Littérature scientifique sur le sujet « Montefiore family »

This Practice Note describes the implementation of a partnership between child welfare and substance use providers in New York City, with the aim of supporting cross-systems collaboration and improving outcomes for dually involved families. Specifically, this report focuses on improving both coordination and communication between a preventive child welfare service provider (Montefiore Family Treatment & Rehabilitation Program), an outpatient substance abuse treatment provider (Montefiore Division of Substance Abuse), and the local department of social services (New York City Administration for Children’s Services). This article identifies general challenges with collaboration, describes how this collaboration was created and implemented in New York City, and provides guidance for other entities that are attempting to create similar collaborations.

This paper outlines a study of surnames used by various Jewish groups in the Land of Israel for Ashkenazic Jews, prior to the First Aliyah (1881), and for Sephardic and Oriental Jews up to the end of the 1930s. For the 16th–18th centuries, the surnames of Jews who lived in Jerusalem, Safed, Tiberias, and Hebron can be mainly extracted from the rabbinic literature. For the 19th century, by far the richest collection is provided by the materials of the censuses organized by Moses Montefiore (1839–1875). For the turn of the 20th century, data for several additional censuses are available, while for the 1930s, we have access to the voter registration lists of Sephardic and Oriental Jews of Jerusalem, Safed, and Haifa. All these major sources were used in this paper to address the following questions: the use or non-use of hereditary family names in various Jewish groups, the geographic roots of Jews that composed the Yishuv, as well as the existence of families continuously present in the Land of Israel for many generations.

Abstract The regulation of cell volume is important for the maintenance of integrity in all cells and is especially critical for the highly specialized red blood cell (RBC) which must withstand pressure changes within the vasculature and remain deformable to traverse small vessels. Disorders that interfere with volume homeostasis result in the premature destruction of RBCs. One protein that appears to play a prominent role in RBC hydration is the recently described nonselective cation channel PIEZO1 which is involved in mechanotransduction. Mutations of PIEZO1 have been associated with an autosomal dominant form of hereditary hemolytic anemia (HHA) characterized by RBC dehydration known as hereditary xerocytosis (HX) (Zarychanski et al., Blood 2012;120:1908). There is evidence that PIEZO1 may also be responsible for a channel activity that participates in the dehydration of sickle cells which exacerbates sickling and vaso-occlusive events in patients with Sickle Cell Disease (reviewed in Gallagher, Curr Opin Hematol 2013, 20:201). Using a Next-Generation sequencing panel containing 27 hemolytic anemia associated genes, we identified and characterized a novel PIEZO1 mutation p.L2023V which results in delayed channel inactivation and a dehydrated RBC phenotype. This single amino acid substitution at a highly conserved site was detected in the heterozygous state in a 15 year old Caucasian young man (CQ15) with chronic hemolysis well compensated with reticulocytosis, along with heterozygosity for the SLC4A1 p.E40K mutation known as band 3 Montefiore. Hematologic characteristics included macrocytosis, elevated MCHC, and a smear showing occasional stomatocytes. Several family members also had hemolysis and jaundice and were given a diagnosis of hereditary pyropoikilocytosis prior to our evaluation. The L2023V mutation was considered possibly damaging by the PolyPhen-2 algorithm with a score of 0.777. The mother was heterozygous for the PIEZO1 L2023V mutation while the father carried the band 3 Montefiore mutation. Ektacytometry was used to evaluate RBC deformability; the mother's RBCs had a profile of classic xerocytosis with decreased Omin and Ohyp, the father had a very mild spherocytosis profile, while the patient's RBCs had mixed ektacytometry characteristics with decreased Ohyp and an intermediate Omin (Figure 1A). Intracellular cation values determined by flame emission spectroscopy for CQ15 and his mother demonstrated K+ loss. The mutation p.L2023V is located at a site predicted to be at the border between membrane and cytoplasm in the carboxy terminal part of the protein, similar to the previously described p.R2456H mutation in a kindred with HX (Zarychanski et al., 2012). To enable detailed physiologic study of the L2023V mutation, we prepared an HEK293 cell line with a stable, single copy integrant of the variant with an inducible promoter. Whole cell patch clamp studies were performed on HEK293 cells expressing wild type PIEZO1 and PIEZO1 L2023V. Traces of mechanically activated currents were recorded from the cells and were normalized to peak current (Figure 1B). The inactivation time constant tau (in ms) was determined from mono-exponential fits for wild type and mutant PIEZO1 channels. The difference in average inactivation time between wild type PIEZO1 and PIEZO1 L2023V was highly significant (Student's t-test; p<0.0001) and is predicted to lead to cellular dehydration. Patients often present with a complex clinical picture and laboratory results and may have combinations of potentially damaging genetic variants identified by Next-Generation sequencing. The examination of clinical, laboratory, and genetic data from family members and, in some cases, in vitro studies are required to clarify the relative contribution of these variants and to arrive at an accurate diagnosis. The data presented here further our understanding of the role of PIEZO1 in RBCs and its potential pathological contribution in HHAs with associated cellular dehydration and may facilitate the future development of therapeutic targets for treatment of these conditions. