Search Results (249)

Hemostasis and thrombosis reflect a delicate balance, regulated by the interplay between procoagulant and anticoagulant mechanisms. Hemophilia is traditionally viewed as a bleeding disorder, but emerging evidence highlights the paradoxical risks of thrombosis in hemophilia patients. We explore the landscape of hemophilia management, emphasizing challenges of balancing hemostasis in the context of aging, novel non-factor replacement therapies (NRTs), and comorbidity-driven thrombotic complications. Therapeutic approaches, including innovative NRTs, such as emicizumab, or rebalancing agents (e.g., concizumab, marstacimab, fitusiran), offer promising advancements in bleeding prophylaxis but may increase thrombotic risks. Conversely, novel anticoagulants, such as FXI inhibitors, offer potential thrombosis protection with minimal bleeding risk. Our review examines the impact of aging-related comorbidities, including cardiovascular disease, atrial fibrillation, HIV-associated complications, and acute coronary syndromes, on thrombotic risk in hemophilia patients. Evidence-based strategies for balancing hemostasis and thrombosis are outlined alongside experimental models, thrombin generation assays, and advancements in rebalancing coagulation through natural anticoagulant modulation. FXI inhibition emerges as a paradigm shift in thrombosis management, offering reduced bleeding risks while preserving vascular health. Finally, this review highlights the need for global laboratory assays to personalize treatments, emphasizing strategies to optimize safety and efficacy, particularly as hemophilia patients live longer with complex comorbidity profiles. Full article

Postpericardiotomy syndrome (PPS) is the most frequent inflammatory after-effect of cardiac surgery and is characterized by high morbidity, delayed hospitalization, and increased long-term mortality rates. Although PPS is common, empirical anti-inflammatory therapy has historically been employed for its prevention, and mechanism-based approaches have not yet been standardized. In this literature review, which was conducted on the basis of randomized controlled trials, meta-analyses, cohort studies, and mechanistic research regarding pharmacologic interventions, surgical modalities, and biomarker-based preventive strategies, the deficiencies of a critical synthesis of existing preventive strategies and emerging risk stratification instruments for PPS are addressed. The review affirms that the most evidence-based pharmacologic intervention is colchicine, which demonstrates a consistent reduction in PPS incidence across a range of randomized trials. Nonsteroidal anti-inflammatory drugs show variable responses, whereas corticosteroids are no longer recommended for routine prophylaxis due to relapse. Specific anti–interleukin-1 therapies represent a promising novel approach for high-risk patients. Surgical interventions, such as pericardial closure using biomaterials and posterior pericardiotomy, are important and do not lead to increased hemodynamic complications, while postoperative effusions, atrial fibrillation, and tamponade are reduced. Less invasive methods may also be employed to mitigate inflammatory causes, particularly in valve-sparing procedures and congenital operations. Emerging biomarker data, including postoperative neutrophil-to-lymphocyte ratios, C-reactive protein levels, and pericardial fluid cytokines, enable the identification of high-risk patients and form the basis for a personalized prevention approach. In summary, pharmacologic prophylaxis, innovative surgical techniques, and biomarker-based risk stratification represent a pathway toward reducing the incidence and burden of PPS in modern cardiac surgery. Full article

Background: Immunomodulatory therapies, including biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) have reshaped the treatment of autoimmune diseases. They alter host defenses, but the current landscape of associated infectious risk is not fully defined. Objective: A scoping review of recent literature was conducted to characterize infectious complications associated with modern immunomodulatory biologic agents, summarize current pathogen patterns, and highlight recommendations for prevention and early recognition in clinical practice. Methods: Following PRISMA-ScR guidelines, a systematic search was performed on Scopus, Science Direct, and PubMed for studies published since 2023. Inclusion criteria focused on adult human subjects, exposure to immunomodulatory therapy, and reported infectious outcomes. Studies focusing exclusively on antineoplastic agents without established use in autoimmune diseases were excluded. After screening 1046 unique records, 16 studies were included in the final review. Findings: High-dose glucocorticoids remain a primary driver of serious infections across autoimmune diseases. Newer agents present mechanism-specific risk profiles. JAK inhibitors are associated with herpes zoster, while TNF-α inhibitors are linked to opportunistic bacterial infections and reactivation of granulomatous infections. B-cell depletion with rituximab correlates with hypogammaglobulinemia and its associated infections, whereas belimumab may offer a lower infection risk in non-renal SLE. Recent post hoc analyses (2023–2025) quantify the elevated risk of herpes zoster with JAK inhibitors compared to TNF inhibitors, particularly in older populations. Conclusions: The infectious risk associated with biologic and targeted DMARDs varies by mechanism. While glucocorticoids remain a primary driver of serious infections, newer data highlights specific vulnerabilities with JAK inhibitors (herpes zoster) and B-cell depletion (hypogammaglobulinemia) that require targeted risk stratification. This review shows the urgent need for individualized risk stratification, targeted prophylaxis (e.g., for Pneumocystis or zoster), and pre-therapy screening to balance therapeutic efficacy with patient safety. Full article

