Retrospective Evaluation of Cystatin C as a Measure of Renal Function in Pediatric Hematopoietic Stem Cell Transplant Patients Receiving Foscarnet for Cytomegalovirus Reactivation.

BACKGROUND: Cytomegalovirus (CMV) infection following allogeneic hematopoietic cell transplantation has considerable morbidity and mortality, and foscarnet is a treatment option that requires renal dose adjustment. Serum creatinine (SCr)-based estimated glomerular filtration rate (eGFR) equations are used to estimate renal function for patients receiving foscarnet, but cystatin C (cysC) has been shown as a possible alternative. Data examining cysC-based eGFR in this population is sparse. Our primary objective was to evaluate outcomes of patients treated with foscarnet dosed utilizing cysC-based eGFR versus SCr-based eGFR. METHODS: We analyzed patients on the transplantation and cellular therapies service at Memorial Sloan Kettering Kids from January 2011 to September 2021 who received allogeneic hematopoietic cell transplantation and ≥14 days of foscarnet for CMV infection. Patients with cysC-based eGFR were compared to a historical cohort of patients who only had SCr-based eGFR. Outcomes included time to CMV clearance, death or change in anti-CMV therapy. Cumulative incidence curves and cause-specific hazards model were used for analysis. RESULTS: In 61 analyzed patients, no differences were found between the cohorts in cumulative incidence of change in anti-CMV therapy ( P = 0.17) or death ( P = 0.69). After adjustment for multiple confounders, patients in the SCr cohort seemed to have a higher chance of CMV clearance compared with the cysC cohort, but the difference was not statistically significant (hazard ratio = 2.42, P = 0.089). Patients who received corticosteroids appeared to have lower incidence of CMV clearance ( P = 0.056). CONCLUSIONS: We did not find differences in outcomes when dosing foscarnet using cysC versus SCr for treatment of CMV infection.

Predictors of SARS-CoV-2 Omicron breakthrough infection after receipt of AZD7442 (tixagevimab-cilgavimab) for pre-exposure prophylaxis among hematologic malignancy patients.

AZD7442 (tixagevimab-cilgavimab) is a combination of two human monoclonal antibodies for pre-exposure prophylaxis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among high-risk patients who do not mount a reliable vaccine response. Foremost among these are hematologic malignancy patients with limited clinical trial or realworld experience to assess the effectiveness of this combination treatment since the emergence of Omicron and its subvariants. We performed a retrospective study of 892 high-risk hematologic malignancy patients who received AZD7442 at Memorial Sloan Kettering Cancer Center in New York City from January 1, 2022 to July 31, 2022. We evaluated demographic, clinical, and laboratory characteristics and performed regression analyses to evaluate risk factors for breakthrough infection. We also evaluated the impact of updated AZD7442 dosing regimens on the risk of breakthrough infection. Among 892 patients, 98 (10.9%) had a breakthrough infection during the study period. A majority received early outpatient treatment (82%) and eventually eight (8.2%) required hospitalization for management of Coronavirus Disease 2019 (COVID-19), with a single instance of severe COVID-19 and death. Patients who received a repeat dose or a higher firsttime dose of AZD7442 had a lower incidence of breakthrough infection. Univariate analyses did not reveal any significant predictors of breakthrough infection. While AZD7442 is effective at reducing SARS-CoV-2 breakthrough infection in patients with hematologic malignancies, no risk factors reliably predicted risk of infection. Patients who received updated dosing regimens as per Food and Drug Administration guidelines had better protection against breakthrough infection.

Sepsis and postoperative surgical site infections.

Surgical site infections remain a significant cause of morbidity and mortality. High-quality evidence supports several measures to prevent surgical site infections that should be applied with high compliance, although effective application remains suboptimal. Recognizing high-risk patients and avoiding potential pitfalls in the diagnosis of surgical site infections is paramount in preventing progression to sepsis, particularly in emergency surgical patients with physiologic derangement. A high index of suspicion postoperatively is critical to identify patients with surgical site infections and to prevent failure to rescue.

Bacterial infections and antibiotic utilization varies by coronavirus disease 19 (COVID-19) severity in hospitalized cancer patients: Analysis from the first phase of the pandemic.

