Lifting Statewide Mask Mandates and COVID-19 Cases: A Synthetic Control Study.

IMPORTANCE: As states reopened their economies state and local officials made decisions on policies and restrictions that had an impact on the evolution of the pandemic and the health of the citizens. Some states made the decision to lift mask mandates starting spring 2021. Data-driven methods help evaluate the appropriateness and consequences of such decisions. OBJECTIVE: To investigate the association of lifting the mask mandate with changes in the cumulative coronavirus case rate. DESIGN: Synthetic control study design on lifting mask mandate in the state of Iowa implemented on February 7, 2021. SETTING: Daily state-level data from the COVID-19 Community Profile Report published by the US Department of Health & Human Services, COVIDcast dataset of the Delphi Research Group, and Google Community Mobility Reports. EXPOSURES AND OUTCOME: Mask mandate policy lift at the state level. State-day observations of the cumulative case rate measured as the cumulative number of new cases per 100,000 people in the previous 7 days. RESULTS: The cumulative case rate in Iowa increased by 20%-30% within 3 weeks of lifting the mask mandate as compared with a synthetic control unit. This association appeared to be related to people, in fact, reducing their mask-wearing habits. CONCLUSIONS: Lifting the mask mandate in Iowa was associated with an increase in new COVID-19 cases. Caution should be applied when making this type of policy decision before having achieved a more stable control of the pandemic.

Midostaurin and cyclosporine drug interaction: A case report.

WHAT IS KNOWN AND OBJECTIVE: Allogeneic stem cell transplantation patients are often on immunosuppression including calcineurin inhibitors post-transplant for prevention of graft-versus-host disease. Recent data suggested that addition of midostaurin, a FLT-3 mutant kinase inhibitor, maintenance can reduce risk of relapse by 46% at 18 months post-transplant. CASE DESCRIPTION: Patient is a post-allogenetic stem cell transplant patient started on midostaurin for maintenance therapy. Patient had stable serum levels of cyclosporine with a sudden 70% increase in serum level shortly after starting midostaurin. Patient had no other medication changes or laboratory abnormalities that would suggest the change was caused by alternate factors. WHAT IS NEW AND CONCLUSION: This data suggest that midostaurin and cyclosporine have a possible previously unidentified drug interaction leading to elevation immunosuppression serum levels that need to be accounted for in practice.

Total body irradiation dose escalation decreases risk of progression and graft rejection after hematopoietic cell transplantation for myelodysplastic syndromes or myeloproliferative neoplasms.

A non-myeloablative regimen of fludarabine and 200 cGy total body irradiation combined with post-grafting immunosuppression with mycophenolate mofetil and a calcineurin inhibitor facilitates allogeneic hematopoietic cell transplantation from HLA-matched related or unrelated donors in older patients and/or those with comorbidities. However, outcomes of prior studies have been disappointing in patients with myelodysplastic syndromes or myeloproliferative neoplasms due to high incidences of progression or graft failure (together termed hematopoietic cell transplantation-failure). We hypothesized that escalating the total body irradiation dose may improve the outcomes and subsequently performed a phase II total body irradiation dose-escalation trial. Patients with median age 66 years were enrolled in two arms to receive non-myeloablative conditioning followed by hematopoietic cell transplantation with total body irradiation dose escalation for excessive hematopoietic cell transplantation-failure: Arm A: myeloproliferative neoplasm/myelodysplastic syndrome low risk (n=36); and Arm B: myelodysplastic syndrome high-risk/chronic myelomonocytic leukemia (n=41). Total body irradiation dose levels were: Level-1 (300 cGy), Level-2 (400 cGy), or Level-3 (450 cGy). Patients received intravenous fludarabine 30 mg/m2 for three days. Total body irradiation was administered on day 0 followed by infusion of peripheral blood stem cells from HLA-matched related (n=30) or unrelated (n=47) donors. Post-grafting immunosuppression with mycophenolate mofetil and cyclosporine was administered. The primary end point was day 200 hematopoietic cell transplant failure, with the objective of reducing the incidence to <20%. The primary end point was reached on Arm A at dose Level-1 (300 cGy total body irradiation) with a cumulative incidence of day 200 hematopoietic cell transplant failure of 11%, and on Arm B at dose Level-3 (450 cGy) with a cumulative incidence of day 200 hematopoietic cell transplant failure of 9%. Increasing the total body irradiation dose leads to a higher success rate with non-myeloablative conditioning by reducing relapse and rejection. Further studies are necessary to decrease non-relapse mortality, especially among patients with high-risk disease. Trial registered under clinicaltrials.gov identifier: NCT00397813.

Prediction of Bloodstream Infection Due to Vancomycin-Resistant Enterococcus in Patients Undergoing Leukemia Induction or Hematopoietic Stem-Cell Transplantation.

