tbuckley/cabot-search huggingface dataset:
Clinical features of patients with megaloblastic anemia diagnosed as diseases of unknown origin at admission
Authors: Chan Meng, Jialin Chen
Journal: BMJ (2016)

Objective
To analyze the clinical features of patients with megaloblastic anemia diagnosed as diseases of unknown origin at admission.


Methods
Seventeen patients admitted during the period of January 2001 to September 2015, who were diagnosed as disease of unknown origin at admission and finally diagnosed as megaloblastic cell anemia, were included in the analysis. The clinical data of patients including age, gender, disease duration, clinical manifestations, laboratory testing, misdiagnosis and treatments were retrospectively analyzed.


Results
Of the 17 patients, 14 were males and 3 were females, the median age is 63 years. The interval from disease onset to consultation was 22 days-60 months with a median time of 7 months. Nine cases had the history of repeated consultations without confirmed diagnoses, 13 cases were misdiagnosed in the first visit or at the admission. Symptoms of neurological(12 cases), digestive(10 cases)and cardiovascular(8 cases)systems were predominant clinical manifestations. The average hemoglobin concentration at admission was (64.9±18.7) g/L, the mean corpuscular volume (MCV) was(112.2±10.5) fl, and 12 cases had pancytopenia. Two cases were diagnosed based on the elevated MCV and hyper-segmented nucleus of neutrophils, respectively. Fifteen patients underwent serum vitamin B12 and folate examination; vitamin B12 levels decreased in all cases, while only 1 had folate under normal range. All 17 patients recovered successfully by vitamin B12 and folate supplement and were doing well during follow-ups.


Conclusions
Megaloblastic anemia is likely to be misdiagnosed, because the clinical manifestations are usually not specific. It is necessary to raise the awareness of the disease for early diagnosis and treatment.


Key words: 
Anemia, megaloblastic; Diagnosis; Vitamin B12
Salvage chemotherapy in the treatment of metastatic melanoma after progression on immunotherapy.
Authors: Payal Shah, Patrick Boland, Anna C. Pavlick
Journal: Journal of Clinical Oncology (2020)

e22019 Background: Immune-checkpoint inhibitors (ICI) have dramatically altered the prognosis of metastatic melanoma (MM); however, fifty percent of patients will not respond to ICI. For these patients, the next choice of treatment includes targeted therapy or a clinical trial if eligible. If these treatment choices have already been utilized or are not available to the patient, there may be value in attempting a course of salvage chemotherapy (CTX). Limited clinical trial evidence has demonstrated unexpected efficacy of CTX after prior progression on ipilimumab, offering higher disease control rates than expected from what is seen in first-line chemotherapy. The phenomenon of a “priming” effect of ICI on CTX efficacy has been shown in patients of various solid tumors after progression on anti-PD1/PD-L1 therapy. The purpose of this retrospective analysis is to evaluate the efficacy of salvage CTX after prior ICI therapy for patients with MM. Patients with ocular melanoma were excluded, as this tumor subtype is known to have reduced response to immunotherapy. Methods: By retrospective analysis, patients were included under an IRB approved waiver of consent. We identified patients with MM treated with ICI therapy between Jan, 2011 and July, 2019 who were subsequently treated with salvage CTX as a result of progression of disease (POD). Salvage CTX included dacarbazine, carboplatin, temozolomide, paclitaxel, or a combination. We assessed response rate, duration of response, and time to progression (TTP) from the onset of salvage CTX. Results: A total of 22 patients who satisfied the above criteria were identified. The majority of this population had a course of single agent ICI as well as a course of combination ICI prior to salvage CTX (72.7%, n = 16/22). 13 (59.1%) patients had POD on salvage CTX with a median TTP of 10.9 weeks. 9 (40.9%) patients responded to salvage CTX. 3 (13.6%) patients achieved a complete response, 4 (18.2%) patients achieved a partial response and 2 (9.1%) patients achieved stable disease. Mean durability of response was 53.6 weeks, ranging from 7-194 weeks. Conclusions: ICI “priming” prior to salvage CTX efficacy may improve disease responsiveness to CTX. This sequence of therapy may offer patients another reasonable treatment option. Despite the small sample size of this study, a prospective clinical trial in MM exploring CTX following ICI progression should be considered.
Risk of disease progression (PD) following discontinuation of BRAF±MEK targeted therapies for reasons other than PD in patients (pts) with metastatic or unresectable melanoma.
Authors: Francesca Corti, Giovanni Randon, Marta Bini, Alessandra Raimondi, Sara Manglaviti, Emma Zattarin, Ilaria Bisogno, Irene Vetrano, Carolina Cimminiello, Filippo G. De Braud, Michele Del Vecchio, Lorenza Di Guardo
Journal: Journal of Clinical Oncology (2020)

