Insertion Site Research Articles

Bloodstream infections among patients receiving therapeutic plasma exchanges in the intensive care unit: a 10 year multicentric study

BackgroundTherapeutic plasma exchanges (TPE), which affect the humoral response, are often performed in combination with immunosuppressive drugs. For this reason, TPE may be associated with an increased susceptibility to infections. We aimed to describe blood stream infection (BSI) incidence in ICU patients treated with TPE and to identify associated risk factors.MethodsWe retrospectively included patients that had received at least one session of TPE in the ICU of one of the 4 participating centers (all in Paris, France) between January 1st 2010 and December 31th 2019. Patients presenting with a BSI during ICU stay were compared to patients without such an infection. Risk factors for BSI were identified by a multivariate logistic regression model.ResultsOver 10 years in the 4 ICUs, 387 patients were included, with a median of 5 [2–7] TPE sessions per patient. Most frequent indications for TPE were thrombotic microangiopathy (47%), central nervous system inflammatory disorders (11%), hyperviscosity syndrome (11%) and ANCA associated vasculitis (8.5%). Thirty-one patients (8%) presented with a BSI during their ICU stay, a median of 7 [3–11] days after start of TPE. In a multivariate logistic regression model, diabetes (OR 3.32 [1.21–8.32]) and total number of TPE sessions (OR 1.14 [1.08–1.20]) were independent risk factors for BSI. There was no difference between TPE catheter infection related BSI (n = 11 (35%)) and other sources of BSI (n = 20 (65%)) regarding catheter insertion site (p = 0.458) or rate of TPE catheter related deep vein thrombosis (p = 0.601). ICU course was severe in patients presenting with BSI when compared to patients without BSI, with higher need for mechanical ventilation (45% vs 18%, p = 0.001), renal replacement therapy (42% vs 20%, p = 0.011), vasopressors (32% vs 12%, p = 0.004) and a higher mortality (19% vs 5%, p = 0.010).ConclusionBlood stream infections are frequent in patients receiving TPE in the ICU, and are associated with a severe ICU course. Vigilant monitoring is crucial particularly for patients receiving a high number of TPE sessions.

Reduced-port robotic pancreaticoduodenectomy with optimized surgical field deployment: early results of single-site plus-two ports method

BackgroundThe adoption of Robotic Pancreaticoduodenectomy (RPD) is increasing globally. Meanwhile, reduced-port RPD (RPRPD) remains uncommon, requiring robot-specific techniques not possible with laparoscopy. We introduce a unique RPRPD technique optimizing surgical field exposure.MethodsOur RPRPD utilizes a single-site plus-two ports technique, facilitated by a single-port platform through a 5-cm incision. The configuration of robotic arms (arm1, arm2, arm3, and arm4) were strategically designed for optimal procedural efficiency, with the arms2 and arm3, alongside the assistant trocar, mounted on the single-port platform, while the arms1 and arm4 were positioned laterally across the abdomen. Drainage was established via channels created at the arm1 and arm4 insertion sites. A “gooseneck traction” was principally employed with the robotic instrument to prop up the specimen rather than grasp, improving the surgical field’s visibility and access. Clinical outcomes of patients who underwent RPRPD performed between August 2020 and September 2023 by a single surgeon across two centers in Taiwan and Japan were reviewed.ResultsFifty patients underwent RPRPD using the single-site plus-two ports technique. The gooseneck traction technique enabled goodsurgical field deployment and allowed for unrestricted movement of robotic arms with no collisions with the assistant instruments. The median operative time was 351 min (250–488 min), including 271 min (219–422 min) of console time and three minutes (2–10 min) of docking time. The median estimated blood loss was 80 mL (1–872 mL). All RPRPD procedures were successfully performed without the need for conversion to open surgery. Postoperative major morbidity (i.e., Clavien-Dindo grade ≥ IIIa) was observed in 6 (12%) patients and median postoperative hospital stay was 13 days.ConclusionsThe single-site plus-two ports RPRPD with the gooseneck traction proves to be a safe, feasible option, facilitating surgical field visibility and robotic arm maneuverability.Graphical

The predominant insertion of the ischiofemoral ligament is a merging to the iliofemoral ligament as demonstrated on magnetic resonance arthrogram studies.

