T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia (T-LBL/T ALL) is an aggressive hematological malignancy arising from malignant transformation of T-cell progenitors with poor prognosis in adult patients. Outcomes are particularly dismal in the relapsed/refractory setting, and therapeutic options are limited in this context. Genomic profiling has shown frequent aberrations in the JAK-STAT pathway, including recurrent mutations in JAK3 (15%-20% of T-ALL cases), suggesting that JAK kinase inhibition may be a promising therapeutic approach. Activating JAK3 mutations are capable of transforming cytokine-dependent progenitor cells in vitro and causing T-ALL-like disease when expressed in hematopoietic progenitors in vivo. We describe a case of relapsed T-ALL in an adult patient, with two JAK3 activating mutations identified by whole-exome sequencing (WES), leading to hypothesis-based treatment with the JAK1 and JAK3 inhibitor, tofacitinib, following failure of salvage chemotherapy reinduction. Despite the molecularly targeted rationale, tofacitinib did not induce an objective clinical response. Our report suggests that the presence of activating JAK3 mutations does not necessarily confer sensitivity to pharmacological JAK3 inhibition.Commentary by Dr James Kimpton and Dr Teck Khong Clinical Pharmacology, St George's, University of London, UKSeries Editor Dr Teck Khong, DTB Associate Editor Clinical Pharmacology, St George's, University of London, UKCommentary on Kraus WE, Bhapkar M, Huffman KM, et al 2 years of calorie restriction and cardiometabolic (CALERIE) exploratory outcomes of a multicentre, phase 2, randomised controlled trial. Lancet Diabetes Endocrinol 2019; 7 673-83.The aim of this review is to explain why the term 'desquamative interstitial pneumonia' (DIP) should be discarded and replaced with modern terminology. Reason 1 DIP is a misnomer. Within a few years after the term was coined, it was shown that the airspace cells in DIP are macrophages not desquamated pneumocytes. Reason 2 As a result of overly simplistic and poorly defined histologic criteria, DIP is currently a mixed bag of smoking-related diseases and unrelated processes in never-smokers. Reason 3 DIP obfuscates the modern concept that smoking causes some forms of parenchymal lung disease. Despite the fact that >80% of cases of DIP are caused by smoking, it is currently classified as a 'smoking-related idiopathic interstitial pneumonia', an oxymoron. Reason 4 The premise that the presence of numerous macrophages within airspaces defines an entity creates problematic histologic overlap with other lung diseases that may feature prominent airspace macrophages. Reason 5 DIP is outdated. It was coined in 1965, when many entities in interstitial lung disease had not been described, smoking-related interstitial lung disease was an unknown concept, computed tomograms of the chest had not been introduced and immunohistochemistry was unavailable. We suggest a way forward, which includes eliminating the term DIP and separating smoking-related lung abnormalities (including accumulation of pigmented airspace macrophages) from cases characterised by numerous non-pigmented macrophages in never-smokers. The laudable goal of smoking cessation is not served well by muddying the relationship between smoking and lung disease with inaccurate, outdated terminology.A 44-year-old woman diagnosed with a HER2 positive early breast cancer, receiving neoadjuvant treatment with paclitaxel and targeted agents, trastuzumab together with pertuzumab, presented to the emergency room with gait instability and upper right limb weakness. The neurological examination was compatible with cerebellar alteration showing right dissymmetry of the finger-nose and heel-knee manoeuvre. A head CT and a brain MRI were performed and negative. The electromyography showed alterations of the pyramidal pathway and somatosensory pathway. In order to determine the cause of the cerebellar affection, a lumbar puncture was performed.  https://www.selleckchem.com/products/Romidepsin-FK228.html  The cerebrospinal fluid analysis was non-specific, but the antineuronal anti-Yo antibody was positive, being diagnosed of a paraneoplastic cerebellar degeneration (PCD). A positron emission tomography CT ruled out metastatic disease. The patient completed four cycles of antiHER2 blockade and weekly paclitaxel, achieving a complete pathological response. One year later, she maintains a complete remission but the PCD still prevails.An elderly woman underwent hardware removal and total joint replacement (TJR) of her right knee. Ipsilateral total tip replacement was performed 7 years earlier, and 12 months later, a supracondylar fracture of the index femur was successfully treated by open reduction internal fixation (ORIF) of the distal femur with a locking compression plate condylar plate. Hardware removal attempt, prior to the arthroplasty, resulted in fracture of the distal femur. Total knee replacement (TKR) was commenced with temporary reduction and final stabilisation of the femur fracture with a condylar plate. Postoperatively, non-union of the femur fracture developed twice with fatigue failure of the plate fixation device in both instances. Refixation of the femur was performed on both occasions and additional bone healing augmentation measures were performed for each subsequent surgery. Femur union was achieved fourteen months after the last surgery.Thalamic deep brain stimulation (DBS) for chronic pain is performed in selected patients with a variable success rate. We report the use of recently developed directional DBS in a patient with hemibody central poststroke pain (CPSP) and its added value in the induction of pleasant, pain-distracting paresthesia's throughout the contralateral body side. A 68-year-old man suffered from multiple strokes in the left hemisphere 11 years before presentation, resulting in medically refractory right-sided hemibody CPSP. He was implanted with a directional DBS electrode in the left ventrocaudal nucleus of the thalamus. A directional single-segment contact configuration produced a better improvement throughout the contralateral body side than ring-mode and other directional configurations. Treatment led to a reduction of almost 50% in pain. This case demonstrates the value of directional DBS in the treatment of chronic pain, as steering increases selectivity and reduces side effects in a small target area surrounded by structures with high functional diversity.