Activation of N-methyl-D-aspartate receptor glycine site temporally ameliorates neuropsychiatric symptoms of Parkinson's disease with dementia.

AIM: We have previously found that sarcosine, a glycine transporter I inhibitor, can improve the psychiatric symptoms of schizophrenia. In this study, we aimed to investigate whether the agent can also ameliorate neuropsychiatric symptoms of Parkinson's disease (PD) patients with dementia. METHODS: An 8-week, double-blind, placebo-controlled trial was conducted in patients who had PD with dementia (PD-D). Neuropsychiatric manifestations were measured before and at week 2 (V1), week 4 (V2) and week 8 (V3) after treatment. Linear regression with the generalized estimating equations was applied for data analysis. RESULTS: Fifteen patients were randomized into a sarcosine group; the other 15 into a placebo group. The generalized estimating equations model revealed significant differences in Hamilton Depression Rating Scale score (P = 0.049) at V1 and Neuropsychiatry Inventory (P = 0.039) at V2 between the treatment and placebo groups. By excluding the advanced patients from analysis, there were significant differences in Unified Parkinson's Disease Rating Scale V2 (P = 0.004) and V3 (P = 0.040), Hamilton Depression Rating Scale V1 (P = 0.014) and V2 (P = 0.047), Neuropsychiatry Inventory V1 (P = 0.002) and V2 (P < 0.001) and Behavior Pathology in Alzheimer's Disease Rating Scale V2 (P = 0.025) in favor of sarcosine. CONCLUSION: Sarcosine temporally improved depression and neuropsychiatric symptoms in PD-D patients without exacerbating the motor or cognitive features; the beneficial effects were more prominent in patients with mild-moderate severity. Enhancement of N-methyl-D-aspartate receptor-glycine cascade may lead to a novel path for the management of PD-D.

Toll-like receptor 9 SNPs are susceptible to the development and progression of membranous glomerulonephritis: 27 years follow-up in Taiwan.

The purpose of this study was to determine whether toll-like receptors 9 (TLR9) gene polymorphisms (rs352139 and rs352140) were markers of susceptibility to the development and progression of membranous nephropathy (MGN) in Taiwanese patients. The polymorphisms were investigated by polymerase chain reaction in 397 Taiwanese individuals (134 MGN patients and 263 controls). Patients with malignancy, chronic infectious diseases, lupus nephritis, or drug-induced secondary MGN were excluded from the study. Data showed AA genotype at rs352139 SNP or GG genotype at rs352140 SNP may indicate higher risk for MGN (odds ratio [OR] = 1.55; 95% confidence interval [CI] = 1.02-2.35, at rs352139 SNP; OR = 1.57; 95% CI = 1.03-2.39, at rs352140 SNP). However, MGN patients with A-G haplotype were susceptible for decreased creatinine clearance rate and for seriously tubule-interstitial fibrosis. The result suggests for the first time that TLR9 (rs352139 and rs352140) polymorphisms may contribute to the development and progression of MGN.

Cerebrolysin enhances cognitive recovery of mild traumatic brain injury patients: double-blind, placebo-controlled, randomized study.

In adults, mild traumatic brain injury (MTBI) frequently results in impairments of cognitive functions which would lead to psychological consequences in the future. Cerebrolysin is a nootropic drug, and can significantly improve cognitive function in patients with Alzheimer's disease and stroke. The purpose of this study was to investigate how Cerebrolysin therapy enhances cognitive recovery for mild traumatic brain injury patients using a double-blinded, placebo-controlled, randomized phase II pilot study. Patients having head injury within 24 h sent to our hospital were screened and recruited if patients were alert and conscious, and had intracranial contusion haemorrhage. From July 2009 to June 2010, totally, thirty-two patients were recruited in the double-blinded, placebo-controlled, and randomized study. Patients were randomized to receive Cerebrolysin (Group A, once daily intravenous infusion of 30 mL Cerebrolysin over a 60-min period for 5 days) or placebo (Group B, same dosage and administration of normal saline as Group A). The primary outcome measures were differences of cognitive function including Mini-Mental Status Examination (MMSE), and Cognitive Abilities Screening Instrument (CASI) scores between baseline and week 1, between baseline and week 4, and between baseline and week 12. Thirty-two patients completed the trial. For Group A, the CASI score difference between baseline and week 12 was 21.0 ± 20.4, a significantly greater change than that of Group B (7.6 ± 12.1) (p = 0.0461). Besides, drawing function (one of the domains of CASI; p = 0.0066) on week 4 and both drawing function (p = 0.0472) and long-term memory (one of the domains of CASI; p = 0.0256) on week 12 were also found to be significantly improved in the patients receiving Cerebrolysin treatment. Our results suggest that Cerebrolysin improves the cognitive function of the MTBI in patients at 3rd month after injury, especially for long-term memory and drawing function.

