tbuckley/cabot-search huggingface dataset:
Mesenchymal stromal (stem) cell therapy modulates miR-193b-5p expression to attenuate sepsis-induced acute lung injury
Authors: Claudia C. dos Santos, Hajera Amatullah, Chirag M. Vaswani, Tatiana Maron-Gutierrez, Michael Kim, Shirley H.J. Mei, Katalin Szaszi, Ana Paula T. Monteiro, Amir K. Varkouhi, Raquel Herreroz, Jose Angel Lorente, James N. Tsoporis, Sahil Gupta, Amin Ektesabi, Nikolaos Kavantzas, Vasileios Salpeas, John C. Marshall, Patricia R.M. Rocco, Philip A. Marsden, Daniel J. Weiss, Duncan J. Stewart, Pingzhao Hu, W. Conrad Liles
Journal: European Respiratory Journal (2021)

Although mesenchymal stromal (stem) cell (MSC) administration attenuates sepsis-induced lung injury in pre-clinical models, the mechanism(s) of action and host immune system contributions to its therapeutic effects remain elusive. We show that treatment with MSCs decreased expression of host-derived microRNA (miR)-193b-5p and increased expression of its target gene, the tight junctional protein occludin (Ocln), in lungs from septic mice. Mutating the Ocln 3' untranslated region miR-193b-5p binding sequence impaired binding to Ocln mRNA. Inhibition of miR-193b-5p in human primary pulmonary microvascular endothelial cells prevents tumour necrosis factor (TNF)-induced decrease in Ocln gene and protein expression and loss of barrier function. MSC-conditioned media mitigated TNF-induced miR-193b-5p upregulation and Ocln downregulation in vitro When administered in vivo, MSC-conditioned media recapitulated the effects of MSC administration on pulmonary miR-193b-5p and Ocln expression. MiR-193b-deficient mice were resistant to pulmonary inflammation and injury induced by lipopolysaccharide (LPS) instillation. Silencing of Ocln in miR-193b-deficient mice partially recovered the susceptibility to LPS-induced lung injury. In vivo inhibition of miR-193b-5p protected mice from endotoxin-induced lung injury. Finally, the clinical significance of these results was supported by the finding of increased miR-193b-5p expression levels in lung autopsy samples from acute respiratory distress syndrome patients who died with diffuse alveolar damage.
SARS-CoV-2 variants in India: a call for genomic surveillance
Authors: Vishal Rao US, Gururaj Arakeri, Rui Amaral Mendes
Journal: BMJ (2021)

Background: Diabetes is rising globally and is the most common cause of both end-stage renal disease and blindness. People on haemodialysis have to attend several dialysis appointments per week which can affect their attendance at diabetic eye screening. In addition, previous literature suggests patients on haemodialysis are more likely to have sight threatening diabetic eye disease. This study aims to determine attendance at the Diabetic Eye Screening Programme in Northern Ireland, diabetic retinopathy severity and use of handheld retinal imaging in people with diabetes attending haemodialysis units in Northern Ireland. Methods: All patients with diabetes attending haemodialysis clinics regionally were screened and graded by the Diabetic Eye Screening Programme in Northern Ireland using a handheld and/or conventional non-mydriatic fundus camera. Results: All eligible 149 people were offered a Diabetic Eye Screening Programme in Northern Ireland appointment, 132 attended, 33.8% of whom have not been seen in &gt;3 years and 15% had never attended Diabetic Eye Screening Programme in Northern Ireland despite multiple previous appointments. Altogether, 12.9% required urgent referral to hospital eye services which is significantly higher than the national average of 0.4%. Conclusions: Those on haemodialysis are at high risk for sight threatening diabetic retinopathy, implementing Diabetic Eye Screening Programme in Northern Ireland in haemodialysis clinics enables timely diagnosis and referral.
Impact of the COVID-19 pandemic on clinical activity during the lockdown in North France: A single center experience.
Authors: Ali Hammoudi, Guillaume Marliot, Margot Cucchi, Naima Mahi, Diane Pannier, Eric Leblanc, Xavier Mirabel, Luc Ceugnart, Yves-Marie Robin, Eric Lartigau, Nicolas Penel
Journal: Journal of Clinical Oncology (2021)

