Study on the efficacy of early treatment with pirfenidone on the lung function of patients with idiopathic pulmonary fibrosis

BACKGROUND Idiopathic pulmonary fibrosis(IPF)is classified under fibrotic interstitial pneumonia,characterized by a chronic and progressive course.The predominant clinical features of IPF include dyspnea and pulmonary dysfunction.AIM To assess the effects of pirfenidone in the early treatment of IPF on lung function in patients.METHODS A retrospective analysis was performed on 113 patients with IPF who were treated in our hospital from November 2017 to January 2023.These patients were divided into two groups:control group(n=53)and observation group(n=60).In the control group,patients received routine therapy in combination with methylprednisolone tablets,while those in the observation group received routine therapy together with pirfenidone.After applying these distinct treatment approaches to the two groups,we assessed several parameters,including the overall effectiveness of clinical therapy,the occurrence of adverse reactions(e.g.,nausea,vomiting,and anorexia),symptom severity scores,pulmonary function index levels,inflammatory marker levels,and the 6-min walk distance before and after treatment in both groups.RESULTS The observation group exhibited significantly higher rates than the control group after therapy,with a clear distinction(P<0.05).After treatment,the observation group experienced significantly fewer adverse reactions than the control group,with a noticeable difference(P<0.05).When analyzing the symptom severity scores between the two groups of patients after treatment,the observation group had significantly lower scores than the control group,with a distinct difference(P<0.05).When comparing the pulmonary function index levels between the two groups of patients after therapy,the observation group displayed significantly higher levels than the control group,with a noticeable difference(P<0.05).Evaluating the inflammatory marker data(C-reactive protein,interleukin-2[IL-2],and IL-8)between the two groups of patients after therapy,the observation group exhibited significantly lower levels than the control group,with significant disparities(P<0.05).Comparison of the 6-min walking distance data between the two groups of patients after treatment showed that the observation group achieved significantly greater distances than the control group,with a marked difference(P<0.05).CONCLUSION Prompt initiation of pirfenidone treatment in individuals diagnosed with IPF can enhance pulmonary function,elevate inflammatory factor levels,and increase the distance covered in the 6-min walk test.This intervention is conducive to effectively decreasing the occurrence of adverse reactions in patients.

Systematic review and network meta-analysis of different nonsteroidal anti-inflammatory drugs for juvenile idiopathic arthritis

BACKGROUND Various non-steroidal anti-inflammatory drugs(NSAIDs)have been used for juvenile idiopathic arthritis(JIA).However,the optimal method for JIA has not yet been developed.AIM To perform a systematic review and network meta-analysis to determine the optimal instructions.METHODS We searched for randomized controlled trials(RCTs)from PubMed,EMBASE,Google Scholar,CNKI,and Wanfang without restriction for publication date or language at August,2023.Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis.The surface under the cumulative ranking curve(SUCRA)analysis was used to rank the treatments.P value less than 0.05 was identified as statistically significant.RESULTS We included 8 RCTs(1127 patients)comparing 8 different instructions including meloxicam(0.125 qd and 0.250 qd),Celecoxib(3 mg/kg bid and 6 mg/kg bid),piroxicam,Naproxen(5.0 mg/kg/d,7.5 mg/kg/d and 12.5 mg/kg/d),inuprofen(30-40 mg/kg/d),Aspirin(60-80 mg/kg/d,75 mg/kg/d,and 55 mg/kg/d),Tolmetin(15 mg/kg/d),Rofecoxib,and placebo.There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response.The SUCRA shows that celecoxib(6 mg/kg bid)ranked first(SUCRA,88.9%),rofecoxib ranked second(SUCRA,68.1%),Celecoxib(3 mg/kg bid)ranked third(SUCRA,51.0%).There were no significant differences between any two NSAIDs regarding adverse events.The SUCRA shows that placebo ranked first(SUCRA,88.2%),piroxicam ranked second(SUCRA,60.5%),rofecoxib(0.6 mg/kg qd)ranked third(SUCRA,56.1%),meloxicam(0.125 mg/kg qd)ranked fourth(SUCRA,56.1%),and rofecoxib(0.3 mg/kg qd)ranked fifth(SUCRA,56.1%).CONCLUSION In summary,celecoxib(6 mg/kg bid)was found to be the most effective NSAID for treating JIA.Rofecoxib,piroxicam,and meloxicam may be safer options,but further research is needed to confirm these findings in larger trials with higher quality studies.

