Specific Indications Research Articles

Evaluation of chromosomal abnormalities in the postnatal cohort: A single-center study on 14,242 patients.

Chromosomal analysis is a laboratory technique used to examine the chromosomes of an individual, offering insights into chromosome numbers, structures, and arrangements to diagnose and comprehend genetic diseases. This retrospective study provides a comprehensive understanding of the distribution by indications in a large cohort of 14,242 patients and the frequency of chromosomal abnormalities in different clinical populations. The study examined various indications for karyotype evaluation, with recurrent pregnancy loss being the most common indication, followed by intellectual disability, dysmorphic features, congenital anomalies, and developmental delay. The overall chromosomal abnormality rate was found to be 5.4%, with numerical abnormalities accounting for the majority of cases (61.7%). Trisomies, particularly trisomy 21, were the most frequent numerical abnormalities. In terms of structural abnormalities, inversions and translocations were the most commonly identified. The rates of chromosomal anomalies varied in specific indications such as amenorrhea, disorders of sex development, and Turner syndrome. The study also highlighted significant differences between males and females in the presence of chromosomal abnormalities across certain indications. Males exhibited a higher incidence of chromosomal abnormalities in cases of Down syndrome and infertility, whereas females showed higher abnormalities in terms of recurrent pregnancy loss. While this study provides valuable insights into the frequency and distribution of chromosomal abnormalities, it has limitations, including its retrospective design and reliance on data from a single medical genetics department. Nevertheless, the findings emphasize the importance of karyotype analysis in diagnosing chromosomal disorders and providing appropriate management, while also pointing to potential gender-related variations in chromosomal abnormalities that warrant further investigation.

Effects of a Nutraceutical Multicompound, with Probiotics, Hericium, PEA, and Undaria in Patients with Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a functional gastrointestinal condition. Probiotics and other nutraceutical compounds can have specific indications in the context of IBS. A retrospective analysis was conducted on 123 IBS patients in order to evaluate the effects of an oral probiotic-based dietary supplement (Colicron, one cps/day for 4 wk) on stool consistency and pain intensity. Different time points were defined as follows: baseline (T0), 2 wk of treatment (T2), and 4 wk of treatment (T4). Stool consistency was assessed by using the Bristol Stool Scale. Pain intensity was evaluated by the Visual Analogue Scale (VAS). Patients who were initially categorized as normal retained regular bowel movements throughout the study. Both patients with constipation and diarrhea showed an improvement in the Bristol Stool Scale. The score increased from 1.5 ± 0.5 to 3.3 ± 0.7 (p < 0.001) and decreased from 6.5 ± 0.7 to 4.3 ± 0.9 (p < 0.001) at T4, respectively, compared to T0. The VAS score for pain in the pooled IBS patients improved from 6.7 ± 2.2 to 2.8 ± 1.9 at T0 vs T4 (p < 0.001), with a similar trend also observed when patients were categorized based on stool consistency: normal (from 5.2 ± 1.9 to 2.9 ± 1.7), constipation (from 7.5 ± 1.3 to 3.2 ± 2.2), and diarrhea (6.7 ± 2.3 to 2.5 ± 1.9) (p < 0.001). Colicron could be useful in symptom relief, reducing abdominal pain and improving stool consistency of IBS patients. However, further controlled clinical trials are needed to confirm these preliminary findings.

Obstructive jaundice: epidemiology, diagnosis and choice of optimal method of biliary decompression

Aim. To analyze epidemiological features and morbidity structure in obstructive jaundice, to estimate the results of diagnosis and treatment of this category of patients and to evaluate factors affecting the effectiveness of the treatment and diagnostic program.Materials and methods. The study was based on four-year experience of treatment of 484 patients with mechanical jaundice. Ultrasound, CT, MRI, endoscopic ultrasound, and cholangioscopy were used to diagnose the level of the obstruction and the causes of obstructive jaundice. The main method of decompression involved transpapillary interventions in 365 patients. Two patients underwent choledochoduodenostomy under endoscopic ultrasound guidance. Percutaneous transhepatic interventions and “rendezvous” method were applied in 82 cases.Results. The efficacy of transpapillary endoscopic retrograde procedures in obstructive jaundice accounted for 93.4%. Complications developed in 33 patients (8.4%) including postmanipulation pancreatitis – in 19 patients (4.9%), pancreatonecrosis – in 2 patients (0.5%), bleeding – in 9 patients (2.3%), retroduodenal perforation – in 2 patients (0.5%), Mallory–Weiss syndrome – in 1 patient (0.3%). The efficacy of antegrade percutaneous transhepatic interventions comprised 95.1%, while liver parenchyma bleeding developed in 3.7% of patients. In-hospital mortality amounted to 0.8% (malignant tumor progression).Conclusion. The increasing share of patients with mechanical jaundice in the structure of general surgical emergencies, as well as the need to use high-tech equipment for diagnosis and treatment, necessitate creating centers for treatment of patients with mechanical jaundice. Retrograde and antegrade minimally invasive surgeries for specific indications are considered to be the main methods of biliary decompression.

