Short-term effectiveness and side effects of ketogenic diet for drug-resistant epilepsy in children with genetic epilepsy syndromes.

Background: Drug-resistant epilepsy (DRE) impacts a significant portion, one-third, of individuals diagnosed with epilepsy. In such cases, exploring non-pharmacological interventions are crucial, with the ketogenic diet (KD) standing out as a valuable option. KD, a high-fat and low-carb dietary approach with roots dating back to the 1920s for managing DRE, triggers the formation of ketone bodies and modifies biochemistry to aid in seizure control. Recent studies have increasingly supported the efficacy of KD in addressing DRE, showcasing positive outcomes. Furthermore, while more research is needed, limited data suggests that KD May also be beneficial for specific genetic epilepsy syndromes (GESs). Objective: This study aimed to assess the short-term efficacy of KD among pediatric patients diagnosed with GESs. Materials and methods: This is a multi-center retrospective analysis of pediatric patients with GESs diagnosed using next-generation sequencing. The enrolled patients followed the keto-clinic protocol, and the KD efficacy was evaluated at 3, 6, and 12-month intervals based on seizure control and compliance. The collection instrument included demographic, baseline, and prognostic data. The collected data was coded and analyzed promptly. Results: We enrolled a cohort of 77 patients with a mean current age of 7.94 ± 3.83 years. The mean age of seizure onset was 15.5 months. Notably, patients experienced seizures at a younger age tended to have less positive response to diet. Overall, 55 patients responded favorably to the diet (71.4%) while 22 patients (28.6%) showed no improvement. Patients with genetic etiology showed a significantly more favorable responses to the dietary intervention. Patients with Lennox-Gastaut syndrome showed the most significant improvement (14/15) followed by patients with Dravet syndrome (6/8), and West syndrome (3/4). The number of used anti-seizure medications also played a significant role in determining their response to the diet. While some patients experienced mild adverse events, the most common being constipation, these occurrences were not serious enough to necessitate discontinuation of the diet. Conclusion: The study revealed a high improvement rate in seizure control, especially among younger patients and those with later seizure onset. The success of dietary treatment hinges greatly on early intervention and the patient's age. Certain genetic mutations responded favorably to the KD, while efficacy varied among various genetic profiles.

Soluble PD-L1 as a novel biomarker predicts poor outcomes and disease progression in de novo myelodysplastic syndromes.

The role of the compromised immune microenvironment, including immune checkpoints, in myelodysplastic syndromes (MDS) has been identified as critical This study aimed to investigate the expression patterns of immune checkpoints, particularly soluble PD-1/PD-L1 (sPD-1/sPD-L1) as well as PD-1 on effector T cell subsets, and assess their prognostic value and potential regulatory roles in MDS. 161 MDS patients were enrolled, including 129 patients were primarily diagnosed with de novo MDS, together with 59 MDS patients who underwent hypomethylating agents (HMAs) therapy. Plasma sPD-L1 level was elevated in newly diagnosed MDS patients, which was also found to be associated with MDS disease progression that further increase in higher IPSS-R score group. Patients with increased sPD-L1 expression at diagnosis exhibited notably poorer overall survival, and multivariate Cox analysis indicated that elevated sPD-L1 was an independent risk factor. Furthermore, the levels of multiple cytokines and membrane-bound PD-1 on T cells were found to correlate with sPD-1/sPD-L1 levels in plasma. Importantly, we also found sPD-L1 levels significantly increased in MDS patients who showed progression of disease following HMAs therapy. In conclusion, we found elevated plasma sPD-L1 levels in MDS patients are associated with disease progression and poorer overall survival. This study showed that sPD-L1 is a potential biomarker for prognosis and a target for immunotherapy in MDS.

Maturation of pluripotent stem cell-derived cardiomyocytes: limitations and challenges from metabolic aspects.

