scholarly journals Plasma pNfH differentiate SBMA from ALS

2019 ◽  
Author(s):  
Vittoria Lombardi ◽  
Bombaci Alessandro ◽  
Luca Zampedri ◽  
Ching-Hua Lu ◽  
Bilal Malik ◽  
...  

AbstractBackground and aim:Spinal bulbar muscular atrophy (SBMA) is a progressive adult-onset X-linked neuromuscular disease. Although traditionally considered a motor neuron disorder, recent advances have highlighted a primary myopathic component. We evaluated levels of phosphorylated neurofilament heavy chain (pNfH), a known biomarker for neurodegeneration, in SBMA.Materials and methods:We collected plasma and serum from 46 SBMA, 50 ALS and 50 healthy control cases, alongside with plasma from a mouse model of SBMA (AR100) and littermate controls. We measured pNfH plasma levels using Single molecule array (Simoa), we assessed functional scales and we gathered demographic data. We analysed data using Mann-Whitney U test, Kruskal-Wallis test and Cox regression analysis.Results:Plasma pNfH levels were significantly increased in ALS, but, intriguingly, there was no change in SBMA. These results were also confirmed in SBMA mice. The ROC curve highlighted that pNfH levels can effectively distinguish between ALS and SBMA (AUC 0.95).Conclusions:Unexpectedly, levels of pNfH are normal in SBMA, whilst they are increased in ALS, and suggest pNfH could serve as a biomarker to differentiate the two diseases. Further, this finding is in agreement with recent evidence showing that primary muscle damage is a crucial feature in SBMA.

2020 ◽  
Vol 86 (2) ◽  
pp. 127-133
Author(s):  
Shengxiang Chen ◽  
Wenfeng Tang ◽  
Randong Yang ◽  
Xiaoxiao Hu ◽  
Zhongrong Li

Adrenal neuroblastoma (NB) is a relatively common malignancy in children. The Surveillance, Epidemiology, and End Results database was used to present demographic data and a survival analysis with the aim of making tumor management better. The Surveillance, Epidemiology, and End Results database was used to search pediatric patients (age £16 years) with NB from 2004 to 2013. The Kaplan-Meier method was used to calculate the overall survival. And, we used Cox regression analysis to determine hazard ratios for prognostic variables. Independent prognostic factors were selected into the nomogram to predict individual's three-, five-, and seven-year overall survival. The study included a total of 1870 pediatric patients with NB in our cohort. Overall, three-, five-, and seven-year survival rates for adrenal NB were 0.777, 0.701, and 0.665, respectively, whereas the rates for nonadrenal NB were 0.891, 0.859, and 0.832, respectively. The multivariate analysis identified age >1 year, no complete resection (CR)/CR, radiation, and regional/distant metastasis as independent predictors of mortality for adrenal NB. Concordance index of the nomogram was 0.665 (95% confidence interval, 0.627–0.703). Pediatric patients with adrenal NB have significantly worse survival than those with nonadrenal NB. Adrenal NB with age <1 year, treated with surgery, no radiation, and localized tumor leads to a better survival. There was no survival difference for patients to receive CR and no CR.


2017 ◽  
Vol 45 (1-3) ◽  
pp. 53-60
Author(s):  
Jing Zhang ◽  
Yiming Li ◽  
Zhiyong Peng

Background: There is controversy about the efficacy and prognostic factors for continuous renal replacement therapy (CRRT) in China due to practice variation. Our aim is to investigate these questions. Method: A total of 613 adult patients receiving CRRT in last 3 years from one Chinese ICU were enrolled. The analysis of demographic data, vital signs, and laboratory tests prior to CRRT and outcomes were performed. The data between pre- and post-CRRT were compared for efficacy analysis. Results: Prior to CRRT, partial pressure of carbon dioxide (PCO2), systolic blood pressure (SBP), gender, age, bilirubin, cystatin C, and mechanical ventilation were correlated with in-hospital mortality. In a binary logistic regression, PCO2, SBP, age, and gender were significant in predicting mortality. Cox regression analysis demonstrated PCO2 independent association with mortality, and lower SBP worse mortality. CRRT could eliminate the fluid and metabolites. Conclusion: CO2 retention and low SBP prior to CRRT were associated with increased mortality. CRRT significantly improved hemeostasis.


