Explore the vast range of titles available.

Infection and rejection are major complications that impact transplant longevity and recipient survival. Balancing their risks is a significant challenge for clinicians. Current strategies aimed at interrogating the degree of immune deficiency or activation and their attendant risks of infection and rejection are imprecise. These include immune (cell counts, function and subsets, immunoglobulin levels) and non-immune (drug levels, viral loads) markers. The shared risk factors between infection and rejection and the bidirectional and intricate relationship between both entities further complicate transplant recipient care and decision-making. Understanding the dynamic changes in the underlying net state of immunity and the overall risk of both complications in parallel is key to optimizing outcomes. The allograft biopsy is the current gold standard for the diagnosis of rejection but is associated with inherent risks that warrant careful consideration. Several biomarkers, in particular, donor derived cell-free-DNA and urinary chemokines (CXCL9 and CXCL10), show significant promise in improving subclinical and clinical rejection risk prediction, which may reduce the need for allograft biopsies in some situations. Integrating conventional and emerging risk assessment tools can help stratify the individual’s short- and longer-term infection and rejection risks in parallel. Individuals identified as having a low risk of rejection may tolerate immunosuppression wean to reduce medication-related toxicity. Serial monitoring following immunosuppression reduction or escalation with minimally invasive tools can help mitigate infection and rejection risks and allow for timely diagnosis and treatment of these complications, ultimately improving allograft and patient outcomes.

To identify risk factors for infection in patients with diffuse large B cell lymphoma (DLBCL) undergoing rituximab, cyclophosphamide, vincristine, adriamycin and prednisolone (R-CHOP) treatment. All patients with DLBCL who received R-CHOP from 2004–2014 in a tertiary Australian hospital were identified and information collected from hospital admission data, laboratory results and medical record review. Infection was defined as hospitalisation with an ICD-10-AM diagnostic code for infection. Risk factors for infection and association between infection and survival were modelled using Cox proportional hazards regression. Over the 10-year period there were 325 patients; 191 (58.8%) males, median age 66 years. 206 (63.4%) patients experienced ≥1 infection. Independent predictors of infection were Charlson comorbidity index score (hazard ratio [HR] 3.60, p = 0.002), Eastern Cooperative Oncology Group (ECOG) performance status (HR 2.09 p = <0.001) and neutropenia (HR 2.46, p = <0.001). 99 (31%) patients died. Infection was an independent predictor of survival (HR 3.27, p = <0.001, as were age (HR 2.49, p = 0.001), Charlson comorbidity index (HR 4.34, p = <0.001), ECOG performance status (HR 4.33, p = 0.045) and neutropenia (HR 1.95, p = 0.047). Infections are common and infection itself is an independent predictor of survival. Patients at highest risk of infection and death are those with multiple comorbidities, poor performance status and neutropenia.

Despite vaccination strategies, people with chronic kidney disease, particularly kidney transplant recipients (KTRs), remained at high risk of poor COVID-19 outcomes. We assessed serological responses to the three-dose COVID-19 vaccine schedule in KTRs and people on dialysis, as well as seroresponse predictors and the relationship between responses and breakthrough infection. Plasma from 30 KTRs and 17 people receiving dialysis was tested for anti-Spike receptor binding domain (RBD) IgG and neutralising antibodies (NAb) to the ancestral and Omicron BA.2 variant after Doses 2 and 3 of vaccination. After three doses, KTRs achieved lower anti-Spike RBD IgG levels (  < 0.001) and NAb titres than people receiving dialysis (  = 0.002). Seropositive cross-reactive Omicron neutralisation levels were achieved in 11/27 (40.7%) KTRs and 11/14 (78.6%) dialysis recipients. ChAdOx1/viral-vector vaccine type, higher mycophenolate dose (> 1 g per day) and lower absolute B-cell counts predicted poor serological responses in KTRs. ChAdOx-1 vaccine type and higher monocyte counts were negative predictors in dialysis recipients. Among ancestral NAb seroresponders, higher NAb levels positively correlated with higher Omicron neutralisation (  = 0.9,  < 0.001). More KTRs contracted SARS-CoV-2 infection (14/30; 47%) than dialysis recipients (5/17; 29%) and had more severe disease. Those with breakthrough infections had significantly lower median interdose incremental change in anti-Spike RBD IgG and ancestral NAb titres. Serological responses to COVID-19 vaccines in KTRs lag behind their dialysis counterparts. KTRs remained at high risk of breakthrough infection after their primary vaccination schedule underlining their need for booster doses, strict infection prevention measures and close surveillance.

