High Associated Mortality Research Articles

Prevalence, Risk Factors, and Outcome of Carbapenem-resistant Acinetobacter Infections in a Community Hospital in Madinah, Saudi Arabia

Abstract Background: Acinetobacter is a Gram-negative bacterium that causes nosocomial infections, increasing healthcare costs, patient morbidity, and mortality. The rate of carbapenem resistance among Acinetobacter species is rising in several countries, including Saudi Arabia. Objective: To determine the risk factors and compare the predictors of mortality in patients infected with carbapenem-susceptible and carbapenem-resistant Acinetobacter strains. Materials and Methods: This retrospective study included patients with Acinetobacter infection who were admitted to a community hospital in Madinah, Saudi Arabia, between January 2017 and June 2021. A logistic regression analysis was conducted to assess the risks of acquiring carbapenem-resistant Acinetobacter infections and the mortality risk associated with these infections. Results: This study included 138 Acinetobacter-infected cases, of which 114 (82%) were carbapenem-resistant infections. Between 2017 and 2020, resistance rates increased from 75% to 87%. Patients with carbapenem-resistant Acinetobacter infections had higher 90-day mortality than those with carbapenem-susceptible infection (62% vs. 29%, P = 0.006). The risk factors for carbapenem-resistant Acinetobacter infections were prior antimicrobial therapy (aOR: 8.36 [1.69–41.29]; P = 0.009) and mechanical ventilation (aOR: 6.07 [1.82–20.20]; P = 0.003). Among all patients with Acinetobacter infections, significant predictors of 90-day mortality were carbapenem resistance (aOR: 3.26 [1.19–8.90]; P = 0.021) and Charlson comorbidity score (aOR: 1.19 [1.06–1.34]; P = 0.004). Conclusion: The increase in carbapenem-resistant Acinetobacter cases in this study was consistent with the findings of other studies from Saudi Arabia. This, together with the high associated mortality rates, indicates the urgent need for effective antimicrobials and infection prevention strategies to combat carbapenem-resistant Acinetobacter infections in hospitals.

A Global Meta-Analysis of the Effects of Greenspaces on COVID-19 Infection and Mortality Rates.

The COVID-19 outbreak in 2020 resulted in rapidly rising infection rates with high associated mortality rates. In response, several epidemiological studies aimed to define ways in which the spread and severity of COVID-19 can be curbed. As a result, there is a steady increase in the evidence linking greenspaces and COVID-19 impact. However, the evidence of the benefits of greenspaces or greenness to human wellbeing in the context of COVID-19 is fragmented and sometimes contradictory. This calls for a meta-analysis of existing studies to clarify the matter. Here, we identified 621 studies across the world on the matter, which were then filtered down to 13 relevant studies for meta-analysis, covering Africa, Asia, Europe, and the USA. These studies were meta-analyzed, with the impacts of greenness on COVID-19 infection rate quantified using regression estimates whereas impacts on mortality rates were measured using mortality rate ratios. We found evidence of significant negative correlations between greenness and both COVID-19 infection and mortality rates. We further found that the impacts on COVID-19 infection and related mortality are moderated by year of publication, greenness metrics, sample size, health and political covariates. This clarification has far-reaching implications for policy development toward the establishment and management of green infrastructure for the benefit of human wellbeing.

The Incidence of Clostridioides difficile Infection in the Post-COVID-19 Era in a Hospital in Northern Greece.

Clostridioides difficile infection (CDI) has evolved to be the most significant cause of healthcare-associated diarrhoea and one of the leading representatives of healthcare-associated infections, with a high associated mortality. The aim of this retrospective study was to record the incidence rates and the epidemiological and clinical features of CDI in a large tertiary hospital of northern Greece in the years 2022-2023. All patients with CDI-compatible symptomatology and a positive CDI diagnostic test (GDH-glutamate dehydrogenase and toxin-positive FIA-Fluorescent Immuno-chromatography-SD Biosensor, and/or film array) were included (104 from a total of 4560 admitted patients). Their demographic, laboratory, and clinical data were recorded and analysed. The incidence of CDI in admitted patients was found to be higher than previous reports in the geographical area, reaching 54.6/10,000 patient days and following a rising trend over the course of the study. Thirty-day mortality was high (39.4%), potentially related to new emerging hypervirulent C. difficile strains. In view of the high prevalence of multidrug-resistant organisms in the region, and the significant mortality associated with this infection, these findings particularly point to the need for the implementation of organized surveillance and infection prevention protocols.

