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Objectives Since 2003, incidences of carbapenemase-producing Gram-negative bacilli (CP-GNB) and vancomycin-resistant Enterococcus faecium (VRE) have steadily increased in France. We therefore conducted a point prevalence study to estimate carriage rates of CP-GNB, VRE and ESBL-producing Enterobacterales (ESBL-PE) and associated risk factors. Methods Between September 2019 and January 2020, all inpatients hospitalized on a given day in 11 teaching hospitals in the Paris urban area were eligible. Patient interviews and rectal swab screening results were recorded by dedicated nurses. The swabs were plated onto selective chromogenic media and processed using the GeneXpert® system. Results Of 2396 patients, 364 (15.2%) yielded at least one multiresistant bacterial isolate, including 29 CP-GNB carriers (1.2%), 13 VRE carriers (0.5%) and 338 ESBL-PE carriers (14%). In 15 patients (4.4% of ESBL-PE carriers and 36.6% of CP-GNB/VRE carriers), concomitant CP-GNB/VRE and ESBL-PE carriage was observed. In 7/29 CP-GNB and 7/13 VRE carriers, carbapenemase production and vanA in the screening samples was only detected with Xpert® tests. The OXA-48 gene was predominant in 13/34 CP-GNB isolates from 29 carriers. From the 338 ESBL-PE carriers, 372 isolates were recovered, mainly Escherichia coli (61.2%). Among 379 children, 1.1% carried a CP-GNB/VRE strain, and 12.4% carried an ESBL strain. Previous hospitalization outside mainland France, previous antimicrobial treatment and previous ESBL-PE carriage were the main risk factors associated with CP-GNB and/or VRE carriage. Conclusions The low CP-GNB and VRE prevalence likely reflects the French policy to limit intrahospital spread of CP-GNB and VRE strains.

In our hospital, during COVID-19 pandemic, overall consumption of antibiotics increased during the three first surges, mainly due to ICU prescription However, antibiotic consumption decreased in the Infectious Diseases Department. Rates of ESBL Enterobacterales remained stable.

Introduction Better understanding how hospital staff members (HSMs), including HCWs, were contaminated by SARS-CoV-2 during the first wave can help refining the control measures, in the context of the current second wave in Europe. Methods From March 5th to May 10th 2020, the infectious diseases unit at Raymond-Poincare teaching Hospital opened a weekday consultation dedicated to HSMs for a PCR testing. While in the waiting room, HSMs were offered to complete a questionnaire on their potential risk exposure to SARS-CoV-2. Results Of the 200 HSMs screened, 70 were positive. Ninety-nine HSMs (including 86 HCWs) completed the questionnaire of whom 28 cases positive. In the multivariable analysis among healthcare workers, age ≥ 44 years-old (aOR = 5.2, 95%CI [1.4-22.5]), not using a facemask systematically when caring for a patient (aOR = 13.9, 95%CI [1.8-293.0]), were significantly associated with SARS-CoV-2 infection. Conversely, working in a ward dedicated to COVID-19 patients (aOR = 0.7, 95%CI [0.2-3.2]) was not significantly associated with SARS-CoV-2 infection. Regarding community related exposures occurring in and outside the hospital among the HSMs, participation to meetings inside the hospital without wearing a facemask (aOR = 21.3, 95%CI [4.5-143.9]) and participation to private gathering (aOR = 10, 95%CI [1.3-91.0]) were significantly associated with SARS-CoV-2 infection. Conclusions Our results support the effectiveness of barrier precautions, underline that in-hospital contaminations not related to patient care may occur, and that part of the contaminations may be related to exposures in the community. Better protecting HCWs against COVID-19 and thereby ensuring workforces is crucial to fight the current second wave of the epidemic.

Hematopoietic cell transplantation (HCT) is physically and psychologically challenging, potentially exposing patients to quality-of-life (QoL) impairments. Adolescent and young adults (AYAs, aged 15 to 39 years) are a vulnerable cohort facing multiple hurdles due to dynamic changes in several aspects of their lives. The AYA population may be particularly prone to QoL issues during HCT. We hypothesized that due to the unique psychosocial challenges faced by AYAs, they would have an inferior quality of life. We studied QoL differences between AYA (aged 15 to 39 years) and older adult (aged 40 to 60 years) allogeneic HCT recipients before and after HCT. Additionally, we determined if pre-HCT QoL for AYA transplant recipients changed over time. QoL data were collected prospectively before and after transplant on 431 recipients aged 15 to 60 years from June 2003 through December 2017 using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) questionnaire. Repeated-measures analysis of variance was used to assess differences among age groups. Pearson correlation (r) was used to determine if baseline QoL had improved after HCT from June 2003 through December 2017 in the AYA cohort. QoL did not differ among younger AYAs, older AYAs, or older adults at any time in the first year after allogeneic HCT. At 1 year post-HCT, total FACT-BMT score and all FACT-BMT domains except physical well-being improved from pre-HCT in all age groups. From 2003 to 2017, AYA allogeneic recipients experienced modest improvement in additional concerns (r = 0.26, P = .003), trial outcome index (r = 0.23, P = .008), and total FACT-BMT score (r = 0.19, P = .031), although no improvements were seen in physical, social, emotional, or functional well-being. Contrary to our hypothesis, we found that QoL in the AYA population is similar to that of older adults before and after HCT. Improvements in QoL of AYA allogeneic patients since 2003 were driven by the additional concerns domain, which addresses multiple psychosocial aspects such as vocation, hobbies, and acceptance of illness. Continued efforts to tailor treatment and support for AYA HCT recipients is critical to improving QoL outcomes.

Psychosocial Assessment of Candidates for Transplant (PACT) is a tool originally developed to address psychosocial risks in solid organ transplant recipients and has the potential for application to hematopoietic cell transplantation (HCT) recipients. In a retrospective cohort study, we reviewed 404 adult allogeneic HCT cases from 2003 to 2014 to identify predictors of adverse psychosocial status as determined by PACT. Final PACT rating was poor/borderline (score 0–1) in 5%, acceptable (score 2) in 22%, good (score 3) in 44%, and excellent (score 4) in 29% recipients. In multivariable regression, higher PACT score was associated with White race (odds ratio [OR] 2.95, P < 0.001), having a related donor (OR 1.61, P = 0.015), and a higher quality of life score (OR 1.22/ 10-point increase in FACT-BMT total score, P < 0.001). PACT score correlated with all quality of life subscales. The final PACT score was associated with non-relapse mortality (HR 0.82/ 1-point increase, p = 0.03) in multivariable analysis that considered patient and disease factors, but not in models that also included transplant-related factors and performance status. PACT score was not associated with overall survival. PACT can be considered as part of a comprehensive psychosocial assessment for identifying patients who may require additional resources around allogeneic HCT.