e13594 Background: During the French COVID-19 pandemic, clinical activity for cancer care has declined and modified the management of patients in cancer institute. France has imposed two national lockdowns of the population (from March 17 to May 11 and from October 30 to December 15 2020). We evaluate the impact of the lockdown period in North France on clinical activity. Methods: We measured and compared key-indicators of clinical activity between different periods: 2019 versus 2020; before and during the first and second lockdown. Results are given as percentage of changes with 95% confidence interval (CI). Results: The comparative analysis between 2019 and 2020 showed that most clinical activities except hospitalizations (-0.0% [-0.2; +0.1%] has changed. There was a significant increase in overall treated patients (+0.4% [+0.3; +0.5], telemedicine +99.9% [+99.4; +99.7], MRI (+8.8% [+8.2; +9.5], ambulatory chemotherapy (+3.5% [+3.3; +3.8]), number of chemotherapies prepared (+2.0 [+.1.9; +2.2]) and admission in palliative care unit (+15.3%, [+10.8; +19.8]). On the contrary, a significant decrease in treated patients aged &gt; 65 years old (-6.4% [-6.9; -5.9]), incidence rate (-3.1% [-3.6; -2.7]), multidisciplinary team meeting on patient assessment (-3.1% [-3.5;-2.5]), pathology reports (-2.9% (-3.3;-2.6]), radiotherapy (-4.6% [-4.7;-4.4]) and surgery (-6.7% [-7.4;-5.6]) were observed. In 2020, before and during the first lockdown all key-indicators declined except telemedicine (+40,400%) and admission in palliative care unit (+35.5% [+31.0-+49.7]). During the first lockdown, key-indicators decreased from -63.0% [-70.3-59.2] for outpatient visits to -5.1% [-7.0-3.8] for chemotherapy. The impact caused by the second lockdown was non-significant compared to the first one since all key-indicators has increased during the second lockdown: from +23.8% [+22.2; +25.5] for radiotherapy to +76.6% [+72.5; +79.5] for the management of new cases. Conclusions: Dramatic changes occurred in 2020 during the COVID-19-related lockdown compared to 2019. An Increase in chemotherapy treatment and admission on palliative care unit and a decrease in surgery and radiotherapy strongly suggests that the clinical activity was changed in 2020 compared to 2019. This was in line with the reduction of cancer screening in 2020. The impact of the first lockdown on clinical activities was higher compared to the second one. These observations should be investigated further in order to better understand the effects of a pandemic-related lockdown on cancer care.
Which therapeutic strategy is less cardiotoxic in the treatment of breast cancer: Using paclitaxel before or after doxorubicin?
Authors: Marcelo Dantas Tavares de Melo, André L.C. Almeida, Aluisio Jose de Oliveira Monteiro Neto, Edval Gomes dos Santos Júnior, Israel Costa Reis, Ludmila Mota, Nilson Lima Lopes, Samuel Oliveira De Afonseca, Thyago Monteiro do Espírito Santo
Journal: Journal of Clinical Oncology (2021)

e12617 Background: The combination of doxorubicin (DOX) with paclitaxel (PTX) is effective in the treatment of breast cancer (BC). However, DOX-associated cardiotoxicity (CTX) is aggravated by the use of PTX. There´s no consensus on which sequence is most safe. Methods: Prospective study of women with primary BC. All of participants received four cycles of DOX and 12 infusions of PTX. Participants were divided into two groups, at the discretion of the oncologist: Group 1-PTX before DOX and Group 2-DOX before PTX. CTX was defined as an absolute reduction in left ventricular ejection fraction (LVEF)&gt;10% to a value &lt;53%. Patients underwent clinical evaluation and echocardiography before treatment (phase 1) and one year after treatment (phase 2). Results: Sixty-nine women were evaluated: 19 in G1 and 50 in G2. The groups had similar clinical characteristics. The doses of radiation, DOX and PTX used were similar. Eight (11.6%) patients developed CTX: two (10.5%) in G1 and six (12.0%) in G2 (p=0.62). LVEF was similar between the groups in phase 1 (G1=65.1±3.5; G2=65.2±3.9; p=0.96), with a significant reduction after one year in both groups: G1=61.4±8.1% (p=0.021) and G2=60.8±7.6% (p&lt;0.001). Although lower, LVEF remained similar between groups after phase 2 (p=0.79). Conclusions: In women with BC who underwent chemotherapy, the incidence of CTX at the end of the first year of treatment was similar regardless of whether DOX was used before or after PTX. [Table: see text]
Primary and secondary resistance mechanisms in first, second and third generation tyrosine kinase inhibitors in EGFR mutant non-small cell lung cancer patients.
Authors: Moushumi Suryavanshi, Sakshi Mattoo, Sanjeev Kumar Sharma, Anurag Mehta, Ullas Batra
Journal: Journal of Clinical Oncology (2021)

