Citations

AbstractIntroductionAtrioventricular nodal reentrant tachycardia (AVNRT) is the most common supraventricular tachycardia referred for ablation. Periprocedural conduction system damage was a primary concern during AVNRT ablation. This study aimed to assess the incidence of permanent atrioventricular (AV) block and the success rate associated with different types of catheters in slow pathway ablation.MethodA literature search was performed to identify studies that compared various techniques, including types of radiofrequency ablation (irrigated and nonirrigated) and different sizes of catheter tip cryoablation (4, 6, and 8‐mm), in terms of their outcomes related to permanent atrioventricular block and success rate. To assess and rank the treatments for the different outcomes, a random‐effects model of network meta‐analysis, along with p‐scores, was employed.ResultsA total of 27 studies with 5110 patients were included in the analysis. Overall success rates ranged from 89.78% to 100%. Point estimation showed 4‐mm cryoablation exhibited an odds ratio of 0.649 (95%CI: 0.202–2.087) when compared to nonirrigated RFA. Similarly, 6‐mm cryoablation had an odds ratio of 0.944 (95%CI: 0.307–2.905), 8‐mm cryoablation had an odds ratio of 0.848 (95%CI: 0.089–8.107), and irrigated RFA had an odds ratio of 0.424 (95%CI: 0.058–3.121) compared to nonirrigated RFA.ConclusionOur study found no significant difference in the incidence of permanent AV block between the types of catheters. The success rates were consistently high across all groups. These findings emphasize the potential of both RF ablation (irrigated and nonirrigated catheter) and cryoablation as viable options for the treatment of AVNRT, with similar safety and efficacy profile.

Background: Multiligamentous knee injuries (MLKIs) are devastating injuries with concomitant injuries that complicate treatment and recovery. Short-term studies have shown satisfactory patient outcomes after surgical treatment; however, evaluations of long-term outcomes remain scarce. Purpose: To evaluate long-term outcomes after surgically reconstructed MLKIs and further investigate the relationship between patient age on clinical outcomes. Study Design: Case series; Level of evidence, 4. Methods: A total of 55 knees (age, 36 ± 11 years; 24% female subjects) who underwent surgical reconstruction for MLKI between 1992 and 2013 met the study inclusion criteria and were evaluated with postoperative patient-reported outcomes (PROs) including International Knee Documentation Committee (IKDC) score, Lysholm score, visual analog scale (VAS) for pain, Forgotten Joint Score, subjective improvement ratings and surgery satisfaction, and Tegner activity scores. PRO scores, revision, and conversion to arthroplasty were analyzed using descriptive statistics, linear regression, Wilcoxon rank-sum, and Fisher exact tests. Results: At final follow-up (mean, 15 ± 5 years; range, 10-31 years), 67% of the cohort reported subjective improvement in their knee, and 82% reported satisfaction with their surgery. Compared with preoperative scores, there were significant improvements in postoperative VAS pain at rest in the full cohort, age ≤30-year cohort, and age >30-year cohort (4 ± 1 vs 2 ± 2; 4 ± 1 vs 2 ± 3; 4 ± 1 vs 1 ± 2, respectively; P≤ .029 for all) but significant reductions in Tegner scores (6 ± 3 vs 4 ± 2; 7 ± 2 vs 5 ± 2; 5 ± 2 vs 3 ± 1; P≤ .003 for all). Younger patients had higher postoperative Tegner scores than older patients (5 ± 2 vs 3 ± 1, respectively; P = .003), but no other differences in PROs were observed based on age. At a mean 15-year follow-up, 3.6% of the cohort underwent revision ligament surgery and 10.9% required arthroplasty. Conclusion: The majority of the cohort reported modest subjective improvement and were satisfied with their surgery. Gradual but expected age-related decreases in Tegner scores were observed, and some patients demonstrated continued symptomatic and functional limitations, but mean PRO scores remained satisfactory. Revision surgery and conversion to arthroplasty were not commonly required.