After 1 year, among 236 hospital staff members (HSMs) tested positive for SARS-CoV-2, we observed five cases of suspected reinfection in our teaching hospital in France. No probable reinfection was retained considering PCR Cycle Threshold and clinical context. Focus should concern COVID-free HSMs still not vaccinated rather than the ones previously infected.

PFRED a software application for the design, analysis, and visualization of antisense oligonucleotides and siRNA is described. The software provides an intuitive user-interface for scientists to design a library of siRNA or antisense oligonucleotides that target a specific gene of interest. Moreover, the tool facilitates the incorporation of various design criteria that have been shown to be important for stability and potency. PFRED has been made available as an open-source project so the code can be easily modified to address the future needs of the oligonucleotide research community. A compiled version is available for downloading at https://github.com/pfred/pfred-gui/releases/tag/v1.0 as a java Jar file. The source code and the links for downloading the precompiled version can be found at https://github.com/pfred.

International audience; Background: Multimodal analgesia, including a regional technique using perineural catheters (PNCs), is recommended for the treatment of moderate-to-severe acute postoperative pain. Perineural catheters are at risk of bacterial colonisation. In this study, we compared the cutaneous antiseptic efficacy of 2% alcoholic chlorhexidine and povidone-iodine-alcohol for preventing the bacterial colonisation of PNCs in orthopaedic surgery. Methods: We performed a randomised, controlled trial, comparing two cutaneous antisepsis strategies, one based on 2% alcoholic chlorhexidine and the other on povidone-iodine-5% alcohol, for placed PNCs before orthopaedic surgery. The primary endpoint was the incidence of catheter bacterial colonisation (threshold > 1000 colony-forming units/ml). The secondary endpoints were the incidence of catheter-related infections and the adverse effects of the antiseptic solutions. Results: From November 2016 to May 2018, we included 113 patients in this study. The use of alcoholic chlorhexidine was associated with a lower incidence of catheter colonisation (15.5% (n = 9) versus 32.7% (n = 18); OR: 0.28 [0.09-0.77], p = 0.01). No catheter-related infections or adverse effects of antiseptic solutions were observed in either group. The risk factors associated with colonisation were a duration of catheter use ≥ 3 days (p = 0.04) and obesity (p = 0.005). The most frequently identified bacterium was Staphylococcus epidermidis. Conclusion: Skin disinfection with 2% alcoholic chlorhexidine decreases bacterial colonisation rates for placed perineural catheters.

Highlights • COVID-19 pneumonia is at risk of transfer in intensive care unit or death • Hydroxychloroquine+azithromycin seems to improve outcome of admitted patients • We report no major cardiac adverse event of this combination therapy, Introduction Interest of anti-infective agents in COVD-19 showed discrepant results. However, there is no evaluation about the impact in changes of practices on the prognosis over time. Methods Single center, retrospective study, conducted from March 5th to April 25th 2020, in adults hospitalized in a medicine ward for a COVID-19. Patient characteristics were compared between 2 periods (before/after March 19th) considering French guidelines issued by learned societies. Aim of the study was to evaluate how medical care impacted unfavorable outcome, namely admission in intensive care unit (ICU) and/or death. Results One hundred thirty-two patients were admitted, mean age was 59.0 ± 16.3 years, mean CRP level was 84.0±71.1 mg/L, 46% had a lymphocyte count

IntroductionHydroxychloroquine (HCQ) with or without azithromycin is currently still debated as a potential treatment for the COVID-19 epidemic. Some studies showed discrepant results. However, timing for the treatment initiation and its setting (in-hospital or out-patient) are not consistent across studies.MethodsMonocentric retrospective study conducted from 2th March to 17th April 2020, in adults hospitalized in a tertiary hospital for COVID-19. Patients characteristics were compared between groups depending on the therapy received (HCQ/azithromycin taken ≥ 48 hours or other treatment). Outcomes were evaluated from admission, by the need for intensive care unit (ICU) support and/or death. Univariate analyses were performed using non-parametric tests and confirmed by a multiple logistic regression using Pearson correlation test.ResultsAmong 132 patients admitted for COVID-19 in the medicine ward, 45 received HCQ/azithromycin ≥ 48 hours, with a favorable outcome in 91.1% of cases (OR=6.2, p=0.002) versus others regimen (n=87). Groups were comparable at the baseline in terms of age, sex, comorbidities, extend in thoracic imaging, and severity.Among patients that required to be transferred to ICU (n=27) (for mechanical ventilation), median delay for transfer was 2 days (IQR 1-3). We report only 1 patient that presented an adverse event (a prolonged QT interval on EKG) that required to discontinue HCQ.ConclusionThe present study suggests a potential interest of the combination therapy using HCQ/azithromycin for the treatment of COVID-19 in in-hospital patients.

Background Infections caused by multidrug-resistant organisms (MDRO) are emerging worldwide. Physicians are increasingly faced with the question of whether patients need empiric antibiotic treatment covering these pathogens. This question is especially essential among MDRO carriers. We aim to determine the occurrence of MDRO bacteraemia among bacteraemic patients colonized with MDRO, and the associated factors with MDRO bacteraemia among this population. Methods We performed a retrospective monocentric study among MDRO carriers hospitalized with bacteraemia between January 2013 and August 2016 in a French hospital. We compared characteristics of patients with MDRO and non-MDRO bacteraemia. Results Overall, 368 episodes of bacteraemia were reviewed; 98/368 (26.6%) occurred among MDRO carriers. Main colonizing bacteria were extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (40/98; 40.8%), ESBL-producing Klebsiella pneumoniae (35/98; 35.7%); methicillin-resistant Staphylococcus aureus (26/98; 26.5%) and multidrug-resistant Pseudomonas aeruginosa (PA) (12/98; 12.2%). There was no significant difference considering population with MDRO bacteraemia vs. non-MDRO bacteraemia, except for immunosuppression [OR 2.86; p = 0.0207], severity of the episode [OR 3.13; p = 0.0232], carriage of PA [OR 5.24; p = 0.0395], and hospital-acquired infection [OR 2.49; p = 0.034]. In the multivariate analysis, factors significantly associated with MDRO bacteraemia among colonized patient were only immunosuppression [OR = 2.96; p = 0.0354] and the hospital-acquired origin of bacteraemia [OR = 2.62; p = 0.0427]. Conclusions According to our study, occurrence of bacteraemia due to MDRO among MDRO carriers was high. Factors associated with MDRO bacteraemia were severity of the episode and hospital-acquired origin of the bacteraemia. Thus, during bacteraemia among patients colonized with MDRO, if such characteristics are present, broad-spectrum antimicrobial treatment is recommended.