Trigonelline mitigates bleomycin-induced idiopathic pulmonary fibrosis in mice

Objective:To evaluate the effect of trigonelline on bleomycin-induced idiopathic pulmonary fibrosis(IPF)and to explore its underlying mechanisms using network pharmacology.Methods:IPF was induced in C57BL/6 mice by a single intratracheal instillation of bleomycin(5 mg/kg).Trigonelline was administered at doses of 25,50,and 100 mg/kg/day orally from the 2nd day post-bleomycin induction up to the 14th day.In IPF-induced mice,lung coefficient,immune cell infiltration in bronchoalveolar lavage fluid,and oxidative stress were measured.Histological alterations in lung tissues were also assessed.Moreover,network pharmacology approach was conducted to reveal molecular interactions of bleomycin and trigonelline with targets of IPF.Results:Trigonelline treatment reduced bleomycin-induced oxidative stress and immune cell infiltration,and mitigated physiological changes in the lung tissues of mice.Moreover,trigonelline alleviated bleomycin-induced histological alterations in lung tissues.Network pharmacology analysis showed that bleomycin and trigonelline interacted with IPF targets,such as NFKB1,HDAC2,HIF1A,and TLR4.Conclusions:The interaction of trigonelline with key IPF targets and its ameliorative effects on lung damage and oxidative stress highlight its potential in treating IPF.It may be considered an antifibrotic agent for further clinical development.

Serum Zinc and Copper Level in Juvenile Idiopathic Arthritis (JIA) Patients and Its Correlation with Disease Duration-A Tertiary Hospital Study

Background: Juvenile Idiopathic Arthritis (JIA) is the most prevalent rheumatic disease in children. It is associated with abnormal levels of serum zinc (Zn) and copper (Cu) as during inflammation serum copper concentration increases and zinc decreases. Objective: To assess the serum Zn and Cu levels in different sub-types of JIA patients and their correlation with the disease duration. Methods: This cross-sectional study was conducted over twelve months at the Pediatric Rheumatology Division, Department of Paediatrics, Bangabandhu Sheikh Mujib Medical University. Sixty-nine JIA cases that fulfilled the International League of Association for Rheumatology (ILAR) criteria were taken as cases and age and sex-matched healthy children were considered as controls. The serum Zn and Cu tests were done using the spectrophotometric method with INDIKO PLUS Drug Analyzer. Data were recorded in a pre-designed questionnaire. Data were checked, verified and analyzed manually where continuous variables were analyzed using unpaired t-test and categorical variables using the ANOVA test. Pearson’s correlation coefficient test was used to see the correlation of serum zinc and copper levels with disease duration. Results: Boys were predominant in both case and control groups, with the majority within the 10 to 16-year-age group. Enthesitis-related arthritis (ERA) was the most common subtype followed by sJIA, Oligo JIA, Poly JIA (RF-) and unclassified subtypes. Disease duration was found less than 12 months in 30.4% of JIA patients. Serum analysis revealed a statistically significant reduction in mean zinc levels and increased copper levels in JIA patients compared to controls. This study observed a negative correlation between serum zinc levels and disease duration, whereas serum copper levels exhibited a positive correlation with disease duration. Conclusion: In conclusion, this study revealed that JIA patients exhibit alterations in serum zinc and copper levels. Serum copper levels showed a positive correlation and serum zinc levels showed a negative correlation with the duration of the disease.

Bone destruction of orbital wall in idiopathic orbital inflammatory pseudotumor:does it always imply malignancy?

