Magnetic resonance cholangiopancreatography in diagnosis of biliary disorders in children - Sharing our experience.

Abstract OBJECTIVE: To evaluate the role of Magnetic Resonance Cholangio-pancreatography in the diagnosis of biliary disorders in children. METHODS: The retrospective study was conducted at Aga Khan University Hospital, Karachi, and comprised data related to the period between August 2005 and December 2013. All children from age of 1 day to 17 years who had undergone Magnetic Rasonance Cholangio-pancreatography examination for suspected pancreaticobiliary disorders were included. Clinical presentation, Magnetic Rasonance Cholangio-pancreatography findings, operative findings and histopathological results were recorded. Sensitivity and specificity of Magnetic Rasonance Cholangio-pancreatography for different diseases was worked out. RESULTS: Of the 50 patients in the study, 12(24%) showed findings of choledochal cyst. Of these patients, 11(91.6%) underwent surgery and operative findings were consistent with choledochal cyst. Only 1(8.3%) who was assessed as biliary atresia was found to have choledochal cyst on surgery Magnetic Resonance Cholangio-pancreatography was found to be 91% sensitive and 100% specific for diagnosis of choledochal cyst with diagnostic accuracy of 98%. CONCLUSIONS: Magnetic Resonance Cholangio-pancreatography is a very accurate non-invasive investigation for the diagnosis of biliary disorders

Magnetic resonance spectroscopy in focal brain lesions

OBJECTIVE: To describe the spectrum of Magnetic Resonance spectroscopy in focal brain lesions and determine its diagnostic accuracy using histopathology as gold standard in differentiating neoplastic and non-neoplastic focal brain lesions. METHODS: The study was conducted in Department of Radiology, Aga Khan University Hospital, Karachi from Dec 2006 till Jan 2009. Fifty three patients found to have focal brain lesions on magnetic resonance imaging (MRI) were included in the study. Magnetic Resonance spectroscopy (MRS) was performed in these focal lesions. These lesions were deemed neoplastic and non-neoplastic on MR Spectrum findings. Correlation of all these findings was done with histopathology obtained in all these patients. Sensitivity, specificity, positive, negative predictive values and diagnostic accuracy of MR Spectroscopy was calculated. Percentage agreement between spectroscopy and histopathology was also calculated using kappa statistics. RESULTS: Increase Choline/creatine and Choline/NAA ratio noted in neoplastic lesions compared to nonneoplastic lesion with significant p-value. MR Spectroscopy has a sensitivity of 93.02%, specificity of 70%, positive predictive value of 93.02%, negative predictive value of 70% and diagnostic accuracy of 88.67% in differentiating neoplastic and non-neoplastic brain lesions. Kappa statistics shows a good agreement between MR Spectroscopy and histopathology (k = 0.630). CONCLUSION: Magnetic Resonance spectroscopy (MRS) is non-invasive sensitive, however, relatively nonspecific modality in differentiating neoplastic and non-neoplastic brain lesions. This modality should be considered as an adjunct to conventional imaging rather than replacement for histopathological evaluation

Refractive Errors: Prevalence and Pattern among Rural Population of Islamabad, Pakistan

Background: Refractive error is the most common cause of correctable visual loss worldwide. Decreased vision due to refractive error can be easily corrected with the help of spectacles, contact lenses and refractive surgery. However, there are 42% of uncorrected refractive errors all over the world. The present study aimed to evaluate different kinds of refractive errors, its prevalence and pattern in patients from rural areas who visited our hospital in the last five years. Material and Methods: This cross-sectional study enrolled 2,138 patients, who visited eye OPD at Rawal Institute of Health Sciences, Islamabad during a period of five years i.e. from September, 2013 to September, 2018. Patients having only refractive error with an age of five years and above were included in the study.  All patients had objective refraction with automated refractometer followed by subjective refraction. Data was entered and analyzed in SPSS version 20.0. Chi-square test was used for comparing groups with a P-value of <0.05 considered as statistically significant. Results: Compound myopic astigmatism was the most common error found in our study population (n=575; 26.9%). The second most frequent complaint was simple myopia (n=501; 23.4%) followed by presbyopia (n=441; 20.6%) and mixed astigmatism (n=235; 11%). Patients with more than one refractive error included 178 (8.3%) with mixed astigmatism and presbyopia and 78 (3.6%) with simple myopia and presbyopia. Compound myopic astigmatism was more prevalent in younger ages compared to older age groups (46.4% vs 19.9%) (P <0.001). Mixed astigmatism (12.4% vs 8.9%), simple myopia (23.8% vs 22.9%) and presbyopia (21.3% vs 19.5%) were slightly greater in females than males (P=0.07), respectively. Conclusions: The prevalence of myopia is significantly higher among female population and young individuals. Mixed astigmatism combined with presbyopia is more common among elderly population. Key words: Astigmatism, Hypermetropia, Myopia, Presbyopia, Refractive error