PROs are increasingly used in HCT to capture symptoms, quality of life, and functional status. At the Cleveland Clinic, PROs are systematically collected prior to ambulatory visits and used in routine clinical care to identify patients (pts) with distress in real-time through a data capture initiative called the "Knowledge Program." Instruments include the Patient Health Questionnaire (PHQ-9), National Comprehensive Cancer Network Distress Thermometer (DT), and Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Health (PH) and Mental Health (MH) assessments. There are limited data on the use of these instruments in the HCT population. We evaluated these PRO measures in HCT recipients and their association with post-HCT outcomes. We identified 292 adult pts undergoing first allogeneic HCT from 2015-2018. Of those, 257 had at least one PRO assessment and were included in this analysis. Time intervals evaluated were: pre-HCT (within 3 months [mos]), 0-6 mos, 6-12 mos, 1-2 years (yrs), and 2-5 yrs post HCT. PHQ-9 assesses depression and categorized as minimal (score 0-4), mild (5-9), moderate (10-14), moderately severe (15-19), and severe (20-27). Higher DT scores indicate more distress and categorized as mild (0-3), moderate (4-7), severe (8-10). Lower scores on PROMIS indicate poorer PH or MH respectively. We evaluated PRO data descriptively for each time interval. Pre-HCT scores were analyzed for association with grade 2-4 acute graft-versus-host disease (GVHD), relapse, non-relapse mortality (NRM), and survival. Figure 1 shows boxplots for mean PHQ-9 and DT scores pre- and post-HCT. Mean scores for the PHQ-9 ranged from 1.1 ± 2.4 (SD) occurring >2 yrs post-HCT to 2.4 ± 3.0 pre-HCT. Mean DT scores were overall low, with highest distress (2.0 ± 2.2) seen pre-HCT. Mean scores for PH and MH were similar at each time intervals, with means ranging 47-48 for PH and 49-51 for MH. Higher PHQ-9 pre-HCT was associated with higher NRM (HR 1.21, 95% CI 1.09-1.34, P PROs such as the PHQ-9, DT, and PROMIS have important clinical utility in allogeneic HCT recipients. Routine clinical use of these assessments not only help identify pts with high levels of distress or depression in real-time, they also demonstrate prognostic value for post-HCT survival outcomes.

Resume Objectif L’objectif de ce travail etait d’emettre des recommandations de bonne pratique concernant l’antibioprophylaxie dans le cadre d’un BUD. Materiels et methodes Des recommandations ont ete elaborees par un groupe de pilotage multidisciplinaire avant d’etre validees par une methode de consensus formalisee par un groupe multidisciplinaire de 12 experts (groupe de cotation). Elles ont ensuite ete validees par un groupe de lecture (experts differents du groupe de cotation). Resultats La realisation d’un examen cytobacteriologique des urines (ECBU) avec antibiogramme est recommandee dans les jours precedant le BUD, pour tous les patients (Accord fort). Chez les sujets ne presentant pas de pathologie neurologique, les facteurs de risque d’infection urinaire apres BUD sont l’âge > 70 ans, les infections urinaires iteratives et un residu post-mictionnel > 100 ml. Chez les sujets ayant une pathologie neurologique, les facteurs de risque d’infection urinaire apres BUD sont les infections urinaires iteratives, le reflux vesico-ureteral, une pression vesicale premictionnelle elevee > 40 cmH2O. Si l’ECBU pre-BUD est sterile, en l’absence de facteur de risque d’infection urinaire, aucune antibioprophylaxie n’est recommandee (Accord fort). Si l’ECBU pre-BUD est sterile mais qu’il existe un ou plusieurs facteur(s) de risque d’infection urinaire, une antibioprophylaxie peut etre, ou non, proposee. Si une antibioprophylaxie est decidee, il est recommande de prescrire une prise unique de fosfomycine-trometamol (3 g par voie orale), deux heures avant le BUD (Accord fort). En cas de colonisation urinaire pre-BUD, une antibiotherapie peut etre, ou non, prescrite (indecision). Si une antibiotherapie est proposee, elle doit etre adaptee a l’antibiogramme de la (ou des) bacterie(s) identifiee(s) (Accord fort). Elle doit etre debutee la veille de l’examen, et etre interrompue apres celui-ci (Accord fort) (sauf pour la fosfomycine-trometamol pour laquelle une seule prise la veille du BUD est necessaire et suffisante) (Accord fort). En cas d’infection urinaire pre-BUD, celle-ci doit etre traitee et l’examen doit etre reporte (Accord fort). Les regles proposees ici n’ont pas a etre modifiees chez les patients porteurs de prothese de hanche ou de genou (Accord fort). Par ailleurs, aucune prophylaxie de l’endocardite infectieuse n’est necessaire, y compris chez les patients porteurs de cardiopathie valvulaire a haut risque (Accord fort). Conclusion Ces nouvelles recommandations devraient contribuer a harmoniser les pratiques et a limiter l’exposition aux antibiotiques. Niveau de preuve 4.

