Nottingham City Hospital

Background/Objectives: The objectives of this study were to systematically review the literature on the effects of prebiotics and synbiotics on asthma control, lung function and asthma-associated inflammation from murine and human trials. Methods: A systematic review was performed following the PRISMA guidelines across multiple databases. A meta-analysis was performed on murine trials assessing asthma-associated inflammation and airway hyperresponsiveness, whilst a narrative review of human studies assessed asthma control, lung function, and inflammation. Results: Seventeen studies met the eligibility criteria for inclusion; eleven murine studies were included for meta-analysis and six human studies were for narrative review. The meta-analysis revealed significant effects of prebiotics and synbiotics on multiple markers of asthma-associated inflammation. Prebiotic intervention significantly reduced airway hyperresponsiveness (AHR) and type 2 cytokines (IL-4, IL-5, IL-13) and various cell counts, including neutrophil, macrophage, lymphocyte, eosinophil, and total bronchoalveolar (BALF). Synbiotics were also effective in reducing type 2 cytokines, including, IL-4, IL-5, IL-13, and lymphocytes, eosinophils, and total BALF cell count. A narrative review of human intervention trials of prebiotics and/or synbiotics revealed improvements in lung function, asthma control, and systemic and airway inflammation. Conclusions: This review indicates that dietary prebiotics and synbiotics may be suitable adjunct treatments to support asthma management, but further well-controlled human RCTs are required.

Background and Objectives: Borderline ovarian tumours (BOTs) predominantly affect women of reproductive age. Following concerns about minimally invasive surgery (MIS) in cervical cancer, the oncological safety of the surgical approach in BOTs requires evaluation, particularly in fertility-sparing procedures where clinical implications are greatest. This study aimed to assess whether MIS is associated with increased recurrence risk in BOTs, with stratified analysis by fertility-sparing status based on a pre-specified hypothesis of differential effects. Materials and Methods: Single-centre cohort study of 91 BOT patients treated at Nottingham City Hospital Cancer Centre between 2014-2023. The primary outcome was progression-free survival comparing MIS versus open surgical approaches. Results: Minimally invasive surgery was associated with higher observed recurrence compared to open surgery (5/25 [20.0%, 95% CI: 6.8-40.7%] vs. 3/66 [4.5%, 95% CI: 0.9-12.7%], absolute risk difference 15.5% [95% CI: 2.1-28.9%]; unadjusted HR 5.29, 95% CI: 1.26-22.17; p = 0.022). Conclusions: This study identifies an association between minimally invasive surgery and higher recurrence in borderline ovarian tumours, particularly in fertility-sparing procedures. While based on small numbers necessitating cautious interpretation, the consistency across analytical approaches, substantial magnitude of observed differences, and biological plausibility warrant validation in larger cohorts to inform surgical counselling.

This editorial narrative review discussed Budd-Chiari syndrome (BCS), which represents a rare but critical vascular liver disease resulting in an obstruction of hepatic venous outflow. Despite having a unifying mechanism, the syndrome shows a large heterogeneity across presentation, cause, and disease trajectory, complicating diagnosis and management. Based on established prognostic scoring systems, the New Clichy Score, the BCS-transjugular intrahepatic portosystemic shunt Index, the Zeitoun Score, and the Pediatric End-stage Liver Disease score were examined. These scoring systems are used for risk stratification and therapeutic decision-making. Although these models deliver suitability information, their static parameters, narrow validation, and limited generalizability reduce their usefulness in diverse populations. Specific challenges are highlighted in pediatric patients, pregnant females, and individuals with myeloproliferative neoplasms for whom current tools often fall short. Moreover, there remains uncertainty regarding the durability of Pediatric End-stage Liver Disease score response and longer-term risks, such as hepatocellular carcinoma. There is a need to have a dynamic prognostic model that uses imaging and genetic factors in future studies. The article discussed enhancing recruitment to improve research. Overall, this article provided a contemporary, evidence-based approach for clinicians to aid in the evaluation and treatment of BCS.