Correction of Trauma-induced Coagulopathy by Goal-directed Therapy: A Secondary Analysis of the ITACTIC Trial.

Trauma hemorrhage induces a coagulopathy with a high associated mortality rate. The Implementing Treatment Algorithms for the Correction of Trauma Induced Coagulopathy (ITACTIC) randomized trial tested two goal-directed treatment algorithms for coagulation management: one guided by conventional coagulation tests and one by viscoelastic hemostatic assays (viscoelastic). The lack of a difference in 28-day mortality led the authors to hypothesize that coagulopathic patients received insufficient treatment to correct coagulopathy. During ITACTIC, two sites were coenrolling patients into an ongoing prospective observational study, which included serial blood sampling at the same intervals as in ITACTIC. The subgroup in both studies had conventional and viscoelastic test results for each patient available for analysis. A goal-directed treatment was defined as one triggered by an ITACTIC algorithm. Coagulopathy was defined as rotational thromboelastometry EXTEM A5 less than 40 mm. The primary outcome was correction of coagulopathy by the 12th unit of erythrocyte transfusion during resuscitation. Full viscoelastic and conventional coagulation test results were available for 133 patients. Of these patients, 71% were coagulopathic on admission, and 16% developed a coagulopathy during resuscitation. ITACTIC viscoelastic hemostatic assay group patients were more likely to receive goal-directed treatment than the standard group (76% vs. 47%; odds ratio, 3.73; 95% CI, 1.64 to 8.49; P = 0.002). However, only 54% of patients received goal-directed treatment, and only 20% corrected their coagulopathy (vs. 0% with empiric treatment alone; not significant). Median time to first goal-directed treatment was 68 (53 to 88) min for viscoelastic and 110 (77 to 123) min for standard (P = 0.005). In ITACTIC, many bleeding trauma patients did not receive an indicated goal-directed treatment. Interventions arrived late during resuscitation and were only partially effective at correcting coagulopathy.

Streptococcus mitis and Klebsiella pneumoniae Mixed Infection in Severe Burn Injury Patient

Burns are a significant problem with high associated morbidity and mortality worldwide. Bacteremia is a serious complication that is important in increasing the overall fatality rate in burn injury patients. In this study, we report a case of Streptococcus mitis and Klebsiella pneumoniae mixed infection in severe burns in a 40-year-old female. The patient was transferred from an outside hospital to the emergency unit after burn injuries in a gas explosion accident at home. The patient underwent surgical debridement and antibiotics treatment but died due to sepsis and multiorgan failure. Our case study will help to underscore the important role of Streptococcus mitis and Klebsiella pneumoniae as human opportunistic pathogens in severe burn injury patients.

Does delay to theatre influence morbidity or mortality in femoral periprosthetic fractures?

Femoral periprosthetic fractures are rising in incidence. Their management is complex and carries a high associated mortality. Unlike native hip fractures, there are no guidelines advising on time to theatre in this group. We aim to determine whether delaying surgical intervention influences morbidity or mortality in femoral periprosthetic fractures. We identified all periprosthetic fractures around a hip or knee arthroplasty from our prospectively collated database between 2012 and 2021. Patients were categorized into early or delayed intervention based on time from admission to surgery (early = ≤ 36 hours, delayed > 36 hours). Patient demographics, existing implants, Unified Classification System fracture subtype, acute medical issues on admission, preoperative haemoglobin, blood transfusion requirement, and length of hospital stay were identified for all patients. Complication and mortality rates were compared between groups. A total of 365 patients were identified: 140 in the early and 225 in the delayed intervention group. Mortality rate was 4.1% at 30 days and 19.2% at one year. There was some indication that those who had surgery within 36 hours had a higher mortality rate, but this did not reach statistical significance at 30 days (p = 0.078) or one year (p = 0.051). Univariate analysis demonstrated that age, preoperative haemoglobin, acute medical issue on admission, and the presence of postoperative complications influenced 30-day and one-year mortality. Using a multivariate model, age and preoperative haemoglobin were independently predictive factors for one-year mortality (odds ratio (OR) 1.071; p < 0.001 and OR 0.980; p = 0.020). There was no association between timing of surgery and postoperative complications. Postoperative complications were more likely with increasing age (OR 1.032; p = 0.001) and revision arthroplasty compared to internal fixation (OR 0.481; p = 0.001). While early intervention may be preferable to reduce prolonged immobilization, there is no evidence that delaying surgery beyond 36 hours increases mortality or complications in patients with a femoral periprosthetic fracture.