2019 ◽  
Vol 19 (1) ◽  
pp. 75-83
Author(s):  
Hairul Izwan Abdul Rahman ◽  
Nor Aida Sanusi ◽  
Muhammad Syafik Ikhwan Salleh ◽  
Ng Yoon Yeen ◽  
Ismail Ali Mohd Jobran ◽  
...  

In 2005, Ministry of Health introduced the Needle Syringe Exchange Program (NSEP) and Methadone Maintenance Therapy (MMT) program as a part of Harm Reduction program to combat HIV infection in Malaysia among people who inject drug (PWIDs). Expenditures were estimated approximately RM10 millions per year to establish and sustain the NSEP and MMT centres. This study examined the impact of MMT program on preventing HIV seroconversion among registered MMT clients that are people who inject drug (PWIDs), and to identify other predictors of HIV seroconversion among this group.  This was a retrospective cohort study done in the state of Perak involving a total of 212 randomly selected MMT clients registered between 2008-2017 in 6 clinics. This study looks at data collected from the last ten-year cohort from baseline to follow-up. A questionnaire was used to obtain socio-demographic data, sexual and drugs abuse history. Test results for HIV were obtained from medical records. Cox regression analysis was performed to examine factors associated with seroconversion and Kaplan-Meier analysis to estimate HIV survival time. This study displayed that both Methadone take home supply (HR 10.4, 95% CI: 1.6 – 68.8) and unprotected sexual practice (HR 5.9, 95%CI: 1.1 – 31.5) shown higher risks of HIV seroconversion compared to DOTS and condom practice among MMT clients respectively. Mean survival for HIV seroconversion among MMT clients was 104.44 (95%CI: 101.85 – 107.04) months.  This study provides reliable evidence that MMT program markedly reduces incidence of HIV infection among people who inject drug (PWIDs).


2019 ◽  
Vol 78 (12) ◽  
pp. 1669-1676 ◽  
Author(s):  
Alexis Mathian ◽  
Suzanne Mouries-Martin ◽  
Karim Dorgham ◽  
Hervé Devilliers ◽  
Hans Yssel ◽  
...  

ObjectivesMaintenance of remission has become central in the management of systemic lupus erythematosus (SLE). The importance of interferon-alpha (IFN-α) in the pathogenesis of SLE notwithstanding, its expression in remission has been poorly studied as yet. To study its expression in remission and its prognostic value in the prediction of a disease relapse, serum IFN-α levels were determined using an ultrasensitive single-molecule array digital immunoassay which enables the measurement of cytokines at physiological concentrations.MethodsA total of 254 SLE patients in remission, according to the Definition of Remission in SLE classification, were included in the study. Serum IFN-α concentrations were determined at baseline and patients were followed up for 1 year. Lupus flares were defined according to the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index Flare Index, whereas the Kaplan-Meier analysis and Cox regression analysis were used to estimate the time to relapse and to identify baseline factors associated with time to relapse, respectively.ResultsOf all patients in remission, 26% displayed abnormally high IFN-α serum levels that were associated with the presence of antibodies specific for ribonucleoprotein (RNP), double stranded (ds)DNA and Ro/SSA60, as well as young age. Importantly, elevated-baseline IFN-α serum levels and remission duration were associated in an independent fashion, with shorter time to relapse, while low serum levels of complement component 3 and anti-dsDNA Abs were not.ConclusionDirect serum IFN-α assessment with highly sensitive digital immunoassay permits clinicians to identify a subgroup of SLE patients, clinically in remission, but at higher risk of relapse.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii137-ii138
Author(s):  
Rusdy Ghazali Malueka ◽  
Henry Sofyan ◽  
Tiara Aninditha ◽  
Rini Andriani