OBJECTIVE: To characterize bacterial infections and antibiotic utilization in hospitalized cancer patients with coronavirus disease 2019 (COVID-19). DESIGN: Retrospective cohort study. SETTING: Tertiary cancer center in New York City. PATIENTS: Hospitalized cancer patients ≥18 years with COVID-19 between March 1, 2020, and May 31, 2020. METHODS: Patients were classified with mild COVID-19 (ie, with room air), moderate COVID-19 (ie, using nasal cannula oxygen), or severe COVID-19 (ie, using high-flow oxygen or mechanical ventilation). The primary outcome was bacterial infection rate within 30 days of COVID-19 onset. Secondary outcomes included the proportion of patients receiving antibiotics and antibiotic length of therapy (LOT). RESULTS: Of 358 study patients, 133 had mild COVID-19, 97 had moderate COVID-19, and 128 had severe COVID-19. Of 358 patients, 234 (65%) had a solid tumor. Also, 200 patients (56%) had 245 bacterial infections, of which 67 (27%) were microbiologically confirmed. The proportion of patients with bacterial infection increased with COVID-19 severity: mild (n = 47, 35%) versus moderate (n = 49, 51%) versus severe (n = 104, 81%) (P < .0001). Also, 274 (77%) received antibiotics for a median of 4 days. The median antibiotic LOTs were 7 days with 1 infection and 20 days with multiple infections (P < .0001). Antibiotic durations were 1 day for patients with mild COVID-19, 4 days for patients with moderate COVID-19, and 8 days for patients with severe COVID-19 (P < .0001). CONCLUSIONS: Hospitalized cancer patients with COVID-19 had a high rate of bacterial infection. As COVID-19 severity increased, the proportion of patients diagnosed with bacterial infection and given antibiotics increased. In mild COVID-19 cases, antibiotic LOT was short, suggesting that empiric antibiotics can be safely avoided or discontinued in this group.

Predictors of Coronavirus Disease 2019 Hospitalization After Sotrovimab in Patients With Hematologic Malignancy During the BA.1 Omicron Surge.

BACKGROUND: Sotrovimab is an anti-spike neutralization monoclonal antibody developed to reduce the risk of coronavirus disease 2019 (COVID-19) progression and advancement to hospitalization in high-risk patients. Currently, there is limited research describing the association of sotrovimab treatment in patients with hematologic malignancy and the predictive factors of hospitalization. METHODS: We performed an observational study of 156 consecutive cancer patients who received sotrovimab at Memorial Sloan Kettering Cancer Center in New York City during the BA.1 Omicron surge. We evaluated the demographic, clinical, and laboratory characteristics of the patients who had subsequent COVID-19-related hospitalization(s) compared to those who did not. RESULTS: Among the 156 study patients, 17 (11%) were hospitalized, of whom 4 were readmitted for COVID-19-related complications; 3 deaths were attributed to COVID-19. Results from multivariable logistic regression show that significant factors associated with hospitalization include patients on anti-CD20 therapy (adjusted odds ratio [aOR], 5.59 [95% confidence interval {CI}, 1.73-18.12]; P = .004) and with relapse/refractory disease (aOR, 5.69 [95% CI, 1.69-19.16]; P = .005). Additionally, whole genome sequencing of severe acute respiratory syndrome coronavirus 2 detected high occurrences of mutations in the spike gene associated with treatment-related resistance longitudinal samples from 11 patients treated with sotrovimab. CONCLUSIONS: While sotrovimab is effective at reducing COVID-19 hospitalization and disease severity in patients with hematologic malignancy when administered early, patients who received anti-CD20 antibodies showed substantial morbidity. Due to the high potential for resistance mutation to sotrovimab and increased morbidity in patients on anti-CD20 therapy, combination treatment should be explored to determine whether it provides added benefits compared to monotherapy.

Analyzing Adherence to the 2016 Infectious Diseases Society of America Guidelines for Candidemia in Cancer Patients.

Background: Candidemia is associated with morbidity and mortality in cancer patients. We analyzed adherence to the 2016 Infectious Diseases Society of America (IDSA) candidiasis guidelines and the reasons for guideline nonadherence. We also investigated whether matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) improved time to effective antifungal therapy compared with historical data (median, 43.2 hours). Methods: Cancer patients with candidemia between 1/1/17 and 12/31/19 were included. Adherence to 7 individual IDSA guideline components was assessed. Composite IDSA guideline adherence (defined as meeting ≥6 guideline components) was also assessed. Charts were reviewed to examine reasons for noncompliance. Results: Of 157 patients with candidemia, 150 (95.5%) had infectious disease (ID) consultation. The median total time from blood culture collection to antifungal initiation was 42.1 hours. Excluding 39 patients with short treatment due to death, there was 100% adherence with surveillance blood cultures, followed by antifungal susceptibility testing (117/118, 99.2%), initial appropriate therapy (117/118, 99.2%), antifungal duration (110/118, 93.2%), line removal (82/91, 90.1%), eye exams (93/118, 78.8%), and step-down therapy (69/94, 73.4%). A quarter (30/118) did not meet composite IDSA guideline adherence. Univariate logistic regression suggested a relationship between poor cancer prognosis and incomplete adherence to the 2016 IDSA candidiasis guidelines (odds ratio, 8.6; 95% CI, 1.6-47). Conclusions: The addition of MALDI-TOF did not shorten time to effective antifungal therapy. Nearly all patients were seen by ID for candidemia. Poor cancer prognosis was a common factor for incomplete composite adherence to the 2016 IDSA candidiasis guidelines.