10053 Background: In pts with metastatic melanoma bearing BRAF V600E/K mutations BRAF V600±MEK inhibitors are administered until PD/unacceptable toxicity. In patients achieving durable responses, outcomes following discontinuation for reasons other than PD are largely unknown. Methods: We identified all patients who interrupted BRAF±MEK inhibitors for reasons other than PD after complete (CR) or partial response (PR) from a clinical dataset of patients with BRAF mutated metastatic/unresectable melanoma treated with targeted therapy at a single Institution. Results: We included 24 pts. Fifteen (62.5%) and 9 (37.5%) pts were treated respectively with BRAF inhibitor monotherapy and BRAF+MEK inhibitor combination. All pts had normal baseline LDH and ECOG PS0, 2 (8%) pts had brain metastases and 15 (62.5%) had multi-organ metastatic involvement. Dose reduction was required for 12 (50%) pts. Median treatment duration was 59 (12-88) months. Causes of discontinuation were unacceptable toxicity (19 pts-79%) and consent withdrawal (5 pts-21%). At the time of discontinuation, 17 (71%) and 7 (29%) pts had achieved respectively CR and PR. At a median follow up of 31 (8-59) months after treatment discontinuation, 9 (37.5%) pts had experienced PD. Median time to PD after treatment discontinuation was 9 (3-16) months. At time of PD, 2 (22%) pts displayed involvement of new organ sites. Risk of PD following discontinuation was respectively 31% and 45% at 12 and 24 months. Neither baseline characteristics nor treatment duration and time to best response influenced risk of PD; we found a non-significant trend towards higher risk of relapse for patients interrupting treatment with residual disease compared to those who interrupted treatment after achieving CR [HR 3.3; 95%CI (0.8–14.1); log-rank p = 0.081]. After PD, 6 pts received BRAF+MEK inhibitors with a response rate of 100% and 3/6 pts achieving CR. Conclusions: In a subset of patients with favorable prognostic characteristics and retained sensitivity to BRAF±MEK inhibitors, treatment discontinuation was associated with relevant risk of relapse with about one third of pts experiencing PD within one year. Biomarker studies are needed to identify pts who might safely discontinue therapy due to sustained toxicity, especially after achieving CR.
Clinical and genomic analysis of non-small cell lung cancer (NSCLC) patients with MET exon14 skipping (METex14) mutations and responses to anti-MET therapy.
Authors: Andrew McKenzie, Arielle Fisher, Mick Correll, Carissa Jones, Jessica Correia, James Thurber, Amanda Misch, Jessica Heritage, Emma Sturgill, Suzanne Fields Jones, Melissa Lynne Johnson, David R. Spigel
Journal: Journal of Clinical Oncology (2020)

9613 Background: MET is a validated oncogene for molecular targeted therapy in non-small-cell lung cancer (NSCLC), and METex14 mutations result in MET overexpression. Studies with MET-targeting therapies have demonstrated high objective response rates and prolonged disease control. There are few clinical and genomic analyses of patients with METex14-positive NSCLC in the community setting. We herein characterize key clinical and genomic findings for patients harboring METex14 mutations. Methods: Sarah Cannon provides clinical research to partnering medical oncology practices who order broad-based NGS, from both tissue and blood, as a part of standard of care. Genospace, a clinico-genomic software tool, was used for identification of patients for clinical trials and analysis of clinical and genomic data. Results: Of 6521 lung cancer patients with NGS results, 66 (1.01%) harbored METex14 mutations (45.5% from blood and 54.5% from in tissue). The mean age at diagnosis was 75.7 and 21.2% developed brain metastases. Of the 66 patients with METex14 mutations, 69.5% are current/former smokers. Nineteen percent of former/current smokers and 7.6% of never smokers had PD-L1 scores of &gt; 50%, respectively. The majority of METex14-positive patients either received standard of care (66.7%) or were unable to take (19.7%) 1 st -line therapy. Patients who received chemotherapy (Chemo), immunotherapy (IO), and Chemo/IO in the first and second line settings responded to SOC treatment, and patients receiving anti-MET therapy benefited from therapy even after front-line SOC (table). Genomic analysis revealed the most common co-occurring mutations to be EGFR, MET, NF1, KRAS, and BRCA2 (Freq = 8.7%, 8.7%, 8.7%, and 7.6%, respectively). Conclusions: Genospace enables real-time patient identification of METex14-positive NSCLC cases and analysis of these cases indicates that anti-MET therapy may be effective at any line of treatment. Genospace’s clinico-genomic database was used to analyze treatment history, clinical correlates, and co-occurring mutations that may reveal novel treatment combination strategies or resistance mechanisms. [Table: see text]
Effects of nutritional risks on clinical outcomes in chronic kidney disease patients
Authors: Yi-qing Zhu, Yong-mei Shi, Hong Ren
Journal: BMJ (2013)