e21142 Background: Different molecular mechanisms of on target and off target primary and secondary resistance have been observed in EGFR mutant NSCLC patients after first(1st), second(2nd) and third (3rd) generation of tyrosine kinase inhibitors(TKIs). Next generation sequencing(NGS) offers a comprehensive method of detecting these mechanisms to decide next line of treatment. Methods: We retrospectively analyzed 430 samples of NSCLC for primary and secondary resistance to 1st, 2nd and 3rd TKIs. NGS was performed using thermofischer Ion Torrent Oncomine Focus 52 gene Assay. These cases were divided into 4 groups.1)Primary resistance to first and second generation TKIs 2)Primary resistance to 3rd generation TKI 3)Secondary resistance to 1st and 2nd generation TKI 4) Secondary resistance to 3rd generation TKI.Last group was further subgrouped into A when 3rd generation TKI was offered as second line after 1st or 2nd generation TKIs on detection of T790M and subgroup B when it was given as first line. Results: Group1 had 13 cases. There were 2 cases of complex EGFR exon 19 mutation p.Glu746_Leu747delinsValPro, 4 cases of EGFR exon 20 insertion, 1 case of dual EGFR L833V &amp; H835L mutation, 2 cases with EGFR amplification with EGFR exon 19 del and PIK3CA C420_P421del along with EGFR exon 19 del. Four cases had no additional abnormality. Group 2 had 5 cases:1 case had L858R and E709A dual mutation, 2 cases had KRAS G13C and KRAS G12V along with EGFR exon 19 del. One case had EGFR amplification and one case had MET amplification along with EGFR exon 19 del respectively.Group 3 had 34 cases including 10 cases of EGFR L858R and 24 cases of exon 19 deletion.T790M mutation was detected in 8 patients, MET amplification in 7 cases,one case had both T790M and MET amplification. One case lost the primary EGFR exon 19 del. Others mutations detected were KRAS G13C, PIK3CA H1047R, TP53 R213Q and TP53 C242fs. Group3 had 15 cases with 7 cases in subgroup A and 9 cases in subgroup B. In subgroup A T790M mutation was lost in 6 out of 7 cases.One case which lost T790M developed ALK translocation.One case of EGFR exon 19 del retained EGFR T790M with EGFR C797S in cis allele. Other mutations detected were PIK3CA E542K and KRAS G12C. In subgroup B one case showed EGFR C797S(both cis and trans) besides the primary EGFR exon 19 del. One case showed BRAF G469A along with EGFR exon 19 del. Other mutations detected were CTNNB1 D32N, KRAS G12V, and PIK3CA E542K. Conclusions: Primary and secondary acquired resistance is unavoidable in EGFR mutant advanced NSCLC on any generation of TKIs. NGS offers an advantage in diagnosing mechanism of resistance for further choice of therapy.
Concrete case: An opportunity to improve cervical cancer prevention—Primary and secondary prevention of cervical cancer in patients with cervical cancer and their families.
Authors: Jurema Telles O Lima, Carla Rameri Alexandre Silva De Azevedo, Candice Lima Lima, Leticia Katz, Mozart j t Sales, Rodrigo alves Pinto, Gabriela Arruda de Andrade, Fernanda Araújo Keller, Paula Marina Carneiro Santos, Igor Gouveia Soares, Beatriz Vieira Moura, Ana Luísa Lopes Marques Coutinho, Maria Julia Gonçalves Mello
Journal: Journal of Clinical Oncology (2021)

