Rechallenge With High-Dose Methotrexate After Treatment With Glucarpidase in Adult Patients With Lymphoma.

PURPOSE: Limited evidence exists regarding methotrexate (MTX) resumption after patients with lymphoma receive glucarpidase for toxic MTX levels and acute kidney injury (AKI). METHODS: This retrospective review included adults with lymphoma treated with glucarpidase after MTX at Mayo Clinic between January 31, 2020, and October 10, 2022. Descriptive statistics summarize patient characteristics and clinical outcomes. RESULTS: Of 11 patients treated with glucarpidase after MTX, seven (64%) were rechallenged with MTX. Indications for MTX rechallenge included confirmed CNS disease (n = 6, 86%) and intravascular lymphoma (n = 1, 14%). Compared with the nonrechallenged subgroup, before receiving MTX that required glucarpidase rescue, the rechallenged patients had lower median pretreatment serum creatinine (Scr; 0.7 v 1.2 mg/dL), and none had AKI with previous MTX doses, n = 0 (0%) versus n = 2 (50%). During the MTX dose requiring glucarpidase rescue, the rechallenged group had lower median peak Scr (1.26 v 3.32 mg/dL) and lower incidence of AKI stage III (n = 1 [14%] v n = 3 [75%]), and none of the rechallenged patients required renal replacement therapy (RRT; n = 0 [0%] v n = 1 [25%]). At the first rechallenge after glucarpidase administration, the median MTX dose reduction was 56% (range, 46%-75%), and the lowest used dose when prescribed according to each treatment protocol schedule was 1.5 g/m2. Two (29%) patients experienced AKI (n = 1 stage I, n = 1 stage II) after MTX rechallenge. Zero patients required RRT, and zero required another glucarpidase administration. Six (86%) patients completed all recommended MTX doses. CONCLUSION: In selected adults with lymphoma who required glucarpidase for toxic MTX levels after administration of high-dose MTX, resumption of MTX therapy at lower doses is safe. Patients selected for MTX resumption had experienced less severe AKI during the previous cycle compared with those not selected for MTX resumption.

Development and validation of a model to predict acute kidney injury following high-dose methotrexate in patients with lymphoma.

STUDY OBJECTIVE: To develop and validate a model for predicting acute kidney injury (AKI) after high-dose methotrexate (HDMTX) exposure. DESIGN: Retrospective analysis. SETTING: Multisite integrated health system throughout Minnesota and Wisconsin. PATIENTS: Adult patients with lymphoma who received HDMTX as a 4-h infusion. MEASUREMENTS AND MAIN RESULTS: LASSO methodology was used to identify factors available at the outset of therapy that predicted incident AKI within 7 days following HDMTX. The model was then validated in an independent cohort. The incidence of AKI within 7 days following HDMTX was 21.6% (95% confidence interval (CI) 18.4%-24.8%) in the derivation cohort (435 unique patients who received a total of 1642 doses of HDMTX) and 15.6% (95% CI 5.3%-24.8%) in the validation cohort (55 unique patients who received a total of 247 doses of HDMTX). Factors significantly associated with AKI after HDMTX in the multivariable model included age ≥ 55 years, male sex, and lower HDMTX dose number. Other factors that were not found to be significantly associated with AKI on multivariable analysis, but were included in the final model, were body surface area, Charlson Comorbidity Index, and estimated glomerular filtration rate. The c-statistic of the model was 0.72 (95% CI 0.69-0.75) in the derivation cohort and 0.72 (95% CI 0.60-0.84) in the validation cohort. CONCLUSION: This model utilizing identified sociodemographic and clinical factors is predictive of AKI following HDMTX administration in adult patients with lymphoma.

Area Deprivation Index is not predictive of worse outcomes after open lower extremity revascularization.