Unlocking Colchicine's Untapped Potential: A Paradigm Shift in Hepatocellular Carcinoma Prevention.

Background: Liver cancer and notably hepatocellular carcinoma (HCC), results in significantly high mortality rates worldwide. Chronic hepatitis and fatty liver, recognized precursors, underscore the imperative need for effective preventive strategies. This study explores colchicine, traditionally acknowledged for its anti-inflammatory properties and investigates its potential in liver cancer prevention. Methods: Utilizing the iHi Data Platform of China Medical University Hospital, Taiwan, this study analyzed two decades of medical data, incorporating 10,353 patients each in the Colchicine and Non-Colchicine cohorts, to investigate the association between colchicine use and liver cancer risk. Results: The study identified that colchicine users exhibited a 19% reduction in liver cancer risk, with a multivariable-adjusted odds ratio of 0.81 after accounting for confounding variables. Additionally, the influence of gender and comorbidities like diabetes mellitus on liver cancer risk was identified, corroborating the existing literature. A notable finding was that the prolonged use of colchicine was associated with improved outcomes, indicating a potential dose-response relationship. Conclusions: This study proposes a potential new role for colchicine in liver cancer prevention, extending beyond its established anti-inflammatory applications. While the findings are promising, further research is essential to validate these results. This research may serve as a foundation for future studies, aiming to further explore colchicine's role via clinical trials and in-depth investigations, potentially impacting preventive strategies for liver cancer.

Patient-derived tumor organoids as a platform of precision treatment for malignant brain tumors.

Malignant brain tumors consist of malignancies originated primarily within the brain and the metastatic lesions disseminated from other organs. In spite of intensive studies, malignant brain tumors remain to be a medical challenge. Patient-derived organoid (PDO) can recapitulate the biological features of the primary tumor it was derived from and has emerged as a promising drug-screening model for precision therapy. Here we show a proof-of-concept based on early clinical study entailing the organoids derived from the surgically resected tumors of 26 patients with advanced malignant brain tumors enrolled during December 2020 to October 2021. The tumors included nine glioma patients, one malignant meningioma, one primary lymphoma patient, and 15 brain metastases. The primary tumor sites of the metastases included five from the lungs, three from the breasts, two from the ovaries, two from the colon, one from the testis, one of melanoma origin, and one of chondrosarcoma. Out of the 26 tissues, 13 (50%) organoids were successfully generated with a culture time of about 2 weeks. Among these patients, three were further pursued to have the organoids derived from their tumor tissues tested for the sensitivity to different therapeutic drugs in parallel to their clinical care. Our results showed that the therapeutic effects observed by the organoid models were consistent to the responses of these patients to their treatments. Our study suggests that PDO can recapitulate patient responses in the clinic with high potential of implementation in personalized medicine of malignant brain tumors.

Unmet supportive care needs of survival patients with breast cancer in different cancer stages and treatment phases.

OBJECTIVE: This study aimed to examine the differences between patients with breast cancer (BC) at different cancer stages and treatment phases in terms of unmet supportive care needs as well as to predict the critical factors that influence the unmet needs of such patients. MATERIALS AND METHODS: A retrospective study was conducted by collecting data from the case consultation and service records of a cancer center in central Taiwan. Information extracted from the case consultation and service records included patients' age, treatment phase, cancer stage, and unmet need domains. RESULTS AND CONCLUSION: Overall, 1129 BC patients were recruited. In the prediction of critical factors influential to the health information needs of patients with BC, in-treatment patients, and those undergoing a follow-up were found to have significantly lower health information needs than patients newly diagnosed with BC. In-treatment and follow-up patients had significantly lower patient care needs than those newly diagnosed with BC. Stage II, III, and IV BC patients had significantly lower nutritional needs than stage I patients. In-treatment patients and those receiving follow-ups had significantly lower nutritional needs than patients newly diagnosed with BC. Relapse and terminal care patients had significantly higher psychosocial needs than patients newly diagnosed with BC. Thus, unmet needs of patients with cancer differ according to their age, cancer stage, and treatment phase. Appropriate and punctual tailored support provided by medical care personnel to address the unmet needs of patients can reduce the unmet supportive care needs in such patients and improve the quality of medical care services they are provided with. Ultimately, the overall quality of life of patients can be improved.

Unmet Supportive Care Needs of Survival Patients with Nasopharyngeal Carcinoma.

