Search Results (273)

Background: Malignant pleural effusion (MPE) is a common complication of advanced malignancy associated with significant symptom burden. Current British Thoracic Society guidance supports early definitive pleural intervention for recurrent MPE; however, these recommendations are largely derived from solid tumour populations, and their applicability to haematological malignancy remains uncertain. Methods: We performed a retrospective cohort study of adult patients with cytology-confirmed haematological malignancy-associated MPE managed by the Oxford Pleural Unit between 2015 and 2025. Consecutive patients undergoing at least one pleural procedure were included. Definitive pleural intervention was defined as indwelling pleural catheter (IPC) insertion, talc pleurodesis, or surgical pleural intervention. The primary outcome was time from first pleural procedure to definitive pleural intervention. Cox proportional hazards regression was used to explore factors associated with progression to definitive intervention. Results: Among 910 patients with cytology-positive MPE, 116 (12.7%) had underlying haematological malignancy. Initial pleural management was therapeutic aspiration in 90 patients (78%), chest drain insertion in 24 (21%), and direct IPC insertion in 2 (2%). Among patients managed with an aspiration-first strategy, 63/90 (70%) avoided definitive pleural intervention entirely. Thirty-six patients (40%) required only a single aspiration before systemic therapy controlled the effusion, while 27 (30%) were managed with repeat aspirations alone. Overall, only 35/116 (30%) patients required definitive pleural intervention during follow-up. Non-chemo-responsive disease was associated with earlier progression to definitive pleural intervention (adjusted HR 1.85, 95% CI 1.10–3.10; p = 0.02). Conclusions: In contrast to solid tumour-associated MPE, many patients with haematological malignancy-associated MPE can be successfully managed without early definitive pleural intervention. An aspiration-first strategy may therefore be appropriate in selected patients with anticipated chemo-responsive disease. Full article

Background/Objectives: Although outcomes in Hodgkin lymphoma (HL) have improved substantially, patients with advanced-stage disease, comorbidities, or relapsed/refractory presentations can still fare poorly. Blood-based indices of systemic inflammation and nutrition are derived from routine tests, but their value beyond established prognostic models is uncertain. We examined the association of the baseline Gustave Roussy Immune Score (GRIm) and Glasgow Prognostic Score (GPS) with treatment response, progression-free survival (PFS), and overall survival (OS) in HL, focusing on their performance relative to the seven-factor International Prognostic Score (IPS-7). Methods: We retrospectively analysed 110 adults with histologically confirmed HL treated at a tertiary haematology centre between January 2015 and December 2025. GPS, GRIm, and IPS-7 were calculated from data recorded at diagnosis. Treatment response was classified as complete versus non-complete. Outcomes were assessed with Kaplan–Meier analysis, log-rank tests, Cox regression, Harrell’s C-index, and likelihood-ratio testing. Results: Most patients had advanced-stage disease (69.1%) and received ABVD-based treatment (94.5%); complete response was achieved in 90 (81.8%). GPS and GRIm were not significantly associated with non-complete response, whereas IPS-7 was. Over a median follow-up of 39.5 months, 28 patients (25.5%) progressed or died and 17 (15.5%) died. In univariable Cox analysis, high GRIm risk (HR = 2.68, 95% CI 1.17–6.14), higher GPS (HR = 2.18 per point, 95% CI 1.23–3.89), and higher IPS-7 (HR = 2.10 per point, 95% CI 1.59–2.77) predicted shorter PFS. For OS, GPS and IPS-7 were significant, whereas GRIm was not. After adjustment for IPS-7, neither GPS nor GRIm remained independently associated with PFS or OS, and adding either score to IPS-7 produced only small, non-significant gains in discrimination. Conclusions: Baseline GPS and GRIm were associated with survival on univariable analysis, particularly for PFS, but their incremental value beyond IPS-7 was limited. These scores may help describe baseline inflammatory and nutritional risk and should not be regarded as alternatives to established HL prognostic models. In particular, GPS and GRIm were not significantly associated with treatment response and should be viewed as supportive markers requiring external validation, rather than as tools that can independently guide treatment decisions. Full article