Penicillin Allergy Testing: An Outpatient Nurse-Driven Program for Patients With Cancer.

BACKGROUND: Penicillin allergy testing (PAT) can decrease the use of unnecessary antibiotics by clarifying who is truly allergic. OBJECTIVES: This article describes the development and implementation of an oncology outpatient nurse-driven PAT program. METHODS: A nurse-driven program, initiated with allergy screening at the first encounter, was designed to identify patients with oncologic diagnoses eligible for PAT. Once verified eligible, patients undergo a three-step testing process (scratch test, intradermal injection, and IV challenge dose) administered by the infusion nurse. FINDINGS: From November 2018 to December 2019, 82 outpatients with reported penicillin allergies were screened; 90% were eligible for PAT, and 97% of patients tested were negative for penicillin allergy. A significant reduction in aztreonam use among patients admitted for hematopoietic stem cell transplantation was also noted as compared to before PAT was offered.

Impact of Eliminating Postprocedural Antibiotic Prophylaxis in Patients without Biliary Instrumentation or Bypass Undergoing Hepatic Artery Embolization for Hepatic Malignancies.

PURPOSE: To assess the infection rate after eliminating postprocedural antibiotics in patients undergoing hepatic artery embolization (HAE) for primary and secondary hepatic malignancies. MATERIAL AND METHODS: In this historical cohort study, adults ≥18 years of age without prior biliary instrumentation or bypass who underwent HAE and received pre- and postprocedure antibiotic prophylaxis between September 1, 2014, and August 31, 2015, comprised group A, whereas similar patients receiving only preprocedure antibiotic prophylaxis between October 1, 2015, and September 30, 2016, comprised group B. Procedures conducted between September 1, 2015, and September 30, 2015, were excluded. The primary outcome was any infection occurring within 30 days of HAE. RESULTS: A total of 150 patients underwent 204 HAE procedures in group A, and 171 patients underwent 221 procedures in group B. Cefazolin given as a 1-g dose (or 2 grams if obese) was administered in 391 of 425 evaluable procedures (92%). Clindamycin plus gentamicin was prescribed in 34 patients (8%) who had severe penicillin allergy. There was significant improvement in adherence to the postprocedure antibiotic regimen, from 68% (138 of 204 procedures) to 98% (216 of 221 procedures) (P < .001) with elimination of postprocedure prophylaxis. There were no significant differences in 30-day infection rates (5 [3%] vs. 5 [2%]; P = .57), hospital readmissions (13 [6%] vs. 12 [5%]; P = .68), or all-cause mortality (3 [1%] vs. 3 [1%]; P = .62) between the 2 groups. CONCLUSIONS: Elimination of postprocedural antibiotics after HAE did not lead to an increase in infectious complications. This finding supports the 2018 Society of Interventional Radiology recommendation for preprocedural prophylaxis only for HAE in the setting of an intact sphincter of Oddi.

Impact of Empiric Treatment for Vancomycin-Resistant Enterococcus in Colonized Patients Early after Allogeneic Hematopoietic Stem Cell Transplantation.

In recent years, vancomycin-resistant Enterococcus (VRE) colonization is being increasingly encountered in transplant recipients, and VRE has become one of the leading causes of bacteremia early after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Data are sparse on the effect of empiric VRE therapy for febrile, neutropenic allo-HSCT recipients colonized with VRE. All allo-HSCT recipients aged ≥18years who developed VRE bacteremia (VREB) between 2005 and 2014 were identified and categorized as to whether they received empiric or directed VRE therapy. There were 434 (33%) VRE-colonized and 872 (67%) non-VRE-colonized patients during the study period, and 172 of the 434 (40%) VRE-colonized patients received empiric therapy. There was no significant difference in incidence of VREB among colonized patients who did or did not receive empiric therapy (28 of 172 [16%] vs 55 of 262 [21%]; P = .22). There were 95 patients with VREB, of which the majority (83 of 95; 87%) was known to be VRE-colonized. Of the 95 VREB episodes, 29 (31%) were treated with empiric VRE therapy, whereas 66 (69%) were treated with directed therapy. No significant differences in clinical outcomes, including median duration of bacteremia (2 days vs 2 days; P = .39), recurrent VREB (3 of 29 [10%] vs 5 of 66 [8%]; P = .65), 30-day all-cause mortality (1 of 29 [3%] vs 4 of 66 [6%]; P = .62), or VRE-attributable mortality (1 of 29 [3%] vs 1 of 66 [2%]; P = .55), were observed between the empiric therapy and directed therapy groups. Kaplan-Meier curve analysis showed no significant difference in survival at 30days in allo-HSCT recipients with VREB who received empiric therapy and those who received directed therapy (97% vs 94%; P = .62). Based on our data, we recommend against empiric use of VRE-active agents for fever and neutropenia in VRE-colonized patients undergoing allo-HSCT.

