Trastuzumab deruxtecan has made breast tumours with minimal HER2 expression therapeutically actionable, and the descriptors HER2-low and HER2-ultralow now carry regulatory weight. Both were defined by immunohistochemical convention and trial eligibility rather than by calibrated measurement. For a receptor-directed particulate carrier the operative question is not whether HER2 is detectable, but whether enough surface-accessible receptor is present, and suitably distributed, to sustain multivalent attachment, clustering, internalisation and payload transfer. This narrative review asks whether principles established in HER2-overexpressing models, in non-HER2 receptor systems and on synthetic interfaces can defensibly be extrapolated to the HER2-low setting, keeping those evidence classes distinct. Antigen density acts at several stages of the delivery cascade rather than at binding alone, jointly with carrier design and tumour transport. An analytical constraint compounds this: fixed-tissue methods report tissue HER2 abundance but do not selectively quantify the accessible receptor pool a carrier can engage. Within the literature identified, no engagement threshold generalisable across platforms was found; the single measured value belongs to one liposomal system studied in vitro. Lesion-level carrier deposition varied widely in both human imaging datasets identified, which illustrate transport heterogeneity but are not comparable. Targetability is platform-specific, and should be measured rather than inferred from categorical HER2 status. No validated model links receptor abundance, ligand density, avidity and internalisation to biological response, so the framework offered is operational.

Chronic venous disease (CVD) in pregnancy is common, poorly codified, and interpreted with diagnostic thresholds, severity instruments and treatment algorithms all derived outside pregnancy. This narrative review synthesises the mechanistic, epidemiological, diagnostic and therapeutic literature, keeping pregnancy-specific evidence separate from evidence extrapolated from non-pregnant populations. Gestational change is characterised principally by increased venous capacitance and vein-wall distension; ambulatory venous hypertension was not demonstrated in the two pregnancy studies assessing it; and new reflux develops in a minority, undetectable postpartum in the one study reporting it. Physiological adaptation, CVD and thrombotic pathology overlap clinically, deep vein thrombosis and superficial vein thrombosis being at once the principal differential diagnoses and potential complications. Management is correspondingly conservative: compression relieves symptoms but has not been shown to prevent varicose veins, routine initiation of venoactive drugs is not supported, and intervention is deferred other than in exceptional circumstances. A venous finding first detected in pregnancy warrants postpartum reassessment before it is taken for established disease. A trimester-stratified framework spanning preconception to late postpartum reassessment is proposed; it is evidence-informed rather than prospectively validated, and is not a guideline.

Background/Objectives: Breast cancer is the most frequently diagnosed malignancy worldwide and remains a major cause of cancer-related mortality among women. Despite advances in screening, molecular classification, and systemic therapies, treatment of advanced and metastatic disease remains challenging because of tumor heterogeneity, multidrug resistance, systemic toxicity, limited drug selectivity, and inadequate penetration into the tumor microenvironment. This review aims to critically evaluate advanced drug delivery systems (DDSs) for breast cancer therapy, emphasizing the relationship between carrier design, tumor biology, therapeutic performance, and clinical translation. Methods: The recent literature on DDSs for breast cancer treatment was comprehensively reviewed, covering liposomes, polymeric nanoparticles and micelles, dendrimers, nanogels, lipid- and inorganic-based nanoparticles, extracellular vesicles, biomimetic platforms, and stimuli-responsive systems. Particular attention was given to active and passive targeting, controlled drug release, strategies for overcoming multidrug resistance and biological barriers, and combination approaches integrating chemotherapy with immunotherapy, gene therapy, and phototherapy. Clinically approved and clinical-stage nanomedicines were also considered. Results: Advanced DDSs can improve drug stability, pharmacokinetics, biodistribution, tumor accumulation, cellular uptake, and controlled release, potentially enhancing therapeutic efficacy while reducing systemic toxicity. Targeted, biomimetic, and stimuli-responsive platforms provide additional opportunities to address tumor heterogeneity, the tumor microenvironment, and therapeutic resistance. Several DDS-based nanomedicines have reached clinical use or advanced clinical development, demonstrating their translational potential. However, manufacturing scalability, reproducibility, long-term safety, regulatory requirements, and patient heterogeneity remain important barriers. Conclusions: Advanced DDSs represent promising tools for improving the precision and efficacy of breast cancer treatment. Future progress will require biologically informed carrier design, reproducible manufacturing, rigorous clinical validation, and patient stratification. Integrating nanomedicine with precision oncology may accelerate the clinical translation of next-generation DDSs and support more effective personalized therapeutic strategies.