Clear cell renal cell carcinoma (ccRCC) accounts for approximately 75% of renal cell carcinomas and is defined by near-universal VHL inactivation, leading to constitutive HIF stabilisation, metabolic reprogramming, and an immunologically distinct tumour microenvironment (TME). Although ccRCC is characterised by abundant immune infiltration, this paradoxically correlates with poor prognosis, reflecting a TME that imposes interconnected physical, immunological, and metabolic barriers to effective immunotherapy. Chimeric antigen receptor (CAR)-based therapies have revolutionised the treatment of haematological malignancies, but their translation to ccRCC has encountered substantial hurdles. The first-in-human trial targeting carbonic anhydrase IX (CAIX) was limited by on-target off-tumour toxicity and CAR immunogenicity—lessons that fundamentally reshaped the field. CD70 has since emerged as the dominant clinical target, expressed in over 80% of ccRCCs with a highly restricted normal tissue distribution. The phase I COBALT-RCC trial of CTX130, an allogeneic CRISPR-Cas9-edited CD70-directed CAR-T cell product, provided formal proof of concept, achieving disease control in 81.3% of heavily pretreated patients and a durable complete response now exceeding three years—the first such sustained remission reported for any CAR-T cell product in a solid malignancy. Nevertheless, the low frequency of durable responses and universal loss of CAR-T cell persistence by day 28 underscore that major barriers remain. Beyond CD70, the field has diversified across multiple platforms, including CAR–natural killer (NK) cells, CAR–natural killer T (NKT) cells, and CAR–macrophages, each offering distinct biological advantages. This review synthesises current knowledge of the ccRCC TME, the preclinical landscape of CAR-based therapies, and emerging clinical evidence from more than 30 registered trials. We discuss target antigens; engineering strategies to overcome TME barriers, including cytokine armouring, chemokine receptor co-expression, switch receptors, and metabolic reprogramming; and rational combination approaches. We argue that the convergence of optimised target selection, cellular engineering, combination strategies, and biomarker-driven trial design may ultimately improve outcomes for patients with ccRCC. However, achieving a cure remains an aspirational goal, and significant barriers must first be overcome. Full article

Background and Clinical Significance: Peristomal pyoderma gangrenosum (PPG) is a rare subtype of pyoderma gangrenosum, most commonly associated with inflammatory bowel disease or haematologic disorders. Its occurrence in patients with solid malignancies is uncommon. PPG in an oncologic setting poses diagnostic and therapeutic challenges because systemic immunosuppressive therapy, wound care, and ongoing chemotherapy must be carefully balanced; Case Presentation: We report the case of a Japanese man in his 50s with stage IVB rectal adenocarcinoma who developed rapidly progressive peristomal ulceration clinically consistent with PPG around a colostomy 12 weeks after initiation of panitumumab-containing systemic chemotherapy. The diagnosis was made on clinical grounds and was strongly supported by the clinical morphology, exclusion of major mimickers, and response to systemic corticosteroid therapy, although histopathological confirmation was not obtained. Because existing diagnostic criteria for pyoderma gangrenosum are not specifically designed for peristomal disease, they were used as supportive rather than definitive diagnostic tools. Skin biopsy was avoided due to the risk of pathergy at the peristomal site. Superficial cultures were not obtained because frequent cleansing and faecal contamination were likely to compromise diagnostic accuracy. To minimise mechanical pathergy, the stoma appliance was changed from a one-piece soft convex system to a two-piece flat system. Multidisciplinary management, including systemic corticosteroids, meticulous stoma care, and selective ultrasonic debridement, resulted in complete epithelialisation by Week 26. Chemotherapy was temporarily withheld during the active inflammatory phase and later resumed. Despite successful control of the peristomal ulceration, the patient died from progressive malignancy at Week 34; Conclusions: This case highlights the clinical challenge of balancing immunosuppressive therapy for clinically suspected PPG with ongoing oncologic treatment. Mechanical pathergy related to stoma appliance use was considered a more likely precipitating factor than chemotherapy alone, although panitumumab may have contributed to impaired cutaneous repair. Close collaboration among dermatologists, oncologists, surgeons, WOC nurses, and family caregivers is essential for multidisciplinary decision-making in complex oncologic settings. Full article

