Successful treatment of acyclovir-resistant herpes simplex virus infection with amenamevir in a patient who received umbilical cord blood transplantation for T-cell prolymphocytic leukemia.

A 34-year-old woman received umbilical cord blood transplantation for refractory T-cell prolymphocytic leukemia after salvage therapy with alemtuzumab. She developed right angular cheilitis on the 46th day after transplantation, which worsened after receiving systemic steroid therapy for extensive chronic graft versus host disease. The treatment dosage of acyclovir (ACV), ganciclovir, and vidarabine ointment was not effective due to ACV-resistant mutations of the herpes simplex virus type 1 (HSV-1) in the thymidine kinase domain. Foscarnet is expected to be effective against ACV-resistant HSV-1 infection. However, it could not be used because the patient developed renal dysfunction. Several viral thymidine kinase mutations related to ACV resistance were found in the patient's sample. Nevertheless, amenamevir, a helicase-primase complex inhibitor, was effective in our patient who was significantly immunocompromised after allogeneic hematopoietic stem cell transplantation (allo-HSCT). ACV-resistant HSV infection after allo-HSCT is an rare but important complication in the era of low-dose long-term ACV prophylaxis. To date, there is no established treatment against ACV-resistant HSV infection. This case report showed that amenamevir could be a promising treatment option for ACV-resistant HSV infection in patients with renal failure after allo-HSCT.

Three cases of suspected pleuroparenchymal fibroelastosis after allogeneic hematopoietic cell transplantation.

This article reports the clinical course and imaging findings of three cases of suspected pleuroparenchymal fibroelastosis (PPFE) after allogeneic hematopoietic cell transplantation (HCT). All patients complained of dyspnea more than 5 years after HCT, had progressive restrictive deficits on respiratory function tests, and presented with pneumothorax, pleural thickening, or exacerbation of consolidation in the upper lobe of the lung. Though lung biopsy was not done in all three cases, the clinical findings and results of spirometry were compatible with those of PPFE. PPFE has been sporadically reported as a pulmonary complication of allogeneic HCT; however, clinical diagnostic criteria other than histological diagnosis and treatment methods have not yet been established. The accumulation of more cases is necessary to improve the prognosis of PPFE complications.

Feasibility of Mechanical Thrombectomy for Acute Ischemic Stroke Patients Aged 90 Years or Older Compared to Younger Patients.

Mechanical thrombectomy (MT) is a proven treatment for acute ischemic stroke (AIS). However, the efficacy of this treatment is uncertain for very elderly patients. This study aimed to investigate the safety and effectiveness of MT in 90 years or older patients compared with younger patients. We retrospectively reviewed AIS patients treated with MT between October 2018 and June 2020 in our institution. Patients were divided into two groups: aged ≥90 and <90 years. We compared the following factors: functional outcome at discharge, in-hospital death, successful recanalization, and complications. Multivariate logistic regression analysis for the good functional outcome was performed. In consideration of pre-stroke basic activities of very elderly patients, we defined the good functional outcome as modified Rankin Scale (mRS) 0-3. In all, 66 patients were included, and 19 patients (28%) were ≥90 years old. Pre-stoke mRS was higher in ≥90-year-old patients (p = 0.01). In ≥90-year-old patients, we achieved successful recanalization in 17 patients (90%), and only one patient experienced hemorrhagic complication related with the procedure. The good functional outcome (mRS: 0-3) at discharge were six patients (32%) in ≥90 years old versus 19 patients (40%) in <90 years old (p = 0.6). Three patients died in hospital in each group (16% versus 6%) (p = 0.3). Only the stroke severity was negatively related with the good functional outcome in a multivariate analysis. In conclusion, for ≥90-year-old patients compared with younger patients, MT is an equally feasible therapy. Patients should not be excluded from MT based on age alone.

A Case of Acute Embolism of the Accessory Middle Cerebral Artery Treated Using ADAPT Thrombectomy without Lesion Passing.

