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Background Context Several studies have shown that factors such as insurance type and patient income are associated with different readmission rates following certain orthopaedic procedures. The literature, however, remains sparse with regard to these demographic characteristics and their associations to perioperative lumbar spine fusion outcomes. Purpose The purpose of this study was to assess the associations between hospital type, insurance type, and patient median income to both 30-day complication and readmission rates following lumbar spine fusion. Patient Sample Patients who underwent primary lumbar spine fusion (n = 596,568) from 2010-2016 were queried from the National Readmissions Database (NRD). Outcome Measures Incidence of 30-day complication and readmission rates Methods All relevant diagnoses and procedures were identified using International Classification of Disease, 9th and 10th Edition (ICD-9, 10) codes. Hospital types were categorized as metropolitan non-teaching (n = 212,131), metropolitan teaching (n = 364,752), and rural (n = 19,685). Insurance types included: Medicare (n = 213,534), Medicaid (n = 78,520), private insurance (n = 196,648), and out-of-pocket (n = 45,025). Patient income was divided into the following quartiles: Q1 (n = 112,083), Q2 (n = 145,755), Q3 (n = 156,276), and Q4 (n = 147,289), wherein quartile 1 corresponded to lower income ranges and quartile 4 to higher ranges. Statistical analysis was conducted in R. Kruskal-Wallis tests with Dunn’s pairwise comparisons were performed to analyze differences in 30-day readmission and complication rates in patients who underwent lumbar spine fusion. Complications analyzed included infection, wound injury, hematoma, neurological injury, thromboembolic event, and hardware failure. Results 30-day readmission was significantly higher in metropolitan teaching hospitals compared to metropolitan non-teaching hospitals and rural hospitals ( P < .05). Patients from metropolitan teaching hospitals had significantly higher rates of infection ( P < .001), wound injury ( P < .001), hematoma ( P = .018), and hardware failure ( P < .002) compared to those treated at metropolitan non-teaching hospitals. Privately insured patients were significantly less likely to be readmitted at 30 days than those paying with Medicare or Medicaid ( P < .01). Patients with private insurance also experienced significantly lower rates of hematoma formation than Medicare beneficiaries and out-of-pocket payers ( P < .01), postoperative wound injury compared to Medicaid patients and out-of-pocket payers ( P < .005), and infection compared to all other groups ( P < .001). Patients in Quartile 4 experienced significantly greater rates of hematoma formation compared to those in Quartiles 1 and 2 and were more likely to experience a thromboembolic event compared to all other groups. Conclusion Patients undergoing lumbar spine fusion at metropolitan non-teaching hospitals and paying with private insurance had significantly lower 30-day readmission rates than their counterparts. Complications within 30 days following lumbar spine fusion were significantly higher in patients treated at metropolitan teaching hospitals and in Medicare and Medicaid beneficiaries. Aside from a few exceptions, however, patient income was generally not associated with differential complication rates.

PURPOSE There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer. METHODS We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of leisure-time physical activity with breast cancer incidence. HRs for high versus low levels of activity were based on a comparison of risk at the 90th versus 10th percentiles of activity. We assessed the linearity of the relationship and examined subtype-specific associations and effect modification across strata of breast cancer risk factors, including adiposity. RESULTS Over a median 11.5 years of follow-up (IQR, 8.0-16.1 years), high versus low levels of leisure-time physical activity were associated with a 6% (HR, 0.94 [95% CI, 0.89 to 0.99]) and a 10% (HR, 0.90 [95% CI, 0.85 to 0.95]) reduction in breast cancer risk, before and after adjustment for BMI, respectively. Tests of nonlinearity suggested an approximately linear relationship ( Pnonlinearity = .94). The inverse association was particularly strong for human epidermal growth factor receptor 2–enriched breast cancer (HR, 0.57 [95% CI, 0.39 to 0.84]; Phet = .07). Associations did not vary significantly across strata of breast cancer risk factors, including subgroups of adiposity. CONCLUSION This large, pooled analysis of cohort studies adds to evidence that engagement in higher levels of leisure-time physical activity may lead to reduced premenopausal breast cancer risk.

