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BACKGROUND: Cobalamin C is the most common inborn error of intracellular cobalamin metabolism caused by biallelic pathogenic variants in the MMACHC gene, leading to impaired conversion of dietary vitamin B12 into its two metabolically active forms, methylcobalamin and adenosylcobalamin. Biochemical hallmarks are elevated plasma total homocysteine (HCYs) and low methionine accompanied by methylmalonic aciduria. This study aimed to evaluate the clinical, biochemical, and molecular analysis of Pakistani patients with CblC defect. METHODS: Medical charts, urine organic acid (UOA) chromatograms, plasma amino acid levels, plasma tHcy and MMACHC gene results of patients presenting at the Biochemical Genetics Clinic, AKUH from 2013-2021 were reviewed. Details were collected on a pre-structured questionnaire. SPSS 22 was used for data analysis. RESULTS: CblC was found in 33 cases (Male:Female 19:14). The median age of symptoms onset and diagnosis were 300 (IQR:135-1800) and 1380 (IQR: 240-2730) days. The most common clinical features were cognitive impairment (n = 29), seizures (n = 23), motor developmental delay (n = 20), hypotonia (n = 17), and sparse/hypopigmented scalp hair (n = 16). The MMACHC gene sequencing revealed homozygous pathogenic variant c.394C > T, (p.Arg132*) in 32 patients, whereas c.609G > A, (p.TRP203*) in one patient whose ancestors had settled in Pakistan from China decades ago. The median age of treatment initiation was 1530 (IQR: 240-2790). The median pre-treatment HCYs levels were 134 (IQR:87.2-155.5) compared to post-treatment levels of 33.3 (IQR: 27.3-44.95) umol/L. CONCLUSIONS: Thirty-three cases of CblC defect from a single center underscores a significant number of the disorder within Pakistan. Late diagnosis emphasizes the need for increased clinical awareness and adequate diagnostic facilities.
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BACKGROUND: Sex disparities have previously been identified in surgical academia. This study examines sex differences in the top-cited contemporary general surgery articles and compares Altimetric Attention Score (AAS) and other impact metrics between male and female corresponding authors (CAs). METHODS: We conducted a bibliometric analysis of the 100 most cited articles published between 2019 and 2021 in each of the top 10 general surgery journals based on the 2021 Journal Impact Factor. Impact metrics included AAS, citation count, and H-index of the CA. We used multivariable regression analyses to investigate whether the sex of the CA or first author (FA) was independently associated with AAS and citation count. RESULTS: Among 1000 articles, 23.1% had female CAs and 27.4% female FAs. Female CA articles had higher AAS (13.0 [2.0-63.0] vs. 8.0 [1.0-28.5]; p < 0.001) and lower H-indices (24.0 [11.0-45.0] vs. 31.0 [17.0-50.0]; p = 0.015). Although median citation count did not differ by CA sex, articles with Level 1 evidence and a female CA were cited more often (35.5 [24.0-85.0] vs. 25.0 [16.0 vs. 46.0]; p < 0.05). In multivariable regression, female CA articles had higher AAS (OR: 1.002 [95% CI: 1.001-1.004]) and lower H-index (OR: 0.987 [95% CI: 0.977-0.997]). CONCLUSION: Despite having similar citation counts, articles authored by female CAs exhibit higher AAS scores compared to those authored by their male counterparts. While it is heartening that research authored by female surgeons achieves significant visibility, it remains to be understood how this translates into academic impact and scholarly recognition.
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BACKGROUND: Despite a large burden of life-limitingillness, there exists a dearth of services of palliative care in Pakistan. International guidelines have questionable applicability in Pakistan due to the socioeconomic differences. We generated a protocol describing the process of developing comprehensive palliative care guidelines and palliative care referral pathways for primary care practitioners to adopt in Pakistan. METHODS: A GRADE-ADOLOPMENT approach with modification has been employed to create guidelines for a Pakistani context. The "National Comprehensive Cancer Network Guidelines Insights: Palliative Care, Version 2.2021" was used as the source guideline. Recommendations from the source guideline were reviewed by two local palliative care specialists to either "Adopt," "Adapt" or "Exclude". The finalized recommendations were incorporated into the local palliative care guideline. Clinical diagnosis and referral pathways were made from the finalized guideline. Any gaps in management found in the pathways were filled by taking existing recommendations from other credible guidelines. RESULTS: Twenty-seven recommendations were adopted without modification. No recommendations were deemed to be adapted and 15 were excluded. The referral care pathways created were reflective of the local guideline and included elements of initial assessment, preliminary management, reassessment, and referral. 6 additional recommendations were made. CONCLUSION: The described clinical practice guidelines and primary care clinical referral pathways will aid to standardize palliative care provision in Pakistan. These can be used by other resource constrained settings to develop guidelines within their own local context.
