Pre-existing Disease Research Articles

Noninvasive respiratory support in the perioperative setting: a narrative review.

The application of preoperative noninvasive respiratory support (NRS) has been expanding with increasing recognition of its potential role in this setting as a physiological optimization for patients with a high risk of developing atelectasis and postoperative pulmonary complications (PPC). The increased availability of high-performance anesthesia ventilator machines providing an easy way for NRS support in patients with reduced lung function should not be under-evaluated. This support can reduce hypoxia, restore lung volumes and theoretically reduce atelectasis formation after general anesthesia. Therapeutic purposes should also be considered in the perioperative setting, such as preoperative NRS to optimize treatment of patients' pre-existing diseases, e.g., sleep-disordered breathing. Finally, the recent guidelines for airway management suggest preoperative NRS application before anesthesia induction in difficult airway management to prolong the time needed to secure the airway with an orotracheal tube. This narrative review aims to revise all these aspects and to provide some practical notes to maximize the efficacy of perioperative noninvasive respiratory support.

The Australian Traumatic Brain Injury Initiative: Systematic Review and Consensus Process to Determine the Predictive Value of Pre-existing Health Conditions for People with Moderate-Severe Traumatic Brain Injury.

The first aim of the Australian Traumatic Brain Injury Initiative (AUS-TBI) encompasses development of a set of measures that comprehensively predict outcomes for people with moderate-severe TBI across Australia. This process engaged diverse stakeholders and information sources across six areas: social, health, and clinical factors; biological markers; treatments; and longer-term outcomes. Here, we report the systematic review of pre-existing health conditions as predictors of outcome for people with moderate-severe TBI. Standardized searches were implemented across databases until March 31, 2022. English-language reports of studies evaluating association between pre-existing health conditions and clinical outcome in at least 10 patients with moderate-severe TBI were included. A predefined algorithm was used to assign a judgement of predictive value to each observed association. The list of identified pre-existing health conditions was then discussed with key stakeholders during a consensus meeting to determine the feasibility of incorporating them into standard care. The searches retrieved 22,217 records, of which 47 articles were included. The process led to identification of 88 unique health predictors (homologized to 21 predictor categories) of 55 outcomes (homologized to 19 outcome categories). Only pre-existing health conditions with high and moderate predictive values were discussed during the consensus meeting. Following the consensus meeting, 5 out of 11 were included (migraine, mental health conditions, ≥4 pre-existing health conditions, osteoporosis, and body mass index [BMI]) as common data elements in the AUS-TBI data dictionary. Upon further discussion, 3 additional pre-existing health conditions were included. These are pre-existing heart disease, frailty score, and previous incidence of TBI.

Good engraftment after reduced intensity targeted busulfan-based conditioning and matched related donor hematopoietic cell transplantation in hemoglobinopathies.

Hematopoietic cell transplantation (HCT) is an established curative therapy for transfusion-dependent thalassemia (TDT) and sickle cell disease (SCD). The latest American Society of Hematology guidelines recommend myeloablative preparative regimen in patients under 18years of age. The objective was to demonstrate safety and efficacy of a reduced intensity conditioning (RIC) regimen including high-dose fludarabine, anti-thymocyte globulin, and targeted busulfan as a single alkylator to sub-myeloablative exposures. Between 2012 and 2021, 11 patients with SCD and five patients with TDT and matched related donor (MRD) HCT were included. The median age at transplantation was 8.3years (range: 3.7-18.8years). The median administered busulfan AUC was 67.4mg/L×h (range: 60.7-80mg/L×h). Overall survival was 93.8% and event-free survival 87.5% with one engrafted SCD patient with pre-existing moyamoya disease succumbing after drainage of a subdural hematoma. One SCD patient developed a secondary graft failure and was treated with a second HCT. Myeloid chimerism was full in all other patients with a median follow-up time of 4.1years (range: 2.0-11.1years), whereas T-cell donor chimerism was frequently mixed. This RIC conditioning followed by MRD HCT is sufficiently myeloablative to cure pediatric patients with hemoglobinopathies without the need for additional total body irradiation or thiotepa.

