Spontaneous Remission Research Articles

Elucidation of the role of XBP1 in the progression of complete hydatidiform mole to invasive mole through RNA-seq

ObjectiveA complete hydatidiform mole (CHM) is a common disease and is known to develop post-molar gestational trophoblast neoplasia (GTN). However, the molecular mechanisms underlying the progression of CHM to post-molar GTN remain largely unknown. In this study, we investigated the molecular factors associated with the progression using RNA-seq. MethodsWe included 13 patients with CHM and performed RNA-seq using freshly frozen samples. We identified differentially expressed genes between patients who developed GTN (GTN group) and those who achieved spontaneous remission after uterine evacuation (SR group), and performed pathway analysis. Then, functional analyses were performed on choriocarcinoma (JAR and JEG-3) and CHM (Hmol1-3B and Hmol1-2C) cells. Moreover, we evaluated the in vivo tumorigenicity of XBP1-overexpressed Hmol1-3B cells. ResultsThe gene expression profiles were separated into two groups, and an upstream regulator analysis was performed using 281 differentially expressed genes. We focused on transcription factors and identified that 33 transcription factors were activated in the GTN group. Then, excluding those with low expression levels in clinical samples and cell lines, XBP1 was selected for further analysis. Additionally, XBP1 downregulation significantly decreased the migration and invasive abilities of choriocarcinoma cells, whereas XBP1 overexpression significantly increased the migration and invasive abilities of CHM cells. Furthermore, animal experiments showed that tumor weight and blood human chorionic gonadotropin (hCG) levels were significantly higher in the XBP1-overexpressing Hmol1-3B-bearing mice than those in the control mice. ConclusionRNA-seq identified XBP1 as a key factor in post-molar GTN, suggesting it contributes to the development of post-molar GTN.

Predictors for spontaneous remission in childhood chronic immune thrombocytopenia.

This study examined the factors associated with spontaneous remission in children with chronic immune thrombocytopenia (ITP). We retrospectively analyzed the medical records of patients diagnosed with ITP from January 1988 to December 2019 at our institute. A total of 104 children with chronic ITP were identified. The median follow-up time from diagnosis of chronic ITP was 3.6 years (IQR 1.2-8.3, range 0.1-31.4). Fifteen (14.4%) patients with severe symptoms received specific platelet-elevating therapies, including splenectomy, rituximab, and thrombopoietin receptor agonists. Seven of them achieved remission. Among the patients with a platelet count < 30 × 109/L at the time of diagnosis of chronic ITP, those who received specific platelet-elevating therapies had a higher remission rate compared to those who did not (HR: 4.66, 95% CI: 1.36-16.0). Sixteen patients (15.4%) developed systemic lupus erythematosus, 46 (44.2%) still had thrombocytopenia after a median follow-up of 6.8 years, and 42 (40.4%) achieved remission with a median time to remission of 2.0 years (IQR 0.6-4.1, range 0.1-15.7). The two independent predictive factors for spontaneous remission in childhood chronic ITP were platelet counts > 30 × 109/L at the time of diagnosis of chronic ITP (HR: 3.16, 95% CI: 1.51-6.62) and persistently negative ANA at follow-up (HR: 6.12, 95% CI: 1.46-25.7). The cumulative probabilities of spontaneous remission at 10 years post-diagnosis of chronic ITP were 72.2% for patients without risk factor compared to 0% for patients with two risk factors.

9363 Spontaneous Cushing Disease Remission Induced By Pituitary Apoplexy

Abstract Disclosure: J.E. Esquivel Vargas: None. F. Ruiz Salazar: None. A.B. Santos Rojo: None. Background: Spontaneous remission of Cushing disease is rare, and it is mainly due to apoplexy of a pituitary tumor. Clinical case: 14-year-old female presented with clinical features of Cushing syndrome. Initial tests were consistent with Cushing disease (CD): elevated 24h urinary cortisol (235µg/24h, n&amp;lt;90µg/24h), abnormal 1 mg dexamethasone overnight test (cortisol after 1 mg dex 3.4µg/dL, n&amp;lt;1.8µg/dL), and elevated ACTH-concentrations (83.5 pg/mL, n 10-60pg/mL). Pituitary adenoma was suspected, and the patient was referred for a transsphenoidal resection of the adenoma. While waiting for surgery the patient presented to the Emergency department with a headache and clinical signs of meningism. Computed axial tomography of the central nervous system was performed, and no structural alterations were found. The symptoms subsided with analgesia. One month later she presented again to the Emergency department with clinical findings of acute adrenal insufficiency (cortisol level of 4.06 µg/dL), and she was noted to have spontaneous biochemical remission associated with resolution of her symptoms of hypercortisolism. Nuclear magnetic resonance imaging was performed describing a 2.6 x 1.8mm hypointense pituitary lesion, suggestive of cerebrospinal fluid, which could be a remnant of a pituitary microadenoma. For that reason, spontaneous CD remission induced by pituitary apoplexy (PA) was diagnosed. The patient has been managed conservatively since the diagnosis and remains in clinical and biochemical remission until the present time after 10 months of follow up. Conclusion: There are 3 unique aspects of our case: the early age of onset of symptoms, the spontaneous remission of CD due to PA which has been rarely reported in the medical literature, and the patient presented a microadenoma because there are less than 10 clinical case reports of PA associated with microadenoma. Presentation: 6/1/2024