Positive outcomes following Autologous Matrix-Induced Chondrogenesis (AMIC) in the treatment of retropatellar chondral lesions: a retrospective analysis of a patient registry

BackgroundThe patellofemoral joint is a challenging environment for treating chondral defects. Among the surgical options for the treatment of chondral defects, the single-stage Autologous Matrix-Induced Chondrogenesis (AMIC) procedure uses a porcine collagen I/III membrane to enhance bone-marrow stimulation. However, longer term outcomes data are rare for this specific indication. In order to provide real-world information, an ongoing registry has been established to record patient data and outcomes when AMIC is used to treat chondral and osteochondral lesions.MethodsPatient data were retrieved from an ongoing, prospective, multisite registry of patients who had undergone AMIC treatment of chondral defects. We identified 64 patients who had undergone AMIC for patellofemoral chondral defects and for whom pre-operative and at least 1 post-operative score were available were included in this retrospective data analysis. Outcomes were assessed via the KOOS, VAS pain, and the Lysholm scores. Outcomes at the post-operative time-points were analysed using a factorial ANOVA with post-hoc testing while linear regression was used to assess associations between the change in the Lysholm score and lesion size.ResultsThere was a significant improvement in Lysholm, VAS pain, and KOOS scores from pre-operative to the 1st year post-operative (p < 0.001), and this was maintained during the follow-up.ConclusionsThe forces exerted on the patellofemoral joint make this a challenging scenario for chondral repair. Our data demonstrates that the AMIC procedure with a collagen I/III membrane is an effective treatment for retropatellar cartilage lesions, and provides reliable results, with decreased pain and improved function. Importantly, these improvements were maintained through the follow-up period.

E7-Conjugated Bio-Inspired Microspheres as a Biological Barrier for Guided Tissue Regeneration.

Guided tissue regeneration (GTR), which is based on creating a physical barrier to prevent the downgrowth of epithelial and connective tissues into the defect site, has been widely used in clinical practice for periodontal regeneration for many years. However, its outcomes remain variable due to highly specific indications, the demand for proficient surgical skills, and frequent occurrence of complications. In this study, we developed a new GTR biomaterial that acts as a biological barrier for epithelial cells and fibroblasts while also serving as a scaffold for bone marrow-derived mesenchymal stem cells (BMSCs) and periodontal ligament stem cells (PDLSCs). This innovative GTR biomaterial is bioinspired injectable microspheres that are self-assembled from nanofibers, and their surfaces are conjugated with E7, a short peptide that selectively promotes BMSC and PDLSC adhesion but inhibits the attachment and spreading of epithelial cells and gingival fibroblasts. The selective affinity afforded by E7 on the surfaces of the nanofibrous microspheres facilitated the colonization of BMSCs in the periodontal defect, thereby substantially improving functional periodontal regeneration, as evidenced by enhanced new bone formation, reduced root exposure, and diminished attachment loss. The remarkable superiority of the bioinspired microspheres over conventional GTR materials in promoting periodontal regeneration underscores the potential of this innovative approach to enhance the efficacy of functional periodontal tissue regeneration.

Unveiling patenting strategies of therapeutics and vaccines: evergreening in the context of COVID-19 pandemic.

In the pharmaceutical sector, evergreening is considered a range of practices applied to extend monopoly protection on existing products. Filing several patent applications related to the same active pharmaceutical ingredient (API) is one of the most common manifestations of evergreening. During the COVID-19 pandemic, several health technologies were developed. This study aimed to analyze the extension of evergreening for selected health technologies for SARS-CoV-2 through patent filing strategies. Starting with the selection of three antivirals, one biological and two vaccines, a patent landscape was built based on public and private databases. Regarding these selected technologies, we analyzed some of the evergreening strategies used by different applicants, academic institutions or pharmaceutical companies and found a total of 29 applications (10 after the pandemic) for antivirals, 3 applications for a biological drug (1 after the pandemic), and 41 applications for vaccines (23 after the pandemic). Despite differences among the technologies, a common aspect found in all analyzed cases is the intense patent filing after the pandemic, aligned to the fact that those technologies were moving through the R&D process up to regulatory approval. The evergreening approach pursued has already been found in other diseases, with the risk of monopoly extension and also bringing legal uncertainty due to the lack of transparency of newer patent applications covering specific medical indications. Therefore, efforts to address evergreening should be pursued by countries, including the adoption of a public health approach to the patent examination of those technologies to prevent the granting of undeserved patents.