Patients with leukemia are at heightened risk for invasive fungal infections (IFIs) due to profound immunosuppression caused by both the malignancy and its treatment. Chemotherapy-induced neutropenia, mucosal barrier disruption, and impaired innate and adaptive immune responses create a highly permissive environment for opportunistic fungal pathogens. Antifungal prophylaxis, particularly in acute myeloid leukemia (AML), has become a cornerstone in reducing IFI-related morbidity and mortality. This review outlines the immunopathogenic mechanisms underlying susceptibility to IFI and discusses current evidence on the optimal timing and therapeutic strategies for antifungal intervention. The clinical utility of key antifungal agents, namely, posaconazole, isavuconazole, and voriconazole, is critically evaluated. We also examine the potential role of emerging agents such as opelconazole, which enables targeted pulmonary delivery and prolonged epithelial retention, representing a promising approach to IFI prevention. Drug-specific considerations, including pharmacokinetics, drug–drug interactions, toxicity profiles, and cost-effectiveness, are analyzed in the context of clinical decision-making. Finally, we emphasize the importance of tailoring antifungal strategies based on leukemia subtype, immunosuppressive status, and individual patient factors to optimize outcomes and support antifungal stewardship in hematologic malignancies. Full article

The complement system is a key component of innate immunity, responsible for mediating the rapid clearance of pathogens and coordinating adaptive immune responses. Although complement activation is essential for effective infection control and prevention, its excessive or dysregulated function contributes to the pathogenesis of various immune-mediated disorders. Therefore, therapeutic inhibition of the overactive complement cascade, in which specific components are selectively blocked to suppress pathological activation, plays an important role in the treatment of various complement (immune)-mediated diseases. This article provides an overview of complement inhibition as a therapeutic strategy, highlighting the infectious risks associated with its use. Disruption of complement-dependent host defence mechanisms increases the risk of invasive infections (caused by encapsulated pathogens, e.g., Neisseria spp., Streptococcus pneumoniae and Haemophilus influenzae type B), which represent a significant clinical challenge. Therefore, the use of complement inhibition should not only be effective but also safe in combination with the application of all possible tools to prevent infections. Strategies, such as vaccination and antibiotic prophylaxis, are crucial to minimise these complications, despite the persistence of the risk of breakthrough infections. Furthermore, this review examines advancements in patient risk stratification, evaluates alternative preventive measures, and identifies key gaps in current clinical practice. Future directions include improving monitoring protocols, creating more selective or locally acting complement inhibitors, and implementing biomarker-driven personalised therapies that maximise benefits while reducing side effects. Full article

