 677 IAs were included. Among the IAs, 400 (58.9%) presented as UIAs and 279 (41.0%) as subarachnoid hemorrhage. The average PHASES score was 2.9 and 6.5 for small (n = 322) and large (n = 355) IAs, respectively. The PHASES score performed significantly lower for predicting rupture in smaller IAs (area under the curve: 0.634) compared with the larger (area under the curve: 0.741) (P = 0.00083). CONCLUSIONS: PHASES was shown to underperform on small IAs. The decision to treat small unruptured IAs remains highly controversial, and the development of a new score to estimate the annual rupture rate while accounting for IA morphology is of great need. Our findings can help encourage future researchers to develop such a score.

Nutritional Status and the Outcomes of Endoscopic Stenting in Benign and Malignant Diseases of Esophagus.

BACKGROUND: Endoscopic stenting (ES) is a widely known method for palliative dysphagia treatment in esophageal strictures. Esophageal cancer is often associated with advanced malnutrition, which may increase the risk of complications of the procedure. The aim of this study was to evaluate complication rates and the impact of nutritional status on the outcomes of ES. PATIENTS AND METHODS: A single-center retrospective study was conducted at Copernicus Hospital in Gdansk, Poland. Adult patients who underwent endoscopic stenting between February 2014 and December 2018 were included. The influence of patient characteristics (age, sex, indications for esophageal stenting, and location of stenosis) and nutritional status (BMI, NRS 2002, GLIM, and dysphagia score) on complication rates and survival were analyzed. RESULTS: Eighty-one patients (69% men) were enrolled in the study. In 69%, the indication for ES was malignancy (mainly esophageal cancer). The median dysphagia score significantly decreased from 2.8 to 0.6 after the procedure (p < 0.001). Complications were observed in 27% (n = 22) of the patients. Early complications were bleeding (2.5%), stent unexpansion (2.5%), and stent migration during the procedure (3.7%). There were no early fatal complications of the procedure. Late complications included: stent migration (6.2%), tissue overgrowth (6.2%), food impaction (2.2%), fistula formation (3.7%), bleeding (3.7%), and stent malposition (1.2%). A total of 76% of the participants scored ≥ 3 points in nutritional screening (NRS2002) and 70% were diagnosed with severe malnutrition (GLIM -stage 2). A stent diameter of < 2.2 cm compared with ≥ 2.2 was associated with a higher rate of migrations (15.5% vs. 2.5%). The median survival time in the malignant group was 90 days. Histopathological diagnosis and patients' nutritional status (BMI, NRS 2002, GLIM, and dysphagia score) had no significant effect on complication rates and survival after esophageal stent insertion. CONCLUSIONS: Endoscopic stenting is a relatively safe procedure for the palliative treatment of esophageal strictures. Severe malnutrition, although common, does not affect the outcomes of the procedure.

CDR3 Variants of the TXB2 Shuttle with Increased TfR1 Association Rate and Enhanced Brain Penetration.

Since the delivery of biologic drugs to the brain is greatly hampered by the existence of the blood-brain barrier (BBB), brain shuttles are being developed to enhance therapeutic efficacy. As we have previously shown, efficient and selective brain delivery was achieved with TXB2, a cross-species reactive, anti-TfR1 VNAR antibody. To further explore the limits of brain penetration, we conducted restricted randomization of the CDR3 loop, followed by phage display to identify improved TXB2 variants. The variants were screened for brain penetration in mice using a 25 nmol/kg (1.875 mg/kg) dose and a single 18 h timepoint. A higher kinetic association rate to TfR1 correlated with improved brain penetration in vivo. The most potent variant, TXB4, showed a 3.6-fold improvement over TXB2, which had on average 14-fold higher brain levels when compared to an isotype control. Like TXB2, TXB4 retained brain specificity with parenchymal penetration and no accumulation in other organs. When fused with a neurotensin (NT) payload, it led to a rapid drop in body temperature upon transport across the BBB. We also showed that fusion of TXB4 to four therapeutic antibodies (anti-CD20, anti-EGFRvIII, anti-PD-L1 and anti-BACE1) improved their brain exposure between 14- to 30-fold. In summary, we enhanced the potency of parental TXB2 brain shuttle and gained a critical mechanistic understanding of brain delivery mediated by the VNAR anti-TfR1 antibody.

Diagnostic performance of point-of-use ultrasound of resuscitation outcomes: A systematic review and meta-analysis of 3265 patients.

