Sphenoclival fibrous dysplasia with cyst formation causing abducens nerve palsy in an older patient: illustrative case.

BACKGROUND: Fibrous dysplasia (FD) is typically asymptomatic but is known to occasionally cause neurological symptoms such as visual disturbances. However, FD-associated abducens nerve palsy is extremely rare. OBSERVATIONS: A 76-year-old woman had a left abducens nerve palsy due to mass effect on the abducens nerve at Dorello's canal caused by FD and its associated cyst, which was resolved by resection of the cyst through an endoscopic transnasal route. LESSONS: Although FD is generally an asymptomatic lesion occurring in younger patients, it can occasionally cause abducens nerve palsy even in older patients. In particular, cystic degeneration within FD tends to trigger a mass effect and thus can require surgical decompression. https://thejns.org/doi/10.3171/CASE24424.

A single-session stereotactic radiosurgery for vagal paraganglioma: Effective tumor reduction and innovative treatment option.

Background: Vagal paragangliomas (VPs) are rare tumors in the upper cervical region. Although surgical resection is the standard treatment for these tumors, it carries significant risks due to the tumor's high vascularity and proximity to vital structures. Stereotactic radiosurgery (SRS) for skull base paraganglioma could be a minimally invasive alternative. Case Description: We report the case of a 47-year-old man with a large, asymptomatic VP who was successfully treated with SRS with Gamma Knife Icon, which was performed in the parapharyngeal space (volume: 25.7 mL) using a marginal dose of 14 Gy to the 45% isodose line. This case illustrates the successful treatment of a lesion near the conventional limits (lower limit of C2 vertebral body) using noninvasive mask fixation. Excellent tumor control without neurological deficits was achieved for 25 months after SRS. The tumor volume decreased by 70% (final volume: 7.6 mL). Conclusion: This study demonstrates the utility of Gamma Knife Icon, which facilitates optimal SRS for upper cervical lesions, including VPs.

Impact of a Cancer History on Cardiovascular Events Among Patients With Myocardial Infarction Who Received Revascularization.

BACKGROUND: It remains controversial whether a cancer history increases the risk of cardiovascular (CV) events among patients with myocardial infarction (MI) who undergo revascularization.Methods and Results: Patients who were confirmed as type 1 acute MI (AMI) by coronary angiography were retrospectively analyzed. Patients who died in hospital or those not undergoing revascularization were excluded. Patients with a cancer history were compared with those without it. A cancer history was examined in the in-hospital cancer registry. The primary outcome was a composite of cardiac death, recurrent type 1 MI, post-discharge coronary revascularization, heart failure hospitalization, and stroke. Among 551 AMI patients, 55 had a cancer history (cancer group) and 496 did not (non-cancer group). Cox proportional hazards model revealed that the risk of composite endpoint was significantly higher in the cancer group than in the non-cancer group (adjusted hazard ratio [HR]: 1.78; 95% confidence interval [CI]: 1.13-2.82). Among the cancer group, patients who were diagnosed as AMI within 6 months after the cancer diagnosis had a higher risk of the composite endpoint than those who were diagnosed as AMI 6 months or later after the cancer diagnosis (adjusted HR: 5.43; 95% CI: 1.55-19.07). CONCLUSIONS: A cancer history increased the risk of CV events after discharge among AMI patients after revascularization.

Plasma Gel Made of Platelet-Poor Plasma: In Vitro Verification as a Carrier of Polyphosphate.

Plasma gel (PG) is a blood-derived biomaterial that can be prepared by heating or chemical cross-linking without the aid of intrinsic coagulation activity and has gradually been applied in the field of esthetic surgery. To explore the applicability of PG in regenerative therapy or tissue engineering, in this study, we focused on the advantages of the heating method and verified the retention capacity of the resulting PG for polyphosphate (polyP), a polyanion that contributes to hemostasis and bone regeneration. Pooled platelet-poor plasma (PPP) was prepared from four healthy male adult donors, mixed with synthetic polyP, and heated at 75 °C for 10 or 30 min to prepare PG in microtubes. The PG was incubated in PBS at 37 °C, and polyP levels in the extra-matrix PBS were determined by the fluorometric method every 24 h. The microstructure of PG was examined using scanning electron microscopy. In the small PG matrices, almost all of the added polyP (~100%) was released within the initial 24 h. In contrast, in the large PG matrices, approximately 50% of the polyP was released within the initial 24 h and thereafter gradually released over time. Owing to its simple chemical structure, linear polyP cannot be theoretically retained in the gel matrices used in this study. However, these findings suggest that thermally prepared PG matrices can be applied as carriers of polyP in tissue engineering and regenerative medicine.