A Critical Combination of Esophageal Rupture and Upside-down Stomach: A Case Report.

Spontaneous esophageal rupture, or Boerhaave syndrome, and upside-down stomach are rare pathologies associated with grave sequelae. Boerhaave syndrome can have a mortality rate as high as 44%. Upside-down stomach accounts for less than 5% of hiatal hernias and can lead to incarceration and volvulus. An 80-year-old woman presented to the emergency department with sudden onset, severe epigastric pain. Physical examination revealed normal vital signs with mild epigastric tenderness. Imaging obtained revealed a large hiatal hernia and findings concerning for esophageal perforation. The patient was started on 3.375 grams of intravenous piperacillin/tazobactam, and transfer to a tertiary care facility was initiated. After transfer, esophagography confirmed a perforation near the gastroesophageal junction and findings consistent with an upside-down stomach. The patient underwent successful repair of the esophageal perforation and gastropexy followed by intensive care unit admission and ultimately discharge. Boerhaave syndrome and upside-down stomach are two conditions with high associated morbidity and mortality requiring prompt intervention. Information obtained in the history and physical examination including acute onset of chest pain after vomiting, tachypnea, subcutaneous emphysema, and hypoxia can assist in the diagnosis of the described pathologies. These signs and symptoms can be subtle on examination but are important in raising clinical suspicion for an otherwise rare etiology for acute onset chest pain.

Implementation of a rapid diagnostic assay package for cryptococcosis, histoplasmosis and tuberculosis in people living with HIV in Paraguay

BackgroundOpportunistic infections (OIs) are common causes of mortality among people living with HIV (PLHIV). We determined prevalence and 30-day mortality due to histoplasmosis, cryptococcosis, and TB in PLHIV with advanced HIV disease (AHD).MethodsPLHIV 18 years and older, with a CD4 + T-cell count of less than 350 cells/mm3 newly diagnosed with HIV infection or re-engaged in care after being without ART for more than 90 days (Group A). The second group included symptomatic PLHIV regardless of ART status or CD4 + T-cell count (Group B); all followed for 30 days. Detection of Histoplasma Ag (HisAg) in urine was done by enzyme immunoassay (EIA), Cryptococcus antigen (CrAg) was detected in serum and cerebrospinal fluid (CSF) specimens by lateral flow assay (LFA), and lipoarabinomannan (LAM) detection in urine was by LFA (TB LAM) and in sputum by GeneXpert for diagnosis of Mycobacterium infections.ResultsFrom August 2021 to June 2022, 491 PLHIV were enrolled; 482 (98%) had a CD4 + T-cell result, and 381 patients (79%) were classified with AHD according to CD4 + T-cell count (< 200 CD4/mm3). Frequency of an OI was 38% (n = 145/381). Antigen test positivity rate was 16% (72/467) for TB-LAM, 9% (43/464) for HisAg, and 11% (51/484) for CrAg. Twenty-one of 34 (62%) patients receiving CSF CrAg tests were positive, confirming meningitis. Significant differences in 30-day mortality were observed in patients with an OI (16%) vs. no OI (7%) (p = 0.002). Mortality was highest in patients with histoplasmosis (25%), co-infection (22%), cryptococcosis (18% overall; 19% for cryptococcal meningitis), and TB (10%).ConclusionsTB and fungal OIs, including co-infection, were common in PLHIV in Paraguay and had high associated mortality. Laboratories and health facilities need access to CD4 + T-cell testing and rapid diagnostic assays.

