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Consensus Guideline for the Management of Patients with Appendiceal Tumors, Part 1: Appendiceal Tumors Without Peritoneal Involvement
No full textBACKGROUND: Appendiceal tumors comprise a heterogeneous group of tumors that may be localized or disseminate throughout the peritoneum. Limited high quality clinical data exist and many practices have been extrapolated from colorectal cancer without validation in appendiceal cohorts. There are many controversies regarding the treatment of appendiceal tumors, and practices vary widely between centers and care settings. A national consensus update of best management practices for appendiceal malignancies was performed to better standardize care.
METHODS: The 2018 Chicago Consensus guideline was updated through a modified Delphi consensus, performed over two rounds using nationally circulated surveys. Supporting evidence was evaluated using rapid systematic reviews. Key systemic therapy concepts were summarized by content experts.
RESULTS: Most supporting literature consists of observational studies, but high-quality studies increasingly are becoming available to drive management. Two consensus-based pathways were generated for localized appendiceal tumors, one for epithelial mucinous neoplasms and another for appendiceal adenocarcinoma. Of 138 participants responding in the first round, 133 (96%) engaged in the second round. Greater than 90% consensus was achieved for all pathway blocks. Key points include minimizing intervention invasiveness where permitted by pathologic classification and margin status, and determining which margin and pathologic findings are indications for consideration of cytoreduction with or without intraperitoneal chemotherapy. Surveillance and systemic therapy recommendations are also presented.
CONCLUSION: With growing but still primarily observational evidence currently dictating care, these consensus recommendations provide expert guidance in the treatment of appendiceal tumors without peritoneal involvement
Liver transplantation for primary and secondary liver tumors: Patient-level meta-analyses compared to UNOS conventional indications
No full textBACKGROUND AND AIMS: Liver transplant (LT) for transplant oncology (TO) indications is being slowly adopted worldwide and has been recommended to be incorporated cautiously due to concerns about mid-long-term survival and its impact on the waiting list.
APPROACH AND RESULTS: We conducted 4 systematic reviews of all series on TO indications (intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma [phCC]) and liver metastases from neuroendocrine tumors (NETs) and colorectal cancer (CRLM) and compared them using patient-level meta-analyses to data obtained from the United Network for Organ Sharing (UNOS) database considering conventional daily-practice indications. Secondary analyses were done for specific selection criteria (Mayo-like protocols for phCC, SECA-2 for CRLM, and Milan criteria for NET). A total of 112,014 LT were analyzed from 2005 to 2020 from the UNOS databases and compared with 345, 721, 494, and 103 patients obtained from meta-analyses on intrahepatic cholangiocarcinoma and phCC, and liver metastases from NET and CRLM, respectively. Five-year overall survival was 53.3%, 56.4%, 68.6%, and 53.8%, respectively. In Mantel-Cox one-to-one comparisons, survival of TO indications was superior to combined LT, second, and third LT and not statistically significantly different from LT in recipients \u3e70 years and high BMI.
CONCLUSIONS: Liver transplantation for TO indications has adequate 5-year survival rates, mostly when performed under the selection criteria available in the literature (Mayo-like protocols for phCC, SECA-2 for CRLM, and Milan for NET). Despite concerns about its impact on the waiting list, some other LT indications are being performed with lower survival rates. These oncological patients should be given the opportunity to have a definitive curative therapy within validated criteria
Ureteroscopy vs Shockwave Lithotripsy for Lower Pole Renal Stones: Treatment Variation and Outcomes in a Surgical Collaborative
No full textPURPOSE: AUA guidelines recommend ureteroscopy (URS) or shockwave lithotripsy (SWL) for lower pole (LP) stones ≤ 1 cm, while SWL is second line for stones \u3e 1 to 2 cm. In the era of increasing URS, there are limited data on the modality used and outcomes. We assessed treatment distribution, stone-free rates (SFR), and unplanned health care.