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Charlie van der Horst, an emeritus professor at the University of North Carolina and a friend of Pathogens and Immunity, disappeared from sight on Friday, June 14 during a marathon swim in the Hudson River. His death was confirmed. Few who knew him would call him Charles as formality was not his strong-suit. Charlie was born in Holland to a Dutch father and a Polish Holocaust survivor mother. His family moved to the Buffalo, New York area and sent Charlie to school at Andover. He attended Duke University where he captained the varsity swim team in 1973-74. He remained a powerful swimmer, competing often in national Masters’ competitions. He received his MD degree from Harvard in 1979 and trained in medicine at Montefiore Medical Center and Infectious Diseases at the University of North Carolina. He was an expert in the management of fungal diseases and when the AIDS epidemic began, he knew he had to commit his career to AIDS research and care. He led a highly successful AIDS Clinical Trials Unit at the University of North Carolina and was a respected leader in this national consortium who gained international recognition and respect for his work. More than most anyone else I know, Charlie was driven to fight for justice, anywhere, any time. At the 2000 IAS meeting in Durban, South Africa he recognized that the greater AIDS need was in the developing world and he redirected his entire career towards the development of research and care programs in Africa. When Ebola hit West Africa, Charlie rushed to Liberia to help. In the U.S., Charlie was on the front lines urging his state legislature to deal fairly with all North Carolinians, working hard to fight for equity in health care. He was beloved by so many, respected for his talents, admired for his decency. He was, as my grandmother would have said—a mentsch—and more. Our world is lucky to have had him and is diminished by his loss.

Currently about 25% of Americans die in nursing homes, many with poorly controlled pain and other symptoms, with minimal provisions for psychosocial support. New models are necessary to lessen structural and process barriers to give effective end-of-life care in nursing homes. Objectives 1) To extend hospital-based Bioethics Consultation Services (BCS) and Palliative Care Services (PCS) at Montefiore Medical Center (MMC) in the Bronx to two local Skilled Nursing Facilities (SNFs), Morningside House Aging in America (MSH) using direct face-to-face consultations and Beth Abraham Health Systems (BAHS) via video consultations (VC); 2) Achieve improvements in quality of life and comfort for elderly residents and their families; 2a) Improve the level of practice and increase staff satisfaction with palliative care content-related knowledge and bioethical analysis. Methods We report preliminary findings of this two group quasi experimental project with results of pre- and post-tests rating content-related knowledge in aspects of end-of-life care for staff. Select pre-test and post-test questions were given to physicians and other staff, but were re-configured for, registered and licensed practice nurses, social workers, and certified nursing assistants from the End-of-Life Physician Education Resource Center (EPERC). Patient, family, and staff ratings of the quality of palliative care were measured with a Palliative Outcomes Scale (POS) one week prior to and post consultation. Results 72 staff attended in-services; 53 completed pre-tests and 49 post-tests. Overall knowledge scores increased for 9 of the 16 items that were analyzed. There were improvements in knowledge scores in 12 of 16 items tested for staff content related knowledge which were statistically significant in regard to management of cancer pain from 63.8% to 81.5% (p = 0.03) and a trend to significance for assessment and management of delirium from 31.6% to 61.9% (p = 0.073). Seventy five POS surveys were completed from 13 video-conferenced Palliative Care consultations and 14 direct face-to-face consultations from March 2008 to January 2009. There were improvements in ratings for some aspects of quality of care on the POS. Patient and staff aggregate response scores for the POS were significantly improved between baseline and follow-up (Wilcoxon signed-rank test p = 0.0143 and p = 0.005) at the videoconsultation site and for family and staff at the face-to-face consultation site (Wilcoxon signed-rank test p = 0.0016 and p = 0.0012). Conclusion Preliminary evidence suggests that use of real time videoconferencing to connect hospital-based Bioethics and Palliative Care clinicians with patients, families, and staff in Skilled Nursing Facilities may enhance some aspects of end-of-life care for their residents, as well as content related knowledge in core aspects of end-of-life care for interdisciplinary groups of staff or caregivers.

