tbuckley/cabot-search huggingface dataset:
AB0157 Paraneoplasic hypercalcemia complicating a b cell non-hodgkin lymphoma (nhl)
Authors: E Karoubi Nordon, E Palazzo, SA Rouidi, O Meyer
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Hypercalcemia is an unfrequent manifestation of B cell NHL. We describe a case report of hypercalcemia secondary to PTH-rp production, inaugurating a B-cell NHL. <h3>Objectives</h3> A 77 year old woman was admitted with dorsalgia. Physical examination was negative except neuropsychological hyperexcitability. Biological data rrevealed an increased calcemia (4.2 mmol/l) with decreased phosphoremia (0.45 mmol/l) suggesting a hyperparathyroidism. However, PTH(RIA) was low (3.5 pg/ml, N = 11.0–62.0) and 1.25(oh)2d3 level was in the normal range (40 yg/l, N = 15–80). PTH-rp was moderatly increased (2.1 ymol/l, N &lt; 1.5). Bone marrow aspiration was normal. No sign for osteolysis was present on bone X-ray, CT scan and MRI. The abdominal CT scan and abdominal MRI revealed a retroperitoneal mass. A needle biopsy was diagnostic for NHL B type. LDH were elevated to 3290U/l (n &lt; 470). Other lymphoid tissue involvment was limited to the spleen. IV farmidronate was successfuly adminitred for treatment of hypercalcemia. <h3>Methods</h3> <h3>Results</h3> Malignat hypercalcemia occurs in 14p.cent of leukaemia and lymphoma. Among NHL, T cell lymphoma positive for HTLV-1, are more frequently associated with hypercalcemia mediated by production of 1–25(OH)2D3 or lymphotoxin/OAF. Less than 3p.cent of B cell NHL are associated with a paraneoplasic hypercalcemia. Two hypercalcemic mediators have been caracterised: PTH-rp and/or OAF <h3>Conclusion</h3> Humoral hypercalcemia mediated by PTH-rp is a rare complication of B cell-NHL. Hypophosphatemia with a decreased PTH plasma level must alert for this mechanism. <h3>References</h3> Orcel P. Hypercalcémie des affections malignes, ed. Masson, 1996 Daroszewska A, Bucknall RC, Chu P, Fraser WD. Severe hypercalcemia in B-cell Lymphoma: combined effects of PTH-rp, IL-6 and TNF. Postgrad Med J. 1999 Hanihara T, Takahashi T. PTH-rp associated Hypercalcemia in probable intravascular lymphoma of B-cell type. Am J Hematol. 1996
SuperTAD: robust detection of hierarchical topologically associated domains with optimized structural information
Authors: Yu Wei Zhang, Meng Bo Wang, Shuai Cheng Li
Journal: Genome biology (2021)

Abstract Topologically associating domains (TADs) are the organizational units of chromosome structures. TADs can contain TADs, thus forming a hierarchy. TAD hierarchies can be inferred from Hi-C data through coding trees. However, the current method for computing coding trees is not optimal. In this paper, we propose optimal algorithms for this computation. In comparison with seven state-of-art methods using two public datasets, from GM12878 and IMR90 cells, SuperTAD shows a significant enrichment of structural proteins around detected boundaries and histone modifications within TADs and displays a high consistency between various resolutions of identical Hi-C matrices.
Frequency and distribution of gastrointestinal oncology patient-reported symptomatic adverse events (SAEs) at a comprehensive cancer center.
