Serum CCL17 level becomes a predictive marker to distinguish between mild/moderate and severe/critical disease in patients with COVID-19.

COVID-19, a novel coronavirus-related illness, has spread worldwide. Patients with apparently mild/moderate symptoms can suddenly develop severe pneumonia. Therefore, almost all COVID-19 patients require hospitalization, which can reduce limited medical resources in addition to overwhelming medical facilities. To identify predictive markers for the development of severe pneumonia, a comprehensive analysis of serum chemokines and cytokines was conducted using serial serum samples from COVID-19 patients. The expression profiles were analyzed along the time axis. Serum samples of common diseases were enrolled from a BioBank to confirm the usefulness of predictive markers. Five factors, IFN-λ3, IL-6, IP-10, CXCL9, and CCL17, were identified as predicting the onset of severe/critical symptoms. The factors were classified into two categories. Category A included IFN-λ3, IL-6, IP-10, and CXCL9, and their values surged and decreased rapidly before the onset of severe pneumonia. Category B included CCL17, which provided complete separation between the mild/moderate and the severe/critical groups at an early phase of SARS-CoV-2 infection. The five markers provided a high predictive value (area under the receiver operating characteristic curve (AUROC): 0.9-1.0, p < 0.001). Low expression of CCL17 was specifically observed in pre-severe COVID-19 patients compared with other common diseases, and the predictive ability of CCL17 was confirmed in validation samples of COVID-19. The factors identified could be promising prognostic markers to distinguish between mild/moderate and severe/critical patients, enabling triage at an early phase of infection, thus avoiding overwhelming medical facilities.

Endovascular Treatment of Patients with Oculomotor Nerve Palsy Induced by Posterior Communicating Artery Aneurysms.

Objective: Whether coiling is the best treatment option for oculomotor nerve palsy (ONP) induced by posterior communicating artery (PComA) aneurysms remains controversial. In this study, we retrospectively analyzed the recovery of ONP caused by PComA aneurysms. Methods: Between 2007 and 2019, 8 patients with PComA aneurysms and ONP underwent coiling at our institution. We retrospectively reviewed ONP recovery, duration from onset of ONP to treatment, and complications of procedures. Results: At the last available clinical follow-up, ONP recovery was complete in 4 patients (50%) and partial in 4 patients (50%). Patients with partial recovery of ONP had sequelae of eye movement impairment that did not affect daily life. In 1 patient, hemiplegia developed due to cerebral infarction of the corona radiata the day after coiling, but it fully recovered 1 year after operation. The delay from the onset of ONP to coiling was significantly related to partial ONP recovery (r = -0.83, p = 0.01). Conclusion: Endovascular treatment is a relatively safe and satisfactory treatment for PComA aneurysms with ONP.

Bipolar dual-lead spinal cord stimulation between two electrodes on the ventral and dorsal sides of the spinal cord: consideration of putative mechanisms.

We have applied bipolar dual-lead spinal cord stimulation (SCS) between two cylinder-type electrodes placed on the ventral and dorsal sides of the spinal cord (dual-VD-SCS). A 36-year-old man suffered from burning pain from his right elbow down to his hand after brachial plexus avulsion. The areas with paresthesia induced by conventional SCS did not include the painful hand area. However, dual-VD-SCS completely induced paresthesia in the painful hand area. We speculate that dual-VD-SCS can be applied to stimulate deeper sites of the dorsal column and dorsal horn than conventional SCS and is useful for pain reduction.

Risk factors of catheter-related bloodstream infection caused by Bacillus cereus: Case-control study in 8 teaching hospitals in Japan.

In this multicenter, matched case-control study, patients diagnosed with catheter-related bloodstream infection (CRBSI) caused by Bacillus cereus (n = 108) were matched to controls (n = 269). In the multivariable analysis, administration of an amino acid preparation and an indwelling peripheral catheter were significant variables for B cereus-related CRBSI.

Importance of Pharmacological Evaluation in the Treatment of Poststroke Pain by Spinal Cord Stimulation.