7102 Pituitary Apoplexy with Eventual Complete Tumour Involution

Abstract Disclosure: A. Ng: None. R. Lai: None. Pituitary apoplexy is an endocrinological emergency resulting from infarction or haemorrhage of the pituitary gland. We present a case of pituitary apoplexy from a non-functioning pituitary macroadenoma, complicated by pituitary insufficiency and subsequent tumour involution. An 80-year-old gentleman presented to the Emergency Department with sudden severe headaches and persistent vomiting and admitted for further evaluation. Computed tomography (CT) imaging of the brain showed a prominent pituitary gland and magnetic resonance imaging (MRI) confirmed a large sellar hyperintense lesion containing blood and proteinaceous material. It measured 1.6 cm by 1.2 cm by 1 cm and indented the optic chiasm. CT angiography did not reveal any aneurysms or intracranial haemorrhage. There were no neurological or visual field deficits at presentation. There was no indication for surgery upon neurosurgical consultation. Initial evaluation of the pituitary axis was consistent with central hypocortisolism (cortisol 75 nmol/L, adrenocorticotropic hormone 1.4 pmol/L [reference range (RR) 1.6-13.9]) and hypoprolactinaemia (prolactin 56 mIU/L, RR 73-351). Luteinising hormone levels were &amp;lt; 1 IU/L (RR 1-9); follicle stimulating hormone levels were 3 IU/L (RR 1-19) and testosterone levels were &amp;lt; 1 nmol/L (RR 5 to 30) as the patient was on androgen deprivation therapy for prostate cancer. Hydrocortisone was started and he was monitored for development of frank diabetes insipidus. He did not require regular desmopressin. He later developed anti-diuretic hormone mediated hyponatraemia (serum sodium nadir of 125 mmol/L, serum osmolality 275 mmol/kg, urine osmolality 390 mmol/kg) that was managed with fluid restriction and solute loading. He also developed central hypothyroidism on day 19 of admission (free thyroxine 11 pmol/L, thyroid stimulating hormone 0.49 mIU/L, RR 0.45-4.5) and oral levothyroxine was started. He was discharged with oral hydrocortisone and levothyroxine replacement. A repeat MRI of the pituitary 2 months later showed complete resolution of the mass and resolution of the mass effects. He was kept on oral hydrocortisone and levothyroxine replacement with regular follow-up.Most pituitary macroadenomas are non-functional, and can present with complications of apoplexy, mass effects or hormonal disturbances. However, the natural history of non-functional macroadenomas is not well known as most are operated on. Spontaneous regression of the tumour can rarely occur, notably in the setting of apoplexy and lymphocytic hypophysitis. Recovery of the pituitary axis may also accompany tumour regression. As spontaneous remission of pituitary macroadenomas may occur, close observation of tumours without visual field defects or significant mass effects may be an alternative to surgery. Presentation: 6/1/2024 12:15:00 PM

A-242 Assessing the efficacy of the one-step diagnostic algorithm for Hepatitis C