MATERIALS AND METHODS: Using the Michigan Urological Surgery Improvement Collaborative registry, we identified URS and SWL cases for LP stones ≤ 2 cm (2016-2021). We assessed the frequency of patients receiving URS or SWL as a proportion of their LP treatment. A logistic model determined predictive probability of treatment modality. Differences in complete SFRs, postoperative emergency department visits, and hospitalizations were assessed by size (≤1 cm, \u3e1-2 cm), adjusted for patient factors and correlation within practice/provider.
RESULTS: There were 3645 procedures from 35 practices (209 surgeons); 2287 (62.7%) had SWL. 80.2% of stones were ≤ 1 cm. There was variation in modality based on practice (P \u3c .001) and surgeon (P \u3c .001). For stones ≤ 1 cm, the SFR was higher for URS (56% vs 39%; P \u3c .001). There were no significant differences in SFRs for \u3e 1 to 2 cm stones. Emergency department visits were higher after URS for stones ≤ 1 cm (OR: 2.95, 95% CI: 1.7-5.0) but not for \u3e 1 to 2 cm stones (OR: 0.97, 95% CI: 0.4-2.2). URS for stones ≤ 1 cm was associated with increased hospitalizations (OR: 4.67, 95% CI: 1.7-12.9) but not for stones \u3e 1 to 2 cm (OR: 0.96, 95% CI: 0.4-2.2).
CONCLUSIONS: In Michigan, SWL is the chosen modality for LP stones ≤ 2 cm. For smaller stones, URS was more effective but had greater morbidity. For larger stones, both modalities demonstrated suboptimal efficacy. Our work demonstrates the need for interventions to improve outcomes
Uncovering genetic diversity and admixture of British Africans with HLA alleles inferred from whole genome sequencing
No full textThe human leukocyte antigen (HLA) region is highly diverse and plays a crucial role in immune regulation and antigen presentation. Accurate HLA typing is essential for understanding disease susceptibility, transplantation compatibility, and pharmacogenetics. However, its application in African descent populations is challenging due to complex linkage disequilibrium patterns and the lack of ancestry-matched populations in HLA reference panels. Here, we leveraged the latest whole-genome sequencing (WGS) data from UK Biobank African individuals to perform better HLA genotyping, and further utilized allelic and haplotypic data to explore population genetics patterns of this region. With WGS-inferred HLA alleles, we identified specific admixture patterns (predominant West and East African and minor European ancestries) within British African population, revealing their complex evolutionary history. Not only did we reveal the genetic diversity within this population, but also highlighted its differences from African Americans, ancestral Africans, and other global populations. We further identified regional ancestry differences in the HLA genomic region, highlighting discordance between global and local admixture estimates. British Africans also presented unique HLA frequency distributions for both typical and disease-associated alleles or haplotypes. These findings emphasize the need for expanding African-specific HLA reference panel and prove better HLA typing can be achieved by coupling sequencing technologies with computational approaches. The HLA genetic characteristics observed in British Africans provide valuable insights into population-specific immune responses and susceptibility. Overall, this study advances our understanding of HLA diversity and genetic admixture in British African population, with important implications for both disease mechanism and clinical utility
Noncardiac Surgery After Transcatheter Aortic Valve Implantation
No full textBACKGROUND AND AIMS: There is a lack of data on perioperative outcomes for patients undergoing non-cardiac surgery (NCS) after transcatheter aortic valve implantation (TAVI). Hence, we aimed to determine the incidence, type of surgery, timing and perioperative outcomes of individuals undergoing elective NCS after TAVI.