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Cuidados Paliativos , Atención Primaria de Salud , Derivación y Consulta , Humanos , Pakistán , Cuidados Paliativos/normas , Cuidados Paliativos/métodos , Derivación y Consulta/normas , Atención Primaria de Salud/métodos , Atención Primaria de Salud/normas , Guías de Práctica Clínica como AsuntoRESUMEN
Optimizing postoperative quality of life (QoL) is an essential aspect of surgical oncology. Minimally invasive surgery (MIS) decreases surgical morbidity and improves QoL outcomes. This meta-analysis aimed to compare post-operative QoL after oncologic resections using different MIS modalities. The PubMed, Embase, Scopus, and CENTRAL databases were searched for articles that compared post-operative QoL in patients undergoing video-assisted thoracoscopic (VATS) or laparoscopic surgery (LS) versus robotic surgery (RS) for malignancy. Quality assessment was performed using the ROBINS-I and Cochrane Risk of Bias 2 (RoB-2) tools. Meta-analysis was performed using an inverse-variance random effects model. 27 studies met the inclusion criteria, including 5 randomized controlled trials (RCTs). 15 studies had a low risk of bias, while 11 had a moderate risk of bias and 1 had serious risk of bias. 8330 patients (RS: 5090, LS/VATS: 3240) from across 25 studies were included in the meta-analysis. Global QoL was significantly better after robotic surgery in the pooled analysis overall (SMD: - 0.28 [95% CI: - 0.49, - 0.08]), as well as in the prostatectomy and gastrectomy subgroups. GRADE certainty of evidence was low. Analysis of EPIC-26 subdomains also suggested greater sexual function after robotic versus laparoscopic prostatectomy. Robotic and conventional MIS approaches produce similar postoperative QoL after oncologic surgery for various tumor types, although advantages may emerge in some patient populations. Our results may assist surgeons in counseling patients who are undergoing oncologic surgery.
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Procedimientos Quirúrgicos Mínimamente Invasivos , Neoplasias , Procedimientos Quirúrgicos Robotizados , Humanos , Neoplasias/cirugía , Calidad de Vida , Procedimientos Quirúrgicos Robotizados/métodosRESUMEN
Spurious hyperphosphatemia, a rare occurrence, typically arises from substances in a patient's blood interfering with the colorimetric method for serum phosphate measurement. We present a case of factitious hyperphosphatemia caused by alteplase-contaminated blood samples in an 88-year-old CKD patient on hemodialysis, leading to misleadingly high phosphorus levels. Thorough investigations ruled out other etiologies, highlighting the necessity of stringent adherence to blood collection protocols to prevent sample contamination and avert erroneous laboratory results. This unique cause of hyperphosphatemia should be considered in the differential diagnosis when encountering unexplained elevations in phosphorus levels, particularly in the context of normal blood calcium levels.
