Citations

Abstract Atrial fibrillation (AF) may be associated with chest wall abnormalities such as pectus excavatum (PE). Pulmonary vein isolation (PVI) has proven to be a useful strategy for radiofrequency catheter ablation (RFCA) of AF. However, the presence of chest wall abnormalities, such as pectus excavatum, imposes certain challenges during ablation due to the anatomic distortion that it causes. We highlight these challenges during ablation in this three‐patient case series.

Abstract In this retrospective study, BRAF mutation status did not correlate with disease extent or (event-free) survival in 156 adults with Langerhans cell histiocytosis. BRAFV600E was associated with an increased incidence of second malignancies, often comprising hematological cancers, which may be clonally related.

PURPOSE We conducted a systematic review to evaluate the outcome of patients with early-stage (stages I-III) mismatch repair deficient (dMMR) colorectal cancer (CRC) receiving neoadjuvant immunotherapy (NIT) with immune checkpoint inhibitor (ICI)–based regimens. METHODS MEDLINE, Scopus, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were searched for publications reporting the outcome of patients with early-stage dMMR CRC receiving NIT. The primary outcome measures were the complete response (CR) rate (clinical CR [cCR] or pathologic CR [pCR]) and the incidence of grade 3 or higher toxicities. RESULTS The search identified 37 publications that included 423 patients with colon (n = 326, 77%) and rectal (n = 97,23%) cancers aged 19-82 years; most patients had stage III CRC (88%). Approximately 67% of patients received monotherapy with anti–PD-1 agents; the rest received dual ICIs (ipilimumab plus nivolumab). The CR rate (pCR + cCR) in the overall population was 72% (305 of 423). The R0 resection and pCR rates were 99.3% and 70% among the patients undergoing surgery, respectively. Only four (0.9%) patients had primary resistance to NIT. After median follow-up periods ranging from 4 to 27 months, 3 (0.7%) patients progressed after an initial response. Grade 3 or higher toxicities were uncommon (6.3%), rarely delaying planned surgery. CONCLUSION NIT in patients with early-stage dMMR CRC is associated with a high response rate, low primary resistance to immunotherapy and cancer recurrence rate, and an excellent safety profile. The findings of the present systematic review support further investigation of NIT in patients with early-stage dMMR CRC, with a particular emphasis on the organ-preserving potential of this strategy.

Abstract Background Atrial fibrillation (AF) is common in hypertrophic cardiomyopathy (HCM). There is limited data regarding the outcomes of AF catheter ablation in HCM patients. In this study, we aimed to synthesize all available evidence on the effectiveness of ablation of AF in patients with HCM compared to those without HCM. Methods and results We systematically reviewed bibliographic databases to identify studies published through February 2023. We included cohort studies with available quantitative information on rates of recurrent atrial arrhythmias, anti-arrhythmic drug (AAD) therapy, and repeat ablation procedures after initial AF ablation in patients with vs without HCM. Estimates were combined using random-effects meta-analysis models and reported as risk ratios (RR) and 95% confidence intervals (CI). Eight studies were included in quantitative synthesis (262 HCM and 642 non-HCM patients). During median follow-up 13–54 months across studies, AF recurrence rates ranged from 13.3% to 92.9% in HCM and 7.6% to 58.8% in non-HCM patients. The pooled RR for recurrent atrial arrhythmia after the first AF ablation in HCM patients compared to non-HCM controls was 1.498 (95% CI = 1.305–1.720; P < 0.001). During follow-up, HCM patients more often required AAD therapy (RR = 2.844; 95% CI = 1.713–4.856; P < 0.001) and repeat AF ablation (RR = 1.544; 95% CI = 1.070–2.228; P = 0.02). The pooled RR for recurrent atrial arrhythmias after the last AF ablation was higher in patients with HCM than those without HCM (RR = 1.607; 95% CI = 1.235–2.090; P < 0.001). Conclusions Compared to non-HCM patients, those with HCM had higher rates of recurrent atrial arrhythmias, AAD use, and need for repeat AF ablation after initial ablation of AF.

