Haseeb Khaliq

Background & objective: Severe dengue is a global health concern and immune dysregulation is a key contributor to its pathogenesis. The aim of this schematic review was to review the association of the cytokine biomarkers mainly interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α) in immune dysregulation among patients suffering from severe dengue. Methodology: The review followed PRISMA 2020 guidelines. The literature was searched from PubMed, Scopus, Web of Science, and Google Scholar up to August 2025. Qualified studies included those which measured IL-6, IL-10 or TNF- α in confirmed dengue patient. Meta-analysis was performed to assess standardized mean differences (SMDs) for key cytokines. The risk of bias was determined using Newcastle-Ottawa Scale and the GRADE approach was applied for certainty of evidence. Results: Higher levels were observed, of IL-6 and IL-10 in severe dengue, and TNF-α with late complications in this study. Meta-analysis correlated high levels of cytokines with severe dengue IL-6 (SMD = 16.79, 95% CI = -15.25-48.84), IL-10 (SMD = 0.13, 95%CI = -0.37-0.63) and TNF-α (SMD = 0.53, 95% CI = 0.25-0.82). The evidence confidence was moderate and high by IL-6 and IL-10 and high in TNF-α respectively. Conclusion: The levels of IL-6 and IL-10 were significantly high in severe dengue cases, but heterogeneity across studies reduced the prognostic integrity. TNF-α emerged as a potent indicator of mild and severe dengue. To establish the clinical uses of these biomarkers as a risk-stratifying tool, standardized, multicentric studies are needed to validate these findings. Abbreviations: DF: dengue fever, DHF: dengue hemorrhagic fever, DSS: dengue shock syndrome, IL-6: Interleukin-6, IL-10: Interleukin-10, SMD: standardized mean differences, TNF-α: tumor necrosis factor-alpha Keywords: Dengue Hemorrhagic Fever (DHF), Cytokine Storm, Biomarkers, Cytokines, IL-6, IL-10, TNF-α Citation: Bukhari AAS, Devi D, Minhas M, Noureen A, Javed H, Zaidi SIA, Khaliq H. Novel insights into immune dysregulation and cytokine signatures in intensive care settings: bridging IL-6, IL-10, TNF-α to endothelial, hepatic, and hematological dysfunction in severe dengue, a schematic meta-analysis. Anaesth. pain intensive care 2025;29(8):1022-1031. DOI: 10.35975/apic.v29i8.3039 Received: October 16, 2025; Revised: October 18, 2025; Accepted: October 18, 2025

Sepsis remains one of the most challenging issues related to the intensive care unit, where the morbidity and mortality remain high, despite progress in diagnostic and treatment. Early identification, early administration of antibiotics, vigorous fluid therapy, source control, and following up with evidence-based bundles are the best approaches to use in mortality reduction. Sepsis is a potentially fatal syndrome of dysregulated host response to infection, which is one of the major causes of ICU hospitalizations all over the world.1 The quest to develop biomarkers has provided hope in the context of precision medicine, the daily routine of sepsis care regularly fails in its simplest processes, which raises a major divide between aspiration and practice.2

Innovations in Intensive Care Units (ICU) have increased survival rates, but several patients experience Post-Intensive Care Syndrome (PICS), which encompasses persistent physical, cognitive, and psychological disability. The research emphasizes the need to identify and treat PICS, as 25-60% of ICU survivors experience it. Lack of standardized diagnostic criteria or a follow-up system has resulted in continued disability and diminished quality of life in patients. The objective of this study was to analyze existing literature on PICS, define its prevalence, identify associated risk factors, and outline strategies for providing post-ICU care. Findings indicated high levels of muscle weakness, cognitive dysfunction, depression, and post-traumatic stress disorder among survivors. The research concludes that post-discharge care gaps can be addressed through early rehabilitation, remote monitoring, mental health support, and patient-centered recovery plans, thereby improving long-term outcomes. Keywords: Critical Illness; Intensive Care Units; Stress Disorders; Post-Traumatic; Cognitive Dysfunction; Rehabilitation Citation: Khaliq H, Minhas M, Ahmed MAA. Post-intensive care syndrome (PICS): A call for continuity beyond discharge. Anaesth. pain intensive care 2025;29(6):441-43. DOI: 10.35975/apic.v29i6.2885 Received: May 14, 2025; Revised: July 11, 2025; Accepted: July 11, 2025

