Acquired cutis laxa secondary to acute generalized exanthematous pustulosis: A case report and mini-review of literature.

Cutis laxa presents as loose redundant skin folds and loss of dermal elastic tissue. Acquired cutis laxa (ACL) is characterized by later onset. It has been reported in association with various kinds of neutrophilic dermatoses, drugs, metabolic disorders, and autoimmune disorders. Acute generalized exanthematous pustulosis (AGEP) is usually classified as a severe cutaneous adverse reaction characterized by T cell-mediated neutrophilic inflammation. We previously reported a mild case of AGEP caused by gemcitabine in a 76-year-old man. Here, we report a case of ACL secondary to AGEP in this patient. He developed AGEP 8 days after gemcitabine administration. Four weeks after beginning chemotherapy, his skin had become atrophic, loose, and darkly pigmented in areas previously affected by AGEP. Histopathological examination revealed edema and perivascular lymphocytic infiltration but no neutrophilic infiltration in the upper dermis. Elastica van Gieson staining showed that the elastic fibers in all layers of the dermis were sparse and shortened. Electron microscopy showed elevated numbers of fibroblasts and altered elastic fibers with irregular surfaces. Finally, he was diagnosed with ACL secondary to AGEP. He was treated with topical corticosteroids and oral antihistamines. Skin atrophy decreased over 3 months. We summarize 36 cases (including our case) with ACL secondary to neutrophilic dermatosis. We discuss these clinical manifestations, causative neutrophilic disorders, treatments, and outcomes. The mean age of patients was 3.5 years. Five patients had an aortic lesion as systemic involvement. The most common causative neutrophilic disorders were Sweet syndrome (24 cases), followed by urticaria-like neutrophilic dermatosis (11 cases). There were no cases of AGEP except for our case. Although treatment for ACL secondary to neutrophilic dermatosis, such as dapsone, oral prednisolone, adalimumab, and plastic surgery were reported, ACL is generally refractory and irreversible. Our patient was considered reversibly cured due to the absence of continuous neutrophil-mediated elastolysis.

Primary Cytomegalovirus Pneumonia Successfully Treated with Corticosteroid Therapy and Valganciclovir.

Cytomegalovirus infection is typically asymptomatic in immunocompetent individuals. A 26-year-old woman was admitted to our hospital with a fever and breathlessness. Chest computed tomography (CT) revealed bilateral diffuse reticulation and nodules. Laboratory investigations showed atypical lymphocytosis and increased transaminases. She was treated with corticosteroid pulse therapy because of acute lung injury, and her clinical condition improved. Based on the presence of cytomegalovirus antibodies, antigen, and polymerase chain reaction findings, she was diagnosed with primary cytomegalovirus pneumonia and treated with valganciclovir. Primary cytomegalovirus pneumonia is very rare in immunocompetent individuals. The efficacy of corticosteroid and valganciclovir against cytomegalovirus pneumonia in this patient is noteworthy.

Comparison of clinical utility of deep learning-based systems for small-bowel capsule endoscopy reading.

BACKGROUND AND AIM: Convolutional neural network (CNN) systems that automatically detect abnormalities from small-bowel capsule endoscopy (SBCE) images are still experimental, and no studies have directly compared the clinical usefulness of different systems. We compared endoscopist readings using an existing and a novel CNN system in a real-world SBCE setting. METHODS: Thirty-six complete SBCE videos, including 43 abnormal lesions (18 mucosal breaks, 8 angioectasia, and 17 protruding lesions), were retrospectively prepared. Three reading processes were compared: (A) endoscopist readings without CNN screening, (B) endoscopist readings after an existing CNN screening, and (C) endoscopist readings after a novel CNN screening. RESULTS: The mean number of small-bowel images was 14 747 per patient. Among these images, existing and novel CNN systems automatically captured 24.3% and 9.4% of the images, respectively. In this process, both systems extracted all 43 abnormal lesions. Next, we focused on the clinical usefulness. The detection rates of abnormalities by trainee endoscopists were not significantly different across the three processes: A, 77%; B, 67%; and C, 79%. The mean reading time of the trainees was the shortest during process C (10.1 min per patient), followed by processes B (23.1 min per patient) and A (33.6 min per patient). The mean psychological stress score while reading videos (scale, 1-5) was the lowest in process C (1.8) but was not significantly different between processes B (2.8) and A (3.2). CONCLUSIONS: Our novel CNN system significantly reduced endoscopist reading time and psychological stress while maintaining the detectability of abnormalities. CNN performance directly affects clinical utility and should be carefully assessed.