Abstract Background The prevalence of renal disease in sickle cell disease (SCD) is strikingly high and is associated with morbidity and mortality (Becker et al 2010, Powars et al 2005). In SCD children there is initially hyperfiltration with high GFRs followed by increasing proteinuria in the adolescent and adult SCD pts. (Becker at al 2010). Historically, hypertension (HTN) has been associated with Renal Disease in the general population and a few adult sickle cell nephropathy studies. HTN has been associated with Stroke in SCD. In an ongoing multicenter, international Renal SCD Cohort Study, we investigated the association Microalbuminuria and Macroalbuminuria to Patients Blood Pressure (SBP and DBP), Hypertension based on CSSCD Group Age Defined BP for SCD patients >90%tile (Pegelow et al 1997), and Family history (FH) of Hypertension and Renal Disease in a Crossectional (Peds and Adults), International, Multicenter group of SCD patients. Methods 272 pediatric and adult SCD (3-59 y/o) patients were recruited at baseline from 6 Centers (USA: Univ of Michigan, Case Medical Center/Rainbow Babies, Albert Einstein-Montefiore Medical Center, Univ of Connecticut; Italy: Univ. of Padova, Univ of Naples; Ghana: Korle-Bu Teaching Hospital). 88%(N=236) were severe SCD (SSorSBeta Zero) and 12%(N=31) were Mild Phenotype (SC or SBetaPlus). 58% were Children (<18y/o) and 42%(>18y/o) adults. FH of HTN and Renal Disease were obtained in 1st and 2nddegree relatives. Clinical history and laboratory studies including Pain crises patterns, SBP, DBP, BMI, CBC, Serum Crt, were collected. We obtained Urine Microalbumin/Crt(UMA) (mg/gm) obtained in 169 patients and categorized patients into 1) No Microalbuminuria(No UMA)<30mg/gm, 2) Microalbuminuria(MicroUMA) 30-299mg/gm and 3) Macroalbuminuria (MacroUMA) and obtained Urine protein/crt gm/gm(UProtCrt) in 101 SCD pts and were categorized 1) No proteinuria(NoUProt) <0.2 and 2) Macroproteinuria(MacroUProt)>0.2. Patient’s HTN was defined based on CSSCD SBP or DBP> 90%tile for each specifically defined age group( Pegelow et al 1997). Results In our SCD Renal Cohort Study, NoUMA in 71%(110/169), MicroUMA in 29%(48/169), MacroUMA in 2.2%(6/169) were observed. We also found NoUProt in 75%(N=75) and MacroUProt in 25%(n=25) within our cohort. Severe SCD pts represented 96%(n=46) of the MicroUMA pts, 100% or MacroUMA pts(N=6), and 92% MacroUProt pts(N=23). Proteinuria was disproportionately represented within the Adult SCD pts : 50% of Adults with MicroUMA(n=31) while only 16%(n=17) of Peds. UMA Mean Adult levels was 102(mean) vs. Peds UMA levels of 22(mean),(p=0.009); Also, Adult UProtCrt=0.21(mean)levels were >Peds=0.16, (p<0.001). HTN defined as SBP>90%tile or DBP >90%tile was present in 30%of the subjects(n=77).Thirty-One Percent(n=32) of Adults and 30%(n=45) of Peds pts had HTN. In a Bivariate Analysis(Pearson’s Correlation), HTN was not associated with UMA levels(p=0.919) or UPrtCrt levels(p=0.330). Further, mean UMA was lower in HTN SCD pts( m=24) vs NonHTN(SBP) pts(m=51). Mean UProt levels lower in the HTN group(0.15 ) vs NonHTN(0.20). SBP alone was not associated with UMA( p=0.083), UPrt( p=0.804) levels, MicroUMA(p=0.596). While FH of HTN was common in 75% of pts, FH HTN was not associated with UMA and UProtCrt levels, MicroUMA, MacroUMA, MacroUProt( p>0.05) patients. FH of Renal Disease was not associated with Proteinuria within our Cohort. However, Age( p<0.001: UProtCrt levels, UMA levels, MicroUMA, SBP) and hemoglobin(p=0.034: UProt Crt levels) was significantly associated with proteinuria within our cohort based on Bivariate Analysis. BMI was associated with SBP(p<0.001) and DBP(p<0.001) but not UProt or UMA levels. Further analysis revealed increasing proteinuria(UMA) within aging SCD pts:( 6-10 UMA= 15, 11-19 UMA =42, >20y/o UMA=114)(p=.035 One Way Anova) Conclusions Systolic Blood Pressure, HTN defined as SBP>90%tile or DBP >90%tile from the CSSCD Group, FH of HTN was not associated with Micro or Macroproteinuria based on UProtCrt and UMA levels in an international, cross-sectional cohort of SCD patients. Hemoglobin level and older age were strongly associated with proteinuria within our cohort of patients, consistent with previously well established studies. These findings are supportive of other factors outside of HTN including those intrinsic to SCD contributing to early onset SCD nephropathy. Disclosures: Perrotta: Novartis: Research Funding.