Metabolically dysfunction-associated steatotic liver disease (MASLD) complicated by type 2 diabetes mellitus (T2DM) represents a clinically aggressive phenotype associated with accelerated hepatic fibrosis progression. The interplay among oxidative stress, systemic inflammation, and the risk of hepatic fibrosis in this context remains incompletely characterised. We conducted a single-centre observational study enrolling 110 adult MASLD patients, stratified into two groups: Group 1 (G1, n = 20), patients with concurrent T2DM, followed longitudinally at three successive time points, and Group 2 (G2, n = 90), non-diabetic controls. Serum oxidative stress biomarkers were assessed using malondialdehyde (MDA) and 8-isoprostaglandin F2α (8-iso-PGF2α). Systemic inflammatory status was quantified through the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR). Hepatic fibrosis risk was estimated using the FIB-4 index. Diabetic MASLD patients exhibited significantly elevated levels of 8-iso-PGF2α (p = 0.014) and NLR (p = 0.016) compared with controls, indicating greater oxidative membrane damage and systemic neutrophilic inflammation. A robust inverse correlation between PLR and FIB-4 was observed across all analytical strata (combined cohort: Spearman r = −0.680, p < 0.001). MLR emerged as the only independent predictor of MDA in G1 (β = 841.78, p = 0.013). Longitudinal analysis demonstrated biomarker stability over time, except for a significant increase in ALT from T1 to T2 (p_adj = 0.014). These findings support the clinical utility of routinely available haematological inflammatory ratios and lipid peroxidation biomarkers for phenotypic characterisation of MASLD in the diabetic context, highlighting the need for larger prospective studies with histological validation. Full article

Background: Neuroendocrine tumours (NETs) are heterogeneous neoplasms with several treatment options. Response rates, disease progression, and haematological toxicities can limit the use of some indicated treatments. Case Presentation: A 73-year-old woman with a well-differentiated grade 2 pancreatic NET (Ki-67 18%) underwent surgical resection and later developed hepatic recurrence. First-line treatment with sunitinib plus octreotide achieved temporary disease stabilisation. Upon progression, peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTATATE was initiated, resulting in stable disease but complicated by grade 3 thrombocytopenia. Two years later, PRRT retreatment was performed due to disease progression, which led to grade 4 thrombocytopenia. Further treatments with capecitabine and everolimus were limited by progression and significant thrombocytopenia. Therapy was switched to streptozocin plus 5-fluorouracil, which resulted in recovery of platelet counts, absence of haematological toxicity, and a sustained radiologic response until March 2025, when she presented with hepatic progression. FOLFOX chemotherapy was initiated but discontinued after one cycle due to severe thrombocytopenia. Deterioration in general condition ultimately led to supportive care and death in March 2026. Conclusions: This case highlights the risk of cumulative haematological toxicity with PRRT, particularly in retreatment settings. Careful patient selection and close monitoring are essential. Streptozocin-based chemotherapy may be an effective and well-tolerated alternative for patients with treatment-limiting toxicity. Full article