OBJECTIVES: Spinal cord stimulation (SCS) is not typically recommended for the treatment of central poststroke pain (CPSP). We examined whether the pharmacological evaluation of CPSP is useful for selecting the candidates for SCS. MATERIALS AND METHODS: Changes in visual analog scale (VAS) scores for pain following pharmacological evaluation using morphine, thiopental, and ketamine were compared with those following SCS in 22 CPSP patients. RESULTS: Twelve of the 22 (54.5%) patients in the ketamine test and thiopental test, and 5 (22.7%) of the 22 patients in the morphine test showed a more than 40% reduction in VAS score and were judged as "sensitive." Pain relief by SCS was estimated as excellent (≧60% VAS score reduction) in three patients, good (30-59% reduction) in nine patients, and fair (10-29% reduction) in seven patients 24 months after the start of SCS. The remaining 3 patients evaluated as having poor pain relief (<10% reduction) only underwent test SCS. VAS score reduction induced by SCS was more significant in ketamine-sensitive patients than in ketamine-resistant patients during the test SCS (p < 0.01, Mann-Whitney's U test) and 24 months after the start of chronic SCS (p < 0.05). However, there were no significant differences in results for thiopental-sensitive/thiopental-resistant or morphine-sensitive/morphine-resistant patients during the test SCS and 24 months after chronic SCS. Analysis of the rate of VAS score reduction by pharmacological evaluation and SCS showed significant correlations with the results of the ketamine test (r = 0.670, p = 0.001, Pearson's correlation coefficient test), but not with those of the thiopental (r = 0.291, p = 0.231) or morphine test (r = 0.327, p = 0.175). CONCLUSION: We speculate that the pharmacological evaluation of CPSP patients can be a useful tool for selecting candidates for SCS.

Successful tocilizumab therapy in seven patients with refractory adult-onset Still's disease.

To evaluate the effects of tocilizumab (TCZ) on adult-onset Still's disease (AOSD), we reviewed medical records of seven patients with refractory AOSD treated with TCZ at our institution. TCZ therapy might allow rapid corticosteroid tapering and help maintain remission status, that is, resolution of clinical symptoms and normalization of biomarkers such as CRP and ferritin. Patients, however, should be monitored for the development of macrophage activation syndrome when TCZ is administered for active AOSD.

Interstitial cystitis associated with primary Sjögren's syndrome successfully treated with a combination of tacrolimus and corticosteroid: A case report and literature review.

We report a case of interstitial cystitis (IC) associated with primary Sjögren's syndrome (SS) successfully controlled with combination therapy of tacrolimus and a corticosteroid. In 2011, a 69-year-old female, who had been diagnosed with primary SS 23 years ago, developed IC and was successfully treated with tacrolimus and prednisolone combination therapy. The mechanism of IC, including the involved autoimmunity, has not been elucidated. Clinical observation studies suggest a potential association between SS and IC. However, IC is currently thought to be underdiagnosed in patients with SS as well as in the general population. Based on our case and others reported previously, IC associated with SS responds well to immunosuppressive therapy. In particular, a combination of a calcineurin inhibitor (tacrolimus or cyclosporine) with a corticosteroid seems to be highly effective. The possibility of IC in patients with SS complaining of lower urinary tract symptoms without features of infection or other identifiable causes should be given attention.

[A Case of Brainstem Hemorrhage Following Embolization of a Large Basilar Aneurysm with Hydrogel-Coated Coils].

OBJECTIVE: Endovascular coil embolization of intracranial aneurysms is associated with better outcomes and a lower mortality rate compared with surgical clip occlusion. However, a principal disadvantage of endovascular therapy is the higher rate of retreatment compared with neurosurgical clipping. Self-expandable hydrogel-coated coils were developed to reduce recanalization rates of cerebral aneurysms by promoting complete volumetric aneurysm occlusion. Herein, we report a case of brainstem hemorrhage following coil embolization of a large basilar aneurysm with hydrogel-coated coils. CASE PRESENTATION: A 65-year-old female with a history of hypertension, who presented with worsening headaches, right hemiplegia, and left oculomotor palsy, underwent endovascular treatment for a large basilar aneurysm. The aneurysm was treated with both hydrogel-coated coils and bare platinum coils. Hydrogel-coated coils represented 46% of the coil length in the aneurysm. The patient was discharged from the hospital with improvement of neurological deficits 6 days after the procedure. However, the patient was readmitted with perianeurysmal edema in the midbrain 23 days after coil embolization. Follow-up angiography 26 days after the procedure showed complete obliteration of the aneurysm. Two weeks later, the patient presented with a large brainstem hemorrhage and died. Pathological findings revealed intraparenchymal hemorrhage in the pons without rupture of the aneurysm. CONCLUSION: Hydrogel-coated coils may cause a marked inflammatory response that may result in intracerebral hemorrhage.