Authors: Nadine Jackson McCleary, Ellana Haakenstad, Jessica Cleveland, Sunyi Zhang, Michael J. Hassett, Deborah Schrag
Journal: Journal of Clinical Oncology (2021)

463 Background: In clinical trials, the systematic collection of patient (pt) reported outcomes has been shown to improve quality of life &amp; overall survival. To develop predictive care models for symptom management, we explored the frequency &amp; distribution of SAEs reported by pts who reported electronic patient reported outcomes (ePRO) prior to outpatient visits to the Gastrointestinal Cancer Center (GCC) at Dana Farber Cancer Institute (DFCI). Methods: ePRO is a modified NCI Patient Reported Outcomes – Common Terminology Criteria for Adverse Events instrument distributed weekly to GCC pts with a medical/surgical/radiation oncology encounter. Responses are available to the care team in the electronic health record. ePRO consists of presence/frequency/severity/interference of 15 core SAEs (fatigue, insomnia, general pain, decreased appetite, nausea, vomiting, constipation, diarrhea, shortness of breath, numbness and tingling, rash, concentration, fever, anxiety, sadness). Responses are scored 0 to 3 (with 2 and 3 indicating moderate and severe SAEs, respectively). We examined the frequency &amp; distribution of grade 2 and 3 SAEs in ePRO responders by age, gender, race/ethnicity. All pts had gastrointestinal cancer and an outpatient visit for treatment, symptom management, follow-up care. Results: From 9/1/2018 to 8/31/2020, 1912 unique pts responded (response rate 23%). Most respondents were age 50-69 years (58% compared to 15% age &lt;50, 27% age ≥70; range 18-95), male (53%), white (75%). Grade 3 SAE frequencies were pain (12%), fatigue (11%), anxiety/constipation/insomnia/decreased appetite (5%), sadness/numbness and tingling/diarrhea (3%), concentration/shortness of breath (2%), nausea/rash (1%), fever/vomiting (0%). Across pts, fatigue, general pain, insomnia, anxiety were the most common grade 2 and 3 SAEs. Shortness of breath, vomiting, rash, fever were least common (Table). Conclusions: In GCC pts responding to ePRO, the most frequent SAEs were pain, fatigue, insomnia, anxiety. Shortness of breath, nausea, vomiting, diarrhea were less often severe. Pts &lt;50 were more likely to report severe anxiety but there were no other major differences based on age, sex, race/ethnicity. Ongoing efforts will increase pt/provider engagement and develop predictive models &amp; symptom management interventions from ePRO responses. [Table: see text]
Germline testing of patients with personal history of colorectal polyposis by cancer genetics counseling services.
Authors: Gideon T Dosunmu, Cassandra Gurganus, Veena Krishnan, Delmer Alfredo Montoya Motino, Sana Ozair, Leander Grimm, Thuy Phung, Jessa Blount, Cindy Nelson, Jamie Rich, Mohd Khushman
Journal: Journal of Clinical Oncology (2021)

47 Background: National Comprehensive Cancer Network (NCCN) guidelines recommend that individuals with &gt;10 adenomatous polyps, ≥2 hamartomatous polyps, or ≥5 serrated polyps proximal to the sigmoid colon have detailed risk assessment and potential genetic testing to rule out polyposis syndrome. Here, we describe germline testing of patients with a personal history of colorectal polyposis by Cancer Genetics Counseling Services. Methods: This is an IRB-approved retrospective chart-review study. Between 2016 and 2020, 1011 unique genetic counseling visits were conducted. Germline testing was recommended by a certified genetic counselor if medically necessary. All patients with a personal history of colorectal polyposis were identified (N=20) and their germline testing results were summarized. Results: The reasons for referral to the Cancer Genetics Counseling Services were personal history of &gt;10 adenomatous polyps (N=13), personal and family history of colorectal polyposis (N=3), personal history of juvenile colorectal polyps (N=3) or personal history of ≥2 hamartomatous polyps (N=1). The median age is 58 years-old (1-84). Ten (50%) patients were females. Caucasians, African Americans and other ethnic backgrounds represented 80%, 10% and 10% respectively. In our cohort, 6 out of 20 (30%) patients had a pathogenic germline mutation, 5 (25%) patients had variant of unknown significance (VUS) and 9 (45%) patients had negative testing. Among patients with pathogenic germline mutations, 3 patients had a pathogenic APC mutation (APC c.1659G&gt;A, APC c.2802C&gt;A and APC c.1643dupT) and were diagnosed with Familial Adenomatous Polyposis (FAP). One patient had 2 pathogenic MUTYH mutations (MUTYH c.536A&gt;G and MUTYH c.1187G&gt;A) and was diagnosed with One patient had a pathogenic PTEN c.634+5G&gt;A mutation and was diagnosed with PTEN Hamartoma Tumor Syndrome. Among the 3 patients with a personal history of juvenile colorectal polyps, one patient had a CHEK2 c.190G&gt;A mutation while the other two had negative genetic test results. The VUS mutations in our cohort were MRE11A c.826C&gt;T, BLM c.3478T&gt;C, BRCA2 c.2519T&gt;C, CHEK2 p.V395L and CTNNA1 c.392dupT. Conclusions: In our cohort of patients with personal history of colorectal polyposis, the majority of patients (45%) had negative germline testing. An underlying pathogenic germline mutation and VUS were identified in 30% and 25% of the patients, respectively. FAP Syndrome was the most commonly diagnosed hereditary polyposis syndrome with 3 patients found to have APC germline mutations. Other pathogenic mutations were identified in the MUTYH, PTEN and CHEK2 genes. Patients with MUTYH and PTEN mutations were diagnosed with MAP and PTEN Hamartoma Tumor Syndromes respectively.