Acute coronary syndromes, such as myocardial infarction (MI), lack effective therapies beyond heart transplantation, which is often hindered by donor scarcity and postoperative complications. Human induced pluripotent stem cells (hiPSCs) offer the possibility of myocardial regeneration by differentiating into cardiomyocytes. However, hiPSC-derived cardiomyocytes (hiPSC-cardiomyocytes) exhibit fetal-like calcium flux and energy metabolism, which inhibits their engraftment. Several strategies have been explored to improve the therapeutic efficacy of hiPSC-cardiomyocytes, such as selectively enhancing energy substrate utilization and improving the transplantation environment. In this review, we have discussed the impact of altered mitochondrial biogenesis and metabolic switching on the maturation of hiPSC-cardiomyocytes. Additionally, we have discussed the limitations inherent in current methodologies for assessing metabolism in hiPSC-cardiomyocytes, and the challenges in achieving sufficient metabolic flexibility akin to that in the healthy adult heart.

A predictive nomogram-based model for lower extremity compartment syndrome after trauma in the United States: a retrospective case-control study.

Purpose: The aim of this study was to utilize the American College of Surgeons Trauma Quality Improvement Program (TQIP) database to identify risk factors associated with developing acute compartment syndrome (ACS) following lower extremity fractures. Specifically, a nomogram of variables was constructed in order to propose a risk calculator for ACS following lower extremity trauma. Methods: A large retrospective case-control study was conducted using the TQIP database to identify risk factors associated with developing ACS following lower extremity fractures. Multivariable regression was used to identify significant risk factors and subsequently, these variables were implemented in a nomogram to develop a predictive model for developing ACS. Results: Novel risk factors identified include venous thromboembolism prophylaxis type particularly unfractionated heparin (odds ratio [OR], 2.67; 95% confidence interval [CI], 2.33-3.05; P<0.001), blood product transfusions (blood per unit: OR 1.13 [95% CI, 1.09-1.18], P<0.001; platelets per unit: OR 1.16 [95% CI, 1.09-1.24], P<0.001; cryoprecipitate per unit: OR 1.13 [95% CI, 1.09-1.22], P=0.003). Conclusions: This study provides evidence to believe that heparin use and blood product transfusions may be additional risk factors to evaluate when considering methods of risk stratification of lower extremity ACS. We propose a risk calculator using previously elucidated risk factors, as well as the risk factors demonstrated in this study. Our nomogram-based risk calculator is a tool that will aid in screening for high-risk patients for ACS and help in clinical decision-making.

Sexual function in women with endometriosis and pelvic floor myofascial pain syndrome.

Objective: To evaluate and compare the sexual function and pelvic floor muscles (PFM) function of women with endometriosis and chronic pelvic pain (CPP) with and without Myofascial Pelvic Pain Syndrome (MPPS). Methods: Cross-sectional study conducted between January 2018 and December 2020. Women with deep endometriosis underwent assessments for trigger points (TP) and PFM function using the PERFECT scale. Electromyographic activity (EMG) and sexual function through Female Sexual Function Index (FSFI) were assessed. Statistical analyses included chi-square and Mann-Whitney tests. Results: There were 46 women. 47% had increased muscle tone and 67% related TP in levator ani muscle (LAM). Weakness in PFM, with P≤2 was noted in 82% and P≥3 in only 17%. Incomplete relaxation of PFM presented in 30%. EMG results were resting 6.0, maximal voluntary isometric contraction (MVIC) 61.9 and Endurance 14.2; FSFI mean total score 24.7. We observed an association between increased muscle tone (P<.001), difficulty in relaxation (P=.019), and lower Endurance on EMG (P=.04) in women with TP in LAM. Participants with TP presented lower total FSFI score (P=.02). TP in the right OIM presented increased muscle tone (P=.01). TP in the left OIM presented lower values to function of PFM by PERFECT (P=.005), and in MVIC (P=.03) on EMG. Conclusion: Trigger points (TP) in pelvic floor muscles (PFM) and obturator internus muscle (OIM) correlates with poorer PFM and sexual function, particularly in left OIM TP cases. Endometriosis and chronic pelvic pain raise muscle tone, weaken muscles, hinder relaxation, elevate resting electrical activity, lower maximum voluntary isometric contraction, and reduce PFM endurance.