OBJECTIVE: Prior research has shown that socioeconomic status (SES) is associated with higher rates of diabetes, peripheral vascular disease, and amputation. We sought to determine whether SES or insurance type increases the risk of mortality, major adverse limb events (MALE), or hospital length of stay (LOS) after open lower extremity revascularization. METHODS: We conducted a retrospective analysis of patients who underwent open lower extremity revascularization at a single tertiary care center from January 2011 to March 2017 (n = 542). SES was determined using state Area Deprivation Index (ADI), a validated metric determined by income, education, employment, and housing quality by census block group. Patients undergoing amputation in this same time period (n = 243) were included to compare rates of revascularization to amputation by ADI and insurance status. For patients undergoing revascularization or amputation procedures on both limbs, each limb was treated individually for this analysis. We performed a multivariate analysis of the association between ADI and insurance type with mortality, MALE, and LOS using Cox proportional hazard models, including confounding variables such as age, gender, smoking status, body mass index, hyperlipidemia, hypertension, and diabetes. The cohort with an ADI quintile of 1, meaning least deprived, and the Medicare cohort were used for reference. P values of <.05 were considered statistically significant. RESULTS: We included 246 patients undergoing open lower extremity revascularization and 168 patients undergoing amputation. Controlling for age, gender, smoking status, body mass index, hyperlipidemia, hypertension, and diabetes, ADI was not an independent predictor of mortality (P = .838), MALE (P = .094), or hospital LOS (P = .912). Controlling for the same confounders, uninsured status was independently predictive of mortality (P = .033), but not MALE (P = .088) or hospital LOS (P = .125). There was no difference in the distribution of revascularizations or amputations by ADI (P = .628), but there was higher proportion of uninsured patients undergoing amputation compared with revascularization (P < .001). CONCLUSIONS: This study suggests that ADI is not associated with an increased risk of mortality or MALE in patients undergoing open lower extremity revascularization, but that uninsured patients are at higher risk of mortality after revascularization. These findings indicate that individuals undergoing open lower extremity revascularization at this single tertiary care teaching hospital received similar care, regardless of their ADI. Further study is warranted to understand the specific barriers that uninsured patients face.

Recurrent upper extremity arterial thrombosis preceding a diagnosis of COVID-19.

Arterial thrombosis occurs when there is endothelial damage in the setting of hypercoagulability and arterial blood stasis. COVID-19 has been theorized to cause both endothelial damage and promote hypercoagulability by causing an imbalance of clotting factors. In many studies, there have been a large proportion of COVID-19 patients that suffered a thromboembolic event, in both the venous and arterial systems. Our patient, who did not have a significant past medical history, presented with a recurrent brachial artery occlusion despite medical and surgical management, and subsequently tested positive for COVID-19 late in his admission. In conclusion, there is high suspicion that there is a relationship between COVID-19 infection and recurrent arterial thrombosis.

High-Dose Methotrexate in Patients With Lymphoma: Predictors of a Complicated Course.

PURPOSE: High-dose methotrexate (HDMTX; > 500 mg/m2) is an important component of lymphoma therapy. Serum MTX monitoring at 48 hours is the standard approach to identify those at increased risk of developing MTX toxicity. Our aim was to characterize the incidence of complications and their association with MTX levels. METHODS: A retrospective review of our institutional electronic medical record was conducted to identify patients with lymphoma who received HDMTX between January 1, 2002, and December 31, 2018. We characterized the incidence of acute kidney injury (AKI), intensive care unit (ICU) admission, length of hospital stay (LOS), and 30-day mortality across 48-hour MTX levels. To establish an association between 48-hour MTX levels and the complications listed, we performed chi-square analysis for dichotomous variables and Kruskal-Wallis for nonparametric data. Receiver operator characteristic curve analysis was performed to identify the MTX level where AKI grade ≥ 2 was more likely. Multivariate logistic regression analysis was performed to identify risk factors for this MTX level. RESULTS: We identified 642 patients with 2,804 cycles of HDMTX. The incidence of AKI was 19.1% with AKI grade ≥ 2 making up 21% of cases. Rates of AKI, ICU admission, and 30-day mortality are associated with elevated 48-hour MTX levels. There was a significant increase in median LOS with elevated MTX levels (P < .001). Receiver operator characteristic curve analysis for AKI grade ≥ 2 demonstrated a 48-hour MTX level threshold of 1.28 µmol/L. Multivariate logistic regression analysis revealed age, male sex, elevated body surface area, higher MTX dose, monotherapy, and first cycle as independent factors. CONCLUSION: Elevated MTX levels are associated with a significant increased rate of AKI, ICU admission, prolonged LOS, and 30-day mortality. Elevated 48-hour MTX levels, particularly > 1.28 µmol/L, should alert clinicians for complications and to initiate measures to reduce MTX levels.

