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

The effectiveness of concurrent exercise (CE) as an emerging approach for type-II diabetes mellitus (T2DM) patients was evaluated through a comprehensive search on Google Scholar, PubMed, Pedro, CINAHL, and Medline from 2015 to March 2023. Sixteen RCTs were selected which evaluated CE (aerobic + resistance in the same session) effects on a minimum of three days/week among T2DM patients, and the control group received usual care or no exercise. Studies that evaluated at least one glycaemic variable, i.e. HbA1C, fasting blood glucose level (FBGL), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), were eligible. Intervention with a follow-up period of ≥8 weeks, patients of any age and gender, and literature in the English language were included. A rigorous review was performed using the Cochrane Collaboration risk of bias tool (RoB 2) to minimise biases, which include the randomisation process, deviation from intended intervention, missing outcome data, outcome measurement, and selection bias. CE significantly improved HbA1C (95% CI of -0.654 to 0.363, I2 = 84.92% moderate heterogeneity), FBGL (95% CI of -0.239 to 1.145, I2 = 93.74% - high level of heterogeneity), and insulin resistance (HOMA-IR) (95% CI of -0.593 to 0.544, I2 = 92.85% - high level of heterogeneity). Collectively, findings indicate the potential of CE as an intervention to impact glycaemic control in T2DM patients positively. However, the relatively high I² values suggest notable variability among studies, and further research to explore the factors contributing to this heterogeneity, exercise protocol along with progression, and duration of diabetes are needed, which is more challenging to determine a precise dose-response relationship. Therefore, more studies are required to provide thorough insights into these components for T2DM management. Key Words: Glycated haemoglobin, Glycaemic control, Insulin resistance, Physical exercise, Type-II diabetes mellitus.

Objective: To construct and validate a prognostic model for osteosarcoma prognostication and therapeutic potential of PANoptosis- related genes.

Study design: Observational study. Place and Duration of the Study: Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China, from August 2021 to January 2024.

Methodology: Transcriptomic data from the GEO and TARGET databases were utilised to construct and validate a prognostic model for osteosarcoma. The analysis involved the use of the LASSO Cox-regression method with the Glmnet R package to identify key PANoptosis-related genes. Differential gene expression analysis was conducted using the Limma R package, and model validation was performed using Kaplan-Meier survival analysis and time-dependent ROC curves.

Results: This model, derived from five key PANoptosis-related genes, demonstrated significant predictive capability for patient survival across training and validation cohorts. Further analysis confirmed the model's effectiveness and identified metastasis stage and risk scores as the robust independent prognostic indicators.

Conclusion: The prognostic model offers a novel tool for osteosarcoma prognostication and underscores the therapeutic potential of targeting PANoptosis-related pathways.

Key words: PANoptosis-related genes, Osteosarcoma, Prognosis, Bioinformatics, Tumour micro-environment.

Objective: To assess the immunomodulatory effects of melatonin on the acquired immunity of immunosuppressed male Wistar rats by checking Interleukin 6 (IL-6) levels, total leucocyte counts (TLC), and differential leucocyte counts.

Study design: Experimental study. Place and Duration of the Study: Animal laboratory, CMH Lahore Medical College, from June to October 2023.

Methodology: Fifty male Wistar rats, weighing 180g to 200g, were included in this study with 10 rats in each of the five groups namely cyclophosphamide (CP), CP + melatonin, CP + immunomodulator, melatonin-only, and control. A calculated dose of CP was administered intraperitoneally for 30 days (from 13/06/23 to 13/07/23) to each group except the control groups. After this, the experimental group was given melatonin CP + Melatonin for 7 days (from 14/07/23 to 20/07/23). CP + Immunomodulatory group was kept for comparison of immunomodulatory effects. Blood samples were drawn from all 5 groups. IL-6 was estimated through ELISA. Other parameters assessed were TLC and absolute differential leucocyte counts.

Results: Melatonin increased IL-6 levels significantly (p = 0.042) as well as the TLC levels (p <0.001) compared to the immuno-suppressed CP group. Melatonin was seen to have an upregulation of IL-6 levels in immunosuppression compared to the administration of immunomodulator preparation (p = 0.506) which was not as effective. Administration of melatonin significantly increased the TLC, neutrophil, lymphocyte, monocyte, and eosinophil count compared to known immunomodulators.

Conclusion: Melatonin as a supplement may have some role in activating multiple immune response processes in immune-depressed states. It was also established that it allows quick recovery of cell components from immunosuppressed states.

