Objective Transmural healing (TH) has been attracting attention as a new therapeutic target for Crohn's disease, but there are few clinical data on TH in Japan. We introduced low-dose computed tomography enterography (CTE) as a monitoring method for Crohn's disease and retrospectively investigated the accuracy of evaluating TH by CTE.
Methods Among Crohn's disease patients who underwent low-dose CTE at our hospital from January 2009 to March 2021, 122 patients who underwent colonoscopy or balloon endoscopy within 2 weeks were included. Results of radiological and endoscopic examinations were reviewed independently by radiologists and gastrointestinal endoscopists, respectively. The concordance rate of the diagnosis between CTE and endoscopy was evaluated.
Results Twenty-six patients (21.3%) achieved TH, and the kappa index was 0.743. On comparing the TH and non-TH groups, the Crohn's disease activity index (p=0.02), endoscopic healing rate (p<0.001), serum albumin (p=0.043), and serum C-reactive protein level (p=0.018) showed significant differences. Among the 122 patients, 69 (56.5%) showed concordance between the diagnosis of CTE and endoscopy, and 22 (18.0%) achieved both TH and endoscopic healing.
Conclusion This study provides real-world data on Crohn's disease evaluated with low-dose CTE in Japan. The TH criterion used in this study has a high kappa coefficient and can be used reproducibly in many institutions.
Objective A high NOBLADS score reflecting the severity of lower gastrointestinal bleeding contributes to the identification of stigmata of recent hemorrhage (SRH) in colonic diverticular bleeding (CDB). The burden of colonoscopy is particularly high in elderly patients; therefore, we investigated the utility of the NOBLADS score for managing CDB by age stratification. The NOBLADS score performance in SRH prediction was estimated by the area under the receiver operating characteristic calculation and a multiple logistic regression model.
Methods This was a single-center, retrospective cohort study. Patients who underwent initial colonoscopy with CDB between April 2008 and December 2019 were divided into a young group (<65 years old) and an elderly group (≥65 years old). We further categorized patients according to colonoscopy findings as SRH-positive, with successful endoscopic hemostasis performance, and SRH-negative, with suspected CDB. The main outcome measure was successful SRH identification.
Results Four-hundred and seventeen CDB patients were included, of whom 250 (60.0%) were elderly. There were 72 (43.1%) SRH-positive patients in the young group and 94 (37.6%) in the elderly group. The areas under the receiver operating characteristic curves of the NOBLADS score predicting SRH identification were 0.76, 0.71, and 0.81 for all ages, young patients, and elderly patients, respectively. A multiple logistic regression analysis showed that SRH identification was significantly associated with NOBLADS scores in both groups. Eighty-one patients (32.4%) scored ≥4 in the elderly group, and 60 of those were SRH-positive (74.1%). All 27 patients (10.8%) who scored ≥4 with extravasation on computed tomography were found to have SRH.
Conclusion The NOBLADS score is useful for predicting SRH identification, especially in elderly patients.
Objective This retrospective, single-center study assessed the effects of interferon (IFN)-free treatment of hepatitis C virus (HCV) infection, which has been approved for seven years; calculated the incidence of hepatocellular carcinoma (HCC) after achieving a sustained virologic response (SVR); and elucidated problems with follow-up for surveillance of post-SVR HCC, particularly the impact of the coronavirus disease 2019 (COVID-19) pandemic.
Methods We summarized the SVR achievement rate of 286 HCV-infected patients who received 301 IFN-free treatments and analyzed the cumulative incidence of initial HCC and the cumulative continuation rate of follow-up after SVR in the 253 patients who achieved SVR and did not have a history of HCC.
Results Among 286 patients who received IFN-free treatments, 14 dropped out, and the 272 remaining patients achieved an SVR after receiving up to third-line treatment. Post-SVR HCC occurred in 18 (7.1%) of the 253 patients without a history of HCC, with a cumulative incidence at 3 and 5 years after SVR of 6.6% and 10.0%, respectively; the incidence of cirrhosis at those time points was 18.2% and 24.6%, respectively.Of the 253 patients analyzed, 58 (22.9%) discontinued follow-up after SVR. Patients who had no experience with IFN-based therapy tended to drop out after SVR. Notably, the number of dropouts per month has increased since the start of the pandemic.
Conclusion Currently, IFN-free treatment is showing great efficacy. However, the incidence of HCC after SVR should continue to be monitored. In this study, the COVID-19 pandemic did not affect treatment outcomes, but it may affect surveillance for post-SVR HCC.
Objective The reference ranges of serum thyroid hormone levels are determined by the values of normal subjects aged 15 or 20 to 60 years old in Japan and may differ from the values in elderly patients. In addition, the relationship between the thyroid function and cognitive function remains controversial. We assessed the thyroid function of elderly subjects ≥60 years old and its impact on the cognitive function in Japanese adults.