FDG PET Imaging in Pneumocystis Pneumonia.

A 69-year-old woman with rheumatoid arthritis and pleuritis presented with dyspnea. On admission, she was afebrile and had an oxygen saturation of 97% on ambient air. Chest radiography and CT revealed only subtle ground-glass opacities. However, FDG PET revealed pathological uptake in both lungs. A diagnosis of Pneumocystis pneumonia was made based on a positive ß-D-glucan assay and polymerase chain reaction amplification of Pneumocystis jirovecii from the sputum. Posttreatment FDG PET revealed resolution of the previously noted uptake. This case illustrates that FDG PET can be used to diagnose Pneumocystis pneumonia when the CT findings are equivocal.

Anti-neutrophil Cytoplasmic Antibody (ANCA)-associated Vasculitis Associated with Primary Biliary Cirrhosis: A Case Report and Literature Review.

We herein report a rare case of microscopic polyangiitis with primary biliary cirrhosis (PBC) and a literature review of six previously reported cases of PBC complicated by anti-neutrophil cytoplasmic antibody-associated vasculitis. Due to the scarcity of similar reports, it was not possible to establish a true overlap syndrome or casual association. When the biliary enzyme levels are elevated in patients with vasculitis, physicians should thus be mindful of the possible coexistence of these diseases.

Rheumatic manifestations and an epipharyngeal mass accompanied by myelodysplastic syndrome.

We herein report two cases of myelodysplastic syndrome with rheumatic manifestations. (Case 1) A 70-year-old man presented with fever, arthritis and bone pain and developed cranial nerve palsy caused by an epipharyngeal mass. Steroid therapy led to a prolonged remission of the febrile condition and mass lesion. (Case 2) An 82-year-old male was treated for intractable polyarthritis and fever with steroid therapy, and serious side effects resulted in lethal pneumonia. We herein describe the entire course of steroid therapy in these two cases. Various rheumatic manifestations in myelodyaplastic syndrome often require empirical steroid therapy. It was effective for the soft tissue mass in Case 1, in which indolent lymphoma could not be denied, and was only partially effective for Case 2 of the febrile and putatively benign conditions, suggesting heterogeneous nature of rheumatic complications in myelodysplastic syndrome.

Differences in fluorodeoxyglucose positron emission tomography/computed tomography findings between elderly onset rheumatoid arthritis and polymyalgia rheumatica.

OBJECTIVES: To compare the fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) findings in patients with elderly-onset rheumatoid arthritis (EORA) with those in patients with polymyalgia rheumatica (PMR), two conditions with similar clinical presentations. METHODS: We retrospectively analyzed the FDG-PET/CT findings in 10 patients with EORA and 27 patients with PMR admitted to our department between 2006 and 2012. RESULTS: No significant difference was observed in the median patient ages at the time of FDG-PET/CT scans in the EORA and PMR groups (73.5 vs. 78.0 years, respectively). Significant differences in both FDG uptake scores and standardized uptake values were observed between the two groups in the ischial tuberosities, spinous processes, and wrists. No significant differences were detected in the shoulders and hips. However, specific uptake patterns were observed in each group: circular and linear uptake patterns were observed around the humeral head in the EORA group, whereas focal and non-linear uptake patterns were observed in the PMR group. Moreover, focal uptake in front of the hip joint, indicating iliopectineal bursitis, tended to be limited to the PMR group. High sensitivity (92.6%) and specificity (90%) were observed for PMR diagnoses when at least three of the following five items were satisfied: characteristic findings of shoulder and iliopectineal bursitis, FDG uptake in ischial tuberosities and spinal spinous processes, and lack of FDG uptake in the wrists. CONCLUSION: The differences in the degree of uptake at each lesion and in uptake patterns at the shoulders and hips are potentially useful for obtaining a definitive diagnosis.

