Study protocol of Phase 2 open-label multicenter randomized controlled trial for granulocyte-colony stimulating factor (GCSF) in post-Kasai Type 3 biliary atresia.

Animal studies support RCT findings of improved liver function and short-term benefits using repurposed Granulocyte Colonic Stimulating Factor GCSF in adults with decompensated cirrhosis. We describe the protocol for phase 2 RCT of sequential Kasai-GCSF under an FDA-approved IND to test that GCSF improves early bile flow and post-Kasai biliary atresia BA clinical outcome. Immediate post-Kasai neonates, age 15-180 days, with biopsy-confirmed type 3 BA, without access to early liver transplantation, will be randomized 1:1 to standard of care SOC + GCSF at 10 ug/kg in 3 daily doses within 4 days of Kasai vs SOC + NO-GCSF (ClinicalTrials.gov NCT0437391). They will be recruited from children's hospitals in Vietnam, Pakistan and one US center. The primary objective is to demonstrate that GCSF decreases the proportion of subjects with a 3-month post-Kasai serum Total Bilirubin ≥ 34 umol/L by 20%, (for a = 0.05, b = 0.80, i.e., calculated sample size of 218 subjects). The secondary objectives are to demonstrate that the frequency of post-Kasai cholangitis at 6-month and 24-month transplant-free survival are improved. The benefits are that GCSF is an affordable BA adjunct therapy, especially in developing countries, to improve biliary complications, enhance quality of liver and survival while diminishing costly liver transplantation.Clinical trial registration: A phase 1 for GCSF dose and safety determination under ClinicalTrials.gov identifier NCT03395028 was completed in 2019. The current Phase 2 trial was registered under NCT04373941.

Simulation-based training in the Paediatric Surgery population: A review of current trends and future direction.

In recent years, simulation-based training in surgery has emerged as a viable accompaniment to traditional teaching methods. Multiple studies have highlighted the benefits of simulation-based training in both learning and teaching aspects of surgical training, with a particular emphasis on the honing of technical skills. However, multiple issues still exist in widespread implementation of simulation-based training, especially in the developing countries. Furthermore, the existing literature needs to be expanded upon in both quantity and quality domains to ensure a more evidence-based transition to simulation-based training in surgery. The current review article was planned to take a look at the existing literature on the current state of simulation-based training in paediatric surgery, its potential to revolutionise paediatric surgical training, and to propose solutions to the issues that are delaying wider implementation.

Infectious Etiologies of Intussusception Among Children <2 Years Old in 4 Asian Countries.

BACKGROUND: The etiology of intussusception, the leading cause of bowel obstruction in infants, is unknown in most cases. Adenovirus has been associated with intussusception and slightly increased risk of intussusception with rotavirus vaccination has been found. We conducted a case-control study among children <2 years old in Bangladesh, Nepal, Pakistan, and Vietnam to evaluate infectious etiologies of intussusception before rotavirus vaccine introduction. METHODS: From 2015 to 2017, we enrolled 1-to-1 matched intussusception cases and hospital controls; 249 pairs were included. Stool specimens were tested for 37 infectious agents using TaqMan Array technology. We used conditional logistic regression to estimate odds ratio (OR) and 95% confidence interval (CI) of each pathogen associated with intussusception in a pooled analysis and quantitative subanalyses. RESULTS: Adenovirus (OR, 2.67; 95% CI, 1.75-4.36) and human herpes virus 6 (OR, 3.50; 95% CI, 1.15-10.63) were detected more frequently in cases than controls. Adenovirus C detection <20 quantification cycles was associated with intussusception (OR, 18.59; 95% CI, 2.45-140.89). Wild-type rotavirus was not associated with intussusception (OR, 1.07; 95% CI, 0.52-2.22). CONCLUSIONS: In this comprehensive evaluation, adenovirus and HHV-6 were associated with intussusception. Future research is needed to better understand mechanisms leading to intussusception, particularly after rotavirus vaccination.

Burden of Ileal Perforations Among Surgical Patients Admitted in Tertiary Care Hospitals of Three Asian countries: Surveillance of Enteric Fever in Asia Project (SEAP), September 2016-September 2019.