The capsular ligaments at the hip joint work in synchrony with the acetabulum and femoral head for articular stability. There is a lack of understanding about ischiofemoral ligament (ISFL) anatomy and function. To assess the insertion of the ISFL in non-arthritic adult hips. A retrospective analysis was performed in 72 patients who underwent magnetic resonance arthrogram (MRA) for the assessment of hip pain. The distribution of the ISFL components, the thickness, and the insertion site were assessed by concomitantly using the axial oblique, coronal, and sagittal MRA images. Two insertions of the ISFL anterior to the center of the femoral head were identified in 71 (99%) hips: (i) predominant anterior merging with the iliofemoral ligament as continuation of zona orbicularis, observed in all hips; and (ii) anterolateral junction of femoral neck and greater trochanter. Two ISFL parts (proximal and distal) were identified in 70 (97%) of the 72 studied hips. The proximal part was always thinner (mean 2.6 ± 0.7 mm) and originated from the ischium at the acetabular rim. The distal part was a continuation of the zona orbicularis, and the mean thickness was 6.7 ± 1.6 mm. Both parts merged as they coursed over the superior portion of the femoral head. The predominant insertion of the ischiofemoral ligament is a merging to the iliofemoral ligament anteriorly. Surgical procedures such as hip arthroscopy involving the ISFL will affect the function of the iliofemoral ligament, and vice versa.

Identification of Two Potential Gene Insertion Sites for Gene Editing on the Chicken Z/W Chromosomes.

The identification of accurate gene insertion sites on chicken sex chromosomes is crucial for advancing sex control breeding materials. In this study, the intergenic region NC_006127.4 on the chicken Z chromosome and the non-repetitive sequence EE0.6 on the W chromosome were selected as potential gene insertion sites. Gene knockout vectors targeting these sites were constructed and transfected into DF-1 cells. T7E1 enzyme cleavage and luciferase reporter enzyme analyses revealed knockout efficiencies of 80.00% (16/20), 75.00% (15/20), and 75.00% (15/20) for the three sgRNAs targeting the EE0.6 site. For the three sgRNAs targeting the NC_006127.4 site, knockout efficiencies were 70.00% (14/20), 60.00% (12/20), and 45.00% (9/20). Gel electrophoresis and high-throughput sequencing were performed to detect potential off-target effects, showing no significant off-target effects for the knockout vectors at the two sites. EdU and CCK-8 proliferation assays revealed no significant difference in cell proliferation activity between the knockout and control groups. These results demonstrate that the EE0.6 and NC_006127.4 sites can serve as gene insertion sites on chicken sex chromosomes for gene editing without affecting normal cell proliferation.

Defects introducing and heterostructures engineering synergistically constructing active sites for achieving stable and fast ion transport in sodium-ion batteries

Bronze phase TiO2 (TiO2(B)) has attracted significant interest as potential anode materials for sodium-ion batteries (SIBs) due to its distinctive open tunnel structure, offering abundant insertion sites for Na+-ions. However, the practical application has been hindered by its poor electrical conductivity and insufficient Na+ diffusion kinetics. Herein, we propose a novel strategy that integrates defect introducing and heterostructures engineering to enhance the performance of TiO2(B) anode. Specifically, we aim to induce oxygen vacancies (OVs) into TiO2(B) through N-doping and in-situ growth on MXenes nanosheets, thereby fabricating N-doped TiO2(B)/MXenes (N-TiO-MX) heterostructures. This strategy leverages the synergistic effects of OVs and N-atoms, along with the formation of heterointerfaces, to effectively reduce the bandgap, increase the number of Na+-ion storage sites, and shorten ion diffusion distances. The robust coupling between TiO2(B) and MXenes ensures the structural integrity of N-TiO-MX heterostructures. Consequently, the N-TiO-MX exhibits a high specific capacity of 211.3 mAh g−1 at 0.1 A g−1 after 400 cycles and superior cycling stability with 163.1 mAh g−1 after 1000 cycles at 1.0 A g−1. The study provides unique insights for designing heterostructure materials to achieve high capacity and excellent fast-charging capability.

Enteropathogenic Providencia alcalifaciens: A Subgroup of P. alcalifaciens That Causes Diarrhea.