HP0023 Managing the impact of osteoarthritis among retired professional footballers: an interpretative phenomenological analysis
Authors: AP Turner, JH Barlow
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> It has been argued that retirement from professional sport poses unique psychosocial challenges. These challenges may be exacerbated if retirement is accompanied by long-term health problems. <h3>Objective</h3> The purpose of this study was to explore the experience of living with osteoarthritis (OA) from the perspective of retired professional footballers in the UK. <h3>Methods</h3> Data were gathered via cross-sectionaI unstructured interviews. It is recognised that the "subtleties" and "personal meanings" inherent in chronic illness are best investigated using qualitative methods. Five retired-professional footballers between the ages of 61 and 68 years were interviewed about the changes experienced as a result of their OA and how they managed these changes. Interviews were transcribed verbatim and analysed using Interpretative Phenomenological Analysis (IPA). <h3>Results</h3> Living with OA involved pain, surgery, medication and restricted mobility. Feelings of frustration were often associated with disruption to work, social and leisure activities. Three broad themes emerged which encapsulated respondents' strategies to manage their OA-related problems: comparing self with former self and others; adapting lifestyle and positive reappraisal. <h3>Conclusion</h3> All of the retired footballers used downward social comparison to manage the emotional turmoil associated with OA. For some this entailed comparing themselves with other retired players and served to reinforce feelings that they had nothing serious to complain about. Respondents continued to perform modified exercise and leisure activities, but were mindful of aggravating painful symptoms. Respondents demonstrated a positive attitude towards their condition. This was evident through the use of humour as a strategy for managing their OA.
Is high-dose glucocorticoid beneficial in COVID-19?
Authors: Valliappan Muthu, Inderpaul Singh Sehgal, Kuruswamy Thurai Prasad, Ritesh Agarwal
Journal: European Respiratory Journal (2021)

We read with interest the article by Edalatifard et al . [1], and we congratulate them for performing a randomised controlled trial amidst the ongoing pandemic. We have a few concerns regarding the methods and interpretation of the current study. While the intervention group's mortality is low, the mortality in the control group is disproportionately high for the severity of illness (acute respiratory distress syndrome (ARDS) not present, patients not intubated). The mortality in ARDS due to coronavirus disease 2019 (COVID-19) among mechanically ventilated patients is 50% or less, and it has improved over time from 42% to 25% [2, 3]. The mortality in the current study's control arm (43%) was worse than the mortality in the control arm of the RECOVERY trial (26%) [4]. The survival difference between the two study groups may be due to the better supportive care provided to the intervention arm due to the trial's unblinded nature. Also, the justification provided for the sample size is inadequate. The authors have cited studies using methylprednisolone in asthma, COPD and pre-operative patients as references for the sample size calculation. High-dose glucocorticoids are not currently recommended for treating severe COVID-19 pneumonia <https://bit.ly/39VQ3O8>
Real-world experience with elective discontinuation of PD-1 inhibitors at 1 year in patients with metastatic melanoma
Authors: Rebecca Pokorny, Jordan P McPherson, Benjamin Haaland, Kenneth F Grossmann, Carolyn Luckett, Benjamin Newell Voorhies, Daniel S Sageser, Jocelyn Wallentine, Zachary Tolman, Siwen Hu-Lieskovan, Umang Swami
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Randomized trials evaluating programmed cell death protein 1 (PD-1) inhibitors in metastatic melanoma either permitted treatment for 2 years (pembrolizumab) or more (nivolumab). The optimal duration of therapy is currently unknown due to limited data, and shorter therapies may be effective. Methods Data of patients with metastatic cutaneous melanoma treated with single-agent PD-1 inhibitors at Huntsman Cancer Institute from January 1, 2015, to December 31, 2018, was reviewed to identify a continuous series of patients who made the joint decision with their provider to electively discontinue therapy at 1 year (&gt;6 months and &lt;18 months) in the setting of ongoing treatment response or disease