Journal of the College of Physicians and Surgeons--Pakistan : JCPSP最新文献

Objective: To determine the microbial profile, antibiotic susceptibility patterns, and mortality rates of early- vs. late-onset ventilator-associated pneumonia (VAP).

Study design: A retrospective cross-sectional study. Place and Duration of the Study: Surgical Intensive Care Unit, Doctors Hospital and Medical Centre, Lahore, Pakistan, from January 2023 to June 2024.

Methodology: Data were collected using a non-probability consecutive sampling method. Data were analysed using IBM SPSS 29.0 Software, and an Excel Sheet was used to make a table of isolates and their sensitivity to antibiotics.

Results: A total of 46 VAP cases were recorded during the study period. Of which, 13 (28.2%) were early-onset, and 33 (71.7%) were late-onset VAP cases. Males were 31 (67.3%), while females were 15 (32.6%). Among the early-onset VAP cases, the most common isolates were Pseudomonas aeruginosa (4, 30.7%), Candida albicans (4, 30.7%), and Klebsiella pneumonia (2, 15.38%), followed by single isolates of Acinetobacter, Burkholderia, and E. coli. In the late-onset VAP, the isolates were Acinetobacter (8, 24.2%), Klebsiella (8, 24.2%), Pseudomonas (7, 21.2%), Staphylococcus aureus (3, 9.09%), Burkholderia (2, 6.06%), Candida (2, 6.02%), Proteus mirabilis (1, 3.03%), E. coli (1, 3.03%), and Enterobacter cloacae (1, 3.03%). Almost all Gram-negative organisms were sensitive to colistin except E. coli. All Pseudomonas and Acinetobacter isolates were resistant to carbapenems (100% resistance), while Klebsiella was 40% sensitive (4 out of 10), E. coli 50% (1 out of 2), Burkholderia 66.6% (2 out of 3), and Proteus mirabilis 100%. Klebsiella was 70% sensitive to chloramphenicol. Minocycline had 100% susceptibility for Acinetobacter, Enterobacter, and Staphylococcus aureus, 60% susceptibility for Klebsiella, and 33.3% for Burkholderia.

Conclusion: VAP is mainly caused by multidrug-resistant (MDR) bacteria, especially Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii, irrespective of the onset duration. It is suggested that empirical therapy should include broad-spectrum coverage for MDR, including colistin, along with Gram-positive coverage, such as vancomycin, linezolid, or teicoplanin, to prevent the onset of early or late VAP.

Key words: Ventilator-associated pneumonia, Intensive care unit, Mechanical ventilation, Early onset VAP, Late onset VAP, Antimicrobial resistance.

Objective: To identify biomarkers capable of specifically diagnosing small cell lung cancer (SCLC).

Study design: A descriptive study. Place and Duration of the Study: The Eighth Medical Centre of Chinese PLA General Hospital, Beijing, China, from January 2024 to December 2024.

Methodology: This study included 196 lung cancer (LC) patients (70 with lung adenocarcinoma [LUAD], 56 with lung squamous cell carcinoma [LUSC], and 70 with SCLC), along with 33 patients with inflammatory pseudotumours, who served as healthy controls (HCs). Tissue samples from the included subjects underwent qRT-PCR and immunohistochemistry. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves, while the Kaplan-Meier analysis was used to generate overall survival (OS) curves.

Results: Mixed Lineage Kinase Domain-Like Protein (MLKL) and Receptor-Interacting Protein Kinase 1 (RIPK1) genes exhibited significantly lower expression in SCLC cases compared to both the LUAD and LUSC groups. ROC curve analysis revealed that MLKL, but not RIPK1, effectively distinguished SCLC from both LUAD and LUSC. Furthermore, SCLC patients with high MLKL expression had a poorer prognosis, whereas no significant correlation between MLKL levels and prognosis was observed in the LUAD or LUSC groups. Additionally, MLKL expression showed specific correlations with SCLC-Y subtypes.

Conclusion: MLKL, associated with necroptosis, plays a crucial role in SCLC progression and may serve as a potential prognostic biomarker.

