Spontaneous Remission Rate Research Articles

Tapering and Sustained Remission of Thrombopoietin Receptor Agonists (TPO-RAs): Is it Time for Paediatric ITP?

Thrombopoietin receptor agonists (TPO-Ras; romiplostim/eltrombopag/avatrombopag) have demonstrated high efficacy rates (59-88%) and a good safety profile in clinical trials with adult patients with immune thrombocytopenia (ITP). Similar efficacy and safety results have been observed with romiplostim and eltrombopag in paediatric cohorts. Continuous treatment with TPO-RAs has shown durable responses with long-term use, up to 3years. The effect of TPO-RAs was generally considered transient, as platelet counts tended to drop to baseline values after a short period of time (about 2weeks), unless treatment was maintained. Several groups have reported successful discontinuation of TPO-RAs without the need for concomitant treatments. This is referred to as sustained remission off treatment (SROT). Both short- and medium-term treatment with TPO-RAs may reduce costs to our healthcare systems and, more importantly, may reduce the potential side effects that may be associated with continuous TPO-RA treatment. The issue of tapering and discontinuation of TPO-RAs in paediatric patients with ITP has received little attention to date. Given that paediatric ITP has much higher rates of spontaneous remission than ITP in adults, we consider that the possibility of SROT of TPO-RAs in paediatric patients with ITP is a neglected but very relevant issue in this subtype of the disease.

Are there differences between patients with unifocal nummular headache and those who progress to bifocal nummular headache? A retrospective observational study.

This retrospective observational cohort study aimed to compare clinical characteristics and treatment responses in patients exclusively experiencing unifocal nummular headache (NH) with those who develop the bifocal variant. A retrospective study was conducted on patients diagnosed with NH who attended a neurology (headache) outpatient clinic between January 2018 and December 2022. The cohort was divided into two groups: Group 1, exclusive unifocal NH; and Group 2, those developing a secondary focal area of pain, i.e., bifocal NH. Data were collected on demographic characteristics, clinical features, other headache comorbidities, and treatment-related information. A total of 23 patients were included in this study: 12 were categorized as unifocal NH (Group 1) and 11 as bifocal NH (Group 2). There were no differences between the two groups in terms of demographic characteristics, clinical features, or treatment response. Nonetheless, patients with bifocal NH exhibited spontaneous remission rates in the first pain area when compared to the unifocal NH group, with statistically significant differences (36% vs. 0%, p = 0.020). In our sample, patients with bifocal NH demonstrated spontaneous remission rates in the initial pain area, a phenomenon not observed in patients with unifocal NH. It is worth noting the limited sample size in the present study, highlighting the need for larger cohorts to validate and further explore our findings.

NELL1 membranous nephropathy: clinical associations provide mechanistic clues.

Neural epidermal growth factor-like 1 (NELL1) membranous nephropathy (MN) is notable for its segmental deposit distribution, IgG1 dominant deposits, and comparatively high rate of spontaneous remission. It has been associated with a variety of exposures and secondary conditions, specifically use of thiol-containing medications - including lipoic acid, bucillamine, and tiopronin - as well as traditional indigenous medications (TIM) particularly those with high mercury content, and non-steroid anti-inflammatory drugs (NSAIDs). Malignancies, graft vs. host disease (GVHD), infection, and autoimmune conditions have also been associated with NELL1 MN. Herein, we provide a detailed summary of the clinicopathologic features of NELL1 and associations with underlying conditions, with a focus on treatment and outcomes. Rare cases of dual NELL1 and phospholipase A2 receptor (PLA2R) positive MN are reviewed. Genome-wide association study of NELL1, role of NELL1 in other physiologic and pathologic processes, and connection between NELL1 MN and malignancy with relevance of NELL1 tumor staining are examined. Finally, relationships and potential disease mechanisms of thiol- and mercury- associated NELL1 MN are discussed.