stability. Patients were excluded if they received PD-1 inhibitors with other systemic therapy, had prior exposure to PD-1 therapy, or discontinued treatment due to disease progression or immune-related adverse event. Best objective response (BOR) per RECIST V.1.1 at treatment discontinuation, progression-free survival (PFS), and retreatment characteristics was analyzed. Results Of 480 patients who received PD-1 inhibitors, 52 met the inclusion criteria. The median treatment duration from first to the last dose was 11.1 months (95% CI 10.5 to 11.4). BOR was complete response in 13 (25%), partial response in 28 (53.8%), and stable disease in 11 (21.2%) patients. After a median follow-up of 20.5 months (range 3–49.2) from treatment discontinuation, 39 (75%) patients remained without disease progression, while 13 (25%) had progression (median PFS 3.9 months; range 0.7–30.9). On multivariable analysis, younger age, history of brain metastasis, and higher lactate dehydrogenase at the time of anti-PD-1 discontinuation were associated with recurrence. Patients with recurrent melanoma were managed with localized treatment, anti-PD-1 therapies, and BRAF-MEK inhibitors. All patients except one were alive at data cutoff. Conclusion In this large real-world, observational cohort study, the majority of patients with metastatic melanoma after 1 year of anti-PD-1 therapy remained without progression on long-term follow-up. The risk of disease progression even in patients with residual disease on imaging was low. After prospective validation, elective PD-1 discontinuation at 1 year may reduce financial and immunotherapy-related toxicity without sacrificing outcomes.
High-precision, gelatin-based, hybrid, bilayer scaffolds using melt electro-writing to repair cartilage injury
Authors: Yu Han, Bo Jia, Meifei Lian, Binbin Sun, Qiang Wu, Benlin Sun, Zhiguang Qiao, Kerong Dai
Journal: Bioactive Materials (2021)

Articular cartilage injury is a common disease in the field of orthopedics. Because cartilage has poor self-repairing ability, medical intervention is needed. Using melt electro-writing (MEW) technology, tissue engineering scaffolds with high porosity and high precision can be prepared. However, ordinary materials, especially natural polymer materials, are difficult to print. In this study, gelatin was mixed with poly (lactic-co-glycolic acid) to prepare high-concentration and high-viscosity printer ink, which had good printability and formability. A composite scaffold with full-layer TGF-β1 loading mixed with hydroxyapatite was prepared, and the scaffold was implanted at the cartilage injury site; microfracture surgery was conducted to induce the mesenchyme in the bone marrow. Quality stem cells thereby promoted the repair of damaged cartilage. In summary, this study developed a novel printing method, explored the molding conditions based on MEW printing ink, and constructed a bioactive cartilage repair scaffold. The scaffold can use autologous bone marrow mesenchymal stem cells and induce their differentiation to promote cartilage repair.
Use of loop and clips to prevent migration of esophageal stent
Authors: Vikas Singla, Shivam Khare, Anil Arora, Ashish Kumar, Praveen Sharma, Naresh Bansal, Shrihari Anil Anikhindi
Journal: Endoscopy (2021)

A 25-year-old gentleman presented with dysphagia for solids and liquids. He had a history of accidental ingestion of high-temperature melted iron particles 4 weeks back while working in the iron industry. Upper gastrointestinal endoscopy revealed a stricture with ulceration in the lower esophagus at 35 cm from the incisors ([Fig. 1]). The 9.8-mm diameter endoscope could not be negotiated beyond the stricture site; further examination with a 5.5-mm-diameter endoscope revealed a stricture length of 3 cm and normal gastric mucosa. The patient underwent four sessions of dilatation with Savary-Gilliard dilators up to 15 mm, but the stricture persisted. A fully covered esophageal self-expandable metal stent (18 × 100 mm; Wallflex, Boston Scientific) was deployed as a rescue treatment ([Fig. 2]). In view of the risk of migration, the stent was fixed to the esophageal wall with the help of an endoloop and clips ([Video 1]). A 30-mm endoloop (model no. MAJ-254; Olympus) was grasped with a forceps and partially pulled inside the channel ([Fig. 3]). The endoloop was released near the upper margin of the stent. One end of the loop was fixed with the help of through-the-scope clips (HX-610-090 L, Olympus) to the upper part of the stent ([Fig. 4]). Six clips were applied to fix the endoloop to the esophageal wall.