Initiative to reduce unnecessary routine daily testing of complete blood counts across 11 safety net hospitals.

National societies recommend against performing routine daily laboratory testing without a specific indication. Unnecessary testing can lead to patient harm, such as hospital-acquired anemia. The objective of this study was to reduce repeat complete blood counts (CBCs) after initial testing. This was a quality improvement initiative implemented across 11 safety net hospitals in New York City. A best practice advisory (BPA) was implemented that asked the user to remove a CBC if the last 2 CBCs within 72 hours had normal white blood cell and platelet counts and unchanged hemoglobin levels. The outcome measure was the rate of CBCs per 1000 patient days preintervention (January 8, 2020, to December 22, 2020) to postintervention (December 23, 2020, to December 7, 2021). The process measure was the acceptance rate of the BPA, defined as the number of times the repeat CBC order was removed through the BPA divided by the total number of times the BPA triggered. Across 11 hospitals, repeat CBC testing decreased by 12.3% (73.05 to 64.04 per 1000 patient days, P < .001). Six of the 11 hospitals exhibited statistically significant decreases, ranging from a 10% to 48.9% decrease of repeat CBCs. The overall BPA action rate was 20.0% (24,029 of 119,944 repeat CBCs). This low-effort, electronic health record-based intervention can effectively reduce unnecessary laboratory testing.

Abstract C027: RSO-021, a first-in-class covalent inhibitor of mitochondrial PRX3: From bench to bedside

Abstract RSO-021 is a first-in-class mitochondrial peroxiredoxin 3 (PRX3) covalent small molecule inhibitor. The safety and tolerability of RSO-021 are currently being tested in the phase 1-2 MITOPE clinical trial in patients with malignant pleural effusion (MPE) arising from malignant mesothelioma or metastatic cancer to the lungs (NCT05278975). Altered redox status, resulting in elevated cellular hydrogen peroxide (H2O2) levels, drives the growth and proliferation of mesothelioma and other solid tumors. PRX3, the primary mitochondrial H2O2 scavenging enzyme, supports tumor cell escape from oxidative stress and aggressive tumor growth. RSO-021 attacks active site cysteine residues in PRX3 covalently to inactivate the enzyme, resulting in elevated H2O2 levels in the mitochondria incompatible with tumor cell survival. RSO-021 showed potent PRX3 inactivation and anti-tumor activity in pre-clinical cell and mouse models of mesothelioma with good tolerability supporting its clinical development. The MITOPE trial (NCT05278975) is an open-label, non-randomized, multicenter, translational phase 1-2 dose-escalation and expansion study designed to determine the safety, tolerability, dose-limiting toxicity (DLT), pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of RSO-021 after intrapleural administration after complete drainage in patients with MPE due to mesothelioma or other metastatic disease. RSO-021 is administered locally as a pleural infusion through an indwelling catheter as a single dose on Day 1, 8 and 15 of each 3-week cycle. Safety is assessed at the end of the 21-day DLT period and efficacy every 6 weeks. PK and PD are assessed on pleural fluid, biopsies and with systemic sampling. RSO-021 is administered until disease progression, unacceptable toxicity, withdrawal of consent or study termination. Currently, MITOPE is actively recruiting patients in 4 open UK sites, with additional 9 sites on-boarding shortly. The dose escalation phase of the trial has 13 patients dosed at either 90, 120 or 180 mg flat dose levels and is anticipated to complete recruitment by the end of 2023. The trial will then continue to recruit patients as part of the dose expansion phase of the trial, which is exploring specific indications, including newly-diagnosed and previously-treated MM with MPE, as well as combination with systemic therapy in patients with refractory solid tumors and MPE. Citation Format: Dean A. Fennell, Sean Dulloo, Peter Szlosarek, Fiona Thistlethwaite, Simon Lord, Najib M Rahman, Brian Cunniff, Joanna Dzialo, Charlotte Poile, Rakesh Panchal, Jarrett Duncan, Pip Graham, Alice Bexon, George N. Naumov, James Spicer. RSO-021, a first-in-class covalent inhibitor of mitochondrial PRX3: From bench to bedside [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C027.

Development of a Protocol for Anaerobic Preparation and Banking of Fecal Microbiota Transplantation Material: Evaluation of Bacterial Richness in the Cultivated Fraction.