Relationship between Delayed Breast Cancer Diagnosis and Behavioral Economic Factors and Personality Characteristics.

BACKGROUND: Delays in breast cancer diagnosis can allow the disease to progress to an incurable stage. However, factors that cause patients to delay seeking treatment are unclear. In this study, we aimed to identify behavioral economic factors and personality characteristics of patients with breast cancer who had a delayed diagnosis. METHODS: We analyzed questionnaires completed by 41 patients with breast cancer. A delayed diagnosis was defined if the time between the first symptom and the medical visit was more than 6 months. RESULTS: We found 11 patients who had a delayed diagnosis. The significant characteristics associated with patients with breast cancer who had delayed diagnosis were: (i) less experience with breast cancer screening; (ii) progressive disease stage; and (iii) low time and future time preference. We found no significant behavioral economic factors other than time preference, and personality that differed between patients with breast cancer who did and did not have a delayed diagnosis. CONCLUSION: Low time preference rate is a characteristic of patients with breast cancer who had a delayed diagnosis.

Aging-Related Catatonia with Reversible Dopamine Transporter Dysfunction in Females with Depressive Symptoms: A Case Series.

OBJECTIVES: The authors describe five depressive patients with initially decreased striatal accumulation of dopamine transporter (DAT) single-photon emission computed tomography (SPECT), which improved in parallel with clinical symptoms. METHODS: Patients who exhibited decreased striatal accumulation and recovery of DATSPECT were identified among patients with the symptoms of depression. Their clinical and neuroimaging data were reviewed. RESULTS: Five patients were identified. All patients were presenile or senile women who presented with catatonia subsequent to symptoms of depression that remitted with treatment. DAT-SPECT showed a decreased striatal accumulation in all patients, which increased after treatment. Two patients had met the diagnostic criteria of probable dementia with Lewy bodies (DLB), but no longer did so after their symptoms improved. CONCLUSIONS: Reversible DAT dysfunction observed in this study suggests that reversible impairment of dopaminergic transmission in the striatum partly underlies catatonia. Careful consideration should be given to diagnosing DLB in patients with decreased DAT-SPECT accumulation, especially when catatonia is present.

TAS2940, a novel brain-penetrable pan-ERBB inhibitor, for tumors with HER2 and EGFR aberrations.

Genetic alterations in human epidermal growth factor receptor type 2 (HER2)/epidermal growth factor receptor (EGFR) are commonly associated with breast and lung cancers and glioblastomas. Cancers with avian erythroblastosis oncogene B (ERBB) deregulation are highly metastatic and can cause primary brain tumors. Currently, no pan-ERBB inhibitor with remarkable brain penetration is available. Here, TAS2940, a novel irreversible pan-ERBB inhibitor with improved brain penetrability, was evaluated for its efficacy against several ERBB aberrant cancer models. The selectivity of TAS2940 was evaluated by enzymatic kinase assays. The inhibitory effects of TAS2940 against ERBB genetic alterations were examined using MCF10A cells expressing various HER2 or EGFR mutations and other generic cell lines harboring deregulated ERBB expression. In vivo efficacy of TAS2940 was examined following oral treatment in subcutaneous or intracranial xenograft cancer models. TAS2940 was highly potent against cells harboring HER2/EGFR alterations. TAS2940 could selectively inhibit phosphorylation of targets and the growth of cancer cells with ERBB aberrations in vitro. TAS2940 also inhibited tumor growth in xenograft mouse models with ERBB aberrations: HER2 amplification, HER2/EGFR exon 20 insertions, and EGFR vIII mutation. TAS2940 was effective in the intracranial xenograft models of HER2/EGFR cancers and improved the survival of these mice. TAS2940 has promising therapeutic effects in preclinical study against cancers harboring HER2/EGFR mutations, especially metastatic and primary brain tumors. Our results highlight potential novel strategies against lung cancers with brain metastases harboring HER2/EGFR exon 20 insertions and glioblastomas with EGFR aberrations.