AIM:To assess the clinical presentations and outcomes of idiopathic orbital inflammatory pseudotumor(IOIP)patients with orbital wall bone destruction(OWBD)and to propose an expanded classification system that includes bone destruction.METHODS:The study retrospectively reviewed clinical presentations,imaging findings,treatment modalities,and outcomes of six patients diagnosed histopathologically with IOIP and OWBD at the Beijing Tongren Hospital,Capital Medical University between October 2018 and June 2021.RESULTS:Over two years,6(10%)of 60 IOIP patients at our hospital exhibited OWBD,but this may overrepresent severe cases.The cohort consisted of three men and three women,aged 17 to 60y(mean 35.5±16.1y).Presenting symptoms included proptosis,eyelid swelling,decreased visual acuity with pain,and palpable mass.Imaging revealed multiple anatomical structures involved with the medial wall being the most common site of bone destruction.Histopathological examination showed classic type in five patients and sclerosing type in one patient.All patients underwent surgical resection followed by methylprednisolone treatment.Follow-up(mean 30.3±3.1mo)indicated three patients had no recurrence,while others had varying degrees of symptom persistence or recurrence.CONCLUSION:IOIP with bone destruction is a rare but significant subtype that mimics malignancy,leading to potential diagnostic and therapeutic challenges.Our findings suggest that complete surgical resection combined with adjunctive glucocorticoid therapy can yield favorable outcomes.However,larger-scale studies are needed to further optimize therapeutic approaches.

Retinal displacement after surgery for idiopathic macular hole

AIM:To review and summarize the mechanism hypothesis,influencing factors and possible consequences of macular retinal displacement after idiopathic macular hole(IMH)surgery.METHODS:PubMed and Web of Science database was searched for studies published before April 2023 on“Retinal displacement”,“Idiopathic macular holes”,and“Macular displacement”.RESULTS:Recently,more academics have begun to focus on retinal displacement following idiopathic macular holes.They found that internal limiting membrane(ILM)peeling was the main cause of inducing postoperative position shift in the macular region.Moreover,several studies have revealed that the macular hole itself,as well as ILM peeling method,will have an impact on the result.In addition,this phenomenon is related to postoperative changes in macular retinal thickness,cone outer segment tips line recovery,the occurrence of dissociated optic nerve fiber layer(DONFL)and the degree of metamorphopsia.CONCLUSION:As a subclinical phenomenon,the clinical significance of postoperative macular displacement cannot be underestimated as it may affect the recovery of anatomy and function.

Early pirfenidone treatment enhances lung function in idiopathic pulmonary fibrosis patients

This editorial comments on the study by Lei et al investigating the efficacy of early treatment with pirfenidone on the lung function of patients with idiopathic pulmonary fibrosis(IPF)published.This study evaluates the efficacy of early treatment with pirfenidone on lung function in patients with IPF.The early and advanced stages of IPF are defined,highlighting the drug's benefits.While prior research indicates pirfenidone's effectiveness in advanced IPF,this study focuses on its advantages in early stages.The study emphasizes the importance of computed tomography imaging alongside biochemical data and lung function tests for a comprehensive analysis of symptom relief.Results show that early intervention with pirfenidone significantly reduces disease progression and preserves lung function,underscoring its potential as a critical treatment strategy in early IPF.

Timing impact on the initiation of pirfenidone therapy on idiopathic pulmonary fibrosis disease progression

In this editorial,we comment on the article by Lei et al,with a specific focus on the timing of the initiation of the antifibrotic agent pirfenidone(PFD)in the management of idiopathic pulmonary fibrosis(IPF)and its impact on lung function of IPF patients.PFD is an antifibrotic agent that is widely used in the management of IPF in both early and advanced stages.It inhibits various pathways and has antifibrotic,anti-inflammatory,and antioxidant properties.Despite dosage lowering,PFD slowed IPF progression and maintained functional capacity.The 6-min walk distance test indicated that patients tolerated adverse events well,and PFD significantly reduced the incidence of progression episodes and death.Even when a single disease-progression event occurred,continuing PFD treatment had benefits.

