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A whole Digital Time Capsule system that helps you Create, Curate and Store your valuable Digital Assets.Dovid Ben Nuchem – Aish Kodesh is an Orthodox shul (synagogue), in Oak Park, Michigan, where Torah observance and study are vibrant, relevant, and meaningful – today. We promote Torah which permeates every part of our existence, and is consistent with all that we do.
Daily minyanim, Torah classes on a wide variety of topics for people on every level of learning, and a warm, inviting atmosphere, make DBN a popular shul for both families and single adults in the greater Detroit area.
Cogregation Dovid ben Nuchim – Aish Kodesh, was founded by Rav Chazkel Grubner, of blessed memory.
Over the years, the shul has grown to be a place that is attractive to all Jews regardless of their background, affiliation or life experience. On any given day at the Shul, you will find a warm and accepting spiritual atmosphere where “Ivdu Es Hashem B’Simcha” – Serving Hashem with Joy – is the core focus.Membership
Dovid ben Nuchim offers a wide-range of programming, classes and events. Please support our diverse and popular offerings.
If you would like to make your contribution in memory or honor of a loved one, please include their name and reason for sponsorship.
Donations may also be sent via regular mail to:
Dovid ben Nuchim
14800 W. Lincoln Road
Oak Park, MI 48237
We continue to rely on the contributions of our members in ensuring our varied and exciting programs and we thank you for your continued support!
Rabbi Ari Kostelitz was raised in Sydney, Australia where he attended Yeshiva College before moving to Bnai Brak to attend High School at the Chasam Sofer Yeshiva. In 1992, he came to Lakewood, New Jersey to attend Beis Medresh Gevohah, the hallowed Lakewood Yeshiva; during which time he met his wife, Toby. Together they moved back to Israel in 1994. Rabbi Kostilitz was given Smicha by Rabbi Moshe Heinemann, shlit”a, of Baltimore and the Beis Din of Jerusalem.
He continued his studies in Mir Yeshiva and honed his skills by teaching adult learners at Yeshivat Ohr Somayach.
In 2005, Rabbi Kostelitz moved to Oak Park to assist his wife’s esteemed grandfather, Rav Chazkel Grubner z’l. He assumed the role of spiritual leader of Congregation Dovid Ben Nuchim – Aish Kodesh after Rav Grubner’s passing.
Rabbi Kostelitz has dedicated immeasurable amounts of time and energy to the Detroit Jewish Community and is regularly called upon my rabbonim, community leaders and baal habatim to aid those in need of charity, counsel and inspiration.
We offer a wife range of programs and Shuirium for people of all levels.
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Congregation Dovid ben Nuchim
14800 W. Lincoln Ave.
Oak Park, MI 48237
Rabbi Ari Kostelitz
rabbi@dbndetroit.org
(248) 569-0192
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Oops! Something went wrong while submitting the formChronic Lymphocytic Leukaemia in 2020: the Future Has Arrived.

Purpose of Review Chronic lymphocytic leukaemia is now recognised as a heterogenous disease with a variety of clinical outcomes. Here we summarise the way it is currently stratified according to genetic risk and patient characteristics and the treatment approaches used for these different subgroups. Recent Findings Certain patients appear to sustain MRD negativity after combination chemoimmunotherapy, leading to the suggestion that their CLL may be cured. However, 17p-deleted, p53-mutated or IGHV-UM subgroups are generally resistant to FCR, and much better responses are seen with ibrutinib and venetoclax, frequently inducing MRD negativity that hopefully will be translated into durable remissions. Summary Small molecule inhibitors have already revolutionised CLL treatment. Going forward, we anticipate their use in the majority of patients, early after diagnosis and with curative intent.


Introduction
Chronic lymphocytic leukaemia (CLL) is the commonest leukaemia in the world, with 4.9 new diagnosis per 100,000 per year in the UK and USA. The malignant clonal proliferation and accumulation of mature B-lymphocytes is predominantly identified in older patients with a median age of 74 at diagnosis [1,2]. The majority of patients are monitored with a 'watch and wait approach' until the balance of risks and benefits favours treatment initiation. In some cases, treatment may never be needed whilst in others, the disease is more aggressive with rapid progression and death from disease-related causes a few years after diagnosis [3]. This disparity in outcome highlights the heterogeneity of CLL and the importance of risk stratification to guide treatment decisions. unlike, its myeloid counterpart-chronic myeloid leukaemia-a pathognomonic driving mutation, BCR-ABL, has not been identified, and this slightly delayed the development of targeted therapies. However, over the last two decades, a dramatic increase in our understanding of the pathogenesis of the disease has led to the development of small molecule inhibitors for CLL targeting the B cell receptor pathway and the apoptotic regulator BCL2. Some of these newer therapies appear to be so effective; they may provide a curative option for patients, previously treatment aimed to establish disease control. In this review, we will briefly discuss recent advances in our understanding of the molecular pathology of CLL and then, in more detail, the way that CLL is managed in the UK.

New Developments in the Understanding of the Pathogenies of CLL
Our understanding of the genetics of CLL and the implications on patient outcome began with the publication by Doner et al. in 2000 which identified four recurrent genetic lesions by fluorescence in situ hybridisation (FISH) and showing that their presence predicted disease prognosis. It was found that a lesion at 17p13 and 11q23 indicated a poor prognosis compared with 13q14 and 12q; this formed the basis of the FISH probe set used routinely during CLL diagnostics [4]. The utility of FISH is limited by the need to identify particular region to probe and by the number of probes that can be used at one time. Unlike FISH, G-banding karyotyping which can be applied to all the chromosomes simultaneously, required cells to be in metaphase, various compounds have been used to raise the yield of metaphase cells in CLL-the combination of DSp30/IL2 has shown to do so without inducing artefactual chromosomal aberrations [5,6]. Using this technique, it has been demonstrated 16-19% of patients have a complex karyotype (3 > abnormalities) that this predicts poor outcome independent of P53 status, and the presence of 5 of more is associated with a P53 mutations and perhaps due to this association, a more aggressive course [7]. These techniques have been replaced in research by chromosomal micro arrays and single nucleotide polymorphisms arrays which do not require the cells to be in the cell cycle and whilst the concordance of these approaches is reported in small studies, their incorporation into large trials is awaited [8].
CLL patients can be categorised into two groups depending on the mutational status, established by PCR or next generation sequencing, of the variable region immunoglobulin heavy chain (IGHV) when compared with germline sequence. During the process of VDJ rearrangement and somatic hypermutation of B cells occurs within the germinal centres generating receptors capable of recognising an extensive range of antigens. IGHV-mutated (IGHV-M) CLL, with a mutation status of > 2%, compared with germline sequence as an immunophenotype and gene expression profile similar to that of post GC CD27+, T cell dependent memory B cells. Whilst IGHV-unmutated (IGHV-UM) CLL cells adopted a phenotype gene expression profile and epigenome that resemble a GC-naïve CD27− B cell [9,10]. This difference is reinforced when comparing the BCRs of the two subtypes with IGHV-UM carrying low affinity, poly-reactive and self-reactive BCR, and IGHV-M has higher affinity, olio or mono reactive receptors [11]. This may contribute