tbuckley/cabot-search huggingface dataset:
Clinical characteristics, treatment and efficacy of calcaneal osteomyelitis: A systematic review with synthesis analysis 1118 reported cases
Authors: Nan Jiang, Peng Chen, Guan-Qiao Liu, Mou-Zhang Huang, Ming-Ye Deng, Ming-Rui Song, Run-Jiu Zhu, Hong-Fa Zhong, Da-Yong Xiang, Bin Yu
Journal: International Journal of Surgery (2024)

Background: Calcaneal osteomyelitis (CO) still poses great challenges to orthopaedic surgeons due to unique anatomic and functional features of the calcaneus. This study summarized the current data regarding clinical characteristics, treatment and efficacy of CO, based on an analysis of literature-reported cases. Materials and Methods: We searched the PubMed, Embase, and Cochrane Library databases to find English and Chinese studies reporting on CO patients between 2000 and 2021, with available data for synthesis analysis. The quality of the included studies was evaluated by the National Institutes of Health (NIH) assessment scale. Effective data were extracted and pooled for analysis. Results: Altogether 198 studies involving 1118 patients were included, with a male-to-female ratio of 2.3 (724 males and 310 females). The median age at CO diagnosis was 46 years, with a median symptom duration of 3 months. Injury-related infections (524 cases) and diabetic foot infections (336 cases) were the two most common causes, with ulcer (468 cases) and wound sinus or exudation (209 cases) being the predominant symptoms. The overall positive culture rate was 80.2%, with polymicrobial infections accounting for 18.1%. Staphylococcus aureus was the most frequently detected pathogen (42.7%), with fungal-related infections isolated in 17 cases. Although most patients received surgical interventions (96.9%), the recurrence rate was 20.1%. The incidence of infection relapse following partial calcanectomy, total calcanectomy, debridement with implantation of local antibiotics, and debridement with or without flap or skin coverage were 31.7%, 45.0%, 16.8%, and 15.1%, respectively. The overall incidence of limb amputation was 12.4%, with all-cause and CO-related mortalities of 2.8% and 0.2%, separately. Conclusions: CO shared similar characteristics with extremity chronic osteomyelitis, primarily affecting young males, with trauma and diabetic foot as the leading causes and Staphylococcus aureus as the most frequently detected pathogen. Despite surgery being the primary treatment modality, clinical outcomes remained unsatisfactory, marked by high rates of infection recurrence and limb amputation.
Neutrophil glucose flux as a therapeutic target in antiphospholipid syndrome
Authors: Ajay Tambralli, Alyssa Harbaugh, Somanathapura K. NaveenKumar, Megan D. Radyk, Christine E. Rysenga, Kaitlyn Sabb, Julia M. Hurley, Gautam J. Sule, Srilakshmi Yalavarthi, Shanea K. Estes, Claire K. Hoy, Tristin Smith, Cyrus Sarosh, Jacqueline A. Madison, Jordan K. Schaefer, Suman L. Sood, Yu Zuo, Amr H. Sawalha, Costas A. Lyssiotis, Jason S. Knight
Journal: Journal of Clinical Investigation (2024)