Risk of cardiovascular events following COVID-19 in people with and without pre-existing chronic respiratory disease

Abstract Background COVID-19 is associated with cardiovascular outcomes in the general population, but it is unknown whether people with chronic respiratory disease (CRD) have a higher risk of cardiovascular events post-COVID-19 compared with the general population and, if so, what respiratory-related factors may modify this risk in these people. Methods Primary and secondary care data from the National Health Service England were used to define a population of adults in England with COVID-19 (index date) between 1 January 2020 and 30 November 2021. Adjusted Cox proportional hazard regression was used to quantify the association between CRD, asthma-related factors, chronic obstructive pulmonary disease (COPD)-related factors, and risk of cardiovascular events. Asthma-specific factors included baseline asthma control, exacerbations, and inhaled corticosteroid (ICS) dose. COPD-specific risk factors included baseline ICS and exacerbations. Secondary objectives quantified the impact of COVID-19 hospitalisation and vaccine dose on cardiovascular outcomes. Results Of 3 670 455 people, those with CRD had a higher risk of cardiovascular events [adjusted hazard ratio (HRadj), 1.08; 95% confidence interval (CI) 1.06–1.11], heart failure (HRadj, 1.17; 95% CI, 1.12–1.22), angina (HRadj, 1.13; 95% CI, 1.06–1.20) and pulmonary emboli (HRadj, 1.24; 95% CI, 1.15–1.33) compared with people without CRD. In people with asthma or COPD, baseline exacerbations were associated with a higher risk of cardiovascular outcomes (HRadj, 1.36; 95% CI, 1.27–1.00 and HRadj, 1.35; 95% CI, 1.24–1.46, respectively). Regardless of CRD, the risk of cardiovascular events was lower with increasing COVID-19 vaccine dose. Conclusions Higher risk of cardiovascular events post-COVID-19 might be explained by the underlying severity of the CRD, and COVID-19 vaccines were beneficial to both people with and those without CRD with regards to cardiovascualr events.

Real-world data of cardio-oncologic interventions for cardiovascular adverse events with oral oncolytics

BackgroundOral cancer therapy-related cardiovascular (CV) toxicity has a wide variety of presentations including arrhythmia, cardiomyopathy, and myocardial infarction, but clinical evidence related to its management is limited. The purpose of this IRB-approved, single-center, retrospective, cohort study was to characterize cardio-oncologic interventions for CV adverse events related to oral oncolytics.MethodsThe cohort included 67 patients who were admitted to a multi-hospital health system between June 1, 2016 and July 31, 2021, had at least one medical record order of oral oncolytics considered to have cardiotoxic potential, and had an ICD10 code for a cardiotoxic event added to their electronic medical records after initiation of oral oncolytics.ResultsThe majority (97%) had pre-existing cardiovascular disease (CVD) or a CV risk factor. The three most common classes of oral oncolytics were aromatase inhibitors (36%), BCR-ABL inhibitors (16%), and VEGFR inhibitors (13%). New-onset or worsening heart failure (HF) (n = 31), which occurred after a median of 148 days (Interquartile range (IQR) 43–476 days) was the most common cardiotoxic event. The most frequent interventions were pharmacological treatment of the CV adverse event (n = 44) and treatment interruption (n = 18), but guideline-directed medication therapy for HF could be further optimized.ConclusionPre-existing CVD or CV risk factors predispose oncology patients to CV adverse events. Real-world practice reveals that CV adverse events require temporary interruption of treatment and initiation of pharmacologic treatment. A multidisciplinary, patient-centered approach that includes discussion of risks/benefits of treatment continuation, and initiation of guideline-directed treatment is recommended until high-quality, drug-specific data for monitoring and treatment become available.