Advance care planning (ACP) includes having conversations with loved ones and health care providers regarding health care wishes in various circumstances. It also includes completing advance directives such as a health care power of attorney and living will as well as preparing a will for finances and estate planning. This process helps patients make plans for their future health care goals and is particularly useful when they are unable to make their own medical decisions. ACP in hematopoietic stem-cell transplant (HSCT) recipients can be particularly challenging, given the treatment's significant morbidity and mortality yet curative potential. (Wang, W. S. et al, 2017). Recognizing this challenge, the Cleveland Clinic Blood and Marrow Transplant Program created a multi-disciplinary committee of social workers, physicians, advanced practice providers (APPs), nurse coordinators and nurses to address the gap in ACP for HSCT recipients to improve the overall quality of care provided to patients and families. As part of this initiative, we created a survey to assess perceptions of ACP within the program and comfort level. A confidential, fourteen question survey was created and administered to providers. The survey included questions on: 1) perceptions of the current approach to ACP in our program, 2)the comfort level of the provider in discussing goals of care, prognosis, and code status, 3) provider's current knowledge base and prior training. Open-ended feedback was also elicited. A total of 38 responded to the survey including 15 physicians, 7 APPs, 8 nurse coordinators, 3 social workers, and 3 inpatient nurses. The years of experience ranged from 0.5 to 21 plus years. The majority of providers felt our current approach to ACP was very good (n=11) or good (n=16). While the perception was overall favorable, less than half of the providers (n=14) felt we had adequate training to have goals of care discussions. Only 7 providers report having formal training in goals of care. Despite not having formal training, nearly all (n=37) thought it was important. The survey also assessed comfort level of initiating goals of care discussions, prognosis, and code status. The majority of providers reported feeling comfortable in all these areas: initiating goals of care n=25 (Figure 1), prognosis n=20 (Figure 2), and code status n=22 (Figure 3). Of the 21 who were comfortable initiating goals of care discussions 21 reported initiating these conversations in their clinical practice. Many providers (n= 37) also felt it was appropriate for all members of the team to initiate these discussions. ACP is an important part of HSCT multi-disciplinary care of patients and their families. This survey demonstrates our institution's perceptions of ACP, need for formal training to improve comfort levels, and highlights the need for ACP in HSCT to be approached by a multi-disciplinary team effort.

Background In France, Carbapenem-Resistant Enterobacteriaceae (CRE) and Vancomycin-Resistant Enterococci (VRE) are considered as Extensively Drug-Resistant (XDR) bacteria. Their management requires reinforcement of hospital’s hygiene policies, and currently there is few consistent data concerning the spontaneous decolonization in XDR colonized patients. Our aim is to study the natural history of decolonization of XDR carriers over time in a hospital setting in a low prevalence country. Material and methods Retrospective multicenter study over 2 years (2015–2016) in 2 different tertiary care hospital sites and units having an agreement for permanent cohorting of such XDR carriers. We gathered the type of microorganisms, risk factors for colonization and rectal swabs from patient’s follow-up. We also evaluated patient care considering isolation precautions. Results We included 125 patients, aged 63+/−19y, including 72.8% of CRE (n = 91), 24.8% of VRE (n = 31) and 2.4% (n = 3) co-colonized with CRE and VRE. CRE were mainly E. coli (n = 54), K. pneumoniae (n = 51) and E. cloacae (n = 6). Mechanisms of resistance were mainly OXA-48 (n = 69), NDM-1 (n = 11), OXA-232 (n = 8) and KPC (n = 3). Prior antibiotic therapy was reported in 38.4% (n = 48) of cases. Conversely, 17.6% (n = 22) received antibiotics during follow-up. Spontaneous decolonization occurred within the first 30 days in 16.4% (n = 19/116) of cases and up to 48.2% after day-90 with a median follow-up of 96 days (0–974). We estimated that XDR carriage was associated with a larger care burden in 13.6% (n = 17) of cases, especially due to a prolongation of hospitalization of 32.5 days (15–300). Conclusions Our study shows that spontaneous decolonization is increasing over time (up to 48.2%). We can regret that only few patients underwent screening after 1 year, emphasizing the need for more monitoring and prospective studies.

Summary Background Whether antibiotic rotation strategies reduce prevalence of antibiotic-resistant, Gram-negative bacteria in intensive care units (ICUs) has not been accurately established. We aimed to assess whether cycling of antibiotics compared with a mixing strategy (changing antibiotic to an alternative class for each consecutive patient) would reduce the prevalence of antibiotic-resistant, Gram-negative bacteria in European intensive care units (ICUs). Methods In a cluster-randomised crossover study, we randomly assigned ICUs to use one of three antibiotic groups (third-generation or fourth-generation cephalosporins, piperacillin–tazobactam, and carbapenems) as preferred empirical treatment during 6-week periods (cycling) or to change preference after every consecutively treated patient (mixing). Computer-based randomisation of intervention and rotated antibiotic sequence was done centrally. Cycling or mixing was applied for 9 months; then, following a washout period, the alternative strategy was implemented. We defined antibiotic-resistant, Gram-negative bacteria as Enterobacteriaceae with extended-spectrum β-lactamase production or piperacillin–tazobactam resistance, and Acinetobacter spp and Pseudomonas aeruginosa with piperacillin–tazobactam or carbapenem resistance. Data were collected for all admissions during the study. The primary endpoint was average, unit-wide, monthly point prevalence of antibiotic-resistant, Gram-negative bacteria in respiratory and perineal swabs with adjustment for potential confounders. This trial is registered with ClinicalTrials.gov, number NCT01293071. Findings Eight ICUs (from Belgium, France, Germany, Portugal, and Slovenia) were randomly assigned and patients enrolled from June 27, 2011, to Feb 16, 2014. 4069 patients were admitted during the cycling periods in total and 4707 were admitted during the mixing periods. Of these, 745 patients during cycling and 853 patients during mixing were present during the monthly point-prevalence surveys, and were included in the main analysis. Mean prevalence of the composite primary endpoint was 23% (168/745) during cycling and 22% (184/853) during mixing (p=0·64), yielding an adjusted incidence rate ratio during mixing of 1·039 (95% CI 0·837–1·291; p=0·73). There was no difference in all-cause in-ICU mortality between intervention periods. Interpretation Antibiotic cycling does not reduce the prevalence of carriage of antibiotic-resistant, Gram-negative bacteria in patients admitted to the ICU. Funding European Union Seventh Framework Programme.