BACKGROUND: Echocardiography in the setting of resuscitation can provide information as to the cause of the cardiac arrest, as well as indicators of futility. This systematic review and meta-analysis were performed to determine the value of point-of-care ultrasonography (PoCUS) in the assessment of survival for adult patients with cardiac arrest. METHODS: This meta-analysis was performed in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, Web of Science, Cochrane have been searched from databases inception until March 2nd 2021. The search was limited to adult patients with cardiac arrest and without publication dates or country restrictions. Papers were chosen if they met the required criteria relating to the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of this diagnostic technique concerning resuscitation outcomes. RESULTS: This systematic review identified 20 studies. Overall, for survival to hospital discharge, PoCUS was 6.2% sensitivity (95% confidence interval [CI] 4.7-8.0%) and 2.1% specific (95% CI 0.8-4.2%). PoCUS sensitivity and specificity for return of spontaneous circulation were 23.8% (95% CI 21.4-26.4%) and 50.7% (95% CI 45.8-55.7%) respectively, and for survival to admission 13.8% (95% CI 12.2-15.5%) and 20.1% (95% CI 16.2-24.3%), respectively. CONCLUSIONS: The results do not allow unambiguous recommendation of PoCUS as a predictor of resuscitation outcomes and further studies based on a large number of patients with full standardization of operators, their training and procedures performed were necessary.

Prevalence and Trends in Percutaneous Endoscopic Gastrostomy Placement: Results From a 10-Year, Nationwide Analysis.

Background: Percutaneous endoscopic gastrostomy (PEG) is the most commonly used access for long-term enteral nutrition. Only a few studies report the prevalence and epidemiology of PEG placements. No previous data concentrated on the healthcare system issues influencing the qualification rates and professional nutritional support for individuals with PEG. Methods: We conducted a retrospective nationwide analysis of PEG placements in Poland from 2010 to 2020. The central data on ICD-10 coding of adult patients with PEG reported to the insurance company were used for the analysis of general and regional prevalence, age, and primary and secondary diseases. Rates of patients with home enteral nutrition (HEN) were calculated with a special focus on patients with cancer. A secondary aim was to determine the causes of regional disparities among administrative regions. Results: A total number of 90,182 PEGs were placed during the observation period. The number was increasing each year with statistical significance. Malnutrition, dysphagia, and cardiorespiratory/metabolic diseases were the most frequently reported primary diseases. A total of 11.98% of all patients were diagnosed with cancer; 49.9% of oncological patients suffered from head and neck cancer (HNC) and 19.9% from esophageal cancer. In total, 6.61% of HNC and 27.46% of patients with esophageal cancer from the Polish National Cancer Registry (NCR) had PEG. The rates of patients in more advanced ages (65-74 and over 85 years) were growing and decreased in younger groups (18-24, 45-54, and 55-64 years). Overall, 27.6% of all (11.86% of cancer) patients with PEG were reimbursed HEN. A high number of patients in nursing care facilities, lower education of citizens, and lower number of hospital beds were associated with more PEG insertions in the administrative regions. Conclusion: The number of PEG placements has been increasing, particularly in the elderly. Systemic solutions must be found to address the problems of regional disparities in PEG's prevalence as well as the lack of inclusion criteria for nutritional support.

The Role of 3D Printing in Planning Complex Medical Procedures and Training of Medical Professionals-Cross-Sectional Multispecialty Review.

Medicine is a rapidly-evolving discipline, with progress picking up pace with each passing decade. This constant evolution results in the introduction of new tools and methods, which in turn occasionally leads to paradigm shifts across the affected medical fields. The following review attempts to showcase how 3D printing has begun to reshape and improve processes across various medical specialties and where it has the potential to make a significant impact. The current state-of-the-art, as well as real-life clinical applications of 3D printing, are reflected in the perspectives of specialists practicing in the selected disciplines, with a focus on pre-procedural planning, simulation (rehearsal) of non-routine procedures, and on medical education and training. A review of the latest multidisciplinary literature on the subject offers a general summary of the advances enabled by 3D printing. Numerous advantages and applications were found, such as gaining better insight into patient-specific anatomy, better pre-operative planning, mock simulated surgeries, simulation-based training and education, development of surgical guides and other tools, patient-specific implants, bioprinted organs or structures, and counseling of patients. It was evident that pre-procedural planning and rehearsing of unusual or difficult procedures and training of medical professionals in these procedures are extremely useful and transformative.