Definition of the Post-COVID syndrome using a symptom-based Post-COVID score in a prospective, multi-center, cross-sectoral cohort of the German National Pandemic Cohort Network (NAPKON)

PurposeThe objective examination of the Post-COVID syndrome (PCS) remains difficult due to heterogeneous definitions and clinical phenotypes. The aim of the study was to verify the functionality and correlates of a recently developed PCS score.MethodsThe PCS score was applied to the prospective, multi-center cross-sectoral cohort (in- and outpatients with SARS-CoV-2 infection) of the "National Pandemic Cohort Network (NAPKON, Germany)". Symptom assessment and patient-reported outcome measure questionnaires were analyzed at 3 and 12 months (3/12MFU) after diagnosis. Scores indicative of PCS severity were compared and correlated to demographic and clinical characteristics as well as quality of life (QoL, EQ-5D-5L).ResultsSix hundred three patients (mean 54.0 years, 60.6% male, 82.0% hospitalized) were included. Among those, 35.7% (215) had no and 64.3% (388) had mild, moderate, or severe PCS. PCS severity groups differed considering sex and pre-existing respiratory diseases. 3MFU PCS worsened with clinical severity of acute infection (p = .011), and number of comorbidities (p = .004). PCS severity was associated with poor QoL at the 3MFU and 12MFU (p < .001).ConclusionThe PCS score correlated with patients’ QoL and demonstrated to be instructive for clinical characterization and stratification across health care settings. Further studies should critically address the high prevalence, clinical relevance, and the role of comorbidities.Trail registration numberThe cohort is registered at www.clinicaltrials.gov under NCT04768998.

Public Health Relevance of US EPA Air Quality Index Activity Recommendations

Reducing exposure to fine particulate matter (<2.5 μm [PM2.5]) air pollution improves cardiopulmonary morbidity and mortality. However, the public health relevance of air quality index (AQI) activity guidelines under present-day environmental conditions in the US has not been critically assessed. To evaluate the public health relevance of following PM2.5 AQI activity guidance in preventing serious atherosclerotic cardiovascular disease (ASCVD) and pulmonary events among adults in the US. This cross-sectional modeling study involved the general adult population and sensitive individuals as designated by the US Environmental Protection Agency (EPA), including adults with preexisting ASCVD or lung disease (asthma or chronic obstructive pulmonary disease). The study was conducted between August 1, 2023, and January 31, 2024. Daily AQI strata for PM2.5 and the corresponding activity recommendations. The main outcome was the number needed to treat (NNT) per day by following activity guidance across daily AQI strata to prevent 1 serious ASCVD or pulmonary event among relevant populations. To calculate PM2.5-induced excess disease event rates per day, estimated baseline disease-specific daily event rates for each group were multiplied by the increase in risks due to PM2.5 levels at each AQI stratum. The number of events prevented per day was calculated by multiplying each excess disease event rate by the percentage in exposure reduction plausibly incurred by following population-specific activity guidance at each AQI level. The NNT is the reciprocal of the number of events prevented. The NNT to prevent ASCVD events was high for the general population and for patients with ASCVD across all AQI strata. The range of values was comparatively lower to prevent pulmonary events among adults with lung disease. During most days (96%) when activity recommendations were promulgated due to elevated PM2.5 (AQI, 101-200), the NNT to prevent a serious disease event remained very high for the general population (>18 million), patients with ASCVD (approximately 1.6-5 million), and adults with lung disease (approximately 66 000-202 000). These findings suggest that existing PM2.5 AQI activity recommendations are of questionable public health relevance in present-day conditions and merit consideration for updating to improve their potential effectiveness.

Missed postoperative metabolic acidosis associated with sodium-glucose transporter 2 inhibitors in cardiac surgery patients: a retrospective analysis

The increasing use of sodium glucose transporter 2 inhibitors (SGLT2i) for treating cardiovascular (CV) diseases and type 2 diabetes (T2D) is accompanied by a rise in euglycemic diabetic ketoacidosis occurrences in cardiac surgery patients. Patients undergoing cardiac surgery, due to their pre-existing CV disease which often requires SGLT2i prescriptions, face an increased risk of postoperative metabolic acidosis (MA) or ketoacidosis (KA) associated with SGLT2i, compounded by fasting and surgical stress. The primary aim of this study is to quantify the incidence of SGLT2i-related postoperative MA or KA and to identify related risk factors. We analyzed data retrospectively of 823 cardiac surgery patients, including 46 treated with SGLT2i from November 2019 to October 2022. Among 46 final cohorts treated preoperatively with SGLT2i, 29 (63%) developed postoperative metabolic complications. Of these 46 patients, stratified into two categories based on postoperative laboratory findings, risk factor analysis were conducted and compared. Analysis indicated a prescription duration over one week significantly elevated the risk of complications (Unadjusted OR, 11.7; p = 0.032*; Adjusted OR, 31.58; p = 0.014*). A subgroup analysis showed that a cardiopulmonary bypass duration of 60 min or less significantly raises the risk of SGLT2i-related postoperative MA in patients with a sufficient prescription duration. We omitted the term "diabetes" in describing complications related to SGLT2i, as these issues are not exclusive to T2D patients. Awareness of SGLT2i-related postoperative MA or KA can help clinicians distinguish between non-life-threatening conditions and severe causes, thereby preventing unnecessary tests and ensuring best practice.