METHODS AND RESULTS: Hospitalizations for TAVI were identified from the US National Readmission Database between 2012 and 2021, and patients who received NCS within six months were included for analysis. Incidence, type, and timing of planned readmissions for NCS were evaluated according to the surgical risk as low, intermediate, and high. The primary outcome was the occurrence of an in-hospital major adverse events (MAE) defined as the composite of death, cardiac complications, and stroke/transient ischemic attack. Multivariable regression models were constructed to identify independent factors associated with MAE. Out of 502,775 TAVI procedures, 2,390 (0.48%) patients were electively readmitted within 6 months after TAVI for NCS. Surgeries were classified as low- (n=321, 13.4%), intermediate- (n=1522, 63.7%), and high-risk (n=547, 22.9%). The median age of the study population was 78 years (IQR 73-84) with 59% of participants being male. Overall surgeries occurred at a median of 83 days (IQR 48-120) after the index TAVI procedure, a time-period which was significantly shorter for those who underwent high-risk surgeries (median 67, IQR 41-109 days, P\u3c 0.001). The overall rate of post-operative MAE was 7.6% (n=181), and these rates did not differ between surgical-risk groups (P=0.46). The primary outcome was driven primarily by cardiac complications (3.6%), while rates of death were low and almost identical between surgical-risk groups (P=0.99). Factors independently associated with the primary outcome were congestive heart failure (aOR: 1.62, CI: 1.23-2.12, P\u3c 0.001), liver disease (aOR: 2.17, CI:1.37-3.45, P=0.001), diabetes mellitus (aOR: 1.44, CI: 1.13-1.82, P=0.003), cancer (aOR: 1.18, CI: 0.92-1.50, P\u3c 0.001), and time to readmission (aOR: 1.00, CI:0.99-1.00, P=0.004).
CONCLUSION: Elective NCS occurred infrequently post TAVI and was associated with low rates of mortality. While diabetes mellitus, congestive heart failure, liver disease, cancer, anemia, and time to readmission were associated with postprocedural adverse events, the surgical risk was not. The risk of NCS after TAVI should be balanced against the risk of delaying an operation
The Tralokinumab Pre-Filled Pen Improved Atopic Dermatitis Signs and Symptoms and Was Well Tolerated in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: A 16-Week, Open-Label, Single-Arm Phase 3 Study (INJECZTRA)
No full textINTRODUCTION: The tralokinumab pre-filled pen was developed to improve patient convenience and deliver 300 mg tralokinumab (the recommended dose for most patients) with one injection. This study evaluated the efficacy, safety, and usability of the tralokinumab pre-filled pen autoinjector in patients with moderate-to-severe atopic dermatitis.
METHODS: This 16-week, open-label, single-arm phase 3 study enrolled patients ≥ 12 years with Investigator\u27s Global Assessment (IGA) score ≥ 3 and Eczema Area and Severity Index (EASI) ≥ 12. Patients received tralokinumab 300 mg via self-administered pre-filled pen every 2 weeks for 16 weeks. The primary endpoints were IGA 0/1 and ≥ 75% improvement in EASI (EASI-75) at week 16. Safety was assessed as the number of adverse events from baseline to week 16.
RESULTS: At week 16, 28.7% (39/136) of patients achieved IGA 0/1 (28.6% [30/105] adults; 29.0% [9/31] adolescents) and 43.4% (59/136) of patients achieved EASI-75 (44.8% [47/105] adults; 38.7% [12/31] adolescents). The tralokinumab pre-filled pen was well tolerated, and the observed safety profile was comparable to the safety profile with the tralokinumab pre-filled syringe.
CONCLUSIONS: Tralokinumab formulated as a pre-filled pen was effective, well tolerated, and easy to use. The tralokinumab pre-filled pen may offer a more convenient method of tralokinumab administration with fewer injections per dose.
TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05194540
Association between UV index and sebaceous carcinoma incidence among various population age groups
No full textIntravenous Versus Oral Iron After Gastrointestinal Bleeding: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
No full textBACKGROUND & OBJECTIVE: Few trials have compared the efficacy of intravenous (IV) iron repletion to oral repletion for patients with gastrointestinal bleeding (GIB). We aim to guide clinical decision-making and optimize treatment strategies through the findings from these studies to provide a step closer to a consensus on the most effective approach to iron supplementation for patients with GIB.
METHODS: A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase, CENTRAL, Scopus, and Web of Science from inception to April 2024. We used the fixed-effects model to report dichotomous outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI). PROSPERO ID: CRD42024542759.
