A Comprehensive Pan-Cancer Analysis Reveals Cyclin-Dependent Kinase Inhibitor 2A Gene as a Potential Diagnostic and Prognostic Biomarker in Colon Adenocarcinoma.

Introduction Cyclin-dependent kinase inhibitor 2A (CDKN2A) is a suppressor carcinogenic gene that is upregulated across various types of cancer including breast, liver, thyroid, and bile duct cancer due to its crucial role in cell cycle regulation and cell division. Nevertheless, it is mostly investigated at the genetic level, but it is still poorly studied on pan-cancer analysis as a biomarker and this study shows its significant potential diagnostic and prognostic characteristics. However, this study aims to investigate the role of CDKN2A as a diagnostic and prognostic biomarker across various types of cancer focusing primarily on colon adenocarcinoma (COAD). Methods We investigated CDKN2A gene expression in a pan-cancer analysis across different types of cancer to show its diagnostic potential characteristics by using various bioinformatic tools, including Tumor Immune Estimation Resource (TIMER) 2.0, Gene Expression Profiling Interactive Analysis (GEPIA), and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) database. TIMER was used to profile gene expression across 32 types of cancer composed of 10,000 RNA-seq samples obtained from the Cancer Genome Atlas (TCGA) and to analyze the tumor-infiltrating immune cells. In addition, GEPIA and UALCAN were further used to analyze gene expression, in terms of gene regulation, pathological stages, and clinical parameters, including gender, age, and race. Therefore, we used GEPIA, UALCAN, and Kaplan-Meier plotter particularly across adenocarcinoma to investigate CDKN2A prognosis by studying its high expression association with the patient's overall survival rate to show the tumor progression. Then, we looked into the genetic alteration of CDKN2A by using the cBio Cancer Genomics Portal (cBioPortal), including 10 pan-cancer studies. We concluded the analysis with gene validation by using a public cohort in Gene Expression Omnibus (GEO). Results CDKN2A showed a trend of upregulation in most cancers and it was significantly upregulated in five cancers, which were commonly identifiable in three databases, including breast invasive carcinoma (p < 0.001), kidney chromophobe (p < 0.001), kidney renal clear cell carcinoma (p < 0.001), kidney renal papillary cell carcinoma (p < 0.001), and COAD (p < 0.001). The upregulation was significantly different in association with pathogenic stages II and III (pr(>F) = 0.00234) which was identifiable significantly in COAD more than in other cancers. The gene showed a high upregulation in association with poor prognosis of patient survival in three cancers, including COAD (log-rank p = 0.011), mesothelioma (log-rank p = 5.9e-07), and liver hepatocellular carcinoma (log-rank p = 0.0045). Therefore, COAD was the only comprehensively analyzed tumor to show a diagnostic and prognostic potential characteristic during high upregulation of CDKN2A. Furthermore, CDKN2A displayed a rare mutation in the form of deep deletion (9%) and revealed an upregulation associated with CD4+ T cells (p = 0.0108), macrophage (p = 0.0073), and neutrophils (p = 0.0272) as immune cells infiltrating COAD.  Conclusion Our study demonstrates the pan-cancer relevance of CDKN2A and revealed a novelty in showing CDKN2A underscores its potential as a diagnostic prognostic biomarker in COAD since CDKN2A is mostly studied at a genetic level across COAD.

Unusual liver tumors: spectrum of imaging findings with pathologic correlation.

The liver is a common location for both primary and secondary cancers of the abdomen. Radiologists become familiar with the typical imaging features of common benign and malignant liver tumors; however, many types of liver tumors are encountered infrequently. Due to the rarity of these lesions, their typical imaging patterns may not be easily recognized, meaning their underlying pathologic features may not be discovered or suggested until an invasive biopsy is performed. In this review article, we discuss multiple hepatic neoplasms that are both unusual and rare. Some have typical imaging patterns, whereas others are non-specific and can only be included in the differential diagnosis. The clinical history and serologic findings are often critical in suggesting these entities; therefore, these are also discussed to familiarize the radiologist with the appropriate clinical setting of each. The article includes an image-rich description of each entity with accompanying figures describing the ultrasonography, computed tomography, and magnetic resonance imaging features of each disease process. Novel therapies and prognosis of several of the diseases are also included in the discussion.