Bifidobacterial GH146 ß-l-Arabinofuranosidase (Bll4HypBA1) as the Last Enzyme for the Complete Removal of Oligoarabinofuranosides from Hydroxyproline-Rich Glycoproteins.

In plant cell walls, the hydroxyproline-rich glycoproteins (HRGPs) such as extensin contain oligoarabinofuranoside linked to a hydroxyproline (Hyp) residue. The mature arabinooligosaccharide was revealed to be a tetrasaccharide (α-l-Araf-(1→3)-ß-l-Araf-(1→2)-ß-l-Araf-(1→2)-ß-l-Araf, l-Araf4 ), whose linkages are targets of the bifidobacterial and Xanthomonas arabinooligosaccharide-degrading enzymes. The l-Araf4 motif was cleaved by GH43 α-l-arabinofuranosidase (Arafase) and converted to an l-Araf3 -linked structure. The latter is then cleaved by GH121 ß-l-arabinobiosidase (HypBA2), producing ß-l-Araf-(1→2)-l-Ara (ß-l-arabinobiose) and mono-ß-l-Araf linked to the HRGP backbone. In bifidobacteria, the ß-l-arabinobiose is then hydrolyzed by GH127 ß-l-Arafase (Bll1HypBA1), a mechanistically unique cysteine glycosidase. We recently identified the distantly related homologue from Xanthomonas euvesicatoria as GH146 ß-l-Arafase along with paralogues from Bifidobacterium longum, one of which, Bll4HypBA1 (BLLJ_0089), can degrade l-Araf1 -Hyp in a similar way to that of GH146. As the chemical synthesis of the extensin hydrophilic motif 1 a, which possesses three distinct linkages that connect four oligoAraf residues [Hyp(l-Arafn ) (n=4, 3, 1)], was achieved previously, we precisely monitored the step-wise enzymatic cleavage of 1 a in addition to that of potato lectin. The results unequivocally revealed that this enzyme specifically degrades the Hyp(l-Araf1 ) motif.

Responses of promyelocytic leukemia HL60 cells as an inflammatory cell lineage model to silica microparticles used to coat blood collection tubes.

BACKGROUND: The preparation of platelet-rich fibrin (PRF) requires glass blood collection tubes, and thus, the shortage or unavailability of such tubes has driven clinicians to search for suitable substitutes, such as silica-coated plastic tubes. However, we have previously demonstrated the cytotoxicity of silica microparticles (MPs) used in plastic tubes to cultured human periosteal cells. To further establish the effects of silica MPs on inflammation, we examined silica MP-induced changes in a human promyelocytic cell model in vitro. METHODS: Human promyelocytic HL60 cells were used either without chemical induction or after differentiation induced using phorbol myristate acetate (PMA) or dimethyl sulfoxide. HL60 cells, osteoblastic MG63, and Balb/c mouse cells were treated with silica MPs, and their surface ultrastructure and numbers were examined using a scanning electron microscope and an automated cell counter, respectively. Differentiation markers, such as acid phosphatase, non-specific esterase, and CD11b, were visualized by cytochemical and immunofluorescent staining, and superoxide dismutase (SOD) activity was quantified. RESULTS: Regardless of SOD activity, silica cytotoxicity was observed in MG63 and Balb/c cells. At sub-toxic doses, silica MPs slightly or moderately upregulated the differentiation markers of the control, PMA-induced monocytic, and dimethyl sulfoxide-induced granulocytic HL60 cells. Although SOD activity was the highest (P < 0.05) in PMA-induced cells, a silica-induced reduction in cell adhesion was observed only in those cells (P < 0.05). CONCLUSIONS: Silica MP contamination of PRF preparations can potentially exacerbate inflammation at implantation sites. Consequently, unless biomedical advantages can be identified, silica-coated plastic blood collection tubes should not be routinely used for PRF preparations.