The number of allogeneic hematopoietic cell transplantation (HCT) survivors is projected to increase and guidelines for screening and management of late effects have been established. Although the value of a systematic process for the long-term care of HCT survivors and screening of late effects is increasingly recognized, best practices for the implementation of survivorship care delivery has not been well described. In October 2016, we established a Survivorship Clinic for allogeneic HCT recipients in our Blood and Marrow Transplant (BMT) Program. A consultative model aimed to augment care provided by the patient's primary transplant and primary care physician was felt to best fit our program's needs. Patients (pts) are seen by a Nurse Practitioner (NP) and social worker (SW) at day 100 and 1 year visits. Visits include a comprehensive history and physical, symptom assessment, and graft-versus-host disease evaluation, as well as review and provision of a treatment summary and care plan. 1-year recommended assessments include: bone density scan, vitamin D, TSH, lipid panel, HbA1c, Ferritin, pulmonary function tests (PFTs), ophthalmic exam, and mammogram and pelvic exam (women). We performed a formal review of follow up with recommended screening guidelines among pts seen in our Survivorship Clinic from 2016-2018. Since its establishment, 161 pts received allogeneic HCT in our Program, of whom 131 pts have been seen at day 100 and 42 have been seen at 1-year. Patients not seen at day 100 were due to relapse, death or acute illness where they were not able to attend the clinic visit. Among pts seen at day 100 but not at 1 year, 7 were international, 2 were deferred due to relapse, 12 died prior to one year follow up, one transferred care to another facility and 67 have not reached their 1-year follow up. Of 42 pts seen at 1 year, all have received a complete treatment summary and care plan at both day 100 and 1 year. 35 pts had an evaluation and follow up with their transplant SW for psychosocial assessment. 41 pts had a bone density scan completed. All 42 pts completed a screening TSH, vitamin D, lipid panel, HbA1c, Ferritin, and PFTs. 36 saw ophthalmology for a yearly exam. Of the 20 women seen at 1 year, all 20 had mammograms done and 19 had gynecologic exams. In summary, this review of our NP run BMT survivorship clinic demonstrates feasibility and a high rate of adherence to recommended late effects screening practices for HCT survivors. As the survivorship program continues to grow, further integration of patient-reported outcomes and interventional research on late effects to improve the well-being of long-term survivors is planned.

Advances in allogeneic hematopoietic cell transplantation (HCT) have led to significantly improved day 100 survival over time. Longer-term (≥1 year) survival, however, has not changed significantly. In an effort to improve outcomes and identify patients (pts) at higher risk for 1-year mortality, we created a day 100 risk assessment tool. The Day 100 Risk Assessment tool includes 11 items: HCT-co-morbidity index, distance from transplant center, performance status (PS) at day 100, GVHD requiring systemic corticosteroids, infection requiring intravenous antimicrobials, caregiver support, poor coping skills/motivation, substance abuse, poor health literacy/access, medication compliance, and “other” concerns from the care team. Pts were given a point for each identified factor and categorized as low risk (score 0-2) or high risk (score≥3). High risk pts were targeted for closer follow up beyond 100 days. Cox regression was used to identify risk factors for overall survival (OS) within the first year after HCT. Between 11/2015-6/2018, 208 pts underwent allogeneic HCT and 161 pts survived without relapse at day 100 (Table). Median follow up is 12 months (range 3-33). 1-year OS for low-risk pts was significantly better than for high-risk pts (82% vs 68%, P=0.006; Figure). Multivariable analysis accounting for both pre-transplant and Day 100 risk factors identified older age (≥55), (HR 2.92, 95% CI 1.21-7.08, P=0.017); high disease risk (HR 2.93, 95% CI 1.34-6.39, P=0.007), and day 100 high-risk score (HR 2.29, 95% CI 1.17-4.48, P=0.015) as significant factors for poor OS. Univariate analysis of individual components of the day 100 risk score identified poor PS at day 100, infection, and caregiving concerns as significant variables, P In sum, we developed a Day 100 Risk Assessment tool and identified factors occurring within the first 100 days beyond traditional pre-transplant variables which significantly impact longer-term outcome. Targeted close follow up of these higher risk pts may help to improve survival of this at-risk population.

We have read with great interest the report by Marshall et al. regarding the efficacy of the combination of ceftazidime-avibactam (CAZ-AVI) and aztreonam (ATM) against metallo-β-lactamase-producing Enterobacteriaceae ([1][1]). These results confirm our experience with two patients treated with CAZ

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is frequently performed in patients with hematologic malignancies. ASCT can result in significant nausea, pain, and discomfort. Supportive care has improved, and pharmacologic therapies are frequently used, but with limitations. Music has been demonstrated to improve nausea and pain in patients undergoing chemotherapy, but little data are available regarding the effects of music therapy in the transplantation setting. In a prospective study, patients with lymphoma or multiple myeloma undergoing ASCT were randomized to receive either interactive music therapy with a board-certified music therapist or no music therapy. The music therapy arm received 2 music therapy sessions on days +1 and +5. Primary outcomes were perception of pain and nausea measured on a visual analog scale. Secondary outcomes were narcotic pain medication use from day −1 to day +5 and impact of ASCT on patient mood as assessed by Profile of Mood States (POMS) on day +5. Eighty-two patients were enrolled, with 37 in the music therapy arm and 45 in the no music therapy arm. Patients who received MT had slightly increased nausea by day +7 compared with the no music therapy patients. The music therapy and no music therapy patients had similar pain scores; however, the patients who received music therapy used significantly less narcotic pain medication (median, 24 mg versus 73 mg; P = .038). Music therapy may be a viable nonpharmacologic method of pain management for patients undergoing ASCT; the music therapy patients required significantly fewer morphine equivalent doses compared with the no music therapy patients. Additional research is needed to better understand the effects of music therapy on patient-perceived symptoms, such as pain and nausea.

Resume L’accreditation des laboratoires par le Comite francais d’accrediation (Cofrac) est desormais obligatoire en France pour realiser les analyses de legionelles dans l’eau. Cet article decrit les differentes etapes qui nous ont permis d’aboutir a l’accreditation de nos laboratoires, les ecueils a surmonter et l’ensemble des processus a maitriser : habilitation et formation des personnels, qualite des locaux et des equipements, metrologie, prelevements et echantillonnages, qualite des essais, validation de methode, maitrise de la phase post-analytique. La visite initiale et les visites de suivi du Cofrac seront egalement decrites.

