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Response to invited commentary: Vitamin D3 supplementation for 8 weeks leads to improved haematological status following the consumption of an iron-fortified breakfast cereal: a double-blind randomised controlled trial in iron-deficient women

Ahmad Fuzi SF, Mushtaq S

Br J Nutr, 2021 Mar 14;125(5):598-600.
PMID: 32406343 DOI: 10.1017/S0007114520001683
Fulltext A case of intussusception secondary to a metastatic malignant melanoma from the nasal cavity

Ng YJ, Loc LJ, Bun KS, Mushtaq S

J Surg Case Rep, 2023 Oct;2023(10):rjad572.
PMID: 37854518 DOI: 10.1093/jscr/rjad572

About 5% of all intussusception are found in adults, up to 90% of these have an anatomical lesion with ~50% of them are malignant. Malignant melanoma commonly metastasizes to the small bowel; however, melanoma causing intussusception is rare. We describe a 57-year-old lady with a history of surgically treated malignant melanoma in her nasal cavity who came with an ambiguous intestinal obstruction. Computed tomography reported ileal-ileal intussusception, which was surgically removed via emergency open laparotomy and bowel resection. Intraoperatively the intussusception was 110 cm from the ileo-cecal valve with multiple palpable lymph nodes. Histopathology confirmed the origin as malignant melanoma with lymphovascular invasion. Our literature review found the mean prevalence of intussusception secondary to melanoma was 6.924% (SD ± 5.155). Minimally invasive techniques are reported non-inferior to open laparotomy. We argue that the open technique can provide informed decisions for adequate resection of affected bowel and lymphatic drainage.
Fulltext Hypertension control among euvolemic hypertensive hemodialysis patients in Malaysia: a prospective follow-up study

Khan A, Khan AH, Adnan AS, Sulaiman SAS, Mushtaq S, Ahmad N, et al.

J Pharm Policy Pract, 2019;12:10.
PMID: 31114693 DOI: 10.1186/s40545-019-0169-y

Objectives: Existing literature does not provide enough information on evaluation of factors associated with pre-dialysis controlled hypertension among euvolemic hemodialysis (HD) patients. We conducted a study to evaluate the rate and factors influencing pre-dialysis controlled hypertension among euvolemic HD patients.
Design: A multicenter prospective follow-up study.
Setting: Tertiary care teaching hospital and its associated private dialysis centers.
Participants: This study included 145 euvolemic eligible hypertensive patients. Various sociodemographic, clinical factors and drugs were investigated and analyzed by using appropriate statistical methods to determine the factors influencing hypertension control among the study participants.
Results: On baseline visit, the mean pre-dialysis systolic and diastolic BP (mmHg) of study participants was 161.2 ± 24. and 79.21 ± 11.8 retrospectively, and 30 (20.6%) patients were on pre-dialysis goal BP. At the end of the 6-months follow-up, the mean pre-dialysis systolic BP and diastolic BP (mmHg) of the patients was 154.6 ± 18.3 and 79.2 ± 11.8 respectively, and 42 (28.9%) were on pre-dialysis goal BP. In multivariate analysis, the use of calcium channel blockers (CCBs) was the only variable which had statistically significant association with pre-dialysis controlled hypertension at baseline (OR = 7.530, p-value = 0.001) and final (OR = 8.988, p-value
Fulltext Prevalence and predictors of depression among hemodialysis patients: a prospective follow-up study

Khan A, Khan AH, Adnan AS, Sulaiman SAS, Mushtaq S

BMC Public Health, 2019 May 09;19(1):531.
PMID: 31072378 DOI: 10.1186/s12889-019-6796-z