e18571 Background: cervical cancer (CC) reveals regional and social inequalities and should be understood not only as an oncological indicator, but essentially as an indicator of social vulnerability and health care needs.CC is the second most incident and the most deadly among women from the Northeast’S Brazil and the third most incident in Brazil Although the HPV vaccine coverage and the Pap smear test are available through the Brazilian public health system, the coverage of the target population is low. objective: Verify the conditions of access/use of the health system by women with cervical cancer (CC) and their families. Methods: Cross-sectional study involving cancer patients admitted to IMIP between 2016 and 2019. The variable data were related to the sociodemographic profile, preventive examination, Human Papillomavirus (HPV) and the influence of the diagnosis of CC on the search for preventive and screening measures by women's family members. Results: Out of the 285 participants,between 9-21 years old and 101 between 25-69 years old. Of the patients studied,55,8% lives urban area. It has a higher performance of biopsies in the public sector (59,5%). The sociodemographic analysis highlights the non-white race (78,2%) and only 6,8% with complete high school. The knowledge about performing the Pap smear reached 88,9% and the disinformation about the HPV reached 44,4%.the school was the largest source of information about the HPV vaccine (30,6%). Related to the influence of cancer, 62,2% said that young family members underwent HPV vaccination and 82,2% related their diagnosis to search for preventive in family members over 25 years old. a much higher percentage than vaccination coverage and preventive exam in the study region report that the diagnosis of cancer influenced the decision to vaccinate (42%) and update the pap test (69%). about 30% of patients had never taken the pap test. the early start (15 - 19y) of the pap test was not significant for the periodic performance of the pap test. 46% reported the lack of information about the importance of the exam as a reason for not performing it and 34% reported fear. conclusion :Strengthening educational activities and offering vaccines against HPV and Pap smears in the diagnosis of a case of cervical cancer can be an opportunity to expand the coverage of preventive measures more effectively among people close to the patient and her community, which cannot be missed. The school was an important source of information about the HPV vaccine and should be directly involved in this fight.Reducing an inequality cycle.
広島市民病院循環器科における下肢閉塞性動脈硬化症(PAD)に対するPTAの成績
Authors: 青景聡之, 井上一郎, 河越卓司, 石原正治, 嶋谷祐二, 栗栖智, 中間泰晴, 大河啓介, 丸橋達也, 香川英介, 臺和興
Journal: Circulation (2007)
Overweight or obese patients may take longer to respond and be less responsive to immune checkpoint inhibitors in non-small cell lung cancer: A retrospective review.
Authors: John P. Palmer, Yenong Cao, Samer Ibrahim, Natasha Dhawan, Muhammad Zubair Afzal, Keisuke Shirai
Journal: Journal of Clinical Oncology (2021)

e21209 Background: Immune checkpoint inhibitors (ICI) are now the standard of care in the treatment of non-small cell lung cancer (NSCLC). ICIs may be used as monotherapy or in combination with chemotherapy. Increased recruitment of inflammatory cells in the tumor micro-environment is associated with a poor response to ICIs. Although obesity is a risk factor for many types of cancers, including lung cancer, it is associated with a low systemic inflammation state. This creates an effect known as the “obesity paradox,” resulting in better treatment-related outcomes in overweight and obese patients receiving ICIs. However, in obese patients, the neutralizing interleukin (IL) - 1β level is high, which can decrease the responsiveness to ICI. We aim to study the effect of increased weight on treatment-related outcomes in NSCLC patients receiving ICI. Methods: We conducted a retrospective analysis on 178 NSCLC patients treated with ICIs, such as pembrolizumab, nivolumab, ipilimumab/nivolumab or atezolizumab, alone or in combination with chemotherapy. Overweight was defined as having a BMI of 25 – 29.9 while obesity was defined as having a BMI of ≥ 30. Overall survival (OS), progression free survival (PFS), best radiographic response, and the time to achieve radiographic response were evaluated. Cox regression univariate and multivariate analyses were performed. Logistic regression and Chi-square tests were applied. Results: Of the 178 patients with NSCLC, 81% had adenocarcinoma, and 19% had squamous, adenosquamous, or large cell carcinoma. The majority of patients were female (56.2% vs. 43.8%). Overall, 48.6% patients were overweight or obese. The objective response rate (ORR) was 45.1% and the disease control rate (DCR) was 75.8%. The ORR was 37% in overweight/obese patients compared to 52% in patients with a normal weight (p = 0.06). The DCR was 76% vs. 73.9%, (p = 0.7). The median time to achieve the best radiographic response was 3.7 months in overweight/obese patients compared to 2.5 months in those of normal weight (p = 0.2). A considerably higher proportion of the patients progressed in overweight/obese category (80.7% vs. 69.3%, P = 0.08). However, there was no significant difference in median PFS between the two categories (7.4 vs. 8.1 months, P = 0.2). The overall survival was not significant different between both categories (15.9 vs. 16.8 months, P = 0.5). Conclusions: Our study suggests that obesity and overweight status can result in a low response rate to ICIs in NSCLC patients and can delay the time to achieve the best radiographic response per RECIST criteria. However, we did not observe any significant impact on the overall or progression-free survival. A large, population-based study will help to elucidate the impact of weight on the responsiveness to ICI.
Association Between Childhood Consumption of Ultraprocessed Food and Adiposity Trajectories in the Avon Longitudinal Study of Parents and Children Birth Cohort
Authors: Kiara Chang, Neha Khandpur, Daniela Neri, Mathilde Touvier, Inge Huybrechts, Christopher Millett, Eszter P. Vamos
Journal: JAMA Pediatrics (2021)