Liver transplantation (LT) is a highly effective treatment for carefully selected patients with hepatocellular carcinoma (HCC). In this review, we explored the development of LT selection criteria and organ allocation policies, comparing original data to underscore their historical progression into the intricate task of quantitatively estimating pre- and post-LT survivals. We emphasized the role of biomarkers such as serum alpha-fetoprotein, Des-gamma-carboxy-prothrombin, circulating tumor cells, and circulating tumor DNA in predicting patient outcomes. Additionally, we examined the transplant-associated survival benefits and the difficulties in accurately calculating these benefits. We also reviewed recent advancements in targeted therapy and checkpoint inhibitors for advanced, inoperable HCC and projected their integration into LT for HCC. We further discussed the growing use of living donor liver transplants in the United States and compared its outcomes with those of deceased donor liver transplants. Furthermore, we examined the progress in machine perfusion techniques, which have shown potential in improving patient outcomes and enlarging the donor pool. These advancements present opportunities to enhance LT patient survivals, refine selection criteria, establish new priority metrics, develop innovative bridging and downstaging strategies, and formulate redesigned LT strategies for HCC treatments.

AbstractThalassemias are a group of inherited monogenic disorders characterized by defects in the synthesis of one or more of the globin chain subunits of the hemoglobin tetramer. Delta‐beta (δβ‐) thalassemia has large deletions in the β globin gene cluster involving δ‐ and β‐globin genes, leading to absent or reduced synthesis of both δ‐ and β‐globin chains. Here, we used direct globin‐chain analysis using tandem mass spectrometry for the diagnosis of δβ‐thalassemia. Two cases from unrelated families were recruited for the study based on clinical and hematological evaluation. Peptides obtained after trypsin digestion of proteins extracted from red blood cell pellets from two affected individuals and their parents were analyzed using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Mass spectrometric analysis revealed a severe reduction in δ, β, and Aγ globin proteins with increased Gγ globin protein in the affected individuals. The diagnosis of Gγ(Aγδβ)0 ‐thalassemia in the homozygous state in the affected individuals and in the heterozygous state in the parents was made from our results. The diagnosis was confirmed at the genetic level using multiplex ligation‐dependent probe amplification (MLPA). Our findings demonstrate the utility of direct globin protein quantitation using LC‐MS/MS to quantify individual globin proteins reflecting changes in globin production. This approach can be utilized for accurate and timely diagnosis of hemoglobinopathies, including rare variants, where existing diagnostic methods provide inconclusive results.

Background The C-C motif chemokine receptor 5 (CCR5)/C-C motif chemokine ligand 5 (CCL5) axis plays a major role in colorectal cancer (CRC). We aimed to characterize the molecular features associated with CCR5 / CCL5 expression in CRC and to determine whether CCR5 / CCL5 levels could impact treatment outcomes. Methods 7604 CRCs tested with NextGen Sequencing on DNA and RNA were analyzed. Molecular features were evaluated according to CCR5 and CCL5 tumor gene expression quartiles. The impact on treatment outcomes was assessed in two cohorts, including 6341 real-world patients and 429 patients from the Cancer and Leukemia Group B (CALGB)/SWOG 80405 trial. Results CCR5 / CCL5 expression was higher in right-sided versus left-sided tumors, and positively associated with consensus molecular subtypes 1 and 4. Higher CCR5 / CCL5 expression was associated with higher tumor mutational burden, deficiency in mismatch repair and programmed cell death ligand 1 (PD-L1) levels. Additionally, high CCR5 / CCL5 were associated with higher immune cell infiltration in the tumor microenvironment (TME) of MMR proficient tumors. Ingenuity pathway analysis revealed upregulation of the programmed cell death protein 1 (PD-1)/PD-L1 cancer immunotherapy pathway, phosphatase and tensin homolog (PTEN) and peroxisome proliferator-activated receptors (PPAR) signaling, and cytotoxic T-lymphocyte antigen 4 (CTLA-4) signaling in cytotoxic T lymphocytes, whereas several inflammation-related pathways were downregulated. Low CCR5 / CCL5 expression was associated with increased benefit from cetuximab-FOLFOX treatment in the CALGB/SWOG 80405 trial, where significant treatment interaction was observed with biologic agents and chemotherapy backbone. Conclusions Our data show a strong association between CCR5/CCL5 gene expression and distinct molecular features, gene expression profiles, TME cell infiltration, and treatment benefit in CRC. Targeting the CCR5/CCL5 axis may have clinical applications in selected CRC subgroups and may play a key role in developing and deploying strategies to modulate the immune TME for CRC treatment.