AbstractBackgroundPneumocystis pneumonia (PCP) is a growing concern as the immunocompromised population expands. Current laboratory approaches are limited. This systematic review aimed to evaluate metagenomic next-generation sequencing (MNGS) tests’ performance in detecting PCP.MethodsFive databases were searched through December 19, 2022, to identify original studies comparing MNGS with clinically diagnosed PCP. To assess the accuracy, symmetric hierarchical summary receiver operating characteristic models were used.ResultsEleven observational studies reporting 1442 patients (424 with PCP) were included. Six studies focused exclusively on recipients of biologic immunosuppression (none with HIV-associated immunosuppression). Six were exclusively on bronchoalveolar lavage, while 1 was on blood samples. The sensitivity of MGNS was 0.96 (95% CI, 0.90–0.99), and specificity was 0.96 (95% CI, 0.92–0.98), with negative and positive likelihood ratios of 0.02 (95% CI, 0.01–0.05) and 19.31 (95% CI, 10.26–36.36), respectively. A subgroup analysis of studies exclusively including bronchoalveolar lavage (BAL) and blood samples demonstrated a sensitivity of 0.94 (95% CI, 0.78–0.99) and 0.93 (95% CI, 0.80–0.98) and a specificity of 0.96 (95% CI, 0.88–0.99) and 0.98 (95% CI, 0.76–1.00), respectively. The sensitivity analysis on recipients of biologic immunosuppression showed a sensitivity and specificity of 0.96 (95% CI, 0.90–0.98) and 0.94 (95% CI, 0.84–0.98), respectively. The overall confidence in the estimates was low.ConclusionsDespite the low certainty of evidence, MNGS detects PCP with high sensitivity and specificity. This also applies to recipients of biologic immunosuppression and tests performed exclusively on blood samples without the need for BAL. Further studies are required in individuals with HIV-associated immunosuppression.

Abstract In a prospective study with records of heart failure (HF) incidence, we present metabolite profiling data from individuals without HF at baseline. We uncovered the interconnectivity of metabolites using data-driven and causal networks augmented with polygenic factors. Exploring the networks, we identified metabolite broadcasters, receivers, mediators, and subnetworks corresponding to functional classes of metabolites, and provided insights into the link between metabolomic architecture and regulation in health. We incorporated the network structure into the identification of metabolites associated with HF to control the effect of confounding metabolites. We identified metabolites associated with higher or lower risk of HF incidence, the associations that were not confounded by the other metabolites, such as glycine, ureidopropionic and glycocholic acids, and LPC 18:2. We revealed the underlying relationships of the findings. For example, asparagine directly influenced glycine, and both were inversely associated with HF. These two metabolites were influenced by polygenic factors and only essential amino acids which are not synthesized in the human body and come directly from the diet. Metabolites may play a critical role in linking genetic background and lifestyle factors to HF progression. Revealing the underlying connectivity of metabolites associated with HF strengthens the findings and facilitates a mechanistic understanding of HF progression.

Abstract Background Pharmacogenomics is an emerging and affordable tool that may improve postoperative pain control. One challenge to successful pain control is the large interindividual variability among analgesics in their efficacy and adverse drug events. Whether preoperative pharmacogenomic testing is worthwhile for patients undergoing TKA is unclear. Questions/purposes (1) Are the results of preoperative pharmacogenetic testing associated with lower postoperative pain scores as measured by the Overall Benefit of Analgesic Score (OBAS)? (2) Do the results of preoperative pharmacogenomic testing lead to less total opioids given? (3) Do the results of preoperative pharmacogenomic testing lead to changes in opioid prescribing patterns? Methods Participants of this randomized trial were enrolled from September 2018 through December 2021 if they were aged 18 to 80 years and were undergoing primary TKA under general anesthesia. Patients were excluded if they had chronic kidney disease, a history of chronic pain or narcotic use before surgery, or if they were undergoing robotic surgery. Preoperatively, patients completed pharmacogenomic testing (RightMed, OneOME) and a questionnaire and were randomly assigned to the experimental group or control group. Of 99 patients screened, 23 were excluded, one before randomization; 11 allocated patients in each group did not receive their allocated interventions for reasons such as surgery canceled, patients ultimately undergoing spinal anesthesia, and change in surgery plan. Another four patients in each group were excluded from the analysis because they were missing an OBAS report. This left 30 patients for analysis in the control group and 38 patients in the experimental group. The control and experimental groups were similar in age, gender, and race. Pharmacogenomic test results for patients in the experimental group were reviewed before surgery by a pharmacist, who recommended perioperative medications to the clinical team. A pharmacist also assessed for clinically relevant drug-gene interactions and recommended drug and dose selection according to guidelines from the Clinical Pharmacogenomics Implementation Consortium for each patient enrolled in the study. Patients were unaware of their pharmacogenomic results. Pharmacogenomic test results for patients in the control group were not reviewed before surgery; instead, standard perioperative medications were administered in adherence to our institutional care pathways. The OBAS (maximum 28 points) was the primary outcome measure, recorded 24 hours postoperatively. A two-sample t-test was used to compare the mean OBAS between groups. Secondary measures were the mean 24-hour pain score, total morphine milligram equivalent, and frequency of opioid use. Postoperatively, patients were assessed for pain with a VAS (range 0 to 10). Opioid use was recorded preoperatively, intraoperatively, in the postanesthesia care unit, and 24 hours after discharge from the postanesthesia care unit. Changes in perioperative opioid use based on pharmacogenomic testing were recorded, as were changes in prescription patterns for postoperative pain control. Preoperative characteristics were also compared between patients with and without various phenotypes ascertained from pharmacogenomic test results. Results The mean OBAS did not differ between groups (mean ± SD 4.7 ± 3.7 in the control group versus 4.2 ± 2.8 in the experimental group, mean difference 0.5 [95% CI -1.1 to 2.1]; p = 0.55). Total opioids given did not differ between groups or at any single perioperative timepoint (preoperative, intraoperative, or postoperative). We found no difference in opioid prescribing pattern. After adjusting for multiple comparisons, no difference was observed between the treatment and control groups in tramadol use (41% versus 71%, proportion difference 0.29 [95% CI 0.05 to 0.53]; nominal p = 0.02; adjusted p > 0.99). Conclusion Routine use of pharmacogenomic testing for patients undergoing TKA did not lead to better pain control or decreased opioid consumption. Future studies might focus on at-risk populations, such as patients with chronic pain or those undergoing complex, painful surgical procedures, to test whether pharmacogenomic results might be beneficial in certain circumstances. Level of Evidence Level I, therapeutic study.

