PubMed Scopus Research Articles

Leveraging the positives from the pandemic to strengthen infectious disease care in low-income and middle-income countries

Leveraging the positives from the pandemic to strengthen infectious disease care in low-income and middle-income countries

Predicting clinical outcomes in people with NAFLD: no need for a crystal ball?

A key challenge in the management of non-alcoholic fatty liver disease (NAFLD), one of the most common chronic liver diseases globally, is to identify people at highest risk of progression to advanced liver disease. 1 Younossi ZM Non-alcoholic fatty liver disease—a global public health perspective. J Hepatol. 2019; 70: 531-544 Summary Full Text Full Text PDF PubMed Scopus (1051) Google Scholar Early detection is crucial so that individuals who are at risk can be offered interventions and appropriate care before they develop liver-related complications. The most important predictor of progression to advanced liver disease and mortality in individuals with NAFLD is the extent of liver fibrosis. 2 Dulai PS Singh S Patel J et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology. 2017; 65: 1557-1565 Crossref PubMed Scopus (1050) Google Scholar Historically, liver biopsy was the only reliable method to assess liver fibrosis. However, it has a number of limitations (eg, cost, invasiveness, sampling bias, and intra-observer and inter-observer variability) and is not a suitable test for screening or monitoring liver disease progression. In clinical practice, non-invasive tests are increasingly used to provide prognostic information about liver disease severity. 3 Sanyal AJ Castéra L Wai-Sun Wong V Non-invasive assessment of liver fibrosis in NAFLD. Clin Gastroenterol Hepatol. 2023; (published online April 14.)https://doi.org/10.1016/j.cgh.2023.03.042 Summary Full Text Full Text PDF Google Scholar The individual participant data meta-analysis reported by Ferenc E Mózes and colleagues in The Lancet Gastroenterology & Hepatology4 Mózes FE Lee JA Vali Y et al. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis. Lancet Gastroenterol Hepatol. 2023; (published online June 5.)https://doi.org/10.1016/S2468-1253(23)00141-3 Google Scholar shows that non-invasive tests can also provide prognostic information about key clinical outcomes. 4 Mózes FE Lee JA Vali Y et al. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis. Lancet Gastroenterol Hepatol. 2023; (published online June 5.)https://doi.org/10.1016/S2468-1253(23)00141-3 Google Scholar Their analysis compared the performance of three non-invasive tests and liver biopsy in predicting a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, and cirrhosis complications in patients with NAFLD. Non-invasive tests were as good as liver biopsy as predictors of clinical outcomes after adjusting for potential confounders. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysisSimple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases. Full-Text PDF Open Access

Sequencing checkpoint inhibitor therapy in renal cell carcinoma

Initial therapy in patients with advanced renal cell carcinoma includes drugs that inhibit immune checkpoints, thereby blocking the negative regulators of an antitumour immune response. Currently, this therapy includes a combination of a PD-1 inhibitor and either a second checkpoint inhibitor, an antibody against CTLA4, or one of several small molecule inhibitors of the VEGF receptor. These PD-1-based combination therapies have improved clinical outcomes including overall survival. 1 Motzer RJ McDermott DF Escudier B et al. Conditional survival and long-term efficacy with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma. Cancer. 2022; 128: 2085-2097 Crossref PubMed Scopus (47) Google Scholar , 2 Rini BI Plimack ER Stus V et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019; 380: 1116-1127 Crossref PubMed Scopus (1841) Google Scholar , 3 Choueiri TK Powles T Burotto M et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021; 384: 829-841 Crossref PubMed Scopus (618) Google Scholar , 4 Motzer R Alekseev B Rha S-Y et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021; 384: 1289-1300 Crossref PubMed Scopus (614) Google Scholar Although use of checkpoint inhibitor-based combination therapy has led to a subset of patients who have a durable response and disease control without the need for further systemic therapy, the majority of patients will progress and require additional treatment. Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trialThe addition of atezolizumab to cabozantinib did not improve clinical outcomes and led to increased toxicity. These results should discourage sequential use of immune checkpoint inhibitors in patients with renal cell carcinoma outside of clinical trials. Full-Text PDF