Precision Imaging in Neurodegeneration: The Superiority of Diffusion Tensor Imaging Over Conventional MRI in Differentiating Parkinson's Disease From Atypical Parkinsonian Syndromes.

Background Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra, leading to motor and non-motor symptoms. Atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP) and essential tremor (ET), present with overlapping clinical features, making differential diagnosis challenging. Conventional MRI has limitations in distinguishing PD from APS, necessitating advanced imaging techniques like diffusion tensor imaging (DTI) for more accurate diagnosis. Objectives This retrospective study aimed to evaluate the diagnostic accuracy of DTI in diagnosing PD and APS, particularly assessing its ability to differentiate these conditions from each other compared to conventional MRI. Additionally, the study sought to determine if DTI could diagnose PD in cases where conventional MRI results were normal, thereby highlighting the potential role of DTI in enhancing diagnostic precision in neurodegenerative disorders. Methodology The study included 30 patients with clinically diagnosed PD or APS who underwent both conventional MRI and DTI. Data were collected retrospectively. Imaging was performed using a Philips Multiva 1.5-Tesla MRI scanner (Philips, Amsterdam, Netherlands). DTI sequences were analyzed for fractional anisotropy (FA) values in the substantia nigra, superior cerebellar peduncle, middle cerebellar peduncle, transverse pontine fibers, and dentate nucleus. The FA values were compared with established normal values, and the findings from DTI were correlated with clinical diagnoses and conventional MRI results. Results Among the 30 patients, 53.3% were clinically diagnosed with PD and 46.7% with APS, including PSP and ET. Conventional MRI findings were normal in 46.7% of cases, indicating its limitations in detecting early or subtle changes in neurodegenerative disorders. In contrast, DTI identified abnormalities in 83.3% of cases, demonstrating its superior diagnostic sensitivity. DTI detected significant FA value reductions in the substantia nigra in PD patients (mean FA: 0.440), which is consistent with the degeneration of dopaminergic neurons characteristic of PD. In PSP patients, the superior cerebellar peduncle showed marked FA reductions (mean FA: 0.523), correlating with the clinical features of PSP, such as bradykinesia and postural instability. ET was identified by reduced FA values in the superior cerebellar peduncle and dentate nucleus, distinguishing it from other forms of parkinsonism. DTI was particularly effective in cases where conventional MRI results were inconclusive or normal, identifying early-stage PD and differentiating it from APS with greater accuracy. The study demonstrated a sensitivity of 95.8% and specificity of 93.8% for DTI in differentiating PD from APS compared to conventional MRI. Conclusion This study highlights DTI as a superior imaging modality for the early diagnosis and differentiation of parkinsonian disorders, particularly when conventional MRI results are inconclusive. DTI's ability to detect significant microstructural changes in specific brain regions, evidenced by FA value reductions, enhances diagnostic accuracy. Incorporating DTI into routine clinical practice is essential for accurate differentiation between PD and APS, facilitating better patient management.

Genetic predisposition to childhood cancer.

The etiology of childhood cancer remains largely unknown. Recent evidence suggests that genetic factors play a substantial role in pediatric tumorigenesis. Unlike adult cancers, pediatric cancers typically have a higher prevalence of germline pathogenic variants in cancer predisposition genes. Inherited cancer predisposition syndromes account for approximately 10% of all childhood cancers. Over the years, the diagnosis of cancer predisposition syndromes was based on clinical suspicion prompting referral to a specialized geneticist. However, advances in molecular technologies have led to a shift toward a "genotype-first" approach. Identification of genetic variants related to cancer predisposition enables tailored treatment, improves clinical outcome, optimizes surveillance, and facilitates genetic counseling of the affected child and the family.

Predictors of survival in autoimmune liver disease overlap syndromes.