Background Chimeric antigen receptor (CAR) modified T-cells are leading to a paradigm shift in the treatment of relapsed/refractory (RR) multiple myeloma (MM). A high proportion of patients treated with CAR T-cells, however, experience prolonged cytopenia, with the mechanism remaining poorly understood. Here, we aimed to explore potential biomarkers that might correlate with cytopenia following CAR T-cell therapy in RRMM. Methods We prospectively collected peripheral blood (PB) of RRMM patients treated with idecabtagen-vicleucel (ide-cel) at the following time points: prior to lymphodepleting chemotherapy (LDC) (baseline), after ide-cel on day 4, 7, 14 and 28, and monthly thereafter. Cytopenia was determined according to the CTCAE version 5.0. Flow cytometry was performed with the following markers: CD45, CD3, CD4, CD8, CD62L, CD45RA, CD19, CD14, CD138, CD38 and a BCMA-CAR-detection marker. Results We included 222 PB samples at different sampling time points from 35 RRMM patients, who were pretreated with a median of 5 therapy lines (range 2-10). All patients were triple-class exposed and, 34 (97%) and 9 (26%) patients underwent autologous and allogeneic stem cell transplant (SCT), respectively. First, we analyzed the relationship between baseline parameters and the duration of grade ≥3 cytopenia after ide-cel (n=35). Notably, patients who received allogeneic SCT or &gt;4 lines of therapy did not develop longer lasting cytopenia than the remaining patients. We found a correlation between the baseline hemoglobin level and the duration of grade ≥3 anemia (r=-0.55, P&lt;0.001). Similarly, low baseline platelet count indicated long duration of grade ≥3 thrombocytopenia (r=-0.48, P=0.003). Moreover, high baseline ferritin level correlated with long duration of grade ≥3 anemia (r=0.52, P&lt;0.001) and thrombocytopenia (r=0.51, P=0.002). Furthermore, the maximum ferritin level after ide-cel was an indicator for long lasting grade ≥3 anemia (r=0.73, P&lt;0.001) and thrombocytopenia (r=0.71, P&lt;0.001). Interestingly, we found significant correlations between the duration of grade ≥3 lymphopenia and baseline CD4+ T-cell frequency (r=0.41, P=0.02), CD8+ T-cell frequency (r=-0.38, P=0.04) and CD4+/CD8+ ratio (r=0.4, P=0.03). Noteworthy, patients with β2-microglobulin level &gt;3.5 mg/l displayed longer duration of grade ≥3 anemia (median: 9 vs 0 day, P=0.007) and neutropenia (median: 43 vs 12 days, P=0.02) compared with the remaining patients, suggesting that high tumor load might be a risk factor for prolonged cytopenia after ide-cel. Second, we divided the follow-up PB samples (n=187) into two groups: early (&lt;d60) and prolonged (≥d60) cytopenia to account for direct toxic effects related to LDC. A high ferritin level was associated with low hemoglobin level (&lt;d60: r=-0.45, P&lt;0.001, ≥d60: r=-0.62, P&lt;0.001) and low platelet count (&lt;d60: r=-0.58, P&lt;0.001, ≥d60: r=-0.81, P&lt;0.001) in both groups. In prolonged cytopenia (≥d60), lymphocyte count correlated with the T-cell count (r=0.7, P&lt;0.001), suggesting that prolonged lymphopenia was mainly attributed to the reduced T-cell count after ide-cel. Of note, the frequency of naïve CD4+ T-cells (CD3+CD4+CD62L+CD45RA+) positively