Adjuvant chemotherapy in nasopharyngeal carcinoma

The value of adjuvant chemotherapy after definitive radiotherapy in locoregionally advanced nasopharyngeal carcinoma has been debated since the landmark publication of the Intergroup-0099 trial. 1 Al-Sarraf M LeBlanc M Giri PG et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998; 16: 1310-1317 Crossref PubMed Google Scholar The differing views occur for two reasons: (1) early chemoradiotherapy trials in the 2000s investigated various platinum-based regimens of concurrent chemoradiotherapy alone or in combination with adjuvant chemotherapy, with both strategies showing survival benefits over radiotherapy alone; and (2) it was generally observed that platinum doublet adjuvant chemotherapy after concurrent chemoradiotherapy was poorly tolerated. 2 Chua MLK Wee JTS Hui EP Chan ATC Nasopharyngeal carcinoma. Lancet. 2016; 387: 1012-1024 Summary Full Text Full Text PDF PubMed Scopus (934) Google Scholar The resistance towards recommending adjuvant chemotherapy to patients in the clinic was compounded after a phase 3 trial in China showed that adjuvant cisplatin–fluorouracil chemotherapy did not significantly improve failure-free survival after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma compared with concurrent chemoradiotherapy alone. 3 Chen L Hu CS Chen XZ et al. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2012; 13: 163-171 Summary Full Text Full Text PDF PubMed Scopus (432) Google Scholar Concurrent chemoradiotherapy followed by adjuvant cisplatin–gemcitabine versus cisplatin–fluorouracil chemotherapy for N2–3 nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trialOur findings suggest that concurrent adjuvant cisplatin–gemcitabine could be used as an adjuvant therapy in the treatment of patients with N2–3 nasopharyngeal carcinoma, although long-term follow-up is required to confirm the optimal therapeutic ratio. Full-Text PDF

Combining next-generation hormonal therapy with PARP inhibition in metastatic castration-resistant prostate cancer

In a paradigm of precision oncology, elegant preclinical work showed that inhibition of poly(ADP-ribose) polymerase (PARP) proteins can exploit a deficiency of cancer cells to repair DNA double-strand breaks through homologous recombination repair (HRR), 1 Lord CJ Ashworth A PARP inhibitors: synthetic lethality in the clinic. Science. 2017; 355: 1152-1158 Crossref PubMed Scopus (1411) Google Scholar and the resulting synthetic lethality was first shown to be clinically effective in ovarian cancer carrying a germline deleterious mutation in BRCA1 or BRCA2, key HRR genes. 2 Banerjee S Moore KN Colombo N et al. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021; 22: 1721-1731 Summary Full Text Full Text PDF PubMed Scopus (92) Google Scholar For prostate cancer, the discovery of alterations in BRCA2 and other HRR-related genes in up to 20% of advanced disease 3 Robinson D Van Allen EM Wu YM et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015; 161: 1215-1228 Summary Full Text Full Text PDF PubMed Scopus (2077) Google Scholar led to the development of several biomarker-driven trials of PARP inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC) 4 Abida W Patnaik A Campbell D et al. Rucaparib in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration. J Clin Oncol. 2020; 38: 3763-3772 Crossref PubMed Scopus (309) Google Scholar , 5 de Bono JS Mehra N Scagliotti GV et al. Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): an open-label, phase 2 trial. Lancet Oncol. 2021; 22: 1250-1264 Summary Full Text Full Text PDF PubMed Scopus (79) Google Scholar , 6 Hussain M Mateo J Fizazi K et al. Survival with olaparib in metastatic castration-resistant prostate cancer. N Engl J Med. 2020; 383: 2345-2357 Crossref PubMed Scopus (289) Google Scholar , 7 Smith MR Scher HI Sandhu S et al. Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2022; 23: 362-373 Summary Full Text Full Text PDF PubMed Scopus (41) Google Scholar and to the regulatory approval of rucaparib and olaparib as monotherapy for the treatment of mCRPC harbouring mutations in BRCA2 and other HRR genes. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trialTalazoparib plus enzalutamide resulted in clinically meaningful and statistically significant improvement in rPFS versus standard of care enzalutamide as first-line treatment for patients with mCRPC. Final overall survival data and additional long-term safety follow-up will further clarify the clinical benefit of the treatment combination in patients with and without tumour HRR gene alterations. Full-Text PDF