The Role of Civil Commitment in the Opioid Crisis.

This article seeks to shed light on civil commitment in the context of the opioid crisis, to sketch the existing legal landscape surrounding civil commitment, and to illustrate the relevant medical, ethical, and legal concerns that policymakers must take into account as they struggle to find appropriate responses to the crisis.

The physiologic impact of pectus excavatum repair.

The adverse physiologic effects of pectus excavatum and subsequent resolution following correction have been a subject of controversy. There are numerous accounts of patients reporting subjective improvement in exercise tolerance after surgery, but studies showing clear and consistent objective data to corroborate this phenomenon physiologically have been elusive. This is partially due to a lack of consistent study methodologies but even more so due to a mere paucity of data. As experts in the repair of pectus excavatum, it is not uncommon for pediatric surgeons to operate on adult patients. For this reason, this review evaluates the contemporary literature to provide an understanding of the physiologic impact of repairing pectus excavatum on pediatric and adult patients separately.

Bleeding at Removal of Nuss Bar: Rare But Sometimes Significant.

BACKGROUND: Hemorrhage during Nuss bar removal is an uncommon but feared complication that can be life threatening if not controlled rapidly. This study aims to identify the incidence and sources of large volume hemorrhage, discuss successful management strategies, and provide patient care recommendations. METHODS: An IRB approved (#15-11-WC-0214), single institution retrospective chart review was performed on patients who underwent Nuss bar removal over a 15-year interval. Estimated blood loss (EBL), source of hemorrhage, management, and outcomes are reported. RESULTS: One thousand six hundred twenty-eight Nuss bar removal procedures were reviewed. EBL >150 mL occurred in 7 patients (0.43%), of whom 2 patients (0.12%) had EBL >2000 mL. Bleeding sources included: lateral soft tissue, lateral ectopic calcium, medial ectopic calcification, and an intercostal vessel. Most bleeding could be controlled with pressure and electrocautery. Only 2 patients (0.12%) required transfusion. One of these had bleeding from an intercostal vessel, and the other bled from a large vein in the medial calcified substernal tract. No patients sustained heart injury or died. CONCLUSION: Large volume hemorrhage after Nuss bar removal is rare, but may require blood transfusion, thoracoscopic exploration, or open exploration through thoracotomy or sternotomy. Nuss bar removal should be performed in centers capable of these interventions. After bar removal, a chest X-ray and a period of postoperative observation up to 6 hours may be beneficial to detect occult hemorrhage.

Multivariate analysis of risk factors for Nuss bar infections: A single center study.

BACKGROUND/PURPOSE: Our previously published data suggested several risk factors for infection after the Nuss procedure. We aimed to further elucidate these findings. METHODS: An IRB-approved (14-03-WC-0034), single institution, retrospective review was performed to evaluate the incidence of postoperative Nuss bar infections associated with seven variables. These were subjected to bivariate and multivariable analyses. A broad definition of infection was used including cellulitis, superficial infection with drainage, or deep infection occurring at any time postoperatively. RESULTS: Over 7years (4/1/2009-7/31/2016), 25 (3.2%) of 781 patients developed a postoperative infection after primary Nuss repair. Multivariable analyses demonstrated an increased risk of infection with perioperative clindamycin versus cefazolin for all infections (AOR 3.72, p=.017), and specifically deep infections (AOR 5.72, p=.004). The risk of a superficial infection was increased when antibiotic infusion completed >60min prior to incision (AOR 10.4, p=.044) and with the use of peri-incisional subcutaneous catheters (OR 8.98, p=.008). CONCLUSION: Following primary Nuss repair, the rate of deep bar infection increased with the use of perioperative clindamycin rather than cefazolin. The rate of superficial infection increased when perioperative antibiotic infusion was completed more than 60min prior to incision and with the use of peri-incisional subcutaneous catheters. Further studies are needed to better understand these findings. TYPE OF STUDY: Retrospective chart review. LEVEL OF EVIDENCE: Level III treatment study.