Ivermectin Inhibits HBV Entry into the Nucleus by Suppressing KPNA2.

Hepatitis B virus (HBV) specifically infects human hepatocytes and increases the risks of cirrhosis and liver cancer. Currently, nucleic acid analogs are the main therapeutics for chronic hepatitis caused by HBV infection. Although nucleic acid analogs can eliminate HBV DNA by inhibiting HBV reverse transcriptase, they cannot lead to negative conversion of covalently closed circular DNA (cccDNA) and hepatitis B surface antigen (HBsAg). In this study, we revealed that the antifilarial drug ivermectin suppresses HBV production by a different mechanism from the nucleic acid analog entecavir or Na+ taurocholate co-transporting polypeptide-mediated entry inhibitor cyclosporin A. Ivermectin reduced the levels of several HBV markers, including HBsAg, in HBV-infected human hepatocellular carcinoma cells (HepG2-hNTCP-C4 cells) and humanized mouse hepatocytes (PXB hepatocytes). In addition, ivermectin significantly decreased the expression of HBV core protein and the nuclear transporter karyopherin α2 (KPNA2) in the nuclei of HepG2-hNTCP-C4 cells. Furthermore, depletion of KPNA1-6 suppressed the production of cccDNA. These results suggest that KPNA1-6 is involved in the nuclear import of HBV and that ivermectin suppresses the nuclear import of HBV by inhibiting KPNA2. This study demonstrates the potential of ivermectin as a novel treatment for hepatitis B.

Predictive Value of Total Small-Vessel Disease Score for Recurrent Stroke in Patients Undergoing Maintenance Hemodialysis.

OBJECTIVES: We sought to examine the validity of the total small-vessel disease (SVD) score in patients receiving maintenance hemodialysis by investigating its predictive value for recurrent stroke. METHODS: We identified 159 patients who showed acute ischemic stroke while receiving maintenance hemodialysis at our institute between January 1, 2008, and December 31, 2020; retrospectively calculated the total SVD score for each patient; and extracted data on demographic factors and comorbidities that could potentially affect recurrent stroke. Death was thought to be a potential competing risk for recurrent stroke because the perceived risk of death was considerably higher than the risk of recurrent stroke in these patients. Thus, we investigated the association between the total SVD score and recurrent stroke by analyzing the competing risk of non-stroke death. RESULTS: The median (interquartile range) age was 72 (62-80) years. A total of 38 (23.9%) recurrent strokes occurred, and 69 (43.4%) patients died during the 505 patient-year follow-up study. The estimated cumulative incidence of recurrent stroke at five years was 13.3%, 13.4%, 24.1%, 50%, and 60% for scores of 0 to 4, respectively, and the hazard ratio (HR), adjusted for variables that had been reported to be risk factors of stroke in dialysis patients, per unit increase in the score was 1.72 (95% CI, 1.34-2.21; p<0.001). CONCLUSION: A higher total SVD score was associated with an increased risk of recurrent stroke in patients undergoing maintenance hemodialysis.

Pembrolizumab-Induced Lichen Planus on the Scalp of a Patient with Non-Small-Cell Lung Carcinoma.

A 67-year-old man with non-small-cell lung carcinoma was referred to our department because of a pruritic rash on his head and upper extremities. Prior to the development of the rash, he had received 4 cycles of combination therapy with pemetrexed, carboplatin, and pembrolizumab, followed by 2 cycles of pembrolizumab monotherapy. On physical examination, violaceous scaly erythema grouped on his scalp and upper extremities. Histologically, the scalp lesions demonstrated irregular acanthosis that formed a characteristic saw-tooth appearance with hypergranulosis and typical lichenoid tissue reaction. These findings suggested that the scalp lesions were lichen planus. Two-week administration of topical corticosteroid dramatically improved the rash. Immunotherapy with pembrolizumab, an anti-PD-1 antibody, can induce T-cell activation that results in various immune-related adverse effects such as lichenoid tissue reaction. However, lichen planus is generally found on the extremities and/or oral mucosa, and unlike in this case, the scalp is rarely affected. Although the exact mechanism underlying predominant scalp involvement is unknown, the present case indicates that anti-PD-1 therapy-induced lichen planus can develop not only on the extremities and oral mucosa but also on the scalp. Interestingly, the lesions were not induced by the combination of chemotherapy and pembrolizumab; rather, they occurred soon after initiation of pembrolizumab monotherapy. In the present case, pembrolizumab-induced T-cell activation which triggered lichenoid tissue reaction may have been suppressed by chemotherapy-induced immunosuppression. Dermatologists should have a thorough knowledge of the cutaneous lesions that manifest as irAEs of anti-PD-1 therapy.