BACKGROUND: Even though depression is one of the most common psychiatric disorders, it is under-recognized in hemodialysis (HD) patients. Existing literature does not provide enough information on evaluation of predictors of depression among HD patients. The objective of the current study was to determine the prevalence and predictors of depression among HD patients.
METHODS: A multicenter prospective follow-up study. All eligible confirmed hypertensive HD patients who were consecutively enrolled for treatment at the study sites were included in the current study. HADS questionnaire was used to assess the depression level among study participants. Patients with physical and/or cognitive limitations that prevent them from being able to answer questions were excluded.
RESULTS: Two hundred twenty patients were judged eligible and completed questionnaire at the baseline visit. Subsequently, 216 and 213 patients completed questionnaire on second and final follow up respectively. The prevalence of depression among patients at baseline, 2nd visit and final visit was 71.3, 78.2 and 84.9% respectively. The results of regression analysis showed that treatment given to patients at non-governmental organizations (NGO's) running HD centers (OR = 0.347, p-value = 0.039) had statistically significant association with prevalence of depression at final visit.
CONCLUSIONS: Depression was prevalent in the current study participants. Negative association observed between depression and hemodialysis therapy at NGO's running centers signifies patients' satisfaction and better depression management practices at these centers.
A 1-h time interval between a meal containing iron and consumption of tea attenuates the inhibitory effects on iron absorption: a controlled trial in a cohort of healthy UK women using a stable iron isotope

Ahmad Fuzi SF, Koller D, Bruggraber S, Pereira DI, Dainty JR, Mushtaq S

Am J Clin Nutr, 2017 Dec;106(6):1413-1421.
PMID: 29046302 DOI: 10.3945/ajcn.117.161364

Background: Tea has been shown to be a potent inhibitor of nonheme iron absorption, but it remains unclear whether the timing of tea consumption relative to a meal influences iron bioavailability.Objective: The aim of the study was to investigate the effect of a 1-h time interval of tea consumption on nonheme iron absorption in an iron-containing meal in a cohort of iron-replete, nonanemic female subjects with the use of a stable isotope (57Fe).Design: Twelve women (mean ± SD age: 24.8 ± 6.9 y) were administered a standardized porridge meal extrinsically labeled with 4 mg 57Fe as FeSO4 on 3 separate occasions, with a 14-d time interval between each test meal (TM). The TM was administered with water (TM-1), with tea administered simultaneously (TM-2), and with tea administered 1 h postmeal (TM-3). Fasted venous blood samples were collected for iron isotopic analysis and measurement of iron status biomarkers. Fractional iron absorption was estimated by the erythrocyte iron incorporation method.Results: Iron absorption was 5.7% ± 8.5% (TM-1), 3.6% ± 4.2% (TM-2), and 5.7% ± 5.4% (TM-3). Mean fractional iron absorption was found to be significantly higher (2.2%) when tea was administered 1 h postmeal (TM-3) than when tea was administered simultaneously with the meal (TM-2) (P = 0.046). An ∼50% reduction in the inhibitory effect of tea (relative to water) was observed, from 37.2% (TM-2) to 18.1% (TM-3).Conclusions: This study shows that tea consumed simultaneously with an iron-containing porridge meal leads to decreased nonheme iron absorption and that a 1-h time interval between a meal and tea consumption attenuates the inhibitory effect, resulting in increased nonheme iron absorption. These findings are not only important in relation to the management of iron deficiency but should also inform dietary advice, especially that given to those at risk of deficiency. This trial was registered at clinicaltrials.gov as NCT02365103.
Fulltext Primary percutaneous coronary intervention in CAD patients: A comparison of major adverse cardiovascular events of second- and third-generation drug-eluting stents