This study examined unmet supportive care needs for nasopharyngeal carcinoma (NPC) patients by cancer stage and treatment phase, as well as the factors associated with these unmet needs. At a cancer center in central Taiwan, information on consultations and services patients received at the resource center was described in the service chart. We extracted data available for NPC patients to evaluate their unmet supportive care needs (health information, patient care, treatment, nutritional, psychosocial, and economic) and their association with sex, age, cancer stage, and treatment phase. The 145 NPC patients were 68.3% male, 60.0% less than 50 years old, and 83.5% diagnosed at stages III and IV. The most prevalent unmet need was nutritional (40.7%), followed by psychosocial and patient care, with economic unmet needs the least (4.8%). Women were more likely than men to have patient care unmet needs (32.6% vs. 15.2%). Nutritional unmet need was higher in older patients than in younger ones (83.3% vs. 35.6%), with an adjusted odds ratio (aOR) of 9.39 (95% confidence interval (CI) = 2.17-40.70). Psychosocial unmet needs were higher in younger patients than old patients (34.5% vs. 0%) and in patients interviewed during follow-up period than those at newly diagnosed (55.2% vs. 23.1%). In conclusion, the most commonly reported concern was nutritional unmet needs for NPC patients. Their unmet needs may vary by demographic and disease factors, including patient sex and age, cancer stage, and treatment phase.

Long-Term Follow-up in Patients with Spontaneous Intracerebral Hemorrhage Treated With or Without Surgical Intervention: a Large-Scale Retrospective Study.

Debates regarding the most beneficial medical or surgical procedures for patients with spontaneous intracerebral hemorrhage (sICH) are still ongoing. We aimed to evaluate the risk of subsequent vascular disease and mortality in patients with sICH treated with and without surgical intervention, in a large-scale Asian population. Patients hospitalized within 2000 to 2013 who were newly diagnosed with sICH were identified using the National Health Insurance Research Database of Taiwan. Neuroendoscopy and craniotomy groups comprised patients who underwent surgical treatment within 1 week, while those in the control group did not undergo early surgical treatment. Outcomes included subsequent hemorrhagic and ischemic stroke, following acute myocardial infarction, congestive heart failure, and mortality. After propensity score matching, there were 663 patients in each group. Compared to that in the control group, the neuroendoscopy and craniotomy groups had a significantly higher risk of secondary vascular events at 1 to 3 months of follow-up (adjusted HR, 2.08 and 1.95; 95% CI, 1.21-3.58 and 1.13-3.35; p < 0.01 and p < 0.05, respectively), but a significantly lower risk after 3 years of follow-up (adjusted HR, 0.52 and 0.52; 95% CI, 0.35-0.78 and 0.35-0.77; p < 0.01 and p < 0.01, respectively). The mortality rate was higher in the craniotomy group at 6 to 12 months of follow-up (adjusted HR, 2.18; 95% CI, 1.06-4.49; p < 0.05) compared to that in the control group. Thus, a timely surgical intervention for hematoma evacuation is advantageous in preventing secondary vascular events and improving outcomes in the long term. However, greater attention to secondary ischemic stroke following the initial sICH episode is needed.

Therapeutic mechanism of combined oral chelation therapy to maximize efficacy of iron removal in transfusion-dependent thalassemia major - a pilot study.

OBJECTIVES: Three iron chelators are used to treat transfusion-dependent beta-thalassemia: desferrioxamine (DFO), deferasirox (DFX), and deferiprone (DFP). Compliance is low for DFO as it cannot be administered orally. Combined administration of DFP and DFX is orally available, however, the therapeutic mechanism is unknown. This pilot study investigated the iron removal mechanisms of DFX and DFP treatment in patients with transfusion-dependent thalassemia major. METHODS: Each patient received three treatments sequentially: (1) DFX monotherapy, (2) DFP monotherapy, and (3) DFX/DFP combination therapy with a four-day washout period between each treatment. Urine and stool specimens were collected to determine the primary outcome of iron excretion volumes. RESULTS: The mean iron excretion was seven times higher after combination therapy with DFX and DFP. Monotherapies also increased excretions volumes, though to a significantly lesser degree. Combined administration of DFX and DFP achieves maximum iron removal in transfusion-dependent thalassemia major compared to monotherapy with either drug. CONCLUSIONS: We suggest combination therapy in chronic severe iron overload cases, especially for patients in poor compliance with DFO/DFP combination therapy or those exhibiting poor iron removal from DFX or DFP monotherapy.

Risk of subsequent stroke, with or without extracranial-intracranial bypass surgery: a nationwide, retrospective, population-based study.