[A case of secondary central nervous system lymphoma presenting marked hypoglycorrhachia].

A 67-year-old male was transferred to our hospital with diplopia, decreased deep tendon reflex and ataxia. He had been suspected Fisher syndrome because of previous upper respiratory tract infection. A cerebrospinal fluid examination showed marked hypoglycorrhachia, pleocytosis and elevated protein, and cytological examination suggested malignant lymphoma. Abdominal computed tomography revealed a left adrenal mass. A biopsy of the left adrenal mass revealed diffuse large B-cell lymphoma. He was treated with a combination of R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin and prednisolone) and intrathecal administration of methotrexate, cytarabine and prednisolone. Neurological symptoms were gradually improved. Malignancy should be considered in addition to bacterial, fungal or tuberculous meningitis in a case with marked hypoglycorrhachia.

Rare Case of Floating Intimal Flap Associated with Atheromatous Carotid Plaque.

BACKGROUND: A mobile carotid plaque can be detected by duplex ultrasonography and is a high-risk factor for embolic stroke. CASE DESCRIPTION: We herein present a case involving an 80-year-old man with an asymptomatic carotid floating flap diagnosed by duplex ultrasonography and treated with carotid endarterectomy. Intraoperatively, an ulceration was found immediately proximal to the neck of the floating flap, and the shape and size of the ulceration were quite similar to those of the floating flap. In a histopathologic examination of the specimen resected by carotid endarterectomy, the plaque lacked the internal elastic lamina (IEL) at the ulceration, calcification was observed in the plaque and medial layer at the ulceration, and the floating flap consisted of the IEL accompanied by calcification, fibrin, and foamy cells. CONCLUSIONS: Progression of the atheroma and Mönckeberg sclerosis might have affected disruption of the IEL, causing the IEL to finally peel off. A floating intimal flap accompanied by an atheroma without intraplaque hemorrhage is a rare cause of mobile plaque formation. This type of mobile plaque might not be dissolved by medical treatment alone. In such cases, surgical treatment is a suitable therapeutic choice to prevent stroke.

Iatrogenic Removal of the Intima in the Middle Cerebral Artery by a Stent Retriever: A Report of Two Cases.

BACKGROUND: Mechanical thrombectomy improves functional outcomes in patients with acute ischemic stroke. However, stent retrievers have the risk of vascular damage. CASE DESCRIPTION: We present 2 cases of patients with acute internal carotid artery occlusion who experienced removal of the intima by a stent retriever. In both patients, a 6 × 30-mm Solitaire stent was fully deployed from the M2 portion and slowly withdrawn. White membranes were retrieved outside the strut in both patients. Histopathologic examination showed that one membrane consisted of thickened intima and internal elastic lamina and the other consisted of calcified intima and internal elastic lamina. One patient who suffered embolic stroke experienced recurrent infarction within 24 hours after operation, and the damaged vessel was occluded on magnetic resonance angiography 21 days after stroke. In another patient with carotid artery dissection, the damaged vessel showed asymptomatic stenosis on magnetic resonance angiography 90 days after stroke. Arteries with both atherosclerosis and vessel dissection may be vulnerable to high radial expansion force. CONCLUSIONS: Full deployment of a relatively large-sized stent into a vulnerable vessel may cause vessel dissection after removal of the intima. Appropriate material selection and treatment strategy while considering stroke etiology and the occlusion site are important to prevent vessel damage.