To explore the effects of nutritional risks on clinical outcomes [length of stay (LOS), hospitalization expense & mortality] in chronic kidney disease (CKD) patients. A total of 127 CKD patients completed the screening of nutritional risks by Nutritional Risk Screening 2002 (NRS-2002) within 24-48 hours of admission. The data of nutritional supports within 2 weeks of admission, LOS, hospitalization expense and mortality were collected. ① Among them, the prevalence of nutritional risks was 18.1%. And the values were 8.2%, 9.4% and 44.1% in early, middle and advanced CKD groups respectively; ② LOS and hospitalization expense in nutritional risk group were significantly more than the non-nutritional risk group (12.5 d vs. 5.2 d, P=0.00; 11 806 vs. 5311 yuan, P=0.00). There was a positive correlation between NRS score and LOS or hospitalization expense; ③ The nutritional support rate of nutritional risk group was only 17.4%. The progression of CKD increased the nutritional risks leading to greater LOS and hospitalization expense. We should pay more attention to the nutritional risk screening and nutritional intervention in moderate-advanced CKD patients.


Key words: 
Renal insufficiency; Malnutrition
Toxicity and tolerance profile of ANTI-EGFRS in metastatic colorectal cancer RAS wild type from the east of Algeria.
Authors: Ammari Abdelaziz, Linda Djebnoune, Besma Khater, Aicha Benmansour, Assia Bensalem
Journal: Journal of Clinical Oncology (2020)

e16032 Background: The results of the different studies showed that the use of anti-EGFRs (Epidermal Growth Factor Receptor) in the management of mCRCs, confront the healthcare team to a new toxicity which until then, were unknown before the era of anti EGFRs. knowing that there were no Algerian patients in these studies, reason for us to do this work. Methods: Between October 2015 and October 2018, our work consists of an epidemiological, observational, descriptive, longitudinal prospective study, including all patients with metastatic colorectal cancer RAS wild type, receiving specific medical treatment with anti EGFR (Panitumumab or Cetuximab) from Medical Oncology Department of Didouche Mourad Hospital of Constantine and the Medical Oncology Department of Batna’s Anti Cancer Center, performance status 0-2, and age 18-75 years. We have completed this work whose main objective is to evaluate the toxicity of anti EGFRs in patients with mCRC RAS wild-type from the east of Algeria. Results: 60 patients received an anti EGFR (Panitumumab or Cetuximab), in our study the most common toxicity was folliculitis with an average onset time of 3.36 weeks and a frequency of 83% of grade 2 and 3. Xerosis was observed in 71% of patients. Paronychia was observed in 50% of patients, in addition to the classical toxicities observed with the different chemotherapy regimens used in mCRCs. For secondary objectives, the median progression free survival in our study was 12 months, with a 95% confidence interval [10,787-13,213]. This median progression-free survival is comparable to those reported in the major anti-EGFR trials. Conclusions: Our results suggest that the Algerian patients with metastatic colorectal cancer RAS wild-type have the same profile of toxicity comparing to the results from different international trials studying anti EGFRs.
Clustering of cardiovascular risk factors in patients of premature stable coronary heart disease complicated with nonalcoholic fatty liver
Authors: Zhong Chen, Gen-shan Ma, Yi Feng, Jia-yi Tong, Cheng-xing Shen, Jia-hong Wang, Xiao-li Zhang
Journal: BMJ (2008)