BACKGROUND: Typhoid fever is caused by Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) and can lead to systemic illness and complications. We aimed to characterize typhoid-related ileal perforation in the context of the population-based Surveillance of Enteric Fever in Asia Project (SEAP) in Bangladesh, Nepal and Pakistan. METHODS: Between September 2016 and September 2019, all cases of nontraumatic ileal perforation with a clinical diagnosis of typhoid were enrolled from 4 tertiary care hospitals in Karachi, 2 pediatric hospitals in Bangladesh, and 2 hospitals in Nepal. Sociodemographic data were collected from patients or their caregivers, and clinical and outcome data were retrieved from medical records. Tissue samples were collected for histopathology and blood cultures where available. RESULTS: Of the 249 enrolled cases, 2 from Bangladesh, 5 from Nepal and 242 from Pakistan. In Pakistan, most of the cases were in the 0-15 (117/242; 48%) and 16-30 (89/242; 37%) age groups. In all countries, males were most affected: Pakistan 74.9% (180/242), Nepal 80% (4/5), and Bangladesh 100% (2/2). Blood culture was done on 76 cases; 8 (11%) were positive for S. Typhi, and all were extensively drug resistant (XDR) S. Typhi. Tissue cultures was done on 86 patients; 3 (3%) were positive for S. Typhi, and all were XDR S. Typhi, out of 86 samples tested for histopathology 4 (5%) revealed ileal perforation with necrosis. Culture or histopathology confirmed total 15 (11%) enteric fever cases with ileal perforation are similar to the clinically diagnosed cases. There were 16/242 (7%) deaths from Pakistan. Cases of ileal perforation who survived were more likely to have sought care before visiting the sentinel hospital (P = .009), visited any hospital for treatment (P = .013) compared to those who survived. CONCLUSIONS: Although surveillance differed substantially by country, one reason for the higher number of ileal perforation cases in Pakistan could be the circulation of XDR strain of S. Typhi in Karachi.

Burden of Culture Confirmed Enteric Fever Cases in Karachi, Pakistan: Surveillance For Enteric Fever in Asia Project (SEAP), 2016-2019.

BACKGROUND: The Surveillance for Enteric Fever in Asia Project (SEAP) is a multicenter, multicountry study conducted in Pakistan, Nepal, and Bangladesh. The objectives of the study were to characterize disease incidence among patients with enteric fever. We report the burden of enteric fever at selected sites of Karachi, Pakistan. METHODS: During September 2016 to September 2019, prospective surveillance was conducted at inpatient, outpatient, surgical departments, and laboratory networks of Aga Khan University Hospital, Kharadar General Hospital, and surgery units of National Institute of Child Health and Jinnah Postgraduate Medical Centre. Socio-demographic, clinical, and laboratory data were obtained from all suspected or confirmed enteric fever cases. RESULTS: Overall, 22% (2230/10 094) of patients enrolled were culture-positive for enteric fever. 94% (2093/2230) of isolates were Salmonella Typhi and 6% (137/2230) were S. Paratyphi. 15% of isolates multi-drug resistant (MDR) to first-line antibiotics and 60% were extensively drug-resistant (XDR), resistant to first-line antibiotics, fluoroquinolones and third generation cephalosporin. CONCLUSION: Enteric fever cases have increased during the last 3 years with large proportion of drug resistant S. Typhi cases. However, the burden of paratyphoid is still relatively low. Strengthening the existing surveillance system for enteric fever and antimicrobial resistance at the national level is recommended in Pakistan to inform prevention measures. While typhoid vaccination can significantly decrease the burden of typhoid and may also impact antimicrobial resistance, water, sanitation, and hygiene improvement is highly recommended to prevent the spread of enteric fever.

Challenges to delivering pediatric surgery services in the midst of COVID 19 crisis: experience from a tertiary care hospital of Pakistan.

Covid-19 pandemic has significantly challenged the healthcare delivery across the world. Surgery departments across the country responded to this challenge by halting all non-emergency procedures. This delay in diagnosis and management of surgical disease could result in significant mortality and morbidity among the most vulnerable population-the children. In this manuscript, we discuss the measures adopted as well as the challenges faced by the pediatric surgery department at Aga Khan University Hospital, Karachi (AKUH), Pakistan, which is a private, not-for-profit entity and providing optimum surgical care to the patients. We also underscore the need for global strategies for tackling such crisis.