P-79 Graves’ Disease associated with alemtuzumab use for multiple sclerosis

Abstract Introduction Alemtuzumab was the first humanized monoclonal antibody to be created and is directed against CD52, a lymphocyte cell surface marker of unknown function. It has been used to treat leukemia and organ transplant rejection. More recently, alemtuzumab has been demonstrated to be highly effective in treating relapsing-remitting multiple sclerosis (MS) disease. Thyroid disease develops in approximately 20% of patients using alemtuzumab for MS, and Graves’ disease is the most common among them. Graves’ disease has not been reported in the use of alemtuzumab for reasons other than MS. Clinical Case A 28-year-old female patient with a 10 year history of MS had been treated with pulse corticosteroid, β-interferon and fingolimod. She received alemtuzumab in May 2019 due to increased relapse rates. After the first dose of alemtuzumab, she could not continue her treatment program due to the COVID-19 pandemic. Thyrotoxic thyroid functions (TSH: <0.015 uIU/mL, free T4: 24.79 pmol/L) were detected in the laboratory examination of the patient who was admitted to the endocrinology outpatient clinic with the complaint of palpitation in April 2021. The review of the patient's past laboratory test results determined she was euthyroid before alemtuzumab treatment. She had no personal or family history of thyroid disease. She had no signs and symptoms of thyroid ophthalmopathy. Ultrasonographic examination of her thyroid gland revealed normal size gland and pseudonodular appearance in the parenchyma. Subsequent thyroid scintigraphy showed diffuse uptake of the radioisotope and reduced counting time of the examination. These results were consistent with Graves’ disease. The patient was started on 5 mg methimazole twice a day. Since the etiology of Graves’ disease was thought to be primarily related to alemtuzumab, the patient's MS treatment was continued with ocrelizumab. She stopped the methimazole treatment within 3 months and did not regularly show up to her follow-up visit. In November 2022, she was admitted to the outpatient department with palpitation, sweating, and irritability symptoms. Thyrotoxic thyroid functions were detected again (TSH:<0,015 uIU/mL, free T4: 26,82 pmol/L). She was restarted on 5 mg methimazole treatment twice a day. In June 2023, she was euthyroid (TSH: 0,496 uIU/mL, free T4: 5,42 pmol/L, free T4: 10,45 pmol/L) and her TSI level was undetectable. The methimazole was reduced to 5 mg once a day. She continues to her treatment and follow-up in our center. Conclusion Graves’ disease is a common complication of alemtuzumab use in MS. Alemtuzumab-associated Graves’ disease follows an atypical course compared to the classical form of the disease. The spontaneous remission rate is less than in the classical form of the disease, and medical treatment is often required. Thyroidectomy may be necessary in cases that do not respond to antithyroid agents. Close monitoring of thyroid function tests is essential in alemtuzumab-associated Graves’ disease.

Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment

Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.

Prognosis of sarcoidosis and factors affecting prognosis.

Sarcoidosis is a multi-system disease of unknown etiology characterized by non-caseating granulomatous inflammation. Determining the characteristics and prognosis of sarcoidosis cases and revealing the factors that may affect the prognosis are important for approach to patient. This study was planned to obtain prognosis data for our country and to determine the factors affecting the prognosis. 188 patients, followed regularly for three years or more, admitted to Ankara University Faculty of Medicine, Department of Chest Diseases between 2012-2017 were evaluated retrospectively. Increased radiological findings, functional impairment and any of the clinical conditions requiring initiation/modification of treatment were accepted as progression. Clinical status of the patients at the last follow-up was defined as remission with treatment, spontaneous remission, stable disease, progression, chronic case and recurrence. Spontaneous remission and remission with treatment, regression, stable disease, and recurrence that followed without treatment and didn't cause symptom or functional impairment were accepted in good prognosis group. Progression, chronic cases that couldn't be followed without treatment and recurrence requiring treatment were included in poor prognosis group. 58% of patients was accepted in good prognosis and 42% had poor prognosis group. During follow-up, spontaneous remission rate was 20.2%, pulmonary hypertension development rate was 10.6% and mortality rate was 4.25%. Low radiological stage, high spirometry and diffusion capacity values, being asymptomatic and having no previous treatment were associated with spontaneous remission and good prognosis. Increase in serum angiotensin converting enzyme and C-reactive protein and decrease in spirometry parameters and diffusion capacity values were associated with progression.