Myeloid malignancies encompass a heterogeneous group of haematological disorders, primarily including myelodysplastic syndromes (MDSs) and myeloproliferative neoplasms (MPNs). MDS is characterised by defective myeloid cell maturation, while MPNs involve the pathological overproduction of myeloid lineage cells. In the absence of timely diagnosis and effective clinical intervention, both entities carry a substantial risk of progression to acute myeloid leukaemia (AML). Although allogeneic haematopoietic stem cell transplantation remains the only potentially curative therapy, its application is frequently constrained by patient-related factors such as advanced age and comorbid conditions. While currently, hypomethylating agent therapy (azacitidine and decitabine) is mainly used in high-risk MDS patients, and ruxolitinib is primarily used in symptomatic primary myelofibrosis (PMF-MPN), their clinical efficacy remains suboptimal. More recently, focus has turned toward the role of the tumour microenvironment (TME) in disease pathogenesis and whether therapeutically targeting the TME, either alone or in combination with conventional therapy, could present a new treatment option. Emerging evidence underscores the significant influence of TME components, particularly macrophages and T cells, in modulating immune responses and shaping the leukaemic niche to either facilitate or hinder malignant progression. In response, a new generation of immune checkpoint inhibitors are being developed to target the TME, including PD-1/CTLA-4 blockers, macrophage-directed agents including CD47 inhibitors, and T cell-targeting checkpoint inhibitors such as TIM-1 and LAG-3. This review will describe the functional role of key TME constituents in the progression of myeloid malignancies and explore the current landscape and future potential of advanced cellular and molecular immunotherapies in the treatment of these disorders. Full article

Objective: This study aimed to assess practicing dentists’ knowledge, attitudes, and self-confidence regarding knowledge about oral manifestations of haematological disorders and interpretation of blood count (BC) tests. Materials and Methods: An online survey was sent to all practicing dentists via email addresses registered with the Dental Chamber. The questionnaire collected sociodemographic data and assessed knowledge of hematological diseases, their oral manifestations, and BC interpretation, as well as dentists’ attitudes toward interdisciplinary collaboration and perceived need for continuing education. In the knowledge section, some questions required a single correct answer, while most allowed multiple selections. For multiple-choice items, any incorrect choice made the response incorrect; responses were partially correct if accurate but incomplete and fully correct only when all correct options were selected. Statistical analysis was performed with p < 0.05. Descriptive statistics, Shapiro–Wilk, Kruskal–Wallis H, Mann–Whitney U, and independent-samples t-tests were used. Results: A total of 308 dentists responded, representing only 7.6% of the national dental workforce. While most recognized the relevance of BC tests and systemic disease indicators in oral health, knowledge gaps were substantial. The mean score on knowledge items was low (2.81 ± 1.52 out of 11), with only 1.3% dentists achieving seven or more correct answers. Interestingly, dentists with higher self-reported confidence in interpreting BC tests had lower knowledge scores, suggesting a potential Dunning-Kruger effect. Knowledge did not differ by specialization or postgraduate education, likely reflecting limited curricular coverage, but was more strongly associated with clinical experience, practice location, and patient load. Most respondents (96.1%) expressed strong interest in further education on the topic. Conclusions: Targeted education and interdisciplinary collaboration are essential to overcome gaps and enhance knowledge and diagnostic accuracy in oral manifestations of blood diseases and BC interpretation. Full article