Abstract Background Hepatitis C virus (HCV) infection can be asymptomatic and may go into spontaneous remission. However, in 60-80% of cases, it becomes chronic and progresses into cirrhosis or hepatocarcinoma. The virus is mainly transmitted parenterally, although cases of sexual and transplacental transmission have also been found. Since the development of direct-acting antiviral (DAA) therapy that can achieve a complete cure in 95% of patients, eradication strategies based on rapid diagnosis and treatment have been promoted. Therefore, the World Health Organization (WHO) has set a goal to eliminate HCV infection as public health threat by 2030. This is a retrospective study on the usefulness and effectiveness of the one-step HCV diagnostic algorithm application from May 2022 to December 2023 in our hospital. Methods The current HCV testing algorithm consists in a reflex HCV RNA testing, in which anti-HCV antibody-positive samples are automatically referred for HCV RNA testing on the same specimen. We used a serological electrochemiluminescence (ECLIA) assay for the detection of anti-HCV antibodies (Cobas e801, Roche Diagnostics®) in serum samples; and then a confirmation of HCV viremia by nucleic acid testing of HCV RNA in plasma samples (Cobas 4800, Roche Diagnostics®). Results A total of 22713 HCV serologies were performed with a total of 221 positive results (1%). Of the HCV cases, 21 patients had a newly diagnosis of active infection (10%) for whom we recommended derivation to the Digestive Service to initiate elimination treatment. 71% were men, with a mean age of 53 years and a standard deviation of 17. The mean age of women was 56 years with a standard deviation of 18. Coinfection with HIV or hepatitis B virus (HBV) was also assessed. Patients with HIV-HCV coinfection represented 9% of cases and were on average 12 years younger than HCV-monoinfected individuals. We did not identify any case of HBV-HCV co-infection. Conclusions The pattern we observed in terms of incidence by age and sex is similar to that reported in the literature, as well as the incidence of new HCV cases. One-step diagnosis enables the laboratory to identify the need for referring to a specialist, reducing the time to treatment for new and known but untreated cases. Therefore, global access to HCV diagnostics will be a keystone to success.

A Case of Spontaneous Remission of Idiopathic Minimal Change Disease in an Adult

A Case of Spontaneous Remission of Idiopathic Minimal Change Disease in an Adult

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.

Spontaneous Remission of Minimal Change Disease during Pregnancy

Spontaneous Remission of Minimal Change Disease during Pregnancy

Spontaneous remission of giant cell arteritis.

Spontaneous remission of giant cell arteritis.

Pathology of the Proximal Radius in Juvenile Pugs.

The aim of this study was to describe the physeal pathology of the proximal radius in four skeletally immature male Pugs. Physical examination, radiography, and computed tomography (CT) of the thoracic limbs were performed in all four dogs. Two Pugs were available for long-term follow-up and two Pugs were euthanatized after the diagnostic imaging results. Four male Pugs, aged between 6 and 7 months, were presented with a history of thoracic limb lameness lasting 2 to 3 months. Radiography and CT of the thoracic limbs showed irregularity of the proximal radial physes with varying degrees of radiolucency within the adjacent metaphyses. The pathology was associated with elbow joint incongruity and angular deformity of the antebrachium. Two dogs were euthanatized, one of which was autopsied, and histopathology of the proximal radius revealed bilateral physeal dysplasia. At long-term follow-up of the two surviving dogs, lameness had resolved. Radiography and CT scans of the thoracic limbs revealed normal bone opacity within the proximal radius and resolution of the radiolucent areas of the proximal radial physes. However, incongruity of the radioulnar joint remained. In this report, the resolution of identified physeal pathology at the proximal radius in juvenile Pugs demonstrates the potential for spontaneous remission despite the presence of notable radiographic changes.

Spontaneous remission of acute myeloid leukemia with NPM1 mutation during pregnancy:a case report

Spontaneous remission of acute myeloid leukemia with NPM1 mutation during pregnancy:a case report

Thrombopoietin Receptor Agonists as Second-Line Treatment in Children With Ongoing Immune Thrombocytopenia