Fecal microbiota transplantation (FMT) has shown highly variable results in indications beyond recurrent Clostridioides difficile infection. Microbiota dysbiosis in many diseases is characterized by the depletion of strictly anaerobic bacteria, which may be crucial for FMT efficacy. We developed a protocol to ensure anaerobic conditions during the entire transplant preparation and banking process, from material collection to administration. The protocol necessitates an anaerobic cabinet, i.e., a non-standard laboratory equipment. We analyzed the population of viable anaerobes by combining cultivation and 16S rRNA gene profiling during the transplant preparation, and after 4, 8, and 12 months of anaerobic or aerobic storage at -80 °C, 78% of fecal species were captured via cultivation. Our findings suggest that strictly anaerobic transplant preparation and storage may preserve species richness better than oxic conditions, but the overall difference was not significant. However, specific anaerobes such as Neglecta and Anaerotruncus were affected by the oxygen exposure. A storage time of up to 12 months did not affect the presence of cultivated taxa. Noteworthy, our analysis focused on the richness of cultivated anaerobes rather than their abundance, which may have been affected. The benefits of the developed anaerobic protocol in FMT for specific indications remain to be demonstrated in clinical trials.

How to Perform a Baseline Ultrasound for Subfertility

The presentation, “How to Perform a Baseline Ultrasound for Subfertility,” delves into the crucial role of ultrasound in assessing and diagnosing subfertility in female patients. This educational session aims to equip healthcare professionals with essential knowledge and skills to perform baseline ultrasounds effectively. The presentation will emphasise the value of ultrasound as a non-invasive and informative diagnostic tool. Attendees will gain insights into the specific indications for baseline ultrasound, including assessment of pelvic structures, antral follicle counting, and evaluation for common pathologies contributing to subfertility. The presentation will then explore the step-by-step procedure for performing a baseline ultrasound, focusing on patient preparation, transducer selection, and image acquisition techniques. Furthermore, the session will delve into common ultrasound findings associated with subfertility, enabling practitioners to recognise and interpret potential abnormalities accurately. Through this presentation, healthcare professionals will enhance their proficiency in baseline ultrasound, empowering them to contribute significantly to the diagnosis and management of subfertility, ultimately supporting their patients on their journey towards achieving successful pregnancies.

سيميائية العنوان والغلاف في رواية "يوتوبيا" للكاتب أحمد خالد توفيق

The research dealt with two prominent components of the novel: the title and the cover. This is because these are the gateways for the reader to enter the world of surprise and interpretation. They are also the trigger that arouses the reader’s passion towards the text and interact with it. The study dealt with these components , their definition, importance and status in guiding the reader, and their role in highlighting the text in an artistic and aesthetic way that helps the recipient to decipher semantics, and to show its artistic and creative dimensions. The analysis began with the title because of its great importance in producing the narrative’s discourse. It is the cornerstone on which the author builds his idea, and carries the most intense and suggestive semantics. The title also constitutes the bridge that connects both the dispatcher and the receiver together. The cover is also an essential component, not only because it contains the text inside, but because it carries symbols that suggest specific indications that the writer wants to allude to . The cover had on it the title, the author's name and biography , critical opinions, and a quote from the novel epitomizing the novel’s tragedy. It also contained many plastic paintings such as a hand, splashed blood, palm trees, buildings, etc., as well as colors and drawings extracted from the text. The research also analyzed the connotations carried by the components of the cover as a whole, and it showed the interrelationship among its different components. It also revealed the core idea of the novel, which indicates consistency, harmony and unity of all the elements that make up the text.

PP128 A Transparent Methodology To Assess Innovativeness Of Health Technologies At Marketing Authorization Time

IntroductionDefining drug innovation can be challenging and there is no consensus on what a truly “innovative” medicine is. The Italian Medicine Agency (AIFA) has established an approach to assess innovativeness based on therapeutic need, added therapeutic value, and quality of evidence. However, judgment can be subjective and may not be adequate for assessment at the time of marketing authorization, when only preliminary evidence – often from non-comparative or non-randomized trials – are available. We developed a transparent methodology for early assessment of innovativeness at the time of marketing authorization, based on AIFA guidelines.MethodsSince the perspective was the marketing authorization date, only data available at agency’s Medical Review or pivotal trial publications were considered. AIFA criteria were revisited, using oncology medicines approved in the last 10 years as a base case. Impact of preliminary evidence and inadequate study design was considered.ResultsEach assessment should refer to the first approved specific indication and predefined clinically relevant outcomes. When more than one study was presented, best methodological quality, larger sample and/or longer follow-up was selected. Four domains were established: Therapeutical need: existence and clinical benefits of alternative therapies; Clinical benefit added when compared to those alternatives; Suitability of study design considering adequate comparator group, relevant outcome assessed and randomization; Risk of bias. For each domain, clear and specific criteria were defined in consensus by a group of experts in health technology assessment (HTA) and were applied to all cancer drugs evaluated.ConclusionsEfficacy evidence available for marketing authorization are often based on preliminary data, arising from single randomized clinical trials or even non-comparative studies, which difficult early assessments of innovativeness. For this reason, transparent and reproducible methodologies can be useful not only to HTA bodies, but also for other key stakeholders in the pharmaceutical market, such as investors, researchers, doctors, and governments.