Haemoglobin (Hb) concentration is a key biomarker for several diseases. Traditional laboratory methods often have limitations due to their time-consuming nature, the need for skilled personnel, or the use of high-cost instrumentation. This work presents a sensing strategy for developing new point-of-care tests (POCTs) for Hb detection via a proof of concept. The proposed sensing approach is implemented using plasmonic plastic optical fiber (POF) sensor chips that integrate an electropolymerized molecularly imprinted polymer (eMIP) film on the plasmonic surface for Hb-selective detection. The developed sensor system demonstrates an ultra-low detection limit of 80 fM in buffer, about five orders of magnitude lower than that of other comparable Hb sensors. Selectivity tests against common interfering proteins, such as bovine serum albumin (BSA) and immunoglobulin G (IgG), confirmed high specificity towards the target analyte. Moreover, the sensor’s performance was tested using a whole-blood sample, yielding results consistent with those of standard haematology analysis. The proposed sensor system, based on simple equipment, provides a quick (about 10 min) and cost-effective (about 10 euros per chip) label-free diagnostic tool for POCTs in real-world scenarios, such as finger-prick sampling, offering a less invasive alternative to traditional laboratory methods, towards devices useful for Internet of Medical Things (IoMT). Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is a heterogeneous disease with substantial variability in clinical manifestations and outcomes, influenced by ethnic and geographical diversity. Remission is the optimal treatment target, while low lupus disease activity state is an accepted alternative goal. Although sustained remission has been associated with reduced organ damage, the impact of early attainment of treatment targets on subsequent damage accrual in SLE remains incompletely defined. To explore a potential window of opportunity, this study aimed to identify factors associated with achieving remission or low lupus disease activity state within the first year of SLE diagnosis and to examine their associations with organ damage. Methods: This retrospective study was conducted across 22 rheumatology centres in Malaysia and included patients with systemic lupus erythematosus (SLE) who had complete follow-up from diagnosis until attainment of treatment targets. Treatment targets were defined as achieving either early remission or a low disease activity state (LDAS). Given the retrospective nature of the study and the unavailability of complete Physician’s Global Assessment data, the definitions of early remission and LDAS were modified by excluding this component. Accordingly, treatment targets were defined as attainment of a clinical SLE Disease Activity Index (cSLEDAI) score of 0 with oral prednisolone doses of ≤5 mg/day and ≤7.5 mg/day, respectively, within 12 months of SLE onset. Multivariable Cox proportional hazards regression and logistic regression analyses were performed to determine factors associated with early remission and organ damage, respectively. Results: A total of 1599 patients were included, the majority of whom were female (92.5%). The cohort was predominantly Malay (68.7%), followed by Chinese (17.4%), Indigenous groups (10.8%) and Indian (3.0%). Early attainment of treatment targets was achieved in 45.7% of patients, while 54.3% experienced delayed attainment. In the multivariable cox regression model, the Malay and Chinese ethnic group demonstrated a significantly lower likelihood of achieving early remission compared to the Indigenous ethnic group. Patients with longer SLE duration, low C4 levels, presence of haematological and renal manifestations at the initial presentation, were identified as additional adverse factors associated with lower likelihood of early remission. Overall, 16.9% of patients accrued organ damage. Independent factors associated with organ damage included Indian ethnicity [OR 5.75, 95% CI 1.39–23.81, p = 0.02], delayed remission [OR 2.97, 95% CI 1.51–5.83) and absence of baseline hydroxychloroquine therapy [OR 4.13, 95% CI 1.21–14.07; p = 0.020]. Conclusions: Ethnic disparities were observed in the early attainment of the treatment targets, as well as in organ damage accrual within the Malaysian multi-ethnic SLE cohort. The significant association between the delay in achieving the treatment targets and organ damage underscores the importance of adopting an early treat-to-target approach in SLE management. Full article

Background/objectives: Gram-negative bacterial infections are associated with significant morbidity and mortality. This targeted literature review (TLR) aimed to descriptively synthesise safety outcomes reported for polymyxins, aminoglycosides, and imipenem/cilastatin/relebactum (IMI/REL) in adult patients with Gram-negative infections. Methods: A TLR was conducted to identify published literature from 2015 to 2025. A database search was conducted on 14 February 2025, using the OVID^® platform and grey literature search reviewed publications from the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) and Infectious Disease (ID) Week. Safety outcomes included nephrotoxicity, other toxicities (e.g., haematological, hepatological), renal impairment, treatment-related (i.e., explicitly related to the antimicrobial treatment or its complications) discontinuation, and treatment-related mortality. Results: Sixty-eight publications were included. Definitions of nephrotoxicity varied between publications; RIFLE and KDIGO classifications were typically used. Definitions of renal impairment included renal risk/injury/failure and acute kidney injury (AKI). Colistin (n = 63) showed nephrotoxicity rates of 30.8–56.4%; renal impairment of 15.0–53.8%; treatment-related discontinuation of 12.5–23.0%; and treatment-related mortality from 20.0 to 39.1%. Polymyxin B showed nephrotoxicity rates of 14.6–54.9%; renal impairment rates ranging from 5.3 to 58.1%; and treatment-related mortality of 7.0% (n = 1). Aminoglycoside data were limited (n = 2) but showed nephrotoxicity rates of 77.8% and renal impairment of 18.8%. IMI/REL (n = 6) demonstrated nephrotoxicity of 10.3–17.2%; renal impairment of 0.0–20.7%; treatment-related discontinuation of 0.0–2.3%; and treatment-related mortality of 0.0–0.7%. Conclusions: Polymyxins/aminoglycosides had more frequently reported safety events. Fewer safety events were reported for IMI/REL across studies. These findings support the clinical use of IMI/REL and may inform Health Technology Assessment (HTA) decisions. Full article

