University Malaya Medical Centre

Bacterial and fungal infections pose significant challenges in the management of patients with haematological malignancies (HM), substantially affecting the impact on clinical outcomes, including prolonged hospitalization and reduced life expectancy. Increased susceptibility to bacterial and/or fungal pathogens can occur due to immunosuppression, either inherent to the haematological disorder or induced by specific therapeutic strategies. In this study, we quantified the plasma levels of four cytokines (interferon-γ, interleukin-5, interleukin-17, and transforming growth factor-β) in a cohort of 75 adult HM patients who developed bacterial and/or fungal infections, using a newly modified enzyme-linked immunosorbent assay platform. We observed significant changes in the plasma cytokine levels at the infection onset. The median concentration levels of T helper 1 (IFN-γ), T helper 2 (IL-5), and T helper 17 (IL-17) cytokines were significantly higher as compared to those during pre-infection and post-infection (P < 0.05). In contrast, the level of regulatory T cells (TGF-β) exhibited a significant decrease at the time of infection compared to the pre-infection time point (P < 0.05). Further analysis revealed an imbalance in cytokine ratios, including Th1/Th2, Th1/Th17, Th1/Treg, Th2/Th17, and Th2/Treg, at the onset of infection, with increased Th1 and Th2-associated cytokines dominating these ratios. Our results highlighted significant changes in the expression levels of several cytokines at the infection onset of HM patients, reflecting a strong correlation between the inflammatory state and cytokine expression, characterised by a predominance of Th1 and Th2-associated cytokines.

ABSTRACT As a highly promising tool, femtosecond lasers are anticipated to become a powerful engine and support for the advancement of frontier science and advanced intelligent manufacturing technologies. This paper explores the fabrication techniques of femtosecond laser micro‐nano structures and their functional applications, unveiling the theoretical models and processing mechanisms of ultrafast laser machining, and detailing the extensive applications in surface modification, laser patterning, and two‐photon polymerization. In addressing the technical challenges of ultrafast lasers related to processing efficiency and accuracy, the footprints of femtosecond laser high‐efficiency precision manufacturing technologies were traced and investigated. Subsequently, the technological characteristics of holographic laser processing are elucidated, creating favorable conditions for the digitization and industrialization of femtosecond laser precision manufacturing with high flexibility, high quality, and high efficiency. The development trajectory and future prospects of holographic femtosecond laser beam shaping in two‐dimensional (2D) and three‐dimensional (3D) processing technologies are also summarized. The findings of this research will provide valuable insights and serve as a reference for forward‐looking and strategic innovation in advanced manufacturing fields such as aerospace, integrated circuits, information processing, and biomedicine.

This paper presents a simplified hybrid modulation method for operating dual-active-bridge (DAB) converters that power inverters by integrating single-phase shift (SPS) and triple-phase shift (TPS) modulation schemes. It covers the design and control algorithm development, performance analysis, as well as highlights its benefits and limitations. While full TPS implementation is highly complex, this work selects a specific TPS operating mode to enhance DAB converter efficiency in low-power conditions with minimal control effort. In the proposed method, a hysteresis controller is employed to regulate the DAB modulation at a defined power threshold. This poses a significant challenge, especially when a single proportional-integral (PI) controller is employed to regulate output power with a minimal set of control parameters applicable to both modulation schemes. Moreover, in addressing these challenges, a trade-off between high efficiency and fast dynamic response is also considered, with greater emphasis placed on efficiency when developing the controllers. Meanwhile, the inverter output voltage is independently controlled regardless of the DAB operation to further simplify the overall process. Small signal modeling and closed-loop control of DAB-based inverter with the proposed hybrid modulation are also presented. Its functionality and performance have been verified through simulation and a developed small-scale DAB-based inverter prototype.

Central venous stenosis (CVS) is a clinically significant complication in patients who depend on long-term hemodialysis access. While digital subtraction angiography remains the diagnostic gold standard, it is invasive, costly, and exposes patients to contrast and radiation. This study examined the diagnostic value of a simple, non-invasive, radiation-free alternative-the ultrasound-guided "sniff test," which assesses dynamic changes in subclavian vein diameter during a forceful sniff to screen for CVS. Despite its potential advantages, the diagnostic performance of this method has not been well established. A prospective study was conducted among 71 end-stage kidney disease (ESKD) patients scheduled for angiography. Each participant underwent a sniff test before the procedure. A reduction of more than 40% in subclavian vein diameter during sniffing was considered normal, indicating absence of stenosis. Angiographic findings were used as the reference standard. Clinical signs-specifically ipsilateral arm swelling and visible chest wall veins-were also evaluated for diagnostic utility. Angiography confirmed CVS in 32 patients (45.1%). The sniff test showed a strong association with stenosis (OR 20.9) and demonstrated solid diagnostic performance, with sensitivity of 84.4%, specificity of 79.5%, and an AUC of 0.82. A normal sniff test accurately excluded stenosis in the majority of patients without CVS (86.1%), whereas an abnormal result was predominantly seen among those with stenosis (77.1%). Arm swelling was also significantly associated with stenosis (OR 20.40) and showed good standalone diagnostic accuracy (sensitivity 75.0%, specificity 87.2%, AUC 0.81). Importantly, combining the sniff test with clinical assessment enhanced overall performance, achieving higher specificity (94.9%) and excellent discriminative ability (AUC 0.90). In conclusion, the ultrasound sniff test is a promising, accessible, and accurate screening tool for CVS. Used alone or alongside clinical findings, it offers a practical method to identify patients who may benefit from confirmatory angiography-particularly valuable in resource-limited or radiation-averse settings.