Methods We compared the thyroid function by age group and gender and investigated the effects of cognitive impairment on the thyroid function. This study was a cross-sectional, multi-institutional joint study.
Patients The serum concentrations of thyroid hormones in 1,136 patients were measured; however, those taking thyroid hormones, anti-thyroid drugs, and steroid hormones were excluded. Among them, 1,016 cases in which the cognitive function was evaluated were divided into five groups according to their free thyroxine (FT4) levels.
Results Excluding overt thyroid dysfunction (5.8%), the average age of the 1,070 remaining patients was 77.5 years old. The rate of cognitive impairment was lowest at FT4 levels of 1.1-1.2 ng/dL and highest at FT4 levels <0.9 ng/dL for both genders. Thyroid-stimulating hormone (TSH) levels in the elderly varied widely by age group and gender. The upper limit of the reference range of TSH for those ≥60 years old may be higher (7.7-9.2 mIU/L for men; 8.2-8.6 mIU/L for women) than the current range for those <60 years old (4.23 mIU/L).
Conclusion The thyroid function seemed to be slightly higher (lower TSH and higher FT4) in the population without cognitive impairment than in those with cognitive impairment, except for men in their 90s.
Introduction Invasive fungal infections have been attracting attention as significant fatal complications in patients with febrile neutropenia (FN) who undergo intensive chemotherapy or hematopoietic stem cell transplantation to treat hematological malignancies. Although clinical trials are already underway in other countries, evidence supporting the use of caspofungin (CAS) in FN patients in Japan is still insufficient.
Methods A retrospective study of patients treated with CAS for FN associated with hematological diseases between April 2015 and March 2018 was conducted to determine the treatment efficacy and safety. The study was conducted as a multicenter collaboration, and the data of 52 patients who met all of the inclusion criteria were analyzed. A five-composite-endpoint method was used, and the treatment was judged to be effective when all five endpoints (defervescence during neutropenia; no breakthrough fungal infections; resolution of baseline fungal infections; a survival for seven days or more after the completion of therapy; and no discontinuation of therapy due to side effects or invalidity) were met.
Results The efficacy rate was 53.8% (28/52), which is close to the average reported efficacy rate. Adverse events included liver dysfunction and electrolyte abnormalities, but no renal dysfunction or serious events were seen.
Conclusion These results suggest that the use of CAS in FN patients with hematological diseases is effective and well-tolerated, and we believe that the use of CAS could become a significant treatment in Japan.
Objective The underlying pathophysiology varies according to stroke subtype. However, stroke heterogeneity among patients with systemic lupus erythematosus (SLE) remains unstudied. We hypothesized that the contribution of SLE to stroke might vary according to its subtype and investigated the associations of SLE and various stroke subtypes.
Methods Diagnostic codes and electronic medical records were used to identify 70 patients with SLE who developed acute cerebral infarction or intracerebral hemorrhaging at four tertiary referral hospitals between 2008 and 2018. Intracerebral hemorrhaging was classified as lobar or deep, while cerebral infarction was classified according to the SSS-TOAST criteria. Physician notes were used to identify SLE activity, and their prevalences were compared among stroke subtypes. Outcomes were collected from the patients' medical records.
Results The most common stroke subtype in patients with SLE was that of undetermined causes (31%), followed by small artery occlusion (16%), cardioaortic embolism (13%), other causes (11%), lobar hemorrhaging (10%), deep hemorrhaging (10%), and large artery atherosclerosis (9%). Stroke onset occurred during a period of high SLE activity in 21 patients (30%). The proportion of patients with high SLE activity varied according to stroke subtype (p=0.039) and was highest for cerebral infarction with undetermined causes. Stroke recurrence or death was observed in 40% of patients within 5 years after the initial stroke onset.
Conclusion The contributions of SLE to stroke varied significantly according to the stroke subtype. Given the unfavorable prognosis, close stroke subtype-specific observation by rheumatologists and stroke specialists is recommended after stroke events.
Objective To examine the continuation of antibody prevalence status after 12 months and background factors in antibody-positive subjects following asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Methods We initially determined the SARS-CoV-2 anti-nucleocapsid protein immunoglobulin G (anti-N IgG) antibody prevalence in 1,603 patients, doctors, and nurses at 65 medical institutions in Kanagawa Prefecture, Japan. We then obtained consent from 33 of the 39 subjects who tested positive and performed follow-up for 12 months.
Results Follow-up for up to 12 months showed that a long-term response of the anti-N IgG antibody could be detected in 6 of the 33 participants (18.2%). The proportions with hypertension, using an angiotensin-receptor blocker, and without a drinking habit were higher among the participants with a long-term anti-N IgG antibody response for up to 12 months than among those without a long-term antibody response.
