An Ecchordosis Physaliphora, a Rare Entity, Involving the Central Nervous System: A Systematic Review of the Literature.

Ecchordosis physaliphora (EP) is a benign notochordal remnant, which is often an incidental finding; however, it can rarely present with neurological symptoms. We performed a systematic review of the literature for cases of symptomatic EP published in PubMed, Web of Science and Embase from January 1982 to May 2023. This is the largest review to date and revealed 60 cases including ours. Headache (55%) and CSF rhinorrhea (32%) were the most frequent clinical manifestations. The majority of symptomatic EP lesions were located in the prepontine region (77%) and required surgical resection (75%). EP should be considered in patients with neurologic symptoms in the setting of prepontine or posterior sphenoid sinus lesions. While symptomatic patients often require surgical intervention, rare cases may respond to oral corticosteroids.

Updated Parkinson's disease motor subtypes classification and correlation to cerebrospinal homovanillic acid and 5-hydroxyindoleacetic acid levels.

Introduction: Motor classifications of Parkinson's Disease (PD) have been widely used. This paper aims to update a subtype classification using the MDS-UPDRS-III and determine if cerebrospinal neurotransmitter profiles (HVA and 5-HIAA) differ between these subtypes in a cohort from the Parkinson's Progression Marker Initiative (PPMI). Methods: UPDRS and MDS-UPDRS scores were collected for 20 PD patients. Akinetic-rigid (AR), Tremor-dominant (TD), and Mixed (MX) subtypes were calculated using a formula derived from UPDRS, and a new ratio was developed for subtyping patients with the MDS-UPDRS. This new formula was subsequently applied to 95 PD patients from the PPMI dataset, and subtyping was correlated to neurotransmitter levels. Data were analyzed using receiver operating characteristic models and ANOVA. Results: Compared to previous UPDRS classifications, the new MDS-UPDRS TD/AR ratios produced significant areas under the curve (AUC) for each subtype. The optimal sensitivity and specificity cutoff scores were ≥0.82 for TD, ≤0.71 for AR, and >0.71 and <0.82 for Mixed. Analysis of variance showed that the AR group had significantly lower HVA and 5-HIAA levels than the TD and HC groups. A logistic model using neurotransmitter levels and MDS-UPDRS-III could predict the subtype classification. Conclusions: This MDS-UPDRS motor classification system provides a method to transition from the original UPDRS to the new MDS-UPDRS. It is a reliable and quantifiable subtyping tool for monitoring disease progression. The TD subtype is associated with lower motor scores and higher HVA levels, while the AR subtype is associated with higher motor scores and lower 5-HIAA levels.

A Patient with Erdheim-Chester Disease Limited to Central Nervous System.

Erdheim-Chester disease (ECD) is a rare, sporadic, non-Langerhans cell histiocytosis, a multisystem disorder, which has higher mortality when presented with CNS involvement. We report a 46-year-old woman who has ECD with exclusive CNS involvement. She presented with intracranial hemorrhage and had a poor response to corticosteroid and interferon. She required multiple debulking procedures and eventually responded well to cobimetinib. She has not had any other organ involvement thus far. This report highlights that CNS involvement may be the only manifestation of ECD and sometimes may require a repeat biopsy with IHC testing for excellent treatment outcomes.

Erdheim-Chester Disease with Isolated CNS Involvement: A Systematic Review of the Literature.

Erdheim-Chester disease (ECD) is a rare, sporadic, non-Langerhans cell histiocytosis that can have various presentations and higher mortality in patients presenting with neurological symptoms. We performed a systematic review to investigate and chronicle the frequency of neurological manifestations, imaging findings, treatments, and outcomes in published ECD patients presenting with neurological symptoms. A PubMed literature search was conducted for articles (published between January 1980 and June 2021) on ECD cases presenting with neurological manifestations. We analyzed the data of 40 patients, including our patient. Cranial neuropathies and ataxia were the most frequent clinical manifestations. A total of 50% of the symptomatic ECD CNS lesions were intraparenchymal and nearly 33% of patients died due to the disease itself or complications. CNS involvement may be the only manifestation of ECD and sometimes may require a repeat biopsy with IHC testing for excellent treatment outcomes.

Urine ALCAM, PF4 and VCAM-1 Surpass Conventional Metrics in Identifying Nephritis Disease Activity in Childhood-Onset Systemic Lupus Erythematosus.