A study of hospitalized COVID-19 patients with AKI in a setting of multiracial developing country

BackgroundThe commonest indication for hospitalization in COVID-19 patients is hypoxemia or severe respiratory symptoms. However, COVID-19 disease may result in extrapulmonary complications including kidney-related pathology. The reported incidence of renal involvement related to COVID infection varies based on geographical location.ObjectiveThis study aimed to assess the incidence rate of AKI in hospitalized COVID-19 patients and identify risk factors and prognostic predictors.MethodIn this retrospective study, we recruited hospitalized COVID-19 patients from January 2021 until June 2021 at the University Malaya Medical Center. The inclusion criteria were hospitalized for ≥ 48 h with confirmed COVID-19 infection and at least 18 years old. Patient demographic and clinical data were collected from electronic medical records. The staging of AKI was based on criteria as per KDIGO guidelines.ResultsOne thousand five hundred twenty-nine COVID patients fulfilled the inclusion criteria with a male-to-female ratio of 759 (49.6%) to 770 (50.3%). The median age was 55 (IQR: 36–66). 500 patients (32.7%) had diabetes, 621 (40.6%) had hypertension, and 5.6% (n = 85) had pre-existing chronic kidney disease (CKD). The incidence rate of AKI was 21.1% (n = 323). The percentage of COVID patients in different AKI stages of 1,2 and 3 were 16.3%, 2.1%, and 2.7%, respectively. Fifteen hospitalized patients (0.98%) required renal replacement therapy. 58.8% (n = 190) of AKI group had complete recovery of kidney function.Demographic factors included age (p < 0.001), diabetes (p < 0.001), hypertension (p < 0.012), CKD (p < 0.001), and vaccination status (p = 0.042) were associated with an increased risk of developing AKI. We found that the AKI cohort had statistically significant lower platelet counts and higher ferritin levels than the non-AKI cohort. AKI is a risk predictor of prolonged hospitalization (p < 0.001) and higher mortality rates (P < 0.001).ConclusionAKI is a common clinical complication among hospitalized COVID-19 patients. The etiology of AKI is multifactorial and may have an adverse impact on patient morbidity and mortality.

Evaluation of Renal Function with Urinary NGAL and Doppler Ultrasonography in ICU Patients: A 1-Year Observational Pilot Study.

We estimated the diagnostic accuracy of urinary NGAL for the diagnosis of AKI. Urinary NGAL and Creatinine were measured daily for up to 3 days. Doppler ultrasonography was performed within 24 h of admission and for the following 3 days. Of the 21 patients, 44% had AKI during their ICU stay. The AKI group presented with higher values of serum Creatinine, renal length, MDRD as well as SAPS II already at admission. Urinary NGAL was significantly higher among patients with AKI and patients AKI-no at T0 (p < 0.0001) and increased steadily on T1 and T2. Urinary NGAL seemed to be a notable diagnostic marker for AKI from the first measurement (T0) with an area under the ROC of 0.93 (95% CI = 0.78-0.99) with a sensitivity of 99%. RRI levels were slightly higher in the AKI group at each time and increased gradually from T0 to T2 but reached statistical significance only at T2 (p = 0.02). Renal length and SAPS II at T0 showed high AuRoc and sensitivity. Urinary NGAL is a valuable marker for AKI in intensive care settings. It seemed that a pre-existing chronic renal disease, the SAPS II and the NGAL at admission represented the principal predictors of AKI.