Despite being considered a normal flora, Providencia alcalifaciens can cause diarrhea. In a previous study, strain 2939/90, obtained from a diarrheal patient, caused invasion and actin condensation in mammalian cells, and diarrhea in a rabbit model. Four TnphoA mutants of 2939/90 produced negligible invasion and actin condensation in mammalian cells. Now, the parent strain and the mutants have been sequenced to locate TnphoA insertion sites and determine the effect on virulence. A TnphoA insertion was detected in the type three secretion system (T3SS) locus on a large plasmid and not in a T3SS locus on the chromosome. In 52 genomes of P. alcalifaciens surveyed, the chromosomal T3SS locus was present in all strains, including both P. alcalifaciens genomic clades, which we classified as group A and group B. Plasmid T3SS was present in 21 of 52 genomes, mostly in group A genomes, which included isolates from an outbreak of hemorrhagic diarrhea in dogs. The TnphoA insertion only in the plasmid T3SS locus affected the invasion phenotype, suggested that this locus is critical for causation of diarrhea. We conclude that a subgroup of P. alcalifaciens that possesses this plasmid-mediated T3SS is an enteric pathogen that can cause diarrheal disease.

Assessing Acceptability of Biodegradable Contraceptive Implants in Kenya and Senegal.

Contraceptive implants are popular in Africa, but barriers to removal exist. Biodegradable implants (BDIs) offer an alternative to the need for removal. This study explored potential user, provider, and other stakeholder perspectives on 2 BDI prototypes, revealing opportunities and challenges for introduction. We conducted focus group discussions (FGDs) and in-depth interviews (IDIs) with women, men, family planning (FP) providers, community influencers, and FP policymakers and program staff in Kenya and Senegal. Characteristics of the 2 BDI prototypes were shared, and participants held and interacted with placebo prototypes. Structural coding was used to analyze the data focused on key product attributes, including biodegradation, removal potential, size, material, insertion site, and duration of effectiveness. We conducted 16 FGDs and 35 IDIs with 106 participants in Kenya and 15 FGDs and 43 IDIs with 102 participants in Senegal. Overall, respondents liked the idea of a BDI, noting the avoidance of pain and scarring and reduced transport and costs as benefits of no removal requirement. Kenyan respondents expressed greater understanding of the biodegradation process than those in Senegal, though potential users in both countries expressed concerns about possible side effects associated with the process. In Senegal, mention of cholesterol in a BDI caused concern, while Kenyan participants responded positively to the same BDI being composed of organic materials. The second BDI product was viewed as more similar to existing implants, which providers preferred. Participants suggested increasing the pregnancy protection duration beyond 18 months. No clear preference between products emerged, and participants liked and disliked some characteristics of both. Kenyan and Senegalese participants expressed interest in the BDI concept but expressed some reservations related to biodegradation, material, and side effects. BDIs offer the opportunity to expand contraceptive choice. However, messaging around product characteristics will be required for successful introduction and uptake.

LINE1-mediated epigenetic repression of androgen receptor transcription causes androgen insensitivity syndrome

Androgen insensitivity syndrome (AIS) is a difference of sex development (DSD) characterized by different degrees of undervirilization in individuals with a 46,XY karyotype despite normal to high gonadal testosterone production. Classically, AIS is explained by hemizygous mutations in the X-chromosomal androgen receptor (AR) gene. Nevertheless, the majority of individuals with clinically diagnosed AIS do not carry an AR gene mutation. Here, we present a patient with a 46,XY karyotype, born with undervirilized genitalia, age-appropriate testosterone levels and no uterus, characteristic for AIS. Diagnostic whole exome sequencing (WES) showed a maternally inherited LINE1 (L1) retrotransposon insertion in the 5′ untranslated region (5′UTR) of the AR gene. Long-read nanopore sequencing confirmed this as an insertion of a truncated L1 element of ≈ 2.7 kb and showed an increased DNA methylation at the L1 insertion site in patient-derived genital skin fibroblasts (GSFs) compared to healthy controls. The insertion coincided with reduced AR transcript and protein levels in patient-derived GSFs confirming the clinical diagnosis AIS. Our results underline the relevance of retrotransposons in human disease, and expand the growing list of human diseases associated with them.

