Metformin-associated lactic acidosis: A mini review of pathophysiology, diagnosis and management in critically ill patients.

Metformin is a common diabetes drug that may reduce lactate clearance by inhibiting mitochondrial oxidative phosphorylation, leading to metformin-associated lactic acidosis (MALA). As diabetes mellitus is a common chronic metabolic condition found in critically ill patients, pre-existing metformin use can often be found in critically ill patients admitted to the intensive care unit or the high dependency unit. The aim of this narrative mini review is therefore to update clinicians about MALA, and to provide a practical approach to its diagnosis and treatment. MALA in critically ill patients may be suspected in a patient who has received metformin and who has a high anion gap metabolic acidosis, and confirmed when lactate exceeds 5 mmol/L. Risk factors include those that reduce renal elimination of metformin (renal impairment from any cause, histamine-2 receptor antagonists, ribociclib) and excessive alcohol consumption (as ethanol oxidation consumes nicotinamide adenine dinucleotides that are also required for lactate metabolism). Treatment of MALA involves immediate cessation of metformin, supportive management, treating other concurrent causes of lactic acidosis like sepsis, and treating any coexisting diabetic ketoacidosis. Severe MALA requires extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement therapy. The optimal time to restart metformin has not been well-studied. It is nonetheless reasonable to first ensure that lactic acidosis has resolved, and then recheck the kidney function post-recovery from critical illness, ensuring that the estimated glomerular filtration rate is 30 mL/min/1.73 m2 or better before restarting metformin.

Diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients: A mini review for clinicians.

Among critically ill patients, severe pulmonary and extrapulmonary tuberculosis has high morbidity and mortality. Yet, it is a diagnostic challenge given its nonspecific clinical symptoms and signs in early stages of the disease. In addition, management of severe pulmonary and extrapulmonary tuberculosis is complicated given the high risk of drug-drug interactions, drug-disease interactions, and adverse drug reactions. To help clinicians acquire an up-to-date approach to severe tuberculosis, this paper will provide a narrative review of contemporary diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients.

Dengue-Associated Hemophagocytic Lymphohistiocytosis: A Narrative Review of Its Identification and Treatment.

Dengue's lack of specific treatments beyond supportive care prompts a focus on uncovering additional pathophysiological factors. Dengue-associated hemophagocytic lymphohistiocytosis (HLH), characterized by dysregulated macrophage activation and cytokine storm, remains underexplored despite its potential to worsen disease severity and mortality. While rare, dengue-associated HLH disproportionately affects severe cases, significantly impacting mortality rates. To mitigate high mortality, early identification and familiarity with dengue-associated HLH are imperative for prompt treatment by clinicians. This narrative review therefore aims to examine the current clinical and therapeutic knowledge on dengue-associated HLH, and act as a resource for clinicians to improve their management of HLH associated with severe dengue. Dengue-associated HLH should be considered for all cases of severe dengue and may be suspected based on the presence of prolonged or recurrent fever for >7 days, or anemia without intravascular hemolysis or massive bleeding. Diagnosis relies on fulfilling at least five of the eight HLH-2004 criteria. Treatment predominantly involves short courses (3-4 days) of high-dose steroids (e.g., dexamethasone 10 mg/m2), with additional therapies considered in more severe presentations. Notably, outcomes can be favorable with steroid therapy alone.

Lung cancer screening for never smokers: current evidence and future directions.

ABSTRACT: Screening for lung cancer using low-dose computed tomography is an established means for early lung cancer detection in smokers, but the role of screening for never smokers is unclear. In the 13 lung cancer screening studies involving unselected never smokers, detection rates ranged from 0.1% to 1.1% and positive predictive values ranged from 0.4% to 4.5%. In three lung cancer screening studies involving selected never smokers, selection was based primarily on occupational asbestos exposure, environmental radon exposure and family history of lung cancer in first-degree relatives. Detection rates ranged from 0.3% to 2.6%, and positive predictive values ranged from 0.7% to 15%. Also, 80%-100% of lung cancer cases discovered by screening were early stage, with limited data suggesting survival benefit. Lung cancer screening for never smokers with selected risk factors may achieve detection rates similar to those of screening for high-risk ever smokers. However, further research on optimal subject selection, alternative screening methods and clinical/economic outcomes is needed.

The Impact of COVID-19 and Non-COVID-19 Vaccinations in Special Populations.

Vaccination to prevent human infection is a key driver for reducing morbidity and mortality [...].

Association of body temperature and mortality in critically ill patients: an observational study using two large databases.