BACKGROUND: Survival in patients with autoimmune liver disease overlap syndromes (AILDOS) compared to those with single autoimmune liver disease is unclear. AIM: To investigate the survival of patients with AILDOS and assess the accuracy of non-invasive serum models for predicting liver-related death. METHODS: Patients with AILDOS were defined as either autoimmune hepatitis and primary biliary cholangitis overlap (AIH-PBC) or autoimmune hepatitis and primary sclerosing cholangitis overlap (AIH-PSC) and were identified from three tertiary centres for this cohort study. Liver-related death or transplantation (liver-related mortality) was determined using a population-based data linkage system. Prognostic scores for liver-related death were compared for accuracy [including liver outcome score (LOS), Hepascore, Mayo Score, model for end-stage liver disease (MELD) score and MELD incorporated with serum sodium (MELD-Na) score]. RESULTS: Twenty-two AILDOS patients were followed for a median of 3.1 years (range, 0.35-7.7). Fourteen were female, the median age was 46.7 years (range, 17.8 to 82.1) and median Hepascore was 1 (range, 0.07-1). At five years post enrolment, 57% of patients remained free from liver-related mortality (74% AIH-PBC, 27% AIH-PSC). There was no significant difference in survival between AIH-PBC and AIH-PSC. LOS was a significant predictor of liver-related mortality (P < 0.05) in patients with AIH-PBC (n = 14) but not AIH-PSC (n = 8). A LOS cut-point of 6 discriminated liver-related mortality in AIH-PBC patients (P = 0.012, log-rank test, 100% sensitivity, 77.8% specificity) (Harrell's C-statistic 0.867). The MELD score, MELD-Na score and Mayo Score were not predictive of liver-related mortality in any group. CONCLUSION: Survival in the rare, AILDOS is unclear. The current study supports the LOS as a predictor of liver-related mortality in AIH-PBC patients. Further trials investigating predictors of survival in AILDOS are required.

The multiple faces of autoimmune Addison's disease in children.

Primary adrenal insufficiency (PAI) is a rare medical condition, characterized by a deficiency in adrenal hormones. Although rare, PAI is a life-threatening disease requiring prompt recognition and treatment. However, symptoms of PAI are often non-specific and diagnosis can be challenging, causing frequent diagnostic delays. In adults, autoimmunity is the most common cause of PAI in industrialized countries, whereas in children, the most frequent etiology is represented by congenital defects of steroidogenesis and, in particular, by congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. A few recent case series from different countries have reported that autoimmunity is the second most common etiology of PAI in the pediatric age group. However, data on autoimmune PAI in children are still scant and the exact epidemiology, clinical manifestations, and long-term outcomes of this condition have yet to be defined. The scope of this review is to summarize the current knowledge on the etiology, presentation, and treatment of autoimmune PAI in childhood and to increase physicians' awareness of the signs that should raise an early suspicion of this condition.

The immunobiology of myelodysplastic neoplasms: a mini-review.

This mini review summarizes the immunobiology of myelodysplastic syndromes, specifically focusing on the interactions between immune cells, cytokines, and dysplastic cells within the tumor microenvironment in the bone marrow. We elucidate in detail how immune dysregulation and evasion influence the initiation and progression of myelodysplastic syndromes, as well as resistance to therapy and progression to AML. In addition, we highlight a range of therapeutic strategies, including the most recent breakthroughs and experimental therapies for treating MDS. Finally, we address the existing knowledge gaps in the understanding of the immunobiology of MDS and propose future research directions, promising advancements toward enhancing clinical outcomes and survival for patients with MDS.

Sturge weber syndrome: A case report.

This report presents a 14-year-old male with seizures and facial port-wine stains, who upon further evaluation was found to have SWS. Early diagnosis and consistent treatment of Sturge-Weber syndrome in children are essential to prevent seizures and improve quality of life. Anti-seizure medications play a crucial role in preventing and controlling seizures.

Hypertrophic Osteoarthropathy Mimicking Rheumatoid Arthritis.