Diagnosis and therapy of membranous nephropathy-2023

Membranous nephropathy (MN) is an immune-complex glomerulonephritis and is one of the most common causes of nephrotic syndrome in adults and is also one of the autoimmune kidney diseases with the highest rate of spontaneous remission. The most common autoantigen (> 70% of cases) is directed against the phospholipase A2 receptor (PLA2-R) and, with its detection and clinical course, allows for excellent diagnostics as well as optimal therapy monitoring. Other autoantigens are constantly being published and will enable an autoantigen-based diagnostic and therapeutic algorithm for MN in the future. In the absence of spontaneous remission, aspecific B‑cell-directed therapy, especially with rituximab, is the initial therapy of choice. Calcineurininhibitors or cyclophosphamide should only be used if they are carefully indicated in the respective clinical context and if there are serious clinical consequences both from the nephrotic syndrome and from loss of kidney function. Since immune complexes within the kidney often require along time to be degraded, proteinuria response can follow the immunological remission after many months. The therapy of MN represents the favorable case of aprecision medicine-based therapy in nephrology, whereby new therapeutic B‑cell antibodies for the rare but difficult forms of MN will find their way into clinical routine in the not-too-distant future.

Hyperreactio Luteinalis and an Incidentally Detected FIGO IIIB Borderline Tumor of the Ovary in Pregnancy - Diagnostic, Therapy and Review of Literature

Adnexal masses affect 2-10% of all pregnancies. The highest incidence of 1-6% can be seen in the first trimester, with a high rate of spontaneous remission. Two percent of these masses are malignant neoplasms or borderline tumors. A rare benign mass of the adnexa in pregnancy is hyperreactio luteinalis characterised by bilateral, multicystic ovaries with a frequent occurrence in the 3rd trimester. Clinical signs include maternal hyperandrogenaemia with virilisation, hyperemesis, nonspecific abdominal pain or laboratory findings of hyperthyroidism and elevated ß-HCG. Hyperreactio luteinalis does not require therapy due to complete spontaneous remission postpartum, but is often treated surgically in graviditate. In our case we report a first-time gravida in the 31st week of pregnancy with a symptomatic 25-cm multicystic, partly solid mass. After antenatal corticosteroid therapy, an exploratory laparotomy with right adnexectomy was performed on suspicion of malignancy. Histology revealed a hyperreactio luteinalis with an incidental finding of a serous borderline tumor of the ovary (FIGO IIIB). At 33 weeks of gestation, a pathological CTG was observed, and an urgent secondary caesarean section by re-longitudinal laparotomy was performed. Postpartum completion surgery revealed no further neoplastic cells.

Prevalence, natural history and dynamic nature of chronic headache and medication overuse headache in Italy: The SPARTACUS study.

Chronic headaches and medication overuse headache are common and burdening conditions. No studies have evaluated the prevalence of chronic headache and medication overuse headache in an unselected Italian population. We performed a three-year cross-sectional and longitudinal population-based study to investigate prevalence, natural history, and prognostic factors of chronic headache. We delivered a self-administered questionnaire to 25,163 subjects. Chronic headache patients were interviewed by General Practitioners. After three years, medication overuse headache patients were invited to undergo a neurological evaluation at our Center. 16,577 individuals completed the questionnaire; 6878 (41,5%) were episodic headache sufferers and 636 (3.8%) were chronic headache subjects. 239 (1.4%) patients were acute medication over-users. All medication overuse headache patients had migraine or headache with migrainous features. At the three-year follow-up of 98 patients, we observed conversion to episodic headaches in 53 (54.1%) patients. 27 (50.9%) patients remitted spontaneously. We present the first prevalence data on chronic headache and medication overuse headache in an unselected Italian population and a high rate of spontaneous remission. These data support the interpretation of medication overuse headache as a specific migraine-related disorder that may reflect chronic migraine's dynamic nature, the need for more specific medication overuse headache diagnostic criteria, and highlight the priority of targeted public health policies.

