Differential diagnosis and clinical management of isolated prolonged activated partial thromboplastin time in a patient with Hashimoto thyroiditis-associated thyroid cancer: A case report.

RATIONALE: Patients preparing for surgery may have isolated, prolonged activated partial thromboplastin time (APTT). Cause analysis is warranted in patients who had neither bleeding symptom nor thromboembolic events because isolated prolongation of APTT may lead to unnecessary delayed surgical intervention or invasive procedure, even ineffective plasma infusion treatments. Here, we report a case of Hashimoto thyroiditis-associated thyroid cancer whose APTT was isolated prolonged and discuss the challenges of diagnosis and clinical management of this patient. PATIENT CONCERNS: A 57-year-old woman was admitted to the hospital due to thyroid cancer. Anticoagulant assay was performed for this patient before surgery, she had normal values for prothrombin time, thrombin time, and fibrinogen, but had isolated prolonged APTT value (20 seconds longer than normal). However, the routine laboratory of the local hospital showed normal APTT and she did not have any abnormal bleeding or thrombotic episodes. Lupus anticoagulant (LA) was strongly positive according to mixing studies and modified dilute Russell viper venom time method, it was responsible for prolonged APTT. DIAGNOSES: Hashimoto thyroiditis-associated thyroid cancer whose APTT was isolated prolonged. INTERVENTIONS: The isolated prolongation of APTT in this patient was due to LA. She had no history of anticoagulant medications and no spontaneous bleeding episodes. There should be no specific intervention before thyroidectomy. OUTCOMES: This thyroid cancer patient had an uneventful surgery and was discharged after a week. LESSONS: Prolonged APTT is not considered an absolute indication for plasma infusion therapy in patients with LA. The correct identification of the cause of APTT prolongation is essential for proper treatment of the individuals.

Phenotypic Variation and Carbapenem Resistance Potential in OXA-499-Producing Acinetobacter pittii.

Acinetobacter pittii is increasingly recognized as a clinically important species. Here, we identified a carbapenem-non-resistant A. pittii clinical isolate, A1254, harboring bla OXA- 499, bla OXA- 826, and bla ADC- 221. The bla OXA- 499 genetic environment in A1254 was identical to that of another OXA-499-producing, but carbapenem-resistant, A. pittii isolate, YMC2010/8/T346, indicating the existence of phenotypic variation among OXA-499-producing A. pittii strains. Under imipenem-selective pressure, the A1254 isolate developed resistance to carbapenems in 60 generations. Two carbapenem-resistant mutants (CAB009 and CAB010) with mutations in the bla OXA- 499 promoter region were isolated from two independently evolved populations (CAB001 and CAB004). The CAB009 mutant, with a mutation at position -14 (A to G), exhibited a four-fold higher carbapenem minimum inhibitory concentration (MIC) and a 4.53 ± 0.19 log2 fold change higher expression level of bla OXA- 499 than the ancestor strain, A1254. The other mutant, CAB010, with a mutation at position -42 (G to A), showed a two-fold higher carbapenem MIC and a 1.65 ± 0.25 log2 fold change higher bla OXA- 499 expression level than the ancestor strain. The bla OXA- 499 gene and its promoter region were amplified from the wild-type strain and two mutant isolates and then individually cloned into the pYMAb2-Hyg r vector and expressed in Acinetobacter baumannii ATCC 17978, A. pittii LMG 1035, and A. pittii A1254. All the transformed strains were resistant to carbapenem, irrespective of whether they harbored the initial or an evolved promoter sequence, and transformed strains expressing the promoter from the most resistant mutant, CAB009, showed the highest carbapenem MICs, with values of 32-64 µg/ml for imipenem and 128 µg/ml for meropenem. RNA sequencing was performed to confirm the contribution of bla OXA- 499 to the development of carbapenem resistance. Although the CAB009 and CAB010 transcriptional patterns were different, bla OXA- 499 was the only differentially expressed gene shared by the two mutants. Our results indicate that carbapenem-non-resistant Acinetobacter spp. strains carrying bla OXA genes have the potential to develop carbapenem resistance and need to be further investigated and monitored to prevent treatment failure due to the development of resistance.

Dual Role of gnaA in Antibiotic Resistance and Virulence in Acinetobacter baumannii.

Acinetobacter baumannii is an important Gram-negative pathogen in hospital-related infections. However, treatment options for A. baumannii infections have become limited due to multidrug resistance. Bacterial virulence is often associated with capsule genes found in the K locus, many of which are essential for biosynthesis of the bacterial envelope. However, the roles of other genes in the K locus remain largely unknown. From an in vitro evolution experiment, we obtained an isolate of the virulent and multidrug-resistant A. baumannii strain MDR-ZJ06, called MDR-ZJ06M, which has an insertion by the ISAba16 transposon in gnaA (encoding UDP-N-acetylglucosamine C-6 dehydrogenase), a gene found in the K locus. The isolate showed an increased resistance toward tigecycline, whereas the MIC decreased in the case of carbapenems, cephalosporins, colistin, and minocycline. By using knockout and complementation experiments, we demonstrated that gnaA is important for the synthesis of lipooligosaccharide and capsular polysaccharide and that disruption of the gene affects the morphology, drug susceptibility, and virulence of the pathogen.