Obstetrical Use of Intravenous Immunoglobulin at a Tertiary Care Canadian Center: A 14-Year Retrospective Study

Introduction: Intravenous immunoglobulin (IVIG) has gained widespread acceptance for the treatment of various medical conditions. However, its availability is limited, it incurs substantial costs, and reports of shortages have raised concerns regarding patient access. Additionally, adverse events with IVIG use underscore the need for prudent administration. While IVIG is approved for specific indications, its off-label use remains significant. Prior studies have addressed the general use of IVIG use and called for measures to ensure its appropriate application, research specific to the obstetrical use of IVIG is lacking. Understanding how IVIG is used in pregnancy could guide future research endeavours and shape policies aimed at optimizing patient care, minimizing unwarranted exposure, and containing healthcare costs. The objectives of this study are three-fold: (1) to assess the frequency, volume, and indications of IVIG use in pregnancy, (2) to assess the congruent use of IVIG with the approved Canadian indications and the approved conditions by the Ontario Immunoglobulin Utilization Management Guidelines, and (3) to compare the volume of IVIG used in pregnancy to the total volumes of IVIG use. Methods: This retrospective cohort study used administrative data and chart reviews to analyze all pregnant individuals between 2007 and 2020 who received IVIG during their pregnancy and delivered at a large tertiary care academic center with high-risk obstetrical care in Ontario, Canada. Data were collected on IVIG volumes, administration regimens, indications, and timing of administration during pregnancy. A descriptive analysis was performed to present the findings. Results: The study cohort comprised 122 pregnant patients, accounting for 136 deliveries. The cumulative volume of IVIG used across all obstetrical patients amounted to 41,107.50 grams, representing 1.6% of the total consumption of IVIG (2,575,766.50 grams) at our center. Among the indications for IVIG administration during pregnancy (Table 1), the most prevalent were maternal thrombocytopenia (77/136 deliveries, 56.6%) and antenatal therapy for Fetal/Neonatal Alloimmune Thrombocytopenia (F/NAIT) (22/136 deliveries, 16.2%). The highest IVIG consumption was observed in F/NAIT, with a total of 26,435 grams (64.3%) used in all pregnancies and a median of 1015 grams per pregnancy (IQR = 542.5, 1938.75). Maternal thrombocytopenia followed, accounting for a total of 6,952.50 grams (16.9%) used in all pregnancies and a median of 70 grams per pregnancy (IQR = 40, 90). We observed an overall increase in the trend of IVIG use in pregnancy and average volumes per delivery, but this remains a small proportion of total IVIG use (Figure 1). In terms of congruent use of IVIG, 38.2% of deliveries (52/136) did not meet the Canadian licensed indications for IVIG use, accounting for a large amount (33,025 grams, 80.3% of total volume used). However, 17.6% of deliveries (24 out of 136) did not adhere to the Ontario guidelines' indications for IVIG use, which constituted a total of 5,475 grams (13% of total volume used). Conclusions: The obstetrical use of IVIG represents a minor proportion of the total volume used at a large Canadian tertiary care center. Hematologic conditions, particularly F/NAIT and maternal thrombocytopenia, are the predominant drivers of IVIG administration during pregnancy. Recent reports on IVIG use in the general population demonstrated similarly high prescribing patterns of IVIG among hematologists, but also neurologists. Rational prescribing and dose minimization are important strategies to improve judicious and cost-effective use of IVIG. However, implementation of such strategies for obstetrical use of IVIG may be limited as evidence generally stems from small, retrospective, observational studies, and reaching a consensus among various specialists may sometimes prove difficult. There is a pressing need for prospective multicenter studies in pregnant individuals, particularly for conditions with high IVIG consumption. These studies would help to examine the efficacy and safety of IVIG during pregnancy and provide essential guidance for appropriate IVIG use in this unique patient population.