Clinical Manifestations and Management of Pediatric Granuloma Annulare: A Systematic Review

To determine the clinical manifestations, management, and outcomes of pediatric granuloma annulare. We searched MEDLINE via PubMed, Latin American and Caribbean Health Sciences (LILACS), and EMBASE from inception to January 2021. We included all original reports of patients < 18 years of age with a diagnosis of GA and all original reports describing any intervention, including topical or systemic agents, in these patients. Two authors independently extracted socio-demographics and clinical data of the study patients, and treatment(s) used. Of 2,440 reports screened, 202 were included (836 patients). The mean age was 5.7 (SD 3.8) years and F:M ratio 1.3:1. Localized GA (n=384, 46.8%) and subcutaneous GA (n=353, 43.0%) were the most prevalent subtypes. The most affected site was lower limbs (n=272/568, 47.9%). Suspected triggering factors were mainly local trauma. Diabetes was associated in 22 (2.6%) patients. The rate of spontaneous remission was high (n=140/155, 90.3%), with a median time of 12 months. The most frequent therapies were surgery and topical corticosteroids. Recurrence was observed in 38.3% (n=168/439) of patients, regardless of treatment. Pediatric GA frequently resolves spontaneously yet displays a high recurrence rate. Hence, in asymptomatic forms, invasive therapies are not recommended as first-line treatment.

Phospholipase A2 Receptor Antibodies and Clinical Prognosis in Patients with Idiopathic Membranous Nephropathy: An Updated Systematic Review and Meta-Analysis

Background: Idiopathic membranous nephropathy (IMN) is the most common form of primary nephrotic syndrome in adults. Antibodies against the M-type phospholipase A2 receptor (PLA2R-ab) are considered as diagnostic biomarkers of IMN. Objective: Here, we performed an updated meta-analysis to assess the diagnostic value of PLA2R-ab for clinical remission in IMN patients. Method: PubMed, Embase, and Cochrane databases were searched for relevant studies published before September 2022. Odds ratios and corresponding 95% confidence intervals were determined using a fixed or random effects model. The heterogeneity among studies was explored by subgroup analysis. Results: Sixteen studies involving 1,761 IMN participants were included. There were significant differences between PLA2R-ab (+) and PLA2R-ab (−) patients in terms of complete remission (CR) and spontaneous remission. The rates of partial remission (PR) and relapse were similar between the two groups. Patients with PLA2R-ab (−) were at a higher CR rate when treated with a calcineurin inhibitor or a treatment course for 3 months and 6 months, while the spontaneous remission rate was higher in PLA2R-ab seronegative patients from Asia. However, the CR and spontaneous remission rate only significantly declined in IMN patients with the highest titer, but not a middle titer, when compared to those with the lowest titer. Conclusion: In contrast with previous meta-analyses, our results verified that PLA2R-ab can likely predict CR and spontaneous remission in IMN patients, instead of PR and relapse. Race, immunosuppressive agents, and duration of treatment may affect the prognostic value of PLA2R-ab. Considering that the remission rate of IMN patients with a middle level of PLA2R-ab was not different from that of patients with the lowest level, a proper cut-off value of PLA2R-ab for prognosis should be clarified.

Clinical and laboratory evaluation of children with congenital hyperinsulinism: a single center experience.