Mouse Acidic Chitinase Effectively Degrades Random-Type Chitosan to Chitooligosaccharides of Variable Lengths under Stomach and Lung Tissue pH Conditions.

Chitooligosaccharides exhibit several biomedical activities, such as inflammation and tumorigenesis reduction in mammals. The mechanism of the chitooligosaccharides' formation in vivo has been, however, poorly understood. Here we report that mouse acidic chitinase (Chia), which is widely expressed in mouse tissues, can produce chitooligosaccharides from deacetylated chitin (chitosan) at pH levels corresponding to stomach and lung tissues. Chia degraded chitin to produce N-acetyl-d-glucosamine (GlcNAc) dimers. The block-type chitosan (heterogenous deacetylation) is soluble at pH 2.0 (optimal condition for mouse Chia) and was degraded into chitooligosaccharides with various sizes ranging from di- to nonamers. The random-type chitosan (homogenous deacetylation) is soluble in water that enables us to examine its degradation at pH 2.0, 5.0, and 7.0. Incubation of these substrates with Chia resulted in the more efficient production of chitooligosaccharides with more variable sizes was from random-type chitosan than from the block-type form of the molecule. The data presented here indicate that Chia digests chitosan acquired by homogenous deacetylation of chitin in vitro and in vivo. The degradation products may then influence different physiological or pathological processes. Our results also suggest that bioactive chitooligosaccharides can be obtained conveniently using homogenously deacetylated chitosan and Chia for various biomedical applications.

Platelet adhesion on commercially pure titanium plates in vitro III: effects of calcium phosphate-blasting on titanium plate biocompatibility.

BACKGROUND: Platelet-rich plasma (PRP) is often used to improve surface biocompatibility. We previously found that platelets rapidly adhere to plain commercially pure titanium (cp-Ti) plates in the absence, but not in the presence, of plasma proteins. To further expand on these findings, in the present study, we switched titanium plates from a plain surface to a rough surface that is blasted with calcium phosphate (CaP) powder and then examined platelet adhesion and activation. METHODS: Elemental distribution in CaP-blasted cp-Ti plates was analyzed using energy-dispersive X-ray spectroscopy. PRP samples prepared from anticoagulated blood samples of six healthy, non-smoking adult male donors were loaded on CaP-blasted cp-Ti plates for 1 h and fixed for examination of platelet morphology and visualization of PDGF-B and platelet surface markers (CD62P, CD63) using scanning electron microscopy and fluorescence microscopy. Plain SUS316L stainless steel plates used in injection needles were also examined for comparison. RESULTS: Significant amounts of calcium and phosphate were detected on the CaP-blasted cp-Ti surface. Platelets rapidly adhered to this surface, leading to higher activation. Platelets also adhered to the plain stainless surface; however, the levels of adhesion and activation were much lower than those observed on the CaP-blasted cp-Ti plate. CONCLUSIONS: The CaP-blasted cp-Ti surface efficiently entraps and activates platelets. Biomolecules released from the activated platelets could be retained by the fibrin matrix on the surface to facilitate regeneration of the surrounding tissues. Thus, PRP immersion could not only eliminate surface air bubbles but also improve the biocompatibility of the implant surface.

Clinical and Angiographic Features of Patients With Out-of-Hospital Cardiac Arrest and Acute Myocardial Infarction.