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Hiperfosfatemia , Insuficiencia Renal Crónica , Humanos , Anciano de 80 o más Años , Hiperfosfatemia/inducido químicamente , Hiperfosfatemia/diagnóstico , Activador de Tejido Plasminógeno/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapia , Diálisis Renal/efectos adversos , Diálisis Renal/métodos , Fósforo , FosfatosRESUMEN
BACKGROUND: Reference intervals (RIs) of serum calcium vary based on age, population demographics, and methods of assessment. However, conventional approaches to establish serum calcium (Ca)RIs pose ethical and practical challenges, especially in the pediatric population. Hence, the use of indirect approaches is beneficial. This study was carried out to estimate the RIs of serum Ca using three indirect approaches in the pediatric and adolescent population of Pakistan. METHODS: Data mining laboratory information systems, for serum Ca results from 2013 - 2021 was done on a target population ranging from birth to 18 years of age. The population was grouped into three categories based on age (birth - 1 year, 2 - 4 years, and 5 - 18 years), as defined previously by Tahmasebi et al. in the CALIPER cohort. Pre-validated indirect algorithms, 'KOSMIC', Bhattacharya, and Hoffman, were used for analyzing the RIs. RESULTS: A total of non-duplicate 40,914 serum Ca tests were retrieved over a period of 6 years, including 38.7% (n = 15,830) from birth - 1 year, 16.3% (n = 6,641) from > 1 - 4 years, and 45.2% (n = 18443) from > 4 - 18 years respectively. The three methods revealed comparable performance with the direct RIs reported by Tahmasebi et al. in the CALIPER cohort. Keeping a stringent total allowable error of 1 mg/dl for Serum Ca as given by Clinical Laboratory Improvement Amendments (CLIA) the KOSMIC method outperformed the other two when compared to Tahmasebi, Houman, et al. Conclusions: The study advocates the use of the indirect approach for calculating RIs for serum calcium in the pediatric population, especially to aid clinical decision making in a low resource setting, due to its ability to reproduce results in line with the direct approach in a more economical, practical, and feasible way.
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Algoritmos , Calcio , Adolescente , Niño , Humanos , Pueblo Asiatico , Calcio/sangre , Toma de Decisiones Clínicas , Pakistán , Recién Nacido , Lactante , Preescolar , Valores de ReferenciaRESUMEN
BACKGROUND: The new eGFR equation without race coefficients was recently developed and published by the CKD-EPI Collaboration. The new equation termed CKD-EPI 2021 has been endorsed by the National Kidney Foundation and the American Society of Nephrology. It is important to understand the impact this new equation might have on clinical decision making in practice; hence, this study is planned to evaluate the CKD-EPI 2021 equation in Pakistani population. To evaluate the performance of CKD-EPI 2021, CKD-EPI 2009, CKD-EPI Pak, and MDRD equations taking CrCl as gold standard. METHODS: This retrospective cross-sectional study was conducted at the section of Chemical Pathology, Department of Pathology and Laboratory Medicine, in collaboration with section of Nephrology, Department of Medicine, Aga Khan University, Karachi. Consecutive laboratory results of subjects above 18 years; tested for CrCl or three months December 2021 to February 2022 was retrieved from the integrated laboratory management system (iLMS). Demographic details including gender and age alongside biochemical results of CrCl and serum Cr were recorded on a prestructured questionnaire. Statistical analysis of the data will be performed using Statistical Package of Social Sciences (SPSS) version 22. RESULTS: After excluding those below 18 years of age, 2,609 cases were included in the final data analysis, with 1,419 (54.4%) males and 1,190 (45.6%) females. Mean age of the group was 52.8 ± 14.9 years. Among the 4 formulae tested against CrCl, CKD-EPI Pak showed the strongest correlation (r2 = 0.83), highest sensitivity 93.2% and negative predictive value of 93.0% with an overall agreement of 88%. CONCLUSIONS: The CKD-EPI Pak equation is more accurate and precise in estimating GFR in Pakistani population. Based on the successful five years of experience of reporting eGFR using this equation by a large tertiary care hospital in Pakistan, this is high time to propagate its incorporation reflexly with SCr laboratory reports with no additional cost constraints.