To evaluate and present the data regarding clinical, laboratory, radiological and the results of molecular genetic analysis of patients with hyperinsulinemic hypoglycemia in our clinics. A total of 9 patients with CHI followed at Istanbul Medipol University. Data related to gender, age at presentation, birth weight, gestational age, consanguinity, glucose and insulin levels at diagnosis, treatment modalities, response to treatment, the results of genetic analysis and radiological evaluation were gathered from the files. The oldest age at presentation was 6months. KATP channel mutation was detected in 55% (n: 5). Diazoxide unresponsiveness was seen in 55% (n: 5). Octreotide was effective in 3 of them. 18F-DOPA PET performed in 4 diazoxide unresponsive patients revealed focal lesion in 3 of them. Spontaneous remission rate was 66% (n:6). All the patients with normal genetic result achieved spontaneous remission. Spontaneous remission was even noted in diazoxide unresponsive patients and in patients with focal lesion on 18F-DOPA PET. Clinical presentation of patients with congenital hypereinsulinism is heterogeneous. Spontaneous remission rate is quite high even in patients with severe clinical presentation. It is important to develop methods that can predict which patients will have spontaneous remission. Reporting the clinical and laboratory data of each patient is important and will help to guide the management of patients with hyperinsulinemic hypoglycemia.

Long Term Follow-up of International Randomised Phase 3 Study of Rituximab Versus a Watch and Wait Approach for Patients with Asymptomatic, Low Tumour Burden Follicular Lymphoma Shows Rituximab Is Highly Effective at Delaying Time to New Treatment without Detrimental Impact Following Next Line of Therapy

Introduction: In the international randomised phase 3 'Watch & Wait' (W&W) trial patients with asymptomatic low tumour burden follicular lymphoma (LTBFL) were randomised between (1) W&W, (2) rituximab induction (RI) or (3) RI followed by rituximab maintenance (RM). The primary endpoints were time to initiation of new treatment (TTNT) and quality of life (QoL) at 7 months. After a median follow up of ~4 years 88% of RM had not initiated new treatment at 3 yrs versus 46% with W&W. There was no significant difference in TTNT between the 2 rituximab (R) arms at 3yrs. There was no difference in overall survival (OS) between the arms. Selected QoL measures were shown to be superior for patients in the RM arm compared to W&W. Follow up of the study was extended to assess if the improvement in TTNT was sustained, and to collect the time to initiation of 2nd new treatment (TT2NT) to explore if the early use of R impacted patients when R-chemotherapy was subsequently given. Here we report the final analysis of the W&W study with median follow-up of 12.3 years (IQR 11.4-13.3). Methods: From Oct 2004 patients age ≥18 with stage II-IV, asymptomatic, LTBFL (grades 1-3a) were randomly assigned 1:1:1 to RI (R 375 mg/m2 weekly for 4 weeks), RM (RI followed by R every 2 months for 12 doses) or W&W. Recruitment to the RI arm was closed early in Sept 2007 and a 2-arm study then continued to recruit until March 2009. The primary endpoint was TTNT (including chemotherapy or radiotherapy). Secondary endpoints included response at 25 months, PFS, OS, cause-specific survival (CSS, including deaths due to lymphoma or treatment) and rates of spontaneous remission and high-grade transformation (HT). TT2NT was measured to compare the efficacy of the composite of (observation +1st systemic therapy) with (rituximab +1st systemic therapy) Results: Of 463 patients recruited from 118 centres in the UK, Australia, New Zealand, Turkey, and Poland, 84 were randomised to the RI arm, 192 to the RM arm and 187 to the W&W arm. New treatment was initiated in 242 patients (W&W 133, RI 42, RM 67). Median TTNT was 2.7 years (95% confidence interval (CI) 2.2-4.0) for the W&W arm, 9.9 years (5.7-not reached) for the RI arm and was not reached for the RM arm. At 10 years 28.8% (22.1%-35.8%) of patients in the W&W arm had not started a new treatment compared to 49.4% (37.4%-60.3%) in the RI arm (p<0.0001) and 64.5% (56.7%-71.2%) in the RM arm (p<0.0001). TTNT was also significantly longer for patients in the RM arm compared to the RI arm (HR = 0.61 (0.41-0.90), p=0.012). Second new treatment was initiated in 75 patients (W&W 35, RI 13, RM 27). The median TT2NT was not reached in any of the 3 arms, with no significant differences observed between the groups. At 25 months the overall response rate (ORR) was 52.4% in the RI arm (complete response (CR) 31.0%, CRu 9.5%) and 76.0% in the RM arm (CR 63.0%, CRu 5.7%). The rate of disease progression by 25 months was 57.8% for the W&W arm, 36.9% for the RI arm and 15.1% for the RM arm. 35 patients in the W&W arm (18.7%) had a confirmed spontaneous remission at any point during follow-up with median time to spontaneous CR of 1.6 years (1.2-1.8) with 24/35 subsequently relapsing or requiring further treatment. The 4-year PFS rates for both treatment arms were superior when compared to W&W (W&W 32.1% (95% CI 25.5%-38.9%) RI - 56.5% (45.2%-66.4%, p=0.0001), RM - 78.4% (71.9%-83.6%, p<0.0001). PFS for the RM arm was also superior compared to the RI arm (HR = 0.41 (0.27-0.65), p<0.001). No significant differences in OS or CSS were observed with 10yr OS rates of 76.4%, 80.3% and 82.5%, and 10 yr CSS rates of 87.1%, 87.9% and 89.7% in W&W, RI and RM respectively. HT occurred in 34 patients (18.2%) in the W&W arm, 9 (10.7%) in the RI arm and 26 (13.5%) in the RM arm, with no significant differences in the time to HT between the 3 groups. Rates of second primary malignancy between the 3 groups were also comparable at 18.7%, 17.9% and 15.6% for the W&W, RI and RM arms respectively. Conclusion: After a long median follow-up of 12.3 years we have shown that rituximab monotherapy is highly effective at deferring TTNT in patients with asymptomatic LTBFL, with RM being superior to RI. Initial treatment with rituximab did not result in inferior outcomes following 1st new treatment compared with an initial period of observation. Upfront rituximab should therefore be considered an effective treatment option for patients who wish to delay chemoimmunotherapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Hypoglycemia Caused by Exogenous Insulin Antibody Syndrome: A Large Single-Center Case Series From China.