Paraneoplastic rheumatologic syndromes encompass a range of clinical conditions that mimic primary rheumatic diseases and occur in the context of malignancy. Hypertrophic osteoarthropathy (HOA) is a notable example of such a syndrome, which is frequently associated with intrathoracic malignancies, including primary lung tumors and metastases. This report presents a case of a patient diagnosed with HOA secondary to lung adenocarcinoma, who was admitted with symmetric polyarthritis that resembled elderly-onset rheumatoid arthritis. Anti-cyclic citrullinated peptide (anti-CCP) antibodies are primarily associated with rheumatoid arthritis, but their levels can be falsely elevated in various other conditions. In clinical practice, it's essential to interpret anti-CCP antibody results in conjunction with other clinical findings and laboratory tests to arrive at an accurate diagnosis. This case underscores the importance of considering HOA in the differential diagnosis of inflammatory arthritis, particularly in patients with a known or suspected malignancy, especially in the presence of positive rheumatoid arthritis-specific antibodies. Also, recognition and treatment of the underlying condition can lead to substantial improvements in both rheumatologic and oncologic aspects.

In vivo glycation-interplay between oxidant and carbonyl stress in bone.

Metabolic syndromes (eg, obesity, type 2 diabetes (T2D), atherosclerosis, and neurodegenerative diseases) and aging, they all have a strong component of carbonyl and reductive-oxidative (redox) stress. Reactive carbonyl (RCS) and oxidant (ROS) stress species are commonly generated as products or byproducts of cellular metabolism or are derived from the environment. RCS and ROS can play a dual role in living organisms. Some RCS and ROS function as signaling molecules, which control cellular defenses against biological and environmental assaults. However, due to their high reactivity, RCS and ROS inadvertently interact with different cellular and extracellular components, which can lead to the formation of undesired posttranslational modifications of bone matrix proteins. These are advanced glycation (AGEs) and glycoxidation (AGOEs) end products generated in vivo by non-enzymatic amino-carbonyl reactions. In this review, metabolic processes involved in generation of AGEs and AGOEs within and on protein surfaces including extracellular bone matrix are discussed from the perspective of cellular metabolism and biochemistry of certain metabolic syndromes. The impact of AGEs and AGOEs on some characteristics of mineral is also discussed. Different therapeutic approaches with the potential to prevent the formation of RCS, ROS, and the resulting formation of AGEs and AGOEs driven by these chemicals are also briefly reviewed. These are antioxidants, scavenging agents of reactive species, and newly emerging technologies for the development of synthetic detoxifying systems. Further research in the area of in vivo glycation and glycoxidation should lead to the development of diverse new strategies for halting the progression of metabolic complications before irreversible damage to body tissues materializes.

[Aberrant mitochondrial dynamics in myeloid neoplasms].

Age-related clonal hematopoiesis and myeloid malignancies arise from hematopoietic stem cells and progenitors with genetic abnormalities. Advances in next-generation sequencing technology have led to the identification of a wide variety of genetic alterations involved in disease onset. However, it remains unclear how diverse genetic alterations, lacking disease specificity, lead to the development of myeloid malignancies and the progression of clonal hematopoiesis. Mitochondrial abnormalities and their roles in various pathological conditions such as aging, inflammation, neurological diseases, cardiac diseases, and cancer have recently been revealed, and have garnered attention as new therapeutic targets. This review focuses on regulation of mitochondrial dynamics and outlines the role of mitochondria in myeloid malignancies and clonal hematopoiesis.

DYNC2H1 splicing variants causing severe prenatal short-rib polydactyly syndrome and postnatal orofaciodigital syndrome.