correlated with neutrophil count (r=0.58, P&lt;0.001), hemoglobin level (r=0.37, P=0.03) and white blood cell count (r=0.5, P=0.002) in the ≥d60 group, suggesting that delayed immune reconstruction with reduced naïve CD4+ T-cells might contribute to prolonged cytopenia after ide-cel. Moreover, in the ≥d60 group, lymphocyte count was related with the frequency of CAR+CD4+ (r=-0.58, P&lt;0.001), CAR+CD8+ (r=0.58, P&lt;0.001), CAR-CD4+ (r=-0.72, P&lt;0.001), CAR-CD8+ (r=0.75, P&lt;0.001) T-cells, as well as the ratios of CAR+CD8+/CAR+CD4+ (r=-0.6, P&lt;0.001) and CAR-CD8+/CAR-CD4+ (r=-0.75, P&lt;0.001). Conclusion Here, we present one of the first prospective studies investigating the factors associated with prolonged cytopenia after CAR T-cell therapy in RRMM. High tumor load, preexisting cytopenia and high ferritin level are related with prolonged cytopenia after ide-cel. Delayed immune reconstruction, characterized by reduced naïve CD4+ T-cell count, indicates prolonged cytopenia following ide-cel therapy. Patients with high CD4+/CD8+ ratio are at risk of prolonged lymphopenia (with reduced T-cell count), which may be a risk factor for infectious complications and an issue for subsequent T-cell based immunotherapies.

AbstractBackgroundRecent clinical trials have evaluated the efficacy of vonoprazan‐amoxicillin (VA) dual therapy as the first‐line treatment for Helicobacter pylori infection in different regions with inconsistent results reported. In this systematic review and meta‐analysis, we aimed to evaluate the efficacy of VA dual therapy compared to the currently recommended therapy for eradicating H. pylori.Materials and MethodsA comprehensive search of the PubMed, Cochrane, and Embase databases was performed using the following search terms: (“Helicobacter” OR “H. pylori” OR “Hp”) AND (“vonoprazan” OR “potassium‐competitive acid blocker” OR “P‐CAB”) AND (“amoxicillin” OR “penicillin”) AND (“dual”). The primary outcome was to evaluate the eradication rate according to intention‐to‐treat and per‐protocol analysis. The secondary outcomes were adverse events and compliance.ResultsA total of 15 studies involving 4, 568 patients were included. The pooled eradication rate of VA dual therapy was 85.0% and 90.0% by intention‐to‐treat and per‐protocol analysis, respectively. The adverse events rate and compliance of VA dual therapy were 17.5% and 96%, respectively. The efficacy of VA dual therapy was superior to proton pump inhibitors‐based triple therapy (82.0% vs. 71.4%, p < 0.01) but lower than vonoprazan‐containing quadruple therapy (83.1% vs. 93.3%, p = 0.02). 7‐day VA dual therapy showed lower eradication rates than 10‐day (χ2 = 24.09, p < 0.01) and 14‐day VA dual therapy (χ2 = 11.87, p < 0.01). The adverse events rate of VA dual therapy was lower than vonoprazan triple therapy (24.6% vs. 30.9%, p = 0.01) and bismuth‐containing quadruple therapy (20.5% vs. 47.9%, p < 0.01). No significant difference of compliance was observed between VA dual therapy and each subgroup.ConclusionVA dual therapy, a novel regimen, showed high efficacy as the first‐line treatment for H. pylori eradication, which should be optimized before application in different regions.