Autoimmune hepatitis (AIH) has long been regarded as an organ-specific disorder. However, increasing evidence supports its systemic nature, with extrahepatic manifestations representing key aspects of clinical management. These manifestations can affect musculoskeletal, gastrointestinal, haematologic, and other systems. They also reflect the complex interplay between systemic inflammation, concomitant autoimmune diseases, and drug-related toxicity. A careful evaluation is therefore essential to distinguish between these scenarios, especially for symptoms like fatigue and cytopenias. This narrative review provides a comprehensive, symptom-based overview of extrahepatic clinical and laboratory findings in AIH. By integrating current evidence with practical diagnostic considerations, it aims to offer clinicians a patient-centred and clinically relevant framework for navigating the multifaceted systemic landscape of AIH. Full article

Background: The landscape of paediatric oncology has undergone a remarkable transformation over recent decades. Advances in both oncological and supportive therapies have dramatically improved survival in children with haematological malignancies and solid tumours, with current survival rates exceeding 80% for many childhood cancers. However, this therapeutic success has brought with it an unexpected consequence: the intensification of treatment protocols has led to a parallel increase in life-threatening complications requiring intensive care support. Current evidence indicates that up to 40% of paediatric oncology patients will require admission to a Paediatric Intensive Care Unit (PICU) at some point during their disease trajectory. Objectives: This comprehensive review synthesises current evidence to provide an updated framework for PICU admission decision-making in oncology haematology patients. We have integrated the most recently published international guidelines, including the groundbreaking Phoenix 2024 sepsis criteria and the updated PALICC-2 2023 recommendations for paediatric acute respiratory distress syndrome. Beyond establishing admission criteria, we critically analyse the efficacy of advanced support strategies and examine emerging therapeutic approaches in this uniquely vulnerable population. Methods: Our methodology encompassed a systematic review of the literature published between 2011 and 2024, complemented by a detailed analysis of current international guidelines and expert consensus statements. We included randomised controlled trials, observational studies, meta-analyses, and consensus conference proceedings specifically addressing the intensive care management of paediatric patients with oncological or haematological conditions. Main Results: Several key findings emerge from our analysis. The Phoenix 2024 criteria represent a fundamental reconceptualisation of paediatric sepsis diagnosis, validated through an unprecedented dataset encompassing more than 3 million paediatric encounters. In the realm of respiratory support, early implementation of non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP) has demonstrated remarkable efficacy, reducing the need for invasive mechanical ventilation by 45% (RR 0.45, 95% CI 0.26–0.78) when applied to appropriately selected patients. Extracorporeal membrane oxygenation (ECMO), whilst increasingly utilised, shows survival to decannulation ranging from 52% to 64%, though survival to hospital discharge remains less encouraging at 36–42%. Continuous renal replacement therapy (CRRT) has proven highly effective for tumour lysis syndrome, achieving metabolic correction in 90% of severe cases. Perhaps most promisingly, emerging biomarkers—particularly interleukin-6, interleukin-10, and procalcitonin—have substantially enhanced our ability to stratify infection risk, demonstrating sensitivity exceeding 85% for bacteraemia detection. Conclusions: The evidence unequivocally supports several core principles for optimising outcomes in this population. Early identification of deterioration through validated scoring systems enables timely intervention before irreversible organ failure develops. Prompt implementation of non-invasive respiratory support, when appropriately applied, can obviate the need for mechanical ventilation with its attendant complications. Perhaps most critically, centralisation of care in centres with dedicated expertise and comprehensive support capabilities fundamentally improves survival. These findings argue compellingly for the establishment of a formal national network of reference centres, implementing standardised protocols and structured care pathways specifically designed for critically ill paediatric oncology haematology patients. Full article