Background & objective: Eclampsia and HELLP syndrome are serious hypertensive diseases of pregnancy that are frequently admitted to the ICU. When it comes to seizure control and hypertension control, standardization of protocols in pain management is well established, although these are not commonly used; yet there is evidence that connects pain and adverse maternal outcomes. This systematic review and meta-analysis were used to assess the effectiveness of acute pain management protocols in reducing the maternal morbidity and other clinical outcomes in pregnant women admitted to the ICU for eclampsia or HELLP syndrome. Methods: This systematic review and meta-analysis was conducted according to PRISMA 2020 guidelines. A systematic search was pursued in [PubMed], Scopus, Web of Science, and Cochrane databases for the studies produced till 2025. Inclusion criteria included RCTs, observational, and case report studies that focused on pain protocols in the obstetric ICUs. The key outcomes were maternal morbidity, ICU stay duration, and maternal-fetal survival. Assessment of risk of bias was done using the Newcastle-Ottawa Scale and Cochrane RoB tool. A random effect model of meta-analysis was used. Results: 12 studies with 10, 153 patients were selected. Protocolized pain management, such as opioid- sparing and regional anesthesia, lowered the rate of maternal complications and stay in the ICU. The pooled OR for the better maternal outcomes was 1.23 (95% CI: 0.86–1.75), though not statistically significant. There was substantial heterogeneity (I² = 77%, p < 0.01), which was explained by protocol variation and disease severity variation. Conclusion: Incorporating the structured pain management protocols in the obstetric ICU care for eclampsia and HELLP syndrome can ameliorate the maternal outcomes, but the current evidence is heterogeneous. Regarding the necessity of RCTs, further multicenter RCTs are needed to standardize pain protocols in the high-risk population. Keywords: HELLP Syndrome; Anesthesia; Maternal Outcomes; Obstetric Complications; Meta-Analysis Citation: Bibi F, Chaudhry S, Riaz H, Gul E, Yasmeen R, Ramzan H, Khaliq H. Integrating acute pain protocols in obstetric intensive care: the effect on maternal morbidity in eclampsia and HELLP syndrome. Anaesth. pain intensive care 2025;29(4):326-33. DOI: 10.35975/apic.v29i4.2817 Received: May 09, 2024; Revised: October 26, 2024; Accepted: January 01, 2025

Artificial intelligence (AI) is rapidly changing the work of perioperative monitoring and making anesthesia reactive as opposed to proactive. Besides the traditional signs of the degree of sedation, artificial intelligence algorithms can be used to integrate a range of different sources that predict unstable hemodynamic processes, oxygen desaturation, and nociceptive changes in advance of clinical symptoms. One of the key elements of the future of precision perioperative medicine is AI-assisted monitoring because of the possibility of offering significant potential for increased patient safety and resource optimization. This can be facilitated by its predictive capacity, whereby the same method of safety can be applied to a heterogeneous group of patients to limit variation in results. The development of AI-assisted anesthesia is not a new part of the current structure, but it is a step towards the new era of perioperative procedures. Keywords: Artificial Intelligence; Closed-loop Anesthesia; Hemodynamic Instability; Nociception Monitoring; Prediction; Predictive Analytics; Perioperative Medicine Citation: Ahmed MAA, Nasar M, Khaliq H. Artificial intelligence–assisted monitoring in anesthesia: from depth of sedation to predicting hemodynamic instability (Editorial). Anaesth. pain intensive care 2025;29(8):825-827. DOI: 10.35975/apic.v29i8.3002 Received: October 23, 2025; Accepted: October 26, 2025

