Relationship Between the Lipidome Profile and Disease Activity in Patients with Rheumatoid Arthritis.

Lipid mediators have been suggested to play important roles in the pathogenesis of rheumatoid arthritis (RA). Lipidomics has recently allowed for the comprehensive analysis of lipids and has revealed the potential of lipids as biomarkers for the early diagnosis of RA and prediction of therapeutic responses. However, the relationship between disease activity and the lipid profile in RA remains unclear. In the present study, we performed a plasma lipidomic analysis of 278 patients with RA during treatment and examined relationships with disease activity using the Disease Activity Score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR). In all patients, five lipids positively correlated and seven lipids negatively correlated with DAS28-ESR. Stearic acid [FA(18:0)] (r = -0.45) and palmitic acid [FA(16:0)] (r = -0.38) showed strong negative correlations. After adjustments for age, body mass index (BMI), and medications, stearic acid, palmitic acid, bilirubin, and lysophosphatidylcholines negatively correlated with disease activity. Stearic acid inhibited osteoclast differentiation from peripheral blood monocytes in in vitro experiments, suggesting its contribution to RA disease activity by affecting bone metabolism. These results indicate that the lipid profile correlates with the disease activity of RA and also that some lipids may be involved in the pathogenesis of RA.

Distribution of Splenic Arterial Flow and Segmental Spleen Volume for Partial Splenic Arterial Embolization.

INTRODUCTION: The spleen is a lymphatic organ that manages immune surveillance of the blood, produces blood cells, and helps filter the blood, remove old blood cells, and fight infection. The normal splenic weight is approximately 65-265 g. This study evaluated spleen volume and segmental volume. METHODS: 121 patients who underwent enhanced CT at our center were analyzed. The spleen was divided into upper, middle, and lower segments according to arterial flow area, and the volume of each segment was measured. Patients were classified into two groups as those with and without liver cirrhosis, and differences in the distribution of the segments in these groups was evaluated. RESULTS: The mean upper, middle, and lower spleen segmental volume ratios were 35.4%, 37.0%, and 27.6%, respectively. In the liver cirrhosis group, the segmental splenic volume ratios for the upper, middle, and lower segments were 34.5%, 38.5%, and 28.0%, respectively, indicating that these ratios remain similar regardless of liver cirrhosis status. CONCLUSION: The present findings on segmental spleen volume are useful for estimating infarction volume in cases of partial splenic arterial embolization.

Evaluation of splenic infarction ratio and platelet increase ratio after partial splenic artery embolization.

OBJECTIVE: The spleen is part of the lymphatic system and is one of the least understood organs of the human body. It is involved in the production of blood cells and helps filter the blood, remove old blood cells, and fight infection. Partial splenic artery embolization (PSE) is widely used to treat pancytopenia and portal hypertension. The efficacy of PSE for improving thrombocytopenia has been well demonstrated. In this study, we evaluated the splenic infarction ratio and platelet increase ratio after PSE. METHODS: Forty-five consecutive patients underwent PSE from January 2014 to August 2022. We retrospectively evaluated the splenic infarction volume and ratio after PSE and analyzed the relationship between the splenic infarction ratio and platelet increase ratio after PSE. RESULTS: The platelet increase ratio was correlated with the splenic infarction ratio after PSE. The cutoff value for the splenic infarction ratio with a two-fold platelet increase was 63.0%. CONCLUSION: We suggest performance of PSE in patients with a splenic infarction ratio of 63% to double the expected platelet count.

Apolipoprotein A2 isoforms associated with exocrine pancreatic insufficiency in early chronic pancreatitis.