BACKGROUND.: Bloodstream infection (BSI) to due vancomycin-resistant Enterococcus (VRE) is an important complication of hematologic malignancy. Determining when to use empiric anti-VRE antibiotic therapy in this population remains a clinical challenge. METHODS.: A single-center cohort representing 664 admissions for induction or hematopoietic stem-cell transplant (HSCT) from 2006 to 2014 was selected. We derived a prediction score using risk factors for VRE BSI and evaluated the model's predictive performance by calculating it for each of 16232 BSI at-risk inpatient days. RESULTS.: VRE BSI incidence was 6.5% of admissions (2.7 VRE BSI per 1000 BSI at-risk days). Adjusted 1-year mortality and length of stay were significantly higher in patients with VRE BSI. VRE colonization (adjusted odds ratio [aOR] = 8.4; 95% confidence interval [CI] = 3.4-20.6; P < .0001), renal insufficiency (aOR = 2.4; 95% CI = 1.0-5.8; P = .046), aminoglycoside use (aOR = 4.7; 95% CI = 2.2-9.8; P < .0001), and antianaerobic antibiotic use (aOR = 2.8; 95% CI = 1.3-5.8; P = .007) correlated most closely with VRE BSI. A prediction model with optimal performance included these factors plus gastrointestinal disturbance, severe neutropenia, and prior beta-lactam antibiotic use. The score effectively risk-stratified patients (area under the receiver operating curve = 0.84; 95% CI = 0.79-0.89). At a threshold of ≥5 points, per day probability of VRE BSI was increased nearly 4-fold. CONCLUSIONS.: This novel predictive score is based on risk factors reflecting a plausible pathophysiological model for VRE BSI in patients with hematological malignancy. Integrating VRE colonization status with risk factors for developing BSI is a promising method of guiding rational use of empiric anti-VRE antimicrobial therapy in patients with hematological malignancy. Validation of this novel predictive score is needed to confirm clinical utility.

Vancomycin-Resistant Enterococcus Colonization and Bacteremia and Hematopoietic Stem Cell Transplantation Outcomes.

The association between pre-hematopoietic stem cell transplantation (HSCT) vancomycin-resistant Enterococcus (VRE) colonization, HSCT-associated VRE bacteremia, and HSCT mortality is disputed. We studied 161 consecutive patients with acute leukemia who underwent HSCT at our hospital between 2006 and 2014, of whom 109 also received leukemia induction/consolidation on our unit. All inpatients had weekly VRE stool surveillance. Pre-HSCT colonization was not associated with increases in HSCT mortality but did identify a subgroup of HSCT recipients with a higher risk for VRE bacteremia and possibly bacteremia from other organisms. The major risk factor for pre-HSCT colonization was the number of hospital inpatient days between initial admission for leukemia and HSCT. One-third of evaluable patients colonized before HSCT were VRE-culture negative on admission for HSCT; these patients had an increased risk for subsequent VRE stool surveillance positivity but not VRE bacteremia. Molecular typing of VRE isolates obtained before and after HSCT showed that VRE strains frequently change. Postengraftment VRE bacteremia was associated with a much higher mortality than pre-engraftment VRE bacteremia. Pre-engraftment bacteremia from any organism was associated with an alternative donor and resulted in an increase in hospital length of stay and cost. Mortality was similar for pre-engraftment VRE bacteremia and pre-engraftment bacteremia due to other organisms, but mortality associated with post-engraftment VRE bacteremia was higher and largely explained by associated severe graft-versus-host disease and relapsed leukemia. These data emphasize the importance of distinguishing between VRE colonization before HSCT and at HSCT, between pre-engraftment and postengraftment VRE bacteremia, and between VRE bacteremia and bacteremia from other organisms.

Optimizing autologous stem cell mobilization strategies to improve patient outcomes: consensus guidelines and recommendations.

Autologous hematopoietic stem cell transplantation (aHSCT) is a well-established treatment for malignancies such as multiple myeloma (MM) and lymphomas. Various changes in the field over the past decade, including the frequent use of tandem aHSCT in MM, the advent of novel therapies for the treatment of MM and lymphoma, and the addition of new stem cell mobilization techniques, have led to the need to reassess current stem cell mobilization strategies. Mobilization failures with traditional strategies are common and result in delays in treatment and increased cost and resource utilization. Recently, plerixafor-containing strategies have been shown to significantly reduce mobilization failure rates, but the ideal method to maximize stem cell yields and minimize costs associated with collection has not yet been determined. A panel of experts convened to discuss the currently available data on autologous hematopoietic stem cell mobilization and transplantation and to devise guidelines to optimize mobilization strategies. Herein is a summary of their discussion and consensus.

A randomized phase II trial of tacrolimus, mycophenolate mofetil and sirolimus after non-myeloablative unrelated donor transplantation.