Approximation to the economic cost of healthcare for hypertensive patients diagnosed with COVID-19.

Many researchers have focused their studies on hypertension due to its over-representation among COVID-19 patients. Both retrospective and observational studies conducted close to the Wuhan area have reported that hypertension is the most common comorbidity observed in patients affected by COVID-19. Our objective is that patients with arterial hypertension have a worse prognosis in terms of evolution leading to higher costs. A retrospective cross-sectional study was conducted. A total of 3,581 patients from La Paz University Hospital (LPUH) during the period between 15 July 2020 and 31 July 2020 were included in this study. It should be noted that 40.71% of the patients were hypertensive. As expected, hypertension was associated with men, among whom we observed a higher prevalence and a higher age (median age of 77 years (IQI: 65-85) versus 52 years (IQI: 37-64), p-value < 0.001). Hypertensive patients had a higher prevalence of dyspnea (52.14% vs. 47.15%, p-value = 0.004) and altered awareness (14.89% vs. 4.30%, p-value <0.001). The non-parametric Kaplan-Meier curve estimates the survival of patients in the two study groups. We can see how patients with hypertension have a higher associated mortality, with the difference being statistically significant, p-value (log-rank) = 0.004. Only for the appearance of complications during hospitalization, the group of hypertensive patients reached the figure of €1,355,901.71 compared to the total of 421,403.48 € for normotensive patients. Our study shows the worse clinical evolution of patients with COVID-19 in terms of associated morbidity and mortality. It also shows that the cost of managing patients with hypertension is greater than that of managing normotensive patients.

The impact of the COVID-19 pandemic on non-COVID-associated mortality: A descriptive longitudinal study of UK data

BackgroundIt has been previously reported in the literature that the COVID-19 pandemic resulted in overall excess deaths and an increase in non-COVID deaths during the pandemic period.Specifically, our research elucidates the impact of the COVID-19 pandemic on non-COVID associated mortality. Study aimTo compare mortality rates in non-COVID conditions before and after the onset of the COVID-19 pandemic in England and Wales. Study designAnnual mortality data for the years 2011–2019 (pre-pandemic) and 2020 (pandemic) in England and Wales were retrieved from the Office for National Statistics (ONS). These data were filtered by ICD-10 codes for nine conditions with high associated mortality. We calculated mortality numbers – overall and age stratified (20–64 and 65+ years) and rates per 100 000, using annual mid-year population estimates. MethodsInterrupted time series analyses were conducted using segmented quasi-Poisson regression to identify whether there was a statistically significant change (p < 0.05) in condition-specific death rates following the pandemic onset. ResultsEight of the nine conditions investigated in this study had significant changes in mortality rate during the pandemic period (2020). All-age mortality rate was significantly increased in: ‘Symptoms Signs and Ill-defined conditions’, ‘Cirrhosis and Other Diseases of the Liver’, and ‘Malignant Neoplasm of the Breast’, whereas ‘Chronic Lower Respiratory Disorders’ saw a significant decrease. Age-stratified analyses also revealed significant increases in the 20–64 age-group in: ‘Cerebrovascular Disorders’, ‘Dementia and Alzheimer's Disease’, and ‘Ischaemic Heart Diseases’. ConclusionTrends in non-COVID condition-specific mortality rates from 2011 to 2020 revealed that some non-COVID conditions were disproportionately affected during the pandemic. This may be due to the direct impact COVID-19 had on these conditions or the effect the public health response had on non-COVID risk factor development and condition-related management. Further work is required to understand the reasons behind these disproportionate changes.