Evolution of treatment options for juvenile idiopathic arthritis

A recent study published in World J Clin Cases addressed the optimal non-steroidal anti-inflammatory drugs(NSAIDs)for juvenile idiopathic arthritis(JIA).Herein,we outline the progress in drug therapy of JIA.NSAIDs have traditionally been the primary treatment for all forms of JIA.NSAIDs are symptom-relief medications,and well tolerated by patients.Additionally,the availability of selective NSAIDs further lower the gastrointestinal adverse reactions compared with traditional NSAIDs.Glucocorticoid is another kind of symptom-relief medications with potent anti-inflammatory effect.However,the frequent adverse events limit the clinical use.Both NSAIDs and glucocorticoid fail to ease or pre-vent joint damage,and the breakthrough comes along with the disease-mo-difying antirheumatic drugs(DMARDs).DMARDs can prevent disease pro-gression and reduce joint destruction.Particularly,the emergence of biologic DMARDs(bDMARDs)has truly revolutionized the therapeutics of JIA,compared with conventional synthetic DMARDs.As a newly developed class of drugs,the places of most bDMARDs in the management of JIA remain to be well estab-lished.Nevertheless,the continuous evolution of bDMARDs raises hopes of improving long-term disease outcomes for JIA.

Idiopathic mesenteric phlebosclerosis missed by a radiologist at initial diagnosis: A case report

BACKGROUND Idiopathic mesenteric phlebosclerosis(IMP)is a rare type of ischemic colitis characterized by thickening of the wall of the right hemicolon and calcification,sclerosis,and fibrosis of mesenteric veins.The diagnosis of IMP is based on typical clinical features and imaging findings.We report a case of IMP that was initially missed by the radiologist.CASE SUMMARY A 77-year-old woman was admitted to the hospital due to chronic diarrhea for over 2 months.She had been consuming Chinese patent medicines(CPM)containing fructus gardeniae for more than 15 years.Colonoscopy revealed an edematous mucosa,bluish-purple discoloration,erosions,and ulcerations throughout the colorectal area.Abdominal computed tomography(CT)showed diffuse mural thickening of the entire colorectum,with tortuous thread-like calcifications in the right hemicolon,left hemicolon,and rectum.Most of the calcifications were located in the mesenteric vein.The diagnosis of IMP was established based on medical history,colonoscopy,CT findings,and histopathological examination.The patient was treated conservatively with papaverine and rifaximin,and CPM was stopped.Her diarrhea symptoms improved,indicating the effectiveness of the treatment.Over the next several years,she took opium alkaloids for an extended period and did not require hospitalization for the aforementioned gastrointestinal disorder.CONCLUSION IMP is a rare gastrointestinal disease affecting Asian populations,possibly related to long-term herbal medicine intake.Accurate imaging analysis is crucial for diagnosis,but insufficient understanding of the disease can lead to misdiagnosis or missed diagnosis.Treatment strategies should be personalized.

Scoliocorrector Fatma-UI for correction of adolescent idiopathic scoliosis: Development, effectivity, safety and functional outcome

BACKGROUND Adolescent idiopathic scoliosis remains a major problem due to its high incidence,high risk,and high cost.One of the aims of the management in scoliosis is to correct the deformity.Many techniques are available to correct scoliosis deformity;however,they are all far from ideal to achieve three-dimensional correction in scoliosis.AIM To develop a set of tools named Scoliocorrector Fatma-UI(SCFUI)to aid threedimensional correction and to evaluate the efficacy,safety,and functional outcome.METHODS This study consists of two stages.In the first stage,we developed the SCFUI and tested it in finite element and biomechanical tests.The second stage was a single-blinded randomized clinical trial to evaluate the SCFUI compared to direct vertebral rotation(DVR).Forty-four subjects with adolescent idiopathic scoliosis were randomly allocated into the DVR group(n=23)and SCFUI group(n=21).Radiological,neurological,and functional outcome was compared between the groups.RESULTS Finite element revealed the maximum stress of the SCFUI components to be between 31.2-252 MPa.Biomechanical analysis revealed the modulus elasticity of SCFUI was 9561324±633277 MPa.Both groups showed improvement in Cobb angle and sagittal profile,however the rotation angle was lower in the SCFUI group(11.59±7.46 vs 18.23±6.39,P=0.001).Neurological and functional outcome were comparable in both groups.CONCLUSION We concluded that SCFUI developed in this study resulted in similar coronal and sagittal but better rotational correction compared to DVR.The safety and functional outcomes were also similar to DVR.