Rheumatoid arthritis-associated aortitis: a case report and literature review.

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disorder that primarily affects the synovial joints. Rheumatoid vasculitis (RV) is an extra-articular manifestation of RA, and its association with aortitis is rare and not widely recognised. Here, we report the case of a 69-year-old woman with RA-associated aortitis and review the literature on rheumatoid aortitis. The mean oral steroid dose administered to RA-associated aortitis patients was 46.3 mg/day prednisolone (PSL). In our patient, the aortitis was also thought to be due to RV because she had findings of RV, such as cutaneous ulceration and a high rheumatoid factor titre, and because a moderate PSL dose dramatically improved the clinical findings. RA-associated aortitis, if left untreated, can be fatal; therefore, early detection and treatment initiation is very important.

Utility of fluorodeoxyglucose positron emission tomography/computed tomography for early diagnosis and evaluation of disease activity of relapsing polychondritis: a case series and literature review.

OBJECTIVE: Relapsing polychondritis (RPC) is relatively rare and early diagnosis is difficult. We investigated the utility of fluorodeoxyglucose (FDG)-PET/CT for the diagnosis of RPC and evaluation of disease activity. METHODS: Five RPC patients undergoing FDG-PET/CT in our hospital between 2006 and 2012 were studied. Eight RPC cases examined by PET reported in the literature were also assessed. Data from a total of 13 patients were analysed. RESULTS: Typical FDG accumulation was noted in the tracheobronchial trees of nine patients, the costal cartilage of five, joints of five, larynx of four, nasal cavity/paranasal sinuses of three, auricles of three, lymph nodes of three and the aorta of one. One patient showed nasal chondritis on a PET scan despite the absence of nasal changes on physical examination. Of five patients with costochondritis, four remained asymptomatic. Of nine patients with airway FDG accumulation, eight developed respiratory symptoms and all had CT abnormalities. In the other patient, airway FDG accumulation was evident despite the absence of airway symptoms and a lack of abnormalities in the respiratory function test and CT. PET also revealed bronchial chondritis in asymptomatic patients. The mean maximum standardized uptake values (SUVmax) of the upper and lower airways was 5.79 (s.d. 2.87) and 6.47 (s.d. 4.08), respectively. In five patients with a PET after treatment, FDG accumulation had diminished with symptomatic and inflammatory improvement. CONCLUSION: FDG-PET/CT is a potentially powerful tool for the early diagnosis of RPC, especially in patients without easily biopsied organ involvement. This modality also facilitates evaluation of disease extent and disease activity during treatment.

A patient with diffuse cutaneous systemic sclerosis complicated by antineutrophil-cytoplasmic antibody-associated vasculitis exhibiting honeycomb lung without volume loss.

We herein report the case of a 72-year-old woman with diffuse cutaneous systemic sclerosis (SSc) complicated by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who exhibited honeycomb lung without volume loss. On admission, chest computed tomography (CT) revealed honeycomb lung without volume loss in addition to increased density of the partition walls. A renal biopsy revealed global sclerosis and cellular crescent formation. Mononeuritis multiple subsequently occurred, and steroid pulse therapy with cyclophosphamide was administered. Repeat chest CT showed that the honeycomb lung was unchanged; however, overall reduced density of the partition walls was observed. It is necessary to recognise that vasculitis may develop in SSc patients who exhibit honeycomb lung without volume loss.

Identification of novel autoantibodies to GABA(B) receptors in patients with neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: The gamma-aminobutyric acid type B receptors (GABAR(B)) are G-protein coupled receptors for GABA, the main inhibitory neurotransmitter in the brain. We identified GABAR(B) subunits as candidate antigens in patients with SLE using a random peptide display library. The aim of this study was to investigate the possible link between anti-GABAR(B) antibodies and disease activity and NPSLE. METHODS: ELISA was performed with recombinant proteins of GABAR(B1b) and GABAR(B2) on serum samples from patients with SLE (n = 88), scleroderma (n = 20), myositis (n = 20) or vasculitis (n = 20) as well as healthy subjects (n = 20). Cerebrospinal fluid (CSF) from 23 patients with SLE was also examined. RESULTS: Autoantibodies to GABAR(Bs) were exclusive to patients with SLE (P < 0.001) and positively associated with SLEDAI (anti-GABAR(B1b), P = 0.001; anti-GABAR(B2), P < 0.001). Of note, autoantibodies were positively linked with NPSLE (anti-GABAR(B1b), P = 0.02; anti-GABAR(B2), P = 0.03). Moreover, anti-GABAR(Bs) was detected in 61.5% of CSF samples from patients with active NPSLE, a frequency that was significantly higher than that for patients with non-SLE syndromes. CONCLUSION: Anti-GABAR(B) antibodies could represent novel candidate markers for disease activity and NPSLE.