PD-1 Overexpression in Sézary Syndrome Is Epigenetically Regulated

PD-1 Overexpression in Sézary Syndrome Is Epigenetically Regulated

Emerging paradigms in exploring the interactions among diet, probiotics, and cancer immunotherapeutic response

Emerging paradigms in exploring the interactions among diet, probiotics, and cancer immunotherapeutic response

Vascular and cardiac ultrasound as the primary imaging tool to safely deliver pacing leads while implanting single-chamber permanent pacemakers: A single-operator experience in a tertiary cardiac center

The use of fluoroscopy to visualize leads used for permanent pacemakers (PPM) has cumulative effects not only on patients but on operators and lab staff including malignancy risk, cataract, hypercholesterolemia, and musculoskeletal injuries due to the weight of radiation protection equipment.( 1 Karatasakis A. Brilakis H.S. Danek B.A. Karacsonyi J. Martinez-Parachini J.R. Nguyen-Trong P.J. et al. Radiation-associated lens changes in the cardiac catheterization laboratory: Results from the IC-CATARACT (CATaracts Attributed to RAdiation in the CaTh lab) study. Catheter Cardiovasc Interv. 2018; 91: 647-654 Crossref PubMed Scopus (43) Google Scholar , 2 Andrew S. Abdelmonem M.R. Kohli S. Dabke H. Evaluation of Back Pain and Lead Apron Use Among Staff at a District General Hospital. Cureus. 2021; 13e18859 PubMed Google Scholar )

In-Hospital Outcomes of Pulmonary Embolism Among Nonagenarians (Insights from the National Inpatient Sample)