Abstract Background: SickleCell Disease (SCD) is a chronic illness characterized by vaso-occlusive complications leading to unpredictable episodes of pain, cumulative organ damage and high health care utilization rates. National estimates of total hospital costs for sickle cell related hospitalizations are approximately $488 billion (Steiner 2006). 30 day readmission rates are used as a quality metric for a variety of chronic diseases: 33% of patients with SCD are readmitted within 30 days, compared to 3.4% for asthma, 12% for pneumonia, 16% for heart failure and 20% for diabetes (Brousseau 2010, Berry 2011). Multiple factors contribute to this high utilization rate and not all are modifiable. Increasing age and psychosocial comorbidities are associated with a greater length of stay (LOS). 18-30 year old patients, public insurance and admissions for pain crisis are associated with a higher 30 day readmission rate. Lack of outpatient follow up with a trained hematologist following hospital admission has been demonstrated to increase SCD readmission rates (Leschke 2012). Debaun et al have noted that written discharge management guidelines alone had low utilization rates, however when intensive ongoing patient and provider education by a nurse educator was also included, the 30 day readmission rate decreased from 28 to 11% (Frei-Jones 2009). Hydroxyurea responders have been shown to have a reduced LOS. Hypothesis: Implementation of an individualized, multimodal care plan during inpatient stay and at inpatient to outpatient discharge will reduce acute care utilization. It is likely that the implementation of the comprehensive care plan at this key transition point will be more effective due to (1) greater psychological readiness in the patient/ family to accept escalation of care soon after an acute event (2) decreased instances of “missed opportunities” in the event that the patient does not follow up with a provider with sickle cell specific expertise and (3) improvement in communication amongst inpatient providers, outpatient providers with specific hematology expertise and the multi-disciplinary team. Methods: A SCD quality improvement effort was initiated at The Children’s Hospital at Montefiore (CHAM) in July 2012 with the specific goals of reducing the 30 day readmission rates and length of stay (LOS). Secondary endpoints included admission rates, ED return rates and cost savings. Our efforts were directed at consistent and comprehensive implementation of best-practice guidelines, improved pain management strategies, a multimodal approach to patient care, andutilization of the hospital admission as an opportunity to design a comprehensive care plan. Representatives from the inpatient team, the primary hematologists, nursing, social work, psychology and pain management met weekly to create the care plan. A pre–post design was utilized, comparing data 3.5 years before to 1 year after the initiation of the transition intervention. Results: A significant reduction rate in LOS by 10% and 30 day readmission rate by 37%, with even greater gains in the 18-21 year age group was noted. This was not accompanied by an increase in ED visits (3 and 7 days) and in fact there was a significant reduction in the 3 day ED return rate in older patients. We also saw an overall reduction in the SCD inpatient admission rate by 22% and increase in hydroxyurea use. Table 1: Outcomes from the ongoing SCD Quality Improvement project Number of admissions 3 Day ED Return (%) 7 Day ED Return (%) 30 Day Readmission Rate % LOS (days) < 18 years National Average 17 4.21 Before 556 3.3 0.95 18.1 4.1 After 140 3.4 1.01 14.7 4.0 p-value 0.9 0.8 0.059 0.6 ≥ 18 years National Average 41.1 6.8 Before 1685 11.5 0.9 41.4 6.6 After 592 5 2.1 18.6 5.4 p-value 0.02 0.2 <0.0001 0.04 All Ages Before 2241 5 0.94 24 4.7 After 732 3 1.23 15 4.2 p-value 0.8 0.52 <0.001 0.018 * “Before” and “After” represent data prior to and after the implementation of the ongoing QI initiatives respectively Conclusion: We demonstrate the feasibility of reducing acute care utilization in SCD patients, with the implementation of an individualized, multimodal, comprehensive care plan during hospital admission and at discharge. Disclosures No relevant conflicts of interest to declare.