Abstract INTRODUCTION Gliomas are one of the most common central nervous system tumors in adults. The Response Assessment Criteria in Neuro-Oncology (RANO) was developed to standardize the radiographic parameters used to assess therapeutic outcomes in glioma patients. A previous study has shown an association between therapeutic response based on RANO criteria and overall survival in glioma patients. However, the feasibility of applying RANO criteria in settings with limited resources has never been reported. This study aims to assess the feasibility of applying RANO criteria in clinical settings in Indonesia. This study also wants to see the role of the RANO criteria as a prognostic factor for gliomas in Indonesia. METHOD Data of glioma patients were retrospectively collected from Dharmais Cancer Hospital in Jakarta, Indonesia. Dharmais Cancer Hospital is the highest referral hospital for brain tumors in the country. Clinical and demographic data were collected from the medical record. RESULTS From 138 identified glioma patients from 2017 to May 2020, only 34 patients can be assessed using RANO criteria. The majority of the patients do not have post-surgical MRI that can be used as a baseline. Among 34 included patients, 38.2% were categorized as responsive, 23.5% as stable disease and 38.2% were categorized as progressive. Kaplan-Meier analysis showed that the median overall survival in the progressive group is significantly shorter than the median survival of responsive/stable group (21.2 vs. 57.5 months respectively, p=0.001). Multivariate cox regression analysis was performed to see the association of RANO criteria and other confounding variables (sex, age, glioma grade, glioma location, and therapy) with overall survival. The result showed that RANO progression was significantly associated with decreased survival (HR 18.38, p=0.045). CONCLUSION This retrospective analysis demonstrates the feasibility of applying RANO criteria in Indonesia and its association with overall survival.


PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0249590
Author(s):  
Amjad Alharbi ◽  
Haifa Bin Dokhi ◽  
Ghadir Almuhaini ◽  
Futoon Alomran ◽  
Emad Masuadi ◽  
...  

Objectives KRAS, NRAS, and BRAF mutations are commonly present in colorectal cancer (CRC). We estimated the frequency of KRAS, NRAS, and BRAF mutations and assessed their impact on survival and other clinical variables among Saudi patients. Design Retrospective cohort study design. Settings Oncology department of a tertiary hospital in Riyadh, Saudi Arabia. We gathered information from 2016 to 2018. Participants Cohort of 248 CRC patients to assess the demographic data, pathological tumour features, response to treatment modalities, disease progression, and metastasis. Statistical analysis used Correlation analysis using the chi-square test. Survival analysis using a Kaplan Meier method. Cox regression analysis to calculate the hazard ratios. Results Demographic data revealed that 84% of patients were diagnosed with CRC above the age of 50 years. Only 27% of patients presented with distant metastasis. KRAS mutations were the most prevalent (49.6%), followed by NRAS mutations (2%) and BRAF mutations (0.4%). Wild type tumours were found among 44.4% of patients. KRAS mutation showed no significant correlation with the site, type, pathological grade, and stage of the tumour. The mean survival time was shorter among patients with KRAS mutations than among patients with wild type KRAS tumours (54.46 vs. 58.02 months). Adjusted analysis showed that the survival time was significantly affected by patients’ age at diagnosis (P = 0.04). Male patients had an increased risk of mortality by 77% (hazard ratio: 1.77). Conclusions Saudi CRC patients had a high frequency of KRAS mutations and a low frequency of BRAF mutations. The KRAS mutation status did not affect the patients’ survival.


Author(s):  
Qi Yan ◽  
Peiyuan Zuo ◽  
Ling Cheng ◽  
Yuanyuan Li ◽  
Kaixin Song ◽  
...  