Management of patients with CHB outside the guidelines: Insights from Egyptian cohort with long-term follow-up.

It is alarming that globally, only 2.2% (6.6 million) of patients with chronic hepatitis B (CHB) received treatment in 2019. One contributing factor to this low treatment rate is the complexity and restrictive nature of clinical practice guidelines. Since 1998, we have adopted a "treat-all" approach to patients with CHB. A retrospective study was conducted involving patients with CHB who received treatment from 1998 to 2020 at 2 institutions in Egypt. These patients underwent evaluation through various clinical and laboratory methods, which included testing for liver enzymes and HBV DNA. The study analyzed 1825 patients with HBV, finding that 27.4% had viremia levels under 2000 IU/mL. Most (88%) were HBeAg-negative, with 12% positive. A large portion (77.6%) had normal alanine aminotransferase levels, though 5.6% exceeded twice the upper limit of normal. About 14.2% were diagnosed with liver cirrhosis, and 9.6% with F3 stage fibrosis at enrollment. Notably, 2% (25 cases) lost HBsAg over a median of 52 months. Patients with HBV DNA <2000 IU/mL had a higher HBsAg loss rate (4.2%) compared to those with levels >2000 IU/mL (1.3%). During follow-up, 9.5% (117 patients) experienced decompensation, with a higher incidence in those with HBV DNA <2000 IU/mL (16.8%) than those >2000 IU/mL (7.1%). HCC developed in 5.2% of patients with lower HBV DNA and 2.6% with higher levels, showing significant differences. Liver-related deaths occurred in 2.8% of the cohort, with a slightly higher rate in those with lower initial HBV DNA levels (3.5% vs. 2.5%). The findings suggest a paradigm shift in CHB management toward early and broader eligibility for antiviral therapy. This could improve patient outcomes and address the global treatment gap in CHB management, especially in regions with high CHB prevalence.

Tumor-like conditions that mimic liver tumors.

Non-neoplastic tumor-like conditions of the liver can appear similar to hepatic neoplasms. In many cases, a biopsy is required to confirm the pathology. However, several tumor-like conditions can be correctly diagnosed or suggested prospectively, thus saving patients from unnecessary anxiety and expense. In this image-focused review, we present the ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography scan features of eight such entities. Clues that indicate the correct pathology are discussed, and the usual clinical setting is described. Many of these lesions are treated differently from true neoplasms, and the current treatment plan is discussed in many of the cases presented. After reviewing this article, the reader will have a better understanding of these lesions and the situations in which they should be included in the differential diagnosis.

Clinical pharmacokinetics and pharmacodynamics of venetoclax, a selective B-cell lymphoma-2 inhibitor.

Venetoclax, a highly potent BCL-2 inhibitor, is indicated for treatment of some hematologic malignancies as monotherapy, and/or in combination with other agents. Venetoclax pharmacokinetics has been extensively characterized in patients and healthy participants. After oral dosing, the median time to reach maximum plasma concentration ranged from 5 to 8 h and harmonic mean half-life ranged from 14 to 18 h. Food increases venetoclax bioavailability by 3-5-fold and venetoclax should be administered with food to ensure adequate and consistent bioavailability. Venetoclax is eliminated via cytochrome P450 (CYP)3A metabolism, and a negligible amount of unchanged drug is excreted in urine. Strong CYP3A/P-glycoprotein inhibitors increased venetoclax exposures (AUC) by 1.44- to 6.90-fold while a significant decrease (71%) has been observed when dosed with strong CYP3 inducers. Venetoclax does not inhibit or induce CYP enzymes or transporters. Venetoclax pharmacokinetics is not appreciably altered by age, weight, sex, but the exposure is up to twofold higher in participants from Asian countries. Mild-to-severe renal impairment or end-stage renal disease do not alter venetoclax exposures, and venetoclax is not cleared by dialysis. Although mild-to-moderate hepatic impairment does not affect venetoclax exposures, twofold higher exposure was observed in subjects with severe hepatic impairment. Venetoclax exposure is comparable across patients with different hematologic malignancies and healthy participants. Overall, venetoclax exposure is only affected by food and CYP3A modulators and is only higher in Asian subjects and subjects with severe hepatic impairment. Venetoclax exposure-response relationships are malignancy-dependent and can be different between monotherapy and combination therapy.