Context.— The pathologic diagnosis of pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is challenging. Objective.— To evaluate the diagnostic usefulness and limitations of current diagnostic strategies for pulmonary MALT lymphoma. Design.— A retrospective review of 120 cases of pulmonary MALT lymphoma from 2014 through 2021 was performed. Results.— Clinicoradiologic presentations overlapped with previous observations in patients with MALT lymphoma, such as a wide age range, female predominance, frequent association with autoimmune disease or immunodeficiency, and broad imaging findings. The histopathologic diagnosis was based on a combination of morphology, immunohistochemistry, and demonstration of B-cell lineage clonality. Two-thirds (76 of 113) of MALT lymphomas had lymphoplasmacytoid cytomorphology. Occasionally, MALT lymphomas were associated with granulomas/giant cells (29%, 35 of 120) or immunoglobulin deposition disease (21%, 25 of 120), including light chain/heavy chain deposition disease, amyloidosis, and/or crystal storing histiocytosis. While CD5, CD10, Bcl-2, and Bcl-6 rarely revealed aberrancies, aberrant CD43 expression either on B-cells or on plasma cells was detected in 42% (27 of 64) of cases, including cases for which proof of clonality could not be obtained. κ/λ in situ hybridization was particularly useful for tumors with lymphoplasmacytoid morphology but performed poorly in lymphomas having no plasmacytic differentiation. κ/λ immunohistochemistry showed no additional usefulness when applied together with κ/λ in situ hybridization. Immunoglobulin gene rearrangement studies by polymerase chain reaction achieved high detection rates of clonality in all cytomorphologic subgroups. Conclusions.— Our study offers a practical evaluation of common diagnostic tests in pulmonary MALT lymphoma. We offer recommendations for a diagnostic workup that takes into consideration the usefulness and the specific limitations of the various diagnostic strategies.

Background: Patients with fungal pneumonias sometimes progress to acute respiratory distress syndrome (ARDS). Mortality has been reported as high as 60% to 90% in this group. Venovenous extracorporeal membrane oxygenation (VV-ECMO) can be used to support such patients, however, outcomes are not well understood. Patients and Methods: This was a retrospective study across the four adult ECMO centers in Minnesota for one decade (2012–2022). The outcomes of interest were duration of ECMO, survival rate, and complications. Data were extracted from the electronic medical record and analyzed using descriptive statistics. Results: Fungal pneumonia was the etiology of ARDS in 22 of 422 (5%) adults supported with VV-ECMO during the 10-year study period. Median patient age was 43 years (interquartile range [IQR], 35–56) and 68% were male. By type of fungal infection, 16 (72%) had blastomycosis, five (22%) had pneumocystis, and one (5%) had cryptococcus. Of the 16 patients with blastomycosis two were immunosuppressed whereas all five of the pneumocystis patients were immunosuppressed. The overall survival rate was 73%; most patients with blastomycosis (67%) and pneumocystis (80%) survived to hospital discharge. The duration of ECMO support was greater for the pneumocystis group (median, 30 days; IQR, 21–43) compared with blastomycosis (median, 10 days; IQR, 8–18). Conclusions: Our findings support the use of VV-ECMO for ARDS caused by fungal pneumonias in select immunocompetent and immunocompromised patients. Although survival was high, patients with pneumocystis required longer ECMO runs.