What Is the Issue? Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelets and an increase in bleeding risk; in the pediatric population, the reported incidence rate varies between 2 and 5 per 100,000 children per year. Spontaneous remission may be observed in up to 70% of patients, while 20% of patients may experience severe bleeding symptoms. In children whose ITP does not respond to first-line corticosteroids, IV immunoglobulin (IVIG), or anti-D immunoglobulin, guidelines recommend the use of thrombopoietin receptor agonists (TPO-RAs), i.e., eltrombopag or romiplostim (avatrombopag did not have a marketing authorization and Notice of Compliance at the time that the review was initiated). Rituximab is considered a subsequent-line of therapy. Splenectomy is not usually considered an appropriate treatment option in children. The goal of therapy in pediatric patients with ITP is to reduce bleeding and improve quality of life. Platelet response is considered a valid and appropriate surrogate end point in studies and routine assessment in clinical practice. Children whose ITP does not respond to available first-line drugs may require subsequent treatment with off-label drugs because they do not have access to TPO-RAs. What Did We Do? We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence. A systematic review of the literature identified 5 studies (4 randomized controlled trials [RCTs] and 1 observational study), which were synthesized narratively. The review addressed the following policy questions: In children with ongoing, active ITP, what is the overall body of evidence supporting the use of TPO-RAs and rituximab after failure of first-line therapies? Based on the level and quality of clinical evidence, should TPO-RAs be reimbursed for use earlier in the treatment sequencing for children with ongoing, active ITP, instead of being reimbursed only after a course of rituximab? What Did We Find? Evidence from 2 RCTs (n = 159) suggests that eltrombopag likely increases and maintains platelet response over time, in addition to decreasing the use of rescue medication and clinically significant bleeding compared to placebo, which were considered clinically meaningful outcomes for pediatric patients with ITP. There was a low risk of bias in the studies, but uncertainty was introduced due to the small sample sizes. Evidence from 1 RCT (n = 62) suggests that romiplostim may also increase and maintain platelet response, as well as reduce clinically significant bleeding compared to placebo. However, there was some concern due to a high risk of bias in the studies and uncertainty due to the small sample size, which suggests a need for caution in the interpretation of the findings. The effectiveness of rituximab was inconclusive due to the lack of evidence, as no comparative RCTs could be identified, while the observational study included presented only descriptive comparisons. No evidence was identified in support of trying rituximab before accessing TPO-RAs. What Does This Mean? Given that ITP is rare in children, there is a gap in available relevant evidence, and robust evidence from large RCTs in this patient population are unlikely to be conducted. Jurisdictions may consider requesting an implementation advice panel for use of eltrombopag and romiplostim after failure of first-line therapies in children with ongoing, active ITP.

Clinical characteristics and outcomes of Brazilian patients with duodenal-type follicular lymphoma: a multicenter retrospective study

Duodenal-type follicular lymphoma (DFL) is a rare subtype classified by the 5th edition of the WHO and international consensus classifications of lymphoid neoplasms, typically presenting as localized disease with favorable outcomes. This multicenter retrospective study examines 53 Brazilian DFL patients with a median age of 58.2 years (33–85), with males comprising 50% (n = 27). According to Lugano GI tract classification, 40 patients (75%) were stage I. Median follow-up was 2.9 years (range 0.1–11). Incidental diagnosis occurred in 28 patients (52.8%) during routine endoscopy; 24 patients (45%) presented mild gastrointestinal symptoms. Treatments included watchful waiting (32 patients, 60.4%), rituximab monotherapy (15 patients, 28.3%), radiotherapy (three patients, 5.7%), and chemoimmunotherapy (three patients, 5.7%). Three patients experienced disease progression; watchful waiting showed three spontaneous remissions. No deaths occurred during follow-up. This study, the first from Latin America, demonstrates a good prognosis across treatments, highlighting Watchful waiting’s effectiveness.

Exploring cognitive impairments and the efficacy of phosphatidylcholine and computer-assisted cognitive training in post-acute COVID-19 and post-acute COVID-19 Vaccination Syndrome.

The COVID-19 pandemic has led to millions of confirmed cases worldwide, resulting in numerous deaths and hospitalizations. Long-term symptoms after infection or vaccination, known as Post-acute COVID-19 Syndrome (PACS) or Post-acute COVID-19 Vaccination Syndrome (PACVS), present a challenge for the healthcare system. Among the various neurological symptoms, cognitive impairments are frequently observed in PACS/PACVS patients. This study aimed to understand cognitive deficits in PACS/PACVS patients and evaluated potential treatment options, including phosphatidylcholine and computer-assisted cognitive training (CCT). The Neuro-COVID Outpatient Clinic at Evangelic Hospital Vienna evaluated n = 29 PACS/PACVS patients from May 2023 to October 2023. Enrolled patients were divided into three therapy schemes: Group A received phosphatidylcholine, B received phosphatidylcholine plus access to a computer-assisted cognitive training program, and C (divided into two subgroups) served as a control group. Cognitive impairments were evaluated in multiple assessments (initial and during therapy) using the COGBAT test. Simultaneously, an assessment of the quality of life was conducted using the WHOQOL-BREF. Primary cognitive impairments, especially attentional deficits were notably evident compared to the general population. While all treatment groups showed cognitive improvement (significant or with a positive trend, but without reaching the level of statistical significance) after therapy, no significant interaction was found between assessment time points and treatment schemes for overall cognitive performance, attention, memory, and executive functions, suggesting consistency across the groups. The WHOQOL-BREF primarily demonstrated deficits in the domains of physical health and psychological well-being. This study examined the impact of PACS/PACVS on cognitive performance and evaluated phosphatidylcholine and CCT as potential treatment options. Patients with PACS/PACVS showed notable cognitive deficits, especially in the domain attention. While the effectiveness of phosphatidylcholine and CCT in treating cognitive deficits was inconclusive, the study indicated the possibility of spontaneous remission of cognitive deficits in PACS/PACVS.