Triphasic computed tomography (CT) scan in focal tumoral liver lesions

OBJECTIVE: To assess the diagnostic accuracy of triphasic spiral CT in differentiating benign from malignant focal tumoral liver lesions. METHODS: The study was conducted in Department of Radiology of Aga Khan University Hospital and Sind Institute of Urology and Transplantation, Karachi from Feb 2006 to Feb 2007. By convenient sampling, 45 patients found to have focal tumoral liver lesions were recruited for one year period and their triphasic CT scans findings were evaluated and later correlated with histopathology. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of triphasic CT scan were calculated. RESULTS: Among 45 patients, 136 liver lesions (11 benign and 125 malignant) were detected with the help of different enhancement patterns. Out of these, 37(82.2%) patients had malignant while 8 (17.8%) had benign lesions. On later histopathological examination, 35 (77.8%) of the total 45 cases had malignant lesions while 10 (22.2%) were diagnosed as benign lesions. Based on these results, it could be assessed that triphasic CT Scan has a sensitivity of 100%, specificity of 80%, positive predictive value of 94.5%, negative predictive value of 100% and diagnostic accuracy of 95.5% in differentiating benign from malignant liver lesions. CONCLUSION: Triphasic CT Scan is a good non-invasive tool in characterizing and differentiating benign from malignant liver lesions

Vitamin B12 deficiency common in primary hypothyroidism

OBJECTIVE: To assess the prevalence and clinical features of B12 deficiency in hypothyroid patients and to evaluate clinical response in symptoms to B12 replacement therapy. METHODS: One hundred and sixteen hypothyroid patients from our endocrine clinic were evaluated for signs and symptoms of vitamin B12 deficiency. Laboratory parameters including Haemoglobin (Hb), MCV, Vitamin B12 levels and presence of anti thyroid antibodies were analyzed. Patients with low B12 levels were treated with parenteral intramuscular vitamin B12 monthly, and monitored for improvement of symptoms. RESULTS: A total of 116 patients (95 females and 21 males) were evaluated. Forty six (39.6%) hypothyroid patients had low vitamin B12 levels. Males and females had the same prevalence of B12 deficiency. Generalized weakness, impaired memory, depression, numbness and decreased reflexes were more frequently noted in B12 deficient patients, but failed to achieve statistical significance when compared with B12 sufficient patients. The mean Hb in B12 deficient group was 11.9 +/- 1.6 mg/dl and 12.4 +/- 1.7 mg/dl in the B12 sufficient group, however the mean MCV did not differ in the two groups. Patients with B12 deficiency did not have a higher prevalence of anaemia. Thyroid antibodies were checked in half the patients and 67% had positive titers for anti thyroid antibodies. Prevalence of vitamin B12 deficiency did not differ in patients with positive antibodies (43.2%) compared to those with negative antibodies (38.9%) (p= 0.759). Twenty four hypothyroid patients with B12 deficiency received intramuscular vitamin B12 injections monthly and improvement in symptoms was noted in 58.3% of these subjects. Additionally, 21 subjects complained of symptoms consistent with B12 deficiency but who had normal range B12, levels and were prescribed monthly B12 injections and 8 (40%) had good subjective clinical response at 6 months. CONCLUSIONS: There is a high (approx 40%) prevalence of B12 deficiency in hypothyroid patients. Traditional symptoms are not a good guide to determining presence of B12 deficiency. Screening for vitamin B12 levels should be undertaken in all hypothyroid patients, irrespective of their thyroid antibody status. Replacement of B12 leads to improvement in symptoms, although a placebo effect cannot be excluded, as a number of patients without B12 deficiency also appeared to respond to B12, administration

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

The Role of Mesenchymal Stromal Cell (MSC) Mitochondrial Transfer in the Suppression of CD4+ and CD8+ T Cell Responses