<h3>Importance</h3> Reports of associations between higher consumption of ultraprocessed foods (UPF) and elevated risks of obesity, noncommunicable diseases, and mortality in adults are increasing. However, associations of UPF consumption with long-term adiposity trajectories have never been investigated in children. <h3>Objective</h3> To assess longitudinal associations between UPF consumption and adiposity trajectories from childhood to early adulthood. <h3>Design, Setting, and Participants</h3> This prospective birth cohort study included children who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC) in Avon County, southwest England. Children were followed up from 7 to 24 years of age during the study period from September 1, 1998, to October 31, 2017. Data were analyzed from March 1, 2020, to January 31, 2021. <h3>Exposures</h3> Baseline dietary intake data were collected using 3-day food diaries. Consumption of UPF (applying the NOVA food classification system) was computed as a percentage of weight contribution in the total daily food intake for each participant and categorized into quintiles. <h3>Main Outcomes and Measures</h3> Repeated recordings of objectively assessed anthropometrics (body mass index [BMI; calculated as weight in kilograms divided by height in meters squared], weight, and waist circumference) and dual-energy x-ray absorptiometry measurements (fat and lean mass indexes [calculated as fat and lean mass, respectively, divided by height in meters squared] and body fat percentage). Associations were evaluated using linear growth curve models and were adjusted for study covariates. <h3>Results</h3> A total of 9025 children (4481 [49.7%] female and 4544 [50.3%] male) were followed up for a median of 10.2 (interquartile range, 5.2-16.4) years. The mean (SD) UPF consumption at baseline was 23.2% (5.0%) in quintile 1, 34.7% (2.5%) in quintile 2, 43.4% (2.5%) in quintile 3, 52.7% (2.8%) in quintile 4, and 67.8% (8.1%) in quintile 5. Among those in the highest quintile of UPF consumption compared with their lowest quintile counterpart, trajectories of BMI increased by an additional 0.06 (95% CI, 0.04-0.08) per year; fat mass index, by an additional 0.03 (95% CI, 0.01-0.05) per year; weight, by an additional 0.20 (95% CI, 0.11-0.28) kg per year; and waist circumference, by an additional 0.17 (95% CI, 0.11-0.22) cm per year. <h3>Conclusions and Relevance</h3> These findings suggest that higher UPF consumption is associated with greater increases in adiposity from childhood to early adulthood. Robust public health measures that promote minimally processed foods and discourage UPF consumption among children are urgently needed to reduce obesity in England and globally.
Artificial intelligence (AI) comparison of social media-based patient-reported outcomes of PD-1, BRAF, and CTLA-4 inhibitors for melanoma treatment.
Authors: Ashley Su, Jeremy Jueng, Léonie Dupuis, Ian Brooks, Ritika Sinha, Brittany Maner, Robert Dellavalle, Vernon Burton, James A. Solomon
Journal: Journal of Clinical Oncology (2021)

e21572 Background: Due to side effects and adverse psychosocial factors, there can often be a disconnect between clinical impression and the patient perspective of treatment. Melanoma patients frequently use social media to discuss their disease sentiments and outcomes, providing a window into patient insight, otherwise not readily attainable. We analyzed publicly available full text posts on multiple social media platforms concerning melanoma treatments PD-1 inhibitors (pembrolizumab/Keytruda, nivolumab), BRAF inhibitors (dabrafenib, vemurafenib), and CTLA-4 inhibitor (ipilimumab/Yervoy) associated with Patient Global Impression of Change (PGIC) terms to compare and identify patient burden. Methods: Millions (12,599,313) of publicly available online social media text data were extracted and run through Brandwatch Artificial Intelligence-powered database and machine learning algorithm to categorize treatment-specific posts with PGIC terms associated with sentiment. Results: Out of 52,962 posts related to a select list of melanoma treatments, we identified Keytruda (6,080), nivolumab (1,614), dabrafenib (529), vemurafenib (329), and ipilimumab (1715) posts. The top ten types of posts by volume for each treatment were predominantly positive for PGIC terms (improving, well, progress) while being associated with negative emotions (fear and sadness). Patient-perceived better treatments were associated with decrease fear. PD-1 inhibitor Keytruda displayed markedly less fear (56.9%) with a very high positive PGIC (92.3%) in comparison with PD-1 inhibitor nivolumab with decreased positive PGIC (78.0%) and increased fear (81.6%). Likewise, this patten was discovered for the BRAF inhibitors and CTLA-4 inhibitor, albeit less distinct: dabrafenib (positive PGIC 86.4%, fear 71.9%), vemurafenib (positive PGIC 78.0%, 81.6%), ipilimumab (positive PGIC 75.0%, fear 79.3%). Conclusions: Our initial results indicate that despite patients reporting good outcomes from melanoma treatment, they remain fearful. Nonetheless, a trend is identified between patient-perceived better treatment and decreased patient fear. This analysis can help bridge the gap of understanding patient perspective and provides an indication for translation into more effective clinical and pharmaceutical response.