Abstract Introduction There are 827 variants of β thalassemia reported to the registry of human hemoglobin variants and thalassemias registry 1. Genetic mutations of β thalassemia are very diverse but can be broadly divided in to non deletion forms and deletion forms. The new mutation is a frame shift insertion in exon 2 of the β globin gene. To the best of our knowledge this mutation has never been described before and presents as a mild form β thalassemia intermedia. Objective To describe the phenotypic presentation of the new β globin variant, due to insertion of 9 nucleotides (AAAGTGCTC) between nucleotides c.207 and c.208. Case report A 22 months-old Hispanic boy who was referred for evaluation of persistent anemia. The new born screening for the child was positive for sickle cell trait. Initial hemoglobin (Hb) was 8.8, hematocrit was 27 and MCV was 65.5, which were decreased. RDW was 25.2, which was increased. Hemoglobin evaluation by acid and alkaline electrophoresis and HPLC revealed a HbS 0%, HbF 6.5% HbA 78.4%, HbA2 4.9% and a Hb variant 10.2%. The interpretation of the results was an α globin variant suggestive of Hb Montefiore and β thalassemia trait. Alpha thalassemia PCR for the 7 most common deletions in the α globin chain was negative. Subsequent α globin gene sequencing revealed no α globin gene mutations. On physical exam there were no bony changes or hepatosplenomegaly. Family History The mother is 29-year-old with HbAA. The father is 39-years-old with the same mutation on beta globin gene analysis. Hb electrophoresis also suggested an α and β globin mutation. Alpha thalassemia PCR was negative and he had a normal α globin gene copy number. At age 19 he had a splenectomy secondary to splenomegaly and hypersplenism. He is consistently anemic with Hb< 9 and MCV < 70. The child has a paternal half brother, who is 21 years old and has similar problems as father. He had a splenectomy at the age of 17 after admission for abdominal pain. The patient has a 5-year-old sibling, who is normal with HbAA and another paternal half sibling reported as no anemia. Discussion Though β thalassemia intermedia is most commonly homozygous or compound heterozygous, less frequently it can be due to single locus mutation. DNA sequencing of the α globin gene of the index case was completely normal and there was normal copy number of the α globin gene in the father. No Hb S was found on Hb electrophoresis. The new mutation adds 9 base pairs to exon 2 and 3 amino acids (Lys-Val-Leu) between amino acid 68 and 69 of the protein. This elongates the beta chain which can lead to instability and precipitation of Hb as well as hemolysis and anemia2. Further studies like short time incubation and pulse chase globin chain synthesis experiments are needed to know the stability of the β globin protein3. In addition, an increase of α globin gene copy number can also be a reason for increasing the severity of β thalassemia trait2. However the α gene copy was normal in the father. Conclusion We present a case of a child with a false positive abnormal newborn screen suggestive of sickle cell trait, as well as a Hb electrophoresis suggestive of an alpha globin mutation. As the father and paternal brother have had a splenectomy in their teen years with noted hepatosplenomegaly, suggestive of increased hemolysis, and the anemia is more severe than usual for β thalassemia trait, this suggests that phenotypically the c.199_207dup variant presents as a mild β thalassemia intermedia. In addition, there does not seem to be any bony abnormalities associated with marrow hyperplasia. As both our patients are heterozygous for this novel mutation with normal α globin gene copy number and alpha globin sequencing, we suspect that elongation of the β globin produces an unstable hemoglobin with a mild β thalassemia intermedia phenotype2. References 1. Databases of human hemoglobin variants and other resources at the globin gene server. Hemoglobin. 25(2):183-93, 2001 May. 2. Galanello R, Cao A. Relationship between genotype and phenotype. Thalassemia intermedia. Annals of the New York Academy of Sciences 1998; 850:325-33. 3. Is hemoglobin instability important in the interaction between hemoglobin E and beta thalassemia? Blood September 15, 1998 vol. 92 no. 6 2141-2146. Disclosures: No relevant conflicts of interest to declare.