Anesthesia Type is Associated with Decreased Cranial Nerve Injury in Carotid Endarterectomy.

BACKGROUND: Anesthesia modalities for carotid endarterectomy continue to vary nationally. We evaluated and compared short-term outcomes after carotid endarterectomy with general anesthesia (GA) and regional anesthesia (RA) in both symptomatic and asymptomatic patients. METHODS: The 2011-2015 American College of Surgeons National Surgical Quality Improvement Program Participant Use Data Files (PUFs) with merged Vascular Procedure-Targeted PUFs for carotid endarterectomy were queried for patients undergoing carotid endarterectomy. Postoperative complications, mortality, and hospital length of stay in patients undergoing GA or RA were compared. RESULTS: A total of 14,447 patients were evaluated: 12,389 (85.7%) with GA and 2,058 (14.3%) with RA. The use of GA was inversely associated with patients' age (88.0% in patients aged 22-64 years vs. 83.4% in patients aged ≥80 years, P < 0.0001) and with symptomatic presentation (odds ratio [OR] = 1.25; 95% confidence interval [CI]: 1.13-1.38). There were no differences between GA and RA for in-hospital mortality, 30-day mortality, or postoperative complications of transient ischemic attack, stroke, bleeding, acute renal failure, or restenosis. However, rates of cranial nerve injury were significantly higher in GA than in RA (2.9% vs. 1.7%, respectively; P < 0.002) and confirmed by multivariable analysis (OR = 1.68; 95% CI: 1.19-2.39). Total operative time was also longer for GA than for RA (median: 115 minutes; Interquartile range (IQR): 89-145 versus median: 93 minutes; IQR: 76-119, respectively; P < 0.0001). Hospital length of stay was greater in GA than in RA (median: 1 day; IQR 1-2 vs. median: 1 day; IQR 1-1, respectively; P < 0.0001), as were 30-day readmission rates (6.7% vs. 5.4%, respectively; P = 0.02). CONCLUSIONS: Iatrogenic nerve injury is a feared complication of carotid endarterectomy, especially in elective asymptomatic patients. RA reduces the rate of cranial nerve injury compared with GA. RA is also not inferior to GA for postoperative complications with the benefit of shorter operative times, lengths of hospital stay, and decreased 30-day readmission rates. Consideration should be given to more widespread adoption of this underused anesthesia modality.

Giant visceral artery pseudoaneurysm treated with endovascular transradial coil embolization.

Visceral artery pseudoaneurysms (PSAs) are relatively rare, and cases associated with distal vasculature of the superior mesenteric artery are largely unreported. Visceral artery PSAs, without intervention, can lead to morbidity or mortality from rupture or mesenteric ischemia. Historically, open aneurysmectomy is the gold standard; however, endovascular modalities have emerged as the first-line treatment in patients who are poor surgical candidates and/or have unfavorable anatomy. Herein, we describe a case of a symptomatic PSA of the distal superior mesenteric artery treated via the transradial approach with endovascular coil embolization, showing successful aneurysmal exclusion and preservation of enteric collateral flow.

Assessment and source quantification of heavy metal(loid)s in surface water using multivariate analyses from the Saigon River, Vietnam.