The Impact of Chronic Comorbidities on Outcomes in Acute Exacerbations of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis is a chronic progressive lung disease of unknown cause with a high associated mortality. We aimed to compare the impact of chronic medical conditions on hospital outcomes of patients with acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). This was a retrospective cohort study using the NIS database from 2016 to 2018. We included patients aged 60 and older hospitalized in academic medical centers with the diagnoses of IPF and acute respiratory failure. We examined factors associated with hospital mortality and length of stay (LOS) using survey-weighted multivariate logistic and negative binomial regression. Out of 4975 patients with AE-IPF, 665 (13.4%) did not survive hospitalization. There was no difference in the mean age between survivors and non-survivors. Patients were more likely to be male, predominantly white, and have Medicare coverage. Most non-survivors were from households with higher median income. Hospital LOS was longer among non-survivors than survivors (9.4 days vs. 9.8 days; p < 0.001). After multivariate-logistic regression, diabetes was found to be protective (aOR 0.62, 95% CI 0.50-0.77; p < 0.0001) while chronic kidney disease (CKD) conferred a significantly higher risk of death after AE-IPF (aOR 6.85, 95% CI 1.90-24.7; p = 0.00). Our multivariate adjusted negative binomial regression model for LOS identified obesity (IRR 0.85, 95% CI 0.76-0.94; p ≤ 0.00) and hypothyroidism (IRR 0.90, 95% CI 0.83-0.98; p = 0.02) to be associated with shorter hospital LOS. Our results suggest that CKD is a significant contributor to hospital mortality in AE-IPF, and diabetes mellitus may be protective. Obesity and hypothyroidism are linked with shorter hospital LOS among patients hospitalized with AE-IPF in US academic medical centers.

2137. Real World Experience with Eravacycline for the Treatment of Infections Caused by Carbapenem-Resistant Acinetobacter baumannii

Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAB) are considered an urgent public health threat responsible for causing severe infections with high associated mortality. CRAB isolates are often resistant to several antibiotic classes thereby limiting treatment options. Eravacycline is a novel tetracycline antibiotic with potent in vitro activity against CRAB. Per the recent Infectious Diseases Society of America (IDSA) Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections, clinical data are limited for eravacycline use for CRAB infections. The purpose of this study was to evaluate clinical outcomes of patients treated with eravacycline for CRAB infections at Montefiore Medical Center. Methods This was a retrospective chart review of patients 18 years of age and older who received eravacycline for at least 72 hours for the treatment of an infection due to CRAB between January 1, 2019 to February 28, 2023. Patients were excluded if they had a urinary tract infection. Patient demographics, risk factors, type/source of infection, clinical outcomes, etc. were collected. Results Eighteen patients received eravacycline for the treatment of non-urinary CRAB infections (Table 1). Ventilator-associated pneumonia was the predominant infection, representing 14/18 (78%) cases. High rates of antibiotic non-susceptibility were demonstrated in all cases. Median eravacycline minimum inhibitory concentration (MIC) was 1 mg/L, with a range of 0.19 – 6 mg/L. Median duration of eravacycline therapy was 7 days. Overall, the clinical success rate was 33% (6/18). Four patients (22%) experienced progression or worsening of symptoms that required a change in antibiotics. Of 11 evaluable patients, three patients (27%) had a recurrent infection caused by CRAB within 30 days of completion of eravacycline therapy. All-cause 30-day mortality was 56% (10/18), with six deaths (33%) attributed to CRAB infection. Conclusion CRAB infections pose a significant challenge in the healthcare setting and are associated with high mortality rates. Eravacycline remains a last resort option for these difficult to treat infections. Further study is warranted for eravacycline use for CRAB infections. Disclosures All Authors: No reported disclosures

Prehospital and emergency department airway management of severe penetrating trauma in Sweden during the past decade