Neutrophil hyperactivity and neutrophil extracellular trap release (NETosis) appear to play important roles in the pathogenesis of the thromboinflammatory autoimmune disease known as antiphospholipid syndrome (APS). The understanding of neutrophil metabolism has advanced tremendously in the past decade, and accumulating evidence suggests that a variety of metabolic pathways guide neutrophil activities in health and disease. Our previous work characterizing the transcriptome of APS neutrophils revealed that genes related to glycolysis, glycogenolysis, and the pentose phosphate pathway (PPP) were significantly upregulated. Here, we found that APS patient neutrophils used glycolysis more avidly than healthy control neutrophils, especially when the neutrophils were from APS patients with a history of microvascular disease. In vitro, inhibiting either glycolysis or the PPP tempered phorbol myristate acetate- and APS IgG-induced NETosis, but not NETosis triggered by a calcium ionophore. In mice, inhibiting either glycolysis or the PPP reduced neutrophil reactive oxygen species production and suppressed APS IgG-induced NETosis ex vivo. When APS-associated thrombosis was evaluated in mice, inhibiting either glycolysis or the PPP markedly suppressed thrombosis and circulating NET remnants. In summary, these data identify a potential role for restraining neutrophil glucose flux in the treatment of APS.
Noninvasive Ventilation for Preoxygenation during Emergency Intubation
Authors: Kevin W. Gibbs, Matthew W. Semler, Brian E. Driver, Kevin P. Seitz, Susan B. Stempek, Caleb Taylor, Daniel Resnick-Ault, Heath D. White, Sheetal Gandotra, Kevin C. Doerschug, Amira Mohamed, Matthew E. Prekker, Akram Khan, John P. Gaillard, Luke Andrea, Neil R. Aggarwal, Jason C. Brainard, LuAnn H. Barnett, Stephen J. Halliday, Veronika Blinder, Alon Dagan, Micah R. Whitson, Steven G. Schauer, James E. Walker, Andrew B. Barker, Jessica A. Palakshappa, Amelia Muhs, Joanne M. Wozniak, Patrick J. Kramer, Cori Withers, Shekhar A. Ghamande, Derek W. Russell, Andrei Schwartz, Ari Moskowitz, Sydney J. Hansen, Gopal Allada, Jordan K. Goranson, Daniel G. Fein, Peter D. Sottile, Nicholas Kelly, Shannon M. Alwood, Micah T. Long, Rishi Malhotra, Nathan I. Shapiro, David B. Page, Brit J. Long, Christopher B. Thomas, Stacy A. Trent, David R. Janz, Todd W. Rice, Wesley H. Self, Vikhyat S. Bebarta, Bradley D. Lloyd, Jillian Rhoads, Kelsey Womack, Brant Imhoff, Adit A. Ginde, Jonathan D. Casey
Journal: New England Journal of Medicine (2024)

Among critically ill adults undergoing tracheal intubation, hypoxemia increases the risk of cardiac arrest and death. The effect of preoxygenation with noninvasive ventilation, as compared with preoxygenation with an oxygen mask, on the incidence of hypoxemia during tracheal intubation is uncertain.
Long-term outcomes of active vaccination against de novo hepatitis B among pediatric recipients of living donor liver transplantations with anti-HBc (+) grafts: a retrospective case-control study
Authors: Chee-Chien Yong, Yu-Hung Lin, Wendell Z. Espinosa, I-Hsuan Chen, Shih-Ho Wang, Yi-Chia Chan, Chao-Long Chen, Chih-Che Lin
Journal: International Journal of Surgery (2024)

Background: Active vaccination has been utilized to prevent de novo hepatitis B virus infection (DNHB) in anti-HBc (+) grafts after liver transplantation (LT). However, the long-term efficacy of active vaccination and graft/patient outcomes of anti-HBc (+) grafts have yet to be comprehensively investigated. Materials and Methods: Among 204 pediatric patients enrolled in the study, 82 recipients received anti-HBc (+) grafts. For DNHB prevention, active vaccination was repeatedly administered prior to transplant. Anti-viral therapy was given to patients with pre-transplant anti-HBs&lt;1000 IU/ ml (non-robust response) for 2 years and discontinued when post-transplant patients achieved anti-HBs&gt;1000 IU/mL, while anti-viral therapy was not given in patients with an anti-HBs titer over 1000 IU/mL. The primary outcome was to investigate the long-term efficacy of active vaccination, while the secondary outcomes included the graft and patient survival rates. Results: Among the 82 anti-HBc (+) transplant patients, 68% of recipients achieved a robust immune response, thus not requiring antiviral therapy. Two patients (2.4%) developed DNHB infection, one of which was due to an escape mutant. With a median follow-up of 150 months, the overall 10-year patient and graft survival rates were significantly worse in recipients of anti-HBc (+) grafts than those of anti-HBc (-) grafts (85.2% vs 93.4%, P =0.026; 85.1% vs 93.4%, P =0.034, respectively). Additionally, the 10-year patient and graft outcomes of the anti-HBc (+) graft recipients were significantly worse than those of the anti-HBc (-) graft recipients after excluding early mortality and non-graft mortality values (90.8% vs 96.6%, P =0.036; 93.0% vs 98.3%, P =0.011, respectively). Conclusion: Our long-term follow-up study demonstrates that active vaccination is a simple, cost-effective strategy against DNHB infection in anti-HBc (+) graft patients, whereby the need for life-long antiviral therapy is removed. Notably, both the anti-HBc (+) grafts and patients exhibited inferior long-term survival rates, although the exact mechanisms remain unclear.
Effect of local prolonged-release incisional doxycycline on surgical site infection prophylaxis in abdominal colorectal surgery: The SHIELD 1 randomized clinical trial
Authors: Oded Zmora, Phillip Fleshner, Philip S. Barie, Lior Segev, George M. Viola, Anthony J. Senagore, Antonino Spinelli, Olga Belotserkovsky, Shmuel Sharoni, Noam Emanuel
Journal: International Journal of Surgery (2024)