Pulmonary embolism (PE) is one of the leading causes of cardiovascular mortality and morbidity. 1 Benjamin EJ Virani SS Callaway CW Chamberlain AM Chang AR Cheng S Chiuve SE Cushman M Delling FN Deo R de Ferranti SD Ferguson JF Fornage M Gillespie C Isasi CR Jiménez MC Jordan LC Judd SE Lackland D Lichtman JH Lisabeth L Liu S Longenecker CT Lutsey PL Mackey JS Matchar DB Matsushita K Mussolino ME Nasir K O'Flaherty M Palaniappan LP Pandey A Pandey DK Reeves MJ Ritchey MD Rodriguez CJ Roth GA Rosamond WD Sampson UKA Satou GM Shah SH Spartano NL Tirschwell DL Tsao CW Voeks JH Willey JZ Wilkins JT Wu JH Alger HM Wong SS Muntner P American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke Statistics-2018 update: a report from the American Heart Association. Circulation. 2018; 137: e67-e492 Crossref PubMed Scopus (4660) Google Scholar The incidence of PE has been increasing in the last decade, with recent advances in imaging modalities that enable the detection of small PE. 2 Stein PD Matta F Hughes MJ. Hospitalizations for high-risk pulmonary embolism. Am J Med. 2021; 134: 621-625 Abstract Full Text Full Text PDF Scopus (2) Google Scholar Despite the advances in treatment modalities, mortality remains high and estimated at 10% within the first 30 days of the index event. 1 Benjamin EJ Virani SS Callaway CW Chamberlain AM Chang AR Cheng S Chiuve SE Cushman M Delling FN Deo R de Ferranti SD Ferguson JF Fornage M Gillespie C Isasi CR Jiménez MC Jordan LC Judd SE Lackland D Lichtman JH Lisabeth L Liu S Longenecker CT Lutsey PL Mackey JS Matchar DB Matsushita K Mussolino ME Nasir K O'Flaherty M Palaniappan LP Pandey A Pandey DK Reeves MJ Ritchey MD Rodriguez CJ Roth GA Rosamond WD Sampson UKA Satou GM Shah SH Spartano NL Tirschwell DL Tsao CW Voeks JH Willey JZ Wilkins JT Wu JH Alger HM Wong SS Muntner P American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke Statistics-2018 update: a report from the American Heart Association. Circulation. 2018; 137: e67-e492 Crossref PubMed Scopus (4660) Google Scholar Older population, especially those with multiple co-morbidities, are at a higher risk of adverse clinical outcomes and treatment complications of PE. The estimated mortality after PE was approximately 18.9% in patients aged >80 years, 3 Polo Friz H Molteni M Del Sorbo D Pasciuti L Crippa M Villa G Meloni DF Primitz L Galli A Rognoni M Cavalieri d'Oro L Arpaia G Cimminiello C Mortality at 30 and 90 days in elderly patients with pulmonary embolism: a retrospective cohort study. Intern Emerg Med. 2015; 10: 431-436 Crossref PubMed Scopus (23) Google Scholar and this cohort is underrepresented in clinical trials. 4 Shenoy P Harugeri A. Elderly patients' participation in clinical trials. Perspect Clin Res. 2015; 6: 184-189 Crossref PubMed Google Scholar Contemporary data about in-hospital outcomes of acute PE in nonagenarians are scarce. To this end, we sought to assess the baseline characteristics and in-hospital outcomes of PE for this cohort in clinical practice in the United States.

Targeting of biomolecular condensates to the autophagy pathway.

Biomolecular condensates are membraneless compartments formed by liquid-liquid phase separation. They can phase transit into gel-like and solid states. The amount and state of biomolecular condensates must be tightly regulated to maintain normal cellular function. Autophagy targets biomolecular condensates to the lysosome for degradation or other purposes, which we term biocondensophagy. In biocondensophagy, autophagy receptors recognize biomolecular condensates and target them to the autophagosome, the vesicle carrier of autophagy. Multiple types of autophagy receptors have been identified and they are specifically involved in targeting biomolecular condensates with different phase transition states. The receptors also organize the phase transition of biomolecular condensate to facilitate biocondensophagy. Here, we briefly discuss the latest discoveries regarding how biomolecular condensates are recognized by autophagy receptors.

Coupling covariance matrix adaptation with continuum modeling for determination of kinetic parameters associated with electrochemical CO2 reduction

Coupling covariance matrix adaptation with continuum modeling for determination of kinetic parameters associated with electrochemical CO2 reduction

Tenecteplase to Replace Alteplase? Comparing Thrombolytic Therapies for Acute Ischemic Stroke: June 2023 Annals of Emergency Medicine Journal Club.

Tenecteplase to Replace Alteplase? Comparing Thrombolytic Therapies for Acute Ischemic Stroke: June 2023 Annals of Emergency Medicine Journal Club.

