Mohd H. Abdul-Aziz, Joel M. Dulhunty, Dorrilyn Rajbhandari, Jason A. Roberts, Jeffrey Lipman
<p>Sepsis affects approximately 49 million people worldwide every year.<span><sup>1</sup></span> An estimated 11 million people die annually from sepsis,<span><sup>1</sup></span> with one death every 2.8 s. In Australia, one quarter of all intensive care unit (ICU) patients have sepsis, and despite having one of the best sepsis-related survival rates in the world,<span><sup>2</sup></span> approximately one in four patients will die from sepsis.<span><sup>3</sup></span> Sepsis also imposes a huge financial burden on society, costing the Australian healthcare system $700 million each year.<span><sup>4</sup></span> Despite modern therapeutic innovations, sepsis-related mortality remains a major problem with optimised antibiotic therapy being one of the few effective strategies for treating sepsis.</p><p>Conventional intermittent dosing remains the current standard of care for beta-lactam antibiotics. However, beta-lactam antibiotics display ‘time-dependent’ bactericidal activity, which is optimised when the free drug concentration remains above the minimum inhibitory concentration (MIC) of the infecting pathogen for at least 40%–70% of the dosing interval.<span><sup>5</sup></span> Prolonged infusions of beta-lactam antibiotics, either by extended infusions (infusion duration of ~50% of dosing interval) or continuous infusions, are a practical strategy to increase the time spent above the MIC. To determine the effectiveness of continuous infusions of beta-lactam antibiotics in the ICU setting, a programme of research was conducted by our group (Fig. 1),<span><sup>6-8</sup></span> culminating in the Beta-Lactam Infusion Group (BLING III) randomised clinical trial (RCT) and a systematic review and meta-analysis of all related sepsis RCTs involving prolonged beta-lactam antibiotic infusions in the ICU setting. Both studies were recently published in <i>JAMA</i>.<span><sup>9, 10</sup></span> The applicability of prolonged beta-lactam antibiotic infusions outside the ICU setting is currently under debate.</p><p>The BLING III trial (<i>n</i> = 7202) was an international, open-label phase 3 RCT conducted in 104 ICUs across Australia, Belgium, France, Malaysia, New Zealand, Sweden and the United Kingdom.<span><sup>9</sup></span> The BLING III trial compared continuous and intermittent infusions of an equivalent 24-h dose of two beta-lactam antibiotics, piperacillin-tazobactam and meropenem, on all-cause 90-day mortality in critically ill patients with sepsis. The mean age of patients was 60 years with a mean Acute Physiology and Chronic Health Evaluation (APACHE) II score of 20 (APACHE II is a disease severity classification system ranging from 0 to 71, with higher scores corresponding to more severe disease and a higher risk of mortality for ICU patients). In the 24 hours prior to randomisation, 71% of patients received inotropes and/or vasopressors. Overall, there was no statistically significant difference in all-cause day 90 mortality between the continu
{"title":"Is it time to implement prolonged infusions of beta-lactam antibiotics in and beyond critical care settings?","authors":"Mohd H. Abdul-Aziz, Joel M. Dulhunty, Dorrilyn Rajbhandari, Jason A. Roberts, Jeffrey Lipman","doi":"10.1111/imj.16584","DOIUrl":"10.1111/imj.16584","url":null,"abstract":"<p>Sepsis affects approximately 49 million people worldwide every year.<span><sup>1</sup></span> An estimated 11 million people die annually from sepsis,<span><sup>1</sup></span> with one death every 2.8 s. In Australia, one quarter of all intensive care unit (ICU) patients have sepsis, and despite having one of the best sepsis-related survival rates in the world,<span><sup>2</sup></span> approximately one in four patients will die from sepsis.