The metal concentration in surface water of a river could be affected by season, position, and oceanic process such as tide. The current study aimed to (1) examine the heavy metal(loid) concentration in surface water from the Saigon River as affected by the combination of season, tide, and position and (2) apportion and quantify pollution sources. Ninety-six surface water samples were collected from 13 sites on the River in four campaigns (rainy season + ebb tide, rainy season + flood tide, dry season + ebb tide, and dry season + flood tide). Eight heavy metal(loid)s (Al, B, Bi, Fe, Mn, Pb, Sr, and Zn) were measured and subjected to multivariate analyses. Three-way ANOVA showed that in the rainy season, the total concentration of the metal(loid)s (TCM) in two tides was not clearly different from each other while in the dry season the TCM was significantly higher during the ebb tide than during the flood tide. Principal component analysis/factor analysis and Pearson correlation matrix showed that the TCM could be derived from three main sources, grouped into anthropogenic activities such as industrial, agricultural, and domestic wastes from inside Ho Chi Minh city, and natural origins from lowland area and acid sulfate soil. Three pollution sources explained 70% and 68% of the total variance of TCM in the rainy and dry seasons, respectively. In brief, the metal(loid) concentration was significantly affected by the season and tide and the pollution sources could be derived from inside Ho Chi Minh City and from lowland areas beyond the river estuary.

Seasonal, spatial variation, and pollution sources of heavy metals in the sediment of the Saigon River, Vietnam.

The current study was conducted to (1) examine seasonal and spatial distribution of heavy metals and metalloid in sediment from the Saigon River and (2) apportion and quantify their pollution sources. Ninety-six sediment samples were taken in the rainy and dry season on 13 sampling sites, distributed over the lower reaches of the River, to analyze for exchangeable concentration of 11 heavy metals and metalloid (Al, B, Cd, Co, Fe, In, Mn, Ni, Pb, Sr, and Zn), pH, EC, organic carbon content, and particle-size distribution. Generally, the concentration of 11 elements was ranked in the order Mn > Al > Fe > Zn > Sr > In > B > Ni > Co > Pb > Cd. Hierarchical cluster analysis grouped 13 sampling sites into two parts based on the similar concentration of the 11 elements. Three-way analysis of variance showed that the total exchangeable concentration of 11 elements was significantly higher in the rainy season than in the dry season and in the upper part than in the lower part of the river. Principal component analysis/factor analysis and correlation analysis revealed that three pollution sources (PS) may contribute to enriching the 11 examined elements in the sediment. These sources included (PS1) from catchment through water erosion over natural areas, explaining 83%, (PS2) mixed sources from catchment through water erosion over agricultural fields and inside Ho Chi Minh City, accounting for 6%, and (PS3) mixed sources from lowland areas, explaining 7.8% of the total variance of the elements. In brief, the sediment concentration of 11 metals and metalloid varied with season and space and three major pollution sources from river catchment, inside Ho Chi Minh City, and lowland contributively enriched the elements in the sediment of the River.

Paediatric use of antibiotics in children with community acquired pneumonia: A survey from Da Nang, Vietnam.

AIM: To characterise paediatricians' antibiotic-prescribing behaviour when managing community acquired pneumonia. METHODS: We conducted a knowledge and attitudes survey of paediatric doctors practicing at a regional provincial hospital in central Vietnam over a 2-week period (from 12 December 2017 to 29 December 2017). RESULTS: Of 79 eligible paediatric doctors, 69 (87.3%) completed the questionnaire, of whom 65 (94.2%) thought that antibiotics were overused in Vietnam. Thirty-eight doctors (55.1%) indicated that they routinely hospitalised children with pneumonia to provide intravenous antibiotics. Most doctors reported discharging children with non-severe pneumonia after 5 days (76.9%) and those with severe pneumonia after 7-10 days (88.4%); older doctors generally continued intravenous antibiotics for longer. The two most important factors driving discharge decisions were clinical assessment (95.6%) and completion of the full course of intravenous antibiotics (80.0%). Antibiotic prescription was influenced by local guidelines (62.3%), drugs used before admission (50.0%) and the opinion of senior clinicians (37.7%). Most doctors believed antibiotic stewardship was necessary (98.6%) and that over-the-counter use of antibiotics should be restricted (97.1%). CONCLUSIONS: Paediatricians recognised an urgent need for more effective regulation and antibiotic stewardship in Vietnam. Routinely completing a full course of intravenous antibiotics leads to unnecessary and prolonged hospitalisation.