Legionella pneumophila , a bacterium that replicates within aquatic amoebae and persists in the environment as a free-living microbe, is the causative agent of Legionnaires' disease. Among the many Legionella species described, L. pneumophila is associated with 90% of human disease, and within the 15 serogroups (Sg), L. pneumophila Sg1 causes more than 84% of Legionnaires' disease worldwide. Thus, rapid and specific identification of L. pneumophila Sg1 is of the utmost importance for evaluation of the contamination of collective water systems and the risk posed. Previously we had shown that about 20 kb of the 33-kb locus carrying the genes coding for the proteins involved in lipopolysaccharide biosynthesis (LPS gene cluster) by L. pneumophila was highly specific for Sg1 strains and that three genes ( lpp0831 , wzm , and wzt ) may serve as genetic markers. Here we report the sequencing and comparative analyses of this specific region of the LPS gene cluster in L. pneumophila Sg6, -10, -12, -13, and -14. Indeed, the wzm and wzt genes were present only in the Sg1 LPS gene cluster, which showed a very specific gene content with respect to the other five serogroups investigated. Based on this observation, we designed primers and developed a classical and a real-time PCR method for the detection and simultaneous identification of L. pneumophila Sg1 in clinical and environmental isolates. Evaluation of the selected primers with 454 Legionella and 38 non- Legionella strains demonstrated 100% specificity. Sensitivity, specificity, and predictive values were further evaluated with 209 DNA extracts from water samples of hospital water supply systems and with 96 respiratory specimens. The results showed that the newly developed quantitative Sg1-specific PCR method is a highly specific and efficient tool for the surveillance and rapid detection of high-risk L. pneumophila Sg1 in water and clinical samples.

Background: Allo HCT candidates undergo comprehensive evaluations including psychosocial assessment, although there are no validated tools to objectively assess psychosocial status prior to transplant. PACT, originally developed to address psychosocial risks in solid organ transplant recipients, has been evaluated by our group in allo HCT patients (Foster et al, BMT, 2009). It consists of 8 subscales which are scored from 1 to 5 (support stability, support availability, psychopathology, risk for psychopathology, health lifestyle, drug and alcohol use, compliance, and relevant knowledge). A final PACT score (range 0-4) provides an overall impression of a patient's suitability for transplantation. Patients and Methods: This retrospective cohort study reviewed 404 adult allo HCT cases between 2003 and 2014 at Cleveland Clinic to identify predictors of adverse psychosocial status prior to allo HCT as determined by PACT. We then studied the association of PACT scores with allo HCT outcomes. Social workers generated a PACT score based on a comprehensive assessment of the patient. Median age of the study population was 50 (range 18-73) years, patients were 46% female, 11% non-White, 20% rural residents, and had mainly AML (41%) or MDS (18%). Majority of patients received HLA matched (84%) unrelated donor (55%) bone marrow grafts (55%) using myeloablative conditioning (78%). Results: Final PACT rating was poor/borderline (score 0/1) in 5% (n= 21), acceptable (score 2) in 22% (87), good (score 3) in 44% (177), and excellent (score 4) in 29% (119) of recipients. In multivariable ordinal logistic regression, higher PACT score at pre-HCT assessment was associated with White race (OR 2.95, [95% CI 1.56-5.58], p Conclusion: Non-White race, lack of a related donor, and lower QOL are associated with adverse psychosocial risk as measured by PACT prior to allo HCT. Low "relevant knowledge" and "final PACT" ratings were associated with NRM and suggest vulnerable populations. PACT can be effectively used as part of a comprehensive psychosocial assessment for identifying patients who may require additional psychological and social resources to help them navigate the transplant process. Disclosures Lee: Kadmon: Research Funding; Onyx: Research Funding; Amgen: Consultancy, Research Funding; Mallinckrodt: Honoraria; Pfizer: Consultancy; Takeda: Research Funding; Incyte: Consultancy. Majhail:Atara: Honoraria; Anthem, Inc.: Consultancy; Incyte: Honoraria.

Background: HCT is physically and psychologically challenging and patients are prone to QoL impairments. AYAs are a unique population that faces hurdles due to dynamic changes in several aspects of their life, and may be particularly prone to QoL issues during HCT. The aim of this study was to determine if QoL differences exist between AYA and older adult HCT recipients pre- and post-HCT. Additionally, we aimed to determine if there has been a change in QoL for AYA transplant recipients in recent years, as more focus has been placed on supporting this unique population. Methods: QoL data were collected prospectively pre-HCT (baseline [BL]) and in follow-up post-transplant on patients undergoing HCT from Jun 2003 through Dec 2017 at Cleveland Clinic. Autologous HCT recipients are followed routinely through day +42 post-transplant, while allogeneic recipients are followed through at least one year or more. QoL was self-reported by patients using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) questionnaire. FACT-BMT consists of five domain scores (Physical Wellbeing [PWB], Social Wellbeing [SWB], Emotional Wellbeing [EWB], Functional Wellbeing [FWB], and Additional Concerns [AC]) and two summary scores (trial outcome index [TOI, PWB+FWB+AC], and Total FACT Score. Scores were compared for younger AYA (age 15-29 years), older AYA (age 30-39 years) and older adults (age 40-60 years). We excluded patients >60 years from analysis as this group may have their own unique challenges. Repeated measures analysis of variance was used to assess differences among age groups and among time points. Pearson correlation (r) was used to determine if BL QOL had improved from 2003-2017 in AYA cohort. Separate analyses were performed for autologous and allogeneic cohorts. Results: Autologous HCT cohort included 128 AYA patients (56 younger AYA) and 355 older adults, and allogeneic HCT cohort included 136 AYA patients (76 younger AYA) and 295 older adults Autologous patients in all three groups were similar for baseline characteristics except for diagnosis (table 1). Among allogeneic patients similar rates of graft-versus host disease were seen for all three groups, and baseline characteristics were similar except for ECOG performance status (table 1). Among autologous recipients, no single QoL domain or composite score differed among the three age groups at baseline or at day +42 post-HCT (Figure 1a). In all age groups, QoL improved from baseline to D+42 in autologous HCT recipients (mean Total Score 149 vs. 152, p=0.001). Similarly, among the allogeneic HCT recipients, no single QoL domain or composite score differed among the three age groups at baseline, day +100, +180, or +365 post-HCT (Figure 1b). Among all patients compared to BL (mean 146), total FACT score improved at day +180 (150, p=0.022) and +365 (152, p=0.005), but not at day 100 (145, p=0.57). Among autologous recipients, none of the BL FACT domains improved over time since 2003. In contrast, AYA allogeneic recipients also had no significant change in BL scores since 2003 for PWB, SWB, EWB, FWB, however there was improvement in AC (r=0.26, p=0.003, TOI (r=0.23, p=0.008), and total FACT score (r=0.19, p=0.03). Conclusions: AYA HCT recipients do not have inferior QoL compared to older adults in the first 42 days after autologous HCT and the first year after allogeneic HCT. Interestingly, QoL improvements in AYA patients have occurred in recent years for allogeneic but not autologous patients. Improvements in QoL of allogeneic patients is driven by the AC domain, which addresses multiple psychosocial aspects which have been emphasized in recent years. Continued efforts to tailor treatment and support for AYA HSCT recipients is critical to improving outcomes. Disclosures Advani: Glycomimetics: Consultancy; Novartis: Consultancy; Amgen: Research Funding; Pfizer: Honoraria, Research Funding. Majhail:Atara: Honoraria; Anthem, Inc.: Consultancy; Incyte: Honoraria.