BACKGROUND: Sudden cardiac arrest is a serious complication of acute myocardial infarction (MI). Although in-hospital mortality from MI has decreased, the mortality of MI patients complicated with out-of-hospital cardiac arrest (OHCA) remains high. However, the features of acute MI patients with OHCA have not been well known. OBJECTIVES: We sought to characterize the clinical and angiographic features of acute MI patients with OHCA comparing with those without OHCA. METHODS: We retrospectively analyzed 480 consecutive patients with acute MI undergoing percutaneous coronary intervention. Patients complicated with OHCA were compared with patients without OHCA. RESULTS: Of the patients, 141 (29%) were complicated with OHCA. Multivariate analysis revealed that age (odds ratio [OR]: 0.8; 95% confidence interval [CI]: 0.7 to 0.9 per 5 years; p < 0.001), estimated glomerular filtration rate (OR: 0.8; 95% CI: 0.7 to 0.8 per 10 ml/min/1.73 m2; p < 0.001), peak creatine kinase-myocardial band (OR: 1.3; 95% CI: 1.2 to 1.4 per 102 U/l; p < 0.001), calcium-channel antagonists use (OR: 0.4; 95% CI: 0.2 to 0.7; p = 0.002), the culprit lesion at the left main coronary artery (OR: 5.3; 95% CI: 1.9 to 15.1; p = 0.002), and the presence of chronic total occlusion (OR: 2.9; 95% CI: 1.5 to 5.7; p = 0.001) were significantly associated with OHCA. CONCLUSIONS: Younger age, no use of calcium-channel antagonists, worse renal function, larger infarct size, culprit lesion in the left main coronary artery, and having chronic total occlusion were associated with OHCA.

A Case of Autoimmune Pulmonary Alveolar Proteinosis with Pulmonary Fibrosis and Asbestosis-Like Features.

A 78-year-old man who had worked in the building industry visited our hospital because of groundglass opacity with smoothly thickened, intralobular interstitial lines and interlobular septal lines on chest high-resolution computed tomography (HRCT). HRCT image also showed a focal area of reticulation and pleural thickening. Lung specimens obtained by surgical lung biopsy showed accumulations of intra-alveolar periodic acid-Schiffpositive materials, usual interstitial pneumonia (UIP)-like subpleural lung fibrosis and asbestos bodies (1 body/cm2 in high-power field, ×400). Serum granulocyte-macrophage colony stimulating factor autoantibody was positive. The patient was diagnosed as having autoimmune pulmonary alveolar proteinosis (PAP) and needed differential diagnosis from secondary PAP caused from pulmonary asbestosis and UIP. Careful observation of the manifestations of pulmonary asbestosis and the progression of fibrosis using HRCT will be necessary in this patient.

A PRIMPOL mutation and variants in multiple genes may contribute to phenotypes in a familial case with chronic progressive external ophthalmoplegia symptoms.

Chronic progressive external ophthalmoplegia (CPEO) is one of the most common mitochondrial disorders. It is characterized by bilateral, slowly progressing loss of extraocular muscle mobility, orbicularis oculi weakness, ptosis, and other neuromuscular symptoms, which are caused by the accumulation of multiple mitochondrial DNA (mtDNA) deletions. Many mutations in different nuclear genes, such as POLG1, POLG2, ANT1, and others, have been described as causing autosomal-inherited CPEO with multiple mtDNA deletions. Most causative genes are involved in mtDNA replication impairment. Here, we report a family with CPEO-like symptoms characterized by multiple muscle mtDNA deletions, ptosis, diabetes, hearing loss, mental retardation, and emotional instability. We performed genetic analyses to identify nuclear gene mutations in the family. DNA from the proband was analyzed by whole-exome sequencing. In addition to possible pathogenic mutations, rare variants were prioritized for gene-functional phenotype interpretation. We found possible pathogenetic mutations in the PRIMPOL, BRCA1, CPT2, and GJB2 genes, and functional polymorphisms in the CARD8, and MEFV genes. Multiple functional polymorphisms and possible pathogenic mutations may contribute to mitochondrial-disease-like phenotypes in a composite manner.

Elevation of pulmonary CD163+ and CD204+ macrophages is associated with the clinical course of idiopathic pulmonary fibrosis patients.