Background Sepsis occurs in 12–27% of patients with haematological malignancy within a year of diagnosis. Sepsis mortality has improved in non-cancer patients in the last two decades, but longitudinal trends in patients with haematological malignancy are not well characterised. We aimed to compare outcomes, including temporal changes, in patients with and without a haematological malignancy admitted to ICU with a primary diagnosis of sepsis in Australia and New Zealand over the past two decades. Methods We performed a retrospective cohort study of 282,627 patients with a primary intensive care unit (ICU) admission diagnosis of sepsis including 17,313 patients with haematological malignancy, admitted to 216 intensive care units (ICUs) in Australia or New Zealand between January 2000 and December 2022. Annual crude and adjusted in-hospital mortality were reported. Risk factors for in-hospital mortality were determined using a mixed methods logistic regression model and were used to calculate annual changes in mortality. Results In-hospital sepsis mortality decreased in patients with haematological malignancy, from 55.6% (95% CI 46.5–64.6%) in 2000 to 23.1% (95% CI 20.8–25.5%) in 2021. In patients without haematological malignancy mortality decreased from 33.1% (95% CI 31.3–35.1%) to 14.4% (95% CI 13.8–14.8%). This decrease remained significant after adjusting for mortality predictors including age, SOFA score and comorbidities, as estimated by adjusted annual odds of in-hospital death. The reduction in odds of death was of greater magnitude in patients with haematological malignancy than those without (OR 0.954, 95% CI 0.947–0.961 vs. OR 0.968, 95% CI 0.966–0.971, p  < 0.001). However, absolute risk of in-hospital mortality remained higher in patients with haematological malignancy. Older age, higher SOFA score, presence of comorbidities, and mechanical ventilation were associated with increased mortality. Leukopenia (white cell count < 1.0 × 10 9  cells/L) was not associated with increased mortality in patients with haematological malignancy ( p  = 0.60). Conclusions Sepsis mortality has improved in patients with haematological malignancy admitted to ICU. However, mortality remains higher in patients with haematological malignancy than those without. Graphical abstract Key points Among patients with haematological malignancy and sepsis admitted to intensive care, mortality has fallen by over 50% in the last two decades. Improvements are independent of organ failure, neutropenia, and age; however, mortality remains higher than for patients with no malignancy.

This narrative review summarizes the current literature relating to pneumococcal vaccination in adult solid organ transplant (SOT) recipients, who are at risk of invasive pneumococcal disease (IPD) with its attendant high morbidity and mortality. The effect of the pneumococcal polysaccharide vaccine has been examined in several small cohort studies in SOT recipients, most of which were kidney transplant recipients. The outcomes for these studies have been laboratory seroresponses or functional antibody titers. Overall, in most of these studies the transplant recipients were capable of generating measurable serological responses to pneumococcal vaccination but these responses were less than those of healthy controls. A mathematical model estimated the effectiveness of polysaccharide vaccination in SOT recipients to be one third less than those of patients with HIV. The evidence for the efficacy of the pneumococcal conjugate vaccine in SOT is based on a small number of randomized controlled trials in liver and kidney transplant recipients. These trials demonstrated that SOT recipients mounted a serological response following vaccination however there was no benefit to the use of prime boosting (conjugate vaccine followed by polysaccharide vaccine). Currently there are no randomized studies investigating the clinical protection rate against IPD after pneumococcal vaccination by either vaccine type or linked to vaccine titers or other responses against pneumococcus. Concerns that vaccination may increase the risk of adverse alloresponses such as rejection and generation of donor specific antibodies are not supported by studies examining this aspect of vaccine safety. Pneumococcal vaccination is a potentially important strategy to reduce IPD in SOT recipients and is associated with excellent safety. Current international recommendations are based on expert opinion from conflicting data, hence there is a clear need for further high-quality studies in this high-risk population examining optimal vaccination regimens. Such studies should focus on strategies to optimize functional immune responses.