BackgroundPrehospital tracheal intubation (TI) is associated with increased mortality in patients with penetrating trauma, and the utility of prehospital advanced airway management is debated. The increased incidence of deadly violence in Sweden warrants a comprehensive evaluation of current airway management for patients with penetrating trauma in the Swedish prehospital environment and on arrival in the emergency department (ED).MethodsThis was an observational, multicenter study of all patients with penetrating trauma and injury severity scores (ISSs) ≥ 15 included in the Swedish national trauma register (SweTrau) between 2011 and 2019. We investigated the frequency and characteristics of prehospital and ED TI, including 30-day mortality and patient characteristics associated with TI.ResultOf 816 included patients, 118 (14.5%) were intubated prehospitally, and 248 (30.4%) were intubated in the ED. Patients who were intubated prehospitally had a higher ISS, 33 (interquartile range [IQR] 25, 75), than those intubated in the ED, 25 (IQR 18, 34). Prehospital TI was associated with a higher associated mortality, OR 4.26 (CI 2.57, 7.27, p < 0.001) than TI in the ED, even when adjusted for ISS (OR 2.88 [CI 1.64, 5.14, p < 0.001]). Hemodynamic collapse (≤ 40 mmHg) and low GCS score (≤ 8) were the characteristics most associated with prehospital TI. Traumatic cardiac arrests (TCAs) occurred in 154 (18.9%) patients, of whom 77 (50%) were intubated prehospitally and 56 (36.4%) were intubated in the ED. A subgroup analysis excluding TCA showed that patients with prehospital TI did not have a higher mortality rate than those with ED TI, OR 2.07 (CI 0.93, 4.51, p = 0.068), with OR 1.39 (0.56, 3.26, p = 0.5) when adjusted for ISS.ConclusionPrehospital TI was associated with a higher mortality rate than those with ED TI, which was specifically related to TCA; intubation did not affect mortality in patients without cardiac arrest. Mortality was high when airway management was needed, regardless of cardiac arrest, thereby emphasizing the challenges posed when anesthesia is needed. Several interventions, including whole blood transfusions, the implementation of second-tier EMS units and measures to shorten scene times, have been initiated in Sweden to counteract these challenges.

1185 SADHemi Study: A Service Evaluation of Operative Treatment of Dislocated Hip Hemiarthroplasty in the UK – Initial Results

Abstract Aim Hip hemiarthroplasty is a common orthopaedic procedure for intra-capsular neck of femur fracture. Dislocation is a rare but serious complication with a reportedly high mortality, but the literature and guidance for management is sparse. This study aims to evaluate the prevalence and determine the UK’s current management of dislocated hip hemiarthroplasty. Method A national collaborative was established to undertake a retrospective evaluation of patients aged ≥60 years with dislocation of a hip hemiarthroplasty carried out between January 2015 to December 2020. Eligible patients were identified by a site lead at each participating centre and data including patient demographics, management and mortality was entered on to REDCap for analysis. Results 16 centres have been recruited and 137 patients entered: 65% female; average age 84 years and ASA grade 3. Median time to first dislocation was 22 days. Only 25.9% failed initial closed reduction. 57 patients re-dislocated (45.9%) and of these 64.9% had a successful closed reduction, and 46.4% had further dislocation episodes. Only 20% of patients were still alive at the time data entry. Conclusions The initial results show the rate of successful closed reduction of first time dislocation was higher, and the rate of re-dislocation was lower, amongst the SADHemi patients than previously estimated in the limited existing literature. There was more success with second closed reduction than previously reported. Early results suggest a high associated mortality. By expanding the national collaborative to gain more data we hope to further this evaluation and perhaps update the current protocols for management.

Successful treatment of severe calciphylaxis in a renal transplant patient with previous total parathyroidectomy.

Calciphylaxis is a rare dermatological condition strongly associated with chronic kidney disease. The clinical course can be devastating, with high associated morbidity and mortality. The pathophysiology and optimum treatment remain uncertain. Calciphylaxis is known mostly to affect dialysis patients but is less frequently reported in renal transplant recipients. We report the case of a renal transplant recipient who had undergone previous total parathyroidectomy. Diagnosis was made at the time of limb amputation, yet despite this relatively late diagnosis she made a good recovery. We believe this resulted from a multi-modal approach including surgical debridement, sodium thiosulphate and vitamin K2 therapy. She remained free from recurrence 2 years after completion of treatment, despite on-going vitamin D replacement. There is much still to ascertain regarding calciphylaxis treatment, including the optimal regimens and duration of therapy, particularly in the transplant recipient population where data are limited.