Incidence and risk factors of neonatal peripherally inserted central catheter-related thrombosis: A systematic review and meta-analysis.

Catheter-related thrombosis is a common complication of the peripherally inserted central catheter (PICC) in neonates, leading to unintended tube removal and significantly affecting neonatal health and safety. Despite widespread reporting on the estimated occurrence and factors contributing to neonatal PICC-related thrombosis, these findings have not been synthesized. The purpose of this study was to determine the incidence and risk factors of neonatal PICC-related thrombosis. Systematic literature review and meta-analysis. Two independent researchers systematically explored multiple databases-such as PubMed, Medline, Embase and the Cochrane Library-from their inception until October 2023. Our study aggregates and scrutinizes studies specifically addressing the incidence and risk factors of neonatal PICC-related thrombosis. Employing the RevMan 5.3 software, a meta-analysis was executed to determine the incidence of both thrombosis and odds ratios (OR), accompanied by their respective 95% confidence intervals (CI) for the risk factors. A total of 327 articles were screened, and data from 24 studies were used in synthesis. Neonatal PICC-related thrombosis incidence varied from 0.23% to 17.91%. The pooled incidence was 2% (95% CI: 1%-2%; I2 = 94%; p < .0001). The study identified 12 risk factors, including insertion sites in the lower extremities (OR = 0.22; 95% CI: 0.09-0.56; p = .001), gestational age <28 weeks, abdominal pathology, fresh frozen plasma by day 5 > 50 mL/kg, PICC tip location (proximal placement), two lumens, three lumens, prolonged hospital stay, infection, mothers' use of anticoagulants, patients with cardiac insufficiency and being twin-to-twin transfusion syndrome donor. The analysis indicates an overall pooled incidence of neonatal PICC-related thrombosis of 2%. Twelve factors were identified as risks associated with neonatal PICC-related thrombosis. Understanding the risk factors can provide evidence-based recommendations for improving awareness, control and treatment and better nursing management. This systematic review and meta-analysis illuminates the incidence and risk factors linked to neonatal PICC-related thrombosis, delivering essential insights pivotal for clinical decision-making and enhancing patient care within neonatal health care settings.

Clinical observation of the treatment of refractory cancer pain with cancer pain information platform and IDDS under home analgesia mode: A retrospective study.

To evaluate the effectiveness and safety of a cancer pain information platform combined with semi-implantable intrathecal drug delivery systems among the patients with refractory cancer pain under a "home analgesia" model. This was a retrospective study. A total of 49 patients underwent semi-implantable intrathecal drug delivery systems with patient-controlled analgesia in conjunction with the establishment of a cancer pain information platform. Numeric rating scales (NRS), Bruggrmann comfort scale (BCS), high-quality sleep duration, and opioid-related adverse effects were recorded at various time points and analyzed: the day on admission (T0), the day of discharge (T1), 30 days post-discharge (T2), 60 days post-discharge (T3), 90 days post-discharge (T4), 120 days post-discharge (T5), 150 days post-discharge (T6), 180 days post-discharge (T7), and the day before death (T8). Compared with T0, NRS significantly decreased and BCS significantly increased at T1 to T8 time points (P < .05). However, NRS and BCS did not show differences at T1 to T8 time points (P > .05). The duration of high-quality sleep was significantly extended, and the incidence of opioid-related adverse effects was significantly reduced. Postoperative complications included 1 case of cerebrospinal fluid leakage, 3 cases of infection at the butterfly needle insertion site, 6 cases of hospital readmission for equipment malfunction, and no cases of respiratory depression. Eleven patients continued standardized antitreatment after IDDS surgery. The mean survival time for all patients was 135.51 ± 102.69 days, and the survival rate at T7 was 30.61%. The cancer pain information platform combined with semi-implantable IDDS is beneficial for the pain management of refractory cancer patients under the "home analgesia" model, improving their quality of life.

Fluorescence labeling strategies for the study of ion channel and receptor cell surface expression: A comprehensive toolkit for extracellular labeling of TRPV1.