Neutropenic sepsis frequently requires admission to an intensive care unit (ICU). Differences between subgroups of patients with neutropenic sepsis are not well characterized. To investigate clinical outcomes among patients with neutropenic sepsis and hematological malignancy, metastatic solid cancer, or no cancer diagnosis. Retrospective cohort study of all patients admitted to ICU in Australia or New Zealand between January 2000 and December 2022 with a primary admission diagnosis of sepsis and total white cell count <1.0 × 10 cells/L. We identified 8617 ICU admissions with neutropenic sepsis (hematological malignancy n = 4660; metastatic solid cancer n = 1034; no cancer n = 2800). Patients with hematological malignancy were younger (median, 61.5 years) with low rates of chronic comorbidities (4.7%) and were usually admitted to ICU from the ward (67.4%). Mechanical ventilation rates were 20.2% and in-hospital mortality was 30.6%. Patients with metastatic solid cancers were older (median, 66.3 years), with higher rates of chronic comorbidities (9.9%), and were usually admitted to the ICU from the emergency department (50.8%). Mechanical ventilation rates were 16.9% and in-hospital mortality was 42.4%. Patients with no documented cancer had highest rates of mechanical ventilation (41.7%) and mortality (46.3%). Neutropenia was independently associated with mortality among patients with solid cancers or no cancer but did not confer increased risk among patients with hematological malignancy (odds ratio, 0.98; 95% confidence interval, .90-1.06; = .60). Patients with neutropenic sepsis and hematological malignancy, metastatic solid cancer, or no cancer diagnosis constitute 3 distinct clinical groups. Management approaches should be tailored accordingly.

The hematology patient cohort was selected for the study population because they are often more susceptible to infections (from underlying disease or treatment), which, in turn, can result in higher rates of morbidity and mortality.2 The outcomes of this study will be used to inform continuation of isolation and infection control measures as the pandemic continues to evolve and afterward. Breakdown of Microbiology Results by Type Variable Year P Value 2019 2020 No. of hematology admissions 1,598 1,488 Positive respiratory PCR results as a percentage of total respiratory PCR samples taken from hematology patient cohort 29 of 143 (20.27) 29 of 266 (10.90) .01 Human metapneumovirus 2 0 Influenza A/B virus 9 5 Parainfluenza virus-1/-2/-3/-4 6 0 Respiratory syncytial virus 2 3 Rhinovirus/enterovirus 10 21 .74 Positive fecal PCR results as a percentage of total fecal PCR samples taken from hematology patient cohort 6 of 75 (8.00) 5 of 74 (6.76) .77 Campylobacter spp 0 1 Clostridium difficile 4 1 Giardia intestinalis 1 1 Norovirus 1 1 Salmonella spp 0 1 Positive blood cultures as a % of total blood cultures taken from hematology patient cohort 27 of 826 (3.27) 28 of 822 (3.41) .88 Gram-positive bacteriaa 10 13 .52 Enterococcus faecium 7 4 Staphylococcus aureus 0 3 Staphylococcus spp (coagulase negative) 1 3 Other gram-positive bacteria 2 3 Gram-negative bacteriaa 19 19 .99 Escherichia coli 6 10 Klebsiella spp 3 7 Pseudomonas aeruginosa 3 0 Enterobacter cloacae complex 2 0 Other gram-negative bacteria 5 2 Note. The notable increase in the rates of rhinovirus/enterovirus in 2020, however, may be due to reduced activity of alcohol-based hand sanitizers on nonenveloped viruses.3 Blood cultures and fecal PCR results did not show statistically different rates of infection; these were mostly commensals or infections less affected by droplet precaution measures implemented during the pandemic. Greater than 75% of all positive respiratory PCR samples were taken within 48 hours of admission, and although the results are unlikely to solely reflect community exposure (ie, our hematology patients frequently attend day treatment centers and other hospital services), a limitation is the difficulty in accounting for the expected reduction of circulating non–COVID-19 respiratory viruses in the community due to government restrictions and public behavior.