Status postpneumonectomy for pulmonary artery sarcoma.

Primary pulmonary artery sarcoma is a rare disease that has a poor survival prognosis due to misdiagnosis with pulmonary thromboembolism or metastatic embolisation, detailed image findings and complicated surgical procedures. Surgical procedures established for treatment include pneumonectomy and pulmonary endarterectomy. Survival after surgery still remains at 1 year survival of 50%. The following case report demonstrates a patient's status postpneumonectomy for pulmonary artery sarcoma that presented with no complications after 1.5-year follow-up.

Geometrically specific imino complexes of the [Re6(µ3-Se)8]2+ core-containing clusters.

The reactions of nitrile complexes of the [Re(6)(µ(3)-Se)(8)](2+) core-containing clusters, [Re(6)(µ(3)-Se)(8)(PEt(3))(n)(CH(3)CN)(6-n)](2+) [n = 5 (1); n = 4, cis- (2) and trans- (3); n = 0 (4)], with organic azides C(6)H(5)CH(CH(3))N(3) and C(6)H(5)CH(2)N(3) produced the corresponding cationic imino complexes of the general formula [Re(6)(µ(3)-Se)(8)(PEt(3))(n)(L)(6-n)](2+) [L = PhN=CHCH(3): n = 5 (5); n = 4, cis- (6) and trans- (7); n = 0 (8) and L = HN=CHPh: n = 5 (9); n = 4, cis- (10) and trans- (11)]. These novel complexes were characterized by NMR spectroscopy ((1)H and (31)P) and single-crystal X-ray diffraction. A mechanism involving the migration of one of the groups on the azido α-C atom to the α-N atom of the azido complex, concerted with the photo-expulsion of N(2), was invoked to rationalize the formation of the imino complexes. Density functional theory (DFT) calculations indicated that due to the coordination with and activation by the cluster core, the energy of the electronic transition responsible for the photo-decomposition of a cluster-bound azide is much reduced with respect to its pure organic counterpart. The observed geometric specificity was rationalized by using the calculated and optimized preferred ground-state conformation of the cluster-azido intermediates.

Cluster-bound nitriles do not click with organic azides: unexpected formation of imino complexes of the [Re(6)(mu(3)-Se)(8)](2+) core-containing clusters.

The reactions of C(6)H(5)CH(CH(3))N(3) with nitrile solvates of the [Re(6)(mu(3)-Se)(8)](2+) core-containing cluster, [Re(6)(mu(3)-Se)(8)(PEt(3))(5)(MeCN)](2+)(1) and cis-[Re(6)(mu(3)-Se)(8)(PEt(3))(4)(MeCN)(2)](2+) (2), afforded the corresponding cationic imino complexes [Re(6)(mu(3)-Se)(8)(PEt(3))(5)(PhN horizontal lineCHCH(3))](2+) (3) and cis-[Re(6)(mu(3)-Se)(8)(PEt(3))(4)(PhN horizontal lineCHCH(3))(2)](2+) (4), respectively. Both compounds were spectroscopically and crystallographically characterized. A mechanism involving a 1,2-shift of one of the groups on the azido alpha-C atom of the cluster-azide intermediate concerted with the photoexpulsion of dinitrogen of the azido ligand is invoked to rationalize the formation of the imino complexes. Density functional theory calculations showed that a cluster-to-ligand transition was responsible for the absorption that promotes the photodecomposition of the cluster-azide complex.