Objectives: Serial kidney biopsy for repeat evaluation and monitoring of lupus nephritis (LN) in childhood-onset Systemic Lupus Erythematosus (cSLE) remains challenging, thus non-invasive biomarkers are needed. Here, we evaluate the performance of ten urine protein markers of diverse nature including cytokines, chemokines, and adhesion molecules in distinguishing disease activity in cSLE. Methods: Eighty-four pediatric patients meeting ≥4 ACR criteria for SLE were prospectively enrolled for urine assay of 10 protein markers normalized to urine creatinine, namely ALCAM, cystatin-C, hemopexin, KIM-1, MCP-1, NGAL, PF-4, Timp-1, TWEAK, and VCAM-1 by ELISA. Samples from active renal (LN) and active non-renal SLE patients were obtained prior to onset/escalation of immunosuppression. SLE disease activity was evaluated using SLEDAI-2000. 59 patients had clinically-active SLE (SLEDAI score ≥4 or having a flare), of whom 29 patients (34.5%) were classified as active renal, and 30 patients (35.7%) were active non-renal. Twenty-five healthy subjects were recruited as controls. Results: Urine concentrations of ALCAM, KIM-1, PF4 and VCAM-1 were significantly increased in active LN patients versus active non-renal SLE, inactive SLE and healthy controls. Five urine proteins differed significantly between 2 (hemopexin, NGAL, MCP1) or 3 (Cystatin-C, TWEAK) groups only, with the highest levels detected in active LN patients. Urine ALCAM, VCAM-1, PF4 and hemopexin correlated best with total SLEDAI as well as renal-SLEDAI scores (p < 0.05). Urine ALCAM, VCAM-1 and hemopexin outperformed conventional laboratory measures (anti-dsDNA, complement C3 and C4) in identifying concurrent SLE disease activity among patients (AUCs 0.75, 0.81, 0.81 respectively), while urine ALCAM, VCAM-1 and PF4 were the best discriminators of renal disease activity in cSLE (AUCs 0.83, 0.88, 0.78 respectively), surpassing conventional biomarkers, including proteinuria. Unsupervised Bayesian network analysis based on conditional probabilities re-affirmed urine ALCAM as being most predictive of active LN in cSLE patients. Conclusion: Urinary ALCAM, PF4, and VCAM-1 are potential biomarkers for predicting kidney disease activity in cSLE and hold potential as surrogate markers of nephritis flares in these patients.

Patient perception of voxelotor treatment benefit in sickle cell disease.

Patients with sickle cell disease (SCD) experience a range of clinical symptoms, including acute and chronic pain, fatigue, and respiratory problems, as well as chronic organ complications that can lead to disability and accelerated mortality. Voxelotor is a first-in-class therapy that targets sickle hemoglobin polymerization, the root cause of SCD. It is approved by the US Food and Drug Administration for treatment of SCD in patients aged 4 years and older and in the European Union and United Arab Emirates for the treatment of SCD in patients aged 12 years and older. Here, we report the single-center experience of both clinician-determined and patient-reported benefits of voxelotor in 27 consecutive patients treated for at least 8 weeks. Clinical Global Impression of Change and Patient Global Impression of Change rating scales were used to capture clinicians' and patients' perceptions of change in overall patient health-related quality-of-life with voxelotor treatment. Laboratory data were also collected to assess clinical response to treatment. As observed in previous clinical studies, hemoglobin concentrations and markers of hemolysis were improved in patients treated with voxelotor. Most patients reported marked improvement in disease symptoms, which correlated well with the clinicians' assessments. Although limited by the retrospective open-label study design, these findings suggest that voxelotor use has a positive impact on outcomes in patients with SCD.

Association between high BMI and high homocysteine levels in Chinese patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) has been associated with an increased prevalence of weight gain and abnormally elevated plasma homocysteine (Hcy) levels. However, the relationship between BMI and Hcy in BD patients has not been investigated. This study aimed to explore this relationship in Chinese patients with BD. METHODS: Plasma Hcy levels, socio-demographic parameters, clinical and anthropometric data were collected from 195 BD inpatients and 84 healthy controls. The level of plasma Hcy was determined by high-performance liquid chromatography. Body mass index (BMI) was calculated by body weight divided by the square of the height. The participants were divided into a high BMI group and a low BMI group using 24 kg/m2 as a threshold. RESULTS: The prevalence of high BMI was slightly elevated in BD patients in comparison to healthy controls. Patients with elevated BMI had significantly higher Hcy levels than patients with low BMI. Hcy level was an independent contributor of the occurrence of high BMI in BD patients. The level of Hcy was positively correlated with BMI in BD patients. In addition, depressive episodes of BD were positively correlated with the prevalence of high BMI and married BD patients were more likely to have high BMI levels. CONCLUSIONS: There is a close relationship between BMI and plasma Hcy levels in patients with BD, suggesting that Hcy may be an important indicator for BD-induced weight gain. This finding provides a new avenue for weight management of BD patients and to help avoid the potential risk of cardiovascular diseases.