Objective To study the characteristics of clustering of cardiovascular risk factors in patients less than 50 years-old of premature stable coronary heart disease(PSCHD)complicated with nonalcoholic fatty liver(NAFL).Methods One hundred and six patients with documented PSCHD were recruited into this study and their clinical data,including biochemical parameters,high-sensitivity C-reactive protein(hsCRP),white blood cell(WBC)count,ete.,were analyzed based on whether they had NAFL by B-type ultrasound scanning and their homeostasis model assessment ratio(Homa-IR)by the criteria for metabolic syndrome formulated by the International Diabetes Federation.Results Thirty-two (30.1percent)of 106 patients of PSCHD complicated with NAFL,and 74(69.9 percent)without NAFL. As compared to patients without NAFL,patients with NAFL had higher fasting blood glucose(FBS),serum level of insulin(INS),total cholesterol(TC),triglyceride(TG),serum activity of alanine aminotransferase(ALT),hsCRP,WBC count,body mass index(BMI),Homa-IR,and higher proportion of those with abnormal blood glucose,hypertension.metabolic syndrome(MS)and carotid atherosclerosis (CA)(P＜0.05),respectively.Bi-variate correlation analysis revealed that hsCRP positively correlated to BMI,TG,ALT and Homa IR(r=0.420,P=0.000;r=0.200,P=0.040;r=0.218,P=0.048:and r=0.546,P=0.000,respectively)and inversely correlated with serum level of high-density lipoprotein cholesterol(HDL-C)(r=-0.220,P=0.023).WBC count positively correlated with FBS(r=0.211,P=0.030).BMI,hsCRP,ALT,and proportions of hypertension,diabetes,MS,NAFL and CA in patients with Homa-IR above median were significantly higher than those in patients with that below median ( P＜0.05,respectively).Conclusions More risk faetors for chronic inflammatory reaction,cardiovascular disease and insulin resistance were clustered more obviously in patients of PSCHD complicated with NAFL.

Key words: 
Fatty liver;  Coronary disease;  Risk factor
Immunohistochemical biomarker expression in gastro-entero-pancreatic neuroendocrine tumors at ENETS Centre of Excellence, University Hospital Zurich, Switzerland.
Authors: Silvia Duschek, Juliane Friemel, Alessandra Curioni Fontecedro, Alexander Rheinhard Siebenhuener
Journal: Journal of Clinical Oncology (2020)

e15673 Background: Gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) are a heterogeneous tumor entity with respect to biological behaviour and prognosis. Definition of new predictive and prognostic biomarkers as well as new therapy targets are of upmost clinical interest. Methods: At the ENETS CoE Zurich tissue microarray (TMA) blocks were constructed with 147 tissue samples of tumors diagnosed from 2000 to 2017, including primary tumors and metastasis. Tissue microarray sections were immunostained for SOX-9, SOX-10, SSTR-2 +, PDL-1, thyroid transcription factor 1 (TTF1), estrogen receptor-α (ER-α) and -β (ER-β), progesterone receptor (PR), androgen receptor (AR), BRAF and HER2. Results: In total 270 patients were screened between 2000 - 2017 and 92 patient’s material were sufficient for TMA analysis. Subgroup analysis showed 32 pancreatic, 37 ileum, 10 duodenum, 7 appendix, 3 colorectal, 3 gastric and 1 NET of gallbladder. 50% were male, the median age 63.5 years (range 19-88y). AR, ER-β, TTF1, PDL-1 and SOX10 was only present in a small number of NETs. HER2 and BRAF were negative in all samples. We found ER-α expression in 27.2%, 30% were PR positive and 67.4% showed SOX9 expression. Conclusions: We identified a frequent expression of new markers as SOX9, progesterone receptor and estrogen receptor-α in a broad amount of samples and a potential correlation with tumor grade. This finding might implicate a prognostic or predictive value of these markers, as well as it reveals new potential therapy targets for GEP-NETs. Therefore, further analyses are planned.
Effect of group cognitive behavioral therapy on blood glucose levels, anxiety and depression in patients with type 2 diabetes mellitus
Authors: Xiaobo Guan, Zheng Lu, Zhen Guo, Tao Lei, Xueli Sun, Chengge Gao
Journal: BMJ (2015)

Objective
To evaluate the clinical effect of group cognitive behavioral therapy on blood glucose levels, anxiety and depression in patients with type2 diabetes mellitus.


Methods
Ninety three patients with type 2 diabetes mellitus were recruited and randomly divided into intervention group (n=48) and control group (n=45). Both groups received diabetes health education, patients in intervention group received additional group cognitive behavioral therapy. The glucose tolerance, glycosylated hemoglobin A1c were measured; the HAMA(Hamilton Anxiety Scale)scores, HAMD(Hamilton Depression Scale)scores and CSQ (Coping Styles Questionnaire)scores in patients were analyzed before and 6 months after treatment.