Key words: Melatonin, Immunomodulation, Rats, Interleukin-6, Acquired immunity, Cyclophosphamide.

Objective: To determine the factors affecting the first 100 days of survival in acute leukaemia patients undergoing allogeneic haematopoietic stem cell transplantation (Allo-HSCT).

Study design: Descriptive study. Place and Duration of the Study: Bone Marrow Transplant Centre, Rawalpindi, Pakistan, from March 2016 to February 2022.

Methodology: Patients with acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL) in complete remission (CR) undergoing Allo-HSCT were included. Data were collected on patient demographics, diagnosis, remission status, pre-transplant analysis, donor compatibility, conditioning regimen, GVHD prophylaxis, engraftment times, post-transplant complications, mortality causes, and overall survival (OS) at 100 days.

Results: Among 101 transplant recipients (mean age of 24 ± 11.05 years; n = 76 males, n = 25 females), 41 had AML and 60 had ALL. Ninety patients underwent matched sibling donor (MSD)-HSCT, while 11 had haplo-identical sibling-HSCT. Patients ≤13 years had higher survival rates than older patients (94.4% vs. 67.5%, p = 0.03). High pre-transplant serum ferritin levels (>2500 mg/dl) predicted lower OS (48.9% vs. 100% in ferritin <1000 mg/dl, p <0.01). AML patients had a survival advantage over ALL patients (82.9% vs. 65%, p = 0.05). Early neutrophil engraftment within 14 days correlated with better survival (96.4% vs. 54.3%, p <0.01). Lastly, severe mucositis also adversely affected survival (60% in Grade III vs. 9.5% in Grade IV, p <0.01).

Conclusion: Identifying modifiable factors can improve long-term support and follow-up, enhancing the patient outcomes in underdeveloped nations.

Key words: Haematopoietic stem cell transplant, Day + 100 survival, Acute leukaemia, Pakistan.

Objective: To determine the coexistence of multiple PML-RARA transcripts in adult APL (acute promyelotic leukaemia) patients, and its impact on  the patients' laboratory parameters, treatment responses, and prognoses.

Study design: Cross-sectional study. Place and Duration of the Study: Department of Medical Genetics, Medical Faculty of Necmettin Erbakan University, Konya, Turkiye, from January 2015 to March 2023.

Methodology: The study group consisted of individuals diagnosed with APL. RNA isolation was performed by taking blood or bone marrow samples and the presence of breakpoints in PML-RARA bcr1, bcr2, and bcr3 was detected using the real-time PCR. However, the quantification of PML-RARA fusion transcripts cannot be provided using the utilised kit.

Results: Twelve women and eight men were examined with a mean age of 38 years (range: 19-80), and 46.5 years (range: 22-60) were examined, respectively. When evaluating patients based on isoforms, it was found that 40% had multiple isoforms. Nineteen (95%) patients achieved haematologic remission after the treatment. Only one patient who had three different isoforms did not achieve remission. The estimated median survival for patients with a single isoform and those with multiple isoforms was 78.1 months (95% CI: 37.8-117.6) and 71.7 months (46.2-97.2), respectively. Two of the patients with multiple isoforms were lost in the early stage, whereas no early-stage mortality was recorded among patients with a single isoform.

Conclusion: Identifying PML-RARA isoform subtypes is important for predicting prognosis and informing clinical follow-up.

Key words: Acute promyelocytic leukaemia, Breakpoint cluster region, Isoform, PML-RARA.

Objective: To measure the effectiveness of localisation and removal of impalpable target lesions without compromising patient safety in a resource-limited setup using preoperative ultrasound and mammography with peroperative use of C-arm image intensifier.

Study design: Descriptive study. Place and Duration of the Study: Department of Breast Surgery, Ittefaq Hospital (Trust), Lahore, Pakistan, from 25th October 2011 to 17th February 2023.

Methodology: All the breast cancer patients who achieved complete clinical response after neoadjuvant systemic treatment and underwent breast conservation surgery during the study period were included. Tumour / clip localisation was done using preoperative ultrasound or image-guided marking, a 2-view mammogram in all cases and the use of an image intensifier to confirm the presence of clips in the excised specimen. The primary outcome was the accurate localisation and removal of the index lesion, while the secondary outcome included the reoperation rate for positive margins and early local recurrence.