BACKGROUND: M2-like/repair macrophages are thought to contribute to fibrotic process of idiopathic pulmonary fibrosis (IPF). We analyzed the association between pulmonary accumulation of M2-like macrophages and survival in IPF patients. METHODS: Lung tissues were obtained by surgical lung biopsy from patients with IPF (n=16), nonspecific interstitial pneumonia (NSIP, n=8) and control subjects (n=14). Samples were also obtained at autopsy from 9 patients who died of acute exacerbation (AE) of IPF. Lung specimens and/or human peripheral blood mononuclear cells-derived macrophages were evaluated by immunohistochemistry for expression of CD68 (pan-macrophage marker), CD163, and CD204 (M2-like macrophage markers), and by in situ mRNA hybridization and ELISA for production of transforming growth factor-ß1 (TGF-ß1). RESULTS: CD68+, CD163+, and CD204+ cell counts and CD163+/CD68+ and CD204+/CD68+ cell ratios were comparable in IPF and NSIP lung tissues and significantly higher than in control tissues. IPF-AE lung samples contained significantly elevated CD68+ and CD163+ cell counts and CD163+/CD68+ cell ratio compared with IPF samples, whereas CD204+ cell counts and CD204+/CD68+ cells ratio did not differ. High CD163+/CD68+ and CD204+/CD68+ cell ratios were significantly associated with shorter overall survival and time-to-AE in IPF patients. In vitro-differentiated human CD163+ and CD204+ macrophages both secreted TGF-ß1; however, the novel IPF drug pentraxin 2/serum amyloid protein could suppress secretion only by CD204+ macrophages. CONCLUSIONS: Pulmonary accumulation of CD163+ and CD204+ macrophages is associated with worse clinical course in IPF patients. Suppression of macrophage activation and TGF-ß1 secretion may be a potential therapeutic target for IPF.

Hepcidin-25/erythroferrone ratio predicts improvement of anaemia in haemodialysis patients treated with ferric citrate hydrate.

BACKGROUND/AIMS: Hepcidin-25 (HEP-25) and erythroferrone (ERFE) are key regulators of iron homeostasis. Correlations among serum ferritin, ERFE and HEP-25 levels and improvements in anaemia have not been evaluated after administration of ferric citrate hydrate (FCH). METHODS: This retrospective observational study investigated 24 patients on haemodialysis with both anaemia (haemoglobin (Hb) < 12 g/dL) and hyperphosphatemia (inorganic phosphorus ≥6 mg/dL). The patients who were administered FCH (1500 mg/day) for 12 consecutive weeks and 12 control patients who were administered a phosphate binder other than FCH were included. Correlations among Hb, HEP-25 and ERFE levels were studied. We then stratified the FCH group into two subgroups using the median baseline values of ferritin, HEP-25, ERFE and HEP-25/ERFE ratio to predict whether these markers could serve as prognostic indicators in the treatment of anaemia. RESULTS: In the FCH group, Hb, transferrin saturation, ferritin, HEP-25 and ERFE levels were all significantly increased, while inorganic phosphorus levels, dosage of erythropoietin-stimulating agent, and erythropoietin resistance index were all significantly decreased after drug administration. A significant inverse correlation was apparent between Hb and HEP-25 levels, and a significant positive correlation was seen between Hb and ERFE levels. A significant inverse correlation was found between HEP-25 and serum ERFE levels. Compared with the high HEP-25/ERFE ratio group, only the low HEP-25/ERFE ratio group exhibited significantly increased Hb levels at 12 weeks. CONCLUSION: HEP-25/ERFE ratio could be a novel prognostic marker for increases in Hb levels following FCH administration.

Fistula between the Thoracic Duct and an Unusual Vessel Aneurysm Branching Off the Abdominal Aorta Revealed by Aneurysm Rupture: A Case Report.

Fistulas between an aneurysm branching off the abdominal aorta and the thoracic duct are rare. We report a case of aneurysmal-thoracic duct fistula diagnosed by angiography when aneurysm ruptured, and we successfully treated by catheter embolization. A 42-year-old man was referred to our hospital with a chief complaint of sudden back and chest pain. Computed tomography showed both post-mediastinal and retroperitoneal hematomas, with the aneurysm from the aorta being connected to the thoracic duct. After confirming the aneurysmal-thoracic duct fistula by angiography, we performed embolization of the aneurysm. The patient has remained well for 3 postoperative months, to date.

