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for failure in this condition.
which markedly increases the patient’s risk
was postponed due to the persistent IFI,
logical remission, stem cell transplantation
Exclusion criteria included pediatric research, case-studies,
bone marrow biopsies revealed hemato-
antifungal treatment. Although repeated
controlled yet and necessitated long-term
chronic Aspergillus infection was not well-
still persisted, thus indicating that the
showed that the hypermetabolic lesions
the follow-up FDG PET/CT scans clearly
of voriconazole. However, the results of
switched and enhanced with the addition
tory; therefore, the antifungal therapy was
that the antifungal therapy was unsatisfac-
the progression of the disease indicating
results of the scans provided evidence for
CT images [Figure 1B, Figure 1C]. The
were not apparent on the corresponding
hypermetabolic lesions, some of which
the appearance of new hepatic and splenic
Moreover, the serial scans demonstrated
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16. Bataille L, Lonneux M, Weynand B, Schoonbroodt D, Collard P, Deprez PH. EUS- 19. Buscarini L, Cavanna L, Fornari F, et al. Ultrasonically guided fine-needle biopsy: pituitary resistance to TH in adult life in practice is to maintain FT4 levels below 20% nity to share information about pregnan-
FNA and FDG-PET are complementary procedures in the diagnosis of enlarged a new useful technique in pathological staging of malignant lymphoma. Acta normal adults born to mothers with RTH of the ULN in women with RTH who are cies and outcomes in these patients.
mediastinal lymph nodes. Acta Gastroenterol Belg 2008; 71 (2): 219-29. Haematol 1985; 73 (3): 150-2.
17. Alsharif M, Andrade RS, Groth SS, Stelow EB, Pambuccian SE. Endobronchial 20. Pontifex AH, Klimo P. Application of aspiration biopsy cytology to lymphomas. [4]. According to the standard clinical prac- carrying wild type fetuses. In this respect,
ultrasound-guided transbronchial fine-needle aspiration: the University of Cancer 1984; 53 (3): 553-6. tice, as reported by Weiss and colleagues [1], it is important to consider the reliability of Correspondence
Minnesota experience, with emphasis on usefulness, adequacy assessment, and 21. Demharter J, Muller P, Wagner T, Schlimok G, Haude K, Bohndorf K. Percutaneous prenatal identification of the fetal genotype thyroid function tests in pregnancy (i.e., to Dr. E. Chertok Shacham
diagnostic difficulties. Am J Clin Pathol 2008; 130 (3): 434-43. core-needle biopsy of enlarged lymph nodes in the diagnosis and subclassification by amniocentesis and judicious treatment of use gestational age-specific reference ranges) Endocrinology Unit, Emek Medical Center, Afula
18. Ernst A, Anantham D, Eberhardt R, Krasnik M, Herth FJ. Diagnosis of mediastinal of malignant lymphomas. Eur Radiol 2001; 11 (2): 276-83. RTH mothers carrying unaffected fetuses to and to remember that in women with RTH 18101, Israel
adenopathy-real-time endobronchial ultrasound guided needle aspiration versus 22. Lefebvre JL, Coche-Dequeant B, Van JT, Buisset E, Adenis A. Cervical lymph nodes fax: (972-4) 814-1506
mediastinoscopy. J Thorac Oncol 2008; 3 (6): 577-82. from an unknown primary tumor in 190 patients. Am J Surg 1990; 160 (4): 443-6. reduce TH levels should be used to maintain the evolution of thyroid function tests in email: elena_ch@clalit.org.il
FT4 levels under 20% above the ULN. This pregnancy is poorly known. In a recent
Capsule treatment can prevent the predictable low retrospective study of 18 pregnancies in 13 References
birth weight and TSH neonatal suppres- women with RTH, Pappa and colleagues [5] 1. Weiss RE, Dumitrescu A, Refetoff S. Approach to
the patient with resistance to thyroid hormone and
Some (re)programming notes on cancer sion. Moreover, prenatal determination of emphasized the role of prenatal diagnosis in pregnancy. J Clin Endocr Metab 2010; 95: 3094-102.
the fetal genotype can prevent unnecessary pregnant women with RTH. They suggested
Epithelial cancers develop resistance to targeted therapies normal lung and normal prostate epithelial cells into SCNCs treatment of RTH mothers carrying fetuses that it may be safe to delay prenatal diagnosis 2. Dumitrescu A, Refetoff S. The syndromes of reduced
sensitivity to thyroid hormone. Biochim Biophys Acta
in a number of different ways. Several cancer types do so that resemble clinical samples. This convergence of molecular harboring the mutation [1]. However, it until FT4 levels exceed 150% of the ULN for 2013; 1830: 3987-4003.
by undergoing phenotypic conversion to a highly aggressive pathways could potentially simplify the development of new should be noted that in women with RTH, gestational age. Their suggestion was based 3. Jonas C, Daumerie C. Conservative management
cancer called small cell neuroendocrine carcinoma (SCNC). therapies for SCNC, which is currently untreatable. miscarriages occur early in the first trimes- on the uneventful outcomes of six pregnan- of pregnancy in patients with resistance to thyroid
Whether distinct cancer types accomplish this “reprogramming” ter of pregnancy, prior amniocentesis. There cies in which the FT4 values of the mothers hormone associated with Hashimoto’s thyroiditis.