Abstract Background The epidemic of COVID-19 presents a special threat to older adults. However, information on kidney damage in older patients with COVID-19 is limited. Acute kidney injury (AKI) is common in hospitalized adults and associated with poor prognosis. We sought to explore the association between AKI and mortality in older patients with COVID-19. Methods We conducted a retrospective, observational cohort study in a large tertiary care university hospital in Wuhan, China. All consecutive inpatients older than 65 years with COVID-19 were enrolled in this cohort. Demographic data, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between patients with AKI and without AKI. The association between AKI and mortality was analyzed. Results Of 1764 in-hospital patients, 882 older adult cases were included in this cohort. The median age was 71 years (interquartile range: 68–77), 440 (49.9%) were men. The most presented comorbidity was cardiovascular diseases (58.2%), followed by diabetes (31.4%). Of 882 older patients, 115 (13%) developed AKI and 128 (14.5%) died. Patients with AKI had higher mortality than those without AKI (68 [59.1%] vs 60 [7.8%]; p &lt; .001). Multivariable Cox regression analysis showed that increasing odds of in-hospital mortality are associated with higher interleukin-6 on admission, myocardial injury, and AKI. Conclusions Acute kidney injury is not an uncommon complication in older patients with COVID-19 but is associated with a high risk of death. Physicians should be aware of the risk of AKI in older patients with COVID-19.


2021 ◽  
Vol 37 (3) ◽  
Author(s):  
Laima Alam ◽  
Rao Saad Ali Khan ◽  
Syed Kumail Hasan Kazmi ◽  
Rafi ud Din

Objective: To analyze the management of severe necrotizing pancreatitis in a specialized center of a lower middle-income country, Pakistan using multiple outcome measures. Methods: All the patients in this prospective observational study with severe necrotizing pancreatitis being referred to Pak Emirates Military Hospital from January 2017 to December 2019 were followed over the course of their admission. Demographic data and disease outcomes were duly noted. Cox regression analysis was used to predict fatality outcome. Results: A total of 57 patients with 48 (84.6%) infected necrotizing pancreatitis were managed in our set up. The most common etiology reported was gall-stones (37%) with male preponderance (72%) and a mean age of 50±11.3 years. The most common complications were acute-kidney-injury (63%), splenic-vein-thrombosis (21%) and ascites (21%). Fourteen patients required mechanical-ventilation with a mean duration of 7±1.4 days on respiratory support. Eight (14%) patients required Endoscopic-Ultra-Sound guided drainage and six (10.5%) underwent surgical-necrosectomy depending upon the patients’ condition and collections characteristics. Mortality, as one of the main outcome measures, was reported to be 12.3% and was statistically related to mechanical-ventilation, organ failure and surgical-necrosectomy while 22 (38.6%) patients were discharged on pancreatic enzymes supplements and 7% required insulin. Conclusion: Survival outcomes with acute severe necrotizing pancreatitis are improving in a dedicated hepato-biliary unit internationally in lieu with a multidisciplinary team approach. Percutaneous and EUS guided drainage of pancreatic collections have turned out to be an important procedure to manage infected pancreatic necrosis that helps to avoid a morbid procedure in the form of necrosectomy. doi: https://doi.org/10.12669/pjms.37.3.3440 How to cite this:Alam L, Khan RSA, Kazmi SKH, Rafi ud Din. Outcome of patients with acute severe necrotizing pancreatitis in a dedicated hepato-biliary unit of Pakistan. Pak J Med Sci. 2021;37(3):---------.   doi: https://doi.org/10.12669/pjms.37.3.3440 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


2020 ◽  
Vol 30 (6) ◽  
pp. 827-833
Author(s):  
Juha Kauppi ◽  
Sari Atula ◽  
Daniel Strbian ◽  
Eric Robinson ◽  
Hanni Alho ◽  
...  