Introduction: Despite advanced infection control practices including preoperative antibiotic prophylaxis, surgical site infection (SSI) remains a challenge. This study aimed to test whether local administration of a novel prolonged-release doxycycline-polymer-lipid encapsulation matrix (D-PLEX) before wound closure, concomitantly with standard of care (SOC), reduces the incidence of incisional SSI after elective abdominal colorectal surgery. Materials and methods: This was a phase 3 randomized, controlled, double-blind, multinational study (SHIELD 1) between June 2020 to June 2022. Patients with at least one abdominal incision length greater than 10 cm were randomized 1:1 to the investigational arm (D‐PLEX+SOC) or control (SOC) arm. The primary outcome was a composite of incisional SSI, incisional reintervention, and all-cause mortality. Results: A total of 974 patients were analyzed, of whom 579 (59.4%) were male. The mean age (±SD) was 64.2±13.0 years. The primary outcome occurred in 9.3% of D-PLEX patients versus 12.1% (SOC) [risk difference estimate (RDE), −2.8%; 95% CI (−6.7%, 1.0%), P =0.1520]. In a pre-specified analysis by incision length, a reduction in the primary outcome was observed in the greater than 20 cm subpopulation: 8% (D-PLEX) versus 17.5% (SOC) [RDE, −9.4%; 95% CI (−15.5%, −3.2%), P =0.0032]. In the greater than 10 to less than or equal to 20 cm subgroup, no reduction was observed: 9.9% versus 7.9% [RDE, 2.0%; 95% CI (−2.8%, 6.7%), P =0.4133]. Exploratory post hoc analyses of patients with increased SSI risk (≥1 patient-specific comorbidity) indicated a reduction in the incidence of the primary outcome: 9.0% (D-PLEX) versus 13.7% (SOC) [RDE, −4.8%; 95% CI (−9.5%, −0.1%), P =0.0472]. The D-PLEX safety profile was good (no difference in treatment-emergent adverse events between the groups). Conclusions: The SHIELD 1 study did not meet its primary outcome of reduced incisional SSI, incisional reinterventions, or all-cause mortality. Pre-specified and post hoc analyses suggested that D-PLEX may reduce the incidence of the primary outcome event in patients with increased SSI risk, including lengthy incisions.
Knowledge mapping and emerging trends in neural stem cell transplantation research for spinal cord injury: A bibliometric analysis (2004-2023)
Authors: Zhicheng Sun, Xiyang Wang, Juhua Xiao, Weiwei Li, Yan Yang, Xiaoyang Pang, Xiongjie Shen
Journal: International Journal of Surgery (2024)

Sun, Zhicheng; Wang, Xiyang; Xiao, Juhua; Li, Weiwei; Yang, Yan; Pang, Xiaoyang; Shen, Xiongjie Author Information
As whooping cough rates rise, we urgently need to increase maternal vaccination rates
Authors: Mohammad S Razai, Sima Berendes, Shobhana Nagraj, Pippa Oakeshott, Asma Khalil
Journal: BMJ (2024)

The UK is experiencing a sharp increase in rates of whooping cough (pertussis), with confirmed cases in England climbing rapidly from 858 in 2023 to reach 2793 in just the first three months of 2024. 1 In that period alone, whooping cough claimed the lives of five infants-a tragic and preventable outcome. 1 The rise in cases may reflect the cyclical nature of pertussis, 2 but it also underscores a worrying decline in vaccine uptake during pregnancy. 3 We urgently need to increase maternal vaccination rates and protect newborns who are too young to be vaccinated.Maternal vaccination is 97% effective against infant death from pertussis. 4 5Despite these benefits, pertussis vaccination coverage in pregnancy has fallen from 70% in September 2017 to just 58% in September 2023. 6Pertussis vaccine uptake is even lower in London, with coverage of only 36% from October to December 2023. 6Historically, pertussis vaccination uptake has been significantly lower in England's deprived regions and among ethnic minorities, particularly black and South Asian women, than among white women. 7e phenomenon referred to as "vaccine hesitancy" is defined as the "delay in acceptance or refusal of safe vaccines despite the availability of vaccine services."It stems from complex cultural and context specific factors that vary by time, place, and vaccine type, influenced by issues such as confidence, communication, complacency, convenience, and sociodemographic contexts. 8Misinformation and conspiracy theories, often amplified by social media, further compound vaccine hesitancy. 9Although widely used, the term "vaccine hesitancy" may not fully capture the breadth of determinants that can lead to delay or refusal of vaccinations.Additionally, structural issues such as health inequalities, socioeconomic disadvantages, systemic racism, and barriers to access are critical factors that undermine vaccine confidence and uptake.
Pediatric Respiratory Syncytial Virus Hospitalizations and Respiratory Support After the COVID-19 Pandemic
Authors: Zachary A. Winthrop, Jennifer M. Perez, Steven J. Staffa, Michael L. McManus, Melody G. Duvall
Journal: JAMA Network Open (2024)