Adhesive Interactions between Mononuclear Phagocytes and Intestinal Epithelium Perturb Normal Epithelial Differentiation and Serve as a Therapeutic Target in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Disturbance of intestinal homeostasis is associated with the development of inflammatory bowel disease [IBD], and TGF-ß signalling impairment in mononuclear phagocytes [MPs] causes murine colitis with goblet cell depletion. Here, we examined an organoid-MP co-culture system to study the role of MPs in intestinal epithelial differentiation and homeostasis. METHODS: Intestinal organoids were co-cultured with lamina propria leukocytes and bone marrow-derived dendritic cells [BMDCs] from CD11c-cre Tgfbr2fl/fl mice. Organoid-MP adhesive interactions were evaluated by microscopy, RT-PCR, and flow cytometry. Murine colitis models (dextran sodium sulphate [DSS], CD11c-cre Tgfbr2fl/fl, T-cell-transfer) were used for histological and immunohistochemical analysis. Anti-E-cadherin antibody treatment or CD11c+-cell-specific CDH1 gene deletion were performed for E-cadherin neutralization or knockout. Colonic biopsies from patients with ulcerative colitis were analysed by flow cytometry. RESULTS: Intestinal organoids co-cultured with CD11c+ lamina propria leukocytes or BMDCs from CD11c-cre Tgfbr2fl/fl mice showed morphological changes and goblet cell depletion with Notch signal activation, analogous to CD11c-cre Tgfbr2fl/fl colitis. E-cadherin was upregulated in CD11c+ MPs, especially CX3CR1+CCR2+ monocytes, of CD11c-cre Tgfbr2fl/fl mice. E-cadherin-mediated BMDC adhesion promoted Notch activation and cystic changes in organoids. Anti-E-cadherin antibody treatment attenuated colitis in CD11c-cre Tgfbr2fl/fl and T-cell-transferred mice. In addition, E-cadherin deletion in CD11c+ cells attenuated colitis in both CD11c-cre Tgfbr2fl/fl and DSS-treated mice. In patients with ulcerative colitis, E-cadherin expressed by intestinal CD11c+ leukocytes was enhanced compared with that in healthy controls. CONCLUSIONS: E-cadherin-mediated MP-epithelium adhesion is associated with the development of colitis, and blocking these adhesions may have therapeutic potential for IBD.

Extranodal NK/T-cell lymphoma of the nasal cavity developed in a patient with intestinal Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorder.

Extranodal NK/T cell lymphoma, nasal type (ENKL) developed in a patient with intestinal Epstein-Barr virus (EBV)-positive T/NK-cell lymphoproliferative disorder (LPD). The patient was a 46-year-old Chinese man who complained of diarrhea and abdominal pain without immune-deficiency. Endoscopy demonstrated ileum ulcers like Crohn's disease, without histological granulomas. His symptoms continued waxing and waning for 3 years until he developed overt lymphoma (ENKL) in the nasal cavity. The ileum lesions exacerbated into a large deep ulcer, and the biopsy specimens from the ileum, including the one 3 years ago, showed infiltration of small lymphocytes containing many EBV-positive T/NK cells without atypia. Thus, the patient illness of intestine was revealed as intestinal EBV-positive T/NK-cell LPD, which might be closely associated with development of ENKL in this patient. In cases of inflammatory bowel disease without typical clinical courses and histological findings, check-up of EBV in the biopsy might help correct diagnosis.

Patterns of stress coping and depression among patients with head and neck cancer: A Japanese cross-sectional study.

OBJECTIVE: Patients with head and neck cancer (HNC) experience many stressful problems with breathing, eating, swallowing, and/or speaking. The aim of this study was to (a) identify the clusters of HNC patients based on their stress coping strategies and (b) evaluate the differences in clinical data and depression among the identified HNC patients' coping clusters. METHODS: We conducted a single-center, cross-sectional study with self-completed questionnaires for patients with HNC between April and August 2013. We measured stress coping (an abbreviated version of the COPE Inventory: Brief COPE) and depression (the Japanese version of the Beck Depression Inventory-II: BDI-II). RESULTS: Of the 116 patients who completed all the questionnaires, 81 (69.8%) participants were 60 to 79 years old and 105 (90.5%) were men. Cluster analysis based on the standardized z score of Brief COPE showed that patients were classified into 3 clusters, labeled "dependent coping," "problem-focused coping," and "resigned coping." The ANOVA revealed that depression (BDI score) was significantly higher in the dependent-coping cluster compared with the problem-focused coping. CONCLUSIONS: This study indicates that patients with a dependent-coping pattern may account for the largest HNC population and are likely to suffer from depression. Dependent coping includes smoking, drinking, seeking support, or engaging self-distraction. In the future, we should develop psychological intervention programs focused on coping strategies and enhancement of the support system for patients with HNC.

Persistence of psychological distress and correlated factors among patients with head and neck cancer.