Regulation of ion channel expression on the plasma membrane is a major determinant of neuronal excitability, and identifying the underlying mechanisms of this expression is critical to our understanding of neurons. A critical aspect of measuring changes in ion channel expression is uniquely identifying ion channels located on the cell surface. To accomplish this goal we demonstrate two orthogonal strategies to label extracellular sites of the ion channel TRPV1 that minimally perturb the function of the channel: 1) We use the amber codon suppression technique to introduce a non-canonical amino acid (ncAA) with tetrazine click chemistry compatible with a trans-cyclooctene coupled fluorescent dye. 2) By inserting the circularly permutated HaloTag (cpHaloTag) in an extracellular loop of TRPV1, we incorporate a click-chemistry site for a chloroalkane-linked fluorescent dye of our choosing. Optimization of ncAA insertion sites was accomplished by screening residue positions between the S1 and S2 transmembrane domains with elevated missense variants in the human population, and we identified T468 as a rapid labeling site (~5 minutes) based on functional as well as biochemical assays in HEK293T/17 cells. After several rounds of adapting the linker lengths and backbone placement of cpHaloTag on the extracellular side of TRPV1, our efforts led to a channel construct that robustly expressed as a fully functional TRPV1exCellHalo fusion with intact wild-type gating properties. The TRPV1exCellHalo construct was used in a single molecule experiment to track TRPV1 on the cell surface and validate studies that show decreased mobility of the channel upon activation. The success of these extracellular label TRPV1 (exCellTRPV1) constructs as tools to track surface expression of the channel will shed significant light on the mechanisms regulating expression and provide a general scheme to introduce similar modifications to other cell surface receptors.

P-313 Additional tubal flushing with ethiodized oil during transvaginal hydrolaparoscopy; feasibility and live birth rate, a pilot study in subfertile women

Abstract Study question Is tubal flushing with ethiodized oil during transvaginal hydrolaparoscopy (THL) feasible and what is the live birth rate within 6 months after THL? Summary answer Additional flushing with ethiodized oil during THL is feasible and safe with a live birth rate of 32.0% compared to 23.4% using solely water-based-contrast (p = 0.25). What is known already The use of ethiodized oil during hysterosalpingography (HSG), an alternative method to test tubal patency, has shown to have a positive effect on the live birth rate, compared to the use of water-based contrast (methylene blue). The benefit of THL over HSG as a tubal testing method is the possibility to also explore tubo-ovarian structures and the pouch of Douglas. Currently, only water-based media are used for tubal flushing during THL. Study design, size, duration A single-center cohort study at Máxima MC, the Netherlands, including 50 subfertile women who underwent THL and in whom there was at least unilateral tubal patency for methylene blue. Outcomes of interest included feasibility, safety and 6- months live birth rate. Our data were compared with a historical cohort of 111 subfertile women who underwent THL using solely water-based contrast (van Kessel MA. et al., 2021). Univariate – and multivariate logistic regression analysis were performed. Participants/materials, setting, methods Women with an iodine allergy and/or manifest thyroid dysfunction were excluded. Participants received additional tubal flushing with ethiodized oil (Lipiodol® Ultra Fluid). Main outcomes were appearance of oil and cell/mucus debris at the tubal fimbriae, pain scores (Visual Analogue Scale, VAS) and acceptability scores (0-10, completely unacceptable-acceptable). Secondary outcomes included; amount of ethiodized oil used, thyroid function four weeks afterwards, adverse events and live birth rate within 6 months after THL. Main results and the role of chance In 48 of the 50 THL procedures there was bilateral patency to methylene blue, ethiodized oil appeared from the tubal fimbriae bilateral in 77% (37/48), unilateral in 17% (8/48), while it did not appear in 6% (3/48). In two procedures there was unilateral patency to methylene blue. Ethiodized oil appeared unilateral in one and did not appear during the other THL. The amount of ethiodized oil used was 5 mL [3.4–6.3). The median reported pain scores on the VAS were 2.9 [IQR 1.0–5.0] after flushing with methylene blue and 3.0 [IQR 1.0–5.0] after ethiodized oil. The acceptability of the procedure was rated as 10 out of 10 [IQR 8–10]. Four weeks after the procedure 14% (6/42) had developed subclinical hypothyroidism, one woman had overt hypothyroidism (FT4 slightly decreased to 11.0 pmol/L, TSH 5.60 mU/L) and one woman had isolated hypothyroxinemia (FT4 11.0 pmol/L, TSH 3.40 mU/L). One adverse event, persistent bleeding at the trocar insertion site was reported, for which a diagnostic laparoscopy was performed. The live birth rate within 6 months after a THL was 32% (16/50), compared to 23% (26/111) in our historical cohort using solely water-based contrast (OR = 1.54, 95% CI 0.74–3.22, P = 0.25). Limitations, reasons for caution As this is a pilot study without a power analysis, the study is presumably underpowered to show an effect on the live birth rate. Also, the control group was historical. Wider implications of the findings By proving feasibility of using ethiodized oil during THL we encourage further research on its effect on pregnancy rates. Furthermore, the direct observation of tubal flushing with ethiodized oil during THL enables further investigation of the contrast characteristics, which are presumably responsible for its positive effect on live birth rate. Trial registration number NL8696