BACKGROUND: Body temperature (BT) is routinely measured and can be controlled in critical care settings. BT can impact patient outcome, but the relationship between BT and mortality has not been well-established. METHODS: A retrospective cohort study was conducted based on the MIMIC-IV (N = 43,537) and eICU (N = 75,184) datasets. The primary outcome and exposure variables were hospital mortality and first 48-h median BT, respectively. Generalized additive models were used to model the associations between exposures and outcomes, while adjusting for patient age, sex, APS-III, SOFA, and Charlson comorbidity scores, temperature gap, as well as ventilation, vasopressor, steroids, and dialysis usage. We conducted subgroup analysis according to ICU setting, diagnoses, and demographics. RESULTS: Optimal BT was 37 °C for the general ICU and subgroup populations. A 10% increase in the proportion of time that BT was within the 36-38 °C range was associated with reduced hospital mortality risk in both MIMIC-IV (OR 0.91; 95% CI 0.90-0.93) and eICU (OR 0.86; 95% CI 0.85-0.87). On the other hand, a 10% increase in the proportion of time when BT < 36 °C was associated with increased mortality risk in both MIMIC-IV (OR 1.08; 95% CI 1.06-1.10) and eICU (OR 1.18; 95% CI 1.16-1.19). Similarly, a 10% increase in the proportion of time when BT > 38 °C was associated with increased mortality risk in both MIMIC-IV (OR 1.09; 95% CI 1.07-1.12) and eICU (OR 1.09; 95% CI 1.08-1.11). All patient subgroups tested consistently showed an optimal temperature within the 36-38 °C range. CONCLUSIONS: A BT of 37 °C is associated with the lowest mortality risk among ICU patients. Further studies to explore the causal relationship between the optimal BT and mortality should be conducted and may help with establishing guidelines for active BT management in critical care settings.

Interventions to promote cost-effectiveness in adult intensive care units: consensus statement and considerations for best practice from a multidisciplinary and multinational eDelphi study.

BACKGROUND: There is limited evidence to guide interventions that promote cost-effectiveness in adult intensive care units (ICU). The aim of this consensus statement is to identify globally applicable interventions for best ICU practice and provide guidance for judicious use of resources. METHODS: A three-round modified online Delphi process, using a web-based platform, sought consensus from 61 multidisciplinary ICU experts (physicians, nurses, allied health, administrators) from 21 countries. Round 1 was qualitative to ascertain opinions on cost-effectiveness criteria based on four key domains of high-value healthcare (foundational elements; infrastructure fundamentals; care delivery priorities; reliability and feedback). Round 2 was qualitative and quantitative, while round 3 was quantitative to reiterate and establish criteria. Both rounds 2 and 3 utilized a five-point Likert scale for voting. Consensus was considered when > 70% of the experts voted for a proposed intervention. Thereafter, the steering committee endorsed interventions that were identified as 'critical' by more than 50% of steering committee members. These interventions and experts' comments were summarized as final considerations for best practice. RESULTS: At the conclusion of round 3, consensus was obtained on 50 best practice considerations for cost-effectiveness in adult ICU. Finally, the steering committee endorsed 9 'critical' best practice considerations. This included adoption of a multidisciplinary ICU model of care, focus on staff training and competency assessment, ongoing quality audits, thus ensuring high quality of critical care services whether within or outside the four walls of ICUs, implementation of a dynamic staff roster, multidisciplinary approach to implementing end-of-life care, early mobilization and promoting international consensus efforts on the Green ICU concept. CONCLUSIONS: This Delphi study with international experts resulted in 9 consensus statements and best practice considerations promoting cost-effectiveness in adult ICUs. Stakeholders (government bodies, professional societies) must lead the efforts to identify locally applicable specifics while working within these best practice considerations with the available resources.

Vaccination for Respiratory Syncytial Virus: A Narrative Review and Primer for Clinicians.

Respiratory syncytial virus (RSV) poses a significant burden on public health, causing lower respiratory tract infections in infants, young children, older adults, and immunocompromised individuals. Recent development and licensure of effective RSV vaccines provide a promising approach to lessening the associated morbidity and mortality of severe infections. This narrative review aims to empower clinicians with the necessary knowledge to make informed decisions regarding RSV vaccination, focusing on the prevention and control of RSV infections, especially among vulnerable populations. The paper explores the available RSV vaccines and existing evidence regarding their efficacy and safety in diverse populations. Synthesizing this information for clinicians can help the latter understand the benefits and considerations associated with RSV vaccination, contributing to improved patient care and public health outcomes.

Hearing Loss after COVID-19 and Non-COVID-19 Vaccination: A Systematic Review.

(1) Background: Vaccine safety is an important topic with public health implications on a global scale. The purpose of this study was to systematically review available literature assessing sensorineural hearing loss (SNHL) incidence and severity following both coronavirus disease 2019 (COVID-19) and non-COVID-19 vaccinations, as well as prognosis and outcomes. (2) Methods: This systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Relevant publications evaluating post-vaccination SNHL were selected from PubMed and Embase, searching from inception to July 2023. (3) Results: From 11 observational studies, the incidence of post-vaccination SNHL was low for both COVID-19 and non-COVID-19 vaccines, ranging from 0.6 to 60.77 per 100,000 person-years, comparable to all-cause SNHL. (4) Conclusions: The incidence rates of SNHL following COVID-19 and non-COVID-19 vaccinations remained reassuringly low. Most patients experienced improved hearing function in the weeks to months following vaccination. This study underscores the importance and safety of vaccinations and encourages ongoing surveillance and detailed reporting of hearing loss cases post-vaccination.

Improving environmental sustainability of intensive care units: A mini-review.

The carbon footprint of healthcare is significantly impacted by intensive care units, which has implications for climate change and planetary health. Considering this, it is crucial to implement widespread efforts to promote environmental sustainability in these units. A literature search for publications relevant to environmental sustainability of intensive care units was done using PubMed. This mini-review seeks to equip intensive care unit practitioners and managers with the knowledge necessary to measure and mitigate the carbon cost of healthcare for critically ill patients. It will also provide an overview of the current progress in this field and its future direction.