BACKGROUND AND AIM: Apolipoprotein A2 (apoA2) isoforms have been reported to undergo the aberrant processing in pancreatic cancer and pancreatic risk populations compared with that in healthy subjects. This study aimed to clarify whether apoA2 isoforms were as useful as N-benzoyl-p-aminobenzoic acid (BT-PABA) test for exocrine pancreatic dysfunction markers in patients with early chronic pancreatitis (ECP). METHODS: Fifty consecutive patients with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) (n = 18), with ECP (n = 20), and asymptomatic patients with pancreatic enzyme abnormalities (AP-P) (n = 12) based on the Rome IV classification and the Japan Pancreatic Association were enrolled in this study. The enrolled patients were evaluated using endoscopic ultrasonography and endoscopic ultrasonography elastography. Five pancreatic enzymes were estimated. Pancreatic exocrine function was analyzed using the BT-PABA test. Lighter and heavier apoA2 isoforms, AT and ATQ levels were measured by enzyme-linked immunosorbent assay methods. RESULTS: There were no significant differences in clinical characteristics such as age, gender, body mass index, alcohol consumption and smoking among patients with AP-P, FD-P, and ECP. The BT-PABA test and lighter apoA2 isoform, AT level in the enrolled patients had a significant correlation (P < 0.01). The BT-PABA test in patients with ECP was significantly lower (P = 0.04) than that in AP-P. ApoA2-AT level in patients with ECP was lower than that in AP-P, albeit, insignificantly. Interestingly, apo A2-AT level was significantly (P = 0.041) associated with exocrine pancreatic insufficiency by multiple logistic regression analysis. CONCLUSIONS: ApoA2-AT level is a useful tool to evaluate exocrine pancreatic insufficiency in the early stage of chronic pancreatitis.

Corrigendum: Senescence of alveolar epithelial cells impacts initiation and chronic phases of murine fibrosing interstitial lung disease.

[This corrects the article DOI: 10.3389/fimmu.2022.935114.].

Retroperitoneal solitary neurofibroma mimicking lymph node metastasis of colon cancer: a case report.

BACKGROUND: A neurofibroma is a benign tumor that arises from Schwann cells and neurofibromas occur throughout the skin of neurofibromatosis type 1 (NF-1: Von Recklinghausen's disease) patients. A retroperitoneal solitary neurofibroma without any clinical signs of NF1 has been rarely reported. Herein, we present a case of a retroperitoneal solitary neurofibroma mimicking lymph node metastasis of colon cancer as well as a literature review. CASE PRESENTATION: An 80-year-old woman with abdominal pain and nausea was transported and diagnosed with bowel obstruction arising from sigmoid colon cancer A colonic stent was inserted to alleviate the bowel obstruction. A computed tomography scan with contrast revealed a liver tumor in segment 3, and an enlarged lymph node around the abdominal aorta. Whole-body 18F-fluorodeoxyglucose-positron emission tomography-CT (FDG-PET-CT) examine revealed increased FDG uptake in the liver tumor and enlarged lymph node. Liver and distant lymph node metastasis were diagnosed and we made a plan for a two-stage operation of the colon cancer and the metastatic lesions because laparotomy resection was needed for the retroperitoneal lymph node. Laparoscopic sigmoid colectomy was performed first. Pathological examination showed a tubular adenocarcinoma. A laparotomy for the metastatic lesions was performed to ensure complete lymph node dissection secondly. Histopathological findings of the liver tumor showed metastasis of sigmoid colon cancer. However, the tissue regarded as the enlarged lymph node was diagnosed as a neurofibroma. No metastasis and recurrence were observed. CONCLUSION: Although most neurofibromas are benign, malignant transformation of a neurofibroma is possible. PET-CT showed our patient had a high accumulated retroperitoneal tumor co-existing with colon cancer and liver metastasis. The treatment strategy of a solitary neurofibroma must be selected carefully considering the site of occurrence and the patient's background and aggressive resection of a tumor co-existing with another malignant tumor is needed.

A Woman with Rheumatoid Arthritis Who Successfully Delivered a Healthy Child with Continuous Administration of Sarilumab Throughout Pregnancy.