Ventilator-associated pneumonia (VAP) is a prevalent and serious infection in intensive care units (ICUs), with timely and accurate diagnosis being crucial for patient outcomes. Conventional diagnostic methods, primarily culture-based, are hampered by long turnaround times and limited sensitivity. Multiplex polymerase chain reaction (PCR) (mPCR) offers rapid detection of multiple pathogens and resistance genes, potentially revolutionizing VAP diagnosis and antimicrobial stewardship. This systematic review aims to compare the diagnostic performance and clinical impact of mPCR versus conventional methods for diagnosing VAP in ICU settings. This review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive search of PubMed/MEDLINE, Embase, Web of Science, Scopus, and the Cochrane Library was performed for studies published between 2020 and 2025. Eligible studies compared mPCR with conventional culture in ICU patients with suspected VAP and reported diagnostic accuracy metrics. Study quality was assessed using the QUADAS-2 tool. A qualitative synthesis was performed due to significant heterogeneity among the included studies. Fifteen studies were included. mPCR demonstrated high pooled sensitivity and specificity, with a consistently high negative predictive value (NPV) frequently approaching 100%. This high NPV provides a strong rationale for discontinuing unnecessary antibiotics when results are negative. However, positive predictive value (PPV) was more variable and often lower, reflecting the challenge of differentiating true infection from colonization. The most significant advantage of mPCR was its drastically reduced turnaround time compared to conventional culture. This rapidity facilitated earlier antibiotic modifications, including de-escalation and targeted therapy, as demonstrated in several studies. mPCR represents a significant advancement for the rapid microbiological diagnosis of VAP, offering high NPV and dramatically faster results than conventional culture. These attributes make it a powerful tool for enhancing antimicrobial stewardship in ICUs. However, its optimal use requires integration into clinical practice with careful interpretation of positive results within the context of clinical signs to distinguish infection from colonization. mPCR should be viewed as a complementary diagnostic tool that augments, rather than replaces, conventional microbiology. Limitations include potential omission of relevant studies due to database restrictions, language barriers, and paywalled articles, which may have influenced the comprehensiveness of study retrieval. Future research should focus on measuring its impact on hard clinical outcomes and conducting formal cost-effectiveness analyses.

Objective: To evaluate trends in insulin delivery and day-to-day variability of insulin requirements over 48 months of hybrid closed-loop use following diagnosis of type 1 diabetes (T1D) in individuals aged 10-16 years. Methods: A secondary analysis of the closed-loop arm of an open-label, multicenter, randomized, parallel hybrid closed-loop trial assessing closed-loop insulin delivery in newly diagnosed children and adolescents with T1D was conducted. Mean total daily dose (TDD) over 24 h and during the night, as well as mean total basal and bolus insulin over 24 h, were calculated. Day-to-day variability of insulin requirements was evaluated over 24 h and at night. Results: TDD increased from 27.2 ± 16.1 units/d (mean ± standard deviation) at 0-3 months following diagnosis to 65.7 ± 24.9 units/d at 42-48 months. The proportion of total daily insulin delivered as basal insulin rose from 41% to 61% over 48 months. Day-to-day variability of insulin requirements after diagnosis was high (coefficient of variation at 0-3 months: 23.3 ± 0.9%) and remained stable over 48 months. No clinically relevant sex-based differences were observed in insulin requirements. Conclusions: During the first 48 months after diagnosis of T1D, insulin requirements in children and adolescents more than double with hybrid closed-loop insulin delivery. Over time, a greater proportion of insulin is administered via the closed-loop algorithm, and the high day-to-day variability in insulin needs underscores the importance of initiating adaptive closed-loop systems from diagnosis.

Aplastic anemia (AA) transformation into myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) is associated with a dismal prognosis. Hematopoietic stem cell transplant offers the sole possibility of cure, but data on long-term survival are scarce. We retrospectively analyzed 270 patients transplanted for MDS, AML, or an isolated cytogenetic abnormality after a diagnosis of AA or paroxysmal nocturnal hemoglobinuria reported to the European Society for Blood and Marrow Transplantation (EBMT). The median age at transplantation was 39 years. The 5-year overall survival rate was 64%, and was unaffected by chromosome 7 abnormalities, age at transplant, sex, interval from clonal evolution to transplant, and intensity of conditioning regimen. The 5-year non-relapse mortality rates were 34% (95% Confidence Interval [CI]: 25-42%) for MDS patients and 19% (95% CI: 7-31%) for AML patients, and were higher following a myeloablative conditioning regimen. The 5-year relapse rate was 12% (95% CI: 6-19%) for MDS and 22% (95% CI: 9-35%) for AML. Our study’s survival estimates reflect a younger cohort of patients, considering the bimodal distribution of AA. Conditioning regimen intensity did not affect relapse. For MDS patients, pretreating before transplant did not improve survival nor reduce relapse. Transplantation is feasible and effective in achieving long-term survival for transplant-eligible post-AA myeloid neoplasm patients. MDS patients may benefit from upfront reduced intensity conditioning transplant, limiting toxicity without higher rates of relapse. Post-transplant maintenance therapies to reduce the relapse incidence among AML patients might be warranted.