Thrombolytic therapy and secular trends (1985-1995) in long-term survival following acute myocardial infarction: the Minnesota Heart Survey
Authors: Sue Duval, Eyal Shahar, Paul G McGovern, David R Jacobs, Alan K Berger, Russell V Luepker
Journal: Circulation (2001)

P38 Both short-term and long-term survival of acute myocardial infarction (AMI) patients have improved remarkably during the 1980s and 1990s. We investigated the contribution of greater utilization of thrombolytic therapy to these secular trends, and compared the survival trends among AMI patients who received thrombolytic therapy to survival trends among their counterparts who did not. The sample included 4,515 patients aged 30-74 years (2743 men, 1772 women) who were discharged from Minneapolis-St. Paul hospitals in 1985, 1990, or 1995 and determined to have had a definite AMI by the study criteria. Age-adjusted three-year mortality following hospitalized AMI decreased significantly over that period from 30% in 1985 to 25% in 1990 to 20% in 1995, with no evidence of heterogeneity of the secular trend by gender. The regression-derived hazard ratio of death - adjusted for age, gender, and history of MI - was 0.61 (95% CI: 0.52,0.71) for AMI patients in 1995 as compared with their counterparts in 1985. The frequency of administration of thrombolytic therapy increased dramatically from 1985 to 1990 (13% to 28%) but did not increase further in 1995 (27%). We estimated the contribution of more frequent administration of thrombolytic therapy to the time trend by modeling an indicator variable for thrombolytic therapy use and computing the percentage decrease in the coefficient for the “year effect” (1995 vs 1985). According to this method, only 11% of the secular trend in AMI mortality could be attributed to greater use of thrombolytic therapy. There was no statistical evidence of differential secular trend by thrombolytic therapy status (p=0.57). However, the estimated reduction in three-year mortality (1995 vs 1985) was larger among AMI patients who did not receive thrombolytic therapy treatment (31% to 22%) than among their counterparts who received that therapy (21% to 16%). Although more frequent use of thrombolytic therapy accounted for some of the favorable trend in AMI survival, other components of AMI care and secondary prevention measures appear to have played an important role.
The impact of primary tumor sidedness on survival in early-onset colorectal cancer by stage: A National Veterans Affairs retrospective analysis.
Authors: Ibrahim Azar, Nada Almasalmeh, Saghi Esfandiarifard, Gurjiwan Virk, Wissam Kiwan, Anthony Frank Shields, Syed Arzoo Mehdi, Philip Agop Philip
Journal: Journal of Clinical Oncology (2021)

31 Background: The incidence of early-onset colorectal cancer (EOCRC) is rising. Left-sided colorectal cancer (LCC) is associated with better survival and response to therapy compared to right-sided colon cancer (RCC) in the metastatic setting. Current NCCN guidelines recommend the addition of EGFR inhibitors to KRAS/NRAS wild-type metastatic CRC originating from the left-side only. Whether primary tumor sidedness impacts survival in loco-regional disease and in EOCRC is of clinical interest. Methods: Data from the National VA Cancer Cube Registry was studied. 65,940 cases of CRC were diagnosed between 2001 and 2015. EOCRC (2,096 cases) was defined as CRC diagnosis at age &lt;50 years. ICD codes C18 to C20 were used to delineate patients with RCC vs. LCC. RCC was defined as cancer from the cecum to the hepatic flexure (C18.0-C18.3), LCC from the splenic flexure to the rectum (C18.5-18.CRC; C19 &amp; C20). Transverse cancer (C18.4), overlapping and unidentified sites (C18.8; C18.9) were excluded. Results: EOCRC is more likely to originate from the left-side (66.65% LCC in EOCRC vs. 58.77% in the whole CRC dataset). Overall, LCC has better 5-year OS than RCC in Stage I, III and better 1-year OS in stage IV (Table). Stage II RCC has better 5-year OS than LCC (RC 53.39% vs LC 49.28%). In EOCRC, there is no statistically significant difference between LCC and RCC in Stages I-III. Stage IV EOCRC patients with LCC and RCC have a 1-year OS of 73.23% and 59.84%, respectively. Conclusions: EOCRC is more likely than CRC to originate from the left side. In EORCRC patients, LCC is associated with better OS than RCC only in patients with metastatic disease. In the overall population, LCC is associated with better OS in all states except Stage II. The better prognosis of Stage II RCC might be due to the reported high incidence of MSI-high tumors in this subpopulation. [Table: see text]