CfDNA Methylation-Based Pan-Hematologic Prognostic Classification

Background: The prognosis in hematologic (heme) malignancies remains challenging due to the complex and diverse biology of these diseases and invasive procedures. Although risk stratification/prognostic methods (e.g., cytogenetics, mutations, clinical parameters) exist for single heme indications, there is a lack of prognostic tools that simultaneously address the biological heterogeneity across multiple hematologic neoplasms. This gap underscores the need for a pan-heme prognostic classifier. Here, we developed a comprehensive prognostic classifier based on targeted methylation sequencing of cfDNA in peripheral blood. Methods: Our pan-heme classifier was trained using 621 heme participants (32 Hodgkin lymphoma, 265 Non-Hodgkin Lymphomas [NHL], 128 myeloproliferative neoplasms, 72 plasma cell neoplasms, 124 monoclonal gammopathy of undetermined significance [MGUS]) and evaluated with a subset of 320 heme patients (18 Hodgkin lymphomas, 188 NHL, 70 myeloproliferative neoplasms, 44 plasma cell neoplasms) from the Circulating Cell-free Genome Atlas substudy 2 using a six-fold nested cross-validation. The top K principal components (PCs) of methylation beta values with age, sex, body mass index, smoking status, stage, and heme subtype were used to fit a Cox model. Personalized risk scores were generated for each sample by exponentiating the linear predictor. The C-index was calculated using risk scores and survival outcomes. Participants were stratified into high- and low-risk groups based on the risk scores of corresponding indications, with scores above 66.7th percentile categorized as high risk and below this threshold categorized as low risk. The risk classification was assessed by Kaplan-Meier curves and log-rank tests. To better understand methylation biology driving the classification performance, we conducted differential methylation analysis between high-risk (N=213) and low-risk (N=107) groups, using beta-binomial regression with an arcsine link function to model the region-level count data. Hypothesis testing was performed by Wald-test for each region. The differentially methylated regions (DMRs) were considered significant if q-value was less than 0.05 and the absolute value of beta-binomial model delta coefficients was greater than 0.1. The closest genes were annotated to significant DMRs, and pathway over-representation analysis was conducted using the annotated genes from significant hypermethylated DMRs or hypomethylated DMRs. Results: Methylation features are significant predictors of survival outcome even after adjusting for clinical covariates. The pan-heme risk stratification achieved an overall C-index of 0.70 (95% CI: 0.62-0.78), indicating good discrimination. The survival of the high- and low-risk groups was significantly different (log-rank p-value&amp;lt;0.0001). Noteworthy results were observed for specific indications: Myelodysplastic syndromes (MDS; N=16) showed a robust discriminatory power with a C-index of 0.86 (95% CI: 0.67-1.00). Hodgkin lymphoma (N=18) achieved a C-index of 0.91 (95% CI: 0.76-1.00). Diffuse large B-cell lymphoma (DLBCL; N=33) yielded a C-index of 0.71 (95% CI: 0.52-0.89). Follicular lymphoma (N=50) reached a C-index of 0.63 (95% CI: 0.39-0.86). Plasma cell neoplasm (N=44) showed a C-index of 0.65 (95% CI: 0.37-0.90). Moreover, the differential methylation analysis identified 4,110 DMRs. Overlapped features in significant DMRs compared to background were enriched in genomic regions, including CpG islands, CpG shelves, and CpG shores. Pathway enrichment analysis of hypermethylated DMRs in high-risk groups revealed significant associations with calcium, cAMP, MAPK, Ras, Rap1, Wnt, and hippo signaling pathways. Conclusions: We developed a novel, minimally-invasive, pan-heme prognostic classifier utilizing cfDNA blood-based targeted methylation sequencing technology. This cfDNA-based approach demonstrated potential for risk stratification across a diverse range of heme malignancies. Further, an approach utilizing a simple, minimally-invasive blood draw instead of a combination of multiple testing modalities, offers a pragmatic approach to disease prognosis across large heterogeneous groups of hematologic malignancies.

Efficacy and Safety of Isoprenaline during Unstable Third-Degree Atrioventricular Block.

Unstable and symptomatic complete atrioventricular block represents a potentially fatal condition that requires prompt therapy while waiting for definitive pacemaker implantation. Although transcutaneous pacing is included in acute management, it could be a difficult approach due to its painfulness and the occasional failure of mechanical capture. Drug therapy is a feasible choice, and current guidelines encompass the use of atropine, dopamine, or epinephrine. Isoprenaline has never been investigated in this setting, and no specific indication of its use has been provided despite its potentially more favorable pharmacological profile. The study population included a consecutive series of patients who presented to the emergency department because of unstable third-degree atrioventricular block and were treated with either isoprenaline or dopamine infusion while waiting for definitive pacemaker implantation. Asymptomatic patients or those with reversible causes of complete atrioventricular block were excluded. The clinical response to the drug was deemed poor if, despite achieving a full drug dose, patients remained symptomatic and/or with hemodynamic instability, ventricular rate and rhythm did not improve or worsened, including if ventricular arrhythmias or asystolic pauses and/or irrepressible nausea/vomiting occurred. Isoprenaline infusion has proved to be safe and tolerated with no arrhythmia induction or hypotensive issues. Isoprenaline has also proven to be more satisfactory in achieving an effective clinical response in 84% of patients rather than dopamine (31%, p < 0.001), reducing the need for temporary artificial pacing. Our data point out the efficacy and safety of isoprenaline infusion and its greater tolerability over dopamine in the acute management of unstable third-degree AV block while waiting for definitive pacemaker implantation.