Key words: Necroptosis, SCLC, Prognosis, Immune checkpoint.

Objective: To compare artificial intelligence (AI)-based analysis of Ki67, PHH3, and p53 immunohistochemical (IHC) biomarkers in glioblastoma multiforme (GBM) with conventional evaluations performed by experienced pathologists, and to assess the consistency and statistical significance of both approaches across different sampling areas.

Study design: A cross-sectional analytical study. Place and Duration of the Study: Department of Medical Pathology, Cigli Training and Research Hospital, Izmir Bakircay University, Izmir, Turkiye, from January 2023 to January 2025.

Methodology: Twenty GBM cases were analysed using IHC staining for Ki67, PHH3, and p53 in formalin-fixed and paraffin-embedded tissue sections. Stained slides were digitised and evaluated by two expert pathologists and AI-based image analysis software. Quantitative assessments were performed on 1 mm2 and 7 mm2 tumour areas. Inter- and intra-method comparisons were performed using Cohen's Kappa for agreement and Spearman's correlation for association.

Results: Intra-method comparisons showed strong consistency for both AI and pathologist assessments at 1 mm2 and 7 mm2 field sizes. In AI analyses, significant correlations were found between Ki67 and PHH3 (r = 0.750, p <0.001 at 1 mm2; r = 0.757, p <0.001 at 7 mm2) and between PHH3 and p53 (r = 0.548, p = 0.012 at 1 mm2; r = 0.701, p = 0.001 at 7 mm2). No correlation was observed between these markers at either field size in pathologist assessments (p >0.05 for all comparisons).

Conclusion: AI-supported digital pathology demonstrates strong potential for improving the objectivity and individualisation of biomarker assessment in aggressive tumours such as GBM.

Key words: Digital pathology, Artificial intelligence, Ki67, p53, PHH3, Glioblastoma.

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Objective: To compare on-table respiratory events during extubation in patients undergoing sinonasal surgery with bilateral occlusive nasal packing versus those without nasal packing.

Study design: An experimental study. Place and Duration of the Study: Department of ENT, Head and Neck Surgery and Department of Anaesthesiology, Dow University Hospital, Karachi, Pakistan, from January to December 2022.

Methodology: A total of 410 patients meeting the inclusion criteria were enroled, with 205 in each group (with and without nasal packing). The primary outcome was respiratory distress during extubation requiring intervention. The chi-square and Fisher's exact tests were applied to assess differences between the groups. A p-value <0.05 was considered statistically significant.

Results: Respiratory distress requiring intervention after extubation occurred in 6.8% of the nasal packing group and 10.2% of the non- packing group. Smokers experienced more difficult extubation events than non-smokers (p = 0.001), with a relative risk (RR) of 2.7 (95% CI: 1.48-5.20). Males had a higher frequency of poor extubation outcomes regardless of pack placement (p = 0.053).

Conclusion: Respiratory distress during extubation may occur following nasal surgery, irrespective of nasal packing, with a higher risk observed in smokers. Preoperative counselling, meticulous surgical technique, and careful airway management at the time of extubation are advised. Complete nasal packing should be avoided in high-risk patients.

Key words: Nasal surgery, Nasal packing, General anaesthesia, Extubation, Respiratory distress.

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Objective: To explore the impact of fatty acid metabolism genes on the prognosis of neuroblastoma and identify potential therapeutic targets.

Study design: An observational study. Place and Duration of the Study: Department of Pathology, Tianjin Cancer Hospital, Airport Hospital, Tianjin, China, from January 2022 to December 2023.