An accessory middle cerebral artery (AMCA) is a variant vessel that branches from the anterior cerebral artery (ACA) and runs through the Sylvian fissure along the middle cerebral artery (MCA). We report a case of acute embolic occlusion of the AMCA that was treated with thrombectomy using direct aspiration first pass technique (ADAPT). An 88-year-old woman with a history of atrial fibrillation, loss of consciousness, and right hemiparesis was referred to our hospital. Diffusion-weighted magnetic resonance imaging (MRI) showed high signal intensity in the left frontal lobe, insular cortex, and deep white matter, and magnetic resonance angiography (MRA) demonstrated left internal carotid artery (ICA) occlusion. Mechanical thrombectomy using the ADAPT technique was performed with complete recanalization. Final angiography revealed left ACA and AMCA because of the thrombus located at the origin of the left ACA and AMCA. In the case of an acute ischemic stroke associated with AMCA, it is difficult to understand and recognize the anatomy of the vessel before thrombectomy. Therefore, the ADAPT technique, which can treat acute embolic occlusion without lesion passing, is recommended due to its safety. If there is a mismatch between the perfusion area of the occluded artery and the ischemic area or the neurological findings before thrombectomy, it is extremely important to keep in mind the presence of vessel variation in the MCA.

The Fornix May Play a Key Role in Korsakoff's Amnesia Secondary to Subcallosal Artery Infarction.

BACKGROUND: Subcallosal artery infarction injures the fornix and anterior corpus callosum and sometimes causes Korsakoff's amnesia. We hypothesized that Korsakoff's amnesia might be caused by fornix dysfunction rather than anterior corpus callosum dysfunction in subcallosal artery infarction. METHODS: A systematic review approach was applied to search PubMed and Google Scholar for articles to compare patients who had both bilateral fornix and corpus callosum infarction due to subcallosal artery territory ischemia (vascular event group; V group) with patients who had undergone anterior corpus callosotomy (callosotomy group; C group). RESULTS: The V group comprised 10 patients (mean age, 63 years; median, 69 years; standard deviation (SD), 14.5 years; 5 males, 5 females). The C group comprised 6 patients (mean age, 23.7 years; median, 20 years; SD, 7.3 years; 3 males, 3 females). Six of 10 patients (60%) with subcallosal artery infarction exhibited Korsakoff's amnesia. One patient showed neither confabulation nor amnesia. Conversely, no amnesia episodes were seen in any patients from the C group (p = 0.034). CONCLUSION: Fornix injury, rather than anterior corpus callosum injury, might be the major cause of Korsakoff's amnesia in patients with subcallosal artery infarction.

Effects of Paraoxonase 1 gene polymorphisms on organophosphate insecticide metabolism in Japanese pest control workers.

OBJECTIVES: Paraoxonase 1 (PON1) in serum detoxifies organophosphate (OP) insecticides by hydrolysis. The present cross-sectional study aimed to clarify the relationship between PON1 single nucleotide polymorphisms (SNPs) and enzyme activities or OP metabolite concentrations in urine of workers occupationally exposed to low-level OPs. METHODS: Among 283 workers in 10 pest control companies located in central Japan who underwent checkups, 230 subjects (male 199, female 31, average age 38.9 ± 11.1 years old) participated in the study. Q192R and L55M polymorphisms were determined by TaqMan assay. PON1 activity was measured using fenitrothion (FNT) oxon, chlorpyrifos-methyl (CPM) oxon, chlorpyrifos (CP) oxon, and phenyl acetate as substrates. Urinary OP metabolite concentrations were measured with gas chromatography-mass spectrometry. RESULTS: The maximum differences in enzyme activities between individuals were 64.6-, 6.3-, 7.7-, and 2.0-fold for FNT oxonase, CPM oxonase, CP oxonase, and arylesterase (ARE), respectively. The activities of CPM oxonase and ARE in workers having the RR genotype were 53.5% and 18.2% lower than in those with the QQ genotype, respectively. CP oxonase activity was 15.0% lower in those having the M allele (LM + MM compared with LL). Urinary metabolite concentrations were not associated with PON1 polymorphisms, but negative associations were observed between the concentrations and activities of FNT oxonase and ARE. CONCLUSIONS: While PON1 SNPs can explain differences in catalytic activities toward some OPs, differences in urinary concentrations of OP metabolites are not attributable to PON1 SNPs but instead are attributable to its serum activities. Its serum activities might be more sensitive biomarkers for estimation of individual susceptibility to OP toxicities.