INTRODUCTION: This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of adjunct systemic corticosteroid therapy in patients admitted to the intensive care unit (ICU) with bacterial community-acquired pneumonia (CAP). METHOD: We searched MEDLINE, Embase and the Cochrane Library to identify randomised controlled trials (RCTs) published from the databases' inception to February 2024. All RCTs evaluating the effect of systemic corticosteroids on mortality, compared to standard of care among adult bacterial CAP patients admitted to ICU were included. Bayesian meta-analysis was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Independent authors reviewed each study for eligibility, extracted data and assessed risk of bias in duplicate, with discrepancies referred to senior reviewers. RESULTS: A total of 6 RCTs comprising 1585 patients were included for analysis. In ICU patients with severe CAP who were treated with corticosteroids, there was no significant reduction in hospital mortality (risk ratio [RR] 0.70, 95% confidence interval [CI] 0.39-1.14, certainty of evidence: ⊕⊕⊝⊝ low) or all-cause mortality (RR 0.68, 95% CI 0.34-1.22, ⊕⊕⊝⊝ low) compared with placebo. The use of corticosteroids showed a significant reduction in mechanical ventilation post-intervention (RR 0.58, 95% CI 0.37-0.86, ⊕⊕⊕⊕ high) compared with placebo. In a subgroup analysis of patients treated with hydrocortisone, hospital mortality was significantly reduced (RR 0.45, 95% CI 0.20-0.88, ⊕⊕⊝⊝ low) compared with placebo. There was no significant increase in gastrointestinal bleeding, secondary infections or hyperglycaemia in patients treated with corticosteroids. CONCLUSION Corticosteroids significantly reduced mechanical ventilation requirements, and hydrocor-tisone significantly reduced hospital mortality. Further work is required to determine whether other corticosteroids reduce mortality among ICU patients with CAP.
Humans ; Adrenal Cortex Hormones/therapeutic use* ; Bayes Theorem ; Community-Acquired Infections/mortality* ; Critical Illness ; Hospital Mortality ; Intensive Care Units ; Pneumonia, Bacterial/mortality* ; Randomized Controlled Trials as Topic ; Respiration, Artificial

INTRODUCTION: Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a curative option for relapse/refractory (R/R) lymphomas that have failed autologous transplantation or for high-risk lymphomas in the upfront setting. We conducted a retrospective analysis on consecutive lymphoma patients who underwent allo-HSCT over a 20-year period (2003- 2022) at Singapore General Hospital and National University Hospital Singapore. METHOD: A total of 121 patients were included in the study. Median age was 41 years. Diagnoses include Hodgkin lymphoma (HL, 15%), B-cell non- Hodgkin lymphoma (B-NHL, 34%), T-cell non-Hodgkin lymphoma (T-NHL, 31%) and natural killer T-cell lymphoma (NKTL, 20%). Moreover, 27% of patients had prior auto-haematopoietic stem cell transplanta-tion (auto-HSCT), and 84% received reduced intensity conditioning (RIC). Donor types were matched sibling donor (45%), matched unrelated donor (29%), haploidentical donor (19%) and cord blood (CB, 7%). RESULTS: After median follow-up of 56 months, estimated 4-year progression-free survival (PFS) and overall survival (OS) for all patients were 38% and 45%, respectively. Non-relapse mortality (NRM) was 15% at day 100 and 24% at 1 year. On univariate analysis, complete remission status at transplant and RIC confers superior OS. On multivariate analysis, HL was associated with superior OS compared to NHL, whereas matched unrelated donor transplant was associated with significantly inferior OS compared to matched sibling donor. CONCLUSION Long-term curative durability was observed with allo-HSCT for patients with relapsed/ refractory lymphomas. This real-world data serves as a valuable historical benchmark for future studies on lymphomas in Singapore and the Asia Pacific region.
Humans ; Singapore/epidemiology* ; Adult ; Male ; Retrospective Studies ; Female ; Hematopoietic Stem Cell Transplantation/methods* ; Middle Aged ; Transplantation, Homologous ; Young Adult ; Transplantation Conditioning/methods* ; Lymphoma/mortality* ; Adolescent ; Hodgkin Disease/mortality* ; Aged ; Lymphoma, B-Cell/mortality*

OBJECTIVE: A subset of patients with recurrent ovarian cancer (ROC) may benefit from antiestrogen therapy with higher response rates reported in tumors that are strongly estrogen receptor (ER)-positive (ER+). PARAGON is a basket trial that incorporates 7 phase 2 trials investigating the activity of anastrozole in patients with ER+ and/or progesterone receptor (PR)-positive (PR+) recurrent/metastatic gynecological cancers. METHODS: Postmenopausal women with ER+ and/or PR+ ROC, who were asymptomatic and had cancer antigen 125 (CA125) progression after response to first line chemotherapy, where chemotherapy was not clinically indicated. Patients received anastrozole 1 mg daily until progression or unacceptable toxicity. RESULTS: Fifty-four patients were enrolled (52 evaluable). Clinical benefit at three months (primary endpoint) was observed in 18 patients (34.6%; 95% confidence interval [CI]=23%–48%). Median progression-free survival (PFS) was 2.7 months (95% CI=2.1–3.1). The median duration of clinical benefit was 6.5 months (95% CI=2.8–11.7). Most patients progressed within 6 months of starting anastrozole but 12 (22%) continued treatment for longer than 6 months. Anastrozole was well tolerated. In the exploratory analysis, ER histoscores and the intensity of ER staining did not correlate with clinical benefit rate or PFS. CONCLUSION: A subset of asymptomatic patients with ER+ and/or PR+ ROC and CA125 progression had durable clinical benefit on anastrozole, with acceptable toxicity. Anastrozole may delay symptomatic progression and the time to subsequent chemotherapy. The future challenge is to identify the subset of patients most likely to benefit from an aromatase inhibitor and whether the clinical benefit could be increased by the addition of other agents.
Aromatase ; Aromatase Inhibitors ; CA-125 Antigen ; Disease-Free Survival ; Drug Therapy ; Estrogen Receptor Modulators ; Estrogens ; Female ; Humans ; Ovarian Neoplasms ; Progesterone ; Receptors, Progesterone