Despite advances in identifying genetic markers of high risk patients and the availability of genetic testing, it remains challenging to efficiently identify women who are at hereditary risk and to manage their care appropriately. HughesRiskApps, an open-source family history collection, risk assessment, and Clinical Decision Support (CDS) software package, was developed to address the shortcomings in our ability to identify and treat the high risk population. This system is designed for use in primary care clinics, breast centers, and cancer risk clinics to collect family history and risk information and provide the necessary CDS to increase quality of care and efficiency. This paper reports on the first implementation of HughesRiskApps in the community hospital setting. HughesRiskApps was implemented at the Newton-Wellesley Hospital. Between April 1, 2007 and March 31, 2008, 32,966 analyses were performed on 25,763 individuals. Within this population, 915 (3.6%) individuals were found to be eligible for risk assessment and possible genetic testing based on the 10% risk of mutation threshold. During the first year of implementation, physicians and patients have fully accepted the system, and 3.6% of patients assessed have been referred to risk assessment and consideration of genetic testing. These early results indicate that the number of patients identified for risk assessment has increased dramatically and that the care of these patients is more efficient and likely more effective.

The self-reporting of cancer history is becoming increasingly important, as it frequently guides medical decision-making. We studied the accuracy of personal cancer history using a self-administered questionnaire, comparing the results with the Tumor Registry at our institution. Among 39,662 records, we identified 3614 women with a single cancer in the Tumor Registry who reported none or one cancer on their questionnaire. The sensitivity in self-reporting cancers was 85.7%, ranging from 92.1% for breast cancer to 42.9% for leukemia. The accuracy for breast cancer and Hodgkin's Lymphoma was significantly better than other cancers (p=0.00027, CI: 1.4-3.88). Analysis of patient's characteristics showed that Caucasians reported breast cancer more accurately than Asian/Pacific Islanders (p=0.008), and those with Jewish ancestry more accurately than non-Jewish (p=0.0435). These results will help us to improve data collection and thus improve medical decision-making.

Staphylococcus aureus nasal carriage is a risk factor for subsequent infection. Estimates of colonization duration vary widely among studies, and factors influencing the time to loss of colonization, especially the impact of antibiotics, remain unclear. We conducted a prospective study on patients naive for S. aureus colonization in 4 French long-term-care facilities. Data on nasal colonization status and potential factors for loss of colonization were collected weekly. We estimated methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) colonization durations using the Kaplan-Meier method and investigated factors for loss of colonization using shared-frailty Cox proportional hazards models. A total of 285 S. aureus colonization episodes were identified in 149 patients. The median time to loss of MRSA or MSSA colonization was 3 weeks (95% confidence interval, 2 to 8 weeks) or 2 weeks (95% confidence interval, 2 to 3 weeks), respectively. In multivariable analyses, the methicillin resistance phenotype was not associated with S. aureus colonization duration ( P = 0.21); the use of fluoroquinolones (hazard ratio, 3.37; 95% confidence interval, 1.31 to 8.71) and having a wound positive for a nonnasal strain (hazard ratio, 2.17; 95% confidence interval, 1.15 to 4.07) were associated with earlier loss of MSSA colonization, while no factor was associated with loss of MRSA colonization. These results suggest that the methicillin resistance phenotype does not influence the S. aureus colonization duration and that fluoroquinolones are associated with loss of MSSA colonization but not with loss of MRSA colonization.

Quality of life (QOL) is an important outcome for hematopoietic cell transplantation (HCT) recipients. Whether pre-HCT QOL adds prognostic information to patient and disease related risk factors has not been well described. We investigated the association of pre-HCT QOL with relapse, non-relapse mortality (NRM), and overall mortality after allogeneic HCT. From 2003 to 2012, the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale instrument was administered before transplantation to 409 first allogeneic HCT recipients. We examined the association of the three outcomes with (1) individual QOL domains, (2) trial outcome index (TOI) and (3) total score. In multivariable models with individual domains, functional well-being (hazard ratio (HR) 0.95, P=0.025) and additional concerns (HR 1.39, P=0.002) were associated with reduced risk of relapse, no domain was associated with NRM, and better physical well-being was associated with reduced risk of overall mortality (HR 0.97, P=0.04). TOI was not associated with relapse or NRM but was associated with reduced risk of overall mortality (HR 0.93, P=0.05). Total score was not associated with any of the three outcomes. HCT-comorbidity index score was prognostic for greater risk of relapse and mortality but not NRM. QOL assessments, particularly physical functioning and functional well-being, may provide independent prognostic information beyond standard clinical measures in allogeneic HCT recipients.

Objectives To perform the first multinational Enterobacter cloacae clonality study, using the MLST scheme newly developed in Japan. Methods The analysis included 195 rectal carriage E. cloacae isolates resistant to expanded-spectrum cephalosporins (ESCs), collected from patients in 12 hospital units across Europe and Israel. All of the isolates were typed by PFGE and 173 isolates were subjected to MLST. ESC resistance was analysed phenotypically; genes encoding ESBLs and carbapenemases were identified by PCR and sequencing. Results MLST distinguished 88 STs, which correlated with the PFGE data. PFGE was more discriminatory, producing 129 pulsotypes (169 patterns). Numerous STs were observed in several countries each. The most widespread were ST66, ST78, ST108 and ST114, each having at least 10 isolates from three to five countries, diversified into multiple pulsotypes, with clusters of related isolates in one or more centres. Analysis of the STs against the MLST database revealed several epidemic clonal complexes, such as those with central genotypes ST74 (including ST78) or ST114 (including ST66). ESC resistance was equally related to overexpression of the AmpC cephalosporinase and to ESBL production. Among ESBL producers some spreading subclones were identified, including specific ST66, ST78 and ST114 pulsotypes, associated with CTX-M-15 production. Several isolates produced carbapenemase VIM-1 or KPC-2. Conclusions Together with the information available in the MLST database, our results suggest that, like Escherichia coli and Klebsiella pneumoniae, E. cloacae harbours clonal lineages of increased epidemic potential that may be associated with resistance spread.