Low positive titer of anti-melanoma differentiation-associated gene 5 antibody is not associated with a poor long-term outcome of interstitial lung disease in patients with dermatomyositis.

BACKGROUND: Anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5-Ab) is associated with fatal rapidly progressive interstitial lung disease (RP-ILD) in patients with dermatomyositis (DM). We attempted to clarify whether anti-MDA5-Ab is associated with long-term outcomes in patients with DM-ILD. METHODS: Thirty-six patients with DM-ILD were retrospectively analyzed for their serum anti-MDA5-Ab by using an enzyme-linked immunosorbent assay. We analyzed the association between clinical parameters, including the serum levels of anti-MDA5-Ab and ferritin. RESULTS: Fourteen patients (39%) were positive for anti-MDA5-Ab. The serum levels of anti-MDA5-Ab and ferritin in 7 patients with acute death were higher than those in the surviving patients. An "unclassifiable pattern" on chest computed tomography and the development of RP-ILD were also prognostic markers. The serum levels of anti-MDA5-Ab and ferritin (cut-off levels, 100 IU/mL and 899 ng/mL, respectively) were markers predictive of acute death, showing good sensitivity (86% and 83%) and specificity (97% and 100%). All 7 patients with acute death developed RP-ILD and were positive for anti-MDA5-Ab, including 6 patients with a high titer (≥100 IU/mL), whereas only 2 patients (29%) developed RP-ILD among the 7 survivors with a low titer of anti-MDA5-Ab ( < 100 IU/mL). In contrast, a low positive titer of anti-MDA5-Ab was not associated with changes in pulmonary function for 2 years. CONCLUSIONS: Although a high serum titer of anti-MDA5-Ab (≥100 IU/mL) is associated with acute death via the development of RP-ILD, outcomes in the chronic phase for patients with a low titer of anti-MDA5-Ab ( < 100 IU/mL) were similar to those of patients without anti-MDA5-Ab.

Mouse model of chorea-acanthocytosis exhibits male infertility caused by impaired sperm motility as a result of ultrastructural morphological abnormalities in the mitochondrial sheath in the sperm midpiece.

Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disease characterized by neurodegeneration in the striatum and acanthocytosis caused by loss-of-function mutations in the Vacuolar Protein Sorting 13 Homolog A (VPS13A) gene, which encodes chorein. We previously produced a ChAc-model mouse with a homozygous deletion of exons 60-61 in Vps13a, which corresponded to the human disease mutation. We found that male ChAc-model mice exhibited complete infertility as a result of severely diminished sperm motility. Immunocytochemical study revealed that chorein-like immunoreactivity is abundant only in the midpiece, mitochondria-rich region, of the sperm of wild type mice. They showed no significant differences from wild types in terms of the adenosine 5'-triphosphate (ATP) concentration of their sperm, sperm count, or sexual activity. Electron microscopy revealed abnormal ultrastructural morphology of the mitochondria in the midpiece of sperm from ChAc-model mice. These results suggest that chorein is essential in mouse sperm for the maintenance of ultrastructural mitochondrial morphology and sperm motility.

Pulmonary pleomorphic carcinoma: A case harboring EGFR mutation treated with EGFR-TKIs.

Pulmonary pleomorphic carcinoma (PPC) is a very rare type of primary lung cancer with an aggressive clinical course. Few reports have documented therapeutic options for PPC with EGFR mutations. Herein, we report a case of PPC with EGFR mutation treated with EGFR-tyrosine kinase inhibitors (TKIs). A 65-year-old Japanese woman was diagnosed with stage IV lung adenocarcinoma with L858R point mutation in exon 21. Despite treatment with erlotinib, the patient died after two weeks as a result of rapid disease progression. Postmortem examination indicated that the thoracic tumors consisted primarily of spindle/sarcomatous components, while expression of the mutated EGFR protein was only observed in adenocarcinoma components. We speculate that the tumor was not driven by EGFR mutation. Clinicians should bear in mind the possibility of pleomorphic carcinoma if EGFR-TKI treatment fails to achieve a clinical response for adenocarcinoma harboring an activating EGFR mutation diagnosed on the basis of small biopsy specimens.