We herein report a patient with rheumatoid arthritis (RA) who successfully delivered a healthy child with continuous administration of sarilumab throughout pregnancy. She delivered her first child, a healthy boy, following in vitro fertilization-embryo transfer (IVF-ET) while using etanercept and low-dose prednisolone. Disease activity persisted after delivery, so etanercept was switched to sarilumab. She became pregnant by IVF-ET again. Because RA was still active, sarilumab was continued during pregnancy. She delivered a healthy girl at the 38th week of gestation by Caesarean section. No abnormalities were detected at or within 6 months after birth. Sarilumab was safe and effective in this pregnant woman with RA.

Two synchronous pseudoaneurysms after bile duct resection for distal cholangiocarcinoma.

Pseudoaneurysm is a potentially life-threatening complication after hepatobiliary pancreatic surgery. Although various measures have been taken to prevent the formation of postoperative pseudoaneurysms, completely avoiding complications can be difficult. An 83-year-old man underwent bile duct resection and systematic regional lymphadenectomies for distal cholangiocarcinoma. Polyethylene glycolic acid mesh with fibrin glue was applied to the pancreas around the distal stump and detached artery to prevent leakage of pancreatic juice and reinforce the arterial wall. Screening contrast-enhanced computed tomography on the 7th postoperative day indicated no pseudoaneurysm. The patient was discharged on the 20th postoperative day after an uneventful course. However, 4 days later, the patient visited the emergency outpatient department with a complaint of fever. Contrast-enhanced computed tomography revealed an abscess formation and a pseudoaneurysm around it. Emergency celiac arteriography revealed two pseudoaneurysms at the left hepatic artery and posterior superior pancreaticoduodenal artery; they were successfully treated with transcatheter arterial embolization using microcoils and covered stent placement. The patient was discharged 9 days after interventional radiology treatment. At the 14 months postoperative follow-up, the patient had no recurrence or stent obstruction. Multiple synchronous pseudoaneurysms are rare; accurately identifying the site by angiography and selecting appropriate treatment for each site is important.

Senescence of alveolar epithelial cells impacts initiation and chronic phases of murine fibrosing interstitial lung disease.

Fibrosing interstitial lung disease (ILD) develops due to the impaired reparative processes following lung tissue damage. Cellular senescence has been reported to contribute to the progression of fibrosis. However, the mechanisms by which these senescent cells initiate and/or drive the progression of lung tissue fibrosis are not yet fully understood. We demonstrated that p21WAF1/CIP1- and p16INK4A-pathway-dependent senescence in type 2 alveolar epithelial cells (AEC2) were both involved in the initiation and progression of lung fibrosis in murine bleomycin (BLM)-induced ILD. p21WAF1/CIP1-senescent AEC2 emerged rapidly, as early as 1 day after the intratracheal instillation of BLM. Their number subsequently increased and persisted until the later fibrosis phase. Very few p16INK4A-senescent AEC2 emerged upon the instillation of BLM, and their increase was slower and milder than that of p21WAF1/CIP1+ AEC2. AEC2 enriched with senescent cells sorted from BLM-ILD lungs expressed senescence-associated secretory phenotype (SASP)-related genes, including Il6, Serpin1, Tnfa, Ccl2, Tgfb, and Pdgfa, at the initiation and chronic phases of fibrosis, exhibiting distinct expression patterns of magnitude that were dependent on the disease phase. Ly6C+ inflammatory monocytes increased in the lungs immediately after the instillation of BLM and interstitial macrophages increased from day 3. The expression of Acta2 and Col1a1 was upregulated as early as day 1, indicating the activation of fibroblasts. We speculated that IL-6, plasminogen activator inhibitor-1 (PAI-1), and TGF-ß contributed to the accumulation of senescent cells during the progression of fibrosis in an autocrine and paracrine manner. In addition, CCL2, produced in large amounts by senescent AEC2, may have induced the infiltration of Ly6C+ inflammatory monocytes in the early phase, and TGF-ß and PDGFa from senescent AEC2 may contribute to the activation of fibroblasts in the very early phases. Our study indicated that senescent AEC2 plays a role in the pathogenesis of fibrosing ILD throughout the course of the disease and provides insights into its pathogenesis, which may lead to the development of new therapeutic methods targeting senescent cells or SASP molecules.