Background Distal medium vessel occlusions (DMVOs) and minor strokes represent emerging frontiers in mechanical thrombectomy (MT). Although several randomized clinical trials (RCTs) are underway, the design characteristics of these trials and the specific questions they aim to address have not been extensively explored. This current study sought to investigate the design and data elements reported in active prospective DMVO and minor stroke studies. Methods The ClinicalTrials.gov database was searched for ongoing prospective studies assessing the role of MT in patients with DMVOs or minor strokes. The Nested Knowledge AutoLit platform was utilized to categorize reported outcomes and inclusion/exclusion criteria. Frequencies of reported data elements were extracted from study protocols. Results A total of 10 (8 DMVO and 2 minor stroke) studies enrolling 3520 patients were included. All DMVO studies employ different criteria regarding target occlusion locations. Five DMVO studies use stent retrievers as the first-line thrombectomy technique (62.5%, 5/8), while three studies allow any MT techniques, generally at the operator’s discretion. Four DMVO studies permit intravenous thrombolysis (IVT) utilization in both intervention and control arms (50%, 4/8). The DISTALS trial excludes patients receiving IVT, while the DUSK trial and Tigertriever registry only enroll patients who are ineligible for IVT or for whom IVT failed to achieve reperfusion. DMVO studies exhibit notable heterogeneity in symptom onset duration thresholds for inclusion (<6 hours: 2 studies; <12 hours: 2 studies; <24 hours: 3 studies). Minor stroke trials employ similar inclusion criteria and outcome measures except for symptom duration thresholds for inclusion (8 hours for ENDOLOW and 23 hours for MOSTE). Conclusions There is considerable heterogeneity among active DMVO trials regarding potential target DMVO locations and time thresholds for inclusion based on the last known well time. Furthermore, our review indicates that the utility of aspiration thrombectomy in DMVOs and the advantages of MT without IVT over IVT alone will remain largely unexplored even after completion of active DMVO trials.

Radiation therapy (RT) is an essential part of the multidisciplinary treatment of pediatric cancer. Over the past five decades, significant advances have been made in the delivery of RT, with better dose delivery to disease targets while minimizing exposure to nearby organs at risk. These advances have led to improved treatment outcomes, increased survival, and reduced treatment-related toxicities. Advanced treatment techniques, however, require significant investment in infrastructural and personnel resources. This review documents what is currently available regarding expertise and infrastructure for pediatric radiation oncology practice in Nigeria. It was performed to serve as a foundation for the creation and design of tailored solutions (initiatives and policies) to increase pediatric radiation availability, accessibility, and equity in Nigeria and ultimately improve pediatric cancer treatment outcomes in the region.

A commentary on Canterino et al. (2024) and Munsiff et al. (2024), articles where clinicians from two large OPAT programs

The application of cryotherapy in the extraction of airway blood clots has gained increased precedence over Fogarty catheter and biopsy forceps. The cryoprobe, passed through a flexible bronchoscope, adheres and aids in the removal of foreign body through cryoadhesion within minutes. Besides blood clots, this method was found to be extremely efficient in removing different kinds of foreign bodies including food particles like peanuts, pills, and inspissated mucus.

Recent therapeutic advances have significantly improved the outcome for patients with multiple myeloma (MM). The backbone of successful standard therapy is the combination of Ikaros degraders, glucocorticoids, and proteasome inhibitors that interfere with the integrity of myeloma-specific superenhancers by directly or indirectly targeting enhancer-bound transcription factors and coactivators that control expression of MM dependency genes. T cell engagers and chimeric antigen receptor T cells redirect patients’ own T cells onto defined tumor antigens to kill MM cells. They have induced complete remissions even in end-stage patients. Unfortunately, responses to both conventional therapy and immunotherapy are not durable, and tumor heterogeneity, antigen loss, and lack of T cell fitness lead to therapy resistance and relapse. Novel approaches are under development to target myeloma-specific vulnerabilities, as is the design of multimodality immunological approaches, including and beyond T cells, that simultaneously recognize multiple epitopes to prevent antigen escape and tumor relapse.