Exogenous insulin antibody syndrome (EIAS) can lead to unexpected and potentially life-threatening recurrent hypoglycemia. We aimed to better define autoimmune hypoglycemia caused by EIAS in patients with diabetes and shed light on the improvements in the identification and intervention for this rare but possibly life-threatening condition. We summarized the clinical characteristics of autoimmune hypoglycemia caused by EIAS in 23 patients with diabetes. Furthermore, we performed human leukocyte antigen (HLA) genotyping of 10 patients. We identified a high frequency of autoimmune comorbidities (21.7%), food or drug allergy (48%), insulin allergy (30%), lipodystrophy at the insulin injection sites (22%), and antinuclear antibodies (25%) in the patients. Alternation between hyperglycemia and hypoglycemia was observed in more than 90% of the patients. Most patients showed a high insulin autoantibody titer (>90%) and inappropriately increased insulin concentration (insulin/C-peptide molar ratio >7, >85%). We detected similar frequencies of DRB1*0405-DQB1*0401 and DRB1*0901-DQB1*0303 compared with previously reported frequencies in type 1 diabetes, and a lower frequency of DRB1*0406 compared with insulin autoimmune syndrome. The spontaneous remission rate exceeded 70%. Predisposing factors for autoimmune hypoglycemia caused by EIAS include a strong autoimmune background. Susceptible HLA genotypes for type 1 diabetes or insulin autoimmune syndrome might not explain susceptibility to this condition. Additionally, insulin autoantibodies and the insulin/C-peptide molar ratio are reliable screening options. The prognosis for this condition is favorable. Monitoring of insulin and insulin autoantibodies may contribute to treatment effectiveness.