Clinical and laboratory features of juvenile idiopathic arthritis with wrist involvement:Results of a retrospective cohort study

BACKGROUND Previous studies in the pre-biological era showed an association of wrist inflammation in juvenile idiopathic arthritis(JIA)with progressive disease course,polyarticular involvement and failure of methotrexate treatment.AIM To describe features of JIA,associated with wrist arthritis.METHODS Data from about 753 JIA patients were included in this retrospective cohort study.The clinical and laboratory features of patients with and without wrist involvement were analyzed.RESULTS Wrist involvement was found in oligoarthritis(5.8%),RF(−)/RF(+)polyarthritis(44.9%/15.0%),enthesitis-related arthritis(17.7%),and systemic(58.6%)JIA categories.Unilateral wrist involvement was typical for oligoarthritis patients,bilateral involvement was either equal to that of unilateral involvement or was more frequent in other categories.Wrist arthritis was found to be associated with female sex,a low incidence of uveitis,and more indications of systemic inflammation,including elevated levels of C-reactive protein,erythrocyte sedimentation rate,and platelets,as well as involvement of the cervical spine,temporomandibular,shoulder,elbow,metacarpophalangeal,proximal interphalangeal,distal interphalangeal,hip,ankle,and tarsus arthritis.The number of patients with hip osteoarthritis and hip replacement was also higher.Wrist arthritis was associated with a lower probability of achieving remission[hazard ratio(HR)=1.3(95%CI:1.0-1.7),P=0.055],and a higher probability of being treated with biologics[HR=1.7(95%CI:1.3-2.10,P=0.00009)].CONCLUSION Wrist arthritis in JIA patients is a marker of a severe disease course,characterized by more intensive inflammation,unfavorable outcomes,and.requiring more intensive treatment with early administration of biologics.Close monitoring of wrist inflammation with ultrasound and MR assessment with early biological treatment might improve the outcomes.

Clinical Observation of Serum Anti-PLA2R Antibody Levels in the Treatment of Idiopathic Membranous Nephropathy with Rituximab

Objective:To investigate the efficacy of rituximab in the treatment of idiopathic membranous nephropathy with varying levels of serum phospholipase A2 receptor antibodies.Methods:A total of 137 patients with idiopathic membranous nephropathy admitted to Beijing Sixth Hospital were selected.Based on their blood PLA2R antibody levels before rituximab treatment,patients were categorized into the PLA2R antibody positive group(n=94)and the PLA2R antibody negative group(n=43).They were followed up for at least 1 year,during which the efficacy,measured through 24-hour urine protein quantification and serum albumin levels,were compared between the two groups before and after treatment.Results:After 3 months of treatment,there was no significant difference in the quantitative levels of 24-hour urine protein between the two groups(P>0.05).However,after 6 and 12 months of treatment,there was a significant difference in the levels of 24-hour urine protein between the two groups(P<0.05).Additionally,after 3 months of treatment,there was a notable difference in the serum albumin levels between the two groups(P<0.05).However,after 6 and 12 months of treatment,there was no significant difference in serum albumin levels between the two groups(P>0.05).Analysis of complications in the two groups revealed that in the positive group,9 individuals experienced thrombosis,5 had infections,and 11 developed acute kidney injury(AKI).In contrast,in the negative group,5 individuals had thrombosis,2 had infections,and 3 developed AKI.There was no statistically significant difference in complications between the two groups(P>0.05).Conclusion:Serum anti-PLA2R antibody levels provide valuable insights into the clinical observation of rituximab treatment for idiopathic membranous nephropathy.They aid in understanding the disease’s pathogenesis,evaluating treatment efficacy,and predicting disease prognosis.