Venetoclax Clinical Pharmacokinetics After Administration of Crushed, Ground or Whole Tablets.

PURPOSE: Venetoclax is a potent, orally bioavailable BCL-2 inhibitor used in the treatment of some hematological malignancies. Crushing tablets may be necessary to help with the administration of venetoclax to patients with swallowing difficulties or patients requiring nasogastric tube feeding. The study was conducted to assess the bioavailability of crushed and finely ground venetoclax tablets relative to whole tablets. METHODS: An open-label, randomized, 3-way, crossover study in 15 healthy adult females was conducted. Venetoclax tablets were administered orally in a crushed, ground or intact form on Day 1 of each period with water following a high-fat breakfast. Pharmacokinetic samples were collected up to 72 hours postdosing. FINDINGS: The crushed and ground tablets met the bioequivalence criteria (0.80-1.25) relative to the intact tablets with respect to area under the concentration-time curve to time of the last measurable concentration (AUCt) and to infinite time (AUCinf) but exhibited a slightly lower maximum plasma concentration (Cmax). This was not considered clinically significant as only venetoclax overall exposure (AUC) has been shown to correlate with clinical efficacy. There was no change in the physical appearance and the evaluated physicochemical properties of crushed and ground venetoclax tablets after 72 hours of storage at 25°C/60% relative humidity. IMPLICATIONS: Crushing or grinding venetoclax tablets before administration could be considered as a viable alternative method of administration for patients who have difficulty swallowing whole venetoclax tablets or patients requiring nasogastric tube feeding. GOV IDENTIFIERS: NCT05909553, registered June 12, 2023.

Identification of the Hub Genes Involved in Chikungunya Viral Infection.

Background Chikungunya virus (CHIKV) infection poses a significant global health threat, necessitating a deeper understanding of its molecular mechanisms for effective management and treatment. This study aimed to understand the molecular and genetic mechanisms of CHIKV infection by analyzing microarray expression data. Methodology National Center for Biotechnology Information (NCBI) GEO2R with an adjusted p-value cut-off of <0.05 and |log2FC ≥ 1.5| was used to identify the differentially expressed genes involved in CHIKV infection using microarray data from the Gene Expression Omnibus (GEO) database, followed by enrichment analysis, protein-protein interaction (PPI) network construction, and, finally, hub gene identification. Results Analysis of the microarray dataset revealed 25 highly significant differentially expressed genes (DEGs), including 21 upregulated and four downregulated genes. PPI network analysis elucidated interactions among these DEGs, with hub genes such as ACTB and CTNNB1 exhibiting central roles. Enrichment analysis identified crucial pathways, including leukocyte transendothelial migration, regulation of actin cytoskeleton, and thyroid hormone signaling, implicating their involvement in CHIKV infection. Furthermore, the study highlights potential therapeutic targets such as ACTB and CTNNB1, which showed significant upregulation in infected cells. Conclusions These findings underscore the complex interplay between viral infection and host cellular processes, shedding light on novel avenues for diagnostic marker discovery and advancing antiviral strategies. In this study, we shed light on the molecular and genetic mechanisms of CHIKV infection and the potential role of ACTB and CTNNB1 genes.

HbA1c or fructosamine on evaluating glucose intolerance in children with beta- thalassemia.

BACKGROUND: Beta-thalassemia major (ß-TM) patients are more likely to experience blood glucose intolerance and to date; the blood markers that could evaluate this are debatable. So, this study aimed to assess the roles of glycated hemoglobin A1c (HbA1c) and fructosamine in evaluating glucose intolerance in children with ß-TM and figuring out role of insulin resistance in these patients. METHODS: One hundred children diagnosed with ß-TM and 100 age and sex-matched controls were enrolled. Fasting plasma glucose (FPG), 2-h post-prandial blood glucose (2-h PG), HbA1c, fructosamine, fasting insulin level (FINS), insulin resistance index (HOMA-IR), and insulin sensitivity index (HOMA-IS) were evaluated. RESULTS: FPG and 2-h PG revealed glucose intolerance in 51 patients (51%), 19 of them had diabetes mellitus. HbA1c, fructosamine, FINS, and HOMA-IR showed a high statistically significant increase in patients compared to controls, (P < 0.001). Results revealed fructosamine was more specific in detecting prediabetes state and more sensitive in identifying diabetes mellitus in our patients when compared to HbA1c. CONCLUSIONS: Despite controversies on HbA1c in children with ß-TM, it is still valuable in glucose intolerance detection. Fructosamine showed more sensitivity and specificity. Furthermore, insulin resistance was prevalent in children with ß-TM highlighting the necessity of regular glycemic state evaluation. IMPACT: Glucose intolerance is a common complication in beta thalassemia patients. Conflicting data was reported about the role of HbA1c and fructosamine in evaluating glucose intolerance in thalassemic patients. Fructosamine does not yet have a threshold that may be used to distinguish between patients who have diabetes mellitus and those who do not. Fructosamine was more specific in detecting blood glucose intolerance compared to HbA1c and was more sensitive for diagnosing diabetes mellitus. Insulin resistance was common in patients with beta-thalassemia and often present before the onset of overt diabetes.