<span><sup>3</sup></span> Sepsis also imposes a huge financial burden on society, costing the Australian healthcare system $700 million each year.<span><sup>4</sup></span> Despite modern therapeutic innovations, sepsis-related mortality remains a major problem with optimised antibiotic therapy being one of the few effective strategies for treating sepsis.</p><p>Conventional intermittent dosing remains the current standard of care for beta-lactam antibiotics. However, beta-lactam antibiotics display ‘time-dependent’ bactericidal activity, which is optimised when the free drug concentration remains above the minimum inhibitory concentration (MIC) of the infecting pathogen for at least 40%–70% of the dosing interval.<span><sup>5</sup></span> Prolonged infusions of beta-lactam antibiotics, either by extended infusions (infusion duration of ~50% of dosing interval) or continuous infusions, are a practical strategy to increase the time spent above the MIC. To determine the effectiveness of continuous infusions of beta-lactam antibiotics in the ICU setting, a programme of research was conducted by our group (Fig. 1),<span><sup>6-8</sup></span> culminating in the Beta-Lactam Infusion Group (BLING III) randomised clinical trial (RCT) and a systematic review and meta-analysis of all related sepsis RCTs involving prolonged beta-lactam antibiotic infusions in the ICU setting. Both studies were recently published in <i>JAMA</i>.<span><sup>9, 10</sup></span> The applicability of prolonged beta-lactam antibiotic infusions outside the ICU setting is currently under debate.</p><p>The BLING III trial (<i>n</i> = 7202) was an international, open-label phase 3 RCT conducted in 104 ICUs across Australia, Belgium, France, Malaysia, New Zealand, Sweden and the United Kingdom.<span><sup>9</sup></span> The BLING III trial compared continuous and intermittent infusions of an equivalent 24-h dose of two beta-lactam antibiotics, piperacillin-tazobactam and meropenem, on all-cause 90-day mortality in critically ill patients with sepsis. The mean age of patients was 60 years with a mean Acute Physiology and Chronic Health Evaluation (APACHE) II score of 20 (APACHE II is a disease severity classification system ranging from 0 to 71, with higher scores corresponding to more severe disease and a higher risk of mortality for ICU patients). In the 24 hours prior to randomisation, 71% of patients received inotropes and/or vasopressors. Overall, there was no statistically significant difference in all-cause day 90 mortality between the continu","PeriodicalId":13625,"journal":{"name":"Internal Medicine Journal","volume":"54 12","pages":"1931-1934"},"PeriodicalIF":1.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imj.16584","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Allison Barraclough, Catherine Tang, Masa Lasica, Elizabeth Smyth, Melita Cirillo, Howard Mutsando, Chan Y. Cheah, Matthew Ku
Mantle cell lymphoma (MCL) is a clinically heterogeneous B-cell neoplasm with unique clinicopathological features, accounting for 5% of all non-Hodgkin lymphoma. Although for many chemoimmunotherapy can lead to durable remissions, those with poor baseline prognostic factors, namely blastoid morphology, TP53 aberrancy and Ki67 >30%, will have less durable responses to conventional therapies. With this in mind, clinical trials have focused on novel targeted therapies to improve outcomes. This review details the recent advances in the understanding of MCL biology and outlines the recommended diagnostic strategies and evidence-based approaches to treatment.