Current research of idiopathic normal pressure hydrocephalus:Pathogenesis,diagnosis and treatment

Idiopathic normal pressure hydrocephalus(iNPH)is caused by impaired cerebrospinal fluid absorption in the elderly;it is a surgically treatable form of dementia.Gait disturbance,dementia,and urinary incontinence are the triad of signs for iNPH.In addition to these clinical findings,imaging studies show characteristic ventricular enlargement.High Evans Index and‘disproportionately enlarged subarachnoid hydrocephalus’are other well-known imaging findings of iNPH.If the tap test shows improved symptoms,shunt surgery is performed.The disease was first described by Hakim and Adams in 1965,followed by the publication of the first,second,and third editions of the guidelines in 2004,2012,and 2020,respectively.Recent studies signal the glymphatic system and classical cerebrospinal fluid(CSF)absorption from the dural lymphatics as aetiological mechanisms of CSF retention.Research is also underway on imaging test and biomarker developments for more precise diagnosis,shunting technique options with fewer sequelae and complications,and the influence of genetics.Particularly,the newly introduced‘suspected iNPH’in the third edition of the guidelines may be useful for earlier diagnosis.However,less well-studied areas remain,such as pharmacotherapy in non-operative indications and neurological findings other than the triadic signs.This review briefly presents previous research on these and future issues.

Successful treatment of patients with refractory idiopathic membranous nephropathy with low-dose Rituximab:A single-center experience

BACKGROUND The recognition of idiopathic membranous nephropathy(IMN)as an autoimmune disease has paved the way for the use of B-cell-depleting agents,such as Rituximab(RTX),which is now a first-line drug for treating IMN with proven safety and efficacy.Nevertheless,the usage of RTX for the treatment of refractory IMN remains controversial and challenging.AIM To evaluate the efficacy and safety of a new low-dose RTX regimen for the treatment of patients with refractory IMN.METHODS A retrospective study was performed on refractory IMN patients that accepted a low-dose RTX regimen(RTX,200 mg,once a month for five months)in the Xiyuan Hospital of Chinese Academy of Chinese Medical Sciences’Department of Nephrology from October 2019 to December 2021.To assess the clinical and immune remission data,we performed a 24 h urinary protein quantification(UTP)test and measured the serum albumin(ALB)and serum creatinine(SCr)levels,phospholipase A2 receptor(PLA2R)antibody titer,and CD19+B-cell count every three months.RESULTS A total of nine refractory IMN patients were analyzed.During follow-up conducted twelve months later,the results from the 24 h UTP decreased from baseline[8.14±6.05 g/d to 1.24±1.34 g/d(P<0.05)]and the ALB levels increased from baseline[28.06±8.42 g/L to 40.93±5.85 g/L(P<0.01)].Notably,after administering RTX for six months,the SCr decreased from 78.13±16.49μmol/L to 109.67±40.87μmol/L(P<0.05).All of the nine patients were positive for serum anti-PLA2R at the beginning,and four patients had normal anti-PLA2R titer levels at six months.The level of CD19+B-cells decreased to 0 at three months,and CD19+B-cell count remained at 0 up until six months of follow-up.CONCLUSION Our low-dose RTX regimen appears to be a promising treatment strategy for refractory IMN.

The Outcome of Posterior Spinal Fusion and Instrumentation of Adolescent Idiopathic Scoliosis without Wound Suction Drainage

Background: In spine surgery postoperative closed suction drainage is used to decrease the potential risks of wound hematoma formation, and reduces the risk of infection, cord compression and neurologic deficit. However, the efficacy of drains used for this purpose in adolescent idiopathic scoliosis is controversial. The purpose of this study is to evaluate outcomes of patients after posterior spinal fusion with instrumentation for adolescent idiopathic scoliosis without wound suction drainage. Methods: A total of 66 Patients who underwent posterior spinal fusion and instrumentation for the correction of Adolescent idiopathic scoliosis without the use of drain from January 2012 to January 2021 were included. Wound dehiscence, wound hematoma, infection, preoperative and postoperative hemoglobin levels and need for transfusion were described as frequency and mean values. Results: The average age was 15.06 years. Hospital stay was 2.2 days. Patients were followed-up over 50.21 months. There was no deep infection, wound hematoma. The difference between just postoperative and three days after operation hemoglobin levels was not significant and no need for transfusion. Only 3 (4.5%) cases with superficial skin infection and 4 (6%) cases with skin and Wound dehiscence were treated with dressing and antibiotics with full recovery. Conclusion: Without using drain for patients with idiopathic scoliosis who underwent posterior spinal fusion and instrumentation, no increase in blood loss, transfusion requirements, wound infection, skin dehiscence, and wound hematoma was observed.