Incidence of medical adhesive-related skin injury: a reduction by changing posture.

Medical adhesive-related skin injuries (MARSI), defined as skin damage associated with the use of medical adhesive products or devices, are a common and under-reported condition that compromises skin integrity. The prevention and management of MARSI that can occur around the needle insertion site of a chest wall implantable port in hospitalised patients with a tumour remain challenging issues. The aim of this study was to explore whether the incidence of MARSI could be reduced by changing the body position during dressing changes. Participants were recruited between May 2019 and November 2020 in the oncology department of a tertiary hospital. Patients were randomly assigned to Group AB (supine followed by semi-recumbent position) and Group BA (semi-recumbent followed by supine position) with a standard intervening recovery interval of 21-28 days. Assessments for typical MARSI included itching, the combination of erythema and oedema, and blisters in the port area, and were graded according to the level of severity. The itch intensity was significantly lower in phase B (semi-recumbent) compared to phase A (supine) (2.35±1.985 versus 5.31±1.332, respectively; p<0.01). Similarly, the severity of erythema and oedema was less severe when comparing phase B to phase A: grade 0 (64.9% versus 10.5%, respectively); grade 1 (28.1% versus 19.3%, respectively); grade 2 (3.5% versus 7.0%, respectively); grade 3 (1.8% versus 45.6%, respectively); and grade 4 (1.8% versus 17.5%, respectively) (Z=5.703; p<0.01). Blisters were found far less frequently in phase B than phase A (1.8% versus 56.1%, respectively; p<0.01). The study provided statistically significant evidence that patients in a semi-recumbent position receiving dressing at a chest wall implantable port had fewer and less severe injection site MARSI than when in a supine position. The authors have no conflicts of interest to declare.

Protect peripheral intravenous catheters: a study protocol for a randomised controlled trial of a novel antimicrobial dressing for peripheral intravenous catheters (ProP trial)

IntroductionPeripheral intravenous catheters (PIVCs) are the most commonly used vascular access device in hospitalised patients. Yet PIVCs may be complicated by local or systemic infections leading to increased healthcare costs....

Genome-wide methylation landscape during somatic embryogenesis in Medicago truncatula reveals correlation between Tnt1 retrotransposition and hyperactive methylation regions.

Medicago truncatula is a model legume for fundamental research on legume biology and symbiotic nitrogen fixation. Tnt1, a retrotransposon from tobacco, was used to generate insertion mutants in M. truncatula R108. Approximately 21 000 insertion lines have been generated and publicly available. Tnt1 retro-transposition event occurs during somatic embryogenesis (SE), a pivotal process that triggers massive methylation changes. We studied the SE of M. truncatula R108 using leaf explants and explored the dynamic shifts in the methylation landscape from leaf explants to callus formation and finally embryogenesis. Higher cytosine methylation in all three contexts of CG, CHG, and CHH patterns was observed during SE compared to the controls. Higher methylation patterns were observed in assumed promoter regions (~2-kb upstream regions of transcription start site) of the genes, while lowest was recorded in the untranslated regions. Differentially methylated promoter region analysis showed a higher CHH methylation in embryogenesis tissue samples when compared to CG and CHG methylation. Strong correlation (89.71%) was identified between the differentially methylated regions (DMRs) and the site of Tnt1 insertions in M.truncatula R108 and stronger hypermethylation of genes correlated with higher number of Tnt1 insertions in all contexts of CG, CHG, and CHH methylation. Gene ontology enrichment and KEGG pathway enrichment analysis identified genes and pathways enriched in the signal peptide processing, ATP hydrolysis, RNA polymerase activity, transport, secondary metabolites, and nitrogen metabolism pathways. Combined gene expression analysis and methylation profiling showed an inverse relationship between methylation in the DMRs (regions spanning genes) and the expression of genes. Our results show that a dynamic shift in methylation happens during the SE process in the context of CG, CHH and CHG methylation, and the Tnt1 retrotransposition correlates with the hyperactive methylation regions.