Resume La legionellose nosocomiale represente 9% des cas de legionellose en France. La prevention de la legionellose nosocomiale repose sur une conception, un entretien et une maintenance des reseaux d'eau sanitaire et des tours aerorefrigerantes qui prennent en compte ce risque sanitaire. La prise en charge des patients immunodeprimes a haut risque de legionellose doit etre adaptee. Le diagnostic repose essentiellement sur la recherche des antigenes urinaires, test rapide; la culture de prelevement d'origine pulmonaire, qui reste le diagnostic de reference; la serologie peu specifique mais qui permet d'identifier des cas tardivement; la PCR, methode d'avenir qui reste a developper.

Background. Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization is a well-established riskfactor for subsequent infection and a key event in interindividual transmission. Some studies have showed an asso-ciation between fluoroquinolones and MRSA colonization or infection. The present study was performed to identifyspecific risk factors for MRSA acquisition in long-term care facilities (LTCFs).Methods. A prospective cohort of patients naive for S. aureus colonization was established and followed(January 2008 through October 2010) in 4 French LTCFs. Nasal colonization status and potential risk factorswere assessed weekly for 13 weeks after inclusion. Variables associated with S. aureus acquisition were identifiedin a nested-matched case-case-control study using conditional logistic regression models. Cases were patientswho acquired MRSA (or methicillin-sensitive S. aureus [MSSA]). Patients whose nasal swab samples were alwaysnegative served as controls. Matching criteria were center, date of first nasal swab sample, and exposure time.Results. Among451includedpatients,76MRSAcaseswerematchedto207controlsand112MSSAcasesto208controls. Multivariable analysis retained fluoroquinolones (odds ratio, 2.17; 95% confidence interval, 1.01–4.67),male sex (2.09; 1.10–3.98), and more intensive care at admission (3.24; 1.74–6.04) as significantly associated withMRSA acquisition, and body-washing assistance (2.85; 1.27–6.42) and use of a urination device (1.79; 1.01–3.18)as significantly associated with MSSA acquisition.Conclusions. OurresultssuggestthatfluoroquinolonesareariskfactorforMRSAacquisition.Controlmeasuresto limit MRSA spread in LTCFs should also be based on optimization of fluoroquinolone use.Keywords. methicillin-resistantStaphylococcusaureus;fluoroquinolone;case-case-controlstudy;long-termcarefacility; acquisition.Staphylococcus aureus is a commensal organism colo-nizing several sites in the human body, especially theanteriornares.ThisGram-positivebacteriumisrespon-sible for numerous infections including skin infections,bacteremia or respiratory diseases. Notably, 30%–50%of healthy adults are colonized by S. aureus, and nasalcolonization is known tobe an important risk factor forsubsequentinfection[1,2],withinfectionrateshigherincarriers than noncarriers [3–5]and individuals usually

Resume Les techniques d'epidemiologie moleculaire sont des outils precieux lors de l'investigation autour d'un ou plusieurs cas de legionellose. En effet, Legionella pneumophila est une bacterie largement presente dans l'environnement aquatique et sa seule presence dans une eau ne permet pas a elle seule d'identifier la source de contamination. Plusieurs techniques sont utilisees : typage plasmidique, ribotypage, polymorphisme de restriction de l'ADN, electrophorese en champ pulse, PCR utilisant des amorces arbitraires, techniques de digestion-amplification, sequencage. Elles doivent etre associees a une enquete epidemiologique detaillee et ne peuvent etre appliquees dans une region donnee qu'apres avoir ete validees sur un grand nombre de souches non reliees epidemiologiquement.

Summary The ubiquity of Legionella pneumophila in aquatic habitats means that epidemiological evaluation is important for the investigation and control of nosocomial outbreaks of legionellosis. Pulsed-field gel electrophoresis (PFGE) of chromosomal DNA following digestion with SfiI is considered to be one of the most discriminative methods for detecting DNA polymorphisms amongst L. pneumophila serogroup 1 (Lp1) isolates. This paper describes an arbitrarily primed PCR (AP-PCR) method with three different primers (20-mers) for detecting DNA polymorphisms of Lp1 isolates. The AP-PCR assay was compared with PFGE analysis. Both experimental methods were found to have good discriminatory power (discrimination index of 98% and 94.3%, respectively) with 27 unrelated isolates from different geographical areas collected between 1987 and 1997. Furthermore, when the AP-PCR was used in the epidemiological investigation of nosocomial cases of infection, convergent results with the three primers allowed an epidemiological link to be established between isolates from patients and their environment. The AP-PCR method, which is rapid and easy to perform, gave results at least as discriminatory as those obtained with the PFGE method and is proposed for use in the molecular typing of Lp1 outbreaks.

Concentrates of late stage parasites of the gametocyte-forming clone HB-3 were mixed with blood rich in reticulocytes from anemic patients, or with normal control blood, and kept under culture conditions for 4 days. Significantly more gametocytes were always formed in the reticulocyte-rich blood than in the control. This was true whether the anemic blood supported a larger asexual parasitemia than the control, or a lower one, or the same and without regard to the cause of the anemia. Gametocytes as a percentage of asexual forms were up to 10 times higher in reticulocyte-rich blood than in normal blood.

We show here that αG-Phila.2βC2 has an increased rate of crystal nucleation compared to α2 βC2 (HbC). We conclude from this finding that position α68, the mutation site of αG-Phila.2 β2 (HbGPhiladelphia), is a contact site in the crystal of HbC. In addition, that HbS enhances HbC crystallization (additive to the effect of αG-Phila, as shown here) and that αG-Phila. inhibits polymerization of HbS are pathogenically relevant previously known facts. All of these findings help explain the phenotype of an individual simultaneously heterozygous for the βS, βC, and the αG-Phila. genes (SCα-G Philadelphia disease). This disease is characterized by a mild clinical course, abundant circulating intraerythrocytic crystals, and increased folded red cells. This phenotype seems to be the result of increased crystallization and decreased polymerization brought about by the opposite effects of the gene product of the αG-Phila. gene on the βC and βS gene products. Some of the intraerythrocytic crystals in this syndrome are unusually long and thin, resembling sugar canes, unlike those seen in SC disease. The mild clinical course associated with increased crystallization implies that, in SC disease, polymerization of HbS is pathogenically more important than the crystallization induced by βC chains. The SCα-G Philadelphia disease is an example of multiple hemoglobin chain interactions (epistatic effect among globin genes) creating a unique phenotype.