Bibi S, Khan A, Khan AH, Khan MN, Mushtaq S, Rashid SA

Front Pharmacol, 2022;13:900798.
PMID: 36467026 DOI: 10.3389/fphar.2022.900798

Background: Biodegradable polymer (BP) drug-eluting stents (DES) have been introduced as a novel solution to the problems of durable polymer (DP) stents. In Pakistan, very few studies are available for the treatment intervention in post-primary percutaneous coronary intervention (PPCI) patients. Our study will compare the major adverse cardiovascular events (MACEs) and their predictors in patients with coronary artery disease (CAD) undergoing PPCI with second- or third-generation DES. Methodology: An observational, retrospective, cohort study was carried out on CAD patients undergoing PPCI with either second- (DP-XIENCE Prime/XIENCE Xpedition) or third-generation (BP-BioMatrix NeoFlex/BioMatrix Alpha) DES. MACEs were assessed after 1 year of PPCI procedure in 341 patients and screened as per inclusion/exclusion criteria (167 in the second-generation group and 174 in the third-generation group). Results: The number of male patients (86.2%) was more than female patients in our study population. MACEs were reported in 4.19% patients after 1 year duration, and the percentage of MACEs was more in the second-generation DES group (4.77%) than in the third-generation group (3.44%); however, statistical analysis has not found any significant difference (p = 0.534). The rate of myocardial infarction (1.19% vs. 0.57%) and stent thrombosis (1.8% vs. 1.15%) was more in the second-generation DES group. However, restenosis (1.19% vs. 1.15%) and cardiac death (0.59% vs. 0.57%) were almost same in both groups. A significant association was found between MACEs and diabetes mellitus (p = 0.025), hypertension (p = 0.035), smoking (p = 0.008), and a family history of CAD (p = 0.018). Conclusion: BP-BioMatrix and DP-XIENCE DES have comparable clinical outcomes. Findings of the current study will assist the policy makers and healthcare providers in the rationalization of scarce resources and evidence-based patient care. However, longer follow-up studies are required for convincing results.
Fulltext Growth performance, haematological assessment and chemical composition of Nile tilapia, Oreochromis niloticus (Linnaeus, 1758) fed different levels of Aloe vera extract as feed additives in a closed aquaculture system

Syed R, Masood Z, Ul Hassan H, Khan W, Mushtaq S, Ali A, et al.

Saudi J Biol Sci, 2022 Jan;29(1):296-303.
PMID: 35002422 DOI: 10.1016/j.sjbs.2021.08.098

A 105-day experimental trial was conducted to assess different levels of dietary Aleo vera extract supplementation on water quality parameters, proximate composition, growth performance and haematological parameters of fry Oreochromis niloticus. Four different percentages of dietary leaf extract powder of Aleo vera (ALE) with a basal feed, designated as, i.e., T0 (Control group; without ALE), T1 (1% ALE), T2 (2% ALE), and T3 (3% ALE). Fish fry was reared in concrete tanks (7.0 m, 1.6 m, 1.0: L, W, H; water volume 11.2 m3/tank), with an average initial weight 4.04 ± 0.03 g/ fry, and each treatment was triplicated. Fry was randomly distributed at a stocking rate of 450 individuals/ tanks. The water quality parameters revealed that temperature, pH, salinity, dissolved oxygen (DO) and nitrates were found in a promising range as given by FAO/WHO limits. However, the record values obtained for Electric Conductivity (EC), Total dissolved solids (TDS), and alkalinities were not found in all tanks' suitable range according to FAO/WHO limits. The results revealed a significant impact of different percentages of dietary ALE supplementation on fry's body composition and haematological parameters. Moreover, the final body weight, final body length, average daily weight gain (g), net weight gain (g) and specific growth rate (%) were significantly higher (p
Spatial analyses of immune cell infiltration in cancer: current methods and future directions: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer

Page DB, Broeckx G, Jahangir CA, Verbandt S, Gupta RR, Thagaard J, et al.

J Pathol, 2023 Aug;260(5):514-532.
PMID: 37608771 DOI: 10.1002/path.6165

Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector-based). We then provide a compendium of spatial immune cell metrics that have been reported in the literature, summarizing prognostic associations in the context of a variety of cancers. We conclude by discussing two well-described clinical biomarkers, the breast cancer stromal tumor infiltrating lymphocytes score and the colon cancer Immunoscore, and describe investigative opportunities to improve clinical utility of these spatial biomarkers. © 2023 The Pathological Society of Great Britain and Ireland.
Fulltext Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer

Thagaard J, Broeckx G, Page DB, Jahangir CA, Verbandt S, Kos Z, et al.

J Pathol, 2023 Aug;260(5):498-513.
PMID: 37608772 DOI: 10.1002/path.6155

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Fulltext Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer

Jahangir CA, Page DB, Broeckx G, Gonzalez CA, Burke C, Murphy C, et al.

J Pathol, 2024 Mar;262(3):271-288.
PMID: 38230434 DOI: 10.1002/path.6238

Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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