Sex differences in the association between suicide attempts and glucose disturbances in first-episode and drug naive patients with major depressive disorder.

BACKGROUND: Glucose metabolism is related to depression, but the relationship between blood glucose and suicide attempts in patients with major depressive disorder (MDD) remains unclear. This large-scale sample explores the relationship between suicide attempts and fasting blood glucose, in addition to sex differences in first-episode and drug naive (FEDN) MDD patients. METHODS: 1718 FEDN MDD patients diagnosed for the first time were recruited, and their demographic data, clinical data, and blood glucose indicators were collected. 17-item Hamilton Depression Rating Scale (HAMD), 14-item Hamilton Anxiety Rating Scale (HAMA), and positive subscale of the Positive and Negative Syndrome Scale (PANSS) were used to assess their depression, anxiety and psychotic symptoms, respectively. RESULTS: The depression, anxiety, psychotic symptoms and blood sugar levels of the suicide attempt group were higher than those of the non-suicide attempt group. Correlation analysis showed that blood glucose was significantly associated with suicide attempts in male and female patients. While binary logistic regression showed that blood glucose levels were significantly associated with suicide attempts in male patients, it showed that suicide attempts were not significantly associated with blood glucose levels in female patients. LIMITATIONS: The main limitations are cross-sectional design and inability to control selection bias. CONCLUSIONS: In male MDD patients, fasting blood glucose level is a potential biomarker of suicide attempt, which deserves attention to avoid suicide risk. However, in female patients, fasting blood glucose has no significant correlation to suicide attempts.

Cross-sectional study of plasma Axl, ferritin, IGFBP4 and sTNFR2 as biomarkers of disease activity in childhood-onset SLE: A study of the Pediatric Nephrology Research Consortium.

OBJECTIVE: To evaluate the performance of 4 plasma protein markers for detecting disease activity in childhood-onset systemic lupus erythematosus (SLE) patients. METHODS: Eighty-three consecutive pediatric patients fulfilling ≥4 ACR criteria for SLE and twenty-five healthy controls were prospectively recruited for serological testing of 4 protein markers identified by antibody-coated microarray screen, namely Axl, ferritin, IGFBP4 and sTNFR2. SLE disease activity was assessed using SLEDAI-2000 score. Fifty-seven patients had clinically active SLE (SLEDAI score ≥4, or having a flare). RESULTS: The plasma concentrations of Axl and ferritin were significantly higher in patients with active SLE than inactive SLE. Plasma Axl levels were significantly higher in active renal versus active non-renal SLE patients. Levels of Axl, ferritin and IGFBP4 correlated significantly with SLEDAI scores. Levels of Axl, IFGBP4 and sTNFR2 inversely correlated with plasma complement C3 levels. Only plasma Axl and ferritin levels correlated with degree of proteinuria. These markers were more specific, but less sensitive, in detecting concurrent SLE activity than elevated anti-dsDNA antibody titer or decreased C3. Ferritin and IGFBP4 levels were more specific for concurrent active lupus nephritis than anti-dsDNA or C3. Plasma ferritin was the best monitor of global SLE activity, followed by C3 then Axl, while both Axl and C3 were best monitors of clinical lupus nephritis activity. CONCLUSION: In childhood-onset SLE patients, plasma ferritin and Axl perform better than traditional yardsticks in identifying disease activity, either global or renal. The performance of these plasma markers should be explored further in longitudinal cohorts of SLE patients.

Bradykinin 1 receptor blockade subdues systemic autoimmunity, renal inflammation, and blood pressure in murine lupus nephritis.