Introduction Infective endocarditis (IE) in young individuals is uncommon but may occur in the presence of congenital heart disease.Congenital bicuspid aortic valve is recognized as a predisposing lesion in the 2023 ESC guideline on IE.Abiotrophia defectiva, a nutritionally variant streptococcus, is rare yet highly aggressive and associated with adverse outcomes.Case Presentation A 19-year-old boy with no prior comorbidity admitted with one month history of lethargy and a brief febrile episode which resolved spontaneously.Notably, he had undergone dental extraction two weeks prior to fever onset.Two days prior to admission, he developed fingernail swelling.Examination revealed finger clubbing and a diastolic murmur at the aortic area.He was haemodynamically stable.Investigations showed normocytic anemia, leucocytosis and elevated C-reactive protein.Echocardiography demonstrated a bicuspid aortic valve with large vegetation and severe aortic regurgitation.Results Blood cultures yielded Abiotrophia defectiva.Intravenous ceftriaxone was initiated.CT thorax, abdomen and pelvis showed no evidence of metastatic infection.Due to the severe aortic regurgitation, he underwent urgent prosthetic aortic valve replacement.Post-operatively, he was maintained on warfarin and completed six weeks of intravenous ceftriaxone in accordance with IE treatment guidelines.Inflammatory markers normalized and repeat cultures were sterile.Discussion Abiotrophia defectiva accounts for <1% of IE but carries a high risk of embolization, relapse, and surgical intervention.Case series report up to 40-50% requiring valve replacement.The 2023 ESC IE guideline emphasizes prolonged -lactam therapy (often in combination with aminoglycosides initially) and early surgical referral in cases with severe valvular dysfunction.Our patient's bicuspid aortic valve provided a substrate for infection, consistent with guideline recognition of congenital lesions as high risk.The temporal relationship with recent dental extraction underscores the importance of oral hygiene and prophylaxis consideration in selected patients.Conclusion This case highlights Abiotrophia defectiva endocarditis in a young patient with bicuspid aortic valve complicated by severe aortic regurgitation, successfully treated with urgent valve replacement and guideline-directed antibiotic therapy.Awareness of this organism's aggressive course is essential for timely diagnosis and management.

Colon cancer located at the splenic flexure exhibits dual lymphatic drainage via the left middle colic artery (lt-MCA) to the superior mesenteric artery (SMA) system and the left colic artery (LCA) to the inferior mesenteric artery (IMA) system. However, an additional pathway-the Arc of Riolan (AoR) artery, central anastomotic vessels connecting the SMA and IMA-may also serve as a route for metastasis. This case highlights the importance of central vascular ligation of the AoR in splenic flexure cancer. We present a rare case of isolated AoR lymph node metastasis in a 72-year-old male with advanced splenic flexure cancer. The patient presented with multiple synchronous tumors (splenic flexure, sigmoid, and rectum) and underwent extended left hemicolectomy with central vascular ligation (CVL) of the AoR, revealing metastatic involvement exclusively in AoR nodes. This represents the first documented case of isolated AoR nodal metastasis, emphasizing the need for AoR lymphadenectomy when present. Recent studies suggest that accessory middle colic arteries (aMCA) and AoR may represent the same anatomical structure, with metastasis rates of 3.7-6.3% in corresponding nodes. Our findings support that AoR should be considered a critical target for CVL in splenic flexure cancer, particularly when identified pre- or intraoperatively. Surgeons should recognize AoR as a possible isolated metastatic pathway and perform thorough nodal dissection along this vessel when present to ensure optimal oncologic outcomes.

TPS607 Background: The combination of atezolizumab and bevacizumab (Atezo-Bev) has transformed the treatment landscape for unresectable hepatocellular carcinoma (HCC). With a response rate of approximately 30%, some patients become eligible for curative locoregional therapies (LRT) after successful systemic treatment. However, it remains unclear whether patients who achieve a partial response (PR) and are converted to a disease-free state with curative LRT have a similar prognosis to patients who achieve a complete response (CR) from Atezo-Bev alone. Additionally, it is unknown whether applying curative LRT improves survival outcomes for patients who achieve a PR. This study aims to address these critical questions. Methods: This multinational, retrospective study will enroll patients with clinically or histologically diagnosed HCC who received first-line Atezo-Bev and achieved a CR or PR according to RECIST v1.1. Patients must have started Atezo-Bev before September 30, 2024. Patients receiving concurrent anti-CTLA4 antibodies will be excluded. Curative LRT is defined as curative surgery, ablation, or definitive radiotherapy performed in patients who achieved a PR with Atezo-Bev treatment during their PR status. The primary endpoint is the recurrence-free survival (RFS) of patients who received curative LRT, compared to that of patients who obtained a CR solely from Atezo-Bev treatment. Secondary endpoints include the time to discontinuation of Atezo-Bev treatment after curative LRT, and the time from initiation of Atezo-Bev treatment to curative LRT; also, the overall survival and progression-free survival of patients who received curative LRT with be compared with those of patients who obtained CR solely from Atezo-Bev treatment and those of patients who obtained a PR after Atezo-Bev treatment but did not receive LRT. Disease-free status after curative surgery must be confirmed by imaging. Time from the best objective response to curative LRT will also be recorded. Data will be collected from up to 30 Asian sites, with an anticipated sample size of approximately 400 patients who received curative LRT and 1,200 patients who achieved a CR or PR without receiving curative LRT. Survival outcomes will be analyzed using Kaplan-Meier methods and compared with the log-rank test. They will be adjusted for baseline characteristics such as age, gender, HCC etiology, tumor extent, liver function reserve, alpha-fetoprotein level, and neutrophil/lymphocyte ratio using Cox proportional hazards models. The study is partially supported by Roche. Clinical trial information: NCT07091942 .