Les lymphocytes T cytotoxiques CD8+ (LTC) et les cellules T helper CD4+ sont des effecteurs clés dans les maladies auto-immunes, les maladies du greffon contre l'hôte et le rejet de greffe. Les cellules stromales mésenchymateuses (CSM) sont des cellules multipotentes auto-renouvelables qui possèdent des propriétés de réparation tissulaire et d'immunomodulation. En raison de leur capacité à réprimer les réponses immunitaires pathogènes, elles présentent un potentiel thérapeutique pour le traitement des maladies à médiation immunitaire. Les CSMs ont la capacité unique d'exporter leurs propres mitochondries vers les cellules voisines en réponse à une blessure ou une inflammation. Cependant, on ne sait pas si le transfert de mitochondries a lieu et s'il joue un rôle dans la répression des réponses des lymphocytes T CD4+ Th1 et CD8+. Nous avons abordé cette question en utilisant un modèle de souris transgénique de la maladie et des CSMs allogéniques dérivées de la moelle osseuse in vitro et in vivo. Nos résultats ont montré :1) Les CSMs ont inhibé l'expansion, le gain du phénotype effecteur et la production de la cytokine effectrice IFNγ in vitro et le potentiel diabétogène in vivo des cellules CD4+ Th1 après activation. De façon remarquable, les cellules T CD4+ ont absorbé les mitochondries des CSMs pendant la suppression. Le transfert de mitochondries de CSMs aux cellules Th1 CD4+ a entraîné une diminution de la prolifération et de la production d'IFNγ. Enfin, nous avons démontré que les CSMs et les mitochondries de CSMs empêchent la régulation à la hausse du facteur de transcription maître Th1 sur les cellules T CD4+ activées.2) Les CSMs ont diminué l'expansion, le gain du phénotype effecteur et la production de la cytokine effectrice IFNγ dans les cellules T CD8+ après activation in vitro. Notamment, nous avons constaté que pendant leur interaction conduisant à la suppression, les CSMs ont également transféré des mitochondries aux LTC. Le transfert des mitochondries des CSM aux cellules T CD8+ a entraîné une diminution de la prolifération et de la production d'IFNγ lors de l'activation, contribuant à l'effet suppressif global des CSMs. Enfin, nous avons démontré que les mitochondries de CSMs et de CSMs régulent de manière différentielle l'équilibre de deux facteurs de transcription clés pour la différenciation des LTC, T-bet et Eomes, sur les cellules T CD8+ activées.CD8+ Cytotoxic T lymphocytes (CTL) and CD4+ T helper cells are key effectors in autoimmune, graft versus host diseases and graft rejection. Mesenchymal Stromal Cells (MSCs) are self-renewing multipotent cells with tissue repair and immunomodulatory properties. Due to their ability to repress pathogenic immune responses they show therapeutic potential for the treatment of immune mediated diseases. MSCs have the unique ability to export their own mitochondria to neighboring cells in response to injury and inflammation. However, whether mitochondrial transfer occurs and has any role in the repression of CD4+ Th1 and CD8+ T cell responses is unknown. We have addressed this issue utilizing a transgenic mouse model of disease and allogeneic bone marrow derived MSCs in vitro and in vivo. Our results showed:1) MSCs inhibited expansion, gain of effector phenotype and the production of the effector cytokine IFNγ in vitro and the diabetogenic potential in vivo of CD4+ Th1 cells after activation. Remarkably, CD4+ T cells took up mitochondria from MSCs during suppression. The transfer of MSC mitochondria to CD4+ Th1 cells resulted in decreased proliferation and production of IFNγ. Finally, we demonstrated that both MSCs and MSC mitochondria prevent the upregulation of the master Th1 transcription factor on activated CD4+ T cells.2) MSCs decreased the expansion, gain of effector phenotype and the production of the effector cytokine IFNγ in CD8+ T cells after activation in vitro. Notably, we found that during their interaction conducting to suppression, MSCs also transferred mitochondria to CTL. MSC mitochondrial transfer to CD8+ T cells resulted in decreased proliferation and production of IFNγ upon activation contributing to the global suppressive effect of MSCs. Finally, we demonstrated that both MSCs and MSC mitochondria differentially regulate the balance of two transcription factors key for CTL differentiation, T-bet and Eomes, on activated CD8+ T cells