Background & objective: Nerve Growth Factor (NGF) plays a key role in the pathophysiology of bronchial asthma through contributing to inflammation of airway, remodeling of airway and neural regulation. This systematic review aimed for the evaluation of mechanisms that contributed to asthma and its relevance to ICU settings. Methodology: The PRISMA 2020 guidelines were followed in this review. Studies that explored NGF expression, regulation and therapeutic targeting in asthma were sought using a comprehensive search of PubMed, Scopus and Google Scholar. Study design, population, NGF measure methods, key findings, and ICU relevance were focused on data extraction. The assessment of risk of any bias was done using Evident Project Risk of Bias Tool. GRADE assessment was used for certainty of evidence. Results: Of the 10 studies included, 6 were based on animal models, 3 were based on human observational studies and the remaining one was a systematic review. Asthma patients exhibited markedly higher NGF levels than control subjects (mean: 3.45 ± 0.76 pg/mL). Eosinophilic counts (r = 0.74, P < 0.01) and inflammatory cytokines correlated in positive with NGF. Airway inflammation decreased by 45.2% (P = 0.002), and airway remodeling by 32% (P = 0.004) via anti-NGF therapy. Similar results were observed by vitamin D supplementation that caused NGF downregulation by 41% (P = 0.003) via the Nrf2/HO-1 pathway. Risk of bias assessment showed that four studies were classified as low risk, five as moderate, and one as high. Conclusion: NGF was significantly stimulated in asthma and contributed to inflammation, reformation and neuroimmune interactions. The correlation of NGF with severe exacerbations and ICU outcomes suggested its potential as a biomarker for therapeutic target. However large scale and long-term evaluation of NGF against asthma was required. Future studies should validate the role of NGF in asthma management particularly in ICU settings. Abbreviations: NGF: Nerve Growth Factor, ICU: Intensive Care Unit, BALF: Bronchoalveolar Lavage Fluid, AHR: Airway Hyperresponsiveness, IL-6: Interleukin-6, IL-1β: Interleukin-1 Beta, CRP: C-Reactive Protein, TRPV1: Transient Receptor Potential Vanilloid 1, Nrf2: Nuclear factor erythroid 2-related factor 2, HO-1: Heme Oxygenase-1, ELISA: Enzyme-Linked Immunosorbent Assay, RT-qPCR: Reverse Transcription Quantitative Polymerase Chain Reaction, GRADE: Grading of Recommendations, Assessment, Development, and Evaluations, PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses, RSV: Respiratory Syncytial Virus, OVA: Ovalbumin, RhoA: Ras homolog family member A, PM: Particulate Matter Keywords: Nerve Growth Factor; Asthma; Airway Remodeling; Inflammation; Neuroimmunomodulation; Intensive Care Units; Critical Care; Biomarkers Citation: Bukhari AAS, Shaikh ARK, Salman W, Bhatti FA, Malik W, Minhas M, Muddasser A, Khaliq H. Pathophysiological role of nerve growth factor (NGF) in asthma: insights into airway inflammation, remodeling, and neural regulation in intensive care settings. Anaesth. pain intensive care 2025;29(3):681-689. DOI: 10.35975/apic.v29i3.2778 Received: February 03, 2025; Revised: February 28, 2025; Accepted: March 05, 2025

Floods will remain the primary cause of intergenerational malnutrition and growing health inequity, unless a resolution to the issue is enforced across the area. The diversity of climate change, malnutrition, and maternal-child health came into sharp focus with the 2022 floods in Pakistan. Meanwhile, the worsening infrastructure, as well as the epidemic outbreak, posed threats to pregnant women as well as newborn babies. It is obvious that the presence of socioeconomic inequalities, gender inequalities, and structural gaps is the main factor to aggravate these threats, yet the presence of community midwives in the local populations can be the key to mitigating the damage. Keywords: Child; Floods; Malnutrition; Child nutrition disorders; Pakistan; Socioeconomic factors Citation: Khaliq H. Floods as catalysts for malnutrition and maternal-child healthcare risks in Pakistan. Anaesth. pain intensive care 2025;29(7):660-662. DOI: 10.35975/apic.v29i7.2951 Received: May 09, 2025; Revised: October 26, 2024; Accepted: January 01, 2025

Background: CRISPR/Cas9 genome-editing technology has revolutionized human stem cell (HSC) research, offering novel therapeutic and diagnostic applications. HSCs play a crucial role in regenerative medicine and genetic therapies due to their ability to self-renew and differentiate into various blood cell lineages. The precise genome-editing capability of CRISPR/Cas9 allows for targeted gene modifications, enabling the correction of inherited disorders, disease modeling and the discovery of novel biomarkers. Despite significant advancements, challenges such as off-target effects, delivery efficiency, and ethical concerns persist, requiring further research and optimization. Objective: This systematic review evaluates the therapeutic and diagnostic potential of CRISPR/Cas9 genome editing in HSCs, focusing on its efficacy in gene correction for hematologic disorders, disease modeling and biomarker discovery. Methods: A systematic review was conducted following PRISMA guidelines, analyzing studies published between 2015 and 2024. Literature searches were performed in PubMed, Web of Science, and Scopus using MeSH-aligned keywords. The inclusion criteria encompassed peer-reviewed studies utilizing CRISPR/Cas9 for gene modification in HSCs for therapeutic and diagnostic applications. Exclusion criteria included studies that lacked experimental validation, did not focus on HSCs, or were non-English publications. Out of 85 initially retrieved studies, 40 met the inclusion criteria, and 15 were selected for final synthesis. Results: CRISPR/Cas9 gene-editing strategies in HSCs were categorized as gene knockout (53%), gene activation (40%), and dual knockout/activation (7%). Hematological disorders, including sickle cell anemia and beta-thalassemia, accounted for 35% of studies, demonstrating up to 90% correction in β-globin mutations. Neurodegenerative diseases constituted 20% of studies, where knockout of amyloid precursor protein (APP) in Alzheimer’s models resulted in a 60% reduction in plaque accumulation. Muscular dystrophy studies (10%) showed 75% improvement in dystrophin expression through gene activation. High-throughput CRISPR screening was employed in 15% of studies for biomarker identification. Despite promising outcomes, off-target mutations were observed in 28% of studies, and viral vector-based delivery methods were used in 65%, raising safety concerns. Conclusion: CRISPR/Cas9 genome editing in HSCs presents a ground-breaking approach for treating genetic disorders and enhancing precision medicine. Its potential to correct disease-causing mutations, model complex disorders, and identify novel therapeutic targets is substantial. However, challenges in delivery methods, long-term safety, and ethical considerations remain barriers to clinical translation. Future research should focus on optimizing high-fidelity Cas9 variants, improving non-viral delivery methods, and addressing ethical concerns to ensure the safe and effective application of CRISPR/Cas9 in regenerative medicine.