Thalidomide Is an Adjunct Therapy for the Refractory Systemic Juvenile Idiopathic Arthritis Patients in a Tertiary Hospital Study

Background: Systemic JIA (sJIA) is one of the subtypes of JIA, which is most difficult to treat among all JIA cases. About 50% of sJIA cases did not respond to traditional disease modifying anti-rheumatic drugs (DMARDs)—metho-trexate (MTX). Thalidomide is an immunomodulating and anti-inflammatory drug that induces sustained improvement of refractory sJIA cases. Objectives: To evaluate the efficacy of thalidomide in refractory sJIA patients. Methods: This was a prospective interventional study carried out in the Paediatric Rheumatology and Immunology follow-up clinic run by the Department of Pediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from January 2019 to July 2020. Twenty-five sJIA patients who were refractory to conventional DMARDs were included in this study. These patients were prescribed thalidomide at a dose of 3 - 5 mg/kg/day for six months and efficacy was assessed by using juvenile arthritis disease activity score (JADAS 27) at 12th and 24th weeks of treatment. Result: Active joint counts and ESR improvement were observed in 90.69%, 97.67% and 69.84%, 100% of sJIA patients respectively at 12th and 24th weeks of treatment. Improvement of physicians and parent global assessment of VAS were 77.56%, 97.43% and 70.62% and 96.04% respectively at 12th and 24th weeks of treatment. Improvement of the total score of JADAS-27 was 77.51% at 12th week and 97.52% at 24th of week follow-up which was statistically significant. Somnolence, constipation and paresthesia were found as common adverse effect in this study. Conclusion: Efficacy of thalidomide was assessed by JADAS 27 criteria showed significant improvement in refractory sJIA patients in this study. It may be concluded that Thalidomide is safe and effective as an adjunct therapy of refractory sJIA patients.

Machine learning-based decision tool for selecting patients with idiopathic acute pancreatitis for endosonography to exclude a biliary aetiology

BACKGROUND Biliary microlithiasis/sludge is detected in approximately 30%of patients with idiopathic acute pancreatitis(IAP).As recurrent biliary pancreatitis can be prevented,the underlying aetiology of IAP should be established.AIM To develop a machine learning(ML)based decision tool for the use of endosonography(EUS)in pancreatitis patients to detect sludge and microlithiasis.METHODS We retrospectively used routinely recorded clinical and laboratory parameters of 218 consecutive patients with confirmed AP admitted to our tertiary care hospital between 2015 and 2020.Patients who did not receive EUS as part of the diagnostic work-up and whose pancreatitis episode could be adequately explained by other causes than biliary sludge and microlithiasis were excluded.We trained supervised ML classifiers using H_(2)O.ai automatically selecting the best suitable predictor model to predict microlithiasis/sludge.The predictor model was further validated in two independent retrospective cohorts from two tertiary care centers(117 patients).RESULTS Twenty-eight categorized patients’variables recorded at admission were identified to compute the predictor model with an accuracy of 0.84[95%confidence interval(CI):0.791-0.9185],positive predictive value of 0.84,and negative predictive value of 0.80 in the identification cohort(218 patients).In the validation cohort,the robustness of the prediction model was confirmed with an accuracy of 0.76(95%CI:0.673-0.8347),positive predictive value of 0.76,and negative predictive value of 0.78(117 patients).CONCLUSION We present a robust and validated ML-based predictor model consisting of routinely recorded parameters at admission that can predict biliary sludge and microlithiasis as the cause of AP.