C1q or IgA deposition in glomeruli of children with primary membranous nephropathy

Objective: To assess the correlation of glomerular C1q or IgA deposition with clinical and pathological features of primary membranous nephropathy (PMN) in children. Methods: The clinical and pathological manifestations including (phospholipase A2 receptor, PLA2R) and IgG subclasses staining in renal biopsies, serum anti-PLA2R antibody and therapeutic response of 33 children diagnosed with PMN in Peking University First Hospital from December 2012 to December 2020 were retrospectively summarized and analyzed. According to results of PLA2R test and findings renal pathological, the patients were divided into PLA2R-related group and non-PLA2R-related group, typical MN group and atypical MN group, C1q deposit group and non-C1q deposit group, as well as IgA deposit group and non-IgA deposit group respectively. T-test, Mann-Whitney U test and Fisher's exact probability test were used for comparison between the groups. Results: Among the 33 children with PMN, there were 20 males and 13 females, of that the age of onset was 11 (8, 13) years, and 32 patients had nephrotic level proteinuria. Renal biopsies were performed at 4.6 (2.1, 11.6) months after onset, and 28 patients (85%) received glucocorticoid or immunosuppressive therapy prior to renal biopsy. There were 20 cases (61%) with PLA2R-related MN and 13 cases (39%) with non-PLA2R-related MN. Compared with the non-PLA2R-related group, the PLA2R-related group had an older age of onset (12 (10, 13) vs. 7 (3, 12) years, Z=-2.52, P=0.011), a lower preceding infection rate (45% (9/20) vs. 11/13, P=0.032) and lower spontaneous remission rate (0 vs. 4/13, P=0.017). Renal PLA2R positivity was significantly associated with predominant or co-deposition of IgG4 (13/17 vs. 5/15, P=0.031) and low albumin levels at renal biopsy ((25±6) vs. (29±7) g/L, t=2.14, P=0.041). There were 12 patients with typical PMN and 21 patients with atypical PMN, and no significant difference in clinical and pathological manifestations was found between these 2 groups (all P>0.05). There were 10 cases (32.3%) with glomerular C1q deposition, and their disease course before renal biopsy was significantly shorter than those without C1q deposition (1.8 (0.8, 5.9) vs. 6.0 (2.5, 22.3) months, Z=-2.27, P=0.023). Twelve cases (36.4%) had glomerular IgA deposition, and their course of disease,clinical and pathological manifestations were not significantly different from those without IgA deposition (all P>0.05). Conclusion: Glomerular C1q or IgA deposition may not affect the clinical manifestations, glomerular PLA2R and IgG subclasses staining pattern, or the response to treatment of PMN in children.

Novel Lung Growth Strategy with Biological Therapy Targeting Airway Remodeling in Childhood Bronchial Asthma.

Anti-inflammatory therapy, centered on inhaled steroids, suppresses airway inflammation in asthma, reduces asthma mortality and hospitalization rates, and achieves clinical remission in many pediatric patients. However, the spontaneous remission rate of childhood asthma in adulthood is not high, and airway inflammation and airway remodeling persist after remission of asthma symptoms. Childhood asthma impairs normal lung maturation, interferes with peak lung function in adolescence, reduces lung function in adulthood, and increases the risk of developing chronic obstructive pulmonary disease (COPD). Early suppression of airway inflammation in childhood and prevention of asthma exacerbations may improve lung maturation, leading to good lung function and prevention of adult COPD. Biological drugs that target T-helper 2 (Th2) cytokines are used in patients with severe pediatric asthma to reduce exacerbations and airway inflammation and improve respiratory function. They may also suppress airway remodeling in childhood and prevent respiratory deterioration in adulthood, reducing the risk of COPD and improving long-term prognosis. No studies have demonstrated a suppressive effect on airway remodeling in childhood severe asthma, and further clinical trials using airway imaging analysis are needed to ascertain the inhibitory effect of biological drugs on airway remodeling in severe childhood asthma. In this review, we describe the natural prognosis of lung function in childhood asthma and the risk of developing adult COPD, the pathophysiology of allergic airway inflammation and airway remodeling via Th2 cytokines, and the inhibitory effect of biological drugs on airway remodeling in childhood asthma.