Nonoperative management of pectus excavatum with vacuum bell therapy: A single center study.

PURPOSE: The purpose of this study was to determine variables predictive of an excellent correction using vacuum bell therapy for nonoperative treatment of pectus excavatum. METHODS: A single institution, retrospective evaluation (IRB 15-01-WC-0024) of variables associated with an excellent outcome in pectus excavatum patients treated with vacuum bell therapy was performed. An excellent correction was defined as a chest wall depth equal to the mean depth of a reference group of 30 male children without pectus excavatum. RESULTS: Over 4years (11/2012-11/2016) there were 180 patients enrolled with 115 available for analysis in the treatment group. The reference group had a mean chest wall depth of 0.51cm. An excellent correction (depth≤0.51cm) was achieved in 23 (20%) patients. Patient characteristics predictive of an excellent outcome included initial age≤11years (OR=3.3,p=.013), initial chest wall depth≤1.5cm (OR=4.6,p=.003), and chest wall flexibility (OR=14.8,p<.001). Patients that used the vacuum bell over 12 consecutive months were more likely to achieve an excellent correction (OR=3.1,p=.030). Follow-up was 4months to 4years (median 12months). CONCLUSION: Nonoperative management of pectus excavatum with vacuum bell therapy results in an excellent correction in a small percentage of patients. Variables predictive of an excellent outcome include age≤11years, chest wall depth≤1.5cm, chest wall flexibility, and vacuum bell use over 12 consecutive months. TYPE OF STUDY: Retrospective chart review. LEVEL OF EVIDENCE: Level III treatment study.

Serious Infections in Patients Receiving Ibrutinib for Treatment of Lymphoid Cancer.

Background: Ibrutinib is a Bruton tyrosine kinase inhibitor that is used for the treatment of lymphoid cancers, including chronic lymphocytic leukemia, Waldenström macroglobulinemia, and mantle cell lymphoma. Several case series have described opportunistic infections among ibrutinib recipients, but the full extent of these infections is unknown. We sought to determine the spectrum of serious infections associated with ibrutinib treatment. Methods: We reviewed the electronic medical records of patients with lymphoid cancer at Memorial Sloan Kettering Cancer Center who received ibrutinib during a 5-year period from 1 January 2012 to 31 December 2016. Serious infections were identified by review of the relevant microbiology, clinical laboratory, and radiology data. Risk factors for infection were determined by means of univariate and multivariate analyses. Results: We analyzed findings in 378 patients with lymphoid cancer who received ibrutinib. The most common underlying cancers were chronic lymphocytic leukemia and mantle cell lymphoma. 84% of patients received ibrutinib as monotherapy. Serious infection developed in 43 patients (11.4%), primarily during the first year of ibrutinib treatment. Invasive bacterial infections developed in 23 (53.5%) of these patients, and invasive fungal infections (IFIs) in 16 (37.2%) .The majority of patients with IFIs during ibrutinib therapy (62.5%) lacked classic clinical risk factors for fungal infection (ie, neutropenia, lymphopenia, and receipt of corticosteroids). Infection resulted in death in 6 of the 43 patients (14%). Conclusions: Patients with lymphoid cancer receiving ibrutinib treatment are at risk for serious infections, including IFIs.

Voriconazole Dosing in Children Younger Than 3 Years Undergoing Cancer Chemotherapy or Hematopoietic Stem Cell Transplantation.

There are limited pediatric population pharmacokinetic data for voriconazole dosing, particularly in younger children. In a cohort of 34 patients younger than 3 years receiving voriconazole, the majority (n = 23, 68%) had a low initial serum concentration <1 mg/L. Among 23 children <2 years old, 19 (83%) had an initial trough <1 mg/L. There was large intra- and interindividual variability in trough levels. Dosing also varied from 3.3 to 19.6 mg/kg per dose. Only 2 of 34 patients had a documented adverse drug reaction attributable to voriconazole. More data are needed to establish optimal dosing in very young children.

Retrospective Analysis of Posaconazole Suspension Dosing Strategies in a Pediatric Oncology Population: Single-Center Experience.

Limited data on optimal posaconazole dosing strategies for pediatric patients exist. In this study, we found that the median initial dose in patients who achieved a posaconazole plasma concentration of 0.7 µg/mL was 22.8 mg/kg per day whereas the median initial dose in those who did not reach the target concentration was 15.8 mg/kg per day; this result suggests that higher initial doses might be warranted.