Background: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition resulting from a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency, leading to the accumulation of ultra-large von Willebrand factor (vWF) multimers and widespread microvascular thrombosis. While therapeutic plasma exchange and immunosuppression have significantly improved response, refractory and relapsed disease are significant challenges. N-acetylcysteine (NAC) has emerged as a biologically plausible adjunctive therapy due to its potential to reduce disulfide bonds in vWF multimers. However, its clinical role is unclear. This systematic review aimed to evaluate the clinical evidence regarding the efficacy and safety of N-acetylcysteine in patients with immune-mediated TTP. Methods: We performed a systematic review in accordance with the PRISMA guidelines. PubMed/MEDLINE, Google Scholar, and ClinicalTrials.gov were searched until January 2026. Studies involving patients with immune-mediated TTP treated with NAC were included. Case reports, case series, and observational studies involving patients with immune-mediated TTP treated with NAC were included. Risk of bias was evaluated using adapted quality assessment tools. Results: Sixteen studies encompassing 69 patients met the inclusion criteria. Most reports were case reports or small case series; two were larger observational cohorts. NAC was predominantly used as adjunctive therapy in relapsed or refractory TTP. Dose regimens varied. Platelet recovery following NAC was reported within 1–15 days in responding cases. Predominantly positive haematological responses were observed in small series. Significant heterogeneity in patient populations, timing of initiation, concomitant therapies, and outcome reporting limited causal inference. Conclusions: The current evidence suggests that NAC has a biologically rational and potentially adjunctive value in TTP, particularly in refractory disease or resource-constrained settings. However, current data are largely heterogeneous and derived from low-level evidence. Well-designed prospective studies and randomized controlled trials are needed to determine whether NAC provides significant clinical benefit beyond standard therapy. Full article

Background: Tuberculosis (TB) remains a major global health threat, particularly in low- and middle-income countries, with TB infection (TBI) serving as the primary source of TB disease. While HIV infection has long been recognised as a major risk factor for TB progression, the rise of Non-Communicable Diseases (NCDs), which may exert immunosuppressive effects, further compounded by their treatment, contributes to increased TB susceptibility. This scoping review synthesises evidence from systematic reviews on medical and behavioural risk factors for TBI progression to TB disease, for both asymptomatic and symptomatic disease. Methods: A preliminary literature search was conducted on 11 January 2025, in PUBMED using the keywords “tuberculosis,” “asymptomatic or subclinical tuberculosis” “risk factors,” and “systematic review” followed by targeted reviews on the identified medical and behavioural risk factors for TB infection progression to TB disease. Results: A total of 25 systematic reviews were included. Medical risk factors for progression from TB infection to TB disease included diabetes mellitus (DM), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), undernutrition (including iron and vitamin D deficiency), cancer—particularly haematological malignancies—and immunosuppressive therapies (TNF-α inhibitors and glucocorticoids). Iron and vitamin D deficiency, particularly severe deficiency, is linked to increased TB risk, especially among people living with HIV. Behavioural risk factors, including tobacco, drug, and alcohol use, were also highlighted. Geographic variations in TB prevalence, diagnostic practices, and healthcare systems contributed to differences in risk estimates across reviews. No systematic reviews were identified that examined risk factors for asymptomatic TB. Conclusions: The convergence of TB with NCDs, compounded by immunosuppressive therapies, poses a public health challenge in high TB burden settings. Effective TB prevention requires targeted screening, along with enhanced management of these NCDs. Nutritional support, particularly screening and treatment of anaemia and vitamin D deficiency, may benefit individuals with TBI, comorbid NCDs, and HIV. A multidisciplinary approach, integrating behavioural interventions and tailored prevention strategies, is essential to achieving WHO’s End TB targets. Addressing the evidence gap on risk factors for asymptomatic TB is also critical to improve early detection and interrupt transmission. Full article