(1) Background: Zinc is an essential micronutrient involved in immune regulation, epithelial barrier integrity, and the host response to bacterial infections. However, the clinical benefits of zinc supplementation across different age groups remain uncertain, with heterogeneous findings and variable dosing strategies reported in the literature. (2) Objectives: To map and summarize randomized controlled trials (RCTs) evaluating zinc supplementation (either as treatment or prophylaxis) for bacterial infection outcomes in neonates, children, and adults, and to identify gaps requiring further research, including the use of zinc-based nanoparticles. (3) Eligibility Criteria: We included English-language RCTs that evaluated zinc supplementation and reported clinical outcomes related to bacterial infections. Observational studies, trials without infection-related outcomes, and studies not involving human participants were excluded. (4) Sources of Evidence: A MEDLINE (PubMed) search was conducted from 2000 to 1 November 2025 using predefined keywords related to zinc supplementation, neonates, children, adults, and bacterial infections. Reference lists of eligible articles were screened to identify additional studies. (5) Charting Methods: Data were charted for each included study, including population characteristics, zinc dosing and regimen, type of supplementation (therapeutic or prophylactic), main infection-related outcomes, and key findings. Data charting was performed independently and verified within the research team. (6) Results: A total of 51 RCTs were included: 10 in neonates, 32 in children, and 9 in adults. In neonates, therapeutic zinc supplementation as an adjunct to antibiotics showed heterogeneous results, with some studies reporting reductions in morbidity, inflammatory markers or mortality, while others found no significant differences in clinical outcomes. In children, zinc supplementation consistently reduced the duration and severity of diarrheal episodes and, in several trials, improved the resolution of respiratory infections. In adults, the evidence was limited but suggested potential benefits in selected populations, such as burn patients or those with zinc deficiency or immunologic dysfunction. Variability in zinc dosage, treatment duration, and outcome definitions limits direct comparison across studies. (7) Conclusions: Zinc supplementation appears to provide benefits in neonates and children, whereas evidence in adults remains mixed and inconclusive. Standardized, well-powered RCTs are needed to define optimal dosing strategies, identify populations most likely to benefit, and clarify the mechanisms underlying zinc’s anti-infective effects. Future research should consider the use of zinc oxide nanoparticles (ZnO-NPs) demonstrated broad-spectrum antimicrobial activity and potential synergy with antibiotics, although clinical data remain still limited. Full article

Background: Venous thromboembolism (VTE) is associated with high morbidity and mortality. The activation of multiple pathways of venous thrombosis occurs after an injury. A prophylaxis protocol is necessary to prevent early and late venous thrombotic complications. Methods: This study aimed to evaluate the outcomes of venous thromboembolism using the Greenfield risk assessment profile score and its association with bleeding complications. This was a retrospective cohort study conducted on trauma cases who were aged 15 years or older. The study was conducted from January 2020 through December 2022. Patients who were admitted to hospital for less than 24 h or those who died during resuscitation or treatment in an emergency room were excluded from this study. Results: We enrolled 580 cases. Among them, 46.6% were categorized as high-risk for developing venous thromboembolism, and 30.4% of these high-risk patients received pharmaco-mechanical thromboprophylaxis. All VTE cases were high risk according to the Greenfield risk assessment profile, accounting for 3% of the entire group and 1.4% of all enrolled cases. All major bleeding complications occurred with a previously diagnosed large subdural hematoma. Conclusions: Assessing VTE risk was crucial for optimal management of prophylaxis. Proper use of pharmacological prophylaxis had to be balanced against the risk of bleeding complications. Full article

Background/Objectives: The current strategy for seasonal influenza prophylaxis relies on updating the vaccine components annually to account for the rapid antigenic drift of viruses and the low cross-protective efficacy of available vaccines. Mutant influenza viruses with truncated or deleted NS1 protein are known to stimulate cross-specific T-cell immune response and provide protection against heterosubtypic influenza A and B viruses. Methods: We generated NS1ΔC influenza A and B viruses with C-terminal NS1 deletions by reverse genetics. In a mouse model, we assessed the safety and immunogenicity of the B/Lee/NS1ΔC strain upon intranasal administration, as well as the mechanism of its cross-protective efficacy against sublethal B/Victoria and B/Yamagata challenges. We then investigated the potential of the intranasal Flu/NS1ΔC vaccine–a trivalent formulation of NS1ΔC A/H1N1, A/H3N2, and B influenza viruses–to protect mice from lethal influenza infection with homologous, heterologous, and antigenically drifted influenza A and B viruses. Results: Intranasal immunization with the B/Lee/NS1ΔC strain was safe in mice. It activated cross-specific T-cell responses in the lungs and protected animals against heterologous challenge by reducing viral load, inflammation, and lung pathology. Immunization with the trivalent Flu/NS1ΔC vaccine formulation improved survival and reduced weight loss and viral load upon challenge with A/H1N1pdm, A/H2N2, A/H5N1, and B/Victoria viruses. Conclusions: The trivalent intranasal Flu/NS1ΔC influenza vaccine is a promising tool to improve seasonal influenza protection and preparedness for an influenza pandemic. Full article