Conclusions The proportion of individuals with subclinical COVID-19 who continuously had a positive result for the anti-N IgG antibody at 12 months was low.
Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) classically present with ventricular arrhythmias and less commonly heart failure. ARVC is an inherited cardiomyopathy and generally based on a variant of desmosomal genes. Recently, the association between myocardial inflammation and ARVC has been a matter of great concern. We encountered a patient with ARVC who had a desmoglein-2 mutation with advanced right ventricular failure accompanying a preserved left ventricular function. Concomitant right ventricular myocarditis was detected four years after the diagnosis of ARVC. ARVC and myocarditis might have a deep pathophysiological association, at least in some cases.
Thyrotoxicosis and sodium-glucose transport protein 2 inhibitors (SGLT2is) are associated with the induction of euglycemic diabetic ketoacidosis (euDKA). We herein report two cases of euDKA in patients with diabetes mellitus wherein both thyrotoxicosis and SGLT2i treatment were the underlying causes. One patient developed thyrotoxicosis during the course of type 2 diabetes mellitus, whereas the other patient was suspected of developing slowly progressive insulin-dependent diabetes mellitus during the course of Graves' disease. Although such cases are rare, there is some concern that similar cases may occur because of the increased frequency of SGLT2i use in recent years.
Fabry disease is an inherited lysosomal disorder caused by mutations in the alpha-galactosidase A gene. We herein report a Fabry disease patient with enzyme replacement therapy (ERT)-resistant proteinuria who showed improvement in the estimated glomerular filtration rate (eGFR) decline rate after uric acid (UA)-lowering therapy. The patient was diagnosed with Fabry disease at 36 years old. After that, even under ERT, proteinuria and eGFR decline persisted. During the clinical course, serum UA levels were elevated with increases in renal tubular damage markers. Febuxostat administration immediately improved tubular damage and prevented further eGFR decline. UA-mediated tubulopathy may become an additional therapeutic target for eGFR decline in Fabry disease.
Lenvatinib, a tyrosine kinase inhibitor (TKI), is a stronger inhibitor of vascular endothelial growth factor receptor, fibroblast growth factor receptors 1 to 4, and platelet-derived growth factor receptor (PDGFR) than other TKIs. We herein report a 77-year-old Japanese woman who received the minimum dose of lenvatinib for treatment of hepatocellular carcinoma. Within one month of starting treatment, she developed severe proteinuria, hypertension, and renal dysfunction. A kidney biopsy showed drug-induced thrombotic microangiopathy, podocytopathy, and polar vasculosis. We also observed damage to the renal tubules, where PDGFR is located. To our knowledge, this is the first report of lenvatinib-induced damage to the renal tubules.
Pulmonary artery pseudoaneurysms (PAPs) are rare but can cause massive hemoptysis if they rupture. Infectious PAPs are often treated by surgery or transcatheter embolization and are rarely treated conservatively with antibiotics. We herein report a case of PAP treated conservatively in a 21-year-old woman with lung abscess. Except for one massive hemoptysis early in the course, the patient responded well to the empirical therapy with ampicillin/sulbactam and systemic hemostatic agents. After six weeks of antibiotics, the pseudoaneurysm disappeared. Conservative therapy with careful observation can be considered in small infectious PAPs when there is a good clinical response to initial conservative therapy.
A 61-year-old patient with cystic bronchiectasis and bronchial artery hyperplasia in the left lung was diagnosed with polymyositis-related interstitial lung disease. After nine months of immunosuppressive therapy, he developed unilateral autoimmune pulmonary alveolar proteinosis (APAP) in the right lung with respiratory failure. After bronchial artery embolization to prevent massive hemoptysis, whole-lung lavage was performed using veno-venous extracorporeal membrane oxygenation. His respiratory condition improved, and he was discharged from the hospital with supplemental oxygen. Three reported cases of APAP with polymyositis-related interstitial lung disease, including the present case, were all positive for anti-glycyl tRNA synthetase antibody and were under immunosuppressive treatment.
BNT162b2 (Pfizer/BioNTech) is a coronavirus disease 2019 (COVID-19) vaccine containing nucleoside-modified messenger RNA encoding the severe acute respiratory syndrome coronavirus 2 spike glycoprotein. Recently, ocular complications of mRNA vaccines have been reported increasingly frequently. However, immunological adverse events due to mRNA vaccines in real-world settings are not fully known. We herein report the novel development of sarcoidosis manifested as uveitis, bilateral hilar lymphadenopathy, angiotensin-converting enzyme elevation, and epithelioid and giant cell granuloma formation in the lung soon after the first BNT162b2 injection and review the current literature, including three reported cases of sarcoid-like reaction following COVID-19 vaccination.