Nocturnal Enuresis

Nocturnal enuresis, or involuntary urination, is a common problem among children. It affects approximately 15% of all children at 5 years old. At our workplace as a primary health care facility, nocturnal enuresis, and incontinence in general, is one of the most common chief complaints presenting to the clinic. Enuresis can be disruptive to normal family life and can generate stress between parents and child. There may be anxiety about events like sleepovers and campouts and there are significant costs in lost time, laundary and bedding, as well as the potential for guilt and loss of self-esteem. Nocturnal enuresis decreases with age, with a spontaneous remission rate of about 15% per year. It can improve with treatment, and improved self-esteem and quality of life have been reported after successful treatment. It is therefore important to offer timely treatment, and to refer children for specialist care when treatments are not effective. In this review we discuss definition, epidemiology, etiology, evaluation and different modalities of treatment for nocturnal enuresis . Key words: Nocturnal enuresis, alarm, desmopressin .

The Spontaneous Remission of Recurrent Lymph Node Metastatic Prostate Cancer With Lowering Serum Prostate-Specific Antigen Level

The incidence rate of spontaneous remission of malignant cancer is very low. Reports on spontaneous remission in advanced prostate cancer are extremely limited. Our patient was treated with androgen deprivation therapy, local radiotherapy, and surgical castration at the initial diagnosis. Approximately nine years after treatment, he experienced a rise in serum prostate-specific antigen level and relapse of obturator lymph node adenopathy. Initially, androgen deprivation therapy was reinitiated, which resulted in castration-resistant prostate cancer. Although androgen deprivation therapy was discontinued, spontaneous remission of recurrent lymph node and spontaneous reduction in serum prostate-specific antigen level was seen. There was no sign of radiological recurrence for over eight years without prostate cancer treatment.

Comparison of infants and children with urolithiasis: a large case series.

We evaluated the demographic features, etiologic risk factors, treatment strategies, and outcome of the infants and children with urolithiasis (UL). A retrospective multicenter study was conducted including 23 Pediatric Nephrology centers in Turkey. The medical records of 2513 children with UL were reviewed. One thousand, three hundred and four boys and 1209 girls (1.1:1) were reported. The mean age at diagnosis was 39.5 ± 35months (0.4-231months), and 1262 patients (50.2%) were in the first year of life (infants). Most of the cases with infantile UL were diagnosed incidentally. Microlithiasis (< 3mm) was found in 794 patients (31.6%), and 64.5% of the patients with microlithiasis were infants. Stones were located in the pelvis-calyces in 63.2% (n: 1530) of the cases. The most common stone type was calcium oxalate (64.6%). Hypocitraturia was the most common metabolic risk factor (MRF) in children older than 12months, but in infancy, hypercalciuria was more common. Fifty-five percent of the patients had received at least one medical treatment, mostly potassium citrate. At the end of a year's follow-up, most of the patients with microlithiasis (85%) showed spontaneous remission. The rate of spontaneous stone resolution in infants was higher than in children. Spontaneous remission rate was higher in cases with MRF (-) stones than in MRF ( +) stones. However, remission rate with medical treatment was higher in cases with MRF ( +) stones. This study represents the results of a large series of infants and children with UL and showed that there are several differences such as underlying metabolic and anatomic abnormalities, clinical course, and stone remission rates between infants and children with urinary stone disease.

Rituximab Is Preferable to Cyclophosphamide for Treatment of Membranous Nephropathy: CON.

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0001842021 and the COMMENTARY: 10.34067/KID.0002492021