Postoperative recurrence (POR) remains a significant challenge in Crohn’s disease (CD) management despite therapeutic advances. Contemporary data show ileocecal resection rates of 18.7%, 28.0%, and 39.5% at one, five, and ten years after diagnosis, with endoscopic recurrence occurring in 22.4–53% of patients within 18–36 months postoperatively. Current understanding of POR pathophysiology includes microbiota dysbiosis, mesenteric inflammation, immune dysregulation, and genetic factors, particularly NOD2 variants. Key risk factors comprehend smoking, penetrating or perianal disease, prior surgeries, and extensive small bowel involvement. The Rutgeerts score remains the endoscopic gold standard for assessing recurrence, though it has never been validated and modifications addressing modern anastomotic techniques have been proposed. Non-invasive monitoring strategies using fecal calprotectin, intestinal ultrasound, and magnetic resonance enterography demonstrate promising diagnostic performance and may reduce the burden of routine endoscopy. Anti-TNF agents and Vedolizumab show superior efficacy in preventing endoscopic recurrence compared to conventional therapies, while other advanced therapies like anti-JAKs, risankizumab and ustekinumab demonstrate potential benefit in postoperative prophylaxis. Management approaches have evolved toward risk-stratified strategies balancing systematic prophylaxis against endoscopy-driven therapy. While medical prophylaxis remains first-line for high-risk patients, the expanding therapeutic armamentarium and improved understanding of pathophysiologic mechanisms enable increasingly personalized postoperative care. Further research is needed to validate risk assessment tools, optimize timing and selection of prophylactic therapies, and define the role of emerging agents in reducing long-term disease burden. Full article

Therapeutic antibodies have revolutionized hematology, offering targeted and effective treatments for both malignant and non-malignant diseases. In hematologic malignancies, anti-CD20, anti-CD19, anti-CD38, and anti–B-cell maturation antigen (BCMA) antibodies have markedly improved survival outcomes, whereas antibody–drug conjugates and bispecific antibodies continue to expand therapeutic possibilities. Besides cancer, complement inhibitors such as eculizumab, ravulizumab, and the recently approved crovalimab have redefined paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome management, and the bispecific antibody emicizumab has transformed prophylaxis in hemophilia A. Furthermore, novel antibody formats such as the trifunctional anti-CD38 × CD3 antibody (Tri-31C2) exhibit enhanced anti-myeloma activity compared to chimeric CD38 antibodies, underscoring the future potential of T-cell–redirecting designs. This review summarizes key developments in therapeutic antibodies for hematological disorders, their action mechanisms, and emerging strategies to further optimize their efficacy and safety. Full article

Background: Tyrosine kinase inhibitors (TKIs) are crucial to treating endocrine-related malignancies, including advanced thyroid cancers and neuroendocrine tumors, but their benefit is tempered by cutaneous adverse events (CAEs) that impair adherence and quality of life. Objective: To summarize the dermatologic toxicities of TKIs used in endocrine oncology and provide practical, multidisciplinary guidance for prevention and management. Methods: Narrative synthesis of clinical trial reports, post-marketing studies, and specialty guidelines pertinent to lenvatinib, vandetanib, cabozantinib, and other commonly used TKIs, integrating dermatologic and endocrine perspectives on mechanisms and care pathways. Results: VEGFR-targeted TKIs frequently cause hand–foot skin reaction, xerosis, fissuring, paronychia, and impaired wound healing; multikinase inhibition also produces alopecia, pigmentary changes, and mucositis. Epidermal growth factor receptor (EGFR) and rearranged during transfection (RET) inhibition with vandetanib is associated with acneiform eruption, photosensitivity, and nail fragility. Pathogenesis reflects on-target inhibition of VEGF/EGFR signaling leading to keratinocyte dysfunction, vascular fragility, and altered eccrine mechanics. Early risk stratification, patient education, and bundle-based prophylaxis (emollients, keratolytics, urea-based creams, sun protection) reduce incidence and severity. Grade-based algorithms combining topical corticosteroids/antibiotics, dose interruptions or reductions, and short systemic courses (e.g., doxycycline, antihistamines) enable symptom control while maintaining anticancer intensity. Close coordination around procedures minimizes wound-healing complications. Conclusions: Dermatologic toxicities are predictable, mechanism-linked, and manageable with proactive, multidisciplinary care. Standardized prevention and treatment pathways tailored to specific TKIs—particularly lenvatinib, vandetanib, and cabozantinib—can preserve dose intensity, optimize quality of life, and sustain antineoplastic efficacy. Full article