OBJECTIVE: The goal of this study was to explore the role of bradykinins and bradykinin 1 receptor (B1R) in murine lupus nephritis. METHODS: C57BL/6 and MRL/lpr mice were compared for renal expression of B1R and B2R by western blot and immunohistochemistry. MRL/lpr lupus-prone mice were administered the B1R antagonist, SSR240612 for 12 weeks, and monitored for blood pressure, proteinuria, renal function, and serum autoantibodies. RESULTS: Renal B1R:B2R ratios were significantly upregulated in MRL/lpr mice compared with B6 controls. B1R blockade ameliorated renal pathology lesions, proteinuria, and blood pressure, accompanied by lower serum IgG and anti-dsDNA autoantibody levels, reduced splenic marginal zone B cells and CD4+ T cells, and renal infiltrating CD4+ T cells, macrophages, and neutrophils. Both urine and renal CCL2 and CCL5 chemokines were also decreased in the B1R blocked MRL/lpr mice. CONCLUSION: Bradykinin receptor B1R blockade ameliorates both systemic immunity and renal inflammation possibly by inhibiting multiple chemokines and renal immune cell infiltration. B1R blockade may be particularly attractive in subjects with concomitant lupus nephritis and hypertension.

Trends in the use of implantable accelerated partial breast irradiation for ductal carcinoma in situ: Implications of the recent amendments to the American Society for Radiation Oncology consensus guidelines.

PURPOSE: In 2009, the American Society for Radiation Oncology (ASTRO) published consensus recommendations that stated ductal carcinoma in situ (DCIS) patients were in a "cautionary" group for accelerated partial breast irradiation (APBI) and should not receive APBI outside of a clinical trial. However, very recently, ASTRO placed low-risk DCIS patients in the "suitable" category. Given this recent change, we aimed to use the Surveillance, Epidemiology, and End Results (SEER) database to evaluate past patterns of implantable APBI (IAPBI) utilization in women with DCIS. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results database was queried for patients from 2000 to 2012 with DCIS that underwent lumpectomy and adjuvant radiation therapy. Patients receiving IAPBI were differentiated from those receiving whole breast radiation therapy. Trends based on treatment year and patient demographics were collected, and multivariable logistic regression determined factors independently predictive of use of IAPBI. RESULTS: Of 52,012 eligible patients, 49,450 (95%) underwent external beam radiation and 2562 (5%) received APBI. Though IAPBI utilization steadily increased from 2000 (0.2% of the study population) to 2008 (9.4%), it abruptly declined in 2009 (7.9%, p = 0.009) and yearly thereafter. The 40-49 age group was proportionally most associated with this decline (8.6% in 2008 to 4.3% in 2009). Factors independently associated with IAPBI receipt included increasing age, hormone receptor negative status, and women living in the South. CONCLUSIONS: Patterns of IAPBI administration in DCIS are described. These trends are important to consider as a benchmark going forward, in light of the very recent change in ASTRO recommendations to include low-risk DCIS patients.

Trends in cardiac mortality in women with ductal carcinoma in situ.

PURPOSE: In certain ductal carcinoma in situ (DCIS) subpopulations, there is no consensus regarding whether to postoperatively irradiate; decisions are often made based on potential risk of cardiac toxicities. Given the utility of Surveillance, Epidemiology, and End Results (SEER) data for studying cardiac mortality in invasive disease, this is the first such study specific for DCIS patients, evaluating trends in cardiac mortality after left-sided radiotherapy (RT). METHODS: The SEER database was queried for patients with DCIS that received RT and had known unilaterality. The central design of this study was to compare cardiac-specific mortality (CSM) between left- and right-sided DCIS patients as stratifying for "older" RT (1973-1982) versus more "modern" RT (1983-1992 or 1993-2002). Survival analysis was performed using Kaplan-Meier methodology and multivariate Cox regression modeling for factors associated with overall survival (OS) and CSS. RESULTS: Left- and right-sided patients were demographically balanced. CSM was worse for left-sided patients with DCIS diagnosed in 1973-1982 [hazard ratio (HR) 1.295; 95% confidence interval (CI) 1.182-1.420], but not in 1983-1992 (HR 1.022; 95% CI 0.949-1.100) or in 1993-2002 (HR 0.989; 95% CI 0.935-1.046)]. On multivariate analysis, laterality was not associated with OS in either decade. However, left-sided laterality was independently associated with CSM during the 1973-1982 time period, but not the more recent time periods. Examining temporal patterns in the 1973-1982 cohort, cardiac mortality was significantly increased during 10-19 and ≥20 years after diagnosis, but there was no significant increase in cardiac mortality for patients diagnosed up to 10 years after diagnosis. CONCLUSIONS: In the largest such DCIS series to date, left-sided RT was an independent risk factor for increased cardiac mortality from 1973 to 1982, but not after 1983. Using modern RT techniques and maintaining low heart doses, RT may not induce excess CSM in the DCIS population.