Large vessel vasculitis in elderly patients: early diagnosis and steroid-response evaluation with FDG-PET/CT and contrast-enhanced CT.

Large vessel vasculitis (LVV) is an often-reported cause of inflammation of unknown origin (IUO) in elderly people. The objective of this study was to describe the usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and contrast-enhanced CT in early diagnosis and treatment follow-up of patients with LVV presenting as elderly onset IUO. We retrospectively compared contrast-enhanced CT findings and FDG-PET/CT findings of the patients diagnosed with LVV and 11 controls; all subjects were 50 years of age or older. We evaluated maximum standardised uptake value (SUV(max)) and PET score of the aortic wall for quantitative comparison of FDG-PET/CT findings. We measured the aortic wall thickness (W) and its ratio against the radius (W/R) for quantitative comparison of aortic wall thickening by contrast-enhanced CT. After steroid treatment, we compared these values with those pre-treatment. Of 124 patients who were hospitalised due to advanced age and IUO, 88 underwent FDG-PET/CT and contrast-enhanced CT. Abnormal findings were observed on images from 78 patients. The findings were indicative of LVV in 13 patients (10.5 %), of whom more than half had only non-specific symptoms. Patients with LVV had significantly higher aortic wall SUV(max) (3.85 vs. 1.95), PET scores by FDG-PET/CT, and aortic wall thicknesses by contrast-enhanced CT (3.8 vs. 2.6 mm) than controls. Significant improvement in aortic wall thickening was evidenced by reduced PET scores and by contrast-enhanced CT findings in patients who were followed up after treatment. LVV is an important cause of IUO with non-specific symptoms in elderly patients. Imaging examination comprising contrast-enhanced CT and FDG-PET/CT is useful for early diagnosis and early treatment evaluation of LVV, allowing for amelioration of reversible aortic wall thickening.

Clinical characteristics and incidence of methotrexate-related lymphoproliferative disorders of patients with rheumatoid arthritis.

OBJECTIVE: To investigate the incidence and clinical features of methotrexate (MTX)-related lymphoproliferative disorders (MTX-LPDs) in patients with rheumatoid arthritis (RA). PATIENTS: In total, 589 RA outpatients were examined at the National Center for Global Health and Medicine in the period from January 1990 to October 2010. RESULTS: MTX was used in 403 cases, and the duration of follow-up was 2379 person-years. Four patients developed MTX-LPDs; the incidence of MTX-LPDs was calculated as 0.00168/person-year and the standardized incidence as 8.21 (95% CI: 0.16-24.30). The mean total dosage of MTX was 1142 ± 871 mg, and the dosage at LPD onset was 7.4 ± 1.9 mg/week. The patients who developed MTX-LPDs had significantly shorter disease duration of RA compared with the patients who had not received MTX, but who had not progressed to LPDs (3.1 years vs. 12.5 years; P = 0.01). The following LPD subtypes were observed: diffuse large B-cell lymphoma (N = 2); Hodgkin's lymphoma (N = 1); and T-cell lymphoma (N = 1). After withdrawal of MTX, two of these patients showed spontaneous regression of the tumor, one did not have a recurrence, while the other patient relapsed and required chemotherapy. CONCLUSION: Our study revealed that MTX-LPDs are not rare complications of RA outpatients. The MTX-LPDs were associated with a relatively shorter RA duration, and half of them showed tumor regression after MTX withdrawal, which suggested an association with MTX. It is important to consider the possibility of MTX-LPD in RA patients who have received MTX.