Non-surgical management of chronic subdural hematoma: insights and future perspectives from an international survey including neurosurgeons from 90 countries worldwide

Background Chronic subdural hematoma (cSDH) is one of the most common neurosurgical conditions. Although surgical evacuation is still the gold standard for treatment, recent advances have led to the development of other management strategies, such as medical therapies and endovascular middle meningeal artery (MMA) embolization. Through this international survey, we investigated the global trends in cSDH management, focusing on medical and endovascular treatments. Design and participants A 14-question, web-based, anonymous survey was distributed to neurosurgeons worldwide. Results Most responders do not perform MMA embolization (69.5%) unless for specific indications (29.6%). These indications include residual cSDH after surgical evacuation (58.9%) or cSDH in patients on antiplatelet medications to avoid surgical evacuation (44.8%). Survey participants from teaching versus non-teaching hospitals (p = 0.002), public versus private hospitals (p = 0.022), and Europe versus other continents (p < 0.001) are the most users of MMA embolization. A large number of participants (51%) declare they use a conservative/medical approach, mainly to avoid surgery in patients with small cSDH (74.8%). Conclusions This survey highlights the current trends of cSDH management, focusing on conservative and MMA embolization treatment strategies. Most responders prefer a conservative approach for patients with small cSDHs not requiring surgical evacuation. However, in higher-risk scenarios such as residual hematomas after surgery or patients on antiplatelet medications, MMA embolization is regarded as a reasonable option by participants. Future studies should clarify the indications of MMA embolization, including appropriate patient selection and efficacy as a stand-alone procedure.

Traqueotomía versus traqueostomía, la necesidad de una aclaración lexicográfica

In the healthcare field, the terms “traqueotomía” and “traqueostomía” are frequently used, often leading to confusion among professionals regarding the appropriate definition for each term or which one should be considered more correct in specific cases. A search was conducted for the terms “traqueotomía” and “traqueostomía” in general Spanish-language dictionaries such as the Dictionary of the Royal Spanish Academy (DRAE) and the Historical Dictionary of the Spanish Language of the Royal Spanish Academy (DHLE), as well as for the English terms “tracheotomy” and “tracheostomy” in English general dictionaries like the Oxford Dictionary, the Cambridge Dictionary, and the Collins English Dictionary. Additionally, searches were performed in medical dictionaries in both Spanish, specifically the Dictionary of Medical Terms of the National Academy of Medicine (DTM), and English, including the Farlex Dictionary. The terms were also explored using the Google search engine. Definitions were analyzed from both lexicographical and etymological perspectives. Definitions found in general dictionaries, in both Spanish and English, were found to be imprecise, limited, and ambiguous, as they mixed outdated indications with criteria that deviated from etymology. In contrast, definitions in medical dictionaries in both languages were more aligned with etymology. “Traqueotomía” strictly identifies the surgical procedure of creating an opening in the anterior face of the trachea. “Traqueostomía” identifies the creation of an opening that connects the trachea to the exterior, involving a modification of the upper airway by providing an additional entry for the respiratory pathway. “Traqueostomía” becomes the sole means of entry to the airway in total laryngectomies. Both terms can be used synonymously when a traqueotomía culminates in a traqueostomía. However, it is not appropriate to use the term “traqueostomía” when the procedure concludes with the closure of the planes and does not result in the creation of a stoma. Traqueostomas can be qualified with adjectives indicating permanence (temporary/permanent), size (large/small), shape (round/elliptical), or depth, without being linked to any specific disease or surgical indication. Not all permanent traqueostomas are the result of total laryngectomies, and they do not necessarily have an irreversible character systematically.