Evaluation of chronic idiopathic tinnitus and its psychosocial triggers

BACKGROUND The tinnitus susceptibility patterns in relation to different psychological and life stressors are unknown in different cultures.AIM To determine the comorbid psychosocial factors and behaviors associated with tinnitus and the predictors for the increase in its severity.METHODS Participants were 230 adults(males=70;females=160;mean age=38.6±3.3).They underwent audiograms,speech discrimination and masking testing,and neuropsychiatric evaluation.Measures used for assessment included tinnitus handicap inventory,depression anxiety stress scale 21(DASS-21),perceived stress scale(PSS),and insomnia severity index(ISI).RESULTS Patients had mean duration of tinnitus of 11.5±2.5 mo.They had intact hearing perception at 250-8000 Hz and 95(41.3%)had aggravation of tinnitus loudness by masking noise.Decompensated tinnitus was reported in 77%(n=177).The majority had clinically significant insomnia(81.3%),somatic symptoms(75%)other than tinnitus and perceived moderate(46.1%)and high(44.3%)stress to tinnitus.The severe/extremely severe symptoms of depression,anxiety and stress were reported in 17.4%,35.7%and 44.3%,respectively.Patients with decompensated type had significantly higher scores for ISI(P=0.001)and DASS-21(depression=0.02,anxiety=0.01,stress=0.001)compared to those with compensated tinnitus.Psychiatric interviewing showed that 35.7%had non-specific anxiety disorder,17.4%had major depression,and 19.6%fulfilled the criteria of somatization disorder.Multivariate analysis showed that the only independent predictors for tinnitus severity were the duration of tinnitus[odd ratios(OR)=0.832,95%CI:0.640-1.158;P=0.001]and PSS(OR=0.835,95%CI:0.540-1.125;P=0.001)scores.CONCLUSION To the best of our knowledge,this is the first study in our culture to evaluate the causal relationship between psychological factors and tinnitus onset,severity and persistence.Tinnitus could be the earliest and dominant somatic symptom induced by life stressors and psychological vulnerabilities.Therefore,multidisciplinary consultation(psychologists,psychiatrists,and neurologists)is important to acknowledge among the audiologists and otolaryngologists who primarily consult patients.

Correlation between Toll-like Receptor Gene Polymorphisms and Idiopathic Nephrotic Syndrome in Chinese Children

Objective Idiopathic nephrotic syndrome(INS)is the most common glomerular disease in children.Toll-like receptors(TLRs)have been reported to be associated with response to steroid treatment in children with INS.Nevertheless,the correlation between TLR genes and the progression of INS has not yet been clarified.The present study aimed to investigate the association of single-nucleotide polymorphisms(SNPs)in TLR2,TLR4,and TLR9 with susceptibility to INS as well as the clinical phenotyping of steroid responsiveness in Chinese children with INS.Methods A total of 183 pediatric inpatients with INS were included and given standard steroid therapy.Based on their clinical response to steroids,the patients were classified into three groups:steroid-sensitive nephrotic syndrome(SSNS),steroid-dependent nephrotic syndrome(SDNS),and steroid-resistant nephrotic syndrome(SRNS).A total of 100 healthy children were employed as controls.The blood genome DNA was extracted from each participant.Six SNPs(rs11536889,rs1927914,rs7869402,rs11536891,rs352140,and rs3804099)in TLR2,TLR4,and TLR9 were selected and detected by multiplex polymerase chain reaction with next-generation sequencing to assess TLR gene polymorphisms.Results Among the 183 patients with INS,89(48.6%)had SSNS,73(39.9%)had SDNS,and 21(11.5%)had SRNS.No significant difference was found in the genotype distribution between healthy children and patients with INS.However,the genotype and allele frequencies of TLR4 rs7869402 were significantly different between SRNS and SSNS.Compared with patients with the C allele and CC genotype,patients with the T allele and CT genotype had an increased risk of SRNS.Conclusion TLR4 rs7869402 affected the steroid response in Chinese children with INS.It might be a predictor for the early detection of SRNS in this population.