Glaucoma, a leading cause of irreversible blindness, is increasingly recognized as a neurodegenerative disease affecting broader neuro-ophthalmic pathways. Brain-derived neurotrophic Factor is a crucial neurotrophin, that supports the growth, maintenance, and survival of neurons and has been implicated in glaucomatous damage where its levels are diminished. Objectives: To focus on the role of Brain-Derived Neurotrophic Factor in the pathophysiology of glaucoma and its therapeutic potential by enhancing the survival of retinal ganglion cells. Methods: The studies in this review are taken from well-known public libraries for scientific research such as PubMed (60%), Science Direct (25%) and Springer Link (15%), in line with PRISMA guidelines. Various works conducted over the past decade from different parts of the world, including North America, Europe, and Asia, have provided evidence that the augmentation of Brain-Derived Neurotrophic Factor signalling may be a very effective approach to managing or halting the progression of glaucomatous optic neuropathy through neuroprotection and improving retinal ganglion cells survival. Results: Studies in both animals and humans indicate that Brain-Derived Neurotrophic Factor and its downstream signals promote the survival of retinal ganglion cells and decrease the extent of apoptotic cell death, oxidative stress, and inflammation in glaucoma. Moreover, enhancements of Brain-Derived Neurotrophic Factor neuroprotective effects are supported by factors such as Nerve growth factor and Brain-Derived Neurotrophic Factor. Conclusion: It was concluded that Brain-derived neurotrophic Factor has the potential to be used as a diagnostic marker for Glaucoma as well as it could be evaluated for its therapeutic potential against the disease.

Objective: The objective of this in-vitro study was to explore the pro-apoptotic potential of eugenol (4-allyl-2-methoxyphenol) on Human Leukemia-60 (HL-60) cell line as a potent phytochemical in intensive care setting to leukemia patients. Methodology: After formal approval by all of the respective ethical committees, this study was simultaneously conducted at all respective institutional departments. The study included culturing HL-60 cell line and its treatment with serial concentrations of eugenol for calculation of subsequent IC50 values (half-maximal inhibitory concentration) via MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay, expression analysis of gene, comparative analysis of relative gene fold (Intrinsic Biomarkers Caspase-3, Caspase-9) as apoptosis mediator markers followed by RT-qPCR. Cellular apoptotic morphology was confirmed via Hoechst 333258 staining. Results: For HL-60 cell line, the IC50 of eugenol (14.1 uM) showed high gene expression of pro-apoptotic biomarkers (Caspase-3 and Caspase-9). Hoechst 333258 staining showed prominent apoptotic bodies leading to nuclear fragmentations. Conclusion: Eugenol proved to possess robust pro-apoptotic potential leading to diagnostic efficacy against leukemia HL-60 cell line. Further studies would help in identifying key mechanisms by which eugenol exhibits anti-cancer potential against HL-60 cell lines. Abbreviations: HL-60 - Human Leukemia-60; IC50 - Half-Maximal Inhibitory Concentration Keywords: Eugenol, Pro-apoptotic Effects, Intensive Care, Anti-Cancer Mechanisms, HL-60, Natural Chemotherapeutics Citation: Khaliq HMH, Bughio R, Nangdev P, Aziz O, Javed W. Integrating eugenol with intensive care in leukemia patients: exploration of pro-apoptotic potential against HL-60, human leukemia cell line. Anaesth. pain intensive care 2024;28(5):871−875; DOI: 10.35975/apic.v28i5.2491 Received: June 18, 2024; Reviewed: August 03, 2024; Accepted: August 11, 2024