Importance After the COVID-19 pandemic, there was a surge of pediatric respiratory syncytial virus (RSV) infections, but national data on hospitalization and intensive care unit use and advanced respiratory support modalities have not been reported. Objective To analyze demographics, respiratory support modes, and clinical outcomes of children with RSV infections at tertiary pediatric hospitals from 2017 to 2023. Design, Setting, and Participants This cross-sectional study evaluated children from 48 freestanding US children’s hospitals registered in the Pediatric Health Information System (PHIS) database. Patients 5 years or younger with RSV from July 1, 2017, to June 30, 2023, were included. Each season was defined from July 1 to June 30. Prepandemic RSV seasons included 2017 to 2018, 2018 to 2019, and 2019 to 2020. The postpandemic season was delineated as 2022 to 2023. Exposure Hospital presentation with RSV infection. Main Outcomes and Measures Data on emergency department presentations, hospital or intensive care unit admission and length of stay, demographics, respiratory support use, mortality, and cardiopulmonary resuscitation were analyzed. Postpandemic season data were compared with prepandemic seasonal averages. Results A total of 288 816 children aged 5 years or younger (median [IQR] age, 8.9 [3.3-21.5] months; 159 348 [55.2%] male) presented to 48 US children’s hospitals with RSV from July 1, 2017, to June 30, 2023. Respiratory syncytial virus hospital presentations increased from 39 698 before the COVID-19 pandemic to 94 347 after the pandemic ( P &amp;amp;lt; .001), with 86.7% more hospitalizations than before the pandemic (50 619 vs 27 114; P &amp;amp;lt; .001). In 2022 to 2023, children were older (median [IQR] age, 11.3 [4.1-26.6] months vs 6.8 [2.6-16.8] months; P &amp;amp;lt; .001) and had fewer comorbidities (17.6% vs 21.8% of hospitalized patients; P &amp;amp;lt; .001) than during prepandemic seasons. Advanced respiratory support use increased 70.1% in 2022 to 2023 (9094 vs 5340; P &amp;amp;lt; .001), and children requiring high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV) were older than during prepandemic seasons (median [IQR] age for HFNC, 6.9 [2.7-16.0] months vs 4.6 [2.0-11.7] months; for NIV, 6.0 [2.1-16.5] months vs 4.3 [1.9-11.9] months). Comorbid conditions were less frequent after the pandemic across all respiratory support modalities (HFNC, 14.9% vs 19.1%, NIV, 22.0% vs 28.5%, invasive mechanical ventilation, 30.5% vs 38.0%; P &amp;amp;lt; .001). Conclusions and Relevance This cross-sectional study identified a postpandemic pediatric RSV surge that resulted in markedly increased hospital volumes and advanced respiratory support needs in older children with fewer comorbidities than prepandemic seasons. These clinical trends may inform novel vaccine allocation to reduce the overall burden during future RSV seasons.
C16ORF70/Mytho promotes healthy ageing in C. elegans and prevents cellular senescence in mammals
Authors: Anais Franco-Romero, Valeria Morbidoni, Giulia Milan, Roberta Sartori, Jesper Wulff, Vanina Romanello, Andrea Armani, Leonardo Salviati, Maria Conte, Stefano Salvioli, Claudio Franceschi, Viviana Buonomo, Casey O. Swoboda, Paolo Grumati, Luca Pannone, Simone Martinelli, Harold B.J. Jefferies, Ivan Dikic, Jennifer van der Laan, Filipe Cabreiro, Douglas P. Millay, Sharon A. Tooze, Eva Trevisson, Marco Sandri
Journal: Journal of Clinical Investigation (2024)