The traditional sequential clinical approach to medical assessment is to take a history, examine the patient, create a differential diagnosis, consider some investigations, confirm the diagnosis and then commence management, see figure 1A.

A. J. M. Ferreri and A. Bazarbachi equally contributing authors. Introduction: Autologous stem cell transplantation (HDC-ASCT) is an effective consolidation option for PCNSL patients (pts) who respond to high-dose methotrexate (HD-MTX) chemoimmunotherapy induction. The correlation between survival and type of response to induction (CR vs. PR vs. PD), conditioning regimen, and type of induction has not been studied in large series. Here, we analyzed data from first-line induction and consolidation options in newly diagnosed PCNSL treated at EBMT centers. Methods: Adult PCNSL pts (≥ 18 years) treated with HD-MTX-based polychemotherapy and HDC-ASCT (2010–2022) were identified in the EBMT registry. The primary endpoint was progression-free survival (PFS), stratified by response to induction. Cox regression model was conducted to assess the impact of age, Karnofsky PS (KPS), induction drugs, disease status at ASCT, and conditioning regimen (Thiotepa (TT)-based vs. others) on patient outcomes. Results: A total of 1545 pts (44% F, 56% M) met the inclusion criteria. Median age at ASCT was 59 years (18–83 years), 93 (6%) had a KPS < 70. ASCT procedures increased over time: 346 (22%; 2010–2018), 395 (26%, 2018–2020), and 804 (52%, 2020–2022). HD-MTX-based induction included high-dose cytarabine in 1388 (90%) pts, TT in 1,018 (66%), and rituximab in 1,264 (82%). Conditioning was based on TT in 1457 (95%) pts. At the time of ASCT, 773 (50%) pts were in CR, 714 (46%) in PR, and 58 (4%) in PD. By +100 days post ASCT, 995 pts (80%) pts were in CR and 252 (20%) had a residual disease. After a median follow-up of 1.4 years (IQR 1.2–1.6), the 2-year PFS and overall survival (OS) were 75% (95% CI 72–78) and 81% (95% CI 80–83), respectively. No significant difference in OS and PFS was observed between pts who received ASCT in CR or PR, with a 2-year PFS of 76% for both (95% CI: 72–79 and 72–80, respectively). Even though pts diagnosed with PD exhibited worse outcomes, yet they demonstrated a 2-year PFS of 50% (95% CI 33–65). TT-based conditioning regimens improved outcomes (2-year PFS and OS 76% vs. 62%, p = 0.015, and 82% vs. 63%, p = 0.002) compared to others. Age at ASCT (HR 1.12, p = 0.002; HR 1.32, p < 0.001) and conditioning regimen used (HR 2.24, p < 0.001; HR 3.24, p = 0.008) were key factors for OS and NRM. The latter significantly correlated also with PFS. Main cause of death (n = 215, 14.5%) were lymphoma (n = 133), infections (n = 20), other transplant-related n = 15), secondary tumors (n = 6), and missing (n = 41). Conclusions: To the best of our knowledge, this is the most extensive series of PCNSL patients treated with consolidative HDC-ASCT in routine practice. Despite the limitations of a registry-based study, such as the lack of image review, this analysis demonstrates that TT-based conditioning regimens were associated with significantly better outcomes and showed similar survival in pts achieving CR and PR at the time of ASCT. Additional investigations are needed to corroborate the beneficial effect of ASCT in some pts in PD after induction Keywords: aggressive B-cell non-Hodgkin lymphoma; extranodal non-Hodgkin lymphoma; stem cell transplant No potential sources of conflict of interest.