IntroductionPatients with hematological malignancies are at high risk of infections due to both the disease and the associated treatments. The use of immunoglobulin (Ig) to prevent infections is increasing in this population, but its cost effectiveness is unknown. This trial-based economic evaluation aimed to compare the cost effectiveness of prophylactic Ig with prophylactic antibiotics in patients with hematological malignancies.MethodsThe economic evaluation used individual patient data from the RATIONAL feasibility trial, which randomly assigned 63 adults with chronic lymphocytic leukemia, multiple myeloma, or lymphoma to prophylactic Ig or prophylactic antibiotics. The following two analyses were conducted to estimate the cost effectiveness of the two treatments over the 12-month trial period from the perspective of the Australian health system:(i) a cost-utility analysis (CUA) to assess the incremental cost per quality-adjusted life-year (QALY) gained using data collected with the EuroQol 5D-5L questionnaire; and(ii) a cost-effectiveness analysis (CEA) to assess the incremental cost per serious infection prevented (grade ≥3) and per infection prevented (any grade).ResultsThe total cost per patient was significantly higher in the Ig arm than in the antibiotic arm (difference AUD29,140 [USD19,000]). There were non-significant differences in health outcomes between the treatment arms: patients treated with Ig had fewer QALYs (difference −0.072) and serious infections (difference −0.26) than those given antibiotics, but more overall infections (difference 0.76). The incremental cost-effectiveness from the CUA indicated that Ig was more costly than antibiotics and associated with fewer QALYs. In the CEA, Ig costed an additional AUD111,262 (USD73,000) per serious infection prevented, but it was more costly than antibiotics and associated with more infections when all infections were included.ConclusionsThese results indicate that, on average, Ig prophylactic treatment may not be cost effective compared with prophylactic antibiotics for the group of patients with hematological malignancies recruited to the RATIONAL feasibility trial. Further research is needed to confirm these findings in a larger population and over the longer term.

IntroductionMultimodal interventions (MMI) are frequently used in various healthcare settings to encourage change in healthcare personnel practices and improve patient safety. In 2013, an MMI conducted in an Australian metropolitan ED used clinician champions, guidelines, education sessions and promotional materials to encourage a reduction in unused and inappropriate peripheral intravenous cannulas (PIVC). A 60-day postintervention demonstrated a successful reduction in the number of unused PIVCs without changes in appropriate insertions. We aimed to investigate if this MMI produced a sustained effect in reducing the frequency of unused PIVCs inserted in this ED.MethodsA single-centre retrospective cohort study of adult patients presenting to the above ED in Victoria, Australia, was conducted in April 2018. A random sample of 380 patients with a PIVC inserted in ED was assessed to determine if the PIVC was used (termed ‘Long-term follow-up’). The appropriateness of unused PIVCs was assessed. Our findings were compared with previously collected data in 2013 (‘Pre-Intervention’ and ‘Immediately Post-Intervention’) to determine a sustained reduction in the frequency of unused PIVC insertions was achieved. Long-term analysis of the MMI, including the overall frequency of PIVC insertions in ED before and after the MMI, was also collected.ResultsIn our Long-term follow-up cohort, 101 of 373 (27.1%, 95% CI 22.6% to 31.9%) PIVCs were unused (seven cases excluded). This was significantly lower than the Pre-Intervention cohort (139/376, 37.0%, 95% CI 32.1% to 42.1%). While not significant, the frequency of unused PIVCs in the Post-Intervention cohort was lower in comparison (73/378, 19.3%, 95% CI 15.4% to 23.7%). No significant change in the appropriateness of unused PIVCs was observed between the Post-Intervention and Long-term follow-up. The overall proportion of patients receiving a PIVC has remained low since the MMI.ConclusionAn MMI aimed at reducing unused PIVC insertions in ED has been effective in eliciting sustained change. Unused but appropriately inserted PIVCs seem unaffected by the intervention.