The study is a randomized phase II trial investigating graft-versus-host disease prophylaxis after non-myeloablative (90 mg/m(2) fludarabine and 2 Gy total body irradiation) human leukocyte antigen matched unrelated donor transplantation. Patients were randomized as follows: arm 1 - tacrolimus 180 days and mycophenolate mofetil 95 days (n=69); arm 2 - tacrolimus 150 days and mycophenolate mofetil 180 days (n=71); arm 3 - tacrolimus 150 days, mycophenolate mofetil 180 days and sirolimus 80 days (n=68). All patients had sustained engraftment. Grade II-IV acute graft-versus-host disease rates in the 3 arms were 64%, 48% and 47% at Day 150, respectively (arm 3 vs. arm 1 (hazard ratio 0.62; P=0.04). Owing to the decreased incidence of acute graft-versus-host disease, systemic steroid use was lower at Day 150 in arm 3 (32% vs. 55% in arm 1 and 49% in arm 2; overall P=0.009 by hazard ratio analysis). The Day 150 incidence of cytomegalovirus reactivation was lower in arm 3 (arm 1, 54%; arm 2, 47%; arm 3, 22%; overall P=0.002 by hazard ratio analysis). Non-relapse mortality was comparable in the three arms at two years (arm 1, 26%; arm 2, 23%; arm 3, 18%). Toxicity rates and other outcome measures were similar between the three arms. The addition of sirolimus to tacrolimus and mycophenolate mofetil is safe and associated with lower incidence of acute graft-versus-host disease and cytomegalovirus reactivation. (clinicaltrials.gov identifier: 00105001).

Synthesis and surface-spectroscopic characterization of photoisomerizable glyco-SAMs on Au(111).

Photoisomerizable glyco-SAMs (self-assembled monolayers), utilizing synthetic azobenzene glycoside derivatives were fabricated. The ultimate goal of this project is to assay the influence of the 3D arrangement of sugar ligands on cell adhesion, and eventually make cell adhesion photoswitchable. However, it is a prerequisite for any biological study on the spatial conditions of carbohydrate recognition, that photoisomerization of the surface molecules can be verified. Here, we employed IRRAS and XPS to spectroscopically characterize glyco-SAMs. In particular and unprecedented to date, we prove reversible E→Z→E isomerization of azobenzene glycoside-terminated SAMs.

Monitoring the reversible photoisomerization of an azobenzene-functionalized molecular triazatriangulene platform on Au(111) by IRRAS.

Spectroscopic evidence of a reversible, photoinduced trans ↔ cis photoisomerization is provided for an azobenzene-functionalized triazatriangulene (TATA) platform on Au(111). As shown by scanning tunneling microscopy (STM) and X-ray photoelectron spectroscopy (XPS), these molecules form a well-ordered self-assembled monolayer (SAM) on Au(111). The surface-adsorbed azo-TATA platforms are also investigated by infrared reflection absorption spectroscopy (IRRAS); a methoxy marker group at the upper phenyl ring of the azo moiety is employed to monitor the switching state. The IRRAS data are analyzed by comparison with theoretical and transmission IR spectra as well as bulk and surface-enhanced Raman spectroscopic (SERS) data. IRRAS shows that the methoxy group is oriented perpendicular to the surface in trans- and tilted with respect to the surface normal in cis-configuration. This indicates that the photoswitching capability of the azobenzene moieties is retained on the gold surface. The lifetime of the cis-configuration is, however, reduced by a factor of ∼10(3) with respect to the homogeneous solution.

Fludarabine and 2-Gy TBI is superior to 2 Gy TBI as conditioning for HLA-matched related hematopoietic cell transplantation: a phase III randomized trial.

The risks and benefits of adding fludarabine to a 2-Gy total body irradiation (TBI) nonmyeloablative regimen are unknown. For this reason, we conducted a prospective randomized trial comparing 2-Gy TBI alone, or in combination with 90 mg/m(2) fludarabine (FLU/TBI), before transplantation of peripheral blood stem cells from HLA-matched related donors. Eighty-five patients with hematological malignancies were randomized to be conditioned with TBI alone (n = 44) or FLU/TBI (n = 41). All patients had initial engraftment. Two graft rejections were observed, both in the TBI group. Infection rates, nonrelapse mortality, and graft-versus-host disease (GVHD) were similar between groups. Three-year overall survival was lower in the TBI group (54% versus 65%; hazard ratio [HR], .57; P = .09), with higher incidences of relapse/progression (55% versus 40%; HR, .55; P = .06), relapse-related mortality (37% versus 28%; HR, .53; P = .09), and a lower progression-free survival (36% versus 53%; HR, .56; P = .05). Median donor T cell chimerism levels were significantly lower in the TBI group at days 28 (61% versus 90%; P < .0001) and 84 (68% versus 92%; P < .0001), as was NK cell chimerism on day 28 (75% versus 96%; P = .0005). In conclusion, this randomized trial demonstrates the importance of fludarabine in augmenting the graft-versus-tumor effect by ensuring prompt and durable high-level donor engraftment early after transplantation.