Acute fatty liver of pregnancy (AFLP) is a rare microvesicular steatotic liver disease of late gestation, linked to impaired mitochondrial fatty acid β-oxidation, in which management centres on recognition and delivery before overt hepatic and multiorgan failure has developed. The Swansea criteria, which require six or more of fourteen features in the absence of an alternative explanation, define AFLP in guidelines and in most published cohorts. This narrative review examines how the criteria behave across the course of the illness and which markers might signal the disease earlier. The criteria are frequently fulfilled once AFLP is clinically established, but their accuracy against an independent reference standard derives from one small, high-prevalence biopsy series, and their specificity against haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome and other causes of acute liver failure appears limited. Because several criteria index established organ failure, the threshold may remain unmet earlier in the illness, a hypothesis consistent with limited retrospective evidence; to our knowledge, no study has evaluated the criteria prospectively at initial presentation. We relate each criterion to hepatic energy failure and appraise candidate early markers, including coagulation indices, antithrombin, conjugated hyperbilirubinaemia, hypocholesterolaemia, soluble fms-like tyrosine kinase-1 and metabolite-level signals of fatty acid oxidation failure; none has a validated early diagnostic threshold. We outline a conceptual, hypothesis-generating framework for prospective research that would complement, not replace, the Swansea case definition.

Cervical excision increases the risk of preterm birth, while active surveillance for grade 2 cervical intraepithelial neoplasia offers no active treatment. Topical therapy for human papillomavirus (HPV)-associated lower genital tract disease could address this gap, yet no agent is approved for intraepithelial neoplasia of the cervix, vagina, or vulva, and a 2026 systematic review left open whether cervical treatment reduces progression. Scarcity does not explain this: 52 randomized trials have evaluated adjuvant treatment after excision, but heterogeneity in phenotype, comparator, and endpoint, and incomplete access to primary reports limit their interpretability. Three problems recur. First, the target epithelial population differs by phenotype and mechanism, yet local exposure was seldom characterized, although measurement strategies are set out here. Second, some antiviral claims rely on systems that do not reproduce the differentiation-dependent HPV life cycle. Third, endpoints are read against spontaneous regression approaching the effect sought. Randomized evidence supports imiquimod as a non-surgical option for appropriately selected women with vulvar high-grade squamous intraepithelial lesions; cervical conclusions depend on comparator and endpoint. We propose a conceptual eight-element sequence from clinical intention to inference, an interpretive aid, and not a validated appraisal instrument. Future studies should prespecify these elements and characterize exposure where feasible.

Caesarean delivery is rising worldwide, and for breech presentation at term, external cephalic version (ECV) reduces non-cephalic presentation at birth and, at very low certainty, caesarean delivery. Procedural evidence is reported per attempt, whereas losses determining whether an eligible woman reaches an attempt occur earlier and, in the literature we retrieved, are rarely measured. This narrative review compares procedural evidence with what is recorded about progression to ECV. Immediate success occurs in roughly half to six in ten attempts. Severe procedure-attributable complications are uncommon under strict definitions, at 0.24% in pooled data and 0.45% in a large series, whereas broader short-term composites reach 6–10% and count different events. Attempt rates were 62.2% and 72.5% of eligible women in two Dutch cohorts and 7.9% of a source-defined cohort in United States data, over non-comparable denominators. No contemporary study identified in our search reports the proportion of eligible women offered ECV in ordinary clinical practice, with eligibility assessed in every term breech presentation, despite an auditable standard targeting 100%. We identified no study measuring procedural effects and losses before the attempt within one population. Utilisation varies markedly, but the extent of any underuse cannot be quantified from this documented, non-exhaustive search. We set out an author-derived nine-state pathway with explicit denominators and three proposed process indicators as a reporting framework, not as validated measures.