The DYNC2H1 gene has been associated with short-rib polydactyly syndrome (SRPS), among other skeletal ciliopathies. Two cases are presented of distinctive phenotypes resulting from splicing variants in DYNC2H1. The first is a 14-week-old fetus with enlarged nuchal translucency, oral hamartoma, malformed uvula, bifid epiglottis, short ribs, micromelia, long bone agenesis, polysyndactyly, heart defect, pancreatic cysts, multicystic dysplastic kidney, megabladder and trident acetabulum. A ciliopathies NGS panel revealed two compound heterozygous variants in DYNC2H1: c.7840-18T>G r.7841_7964del p.Gly2614Aspfs*5 and c.11070G>A r.11044_11116del p.Ile3682Aspfs*2. Both variants were initially classified as variants of uncertain significance but were reclassified as likely pathogenic after PCR-based RNA testing. The second is an 11-year-old overweight male with multiple accessory oral frenula, median cleft lip and alveolar ridge, polysyndactyly, brachydactyly, normal rib length, and hypogonadism. Exome sequencing revealed two compound heterozygous variants in DYNC2H1: c.6315del p.(Thr2106Glnfs*7), classified as likely pathogenic, and c.3303-16A>G p.(?), classified as a variant of uncertain significance. PCR-based RNA testing suggested that c.3303-16A>G induces an in-frame deletion: r.3303_3458del p.Asp1102_Arg1153del, although the normal transcript is still produced. These results are consistent with both SRPS type I/III in the first case and orofaciodigital syndrome in the second, an unprecedented description. This work thus improves the clinical and molecular knowledge of the phenotypes associated with splicing variants in the DYNC2H1 gene.

Measurable residual disease assessment prior to allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia and myelodysplastic syndromes: a 20-year monocentric study.

Patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) who undergo allogeneic hematopoietic stem-cell transplantation (alloHSCT) can have divergent survival outcomes while all in morphological complete remission (CR). Techniques of measurable residual disease (MRD) have allowed us to refine their prognosis in two categories: MRD-positive and MRD-negative patients. We conducted a monocentric retrospective study (01/2000-12/2020) to assess the prognosis of pretransplant MRD status measured by multiparametric flow cytometry (MFC) and molecular biology assessed by PCR. 192 patients were included. The median follow-up period was 77 months. Among patients undergoing alloHSCT in CR, overall survival (median-OS: 130.6 vs. 16.0 months, P < 0.001), disease-free survival (median-DFS: 109.6 vs. 7.1 months, P < 0.001) and cumulative incidence of relapse (12-month CIR: 7.3% vs. 33.7%, P < 0.0001) were significantly different between MRD-negative and MRD-positive patients. Patients with discordant intermethod results had intermediate DFS. MRD-negative patients according to molecular PCR-based techniques, WT1 overexpression and MFC had longer median-DFS, compared to MRD-positive patients (P = 0.001, P < 0.001, P < 0.001, respectively). Looking into subgroups, MRD-positive patients among the ELN2017 adverse-category (P < 0.0001), myeloablative and reduced-intensity conditioning regimens (P < 0.0001, P = 0.005), < 60-year patients (P < 0.001) and AML patients (P < 0.001) were associated with lower DFS. This difference was not found in ≥ 60-year patients (P = 0.27) and MDS patients (P = 0.70). MRD-positive patients within the favorable/intermediate ELN2017 category trended toward lower DFS (P = 0.05). We confirmed that MRD status prior to alloHSCT is a strong prognostic factor for OS, DFS and CIR. Combining MFC and molecular-PCR techniques to assess MRD seems primordial as inter-method discordance can be consequential.

They Will Surveil You to Death: Gangstalking as a Cultural Concept of Distress.

Understanding local worldviews is a challenge during clinical encounters, especially when they involve cultural references without acceptance from the medical community. Gangstalking is a Western cultural notion which refers to systematic harassment, surveillance, and torture from unseen or covert assailants or networks. It is not a 'real phenomenon' compared with genuine stalking, but experients report worse depression, post-traumatic symptoms, suicidal ideation, and longer lasting encounters. They report physical pain and impossible feats of espionage technologically orchestrated by unknown malevolent actors. Using conversational data from targeted individual podcasts, I explore gangstalking as a cultural concept of distress (CCD) by highlighting associated explanations, idioms, and symptoms. Clinically, gangstalking is likely diagnosed as paranoid schizophrenia. However, its association with frightening events parallels Susto and Nervios. Physical symptoms parallel Open Mole and Brain Fag Syndrome. Like many CCDs, gangstalking is a multi-dimensional phenomenon not neatly mapped onto psychiatric categories. Misinterpreting gangstalking cases as unique or isolated is a likely outcome even when they fit within a well-known Western subculture and techno-science belief system. Moving past prior, outdated notions of folk illnesses and culture-bound syndromes, gangstalking as a CCD helps end the assumption that only the other has exotic or non-psychiatric categories of distress.