P103 A retrospective observational study of toxic epidermal necrolysis at a tertiary referral centre from 2015 to 2022

Abstract Toxic epidermal necrolysis (TEN) is associated with high mortality and morbidity. Owing to a lack of robust evidence, treatment guidelines are ambiguous and clinicians must use discretion in management decisions, specifically with regard to the use and choice of systemic agents, including immunosuppressants. We present a retrospective study of cases referred to a tertiary referral centre between 2015 and 2022. Cases were identified using histopathology coding and a database compiled by clinicians. Forty cases were categorized as follows: TEN (n = 12); Stevens–Johnson syndrome (SJS)/TEN overlap (n = 5); SJS (n = 5); unclear (n = 9); insufficient information (n = 5) and others [n = 9 (lupus, n = 4; erythema multiforme major, n = 3; burn, n = 1; recurrent erythema multiforme, n = 1)]. The median age of patients with TEN was 66 [interquartile range (IQR) 53.3–74; 33% men, 67% women]. The median percentage body surface area of epidermal loss was 40% (n = 8; IQR 30–70). Forty-two per cent of patients had an underlying malignancy. Implicated medications included nivolumab/ipilimumab (n = 2), co-trimoxazole (n = 2), carbamazepine (n = 1) and proton pump inhibitors (n = 3). Sixty-seven per cent of patients with TEN were managed by the burns centre, with a further 17% admitted to the intensive care unit. One patient presented directly to the dermatology team and 58% were transferred from other hospitals. The median time from the documented onset of rash to transfer to specialist care was 5 days (IQR 2.8–11.5). Thirty-three per cent of patients were given immunosuppression (intravenous methylprednisolone). The median duration of admission was 14 days (IQR 7.5–21.5). Fifty-eight per cent of patients (n = 7) survived. None of the five patients who died had received immunosuppression. The median time from onset of rash to receiving specialist care was 3.5 days for those who survived (n = 4) vs. 10 days for those who did not (n = 3; P = 0.03). Thirty-three per cent of patients had documented chronic complications (severe ophthalmic sequelae, n = 2; circumcision for phimosis, n = 1). This study was limited by the retrospective collection of data and the method used to identify cases. The current evidence for the treatment of TEN is primarily derived from small case series that often combine heterogeneous cases of TEN, SJS/TEN overlap and SJS. This is highly problematic as the risk–benefit dynamic varies greatly between patients with SJS, who have an excellent prognosis without treatment, and patients with TEN with a high associated mortality, who potentially have more to gain from immunosuppression. Our data support the need for patients to access specialist care promptly, to allow for early consideration of immunosuppression. Future research should focus on effective treatments for reducing mortality in cases of TEN specifically.

Incidence, trends, and significance of putative koala retrovirus-associated diseases in monitored wild koala populations in southeast Queensland. In Proceedings of the Second Koala Retrovirus Workshop, ed. D. E. Alquezar-Planas, D. P. Higgins, C. L. Singleton, and A. D. Greenwood

Research indicates that northern koalas (Phascolarctos cinereus) are ubiquitously infected with koala retrovirus (KoRV). There is increasing evidence linking KoRV with neoplasia and a range of disorders associated with immunodeficiency, conditions observed at high rates in captive colonies, and sick koalas presenting to wildlife hospitals. However, less is known about the occurrence of these putative KoRV-associated diseases in wild populations. We analysed health data collected at the veterinary examinations of 691 koalas inhabiting three monitored wild koala populations in southeast Queensland between 2013 and 2020. At initial presentation, neoplasia and AIDS-like syndrome were detected at a prevalence of 1.16% (8/691; 95% CI 0.5–2.19%). Longitudinal data from koalas recruited into the monitoring programmes and receiving one or more subsequent examination revealed an incidence rate of 3.5 cases/100 koalas/year (95% CI 2.35–4.9). These findings indicate that a relatively small proportion of the populations studied were affected by these putative KoRV-associated diseases. However, the impact on individuals was severe, with high associated mortality in the diseased cohort. Furthermore, northern koala populations endure multiple threats, suffering severe declines in recent decades. We propose that the significance of putative KoRV-associated diseases on these populations should be considered within this context and that further research into the interactions between KoRV and other drivers of decline is warranted.