Advances in endoscopic management of colonic diverticular bleeding.

PURPOSE OF REVIEW: This review is focused on diagnostic and management strategies for colonic diverticular bleeding (CDB). It aims to present the current state of the field, highlighting the available techniques, and emphasizing findings that influence the choice of therapy. RECENT FINDINGS: Recent guidelines recommend nonurgent colonoscopy (>24 h) for CDB. However, factors such as a shock index ≥1, which may warrant an urgent colonoscopy, remain under investigation.The standard approach to detecting the source of CDB requires a water-jet scope equipped with a cap. Innovative diagnostic techniques, such as the long-cap and tapered-cap, have proven effective in identifying stigmata of recent hemorrhage (SRH). Furthermore, the water or gel immersion methods may aid in managing massive hemorrhage by improving the visualization and stabilization of the bleeding site for subsequent intervention. Innovations in endoscopic hemostasis have significantly improved the management of CDB. New therapeutic methods such as endoscopic band ligation and direct clipping have substantially diminished the incidence of recurrent bleeding. Recent reports also have demonstrated the efficacy of cutting-edge techniques such as over-the-scope clips, which have significantly improved outcomes in complex cases that have historically necessitated surgical intervention. SUMMARY: Currently available endoscopic diagnostic and hemostatic methods for CDB have evolved with improved outcomes. Further research is necessary to refine the criteria for urgent colonoscopy and to confirm the effectiveness of new endoscopic hemostasis techniques.

Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial.

In this prospective, interventional phase 1 study for individuals with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T cells (HER2 CAR T cells) after lymphodepletion with fludarabine (Flu) ± cyclophosphamide (Cy): 1 × 108 T cells per m2 after Flu (cohort A) or Flu/Cy (cohort B) and 1 × 108 CAR+ T cells per m2 after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2 CAR T cells after lymphodepletion. Determination of antitumor responses was the secondary outcome. Thirteen individuals were treated in 14 enrollments, and seven received multiple infusions. HER2 CAR T cells expanded after 19 of 21 infusions. Nine of 12 individuals in cohorts A and B developed grade 1-2 cytokine release syndrome. Two individuals in cohort C experienced dose-limiting toxicity with grade 3-4 cytokine release syndrome. Antitumor activity was observed with clinical benefit in 50% of individuals treated. The tumor samples analyzed showed spatial heterogeneity of immune cells and clustering by sarcoma type and by treatment response. Our results affirm HER2 as a CAR T cell target and demonstrate the safety of this therapeutic approach in sarcoma. ClinicalTrials.gov registration: NCT00902044 .

Drug-Drug Interactions and Actual Harm to Hospitalized Patients: A Multicentre Study Examining the Prevalence Pre- and Post-Electronic Medication System Implementation.