OBJECTIVEAlthough no benefits of extracranial-intracranial (EC-IC) bypass surgery in preventing secondary stroke have been identified previously, the outcomes of initial symptomatic ischemic stroke and stenosis and/or occlusion among the Asian population in patients with or without bypass intervention have yet to be discussed. The authors aimed to evaluate the subsequent risk of secondary vascular disease and cardiac events in patients with and without a history of this intervention.METHODSThis retrospective nationwide population-based Taiwanese registry study included 205,991 patients with initial symptomatic ischemic stroke and stenosis and/or occlusion, with imaging data obtained between 2001 and 2010. Patients who underwent EC-IC bypass (bypass group) were compared with those who had not undergone EC-IC bypass, carotid artery stenting, or carotid artery endarterectomy (nonbypass group). Patients with any previous diagnosis of ischemic or hemorrhagic stroke, moyamoya disease, cancer, or trauma were all excluded.RESULTSThe risk of subsequent ischemic stroke events decreased by 41% in the bypass group (adjusted hazard ratio [HR] 0.59, 95% CI 0.46-0.76, p < 0.001) compared with the nonbypass group. The risk of subsequent hemorrhagic stroke events increased in the bypass group (adjusted HR 2.47, 95% CI 1.67-3.64, p < 0.001) compared with the nonbypass group.CONCLUSIONSBypass surgery does play an important role in revascularization of the ischemic brain, while also increasing the risk of hemorrhage in the early postoperative period. This study highlights the fact that the high risk of bypass surgery obscures the true benefit of revascularization of the ischemic brain and also emphasizes the importance of developing improved surgical technique to treat these high-risk patients.

Inhibition of astrocytic activity alleviates sequela in acute stages of intracerebral hemorrhage.

Neurological deterioration of intracerebral hemorrhage (ICH) mostly occurs within the first 24 hours. Together with the microglia/macrophages (MMΦ), astrocytes are important cell population responsible for many brain injuries but rarely being highlighted in acute stage of ICH. In present study, we induced rats ICH either by collagenase or autologous blood injection. Experimental groups were classified as vehicle or Ethyl-1-(4-(2,3,3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (Pyr3) treatment group (n = 9, each group). MRI assessments after ICH were used to evaluate the hematoma progression and blood-brain barrier (BBB) integrity. The glia cells accumulations were examined by GFAP and Iba1 immunohistochemistry, respectively. Abundant astrocytes but few MMΦ were observed in hyperacute and acute ICH. Upon suppression of astrocyte activity, ICH rats exhibited decreased size of hematoma expansion, less BBB destruction, reduced astrocyte accumulation in perihematomal regions, postponed course of hemoresolution and gain better outcomes. These finding provide evidence that activated astrocytes are crucial cell populations in hyperacute and acute ICH, and their modulation may offer opportunities for novel therapy and patient management.

PG2 for patients with acute spontaneous intracerebral hemorrhage: a double-blind, randomized, placebo-controlled study.

PG2 is an infusible polysaccharide extracted from Astragalus membranaceus, which is a Chinese herb traditionally used for stroke treatment. We investigated the effect of PG2 on patients with spontaneous acute intracerebral hemorrhage (ICH). A total of 61 patients with acute spontaneous ICH were randomized to either the treatment group (TG, 30 patients), which received 3 doses of PG2 (500 mg, IV) per week for 2 weeks, or the control group (CG, 31 patients), which received PG2 placebo. At 84 days after PG2 administration, the percentage of patients with a good Glasgow outcome scale (GOS 4-5) score in the TG was similar to that in the CG (69.0% vs. 48.4%; p = 0.2). The percentage of good mRS scores (0-2) in the TG was similar to that in the CG (62.1% vs. 45.2%; p = 0.3). In addition, no significant differences were seen when comparing differences in the C-reactive protein, erythrocyte sedimentation rate, interleukin-6 (IL-6), IL-1ß, tumor necrosis factor-α, and S100B levels between baseline and days 4, 7, and 14 after PG2 administration (all p > 0.05). The results are preliminary, necessitating a more thorough assessment.

Wiskott-Aldrich syndrome with IgA nephropathy: a case report and literature review.

The pathogenesis of renal involvement in Wiskott-Aldrich syndrome (WAS) is unclear and renal outcome is generally poor in such situations. Here we present the case of an 8-year-old boy with WAS who developed hematuria, proteinuria, and declining renal function that did not improve with the combined use of immunosuppressive agents and angiotensin-converting-enzyme inhibitor. Renal pathology revealed IgA nephropathy (IgAN). The patient underwent splenectomy for refractory thrombocytopenia. The proteinuria remitted and renal function improved after splenectomy, long-term antibiotic prophylaxis, and tapering of immunosuppressive agents.