Role of a Pharmacist in Postdischarge Care for Patients With Kidney Disease: A Scoping Review.

The objective was to explore and describe the role of pharmacists in providing postdischarge care to patients with kidney disease. PubMed, Embase (Elsevier), CINAHL (Ebscohost), Web of Science Core Collection, and Scopus were searched on January 30, 2023. Publication date limits were not included. Search terms were identified based on 3 concepts: kidney disease, pharmacy services, and patient discharge. Experimental, quasi-experimental, observational, and qualitative studies, or study protocols, describing the pharmacist's role in providing postdischarge care for patients with kidney disease, excluding kidney transplant recipients, were eligible. Six unique interventions were described in 10 studies meeting inclusion criteria. Four interventions targeted patients with acute kidney injury (AKI) during hospitalization and 2 evaluated patients with pre-existing chronic kidney disease. Pharmacists were a multidisciplinary care team (MDCT) member in 5 interventions and were the sole provider in 1. Roles commonly identified include medication review, medication reconciliation, medication action plan formation, kidney function assessment, drug dose adjustments, and disease education. Some studies showed improvements in diagnostic coding, laboratory monitoring, medication therapy problem (MTP) resolution, and patient education; prevention of hospital readmission was inconsistent. Limitations include lack of standardized reporting of kidney disease, transitions of care processes, and differences in outcomes evaluated. This review identifies potential roles of a pharmacist as part of a postdischarge MDCT for patients with varying degrees of kidney disease. The pharmacist's role in providing postdischarge care to patients with kidney disease is inconsistent. Multidisciplinary care teams including a pharmacist provided consistent identification and resolution of MTPs, improved patient education, and increased self-awareness of diagnosis.

Safety of perioperative intravenous lidocaine in liver surgery - A pilot study.

Perioperative lidocaine infusion has many interesting properties such as analgesic effects in the context of enhanced recovery after surgery. However, its use is limited in liver surgery due to its hepatic metabolism. This prospective, monocentric study was conducted from 2020 to 2021. Patients undergoing liver surgery were included. They received a lidocaine infusion protocol until the beginning of hepatic transection (bolus dose of 1.5 mg kg-1, then a continuous infusion of 2 mg kg-1 h-1). Plasma concentrations of lidocaine were measured four times during and after lidocaine infusion. Twenty subjects who underwent liver resection were analyzed. There was 35% of preexisting liver disease before tumor diagnosis, and 75% of liver resection was defined as "major hepatectomy." Plasmatic levels of lidocaine were in the therapeutic range. No blood sample showed a concentration above the toxicity threshold: 1.6 (1.3-2.1) μg ml-1 one hour after the start of infusion, 2.5 (1.7-2.8) μg ml-1 at the end of hepatic transection, 1.7 (1.3-2.0) μg ml-1 one hour after the end of infusion, and 1.2 (0.8-1.4) μg ml-1 at the end of surgery. Comparative analysis between the presence of a preexisting liver disease or not and the association of intraoperative vascular clamping or not did not show significant difference concerning lidocaine blood levels. Perioperative lidocaine infusion seems safe in the field of liver surgery. Nevertheless, additional prospective studies need to assess the clinical usefulness in terms of analgesia and antitumoral effects.

Does pre-existing respiratory disease affect 3-month outcome following COVID hospitalisation across 4 waves: A prospective cohort analysis

Does pre-existing respiratory disease affect 3-month outcome following COVID hospitalisation across 4 waves: A prospective cohort analysis

Kaposi’s Varicelliform Eruption in a Patient with Darier’s Disease: A Rare Case Report

Darier's disease is a rare autosomal dominant disorder, characterized clinically by the appearance of multiple, pruritic, discrete, and scaly papules affecting seborrheic areas coupled with palmar pits, nail changes, and mucosal involvement. Histologically, the lesions show supra-basal clefts with acantholytic and dyskeratotic cells. Kaposi's varicelliform eruption (KVE) is the dissemination of the herpes simplex virus in the setting of preexisting skin disease, presenting with disseminated vesico-pustules. Darier's disease presenting as KVE is a rare occurrence. If misdiagnosed or left untreated can increase the rate of mortality. Here, we report the case of a 25-year-old male patient who presented with multiple vesicles and crusted lesions over the face, neck, chest, and upper back. After thorough cutaneous examination, he was found to have multiple hyperkeratotic, dirty-warty papules over seborrheic areas, present since childhood. With detailed clinical and laboratory evaluation, we arrived at the diagnosis of KVE with underlying Darier disease.