Plasma vitamin D levels are correlated with the pathogenesis of human T-cell leukemia virus type 1-associated diseases.

The active form of vitamin D (VD) exerts hormonal effects by regulating the expression of genes involved in T-cell activity, cell differentiation, and proliferation. Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of life-threatening diseases, adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy (HAM). Among ATL patients, hypercalcemia is one of the most serious complications due to bone resorption. In this study, wild-type mice administered UV-irradiated HTLV-1-infected cells showed up to 47% decrease of plasma VD level compared with untreated mice. To clarify the effect of HTLV-1 on plasma VD level, 315 samples registered in nationwide cohort study on ATL onset were measured. The VD level in HAM (14.98 ± 8.5 ng/mL) was significantly lower than those in asymptomatic carriers and ATL (p < 0.05). Upon comparing the VD levels in ATL stratified by disease subtypes, acute ATL showed a lower level (15.81 ± 12.0 ng/mL) than chronic and smoldering types (p < 0.05). In the longitudinal observation, VD levels were significantly higher in untreated spontaneous remission cases than in ATL progression cases, in which the VD levels decreased approximately 40% after onset. In cases of relapse after transplantation, the plasma VD level dropped to 38.7% of the pre-relapse level, while in cases of complete remission, the VD level increased with improvement of the performance status. Taken together, these results suggest that plasma VD level is a potential indicator for the onset and relapse of HTLV-1-associated diseases.

Experience with Pediatric Chronic Immune Thrombocytopenia over 30 Years in the Era before Eltrombopag.

There is limited information on the natural course of chronic ITP in children. We aimed to evaluate the clinical and demographic characteristics of children with chronic ITP in the era before the availability of eltrombopag. A total of 86 children with chronic ITP between 1978-2014 were included. Demographic findings, laboratory results, clinical signs, bleeding scores, response time and time of complete remission were recorded. The male/female ratio was 1.09, and median follow-up time was 3 years (range: 1.5-17 years). The median age at diagnosis of chronic ITP was 7 years (range: 2-17), and the median initial platelet count was 10 × 109/L (range: 1-66 × 109/L). Petechiae/ecchymoses were the most common clinical sign (86%) and followed by mucosal bleeding (39.5%). Severe bleeding was seen in 5% of the patients. None of them had intracranial hemorrhage. Twenty patients underwent splenectomy, and the rate of complete remission was 70%. Spontaneous complete remission was seen in 29% of the patients, and the median time to spontaneous complete remission was 3 years. Our study showed that almost one-third of patients with chronic ITP experienced spontaneous complete remission in an average of 3 years, and splenectomy provided satisfactory results in severe cases. This study demonstrates the natural history of chronic ITP in childhood before the era of eltrombopag.

Duodenal-type follicular lymphoma: comprehensive insights into disease characteristics and established treatment strategies.

This review aims to detail the characteristics and outcomes of duodenal-type follicular lymphoma (DTFL), a rare lymphoma variant. It focuses on integrating recent reports in treatment modalities and highlights emerging insights into the unique biological features of the disease. Recent studies confirm the indolent nature of DTFL, with extended follow-up periods showing favorable outcomes under watchful waiting strategies and a notable proportion of patients experiencing spontaneous remission. Additionally, advancements in understanding the disease's biology revealed that the tumor microenvironment is marked by specific genomic expressions indicative of chronic inflammation. The observations of spontaneous resolution and the generally favorable progression of DTFL call for a conservative approach in initiating treatment. Clinical management should judiciously consider the disease's typically benign course against the potential risks of intervention, promoting customized treatment protocols tailored for cases with clinical necessity. Additionally, the discovery of an inflammatory tumor microenvironment and molecular evidence suggesting an antigen-driven process highlight critical areas for future research.

Spontaneous remission of de novo membranous nephropathy in post-allogeneic hematopoietic stem cell transplantation patients: A report of two cases.