Background The American Board of Medical Specialties definition of medical professionalism cites the need to acquire, maintain, and advance a value system serving the patients’ and public’s interests above self-interests.4 Medical professionalism is a one of the core physician competencies assessed by both the ACGME training program evaluation and the ABA certification process. However, a growing concern for the decline of professionalism and altruism in medicine resulted in increased publications on the matter, citing various potential sources for the issue. Methods All residents and fellows (Focus Group 1) of the Anesthesiology Department of Montefiore Medical Center in Bronx, NY were invited to participate in a semi-structured interview via Zoom, held on two separate dates. A separate invitation was sent to the faculty of the department (Focus Group 2), held on one date. During the interview, guiding questions were provided by the 4 interviews to facilitate discussion. The interviewers, all members of the anesthesia faculty, took notes as the interviews progressed. The notes were reviewed for common themes as well as supporting and contradicting quotations. Results A total of 23 residents and fellows and a total of 25 faculty members within the Anesthesiology department at Montefiore Medical Center were interviewed. Amongst the findings, common discussions concerned motivating and demotivating factors contributing to the professionalism and altruism exhibited by the residents and fellows when caring for critical COVID-19 patients during the height of the pandemic. It was widely regarded that patient improvement, community and team support, as well as intrinsic desire to help greatly motivated the team while continuous patient deterioration, uncertainty in staffing and treatment, and concerns for personal and family safety were sources of discouragement. Overall, faculty perceived an increased demonstration of altruism amongst residents and fellows. The statements made by the residents and fellows during their interviews supported this observation. Conclusions The actions of the Montefiore Anesthesiology residents and fellows demonstrated that altruism and professionalism were readily available amongst physicians. Increased levels of empathy and responsibility contributed to a demonstration of professionalism that challenges previous views of a perceived decline of these attributes in the medical field. The findings of this study stress the importance of creating a curriculum and exercise that stress empathy-based care and altruism in order to improve resident satisfaction and decrease feelings of burnout. Additionally, curriculum additions to facilitate professionalism are proposed.

Inspired by Oxford University’s Christian social reform clubs in the early 20 th century, Basil Henriques a young Jewish gentleman from a distinguished, upper middle-class family in London determined to establish a Jewish boys’ club in London’s East End. Influenced first by his mother’s devotion to Judaism and then by the progressive views of Jewish scholar, Claude Montefiore and his Oxford history professor, Kenneth Leys, Henriques established the Oxford and St.George’s Jewish Boys’ Club in 1914. An anti-Zionist, Henriques believed strongly in establishing a club that would socialize Jewish youth to become both proud Jews and proud citizens of Great Britain. The club soon served both boys and girls and, by 1919, it had acquired larger premises and become a settlement. Changing demographics in London’s Whitechapel and the rise of the welfare state eventually led to the settlements’ relocation in 1973 and then to its eventual demise.