Cardiovascular risk associated with chronic treatment of paliperidone, olanzapine, risperidone and aripiprazole

IntroductionWeight gain, QT interval prolongation, and dyslipidemias associated with the chronic use of some antipsychotic medications can explain a higher prevalence of cardiovascular risk in these psychiatric population. The D’Agostino Index include some factors such as age, total cholesterol, high-density lipoproteins, systolic blood pressure increased, antihypertensive treatment, smoking, and diabetes, to estimate an individual’s risk (low, moderate or severe) of developing a cardiovascular event through a period of 10 years or throughout the patient’s lifetime.ObjectivesTo compare the degree of cardiovascular risk using the D’Agostino Index, among different antipsychotic medications.MethodsAn estimation of cardiovascular risk (low, moderate, or high) was performed with the D´Agostino index in a sample of 144 patients (82 men and 62 women) mean age 45,2 +/- 10.13. All patients were treated for at least one year at a therapeutic dose and adhered to their treatment regimen correctly. Subjects with some relevant pre-existing unstable heart disease were excluded. All patients previously provided informed consent and were of legal age. Clinical data on medical history, concomitant medications, and risk factors were collected. A completed physical exam, waist circumference, lab sample, a lifestyle scale, and an evaluation of vital signs in accordance with European Society of Hypertension were evaluated. Statistical analysis was carried out using the statistical software SPSS version 26.0. A significance level α=0.05 was considered throughout the study.ResultsThe four most consumed antipsychotics were risperidone 9.72% (n=14), paliperidone 25.7% (n=37), olanzapine 14.6% (n=21), and aripiprazole 34.7% (n=50). Descriptively, it was observed that the drugs most associated with moderate or high risks were paliperidone (37.8%) and olanzapine (33.3%), risperidone (28.6 %). Aripiprazol (22%) was the less associated compound with moderate/high cardiovascular risk.ConclusionsSubjects treated with olanzapine and paliperidone showed a higher association with cardiovascular risk. Predicting cardiovascular risk could provide individual benefits by enabling lifestyle modifications, pharmacological treatment changes, or closer monitoring to reduce cardiovascular risk.Disclosure of InterestA. Montejo Grant / Research support from: This study has been funded by the Instituto de Salud Carlos III (ISCIII) through the project PI19/1596 and co-funded by the European Union., C. Bermejo: None Declared, J. Matías: None Declared, T. Martín: None Declared, J. Matías-Polo: None Declared, Y. Santana: None Declared, J. López-López: None Declared, R. de Alarcón: None Declared, J. Acosta: None Declared

Affected by Surgery, Healed by Medicine a Successful Story

ABSTRACT Infective endocarditis (IE) is relatively less common in children compared to adults but can result in significant morbidity and mortality. The epidemiology of IE has shifted in recent years, from rheumatic heart disease (less prevalence) to congenital heart disease (increased survival) and an increase in the use of central venous catheters in children with chronic illness. Children with no preexisting cardiac disease can be affected rarely. We present a case of a 13-year-old boy with no cardiac disease, presented with a fever. He had a history of surgery for hypospadias 3 weeks before presentation. He was diagnosed with IE according to modified Duke criteria. The blood cultures grew methicillin-resistant Staphylococci aureus. The case was surgically deferred in view of his clinical condition and was managed medically. We emphasize the importance of having a high index of suspicion for endocarditis in children with fever even without cardiac disease.