The scarcity of liver grafts has prompted developments in living donor liver transplantations (LDLT), with previous literature illustrating similar outcomes in recipients compared to deceased donor transplants. However, significant concerns regarding living donor morbidity and mortality have yet to be examined comprehensively. This study aims to provide estimates of the incidence of various outcomes in living liver donors. In this meta-analysis, Medline and Embase were searched from inception to July 2022 for articles assessing the incidence of outcomes in LDLT donors. Complications in the included studies were classified into respective organ systems. Analysis of incidence was conducted using a generalized linear mixed model with Clopper-Pearson intervals. Eighty-seven articles involving 60,829 living liver donors were included. The overall pooled incidence of complications in LDLT donors was 24.7% (CI: 21.6%–28.1%). The incidence of minor complications was 17.3% (CI: 14.7%–20.3%), while the incidence of major complications was lower at 5.5% (CI: 4.5%–6.7%). The overall incidence of donor mortality was 0.06% (CI: 0.0%–0.1%) in 49,027 individuals. Psychological complications (7.6%, CI: 4.9%–11.5%) were the most common among LDLT donors, followed by wound-related (5.2%, CI: 4.4%–6.2%) and respiratory complications (4.9%, CI: 3.8%–6.3%). Conversely, cardiovascular complications had the lowest incidence among the subgroups at 0.8% (CI: 0.4%–1.3%). This study presents the incidence of post-LDLT outcomes in living liver donors, illustrating significant psychological, wound-related, and respiratory complications. While significant advancements in recent decades have contributed towards decreased morbidity in living donors, our findings call for targeted measures and continued efforts to ensure the safety and quality of life of liver donors post-LDLT.

Abstract Background/Introduction Hypertension (HTN) and metabolic syndrome (MetS) are both leading risk factors for major cardiovascular diseases, which frequently coexist as a complicated cardiometabolic disorder. The cardiac hormone atrial natriuretic peptide (ANP) plays a key role in both blood pressure and metabolic regulation through activation of the guanylyl cyclase-A receptor (GC-A) and the second messenger 3’,5’ cyclic guanosine monophosphate (cGMP). Indeed, ANP decreases blood pressure, induces lipolysis by increasing plasma levels of non-esterified fatty acids (NEFA) and improves insulin-sensitivity. MANP is a new Mayo Clinic designed natriuretic peptide consisting of the native ANP with a 12-amino-acid C-terminus extension and its biological actions are mediated by the GC-A/cGMP pathway. MANP is less susceptible to neprilysin degradation and exert more sustained cGMP dependent biological actions than ANP. Purpose In a proof-of-principle human study, for the first time we aimed to determine the cardiovascular and metabolic properties of MANP, a novel ANP analog, in the clinical setting of HTN with MetS. Methods We conducted a double-blind, placebo-controlled trial in 22 patients (17 receiving MANP) with HTN and MetS involving single subcutaneous injection of MANP (2.5 µg/kg) or placebo (NCT03781739). Blood pressure (BP) and circulating cGMP were monitored for 24 hours post treatment. Circulating metabolic parameters including insulin, glucose, non-esterified fatty acids (NEFA) and insulin resistance (HOMA-IR) and insulin sensitivity (HOMA-IS) indexes were assessed for the first 4 hours post treatment. Results Compared to baseline, MANP increased plasma cGMP at 30 minutes (delta: 4.8 ± 2.0 pmol/mL, P = 0.02) and 1 hour (delta: 2.9 ± 1.3 pmol/mL, P = 0.03) post injection. At 6 hours, systolic BP decreased by 5.7 ± 2.9 mmHg (P = 0.06) in the MANP group, whereas no reduction in BP was observed in placebo group. Among the 17 subjects receiving MANP, lower baseline cGMP levels were associated with greater mean reductions in systolic BP (ρ = 0.66, P = 0.005). After MANP injection, glucose levels decreased at 2 (delta: -4.7 ± 2.1 mg/mL, P = 0.04) and 4 hours (delta: -13.1 ± 3.9 mg/mL, P = 0.003) compared to baseline while insulin levels remained stable. During the first 4 hours post injection, we also observed a trend of increase in insulin sensitivity index (HOMA2-IS) and decrease in insulin resistance index (HOMA2-IR) with MANP, both were opposite to the trends in placebo. At 1 hour post MANP administration, NEFA increased by 108.2 ± 37.4 µM compared to baseline (P = 0.01). Conclusion(s) Our findings support the favorable cardiovascular and metabolic actions of MANP as a potential therapeutic strategy for HTN with MetS.