Stroke at High Altitude in an Experienced Sherpa Climber: A Case Report.

Sherpa, Mingma Thsering, and Raksha Shrestha. Stroke at high altitude in an experienced Sherpa climber: A case report. High Alt Med Biol. 21:406-408, 2020.-A 44-year-old experienced Sherpa climber had dizziness with nausea and several episodes of vomiting while at Camp 2 of Mount Everest (6400 m). He was airlifted from Everest Base Camp to Kathmandu for further treatment. Neurological assessment revealed cerebellar signs with ataxia. Sensory examination revealed hypoesthesia on the extremities of the left side and right half of the face. Laboratory workup revealed increased hemoglobin and hematocrit levels. Magnetic resonance imaging of brain revealed ischemic infarction of right cerebellar hemisphere in the right posterior inferior cerebellar artery territory extending to medulla. Patient was managed with aspirin, supportive measures, and physiotherapy, and made a complete recovery after 2 months. This is the first documented case of ischemic stroke in a healthy experienced Sherpa climber. Although the exact cause of stroke in our patient remains uncertain, the prothrombotic state due to high altitude compounded by impaired cerebral autoregulation and dehydration may have been contributory factors.

Molecular pathogenesis of progression to myeloid leukemia from TET-insufficient status.

Loss-of-function mutations in ten-eleven translocation-2 (TET2) are recurrent events in acute myeloid leukemia (AML) as well as in preleukemic hematopoietic stem cells (HSCs) of age-related clonal hematopoiesis. TET3 mutations are infrequent in AML, but the level of TET3 expression in HSCs has been found to decline with age. We examined the impact of gradual decrease of TET function in AML development by generating mice with Tet deficiency at various degrees. Tet2f/f and Tet3f/f mice were crossed with mice expressing Mx1-Cre to generate Tet2f/wtTet3f/fMx-Cre+ (T2ΔT3), Tet2f/fTet3f/wtMx-Cre+ (ΔT2T3), and Tet2f/fTet3f/fMx-Cre+ (ΔT2ΔT3) mice. All ΔT2ΔT3 mice died of aggressive AML at a median survival of 10.7 weeks. By comparison, T2ΔT3 and ΔT2T3 mice developed AML at longer latencies, with a median survival of ∼27 weeks. Remarkably, all 9 T2ΔT3 and 8 ΔT2T3 mice with AML showed inactivation of the remaining nontargeted Tet2 or Tet3 allele, respectively, owing to exonic loss in either gene or stop-gain mutations in Tet3. Recurrent mutations other than Tet3 were not noted in any mice by whole-exome sequencing. Spontaneous inactivation of residual Tet2 or Tet3 alleles is a recurrent genetic event during the development of AML with Tet insufficiency.