Periappendiceal fluid collection on preoperative computed tomography can be an indication for interval appendectomy: a retrospective study.

BACKGROUND: The treatment strategies for acute appendicitis, such as emergency appendectomy (EA), interval appendectomy (IA), and repeating nonoperative management (NOM), are controversial. In this study, we examined the preoperative factors that can be used to distinguish which patients should undergo IA. METHODS: We retrospectively identified 902 patients who underwent surgery for appendicitis in our hospital from January 2010 to December 2021. Of these patients, 776 were included in this study. The patients were divided into two groups: those with a periappendiceal fluid collection (PAFC) on preoperative computed tomography (PAFC-positive group, n = 170) and those without a PAFC (PAFC-negative group, n = 606). In each group, we compared patients who underwent EA and IA. RESULTS: In the PAFC-positive group, patients who underwent EA had a significantly higher postoperative complication rate than those who underwent IA (40.5% vs. 24.0%, p = 0.037). In the multivariate analysis, only the presence of PAFC was significantly associated with an increased risk of postoperative complications (odds ratio, 7.11; 95% confidence interval, 2.73-18.60; p < 0.001). The presence of PAFC alone was not significantly associated with an increased risk of IA or NOM failure (odds ratio, 1.48; 95% confidence interval, 0.19-11.7; p = 0.71). The rate of neoplasia on pathologic examination was significantly higher in the PAFC-positive than PAFC-negative group (7.6% vs. 1.5%, p < 0.001); the rate of carcinoma was also higher in the PAFC-positive group (2.4% vs. 0.17%, p = 0.02). CONCLUSIONS: The presence of PAFC on preoperative computed tomography was found to be a risk factor for postoperative complications but not IA or NOM failure. It was also correlated with neoplasia as the etiology of appendicitis. Therefore, PAFC positivity is useful as an indication for IA.

Organizing pneumonia as a possible pulmonary manifestation of systemic lupus erythematosus: Three cases and a review of literature.

Background: Organizing pneumonia (OP) is a rare manifestation of systemic lupus erythematosus (SLE). It has been described in very few case reports.Purpose and Methods: We encountered OP in three patients with SLE in 1 year; two manifested OP as an initial presentation of SLE, while the third manifested OP when SLE relapsed. To elucidate the clinical features and outcomes of OP in patients with SLE, we screened the PubMed database for cases diagnosed with OP either at or after the diagnosis of SLE; the search was restricted to articles that were published after 1990, when OP became widely recognized.Results: We identified 15 cases of OP in patients with SLE. Thus, we analyzed a total of 18 cases (including our three). OP developed at the initial diagnosis of SLE in 15 cases and at relapse of SLE in three cases. In most cases, the disease activity of SLE was moderate or high. In all cases, OP was accompanied by other extrapulmonary symptoms of SLE, namely, fever (77.8%), cutaneous manifestations (61.1%), arthralgia/arthritis (50%), and lupus nephritis (33.3%). Steroid monotherapy or increasing the dose of the steroids was effective in seven cases (38.8%); however, steroid monotherapy was ineffective and led to death due to respiratory failure in two cases (11.1%). Combination therapies of steroids with hydroxychloroquine, azathioprine, tacrolimus, mycophenolate mofetil, intravenous pulse cyclophosphamide therapy, and belimumab were effective in seven cases (38.8%).Conclusions: Based on the review of previously reported and our cases, we concluded that OP is an important pulmonary manifestation of SLE. Clinicians should be aware of it as it may require intensive immunosuppressive therapy either at or after the diagnosis of SLE.