Optimal fluoroscopic viewing angles for stenting of the coronary aorto-ostial lesions.

BACKGROUND: Long-term results after stenting aorto-coronary ostial lesions (AOL) are worse than those achieved in non-ostial locations. AOL interventions still pose a substantial challenge for interventional cardiologists. The aim of the study was to determine the optimal fluoroscopic viewing angles of the left and right coronary ostia, based on multislice computed tomography (MSCT) data. METHODS: Cardiac MSCT exams of 30 patients with clinical suspicion of coronary artery disease were analyzed. En face angles of both coronary ostia, as well as their optimal projection curves, were determined by 2 independent observers in a standard Dicom viewer, without any additional, specialized software add-ons, using a systematic, step-by-step approach. Spatial relations between the ostial plane and the aorta were also assessed. RESULTS: The average en face angle of the left coronary ostium was RAO 23°, CAU 45°; for the right coronary ostium RAO 18°, CRA 5°. The mean inter-observer differences for the en face angles of the left and right coronary arteries were 5° and 7°, respectively. CONCLUSIONS: Multislice computed tomography data provide precise spatial information on the orientation of the coronary ostia and their relation to the aortic root. Their utilization for determining the patient-specific viewing angle may substantially facilitate percutaneous coronary interventions in AOL.

The Impact of COVID-19 Pandemic on Children with Pulmonary Arterial Hypertension. Parental Anxiety and Attitudes. Follow-Up Data from the Polish Registry of Pulmonary Hypertension (BNP-PL).

The COVID-19 pandemic has impacted healthcare systems worldwide. Little is known about the impact of the pandemic on medical and psycho-social aspects of children with rare diseases such as pulmonary arterial hypertension and their parents. The study is based on children registered in The Database of Pulmonary Hypertension in the Polish Population and a parent-reported survey deployed during the first 6 months of the pandemic. The questionnaire consisted of six question panels: demographic data, fear of COVID-19, General Anxiety Disorder-7 (GAD-7), social impact of pandemic, patients' medical status, and alarming symptoms (appearance or exacerbation). Out of 80 children registered, we collected 58 responses (72.5% response rate). Responders (parents) were mostly female (n = 55; 94.8%) at a mean age of 40.6 ± 6.9 years. Patients (children) were both females (n = 32; 55%) and males with a mean age of 10.0 ± 5.1 years. Eleven (19%) children had symptoms of potential disease exacerbation. Eight parents (72.7%) decided for watchful waiting while others contacted their GPs or cardiologists (n = 6; 54.5%). Three children had to be hospitalized (27.3%). Most planned hospitalizations (27/48; 56.2%) and out-patient visits (20/35; 57.1%) were cancelled, delayed, or substituted by telehealth services. Among the participating parents, the study shows very high levels of anxiety (n = 20; 34.5%) and concern (n = 55; 94.8%) and the need for detailed information (52; 89.6%) regarding COVID-19 and medical service preparedness during the pandemic. The COVID-19 pandemic has influenced child healthcare and caused high levels of anxiety among parents.

Efficacy of Targeted Temperature Management after Pediatric Cardiac Arrest: A Meta-Analysis of 2002 Patients.

Cardiac arrest (CA) is associated with high mortality and poor life quality. Targeted temperature management (TTM) or therapeutic hypothermia is a therapy increasing the survival of adult patients after CA. The study aim was to assess the feasibility of therapeutic hypothermia after pediatric CA. We performed a systematic review and meta-analysis of randomized controlled trials and observational studies evaluating the use of TTM after pediatric CA. The primary outcome was survival to hospital discharge or 30-day survival. Secondary outcomes included a one-year survival rate, survival with a Vineland adaptive behavior scale (VABS-II) score ≥ 70, and occurrence of adverse events. Ten articles (n = 2002 patients) were included, comparing TTM patients (n = 638) with controls (n = 1364). In a fixed-effects meta-analysis, survival to hospital discharge in the TTM group was 49.7%, which was higher than in the non-TTM group (43.5%; odds ratio, OR = 1.22; 95% confidence interval, CI: 1.00, 1.50; p = 0.06). There were no differences in the one-year survival rate or the occurrence of adverse events between the TTM and non-TTM groups. Altogether, the use of TTM was associated with a higher survival to hospital discharge; however, it did not significantly increase the annual survival. Additional high-quality prospective studies are necessary to confer additional TTM benefits.