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Insuficiencia Renal Crónica , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Tasa de Filtración Glomerular , Creatinina , Estudios Retrospectivos , Insuficiencia Renal Crónica/diagnóstico , Estudios TransversalesRESUMEN
L-2-hydroxyglutaric aciduria (L2HGA) is an autosomal recessive, slowly progressive neurodegenerative disease characterized by psychomotor delay and cerebellar dysfunction. The biochemical hallmark is increased concentrations of L2HG in body fluids. Brain MRI exhibits characteristic centripetal extension of the white matter involvement that differentiates it from other leukodystrophies. The authors report two sisters from Pakistan with L2HGA with 4 years of follow-up. The authors have also compared the clinical outcome of our patients with 45 previously reported patients with L2HGA for whom treatment and clinical outcome was reported. Case presentation: The authors report two sisters with L2HGA from Pakistan born to consanguineous parents. The 15- and 17-year-old girls presented with psychomotor delay, seizures, ataxia, intentional tremors, and dysarthria. Both had normal anthropometric measurements for age. Exaggerated tendon reflexes and bilateral sustained ankle clonus were observed in addition to cerebellar signs. Urine organic acids analysis showed marked excretion of 2-hydroxyglutaric acid, chiral differentiation of 2-hydroxyglutaric acid showed it to be L2HGA. Brain MRI of the 15-year-old showed diffuse subcortical white matter changes evident by T2/FLAIR hyperintense signals bilaterally, particularly in the frontal region in the centripetal distribution with some diffusion restriction along involvement of globus pallidus. The characteristic MRI pattern raised the suspicion of L2HGA. Targeted L2HGDH sequencing identified a homozygous pathogenic variant, c.829C>T (p.Arg227*) in L2HGDH gene in both girls. Both parents were heterozygous carriers of the familial variant. Conclusion: Neuroradiological features of centripetal subcortical leukoencephalopathy with basal ganglia and dentate nuclei involvement are rather specific to L2HGA and should lead to further biochemical investigations to look for L2HGA and L2HGDH gene sequencing.
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COVID-19 has proved to be a serious, and consequential disease that has affected millions of people globally. Previously, the adverse effects of proton pump inhibitors (PPI) have been observed with increasing the risk of pneumonia and COVID-19. This meta-analysis aims to address the relationship between the use of PPI and the severity of COVID-19 infection. We conducted a systemic literature search from PUBMED, Science Direct, and Cinahl from December 2019 to January 2022. Published and unpublished randomized control trials and cohort studies were included. Review Manager was used for all statistical analyses. In total, 14 studies were included in this systemic review and meta-analysis. Outcomes of interest include: (1) susceptibility of COVID-19 infection and (2) severity of COVID-19 (defined as the composite of poor outcomes: ICU admission, need for oxygen therapy, need for a ventilator, or death), and (3) mortality due to COVID-19. PPI use was marginally associated with a nominal but statistically significant increase in the risk of COVID-19 infection (OR 1.05 [1.01, 1.09]; I2 97%, p = 0.007). PPI use also increased the risk of the composite poor outcome (OR 1.84 [1.71, 1.99]; I2 98%, p < 0.00001) and mortality (OR 1.12 [1.00, 1.25]; I2 84%, p = 0.05) in patients with COVID-19.
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Objectives This study was conceived with the objective of assessing the correlation between ovarian reserve markers and vitamin D deficiency (VDD) in a selected group of Pakistani subfertile women presenting at a specialized subfertility treatment centre. The measurements of antral follicle count (AFC), serum anti-Müllerian hormone (AMH), serum follicle-stimulating hormone (FSH), and serum vitamin D (VD) levels were the main tools used for the assessment of ovarian reserve. Materials and methods All female patients aged 18 to 45 years presenting with primary and/or secondary subfertility at the Australian Concept Medical Centre in Karachi, Pakistan from August 2016 to July 2021 were included in the study. The data of all eligible patients were recorded in the pre-defined Performa designed for this study. The Kruskal-Wallis test was applied to report the distribution of the data. The correlation between the categorical variables (25-hydroxyvitamin D [25-OHD] levels with AFC and AMH) was assessed using the chi-square test and Spearman correlation. The comparison was based on vitamin D levels grouped into three categories: deficiency (<20 ng/ml), insufficiency (21-29 ng/ml), and sufficiency (>30 ng/ml). Results One hundred ninety-nine cases were evaluated for AFC and hormone analysis. The mean age and BMI were 32.87±5.49 years and 28.27±4.97 kg/m2.VDD was noted in 127 (68.4%) cases. No significant difference was noted across BMI, age, duration of subfertility, AMH, and FSH across the VD categories. Moreover, a poor correlation was noted between VD, AMH and FSH on the scatter plot, between VD and FSH (r = -0.003, p = 0.966) and between VD and AMH (r = -0.068, p = 0.342), respectively. Conclusions This study showed a high frequency of VDD in Pakistani subfertile women, from a specialized subfertility center in the largest metropolis in the country. However, a statistically significant association was not found between the markers of ovarian reserve and VD, showing no ethnic differences in the native Pakistani population. Hence, VD supplementation is unlikely to have an impact on correcting the ovarian reserve status in subfertile women in Pakistan. However, this is a potential area of interest, and evaluation of other indices of reproduction/ovarian reserve and the effect of confounders is required to test this hypothesis longitudinally.
