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It remains challenging in chronic lymphocytic leukemia (CLL) to distinguish between patients with favorable and unfavorable time to first treatment (TTFT). Additionally, the downstream protein correlates of well-known molecular features of CLL are not always clear. To address this, we selected 40 CLL patients with TTFT ≤ 24 months and compared their B cell intracellular protein expression with 40 age- and sex-matched CLL patients with TTFT > 24 months using mass spectrometry. In total, 3268 proteins were quantified in the cohort. IGHV mutational status and trisomy 12 were most impactful on the CLL proteome. Comparing cases to controls, five proteins were significantly upregulated, whereas three proteins where significantly downregulated. Of these, only THEMIS2, a signaling protein acting downstream of the B cell receptor, was significantly associated with TTFT, independently of IGHV and TP53 mutational status (HR 2.49, [95%CI 1.62–3.84], P

Anti-tumour necrosis factor-α (TNFα) agents are effective in diseases including Crohn's disease but may cause cytopenias. The mechanisms involved in anti-TNFα agent-induced thrombocytopenia are scarce. We report a 73-year-old male with Crohn's disease for which he currently used adalimumab, an anti-TNFα agent. He had received mesalazine and infliximab before the treatment of adalimumab. No comorbidities were present. Routine laboratory tests revealed a deep thrombocytopenia (thrombocytes 24 × 109 /L), after which adalimumab was discontinued. Bleeding symptoms included cutaneous haematomas and mild epistaxis. Direct monoclonal antibody-specific immobilization of platelet antigens revealed autoantibodies specific to glycoprotein IIb/IIIa and glycoprotein V platelet receptors. There was no bone marrow suppression. Other causes of the thrombocytopenia were ruled out. The platelet count normalized after adalimumab discontinuation. No further interventions were required. Monitoring thrombocyte levels after initiating anti-TNFα agents is recommended, which could lead to prevention of this potentially fatal phenomenon.

Presented is a patient with dyspnea and painful ulcers finally resulting in multi-organ failure. A detailed history resulted in positive PCR testing for Chlamydia psittaci. We emphasize the importance of a definitive history in establishing the correct diagnosis. When clinicians observe dyspnea with multi-organ failure, they should be aware of psittacosis.

Anti-tumor necrosis factor alpha (TNFα) agents are effective in diseases including Crohn’s disease (CD) but may cause cytopenias. The mechanisms involved in anti-TNFα agents induced thrombocytopenia are scarce. We report a 73-year-old male with Crohn’s disease for which he currently used adalimumab, an anti-TNFα agent. He had received mesalazine and infliximab before the treatment of adalimumab. No comorbidities were present. Routine laboratory tests revealed a deep thrombocytopenia (thrombocytes 24x10*9/L) after which adalimumab was discontinued. Bleeding symptoms included cutaneous hematomas and mild epistaxis. Direct monoclonal antibody-specific immobilization of platelet antigens (MAIPA assay) revealed autoantibodies specific to glycoprotein IIb/IIIa (GPIIb/IIIa) and glycoprotein V (GPV) platelet receptors. There was no bone marrow suppression. Other causes of the thrombocytopenia were ruled out. The platelet count normalized after adalimumab discontinuation. No further interventions were required. Monitoring thrombocyte levels after initiating anti-TNFα agents is recommended, which could lead to prevention of this potential fatal phenomenon.

Introduction Congenital long-QT (LQT) syndrome can lead to torsades de pointes (TdP), which can deteriorate into ventricular fibrillation resulting in sudden death. Thus far, more than 16 genes have been linked to the LQT syndrome. We report an orgasm-induced TdP in a patient with LQT syndrome type 2 with a novel mutation in the KCNH2 gene. Case presentation A 24-year-old Caucasian woman with a medical history of depression, no medication use and no family history of sudden death, presented with recurrent syncope during sexual activity. Immediately after achieving orgasm during sexual intercourse she lost consciousness. Baseline 12-lead electrocardiogram revealed a wide based T-wave with a prolonged QTc-interval of 507 ms. During hospital admission runs of TdP were recorded. The patient was treated with magnesium, an oral beta-blocker, and an implantable cardioverter-defibrillator. Genetic testing (Sanger sequencing) revealed a novel mutation (c.361del) in the KCNH2 gene (chromosome 7q36). Discussion To date, orgasm-induced TdP as a first symptom in a patient with LQT2 has not been published previously. In studies with continuous blood sampling in healthy volunteers, large peaks in plasma epinephrine levels during orgasm were observed with fast post-orgasmic decline. However, in a large cohort study (402 patients of which 129 with LQT2), no patients experienced cardiac events during sexual activity, suggesting that these are indeed very rare. Nevertheless, the high levels of sympathetic adrenal hormones during orgasm may explain the timing of the TdP in our patient. The patient has remained free of syncope at 6 months of follow-up.

The differential diagnosis of nephrotic syndrome is diverse. Systemic conditions and medication such as NSAIDs can cause this syndrome.A 33-year-old male with Crohn's disease for which he was receiving adalimumab noticed he was gaining weight and had swollen ankles. Examination revealed nephrotic syndrome without renal insufficiency. Renal biopsy showed a membranous glomerulopathy. We excluded secondary causes of membranous glomerulopathy such as diabetes mellitus, systemic lupus erythematosus, viral infection or malignancy. We treated the patient with high-dose glucocorticoids on a weaning schedule and adalimumab was discontinued. This regimen resulted in complete remission. It is likely that the nephrotic syndrome with membranous glomerulopathy was associated with adalimumab.In patients with nephrotic syndrome based on membranous glomerulopathy both primary and secondary causes, such as use of medication, need to be excluded.