Salinization, inundation and tree mortality interact to affect greenhouse gas emissions from stressed coastal forests

Sea level rise and intensifying storms cause salinization and freshwater inundation of coastal forest soils which can result in tree mortality and altered ecosystem carbon (C) cycling. However, it is not yet clear if increased salinity and inundation will affect greenhouse gas (GHG) emissions to feed back with climate change. To assess the impacts of in situ chronic and pulsed salinity on GHG fluxes from coastal forests, we made continuous measurements of carbon dioxide and methane fluxes from intact soil cores collected in 1) an upland forest dominated by loblolly pine (Pinus taeda) and a freshwater swamp dominated by baldcypress (Taxodium distichum) 2) adjacent forest stands within forest types experiencing high versus low salinization and associated tree mortality and 3) before and after pulsed salinity from a hurricane related storm surge. In lab mesocosms, all soil cores were exposed to three levels of rainwater addition to assess potential interactive effects between salinization and inundation. We found that chronic salinization and associated tree mortality decreased soil CO2 fluxes in loblolly, but not baldcypress forest with in situ soil inundation patterns potentially driving the site effect. Additionally, in an upland loblolly forest, pulsed salinity from a storm surge exhibited the potential to increase CH4 fluxes. Finally, the effect of rainwater inundation on CH4 fluxes was greater in low compared to high salinity stands suggesting that salinization may have suppressed the effects of rainwater inundation on CH4 fluxes. Overall, we show that complex interactions between biotic and abiotic conditions in stressed coastal forests can alter GHG emissions, highlighting a need for future research focused on understanding the mechanisms driving GHG fluxes from coastal forests under changing environmental conditions.

Healthcare utilization and adverse outcomes stratified by sex, age and long-term care residency using the Alberta COVID-19 Analytics and Research Database (ACARD): a population-based descriptive study

BackgroundUnderstanding the epidemiology of Coronavirus Disease of 2019 (COVID-19) in a local context is valuable for both future pandemic preparedness and potential increases in COVID-19 case volume, particularly due to variant strains.MethodsOur work allowed us to complete a population-based study on patients who tested positive for COVID-19 in Alberta from March 1, 2020 to December 15, 2021. We completed a multi-centre, retrospective population-based descriptive study using secondary data sources in Alberta, Canada. We identified all adult patients (≥ 18 years of age) tested and subsequently positive for COVID-19 (including only the first incident case of COVID-19) on a laboratory test. We determined positive COVID-19 tests, gender, age, comorbidities, residency in a long-term care (LTC) facility, time to hospitalization, length of stay (LOS) in hospital, and mortality. Patients were followed for 60 days from a COVID-19 positive test.ResultsBetween March 1, 2020 and December 15, 2021, 255,037 adults were identified with COVID-19 in Alberta. Most confirmed cases occurred among those less than 60 years of age (84.3%); however, most deaths (89.3%) occurred among those older than 60 years. Overall hospitalization rate among those who tested positive was 5.9%. Being a resident of LTC was associated with substantial mortality of 24.6% within 60 days of a positive COVID-19 test. The most common comorbidity among those with COVID-19 was depression. Across all patients 17.3% of males and 18.6% of females had an unplanned ambulatory visit subsequent to their positive COVID-19 test.ConclusionsCOVID-19 is associated with extensive healthcare utilization. Residents of LTC were substantially impacted during the COVID-19 pandemic with high associated mortality. Further work should be done to better understand the economic burden associated with related healthcare utilization following a COVID-19 infection to inform healthcare system resource allocation, planning, and forecasting.

Roles and Molecular Mechanisms of Biomarkers in Hepatocellular Carcinoma with Microvascular Invasion: A Review.

Hepatocellular carcinoma (HCC) being a leading cause of cancer-related death, has high associated mortality and recurrence rates. It has been of great necessity and urgency to find effective HCC diagnosis and treatment measures. Studies have shown that microvascular invasion (MVI) is an independent risk factor for poor prognosis after hepatectomy. The abnormal expression of biomacromolecules such as circ-RNAs, lncRNAs, STIP1, and PD-L1 in HCC patients is strongly correlated with MVI. Deregulation of several markers mentioned in this review affects the proliferation, invasion, metastasis, EMT, and anti-apoptotic processes of HCC cells through multiple complex mechanisms. Therefore, these biomarkers may have an important clinical role and serve as promising interventional targets for HCC. In this review, we provide a comprehensive overview on the functions and regulatory mechanisms of MVI-related biomarkers in HCC.