T-cell Subset Profile in Kidney Recipients of Extended or Standard Donors

IntroductionThe usage of extended-criteria donors (ECD) became a routinely accepted manner in the last decade. ECD is a potential risk factor for antibody-mediated rejection. Analysis of lymphocyte subsets might be a complementary diagnostic toolkit because there is limited knowledge about this term.MethodBetween May 12, 2016, and September 4, 2019, a total of 130 patients who had undergone kidney transplant were investigated. Patients were divided in ECD and standard criteria donor (SCD) groups. Blood samples were collected before the operation, then in the first week and after 30, 60, 180, and 365 days. Besides routine laboratory tests, multicolor flow cytometry was performed for lymphocyte subsets.ResultsECD grafts were transplanted to older recipients. The number of CD4+ cells increased in the SCDs from the first week to until the end of first month, and then decreased. The number of CD4+ cells decreased from the beginning of the study until the end of first year to 66% of its original value in ECDs. At the first month, the number of CD19+ cells was higher in SCD compared with ECD cases; the number then decreased in both groups. T-regulatory cells had a drop at the first week that lasted until the first month. A bigger increase in SCD and a moderate increase in ECD group were then observed. The kinetics of CD19+ and CD19+ naive cells are similar in the ECD and SCD groups. In the SCD group, cell count decreased in both CD19+ (13%) and CD19+ naive (12%) between third and sixth month. The count of CD19+ cells decreased by 9%, but the count of CD19+ naive cells increased by 11% between the sixth month and first year.DiscussionThe prolonged postoperative uremic state caused by the poorer initial function, together with an aging immune system, explains the weaker immune response in ECD patients, which may be the cause of the decreased number of memory and regulatory T cells. Older patients with an ECD graft need a tailored, personalized, and less aggressive immunosuppressive treatment.     

Bi-allelic pathogenic variations in DNAJB11 cause Ivemark II syndrome,a renal-hepatic-pancreatic dysplasia

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Durable remissions with venetoclax monotherapy in secondary AML refractory to hypomethylating agents and high expression of BCL‐2 and/or BIM

Acute myeloid leukemia (AML) is a disease of the elderly population and survival remains poor after failure of hypomethylating agents (HMA). The BCL‐2 inhibitor venetoclax demonstrated activity as monotherapy and in combination with chemotherapy or HMA in AML. In this case series, patients with secondary AML (sAML) not eligible for intensive chemotherapy and refractory to HMA were treated with venetoclax within a named patient program at our tertiary cancer center in Salzburg, Austria. Between April 2017 and September 2018, seven patients with sAML received venetoclax therapy. Two out of seven patients achieved a complete remission upon venetoclax initiation with a PFS of 505 days and 352 days and another patient achieved complete peripheral blood blast clearing within nine days after start of venetoclax. Among the venetoclax responders, primary refractory disease to prior HMA therapy was documented, 2 patients harbored IDH1/IDH2 mutations and one patient had an antecedent myeloproliferative neoplasm. High BCL‐2 and/or BIM expression in myeloblasts was found in venetoclax responders and response was significantly associated with overall survival (responders: 364 days versus non‐responders: 24 days, P = 0.018). Venetoclax monotherapy is safe and is able to induce durable responses in elderly patients with secondary AML after treatment failure with HMA.     

Analgesic treatments in people with dementia - how safe are they? A systematic review

Introduction: People with dementia may be unable to verbally express pain and suffer from untreated pain. Use of analgesics in people with dementia has increased during the last decade, in particular opioid analgesics with high potential for adverse effects.

Areas covered: This article presents a systematic review of the current evidence for safety and tolerability of analgesic drugs from randomized controlled trials in people with dementia. Relevant trials were identified by a literature search in the EMBASE, MEDLINE, and Cochrane databases from inception to November 2018. The search included the main terms ‘dementia’ and ‘analgesic’ or their subterms, and was filtered to limit results to clinical trials.

Expert opinion: Although pain treatment is increasingly recognized as an important clinical issue in people with advanced dementia, there is currently a lack of evidence to support safety evaluations of commonly used analgesics in this group. To inform treatment decisions and enable care providers to appropriately monitor patients at risk of adverse effects, it is necessary to conduct well-designed clinical trials to investigate the relative efficacy and safety of analgesics in people with dementia, with particular emphasis on harmful effects of long-term opioid use as well as short-term use of nonsteroidal anti-inflammatory drugs.