OBJECTIVE: Many patients with head and neck cancer (HNC) suffer from psychological distress associated with dysfunction and/or disfigurement. Our aim was to evaluate the ratio of patients with persistence of psychological distress during hospitalization and identify the predictors of persistence or change in psychological distress among HNC patients. METHOD: We conducted a single-center longitudinal study with self-completed questionnaires. We evaluated psychological distress (the Hospital Anxiety and Depression Scale; HADS) and functional level (the Functional Assessment of Cancer Therapy-Head and Neck Scale; FACT-H&N) among patients during hospitalization at the Medical Hospital of Tokyo Medical and Dental University. RESULTS: Of 160 patients, 117 (73.1%) completed the questionnaire at both admission and discharge. Some 42 (52.5%) patients reported persistent psychological distress. The physical well-being of patients with continued distress was significantly lower than that of other patients (21.7 ± 4.7, 19.4 ± 6.1, 19.5 ± 5.4; p < 0.01), and the emotional well-being of patients with continued distress was significantly lower than that in patients with no distress and reduced distress (22.3 ± 3.5, 20.5 ± 2.5; p < 0.01). Significant of results: Impaired physical and emotional function appears to be associated with persistent psychological distress among HNC patients. Psychological interventions focused on relaxation, cognition, or behavior may be efficacious in preventing such persistent distress.

[Clinical Study of Acute Uncomplicated Cystitis].

Escherichia coli is the most commonly isolated bacterium in urinary tract infections, especially in acute uncomplicated cystitis. It is reported that fluoroquinolone-resistant E. coli is increasing. However, according to the guidelines for antimicrobial use published by the Japanese Associations for Infectious Diseases (JAID) and the Japanese Society of Chemotherapy (JSC) in 2014, the first line antimicrobial regimen for the treatment of acute uncomplicated cystitis is a 3-day regimen with fluoroquinolone. We analyzed the causative bacteria and clinical efficacy of antimicrobial treatment in acute uncomplicated cystitis cases at our institute. Patients diagnosed as having acute uncomplicated cystitis who had ≥ 10(4) colony-forming units/mL of bacteria in their midstream urine in our outpatient clinic between 2012 and 2013 were enrolled in this study. We analyzed their clinical data retrospectively. From 173 patients, 212 strains were isolated. Of these, 135 (63.7%) were E. coli, including 15 strains (11.1%) that were levofloxacin resistant. One hundred twenty-three patients (63.7%) were treated with cephalosporin, and 46 patients (26.6%) were treated with fluoroquinolone. In all, 140 patients (80.9%) visited the outpatient clinic for an average of 8.4 days after their treatment. For 130 patients (92.6%), the clinical outcomes of antimicrobial treatment were judged as effective. The clinical outcomes were effective in 92.1% of the patients with cephalosporin treatment and in 97.1% of those with fluoroquinolone treatment. Only one patient who had levofloxacin-resistant E. coli in her urine was treated with fluoroquinolone. The clinical outcome was effective. Of the E. coli isolated from acute uncomplicated cystitis patients, 11.1% were levofloxacin-resistant strains. However, the clinical efficacy of antimicrobial treatment was relatively high (92.9%) in this study. The antimicrobial treatment for acute uncomplicated cystitis recommended by the guidelines published by the JAID and JSC was effective in the current situation.

Reliability and validity of the Head and Neck Cancer Inventory (HNCI) in Japanese patients.

OBJECTIVE: This project evaluated the psychometric properties of a translated version of the Head and Neck Cancer Inventory (HNCI) for use with Japanese patients. The HNCI is a measure for assessing the quality of life (QoL) of head and neck cancer patients and survivors. The present study was aimed at investigating the reliability and validity of this translated instrument. METHOD: Some 165 patients with head and neck cancer (HNC) were enrolled at the Tokyo Medical and Dental University Hospital. The instrument's internal consistency and test-retest reliability were evaluated. Criterion-related validity was assessed by correlations between the HNCI and the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) scales. RESULTS: Some 29 of the 30 items in the original version were selected to comprise the Japanese version of the HNCI (Japanese HNCI). Investigation of criterion-related validity using the FACT-H&N demonstrated significant correlations (Spearman's ρ = 0.47-0.63). The value of Cronbach's α for each subscale ranged from 0.84 to 0.87. Test-retest reliability showed an intraclass correlation coefficient (ICC) of 0.62-0.79. SIGNIFICANCE OF RESULTS: The reliability and validity of the Japanese HNCI were evaluated. Although its classification is different from the original U.S. version, the Japanese HNCI is a self-administered questionnaire that can assess quality of life (QoL) in patients with head and neck cancer.