Methodology: A retrospective in silico analysis of public datasets (GSE49710 and E-MTAB-8248) was carried out. Patients were clustered based on fatty acid metabolism gene expression using a hierarchical clustering method. Survival differences between clusters were analysed using the Kaplan-Meier method and the log-rank test. Immune infiltration was assessed using the ESTIMATE, MCP-counter, and CIBERSORT algorithms, while immunotherapy response predictions were made using the tumour immune dysfunction and exclusion (TIDE) and immunophenoscore (IPS) algorithms. Therapeutic potentials were evaluated using the Connectivity Map (CMAP) database. Statistical significance of differences in gene expression and immune cell proportions was determined using Student's t-test or Wilcoxon rank-sum test, as appropriate. A four-gene prognostic model was developed using a random forest algorithm and validated externally, assessing its performance through ROC curves and decision curve analysis (DCA).

Results: Distinct clusters showed varying survival, immune profiles, and therapy responses. Time-dependent areas under the curve (AUC) at 1/3/5 years were 0.861/0.897/0.883 (in the cohort training, GSE49710) and 0.872/0.830/0.822 (in the external validation cohort, E-MTAB-8248). The four-gene model outperformed traditional clinical markers, predicting better survival outcomes.

Conclusion: Fatty acid metabolism genes are crucial in neuroblastoma prognosis, offering insights for personalised therapy and highlighting the four-gene model's predictive superiority.

Key words: Neuroblastoma, Fatty acid metabolism, Immune infiltration, Prognostic biomarkers, HDAC Inhibitors.

Hepatocellular carcinoma (HCC) at Barcelona-Clinic Liver Cancer (BCLC) stage C poses substantial therapeutic challenges and is typically associated with a poor survival prognosis. Triple therapy regimen comprising hepatic artery infusion chemotherapy (HAIC), programmed death receptor-1 (PD-1) inhibitors, and anti-angiogenic therapy is currently under investigation for this stage of HCC. In this study, nine advanced cases are reported that achieved complete response (CR) following this triple combination therapy. CR was defined by the complete disappearance of all lesions or the absence of arterial-phase enhancement on CT or MRI, no evidence of new lesions, and normalisation of alpha-fetoprotein (AFP) levels. Time to CR, changes in AFP levels during follow-up, and recurrence rates were analysed. Among 214 patients with HCC treated with this triple therapy at the centre from January 2021 to December 2023, 9 (4.2%) patients achieved CR. The time to CR ranged from 2 to 10 months, with a mean duration of 5.3 months. The duration for AFP levels to normalise varied from 79 to 259 days, with a median duration of 118 days. These findings indicate that the triple combination therapy of HAIC, PD-1 inhibitors, and anti-angiogenic agents has a modest probability of inducing CR in advanced HCC, with relatively rapid onset in responders. Key Words: Hepatocellular carcinoma, Hepatic arterial infusion chemotherapy, Programmed death receptor-1 inhibitors, Anti-angiogenic therapy, Complete remission.

Objective: To investigate the expression of angiogenesis-related markers in lung adenocarcinoma (LUAD) harbouring EGFR 19Del mutation and EGFR 21L858R mutation.

Study design: A descriptive study. Place and Duration of the Study: Department of Oncology, Chongqing University Fuling Hospital, Chongqing, China, from July 2021 to May 2024.

Methodology: Clinicopathological data and tumour specimens were collected from 69 patients with pathologically confirmed LUAD who underwent molecular profiling. Protein expression was assessed using immunohistochemistry (IHC) for angiogenic markers (VEGFA, VEGFR1, VEGFR2) and endothelial markers (CD31, CD34). Statistical analyses were performed using Prism 10.

Results: Significant demographic and anatomical differences were observed between the 19Del and 21L858R subtypes. The 21L858R mutation was more frequent in non-smokers and female patients. Anatomically, 19Del tumours predominated in the left lung, while 21L858R tumours were more common in the right lung (p <0.05). IHC analysis revealed higher VEGFR1 expression and significantly elevated CD34+ microvessel density in 21L858R tumours compared to 19Del tumours (p <0.05).

Conclusion: EGFR 19Del and 21L858R mutations are associated with distinct expression patterns of VEGFR1 and CD34, which may underlie differential responses to anti-angiogenic therapy and inform future combination treatment strategies.

Key words: Lung adenocarcinoma, Epidermal growth factor receptor, Vascular endothelial growth factor and receptors, CD31, CD34.