COMPARATIVE STUDY OF REVISION HIP ARTHROPLASTY AFTER SHORT STEM VERSUS AFTER CONVENTIONAL STEM

AbstractObjectiveShort-stem total hip arthroplasty (THA) aims to preserve the proximal bone stock for future revisions, so that the first revision should resemble a primary intervention rather than a revision. This study aimed to compare the clinical and radiological outcomes in revision THA after failed short stem versus after failed conventional stem THA.MethodsThis study included forty-five patients with revision THA divided into three groups (15 each); group A: revision after short stem, group B: revision after conventional cementless stem and group C revision after conventional cemented stem. The studied groups were compared regarding 31 variables including demographic data, details of the primary and revision procedures, postoperative radiological subsidence, hospital stay, time for full weight bearing (FWB), preoperative and postoperative clinical scores.ResultsEarly stem subsidence (40%) was the main indication of revision in group A compared to peri-prosthetic femoral fractures (PFFs) (73.3%) and aseptic loosening (53.3%) in group B and C respectively (P=0.021). The mean time to revision was significantly shorter in group A (15 months) compared to 95.33 and 189.40 months in group B and C respectively. (P=0.005). Sixty % (9 patients) in group A were revised in the first year. The mean operative time, blood loss, postoperative blood transfusion and hospital stay were significantly lower in group A compared to group B and C (P&lt;0.001, &lt;0.001, 0.002 and 0.001 respectively). Revisions in group A were performed using either short stems (13.3%) or conventional stems (86.7%) whilst 80% of patients needed long stems and 20% of patients needed conventional stems in group B and C (P&lt;0.001). The mean postoperative Harris Hip Score (HHS) at the latest follow up was 87.07, 87.53 and 85.47 in group A, B and C respectively. All PFFS had excellent results according to Beal's and Tower's criteria; all fractures healed and the implants were stable.ConclusionThe most common cause of failure of short stems is early stem subsidence. Short stem THA has specific indications and patient selection is very crucial. Preoperative templating for short stems and a detailed analysis of the individual patient anatomy in anteroposterior and lateral views are mandatory to predict the correct implant size more accurately. The use of intraoperative imaging can verify the sizing, implant position, and sufficient contact with the lateral cortex. Revision of short stem THA resembled the primary THA. If a standard implant can be used in a surgical revision instead of a longer revision stem, this can be considered as an advantage for the hip arthroplasty treatment concept. However, this only applies if the longevity of the first treatment with a short stem is comparable with that of a standard stem.Declaration of Interest(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Postmastectomy dual-plane submuscular-subcutaneous implant-based reconstruction: a series of 100 consecutive patients.

Advances in cancer knowledge and surgical techniques over the last decades have enabled plastic surgeons to use muscle-sparing procedures and more conservative approaches for implant-based reconstructions. In this paper, the authors describe an innovative subpectoral/subcutaneous implant pocket that represents an evolution of the classical submuscular technique and they report on the first consecutive hundred patients undergoing this procedure. Between April 2019 and May 2022, 100 consecutive patients underwent immediate postmastectomy implant-based reconstruction using the subpectoral/subcutaneous space, for a total of 122 procedures. Medical records were retrospectively reviewed and patients were prospectively followed. During plastic consultations, medical photographs were taken and aesthetic outcomes were scored with patients. Mean follow-up was 18months (range 6-46). Implant loss was observed in two patients (2%). Early minor complications were registered in 19 patients. A total of 80 out of 100 patients completed satisfaction survey assessing their postoperative outcomes. Results were considered satisfactory or very satisfactory by the surgeons and patients in more than 90% of cases. The submuscular/subcutaneous pocket can be considered a new tool in the armamentarium of reconstructive procedures, in between submuscular/subfascial procedures and prepectoral ones. It is a one-stage procedure, its a simple and short time surgery, reproducible, its very well accepted by patients. It has specific indications, advantages, and drawbacks, a careful indication and an accurate surgical technique are mandatory to achieve good results.

Diagnosis and Management of Atrial Fibrillation in Acute Ischemic Stroke in the Setting of Reperfusion Therapy: Insights and Strategies for Optimized Care.

Reperfusion therapy in the form of intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) has revolutionised the field of stroke medicine. Atrial fibrillation (AF) patients constitute a major portion of the overall stroke population; however, the prevalence of AF amongst acute ischemic stroke (AIS) patients receiving reperfusion therapy remains unclear. Limitations in our understanding of prevalence in this group of patients are exacerbated by difficulties in appropriately diagnosing AF. Additionally, the benefits of reperfusion therapy are not consistent across all subgroups of AIS patients. More specifically, AIS patients with AF often tend to have poor prognoses despite treatment relative to those without AF. This article aims to present an overview of the diagnostic and therapeutic management of AF and how it mediates outcomes following stroke, most specifically in AIS patients treated with reperfusion therapy. We provide unique insights into AF prevalence and outcomes that could allow healthcare professionals to optimise the treatment and prognosis for AIS patients with AF. Specific indications on acute neurovascular management and secondary stroke prevention in AIS patients with AF are also discussed.