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BACKGROUND: We aim to study the utility of Google Trends search history data for demonstrating if a correlation may exist between web-based information and actual coronavirus disease 2019 (COVID-19) cases, as well as if such data can be used to forecast patterns of disease spikes. PATIENTS & METHODS: Weekly data of COVID-19 cases in Pakistan was retrieved from online COVID-19 data banks for a period of 60 weeks. Search history related to COVID-19, coronavirus and the most common symptoms of disease was retrieved from Google Trends during the same period. Statistical analysis was performed to analyze the correlation between the two data sets. Search terms were adjusted for time-lag over weeks, to find the highest cross-correlation for each of the search terms. RESULTS: Search terms of 'fever' and 'cough' were the most commonly searched online, followed by coronavirus and COVID. The highest peak correlations with the weekly case series, with a 1-week backlog, was noted for loss of smell and loss of taste. The combined model yielded a modest performance for forecasting positive cases. The linear regression model revealed loss of smell (adjusted R2 of 0.7) with significant 1-week, 2-week and 3-week lagged time series, as the best predictor of weekly positive case counts. CONCLUSIONS: Our local analysis of Pakistan-based data seemingly confirms that Google trends can be used as an important tool for anticipating and predicting pandemic patterns and pre-hand preparedness in such unprecedented pandemic crisis.
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INTRODUCTION: Distinguishing between inflammatory bowel disease (IBD) and functional gastrointestinal disorders is a diagnostic challenge. The need for non-invasive biomarker as a diagnostic tool in the assessment of gastrointestinal symptoms is required. The objectives of current study were to determine the spectrum of clinical features in patients tested for fecal calprotectin presenting with high levels and to compare calprotectin levels among already diagnosed patients known to have IBD as per biopsy findings and documented on patients' file with newly presenting patients who were being investigated and did not have a diagnosis. METHODS: This retrospective cross-sectional study was conducted in the Department of Pathology and Laboratory Medicine and Department of Medicine, Aga Khan University, Karachi, Pakistan from January 2017 to December 2019. Subjects tested for fecal calprotectin who had elevated fecal calprotectin levels (n = 150) were included in the current study. Each patient deposited a random stool sample in an airtight container for calprotectin analysis. Biochemical analysis of calprotectin was performed by enzyme-linked immunosorbent assay using epitope calprotectin test kit (Epitope Diagnostics, Italy) on ETI-Max 3000 immunoassay analyzer (DiaSorin, Italy). A structured history form was used for data collection. Results: One hundred and fifty patients were available for inclusion in the ï¬nal analysis. Majority of the patients (n = 117, 78%) were adults (>18 years of age), and 52.7% (n = 79) were females. Median fecal calprotectin (IQR) was 317.3 µg/g (549.10 - 239.2 µg/g) in children (n = 33) and 305 µg/g (609.9 - 201.6 µg/g) in adults; the difference was statistically non-significant (p value > 0.05). On categorization according to disease, fecal calprotectin levels were significantly elevated (p value = 0.033) in IBD patients compared to normal subjects, 644 µg/g (644 - 587.8 µg/g) vs 308.5 µg/g (505.4 - 233.8 µg/g), respectively. Diarrhea (n = 13, 38.4%), abdominal cramps (n = 12, 36.4%), and weight loss (n = 11, 33.3%) were the most common complaints noted in children with high fecal calprotectin levels, whereas in adults, abdominal cramps (n = 60, 51.3%), diarrhea (n = 59, 50.4%), and weight loss (n = 46, 39.3%) were the common complaints. The median fecal calprotectin levels in children already known to have IBD (n = 3) were higher than the levels noted in children with no diagnosis (n = 30); p value > 0.05. Similarly, median fecal calprotectin levels in adults with IBD (n = 28) were higher than the levels noted in patients with no specific diagnosis (n = 91), 400.7 µg/g (656.6 - 244.3 µg/g) vs 302.7 µg/g (564.6 - 206 µg/g); p value > 0.05. CONCLUSION: Current study affirms that the fecal calprotectin test can be used in identifying IBD patients in all age groups.