Abstract OBJECTIVES We investigated long-term symptom control of myasthenia gravis following robotic-assisted thoracic surgery (RATS) versus video-assisted thoracic surgery (VATS) thymectomy in a retrospective single-centre cohort. METHODS From 1999 to 2015, a total of 147 patients underwent thymectomy for myasthenia gravis. Demographic data, medications, operative details, hospital length of stay (LOS), procedure complications and follow-up data were collected by chart review. The Myasthenia Gravis Foundation of America classification was used to evaluate preoperative and postoperative myasthenia gravis status. The primary outcome was complete stable remission (CSR) status. RESULTS Of the 147 patients, 86 (59%) patients underwent VATS thymectomy and 61 (42%) patients underwent RATS thymectomy. There was no operative mortality. The median follow-up was 12 years in the VATS group [interquartile range (IQR) 9–14 years] and 5 years in the RATS group (IQR 3–6 years) (P = 0.001). Two patients in the VATS (2%) and 2 patients (3%) in the RATS group had Clavien–Dindo grade 3 complications. The median LOS was 3 days in the VATS group (IQR 2–4 days) and 2 days in the RATS group (IQR 2–3 days) (P = 0.013). The rate of CSR was 18% (14/65) in the VATS group compared to 26% (16/44) in the RATS group (P = 0.06). Younger age, RATS approach and preoperative medical remission were independently predictive of CSR by Cox regression analysis. CONCLUSIONS Patients who underwent RATS thymectomy and were younger or medically remitted before surgery were more likely to achieve CSR. Both methods yield excellent perioperative outcome.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 153-153
Author(s):  
Shalini Moningi ◽  
Jaffer A. Ajani ◽  
Brian D. Badgwell ◽  
Paul F. Mansfield ◽  
Mariela A. Blum Murphy ◽  
...  

153 Background: Two trials are currently investigating preoperative chemoradiation (CRT) for localized gastric adenocarcinoma. However, radiation therapy (RT) can be associated with relatively high rates of acute toxicity. Newer techniques, such as intensity modulated RT (IMRT), could reduce toxicity by reducing radiation dose to normal structures. Our goal was to compare rates of toxicity and toxicity-related events in patients treated with IMRT compared to 3D conformal RT (3DCRT). Methods: The records of 202 gastric cancer patients treated with preoperative intent RT at our institution from 1998-2018 were retrospectively reviewed. Demographic data, treatment details, acute and late toxicities (CTCAE 4.0 criteria), progression and survival data were recorded. Patients who had stage IV disease were excluded. Statistical analysis included descriptive statistics, Cox regression analysis, and Kaplan-Meier survival. Results: 54% were male and the median age was 63. 82 patients received 3DCRT and 120 patients received IMRT (median 45Gy, IQR, 45-45Gy in each group). 78% of patients in the 3DCRT group and 91% of patients in the IMRT group received neoadjuvant chemotherapy prior to RT. 99% of patients received concurrent chemotherapy. The rate of grade 3-4 acute toxicity was significantly lower in patients treated with IMRT compared to 3DCRT (53% vs. 73%, p = 0.004). The composite rate of toxicity-related events (hospitalization, feeding tube, IV rehydration, or RT break) was also significantly lower in patients treated with IMRT compared to 3DCRT (80% vs. 91%, p = 0.031). 72% of patients who received 3DCRT and 68% of patients who received IMRT underwent subsequent surgical resection. The 3-year OS rate was 58.1% for patients receiving IMRT and 60.2% for patients receiving 3DCRT (p = 0.649). The 3-year PFS rate was 47.5% for patients receiving IMRT and 52.7% for patients receiving 3DCRT (p = 0.486). Conclusions: Our study indicates a marked reduction in the rates of grade 3-4 acute toxicity and toxicity-associated events in patients treated with IMRT compared to 3DCRT. These findings suggest that IMRT should be considered as the radiation modality in patients treated with preoperative CRT for gastric cancer.


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