Treatment with an Anti-CX3CL1 Antibody Suppresses M1 Macrophage Infiltration in Interstitial Lung Disease in SKG Mice.

CX3C Motif Chemokine Ligand 1 (CX3CL1; fractalkine) has been implicated in the pathogenesis of rheumatoid arthritis (RA) and its inhibition was found to attenuate arthritis in mice as well as in a clinical trial. Therefore, we investigated the effects of an anti-CX3CL1 monoclonal antibody (mAb) on immune-mediated interstitial lung disease (ILD) in SKG mice, which exhibit similar pathological and clinical features to human RA-ILD. CX3CL1 and CX3C chemokine receptor 1 (CX3CR1), the receptor for CX3CL1, were both expressed in the fibroblastic foci of lung tissue and the number of bronchoalveolar fluid (BALF) cells was elevated in ILD in SKG mice. No significant changes were observed in lung fibrosis or the number of BALF cells by the treatment with anti-CX3CL1 mAb. However, significantly greater reductions were observed in the number of M1 macrophages than in M2 macrophages in the BALF of treated mice. Furthermore, CX3CR1 expression levels were significantly higher in M1 macrophages than in M2 macrophages. These results suggest the stronger inhibitory effects of the anti-CX3CL1 mAb treatment against the alveolar infiltration of M1 macrophages than M2 macrophages in ILD in SKG mice. Thus, the CX3CL1-CX3CR1 axis may be involved in the infiltration of inflammatory M1 macrophages in RA-ILD.

A Case of Chronic Mesenteric Ischemia: Complete Revascularization Using Multiple Procedures.

Chronic mesenteric ischemia (CMI) involving occlusion and/or stenosis of multiple mesenteric arteries is rare. We report our experience with a 66-year-old man who presented with a more than 3 months history of abdominal pain and vomiting/diarrhea. A diagnosis of CMI due to occlusion of the superior mesenteric artery (SMA) and severe stenosis of the celiac artery by median arcuate ligament syndrome was made. Complete revascularization through iliac artery-SMA bypass grafting and arcuate ligament dissection assisted with staged-catheter intervention successfully alleviated the patient's symptoms. The patient has maintained a normal daily diet for 6 months postoperatively.

Treatment of Advanced Pancreatic Body and Tail Cancer by En Bloc Distal Pancreatectomy with Transverse Mesocolon Resection Using a Mesenteric Approach.

BACKGROUND: Pancreatic body and tail cancer easily invades retroperitoneal tissue, including the transverse mesocolon. It is difficult to ensure a dissected peripancreatic margin with standard distal pancreatectomy for advanced pancreatic body and tail cancer. Thus, we developed a novel surgical procedure to ensure dissection of the peripancreatic margin. This involved performing dissection deeper than the fusion fascia of Toldt and further extensive en bloc resection of the root of the transverse mesocolon. We performed distal pancreatectomy with transverse mesocolon resection (DP-TCR) using a mesenteric approach and achieved good outcomes. METHODS: There are two main considerations for surgical procedures using a mesenteric approach: 1) dissection deeper than the fusion fascia of Toldt (securing the vertical margin) and 2) modular resection of the pancreatic body and tail, with the root of the transverse mesocolon and adjacent organs in a horizontal direction (ensuring the caudal margin). RESULTS: From 2017 to 2019, we performed DP-TCR using a mesenteric approach for six patients with advanced pancreatic body and tail cancer. Histopathological radical surgery was possible in all patients who underwent DP-TCR. No Clavien-Dindo grade IIIa or worse perioperative complications were observed in any patient. CONCLUSIONS: We believe that DP-TCR is useful as a radical surgery for advanced pancreatic body and tail cancer with extrapancreatic invasion.

Clinical effectiveness of iguratimod based on real-world data of patients with rheumatoid arthritis.