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetically determined disorders that lead to immune dysfunction, recurrent infections, and organ-specific complications. The lungs are among the most commonly affected organs, with both infectious and noninfectious manifestations that significantly contribute to morbidity and mortality. This study aimed to provide a comprehensive overview of pulmonary manifestations in IEI, with emphasis on pathophysiological mechanisms, diagnostic approaches, and therapeutic strategies. Methods: A narrative review and synthesis of current literature and clinical guidelines were conducted, focusing on pulmonary involvement in IEI as classified by the International Union of Immunological Societies (IUIS). The analysis included data on infectious and noninfectious complications, imaging findings, immunological assessments, and management strategies, supported by clinical evidence and expert consensus. Results: Pulmonary manifestations in IEI encompass a wide spectrum of conditions. Infectious complications include recurrent bacterial pneumonias, bronchitis, and opportunistic infections, frequently resulting in irreversible lung damage such as bronchiectasis. Noninfectious complications, including granulomatous–lymphocytic interstitial lung disease (GLILD) and interstitial lung disease (ILD), are common in disorders such as common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA). Early diagnosis using high-resolution computed tomography (HRCT) and immunological testing, combined with the timely initiation of immunoglobulin replacement therapy and anti-biotic prophylaxis, significantly improves prognosis. Conclusions: Pulmonary complications are key clinical indicators of IEI and often precede systemic manifestations. Early, integrated, and interdisciplinary diagnostic and therapeutic management are crucial for preventing irreversible lung damage and improving patient outcomes. Regular monitoring and individualized therapy, including immunoglobulin replacement, targeted immunosuppression, and vaccination, are the cornerstones of effective long-term care in IEI. Full article

Antimicrobial resistance (AMR) is a growing global health concern with profound implications for ophthalmology, where it compromises the management of ocular infections such as bacterial keratitis, conjunctivitis, endophthalmitis, and postoperative complications. Resistance in common ocular pathogens, including Staphylococcus aureus (S. aureus), Streptococcus pneumoniae (S. pneumoniae), Pseudomonas aeruginosa (P. aeruginosa), and coagulase-negative staphylococci (CoNS) emerge through genetic mutations, horizontal gene transfer, and biochemical mechanisms such as enzymatic degradation, target modification, efflux pumps, and reduced membrane permeability. Biofilm formation further complicates eradication on the ocular surface and interior. The key drivers of resistance include inappropriate or prolonged topical antibiotic use, routine prophylaxis in ocular surgery, subtherapeutic dosing, and cross-resistance with systemic antimicrobials. The rise in multidrug-resistant strains, particularly methicillin-resistant S. aureus, fluoroquinolone-resistant P. aeruginosa, and drug-resistant S. pneumoniae has been linked to delayed treatment response, increased healthcare costs, and sight-threatening outcomes. Recent advances in rapid diagnostics, molecular assays, and point-of-care testing support earlier and more precise detection of resistance, enabling timely therapeutic decisions. Promising strategies to address AMR in ophthalmology include antimicrobial stewardship, novel drug delivery platforms, and alternative approaches such as bacteriophage therapy and antimicrobial peptides. Emerging tools, including genomic surveillance, artificial intelligence (AI)-driven resistance prediction, and personalized antimicrobial regimens, further expand opportunities for innovation. Collectively, this review synthesizes current evidence on AMR in ocular disease, summarizing patterns of resistance, underlying mechanisms, and clinical consequences, while highlighting strategies for mitigation and underscoring the need for global awareness and collaboration among clinicians, researchers, and policymakers to safeguard vision. Full article