Results
After 6-month treatment the fasting blood glucose(6.33 mmol/L vs. 5.94 mmol/L), 1 h postprandial plasma glucose(12.40 mmol/L vs. 11.46 mmol/L), 2 h postprandial plasma glucose (10.24 mmol/L vs. 9.13 mmol/L), A1c(6.31% vs. 6.07%)in intervention group were decreased significantly, compared to baseline values (all P<0.05). The HAMA total score(9.98 vs. 8.14), somatic anxiety (3.98 vs. 3.48), psychic anxiety(6.00 vs. 4.67), HAMD total score(10.74 vs. 6.93), anxiety somatic(5.02 vs. 3.26), block(2.24 vs. 1.38)and sleep disorders(2.40 vs. 1.40)in intervention group were all decreased significantly(P<0.01 or 0.05). There were significant differences in HAMA total score(8.14 vs. 9.15), HAMD total score(6.93 vs. 9.33), anxiety somatic(3.26 vs. 4.38), block(1.38 vs. 1.98)and sleep disorders(1.40 vs. 2.03)between the intervention group and control group(P<0.01 or 0.05). And the negative coping style scores in intervention group was also lower than that of the baseline(26.74 vs..29.43).


Conclusion
The group cognitive behavioral therapy combined with diabetes health education for patients with type 2 diabetes mellitus may improve the glucose metabolism and depression and anxiety status of patients.


Key words: 
Diabetes mellitus, type 2; Anxiety; Depression; Cognitive therapy
Cryptogenic organizing pneumonia: a case report and literature review
Authors: Zhen-shun Cheng, Jiong Yang, Yu-hui Lin, Yan-qing Ye, Bing Liu, Han Zhang
Journal: BMJ (2010)

We reported a case of cryptogenic organizing pneumonia ( COP) who was admitted to the hospital in July 2008 and reviewed the Chinese literature of COP from 2003 to 2008. The most common symptoms of COP are fever, cough and exertional dyspnea. The imaging characteristics of COP are similar to those of pneumonia, therefore is often misdiagnosed as pneumonia with a high misdiagnosis rate. Lung biopsy is the main method for pathological diagnosis; polypoid growth of granulation tissue was noted within respiratory bronchioles, small airways and alveolar spaces.

Key words: 
Pneumonia;  Diagnosis
Utilizing phenotypic characteristics of metastatic brain tumors to predict the probability of circulating tumor DNA detection from cerebrospinal fluid.
Authors: Meichen Li, Delan Li, Xue Hou, Xiangheng Zhang, Na Wang, Jianzhong Liang, Jing Chen, Kaicheng Wang, Fufeng Wang, Yedan Chen, Xian Zhang, Hua Bao, Xue Wu, Xiaonan Wang, Yang Shao, Likun Chen
Journal: Journal of Clinical Oncology (2020)

2507 Background: Brain metastases occur in approximately 20% of tumor patients and is often associated with terminal events and poor prognosis. Cerebrospinal fluid (CSF) can be a promising source for detecting circulating tumor DNA (ctDNA) specific to the central nervous system (CNS) instead of peripheral blood due to the blood-brain barrier. However, CSF’s suboptimal ctDNA detection rate might limit its clinical application. Precise screening of suitable patients is needed to maximize clinical benefit. Methods: We sequenced 425 cancer-relevant genes in CSF and matched extracranial tissue or blood samples obtained from 67 lung cancer patients with brain metastases. The impact of clinical factors, including age, gender, tumor size, number of lesions, and distance of lesions to the ventricle on CSF ctDNA detection was then evaluated by univariate logistic regression. To predict the probability of successful CSF ctDNA detection, best subsets regression was employed for feature selection and cross validation was used for performance assessment to determine the final model. Results: We detected somatic alterations in 39/67 (58%) CSF ctDNA, 57/66 (86%) plasma ctDNA and 45/49 (92%) tissue samples. Mutation detection rate of CSF ctDNA was significantly lower than that from extracranial tissue and plasma (P &lt; 0.001). Univariate analysis revealed significant association (P &lt; 0.05) of high CSF ctDNA detection rate with the following features: (1) intracranial lesion size ( T), (2) shortest distance between the largest lesion and the ventricle ( D top ), and (3) shortest distance between all intracranial lesion and the ventricle ( D all ). We also revealed a trend of higher detection rate in patients with CNS symptoms ( S CNS ). Subsequent best subsets analysis and cross validation suggested best prediction power with lesion size and largest lesion-ventriclar distance (area under curve [AUC], 0.76 [95% CI, 0.71 to 0.85]; accuracy, 0.75 [95% CI, 0.70 to 0.81]). Final probability can then be derived from Logit P = 0.11×T−0.16×D all (AUC, 0.82; sensitivity, 0.91; specificity, 0.74). The detection of CSF ctDNA was significantly improved from 58% to 83% (P = 0.03) based on the model. Conclusions: This study established a regression model to predict the probability of CSF ctDNA that can be useful to facilitate clinical decisions and avoid excessive practice when monitoring tumor evolution in the brain.