OBJECTIVES: Iguratimod (IGU) is a conventional synthetic disease-modifying drug that has been approved based on its additive effects with methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). The objective of the study is to establish the effectiveness of IGU with versus IGU without MTX irrespective of whether MTX is well tolerated or not by the patients. METHODS: Disease activity scores in 177 RA patients treated using IGU were retrospectively evaluated at baseline and after 4, 12, and 24 weeks, and adverse events (AEs) were noted. RESULTS: IGU reduced the disease activity parameters, disease activity score (DAS)-ESR, DAS-CRP, the simplified disease activity index (SDAI), and clinical disease activity index (CDAI) in the concomitant MTX and non-MTX, female and male, and young and elderly patient groups after 24 weeks. Multivariate analysis demonstrated that IGU was more effective with concomitant MTX and in elderly and male patients. Severe AEs were observed only in the elderly group: two cases of pneumonia, 1 of pneumocystis pneumonia, 1 of heart failure, and 1 of salivary gland adenoma. CONCLUSIONS: IGU is effective for RA, especially with concomitant MTX, and in elderly and male patients. Key Points • Iguratimod is effective for RA, especially with concomitant MTX, and in elderly and male patients. • Since all serious adverse events were in the elderly group in this study, sufficient monitoring for adverse events, especially for elderly RA patients, is needed during iguratimod therapy.

Preventive replacement policies with time of operations, mission durations, minimal repairs and maintenance triggering approaches.

When a mission arrives at a random time and lasts for a duration, it becomes an interesting problem to plan replacement policies according to the health condition and repair history of the operating unit, as the reliability is required at mission time and no replacement can be done preventively during the mission duration. From this viewpoint, this paper proposes that effective replacement policies should be collaborative ones gathering data from time of operations, mission durations, minimal repairs and maintenance triggering approaches. We firstly discuss replacement policies with time of operations and random arrival times of mission durations, model the policies and find optimum replacement times and mission durations to minimize the expected replacement cost rates analytically. Secondly, replacement policies with minimal repairs and mission durations are discussed in a similar analytical way. Furthermore, the maintenance triggering approaches, i.e., replacement first and last, are also considered into respective replacement policies. Numerical examples are illustrated when the arrival time of the mission has a gamma distribution and the failure time of the unit has a Weibull distribution. In addition, simple case illustrations of maintaining the production system in glass factories are given based on the assumed data.

Förster resonance energy transfer (FRET)-Labeled nanoprobe enables real-time diagnosis of pancreatic juice activation due to postoperative pancreatic fistula.

OBJECTIVES: Postoperative pancreatic fistula (POPF) subsequent to pancreatectomy often causes activation of pancreatic juice, resulting in serious complications. In POPF, the types of pancreatic juices found are active and inactive, and the identification of these two types of pancreatic juice greatly contributes to the development of postoperative management after pancreatectomy. This study reports favorable results of the clinical application of the Förster resonance energy transfer (FRET) nanoprobe that was independently developed to distinguish between the active and inactive types of pancreatic juice. METHODS: The FRET nanoprobe developed was a nanoprotein capsule. It exuded a red color when the capsule structure was maintained. When activated protease in the pancreatic juice acts on it, the capsules are reduced quantitatively and FRET is abolished, resulting in a change in color from red to green. Pancreatic juice activation can be measured by the FRET signal. A total of 117 drainage fluid samples from 16 postpancreatoduodenectomy cases were obtained and evaluated. RESULTS: The diagnosis of pancreatic juice activation was possible using the FRET signal with a cut-off value of 1.6. Pancreatic juice activation was not associated with drainage fluid amylase (AMY) levels. The results demonstrated that pancreatic juice was activated when drainage fluid was infected. CONCLUSION: The use of a FRET nanoprobe enabled real-time detection of the presence or absence of pancreatic juice activation in pancreatic fistula after pancreatic surgery. There was an adequate correlation between infection and pancreatic juice activation regardless of drain AMY levels.