Delayed Diagnosis of Vasopressor-induced Symmetrical Peripheral Gangrene in Septic Shock Patient

Vasopressors are powerful vasoconstrictors used in critically ill patients to raise blood pressure after volume resuscitation attempts fail. These medications, while lifesaving, carry the risk of severe and under-reported side effects, digital ischemia, and gangrene due to decreased digital perfusion. We here present a case of vasopressin-induced digital gangrene in a female patient who underwent elective surgery for nephrolithiasis without any pre-existing peripheral vascular disease or smoking. The patient developed bilateral upper and lower limb symmetrical acronecrosis. The causality assessment as per the World Health Organisation – Uppsala Monitoring Centre scale was suggestive of a “Possible adverse” event. The patient denied surgical intervention, eventually developed multiorgan failure, and died of cardiopulmonary arrest. Although lifesaving, vasopressors due to alpha constricting activity can cause severe limb ischemia with dreadful consequences. These drugs should be used judiciously with careful monitoring and tapering as soon as possible when the condition improves. The consequences could be dreadful if timely surgical intervention and measures are not taken.

In Vitro Hepatotoxicity of Routinely Used Opioids and Sedative Drugs.

A hepatocyte cell line was used to determine the hepatotoxicity of sedatives and opioids, as the hepatotoxicity of these drugs has not yet been well characterized. This might pose a threat, especially to critically ill patients, as they often receive high cumulative doses for daily analgosedation and often already have impaired liver function due to an underlying disease or complications during treatment. A well-established biosensor based on HepG2/C3A cells was used for the determination of the hepatotoxicity of commonly used sedatives and opioids in the intensive care setting (midazolam, propofol, s-ketamin, thiopental, fentanyl, remifentanil, and sufentanil). The incubation time was 2 × 3 days with clinically relevant (Cmax) and higher concentrations (C5× and C10×) of each drug in cell culture medium or human plasma. Afterward, we measured the cell count, vitality, lactate dehydrogenase (LDH), mitochondrial dehydrogenase activity, cytochrome P 450 1A2 (CYP1A2), and albumin synthesis. All tested substances reduced the viability of hepatocyte cells, but sufentanil and remifentanil showed more pronounced effects. The cell count was diminished by sufentanil in both the medium and plasma and by remifentanil only in plasma. Sufentanil and remifentanil also led to higher values of LDH in the cell culture supernatant. A reduction of mitochondrial dehydrogenase activity was seen with the use of midazolam and s-ketamine. Microalbumin synthesis was reduced in plasma after its incubation with higher concentrations of sufentanil and remifentanil. Remifentanil and s-ketamine reduced CYP1A2 activity, while propofol and thiopental increased it. Our findings suggest that none of the tested sedatives and opioids have pronounced hepatotoxicity. Sufentanil, remifentanil, and s-ketamine showed moderate hepatotoxic effects in vitro. These drugs should be given with caution to patients vulnerable to hepatotoxic drugs, e.g., patients with pre-existing liver disease or liver impairment as part of their underlying disease (e.g., hypoxic hepatitis or cholestatic liver dysfunction in sepsis). Further studies are indicated for this topic, which may use more complex cell culture models and global pharmacovigilance reports, addressing the limitation of the used cell model: HepG2/C3A cells have a lower metabolic capacity due to their low levels of CYP enzymes compared to primary hepatocytes. However, while the test model is suitable for parental substances, it is not for toxicity testing of metabolites.

Long-term impact of COVID-19 hospitalisation among individuals with pre-existing airway diseases in the UK: a multicentre, longitudinal cohort study - PHOSP-COVID.

The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p<0.001), had higher burden of anxiety (29.1% versus 22.0%, p=0.002), depression (31.2% versus 24.7%, p=0.006), higher percentage of impaired mobility using short physical performance battery ≤10 (57.4% versus 45.2%, p<0.001) and 27% had a new disability (assessed by the Washington Group Short Set on Functioning) versus 16.6%, p=0.014. HRQoL assessed using EQ-5D-5L Utility Index was lower in the airways group (mean±SD 0.64±0.27 versus 0.73±0.25, p<0.001). Burden of breathlessness, fatigue and cough measured using a study-specific tool was higher in the airways group. Individuals with pre-existing airway diseases hospitalised due to COVID-19 were less likely to feel fully recovered, had lower physiological performance measurements, more burden of symptoms and reduced HRQoL up to 1 year post-hospital discharge.

Risk Factors for Thyroid Dysfunction in Pregnancy: An Individual Participant Data Meta-Analysis.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.