INTRODUCTION: Drug-drug interactions (DDIs) have potential to cause patient harm, including lowering therapeutic efficacy. This study aimed to (i) determine the prevalence of potential DDIs (pDDIs); clinically relevant DDIs (cDDIs), that is, DDIs that could lead to patient harm, taking into account a patient's individual clinical profile, drug effects and severity of potential harmful outcome; and subsequent actual harm among hospitalized patients and (ii) examine the impact of transitioning from paper-based medication charts to electronic medication management (eMM) on DDIs and patient harms. METHODS: This was a secondary analysis of the control arm of a controlled pre-post study. Patients were randomly selected from three Australian hospitals. Retrospective chart review was conducted before and after the implementation of an eMM system, without accompanying clinical decision support alerts for DDIs. Harm was assessed by an expert panel. RESULTS: Of 1186 patient admissions, 70.1% (n = 831) experienced a pDDI, 42.6% (n = 505) a cDDI and 0.9% (n = 11) an actual harm in hospital. Of 15,860 pDDIs identified, 27.0% (n = 4285) were classified as cDDIs. The median number of pDDIs and cDDIs per 10 drugs were 6 [interquartile range (IQR) 2-13] and 0 (IQR 0-2), respectively. In cases where a cDDI was identified, both drugs were 44% less likely to be co-administered following eMM (adjusted odds ratio 0.56, 95% confidence interval 0.46-0.73). CONCLUSION: Although most patients experienced a pDDI during their hospital stay, less than one-third of pDDIs were clinically relevant. The low prevalence of harm identified raises questions about the value of incorporating DDI decision support into systems given the potential negative impacts of DDI alerts.

Elevating Chest X-ray Image Super-Resolution with Residual Network Enhancement.

Chest X-ray (CXR) imaging plays a pivotal role in diagnosing various pulmonary diseases, which account for a significant portion of the global mortality rate, as recognized by the World Health Organization (WHO). Medical practitioners routinely depend on CXR images to identify anomalies and make critical clinical decisions. Dramatic improvements in super-resolution (SR) have been achieved by applying deep learning techniques. However, some SR methods are very difficult to utilize due to their low-resolution inputs and features containing abundant low-frequency information, similar to the case of X-ray image super-resolution. In this paper, we introduce an advanced deep learning-based SR approach that incorporates the innovative residual-in-residual (RIR) structure to augment the diagnostic potential of CXR imaging. Specifically, we propose forming a light network consisting of residual groups built by residual blocks, with multiple skip connections to facilitate the efficient bypassing of abundant low-frequency information through multiple skip connections. This approach allows the main network to concentrate on learning high-frequency information. In addition, we adopted the dense feature fusion within residual groups and designed high parallel residual blocks for better feature extraction. Our proposed methods exhibit superior performance compared to existing state-of-the-art (SOTA) SR methods, delivering enhanced accuracy and notable visual improvements, as evidenced by our results.

Pharmacokinetic Modeling Using Real-World Data to Optimize Unfractionated Heparin Dosing in Pediatric Patients on Extracorporeal Membrane Oxygenation and Evaluate Target Achievement-Clinical Outcomes Relationship.

Unfractionated heparin (UFH) is a commonly used anticoagulant for pediatric patients undergoing extracorporeal membrane oxygenation (ECMO), but evidence is lacking on the ideal dosing. We aimed to (1) develop a population pharmacokinetic (PK) model for UFH, measured through anti-factor Xa assay; (2) optimize UFH starting infusions and dose titrations through simulations; and (3) explore UFH exposure-clinical outcomes relationship. Data from 218 patients admitted to Utah's Primary Children's Hospital were retrospectively collected. A 1-compartment PK model with time-varying clearance (CL) adequately described UFH PK. Weight on CL and volume of distribution and ECMO circuit change on CL were significant covariates. The typical estimates for initial CL and first-order rate constant to reach steady-state CL were 0.57 L/(h·10 kg) and 0.02/h. Comparable to non-ECMO patients, the typical steady-state CL was 0.81 L/(h·10 kg). Simulations showed that a 75 IU/kg UFH bolus dose followed by starting infusions of 25 and 20 IU/h/kg for patients aged younger than 6 years and 6 years or older, respectively, achieved the therapeutic target in 56.6% of all patients, whereas only 3.1% exceeded the target. The proposed UFH titration schemes achieved the target in more than 90% of patients while less than 0.63% were above the target after 24 and 48 hours of treatment. The median intensive care unit survival time in patients within and below the target at 24 hours was 136 and 66 hours, respectively. In conclusion, PK model of UFH was developed for pediatric patients on ECMO. The proposed UFH dosing scheme attained the anti-factor Xa target rapidly and safely.

Venetoclax in biomarker-selected multiple myeloma patients: Impact of exposure on clinical efficacy and safety.