A 52-year-old man presented with palatine tonsillar swelling caused by follicular lymphoma. His tumor burden was low, but exacerbation of snoring and dysphagia was observed. Considering the first wave of coronavirus disease 2019 (COVID-19) pandemic, he received palliative 4-Gy irradiation to the tonsils in 2 fractions, which induced partial regression of tonsillar swellings and eradication of the circulating lymphoma cells. We suggest that low-dose radiotherapy triggered an abscopal effect of lymphoma, which allowed the patient time to receive COVID-19 vaccination before starting immunosuppressive chemo-immunotherapy.
The most common neurological symptom of spontaneous intracranial hypotension (SIH) is abducens nerve paresis, and the precise pathophysiology is unclear. The accepted explanation is traction on the cranial nerves caused by the downward displacement of the cranial content. We herein report magnetic resonance imaging of SIH that can explain the mechanism underlying abducens nerve paresis. The cavernous sinuses were particularly thickened compared with the surrounding dura. This phenomenon can be explained by venous swelling, which can occur after leakage of cerebrospinal fluid in a closed cavity. This swelling pushes the abducens nerve up, which then causes abducens nerve paresis.
Cat scratch disease (CSD) is a zoonotic infection caused by Bartonella henselae typically resulting in self-limited regional lymphadenopathy. Encephalitis is a complication with a supposedly benign prognosis, but we encountered an exceptional case. A 19-year-old Japanese woman presented with status epilepticus. She was diagnosed with CSD-associated encephalitis based on her history of contact with a kitten and a high titre of serum IgG to B. henselae. Multimodal treatment ameliorated her encephalitis, but neurological sequelae including spastic paraparesis, persisted. After several months, she developed age-disproportionate parkinsonism inconsistent with a neurodegenerative disease. In conclusion, CSD-associated encephalitis can result in severe neurological sequelae and post-encephalitic parkinsonism.
A 36-year-old man was admitted to our hospital with complaints of dysphagia and photophobia. A neurological examination showed oropharyngeal palsy and bilateral mydriasis with loss of light reflexes in the absence of external ophthalmoplegia. Bilateral pupils were supersensitive to pilocarpine 0.1%, which was compatible with Adie's tonic pupils. Serum IgG reacted with GQ1b, GT1a, GalNAc-GD1a, and GD3. Intravenous high-dose immunoglobulin therapy improved his neurological symptoms within three weeks. To our knowledge, there is no medical literature describing acute oropharyngeal palsy with Adie's tonic pupils. We recommend evaluating antiganglioside antibodies to clarify the cause of oropharyngeal palsy and Adie's tonic pupils.
We herein report a case of systemic sclerosis (SSc)-related pericarditis successfully treated with mycophenolate mofetil (MMF) and low-dose prednisolone (PSL). The patient was a 72-year-old woman with anti-centromere antibody. Her clinical manifestations were Raynaud phenomenon, bilateral pleural effusion, pericardial effusion and skin tightness. Based on the findings of exudative pericardial effusion with the absence of pulmonary arterial hypertension from the results of the cardiac catheter and pericardiocentesis, she was diagnosed with SSc-related pericarditis and treated with PSL10 mg and MMF 1 g per day, leading to the complete resolution of pericarditis. These findings suggested that MMF and low-dose PSL were effective for SSc-related pericarditis.
Neuropsychiatric systemic lupus erythematosus (NPSLE) with cerebral vasculitis is rare, and its prognosis is unfavorable. High-dose glucocorticoids and cyclophosphamide are widely used for the treatment of NPSLE, but cyclophosphamide has a risk of cervical intraepithelial neoplasia and ovarian insufficiency, which may discourage its use in young women. We experienced a case of NPSLE with cerebral vasculitis and lupus nephritis that responded successfully to glucocorticoids and mycophenolate mofetil (MMF). MMF might be a treatment option for NPSLE without concern for reproductive toxicity. However, there are only a few reports on the efficacy of MMF in NPSLE, and further investigations are needed.
A 28-year-old woman exhibited a spiking fever, arthritis, and liver disfunction when she was 22 weeks pregnant. She was diagnosed with adult-onset Still's disease (AOSD). As her condition was resistant to corticosteroid therapy, tocilizumab (TCZ) was selected. The TCZ treatment was effective, and she delivered a healthy child while receiving TCZ treatment. Cases in which AOSD first arises during pregnancy are rare, and there have been no reports of TCZ treatment for AOSD being initiated during pregnancy. Although the safety of TCZ treatment during pregnancy has not been established, it may be effective against severe AOSD that develops during pregnancy.