Effect of puncture position on catheter patency rate during tunnelled dialysis catheter insertion from the right internal jugular vein.

No recommendations have been made regarding the puncture position during tunnelled dialysis catheter (TDC) insertion from right internal jugular vein (RIJV). We investigated the effect of puncture positioning along with other characteristics and clinical factors associated with TDCs to determine their correlation with catheter patency rate. We retrospectively reviewed TDC insertion procedures performed between January 2018 and December 2020 at a single institution. Patients were monitored for at least 1 year or until TDC removal or replacement. The distance on the post-operative chest radiography were measured to determine the height of puncture position. End points were freedom from catheter dysfunction. Total 949 catheters met the eligibility criteria. Catheter dysfunction occurred in 233 patients and catheter infection in 127 patients. By multivariate analysis, female sex [hazard ratio (HR) =1.497, 95% confidence interval (CI): 1.119-2.002; P=0.007] and split-tip catheter (HR =1.453, 95% CI: 1.087-1.944; P=0.012) were associated with an increased rate of catheter dysfunction. Every 10-year increment in age (HR =1.243, 95% CI: 1.123-1.376; P<0.001) and every 1-cm increase in the height of the catheter insertion site (HR =1.270, 95% CI: 1.096-1.473; P=0.001) were also associated with an increased rate of catheter dysfunction. After classifying the height of puncture position into 3 groups, significant worse patency was observed in the catheter with puncture height more than 4 cm (P=0.025). No immediate complications were observed. TDC insertion at a high puncture site correlates with an increased risk of catheter dysfunction. Puncturing the RIJV close to the clavicle is safe and enhances catheter patency.

Impact of Epidural Catheter-Incision Congruency on Postoperative Analgesia after Major Abdominal Surgery: An Observational Study in a Teaching Hospital.

To determine the frequency of appropriate epidural catheter-incision congruency in adult patients undergoing major abdominal surgeries, as well as the frequency of ineffective postoperative analgesia with continuous epidural infusion, side effects, and complications of epidural insertion and epidural catheter infusion. Observational study. Place and Duration of the Study: Department of Anaesthesiology, The Aga Khan University Hospital, Karachi, Pakistan, from September to November 2022. All adult patients who underwent elective major abdominal surgery under general anaesthesia with epidural analgesia were included in this study. Data were collected by chart review of the patients enrolled in Acute Pain Service for the study period. Intraoperative anaesthesia form, epidural infusion form and all records of acute pain service for the postoperative period were reviewed and recorded. One hundred and eighty-two patients were included in this study. The epidural catheter was inserted congruent to the surgical incision i.e. T10-T11 level or above in 43 (23.6%) patients only. In the postoperative period, overall effective epidural analgesia was observed in 79 (43.4%) of the patients. Motor block in lower limbs was observed in 66 (36.26%) of patients in the immediate postoperative period. The present study shows appropriate epidural catheter-incision congruency in only 23.6% of the patients. This could be one of the common reasons for ineffective postoperative pain relief via epidural analgesia in 56.6% of patients. Epidural catheter insertion site, Major abdominal surgeries, Postoperative analgesia.