A Rare Presentation of Posterior Circulation Strokes: A Case Report of Nine Syndrome.

Nine syndrome is a rare variant of one-and-a-half syndrome that results from a stroke in the posterior circulation, mainly manifesting as ipsilateral horizontal gaze palsy, facial palsy, and contralateral hemiataxia. Awareness of the clinical signs of this syndrome is crucial for accurate localization of the lesion and guiding further investigations. We report a case of nine syndrome presenting with signs of one-and-a-half syndrome, ipsilateral facial nerve palsy, hemiataxia, and hemiparesis. There are only a few cases of nine syndrome reported in the literature.

SEND-PD in Parkinsonian Syndromes: Results of a Monocentric Cross-Sectional Study.

Introduction: Neuropsychiatric symptoms in particular impair health-related quality of life (QoL) of patients with Parkinson's disease and atypical Parkinsonian syndromes. For this reason, various scales have been developed for detection of neuropsychiatric symptoms, such as the Scale for evaluation of neuropsychiatric disorders in Parkinson's disease (SEND-PD). Objective: First, the objective of this study was to explore the interrelation between the SEND-PD and clinical parameters in patients with Parkinson's disease and thus confirm its validity. In addition, the applicability in a well-defined cohort of patients with atypical Parkinsonian syndromes was investigated for the very first time. Methods: A clinically well-defined cohort of 122 patients with Parkinson's disease (PD), 55 patients with Progressive Supranuclear Palsy (PSP) and 33 patients with Multiple System Atrophy (MSA) were analyzed. First, the SEND-PD was correlated with established disease-specific scores in patients with PD. Next, the results of the SEND-PD were compared between the different Parkinsonian syndromes. Results: The SEND-PD showed a strong significant correlation with several scores, especially the UPDRS I (Rho = 0.655) and GDS-15 (Rho = 0.645). Depressive burden was significantly higher in MSA patients in comparison to the PD patient cohort (PD, 3.8 ± 3.3; MSA, 5.45 ± 3.87), while PSP patients showed significantly less psychotic (PD 1.6 ± 2.1; PSP 0.6 ± 0.9) and impulse control disorders (PD 0.3 ± 1.0; PSP 0.02 ± 0.1). Conclusion: The SEND-PD is a useful, brief and highly applicable screening tool for neuropsychiatric symptoms in PD, but not in atypical Parkinsonism, as their unique neuropsychiatric symptom composition is not fully captured.

Targeted therapies for myelodysplastic Syndromes/Neoplasms (MDS): current landscape and future directions.

INTRODUCTION: Myelodysplastic syndromes/neoplasms (MDS) are a heterogeneous group of hematologic malignancies that are stratified into high-risk (HR-MDS) and low-risk (LR-MDS) categories. Until recently LR-MDS has been typically managed by supportive measures and erythropoiesis-stimulating agents (ESAs); whereas, management of HR-MDS, typically included hypomethylating agents and allogeneic hematopoietic stem cell transplant. However, the limited rates and duration of response observed with these interventions prompted the search for targeted therapies to improve the outcomes among patients with MDS. AREAS COVERED: Here we review the current landscape of targeted therapies in MDS. These include pyruvate kinase and hypoxia-inducible factor (HIF) activators; TGF-beta, telomerase, BCL2 and isocitrate dehydrogenase (IDH) inhibitors; as well as novel approaches targeting inflammation, pyroptosis, immune evasion and RNA splicing machinery. EXPERT OPINION: This review highlights the progress and challenges in MDS treatment. Despite some promising results, many therapies remain in early development or have faced setbacks, emphasizing the need for a more comprehensive understanding of the disease's pathobiology. Continued research into targeted therapies, homogenous clinical trial designs, as well as increased incorporation of molecular prognostic tools and artificial intelligence into trial design are essential for developing effective treatments for MDS and improving patient outcomes.