Venetoclax, a potent BCL-2 inhibitor, is currently under development for treatment of t(11;14) Multiple myeloma (MM). The objective of this research was to investigate the exposure-response relationships of venetoclax for a phase 1/2 study evaluating venetoclax monotherapy or in combination with dexamethasone in relapsed or refractory MM. A total of 117 patients receiving venetoclax at 300, 600, 800, 900, or 1200 mg were included in the analysis. The impact of venetoclax exposures on efficacy (objective response rate [ORR], progression-free survival [PFS] and overall survival [OS]) as well as safety (treatment-emergent adverse effects (grade ≥3) of neutropenia, infection, and any grade of serious treatment-emergent adverse effects) was evaluated. In the t(11;14)-positive subpopulation, venetoclax exposure relationships to PFS and OS indicated a trend of longer PFS and OS with higher exposures. Moreover, logistic regression analyses for clinical response (ORR and ≥VGPR rate) demonstrated a statistically significant (p < 0.05) relationship with exposure. Evaluation of the exposure-safety relationships demonstrated a lack of a relationship between venetoclax exposures (AUCavg ) and grade ≥3 infections, grade ≥3 neutropenia, grade ≥3 treatment-emergent adverse events or any grade serious treatment-emergent adverse events. These findings support further study of venetoclax at 800 mg QD dose in combination with dexamethasone in the t(11;14)-positive patient population where increased efficacy was observed without an increase in safety events.Clinical Trial: NCT01794520 registered 20 February 2013.

Venetoclax pharmacokinetics in participants with end-stage renal disease undergoing haemodialysis.

AIMS: Renal insufficiency is a common comorbidity in patients with haematological malignancies. This study aimed to assess how end-stage renal disease (ESRD) might affect the pharmacokinetics of venetoclax, a Bcl-2 inhibitor, in participants with ESRD undergoing haemodialysis. METHODS: Venetoclax was administered as a single 100-mg dose to 6 female participants with ESRD (estimated glomerular filtration rate <15 mL/min) both prior to haemodialysis and between haemodialysis days and 7 healthy female participants with normal renal function (estimated glomerular filtration rate >90 mL/min). Intensive pharmacokinetic and protein binding samples were collected from all participants. Arterial and venous samples were collected from ESRD participants during haemodialysis to assess the effect of haemodialysis on venetoclax pharmacokinetics. Pharmacokinetic parameters were estimated using noncompartmental methods. RESULTS: There was no difference in plasma venetoclax concentrations between arterial and venous samples, suggesting that haemodialysis did not affect the pharmacokinetics of venetoclax. The fraction unbound (fu ) of venetoclax was ~2-fold higher for participants with ESRD compared to participants with normal renal function. The unbound maximum plasma concentration and area under the plasma concentration-time curve from time 0 to 48 h were comparable between ESRD and normal function groups. The mean half-life ranged from 10.4 to 12.2 h across groups, demonstrating that ESRD did not affect the half-life of venetoclax. No new safety signals were observed during this study. CONCLUSION: ESRD and dialysis do not alter unbound venetoclax plasma concentrations. No pharmacokinetics driven dose adjustment is needed for patients with renal insufficiency.

Surgical Outcomes of Laparoscopic-assisted Distal Gastrectomy Versus Totally Laparoscopic Distal Gastrectomy Billroth I for Gastric Cancer.

OBJECTIVE: The present study aimed to compare intraoperative and postoperative outcomes of laparoscopic-assisted distal gastrectomy versus totally laparoscopic distal gastrectomy (TLDG) Billroth I (BI) for gastric cancer and to assess the impact of the initial introduction phase of TLDG BI anastomosis. PATIENTS AND METHODS: The study analyzed the prospectively collected data of patients who underwent laparoscopic distal gastrectomy BI from 2014 to 2021 at Seoul National University Hospital. RESULTS: Among 1116 patients, laparoscopic-assisted distal gastrectomy BI was performed in 566 patients and TLDG BI was performed in 550 patients. The total laparoscopic arm had a faster mean operative time (190 vs 208 min; P < 0.001) and a shorter postoperative hospital stay (7.4 vs 7.9 d; P < 0.001). Local complications were higher in the total laparoscopic group (17.6% vs 9.9%; P = 0.008) during the early introduction phase. CONCLUSION: The total laparoscopic approach for BI reconstruction is safe and effective with faster operative time, shorter hospital stays, and less wound infection, but it may be associated with an increase in postoperative surgical complications and hospital stay in the early introduction phase.