Background: Severe traumatic brain injury (TBI) often leads to elevated intracranial pressure (ICP) that requires aggressive management. Inducing burst suppression with deep sedation is an established therapy for refractory intracranial hypertension. Traditionally, barbiturate coma has been used to achieve burst-suppression EEG in TBI patients, but alternative sedative agents (propofol, midazolam, ketamine, dexmedetomidine) are increasingly utilized in modern neurocritical care. This review compares barbiturates with these alternatives for inducing burst suppression in adult TBI, focusing on protocols, mechanisms, efficacy in controlling ICP, safety profiles, and impacts on neurological outcomes. Methods: A search of the literature was performed, including clinical trials, observational studies, and guidelines on deep sedation for ICP control in adult TBI. Studies comparing high-dose barbiturates to other sedatives (propofol, midazolam, ketamine, dexmedetomidine) in the context of burst suppression or severe TBI management were included. Data on sedative protocols (dosing and EEG targets), mechanisms of action, ICP-lowering efficacy, complications, and patient outcomes were extracted and analyzed qualitatively. Results: High-dose barbiturates (e.g., pentobarbital or thiopental) and propofol are both effective at inducing burst-suppression EEG and reducing ICP via cerebral metabolic suppression. Barbiturate coma remains a third-tier intervention reserved for ICP refractory to other treatments. Propofol infusion has become first-line for routine ICP control due to rapid titratability and shorter half-life, though it can also achieve burst suppression at high doses. Midazolam infusions provide sedation and seizure prophylaxis but yield less metabolic suppression and ICP reduction compared to barbiturates or propofol, and are associated with longer ventilation duration and delirium. Ketamine, once avoided for fear of raising ICP, has shown neutral or lowering effects on ICP when used in ventilated TBI patients, thanks to its analgesic properties and maintenance of blood pressure; however, ketamine alone does not reliably produce burst-suppression patterns. Dexmedetomidine offers sedative and anti-delirium benefits with minimal respiratory depression, but it is generally insufficient for deep burst-suppressive sedation and has only a modest effect on ICP. In comparative clinical evidence, propofol and barbiturates both effectively lower ICP, but neither has demonstrated clear improvement in long-term neurological outcome when used prophylactically. Early routine use of barbiturate coma may increase complications (hypotension, immunosuppression), and thus, current practice restricts it to refractory cases. Modern sedation protocols emphasize using the minimal necessary sedation to maintain ICP < 22 mmHg, with continuous EEG monitoring to titrate therapy to a burst-suppression target (commonly 2–5 bursts per minute) when deep coma is employed. Conclusions: In adult TBI patients with intracranial hypertension, propofol-based sedation is favored for first-line ICP control and can achieve burst suppression if needed, whereas high-dose barbiturates are reserved for ICP crises unresponsive to standard measures. Compared to barbiturates, alternative agents (propofol, midazolam, ketamine, dexmedetomidine) offer differing advantages: propofol provides potent, fast-acting metabolic suppression; midazolam adds anticonvulsant sedation for prolonged use at the cost of slower wake-up; ketamine supports hemodynamics and analgesia; dexmedetomidine aids lighter sedation and delirium control. The choice of agent is guided by the clinical scenario, balancing ICP reduction needs against side effect profiles. While all sedatives can transiently reduce ICP, careful monitoring and a tiered therapy approach are essential, as no sedative has conclusively improved long-term neurological outcomes in TBI. EEG monitoring for burst suppression and meticulous titration is required when employing barbiturate or propofol coma. Ongoing research into optimal combinations and protocols may further refine sedation strategies to improve safety and outcomes in severe TBI. Full article

Background/Objectives: Lithium remains the first choice for long-term prophylaxis of mood episodes in bipolar disorder (BD), but only 30% of patients will respond, and there is no reliable method by which to predict treatment response. Ketamine is a rapid antidepressant therapy which ostensibly yields greater results in patients with clinical phenotypes that are classically associated with lithium non-response. This inspired a scoping review to map the overlapping and divergent clinical and mechanistic evidence for acute ketamine response and long-term prophylactic lithium therapy in BD. Methods: We conducted a scoping review of clinical and preclinical studies that examine convergent and divergent predictors and mechanisms of acute response to ketamine and long-term response to lithium. Results: Data from 19 preclinical studies show mechanistic convergence of ketamine and lithium on the GSK-3β/mTOR pathways, and enhancement of synaptic plasticity. Furthermore, lithium appears to consistently limit ketamine-related oxidative stress and hyperlocomotion. However, data from the 23 clinical studies suggest divergence of predictors of response to ketamine and lithium in BD, with ketamine response associated with metabolic risk factors, anxiety/mixed features, and non-melancholic presentations, which are generally predictors of poorer prophylactic lithium response. No study directly tested ketamine response as a predictor of prophylactic lithium response. An important limitation is that clinical studies of ketamine are enriched for lithium-refractory populations and have often included mixed unipolar and bipolar cases. Conclusions: Overall, existing data support mechanistic overlap but clinical divergence between ketamine and lithium responders, though this is confounded by sampling bias. We must therefore undertake longitudinal studies of prophylactic lithium therapy among patients with BD who received ketamine for acute antidepressant treatment in order to investigate if responsiveness to ketamine predicts response to lithium, and establish control over BD earlier in the course of illness. Full article