Mono-material product design with bio-based, circular, and biodegradable polymers

Mono-material product design with bio-based, circular, and biodegradable polymers

CO2 electroreduction to multicarbon products from carbonate capture liquid

CO2 electroreduction to multicarbon products from carbonate capture liquid

Modeling atmospheric microplastic cycle by GEOS-Chem: An optimized estimation by a global dataset suggests likely 50 times lower ocean emissions

Modeling atmospheric microplastic cycle by GEOS-Chem: An optimized estimation by a global dataset suggests likely 50 times lower ocean emissions

The role of electricity market design for energy storage in cost-efficient decarbonization

The role of electricity market design for energy storage in cost-efficient decarbonization

PTEN potentiation of oncolytic HSV therapy for glioblastoma

PTEN potentiation of oncolytic HSV therapy for glioblastoma

Building back better: Granular energy technologies in green recovery funding programs

Building back better: Granular energy technologies in green recovery funding programs

Low-cost photoreactors for highly photon/energy-efficient solar-driven synthesis

Low-cost photoreactors for highly photon/energy-efficient solar-driven synthesis

Localized Bullous Pemphigoid

A man in his 80s presented with a pruritic, focally ulcerated pink plaque with overlying blisters on the left lateral thigh (Figures 1 and 2). This had been the site of an excision 9 months earlier. Over time, pruritic vesicles and bullae developed at the surgical site. Punch biopsies showed a subepidermal bulla with extensive eosinophilic infiltrate on histopathology and linear deposition of C3 and immunoglobulin G (IgG) at the basement membrane zone on direct immunofluorescence, confirming the diagnosis of localized bullous pemphigoid (BP).Figure 2Close-up view of vesicles and bullae at the periphery.View Large Image Figure ViewerDownload Hi-res image Download (PPT) BP is a subepidermal autoimmune blistering disease caused by autoantibodies to hemidesmosome proteins BP180 (BP antigen 2) or BP230 (BP antigen 1). Classically, patients present with pruritic urticarial papules and plaques and tense vesicles and bullae. Diagnosis is made by examination of the tissue and direct immunofluorescence, which show a subepidermal accumulation of eosinophils and linear deposition of IgG and/or C3 in an n-serrated pattern along the basement membrane zone, respectively. Enzyme-linked immunosorbent assay (ELISA) for autoantibodies to the NC16a domain of BP180 and to BP230 is supportive, and anti-BP180-NC16a ELISA may aid in monitoring disease activity during treatment.1Schmidt E. Zillikens D. Pemphigoid diseases.Lancet. 2013; 381: 320-332https://doi.org/10.1016/S0140-6736(12)61140-4Abstract Full Text Full Text PDF PubMed Scopus (705) Google Scholar,2Feliciani C. Joly P. Jonkman M.F. et al.Management of bullous pemphigoid: the European Dermatology Forum consensus in collaboration with the European Academy of Dermatology and Venereology.Br J Dermatol. 2015; 172: 867-877https://doi.org/10.1111/bjd.13717Crossref PubMed Scopus (233) Google Scholar Most cases of BP are generalized. Rarely, it is localized, usually to sites of previous skin injury, surgery, radiation, or venous insufficiency.3Ständer S. Kasperkiewicz M. Thaçi D. et al.Prevalence and presumptive triggers of localized bullous pemphigoid.J Dermatol. 2021; 48: 1257-1261https://doi.org/10.1111/1346-8138.15912Crossref PubMed Scopus (4) Google Scholar Although the pathophysiology of localized BP is not well understood,4Danescu S. Chiorean R. Macovei V. Sitaru C. Baican A. Role of physical factors in the pathogenesis of bullous pemphigoid: case report series and a comprehensive review of the published work.J Dermatol. 2016; 43: 134-140https://doi.org/10.1111/1346-8138.13031Crossref PubMed Scopus (39) Google Scholar topical steroids are first-line therapy and are generally effective.2Feliciani C. Joly P. Jonkman M.F. et al.Management of bullous pemphigoid: the European Dermatology Forum consensus in collaboration with the European Academy of Dermatology and Venereology.Br J Dermatol. 2015; 172: 867-877https://doi.org/10.1111/bjd.13717Crossref PubMed Scopus (233) Google Scholar Our patient was treated with topical clobetasol 0.05% ointment twice daily for 3 weeks with excellent results, and subsequent use as needed to maintain clearance. The authors report no competing interests.