套细胞淋巴瘤(MCL)是一种临床病理特征独特的异质性 B 细胞肿瘤,占所有非霍奇金淋巴瘤的 5%。虽然对许多患者来说,化疗免疫疗法可以带来持久的缓解,但那些基线预后因素较差的患者,即胚泡形态、TP53畸变和Ki67>30%的患者,对传统疗法的持久反应较差。有鉴于此,临床试验重点关注新型靶向疗法,以改善预后。本综述详细介绍了对 MCL 生物学认识的最新进展,并概述了推荐的诊断策略和循证治疗方法。
{"title":"Diagnosis and management of mantle cell lymphoma: a consensus practice statement from the Australasian Lymphoma Alliance","authors":"Allison Barraclough, Catherine Tang, Masa Lasica, Elizabeth Smyth, Melita Cirillo, Howard Mutsando, Chan Y. Cheah, Matthew Ku","doi":"10.1111/imj.16561","DOIUrl":"10.1111/imj.16561","url":null,"abstract":"<p>Mantle cell lymphoma (MCL) is a clinically heterogeneous B-cell neoplasm with unique clinicopathological features, accounting for 5% of all non-Hodgkin lymphoma. Although for many chemoimmunotherapy can lead to durable remissions, those with poor baseline prognostic factors, namely blastoid morphology, <i>TP53</i> aberrancy and Ki67 >30%, will have less durable responses to conventional therapies. With this in mind, clinical trials have focused on novel targeted therapies to improve outcomes. This review details the recent advances in the understanding of MCL biology and outlines the recommended diagnostic strategies and evidence-based approaches to treatment.</p>","PeriodicalId":13625,"journal":{"name":"Internal Medicine Journal","volume":"55 1","pages":"117-129"},"PeriodicalIF":1.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seshika Ratwatte, Rachael L. Cordina, David Baker, Edmund Lau, David S. Celermajer
We evaluated whether fluid status could be accurately assessed (and corrected if necessary) prior to right heart catheterisation (RHC), to diagnose accurately post-capillary pulmonary hypertension (PHT) in patients with left heart disease risk factors. A non-invasive measure of fluid status prior to RHC identified fluid-depleted patients. Baseline RHC measurements were performed, and a novel provocation technique (passive leg raise) was compared to a ‘one-dose-fits-all’ fluid challenge and found to be equivalent.
{"title":"The importance of assessing and correcting hydration status prior to right heart catheterisation: a pilot study","authors":"Seshika Ratwatte, Rachael L. Cordina, David Baker, Edmund Lau, David S. Celermajer","doi":"10.1111/imj.16577","DOIUrl":"10.1111/imj.16577","url":null,"abstract":"<p>We evaluated whether fluid status could be accurately assessed (and corrected if necessary) prior to right heart catheterisation (RHC), to diagnose accurately post-capillary pulmonary hypertension (PHT) in patients with left heart disease risk factors. A non-invasive measure of fluid status prior to RHC identified fluid-depleted patients. Baseline RHC measurements were performed, and a novel provocation technique (passive leg raise) was compared to a ‘one-dose-fits-all’ fluid challenge and found to be equivalent.</p>","PeriodicalId":13625,"journal":{"name":"Internal Medicine Journal","volume":"55 2","pages":"320-324"},"PeriodicalIF":1.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imj.16577","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heparin-induced thrombocytopenia (HIT) is a serious adverse reaction to heparin. Other HIT-like syndromes are increasingly recognised, mediated by antibodies binding to platelet factor 4, with or without identifiable polyanions. The history of heparin exposure is atypical for classical HIT and standard HIT laboratory tests may be negative. This manuscript describes subtypes of HIT-like syndromes and highlights practical tips for diagnosis and therapy.
肝素诱导的血小板减少症(HIT)是肝素的一种严重不良反应。其他类似 HIT 的综合征也日益得到认可,这些综合征由与血小板因子 4 结合的抗体介导,伴有或不伴有可识别的多聚阳离子。经典 HIT 的肝素暴露史并不典型,标准的 HIT 实验室检测可能呈阴性。本手稿描述了 HIT-like 综合征的亚型,并重点介绍了诊断和治疗的实用技巧。
{"title":"Platelet factor 4 immune disease: medical emergencies that look like heparin-induced thrombocytopenia","authors":"Ashwini Bennett, Phil Y. Choi, Chee Wee Tan","doi":"10.1111/imj.16546","DOIUrl":"10.1111/imj.16546","url":null,"abstract":"<p>Heparin-induced thrombocytopenia (HIT) is a serious adverse reaction to heparin. Other HIT-like syndromes are increasingly recognised, mediated by antibodies binding to platelet factor 4, with or without identifiable polyanions. The history of heparin exposure is atypical for classical HIT and standard HIT laboratory tests may be negative. This manuscript describes subtypes of HIT-like syndromes and highlights practical tips for diagnosis and therapy.</p>","PeriodicalId":13625,"journal":{"name":"Internal Medicine Journal","volume":"54 12","pages":"2072-2076"},"PeriodicalIF":1.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}