Presence of Acanthamoeba and diversified bacterial flora in poorly maintained contact lens cases.

Acanthamoeba can cause visually destructive Acanthamoeba keratitis (AK) in contact lens (CL) users. The purpose of this study was to determine whether Acanthamoeba was present in the CL cases of CL wearers and to develop techniques to prevent the contaminations. To accomplish this, 512 CL case samples were collected from 305 healthy CL wearers. Using real-time PCR, Acanthamoeba DNA was detected in 19.1% of CL cases, however their presence was not directly associated with poor CL case care. Instead, the presence of Acanthamoeba DNA was associated with significant levels of many different bacterial species. When the CL cases underwent metagenomic analysis, the most abundant bacterial orders were Enterobacteriales followed by Burkholderiales, Pseudomonadales, and Flavobacteriales. The presence of Acanthamoeba was characterized by Propionibacterium acnes and Rothia aeria and was also associated with an increase in the α diversity. Collectively, Acanthamoeba contamination occurs when a diversified bacterial flora is present in CL cases. This can effectively be prevented by careful and thorough CL case care.

Thermodynamic study of the acid-induced decontamination of waste green sand generated in a brass foundry.

Waste foundry sand (WFS) from the brass and bronze casting and molding process include various potentially toxic elements (PTEs), such as copper, zinc, tin, and lead. Hence, the utilization of WFS in construction and geotechnical applications evokes environmental concerns due to the rain-induced leaching of PTEs into the groundwater system. The present study investigated the extractive decontamination of WFS using mineral acids, e.g., HCl, H2SO4, or HNO3. Favorable extraction efficiency was achieved with HCl as compared to the other mineral acids, which was further enhanced at high temperatures and increased acid concentrations. The thermodynamic analysis indicated that ≥ 4 mol L-1 of HCl and ≤ 100 °C temperature ensured maximum extraction of PTEs due to the endothermic interactions between the HCl and PTEs. The HCl-treated WFS needed to be rinsed with water to restrict the after treatment elution of PTEs. The hazardous environmental impact of acid-treated WFS was evaluated following the standard leaching test and comparison with legislative recommendations for PTEs, which showed the water-assisted leaching rate of all the PTEs are within the regulatory limits.

A questionnaire survey on the efficacy of various treatments for dyskinetic cerebral palsy due to preterm bilirubin encephalopathy.

OBJECTIVES: Preterm children with severe dyskinetic cerebral palsy due to bilirubin encephalopathy often suffer from marked generalised hypertonus as they age. We performed a questionnaire survey to investigate patient-reported outcomes of treatments for improving their activities of daily life. METHODS: A mail questionnaire was administered to the caregivers of 67 children with preterm bilirubin encephalopathy aged >4 years. We asked about the type of treatments they received and their efficacy using a five-point subjective scale for the following five domains: motor function, postural stability, sleep, pain, and care burden. The names of oral drugs and their efficacies were also explored. RESULTS: The response rate of the questionnaires was 62.7% (42/67), and we analysed the results from 41 validated cases. All children underwent rehabilitation. A total of 30 children received oral drugs, 22 botulinum toxin, 12 orthopaedic surgery, and 3 intrathecal baclofen. Each of these treatments was subjectively reported to be effective in more than half of the recipients for each of the five domains, whereas 23 (56%) required more than two types of treatments other than rehabilitation. Chlordiazepoxide was the most commonly used oral drug, by 28 children (68%), and was discontinued in 7 patients (25%) only. In the sleep domain, the rate of a positive effect was significantly higher for oral drugs (92.7%) than the other treatments (p < 0.01). CONCLUSION: All treatments were partially effective, but their appropriate combination based on a multidisciplinary approach is essential for muscle tone management in children with preterm bilirubin encephalopathy.