RESULTS: Three RCTs that included 254 patients were included. IV iron was significantly associated with increased complete response (RR: 1.60 with 95% CI [1.24, 2.07], p \u3c 0.01) compared to oral iron, with no significant difference between IV iron and oral iron in partial response (RR: 2.13 with 95% CI [0.60, 7.50], p = 0.24). IV iron was significantly associated with increased Hb concentration (MD: 1.45 g/dL with 95% CI [0.50, 2.40], p \u3c 0.01) and ferritin change (MD: 220.02 μg/L with 95% CI [22.31, 417.73], p = 0.03) compared to oral iron. However, there was no significant difference between IV and oral iron in transferrin saturation (MD: 4.71% with 95% CI [-5.96, 15.38], p = 0.39).
CONCLUSION: With uncertain evidence, IV iron demonstrated increased hemoglobin and ferritin concentrations and achieved complete response rates in patients with GIB
RGI-2001 for the Prophylaxis of Acute Graft-Versus-Host Disease Following Allogeneic HCT
No full textRGI-2001, a liposomal glycolipid that binds CD1d receptor of antigen-presenting cells, can activate invariant natural killer T cells and stimulate cytokine-dependent proliferation of regulatory T-cells (Tregs). This open-label, single-arm, multicenter phase 2b trial evaluated the safety and efficacy of RGI-2001 in combination with standard graft-versus-host disease (GVHD) prophylaxis in participants receiving myeloablative allogeneic hematopoietic cell transplantation (HCT) for hematologic malignancies. RGI-2001 was infused at a dose of 100 ug/kg for six weekly doses starting on Day 0 of HCT. The primary endpoint was grades II-IV acute GVHD by Day 100 after HCT. Forty-nine participants received RGI-2001 in combination with tacrolimus and methotrexate. RGI-2001 was well tolerated, with no serious infusion reactions. Sixteen participants experienced grade ≥3 treatment-related adverse events, with the most common being decreased appetite, leukopenia, thrombocytopenia and stomatitis. The estimated probability of grades II-IV and III-IV acute GVHD were 24.9% and 4.1%, respectively. Compared to controls from the Center for International Blood and Marrow Research Transplant registry, participants receiving RGI-2001 experienced superior clinical outcomes, including Day-180 grades II-IV acute GVHD-free survival (70.8% vs 50.7%, adjusted hazard ratio 0.45, 95% CI 0.30-0.68). Increasing NKT and Treg populations were observed after HCT, consistent with the proposed action of RGI-2001. In conclusion, RGI-2001 was well tolerated and was associated with low rates of acute GVHD and encouraging survival after myeloablative HCT. These results support strategies that target NKT and Treg cell populations to augment immunological changes in allogeneic HCT recipients. This trial was registered at www.clinicaltrials.gov as NCT04014790
Helicobacter pylori real-time quantitative PCR to examine efficacy of endoscope processing
No full textBACKGROUND: Helicobacter pylori (H. pylori) is the main cause of peptic ulcer disease. The primary aim of this research is to determine the effectiveness of current endoscope High-Level Disinfection (HLD) at clearing H. pylori. The secondary aim is to evaluate the prevalence of H. pylori in patients undergoing esophagogastric-duodenoscopy (EGD).
METHODS: This is a prospective study collecting samples from esophagogastroduodenoscopy (EGD) for H. pylori. testing via gastric lavage and after HLD via flushing endoscope with sterile water. The patients\u27 records were reviewed and the fluid obtained was tested for microbiologic culture; urease testing, and qPCR testing using UreA primers and probe.
RESULTS: The study included 202 samples (101 patients). H. pylori was positive in 37%, 21.9% and 2.4% of samples using Urease testing, culture and biopsy respectively. H. pylori was four times more likely to be identified via gastric lavage than by biopsy. qPCR was significantly more likely to be negative after HLD (27 vs 3 patients).
CONCLUSIONS: HLD was effective in reducing H. pylori but was not able to totally eliminate H. pylori DNA. qPCR is more sensitive than routine culture but can\u27t accurately determine potential for infection transmission. Gastric lavage may be more effective in detecting H. pylori than histology