Efficacy and Safety of Combined Deferiprone and Deferasirox in Iron-Overloaded Patients: A Systematic Review.

Despite the established efficacy of iron chelation therapy in transfusion-induced iron-overloaded patients, there is no universal agreement regarding the choice of an optimal chelating regimen. Deferasirox (DFX) and deferiprone (DFP) are two oral iron chelators, and combination usage demonstrated effectiveness as an alternative to monotherapies in patients with a limited response to monotherapy. The present systematic review aimed to assess the evidence regarding the outcomes of combined DFP and DFX in iron-overloaded patients. An online search was conducted in PubMed, Scopus, Web of Science, and CENTRAL databases. Interventional and observational studies that assessed the outcomes of combined DFP and DFX in iron-overloaded patients were included. Eleven studies (12 reports) were considered in this meta-analysis. The studies included dual iron chelation strategies for a number of diagnoses. Single-arm studies (n =7) showed a reduction of serum ferritin, which reached the level of statistical significance in three studies. Likewise, most studies reported a numerical reduction in liver iron concentration (LIC) and increased cardiac MRI-T2* values after chelating therapy. Alternatively, comparative studies showed no significant difference in post-treatment serum ferritin between DFX plus DFP and DFX/DFP plus deferoxamine (DFO). The adherence to combination therapy was good to average in nearly 66.7-100% of the patients across four studies. One study reported a poor adherence rate. The combined regimen was generally tolerable, with no reported incidence of serious adverse events among the included studies. In conclusion, the DFP and DFX combination is a safe and feasible option for iron overload patients with a limited response to monotherapy.

Cost-Effectiveness of Recombinant Zoster Vaccine for the Prevention of Herpes Zoster in Hematopoietic Stem Cell Transplant Recipients and Other Immunocompromised Adults in the United States.

INTRODUCTION: Immunocompromised (IC) adults are at increased risk of developing herpes zoster (HZ) and HZ-related complications due to therapy or underlying disease. This study evaluated the cost effectiveness of recombinant zoster vaccine (RZV) versus no vaccine for the prevention of HZ in hematopoietic stem cell transplant (HSCT) recipients and other IC adults aged ≥ 18 years in the United States (US). METHODS: A static Markov model simulated cohorts of IC individuals using a 1-year cycle length and 30-year time horizon to estimate the cost effectiveness of RZV. Inputs were sourced from clinical trial results and publicly available sources/literature. Modeled populations included US adult HSCT recipients (base case), patients with human immunodeficiency virus (HIV), patients with breast cancer, patients with Hodgkin's lymphoma, and renal transplant recipients. The model reported societal costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity and threshold analyses were conducted. RESULTS: In the base case of 19,671 US adult HSCT recipients, RZV resulted in total societal cost savings of US$0.1 million and 109 incremental QALYs versus no vaccine. RZV was a 'dominant strategy' versus no vaccine because vaccination resulted in cost savings with QALY gains. RZV was also cost saving in renal transplant recipients, and cost effective at a willingness-to-pay threshold of US$100,000 per QALY gained in patients with HIV, breast cancer, and Hodgkin's lymphoma, with ICERs of US$33,268, US$67,682, and US$95,972 per QALY gained, respectively, versus no vaccine. CONCLUSIONS: Model results show RZV is potentially cost saving for the prevention of HZ in US adult HSCT recipients and US adults with selected immunocompromising conditions, and cost effective for others, supporting the use of RZV to prevent HZ and HZ-related complications in IC adults.

Developing the next generation of renewable energy technologies: an overview of low-TRL EU-funded research projects.

A cluster of eleven research and innovation projects, funded under the same call of the EU's H2020 programme, are developing breakthrough and game-changing renewable energy technologies that will form the backbone of the energy system by 2030 and 2050 are, at present, at an early stage of development. These projects have joined forces at a collaborative workshop, entitled ' Low-TRL Renewable Energy Technologies', at the 10th Sustainable Places Conference (SP2022), to share their insights, present their projects' progress and achievements to date, and expose their approach for exploitation and market uptake of their solutions.