Membranous nephropathy (MN) is one of the most common de novo glomerular diseases developing in patients after allogeneic hematopoietic stem cell transplantation (HSCT). Most authors have used immunosuppression for its treatment to target the underlying immune-mediated processes, akin to graft-versus-host disease, but the optimal management is currently unclear. Limited reports in the literature described the use of a conservative approach with success, particularly in cases with lower risks of progression, such as non-nephrotic-range proteinuria or early reduction of proteinuria by 6 months. We report two cases of post-HSCT MN with moderate risk features, namely prolonged durations of nephrotic-range proteinuria, that spontaneously resolved with conservative treatment. Patient 1 was of advanced age and in an immunocompromised state, while patient 2 was in need of a greater graft-versus-disease effect from the donor's immune system, which necessitated a balance between the risk of immunosuppression and the risk of progressive kidney function loss. These cases demonstrated that conservative treatment can be a reasonable approach in selected patients with post-HSCT MN, including those with moderate risk.

Early Boost of Linguistic Skills? Individualized Non-Invasive Brain Stimulation in Early Postacute Aphasia.

Non-invasive brain stimulation, such as transcranial direct current stimulation (tDCS), has been shown to increase the outcome of speech and language therapy (SLT) in chronic aphasia. Only a few studies have investigated the effect of add-on tDCS on SLT in the early stage of aphasia; this may be due to methodological reasons, in particular the influence of spontaneous remission and the difficulty of establishing stimulation protocols in clinical routines. Thirty-seven participants with subacute aphasia (PwA) after stroke (23 men, 14 women; mean age 62 ± 12 years; mean duration 49 ± 28 days) were included in two consecutive periods of treatment lasting two weeks each. During the first period (P1) the participants received 10 sessions of SLT, during the second period (P2) the aphasia therapy was supplemented by anodal left hemispheric 2 mA tDCS over the left hemisphere. Severity-specific language tests (Aachen Aphasia Test (AAT), n = 27 and Bielefeld Aphasia Screening-Reha (BIAS-R), n = 10) were administered before P1, between P1 and P2, and after P2. Where information was available, the results were corrected for spontaneous remission (AAT sample), and the therapy outcomes of P1 and P2 were compared. Participants' overall language abilities improved significantly during P1 and P2. However, improvement-as measured by the AAT profile level or the BIAS-R mean percentage value-during P2 (with tDCS) was significantly higher than during P1 (p < 0.001; AAT sample and p = 0.005; BIAS-R sample). Thus, tDCS protocols can be implemented in early aphasia rehabilitation. Despite the limitations of the research design, which are also discussed from an implementation science perspective, this is preliminary evidence that an individually tailored anodal tDCS can have a significant add-on effect on the outcome of behavioral aphasia therapy in subacute aphasia.

Observation and Management of Juvenile Myelomonocytic Leukemia and Noonan Syndrome-Associated Myeloproliferative Disorder: A Real-World Experience.

Juvenile Myelomonocytic Leukemia (JMML) is a rare and clonal hematopoietic disorder of infancy and early childhood with myeloproliferative/myelodysplastic features resulting from germline or somatic mutations in the RAS pathway. Treatment is not uniform, with management varying from observation to stem cell transplant. The aim of our retrospective review is to describe the treatment and outcomes of a cohort of patients with JMML or Noonan Syndrome-associated Myeloproliferative Disorder (NS-MPD) to provide management guidance for this rare and heterogeneous disease. We report on 22 patients with JMML or NS-MPD managed at three institutions in the Texas Medical Center. Of patients with known genetic mutations and cytogenetics, 6 harbored germline mutations, 12 had somatic mutations, and 9 showed cytogenetic abnormalities. Overall, 14/22 patients are alive. Spontaneous clinical remission occurred in one patient with somatic NRAS mutation, as well as two with germline PTPN11 mutations with NS-MPD, and two others with germline PTPN11 mutations and NS-MPD remain under surveillance. Patients with NS-MPD were excluded from treatment analysis as none required chemotherapeutic intervention. All patients (5/5) treated with 5-azacitidine alone and one of the four treated with 6-mercaptopurine monotherapy had a reduction in mutant variant allele frequency. Transformation to acute myeloid leukemia was seen in two patients who both died. Among patients who received transplants, 7/13 are alive, and relapse post-transplant occurred in 3/13 with a median time to relapse of 3.55 months. This report provides insight into therapy responses and long-term outcomes across different genetic subsets of JMML and lends insight into the expected time to spontaneous resolution in patients with NS-MPD with germline PTPN11 mutations.