The identification of genes that confer either extension of lifespan or accelerate age-related decline was a step forward in understanding the mechanisms of ageing and revealed that it is partially controlled by genetics and transcriptional programs. Here we discovered that the human DNA sequence C16ORF70 encoded for a protein, named MYTHO (Macroautophagy and YouTH Optimizer), which controls life- and health-span. MYTHO protein is conserved from C. elegans to humans and its mRNA was upregulated in aged mice and elderly people. Deletion of the ortholog myt-1 gene in C. elegans dramatically shortened lifespan and decreased animal survival upon exposure to oxidative stress. Mechanistically, MYTHO is required for autophagy likely because it acts as a scaffold that binds WIPI2 and BCAS3 to recruit and assemble the conjugation system at the phagophore, the nascent autophagosome. We conclude that MYTHO is a transcriptionally regulated initiator of autophagy that is central in promoting stress resistance and healthy ageing.
A Phase II Study of Potentiation of Pembrolizumab with Binimetinib and Bevacizumab in Refractory Microsatellite-Stable Colorectal Cancer
Authors: Robert W. Lentz, Tyler J. Friedrich, Patrick J. Blatchford, Kimberly R. Jordan, Todd M. Pitts, Hannah R. Robinson, S. Lindsey Davis, Sunnie S. Kim, Alexis D. Leal, Matthew R. Lee, Meredith R.N. Waring, Anne C. Martin, Adrian T.A. Dominguez, Stacey M. Bagby, Sarah J. Hartman, S. Gail Eckhardt, Wells A. Messersmith, Christopher H. Lieu
Journal: Clinical Cancer Research (2024)

Abstract Purpose: In this single-institution phase II investigator-initiated study, we assessed the ability of MAPK and VEGF pathway blockade to overcome resistance to immunotherapy in microsatellite-stable metastatic colorectal cancer (MSS mCRC). Patients and Methods: Patients with MSS, BRAF wild-type mCRC who progressed on ≥2 prior lines of therapy received pembrolizumab, binimetinib, and bevacizumab until disease progression or unacceptable toxicity. After a safety run-in, patients were randomized to a 7-day run-in of binimetinib or simultaneous initiation of all study drugs, to explore whether MEK inhibition may increase tumor immunogenicity. The primary endpoint was objective response rate (ORR) in all patients combined (by Response Evaluation Criteria in Solid Tumors v1.1). Results: Fifty patients received study drug treatment; 54% were male with a median age of 55 years (range, 31–79). The primary endpoint, ORR, was 12.0% [95% confidence interval (CI) 4.5%–24.3%], which was not statistically different than the historical control data of 5% (P = 0.038, exceeding prespecified threshold of 0.025). The disease control rate was 70.0% (95% CI, 55.4%–82.1%), the median progression-free survival 5.9 months (95% CI, 4.2–8.7 months), and the median overall survival 9.3 months (95% CI, 6.7–12.2 months). No difference in efficacy was observed between the randomized cohorts. Grade 3 and 4 adverse events were observed in 56% and 8% of patients, respectively; the most common were rash (12%) and increased aspartate aminotransferase (12%). Conclusions: Pembrolizumab, binimetinib, and bevacizumab failed to meet its primary endpoint of higher ORR compared with historical control data, demonstrated a high disease control rate, and demonstrated acceptable tolerability in refractory MSS mCRC.
Costs and Essential Drug Access—The Case of Naloxone
Authors: Leo Beletsky, Max Jordan Nguemeni Tiako
Journal: JAMA (2024)

Since the turn of this century, fatal drug overdoses involving opioids have continued to mount. Despite rhetorical assertions to the contrary, too little investment has been made in the science-based responses to this crisis and progress has been stymied by systems-level factors.1
Microbiota dictate T cell clonal selection to augment graft-versus-host disease after stem cell transplantation
Authors: Albert C. Yeh, Motoko Koyama, Olivia G. Waltner, Simone A. Minnie, Julie R. Boiko, Tamer B. Shabaneh, Shuichiro Takahashi, Ping Zhang, Kathleen S. Ensbey, Christine R. Schmidt, Samuel R.W. Legg, Tomoko Sekiguchi, Ethan Nelson, Shruti S. Bhise, Andrew R. Stevens, Tracy Goodpaster, Saranya Chakka, Scott N. Furlan, Kate A. Markey, Marie E. Bleakley, Charles O. Elson, Philip H. Bradley, Geoffrey R. Hill
Journal: Immunity (2024)
Trends in Naloxone Dispensing From Retail Pharmacies in the US
Authors: S. Michaela Rikard, Andrea E. Strahan, Lyna Z. Schieber, Gery P. Guy
Journal: JAMA (2024)

This cross-sectional study examines trends in naloxone dispensing by US retail pharmacies from 2019 to 2023, including prescriber specialty and product brand.