Results: Data from 144 patients were reviewed. Successful localisation was done in all the patients; only one patient had a positive margin for ductal carcinoma-in situ (DCIS), achieving a 99.3% clear margin rate. Local recurrence within two years after primary operation was seen in one patient only.  Conclusion: By a combined approach of preoperative ultrasound-guided marking, a 2-view mammogram, and the use of image intensifier, successful localisation of an impalpable breast lesion is possible without compromising oncological and aesthetic principles.

Key words: Breast conservation surgery, Localisation, Non-palpable, Margins, Image intensifier.

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Objective: To analyse the relationship between the preoperative systemic immune-inflammation index (SII) and the relapse-free survival (RFS) of paediatric patients with Wilms' tumour (WT) after radical surgery, and to establish and validate a prognostic survival model.

Study design: Observational study. Place and Duration of the Study: Department of Oncologic Surgery, Anhui Children's Hospital of Fudan University, Hefei, China, from January 2013 to August 2023.

Methodology: A retrospective analysis was conducted on 79 WT patients treated with radical resection, with their preoperative SII values computed. The best cut-off for SII was determined through the ROC curve, categorising patients into high and low SII groups. The Kaplan-Meier method and Cox-regression were used for survival analysis. A survival prognostic model was constructed and its predictive capability gauged (AUC of the ROC).

Results: The study included 79 WT patients with a median RFS of 65 months and an average of 75.5 ± 3.4 months. The optimal cut-off value for SII was 534.95. The low SII group had a higher RFS (Log-rank: χ2 = 9.380, p = 0.002). Preoperative SII (HR = 3.277, 95% CI: 1.167 - 9.200, p = 0.024), clinical staging (HR = 8.408, 95% CI: 2.604 - 27.147, p <0.001), and tissue differentiation (HR = 2.237, 95% CI: 1.043 - 5.828, p = 0.039) were independent risk factors for RFS. The model's diagnostic performance was 0.749 (95% CI: 0.636 - 0.861). Internal validation showed an AUC of 0.723 (95% CI: 0.608 - 0.838).

Conclusion: Lower preoperative SII suggests a more favourable prognosis. The SII-based nomogram efficiently forecasts post-radical surgery prognosis for WT.

Key words: Wilms' Tumour, Systemic immune-inflammation index, Relapse-free survival, Nomogram.

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Objective: Evaluation of the diagnostic accuracy of combined detection of serum homocysteine (Hcy), C-reactive protein (CRP), and serum ferritin (SF) levels in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI).

Study design: Descriptive study. Place and Duration of the Study: Clinical Laboratory Section, Affiliated Hospital of Hebei University, Baoding, Heibei, China, from May 2022 to June 2023.

Methodology: Data of 120 patients with memory decline were retrospectively collected. They were divided into an MCI group and an AD group. A further 50 healthy participants were used as a normal control (NC) group. Differences in the Hcy, CRP, and SF levels between the three groups were evaluated. The specificity, accuracy, and sensitivity of these three indices in the combined or single diagnosis of AD and MCI were compared. Their associations with the severity of AD and MCI were also compared.

Results: The AD group had the highest levels of Hcy, CRP, and SF (18.79 ± 4.50, 6.35 ± 2.04, and 355.69 ± 120.36), followed by MCI (16.75 ± 3.06, 4.58 ± 2.31, and 203.48 ± 12.76), and NC group (14.32 ± 2.06, 2.06 ± 0.76, and 98.46 ± 5.06), with statistically significant differences (all p <0.001). The diagnostic efficacy of AD for CRP was 98.50%, sensitivity was 96.00%, and specificity was 94.00%, which was higher than Hcy and SF. Tested together, the area under the ROC curve was 99.90%, specificity was 98.00%, and sensitivity was 98.00%. The diagnostic efficacy of SF for MCI had sensitivity of 100.00%, and specificity of 100.00%, which was higher than that of Hcy and CRP. When the three were combined for detection, the area under the curve of SF was 100.00%, sensitivity of 100.00%, and specificity of 100.00%. The levels of Hcy, CRP, and SF were positively correlated with the severity of AD (p <0.01), while negatively correlated with the mini-mental state examination (MMSE) score (p <0.01).

Conclusion: The combined detection of Hcy, CRP, and SF improved the diagnostic accuracy of comorbid AD and MCI.

Key words: Homocysteine, C-reactive protein, Cognitive impairment, Serum ferritin, Alzheimer's disease.