A Review on Indole as a Cardinal Scaffold for Anticancer Drugs Development

Abstract: Chemotherapy is the mainstay of therapeutic cancer therapy; however, the development of resistance typically makes it less effective. There are continuous efforts by researchers to find novel lead compounds with potent anti-cancer activity. Generally, synthetic or natural heterocyclic compounds have been investigated in detail as a scaffold for cancer therapeutics. Among them, indole, owing to its unique physiochemical and biological properties, provides a promising platform for the development of pharmacophores for drug development against cancer, acting via various mechanisms. Till now, several indole-based derivatives have been identified as anti-cancer agents, which are either being used in clinics or are in various phases of clinical trials, suggesting their importance in anti-cancer drug development. These anti-cancer drugs have been classified into different classes depending on their mechanism of action. For example, histone deacetylase inhibitors (HDAC inhibitors), silent mating type information regulation 2 homolog (SIRT) inhibitors, tubulin inhibitors, proviral insertion site in Moloney murine leukemia virus (Pim) inhibitors, DNA Topoisomerase inhibitors, and kinase inhibitors. In this review, the author's approach is to compile the recent developments on indole-based anti-cancer drugs and provide insight into the respective structureactivity relationships (SARs) of the compounds. We hope the review will provide a thorough understanding to the reader and guide to developing novel and potent indole-based anticancer agents against drug-sensitive and drug-resistant cancer in the future.

Gravity- vs Wall Suction-Driven Large-Volume Thoracentesis: A Randomized Controlled Study

Prior studies have found no differences in procedural chest discomfort for patients undergoing manual syringe aspiration or drainage with gravity after thoracentesis. However, whether gravity drainage could protect against chest pain due to the larger negative-pressure gradient generated by wall suction has not been investigated. Does wall suction drainage result in more chest discomfort compared with gravity drainage in patients undergoing large-volume thoracentesis? In this multicenter, single-blinded, randomized controlled trial, patients with large free-flowing effusions of≥ 500mL were assigned at a 1:1 ratio to wall suction or gravity drainage. Wall suction was performed with a suction system attached to the suction tubing and with vacuum pressure adjusted to full vacuum. Gravity drainage was performed with a drainage bag placed 100cm below the catheter insertion site and connected via straight tubing. Patients rated chest discomfort on a 100-mm visual analog scale before, during, and after drainage. The primary outcome was postprocedural chest discomfort at 5 min. Secondary outcomes included measures of postprocedure chest discomfort, breathlessness, procedure time, volume of fluid drained, and complication rates. Of the 228 patients initially randomized, 221 were included in the final analysis. The primary outcome of procedural chest discomfort did not differ significantly between the groups (P= .08), nor did the secondary outcomes of postprocedural discomfort and dyspnea. Similar volumes were drained in both groups, but the procedure duration was longer in the gravity arm by approximately 3 min. No differences in rate of pneumothorax or reexpansion pulmonary edema were noted between the two groups. Thoracentesis via wall suction and gravity drainage results in similar levels of procedural discomfort and dyspnea improvement. ClinicalTrials.gov; No.: NCT05131945; URL: www. gov.

Assessment of Bone Thickness at the Infra Zygomatic Crest Region for Various Orthodontic Miniscrew Implant (OMSI) Insertion Angles: A Cone-Beam Computed Tomographic Study.

To evaluate the infrazygomatic crest (IZC) bone and develop guidelines for the optimum placement of orthodontic miniscrew implants (OMSIs) along the distobuccal root of the permanent maxillary first molar. Bone thickness of the IZC region of 50 young adults (25 males and 25 females) aged 18-30 years were evaluated using cone-beam computed tomography images. The infrazygomatic bone thickness along the distobuccal root of the permanent maxillary first molar was assessed at various insertion angles (40° to 75° i.r.t the maxillary occlusal plane) with an increment of 5°. Student's t-test was used to compare the IZC bone thickness and height at the orthodontic miniscrew insertion site for males and females on the right and left sides. The bone thickness of the IZC region above the distobuccal root of the permanent maxillary first molar was estimated between 4.39±0.25 mm and 9.03±0.45 mm for insertion angles from 40° to 75° to the maxillary occlusal plane. The corresponding OMSI insertion heights were 17.71±0.61 mm to 13.69±0.75 mm, respectively, above the maxillary occlusal plane. There were statistically significant gender and side-wise variations in bone thickness at the IZC area and insertion height. The safe position for OMSI placement at the IZC was 13.69-16 mm from the maxillary occlusal plane with an insertion angle between 55° and 75°. These parameters provide the optimum placement of OMSIs along the distobuccal root of the permanent maxillary first molar.