Thyroid 2014; 24: 1656-61.
through the same mechanism has been unclear. park et al. Science 2018;362:91 is also a small risk of miscarriage associated were close to 50% above the ULN [5]. 4. Srichomkwun P, Anselmo J, Liao XH, et al. Fetal
showed that the same set of oncogenic factors transforms both Eitan Israeli with amniocentesis (about 1%) that should exposure to high maternal thyroid hormone levels
be considered. COnCluSIOnS causes central resistance to thyroid hormone in adult
humans and mice. J Clin Endocrinol Metab 2017;
Capsule In our patient, we opted for a cautious Pregnancy in women with RTH should be 102: 3234-40.
approach and began propylthiouracil treat- planned, if possible, and closely followed. 5. Pappa T, Anselmo J, Mamanasiri S, Dumitrescu AM,
gene for preeclampsia ment at a low daily dose (150 mg) before Given the rarity of this condition, we think Weiss RE, Refetoff S. Prenatal diagnosis of resistance
to thyroid hormone and its clinical implications.
we knew the fetal genotype. The standard it would be helpful for the medical commu- J Clin Endocrinol Metab 2017; 102: 3775-82.
Preeclampsia is a serious complication of pregnancy that women, they found that preeclampsia was associated with the
often presents as an increase in maternal blood pressure. APOL1 high-risk genotype. Interestingly, it was the genotype
The disorder is more prevalent and severe in women with of the fetus, not the mother, that mattered. The fetal APOL1 Capsule
African ancestry, most likely because of genetic factors. Reidy high-risk genotype may be linked to one in eight cases of 131118-COHANIM - 131118-COHANIM | 2 - A | 18-11-13 | 11:24:13 | SR:-- | Magenta 131118-COHANIM - 131118-COHANIM | 2 - A | 18-11-13 | 11:24:13 | SR:-- | Yellow #131118-COHANIM - 131118-COHANIM | 2 - A | 18-11-13 | 11:24:13 | SR:-- | Black 131118-COHANIM - 131118-COHANIM | 2 - A | 18-11-13 | 11:24:13 | SR:-- | Cyan
and colleagues investigated a variant of the gene encoding preeclampsia in black women. Stressed out by influenza virus
apolipoprotein L1 (APOL1), which was previously shown
to confer a high risk of kidney disease in black Americans. Am J Hum Genet 2018; 103: 367 Viral infection leads to cellular stress, which can act to the the next rounds of transcription initiation. The viral protein
Studying two independent populations of pregnant black Eitan Israeli host’s advantage to curb infection; however, the virus can also NS1 is responsible for this effect and can be modulated by
subvert stress responses for its own gain. zhao et al. found SUMOylation. Although whether this stress response tilts in
that influenza A virus (IAV) infection led to global deregulation favor of host survival or facilitates viral replication is unknown,
Capsule of transcription. After IAV infection, RNA polymerase II runs it might help explain the differences in pathogenicity seen in
through the transcription termination site of almost all different IAV strains with divergent NS1.
necroptosis microenvironment directs lineage commitment in liver cancer active genes. This process down-regulates gene expression Nat Struct Mol Biol 2018; 25: 885
by affecting the splicing of some transcripts and delaying Eitan Israeli
Primary liver cancer represents a major health problem. It hepatocytes, hepatocytes containing identical oncogenic drivers
comprises hepatocellular carcinoma (HCC) and intrahepatic give rise to HCC if they are surrounded by apoptotic hepatocytes.
cholangiocarcinoma (ICC), which differ markedly with regards to Epigenome and transcriptome profiling of mouse HCC and Capsule
their morphology, metastatic potential, and responses to therapy. ICC singled out Tbx3 and Prdm5 as major microenvironment-
However, the regulatory molecules and tissue context that dependent and epigenetically regulated lineage-commitment
commit transformed hepatic cells toward HCC or ICC are largely factors, a function that is conserved in humans. Together, Impaired constriction in Duchenne muscular dystrophy
unknown. Seehawer and colleagues showed that the hepatic these results provide insight into lineage commitment in liver Duchenne muscular dystrophy (DMD) is a hereditary disease model of DMD than in controls. These clusters colocalize with
microenvironment epigenetically shapes lineage commitment tumorigenesis, and explain molecularly why common liver- caused by mutations in the gene that encodes the protein Ca 2+ -activated K + (BK) channels on the channel membrane.
in mosaic mouse models of liver tumorigenesis. Although a damaging risk factors can lead to either HCC or ICC. dystrophin. Dystrophin is also expressed in vascular smooth The resulting higher activity of the BK channels causes
necroptosis-associated hepatic cytokine microenvironment Nature 2018; 562: 69 muscle cells (SMCs). A lack of dystrophin during disease impaired vasoconstriction in the cerebral microvessels of
determines ICC outgrowth from oncogenically transformed Eitan Israeli causes damage to both skeletal and cardiac muscle. pritchard mutant mice. This effect might contribute to DMD-associated
and co-authors used superresolution microscopy to show cognitive impairment.
that clusters of ryanodine receptors, which release Ca 2+ from Proc Natl Acad Sci USA 2018; 115: E9745
“Inaction saps the vigor of the mind” the sarcoplasmic reticulum, are larger in SMCs from a mouse Eitan Israeli
Leonardo da Vinci, (1452–1519), Italian Renaissance scientist, mathematician, engineer, inventor, anatomist, painter, sculptor PERFECTOR
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