Laparoscopic total colectomy in an eight-year-old with familial adenomatous polyposis: A case report.

Familial Adenomatous Polyposis accounts for <1% of all the colorectal cancer cases, with progression to colorectal cancer usually at >20 years of age. Endoscopy is essential for the diagnosis with definitive treatment involving prophylactic total colectomy. With current surgical advances, this is routinely being performed with the aid of laparoscopy. Due to resource limitations and non-availability of the screening programs in the developing world, such cases remain under diagnosed. Genetic testing is necessary for prognostication of both the index case and their at-risk family members. Thus, we present a rare case of an eight-year-old female, with an early onset progression to colorectal cancer with Familial Adenomatous Polyposis. We performed a prophylactic laparoscopic total procto-colectomy with ileo-anal anastomosis, which to our knowledge is the first ever-performed procedure in Pakistan. We conclude that progression to colorectal carcinoma in familial adenomatous polyposis can present at an earlier age than that reported in the literature. Laparoscopic total colectomy has similar outcomes than open surgical methods with better cosmetic results.

Amoebic liver abscess: Outcomes of percutaneous needle aspiration vs drain placement in paediatric population.

OBJECTIVE: To compare the effectiveness of percutaneous catheter drain placement with percutaneous needle aspiration in terms of hospital stay, time to resolution of symptoms and cost of intervention performed. Methods: The retrospective cohort study was conducted at Aga Khan University Hospital, Karachi, and comprised data of patients with amoebic liver abscess from, January 2006 to December 2016 which was collected using non-probability purposeful sampling. Primary outcome included length of hospital stay, time to resolution of symptoms and cost of intervention. Secondary outcomes included development of complications, need for re-intervention and abscess resolution. SPSS 22 was used for data analysis. . Results: Of the 62 patients, 36(58%) underwent percutaneous needle aspiration Group A, and 26(42%) were treated with percutaneous catheter drain placement Group B. Both groups were malnourished and anaemic at presentation. Overall, 56(90.3%) patients had single abscess and 44(71%) had it in the right lobe. Mean duration of symptoms was less in Group B compared to Group A (11.2±4.5 versus 16.4±3.2 days). Mean abscess size was 6.13cm ± 9.75cm in Group A and 7.40cm ± 8.40cm in Group B. The mean length of hospital stay Group A was shorter than in Group B (p=0.047) with earlier resolution of symptoms (p=0.027). Conclusion: Both methods were found to be effective in treating amoebic liver abscess in children, but percutaneous needle aspiration was more effective.

Global perspective of paediatric surgery in low and middle income countries.

There is huge burden of paediatric surgical diseases in low and middle income countries. Issues behind such a scenario include lack of trained paediatric surgeons, higher mortality due to infections, and poor postoperative care. The possible solution is improvement in the existing structure, which is government hospitals, because they are the most prevalent form of healthcare delivery in such countries. Proper coding system, research and identification of paediatric bellwether procedures can improve the existing health system. Task shifting and sharing can help in many areas. The doctors leaving their countries for better training and employment options should be properly incentivised locally. A lot can be done in terms of providing infrastructure, finances, changing mind-sets, developing expertise, making registry and rehabilitation. By doing so, millions of paediatric mortalities can be prevented in low and middle income countries.

Pediatric laparoscopic surgery; initial experience from Pakistan; first 100 cases in single center.

In a developing country like Pakistan, laparoscopic surgeries are not considered favourable by many, possibly because of high costs or a lack of expertise. It is an established fact that laparoscopic surgery offers better surgical treatments with a shorter hospital stay and fewer complications. The current retrospective study was conducted at a tertiary care hospital in Karachi and comprised of laparoscopy cases performed by a single surgeon from March 2012 to September of 2014. A total of 100laparoscopic surgeries were performed; mostly appendectomies 49(49%) and undescended testes (UDTs) 34(34%). Overall, there were 70(70%) male patients. The mean age of the patients was 7.1 years and standard deviation (SD) of 2. Four (4%) patients had cellulitis. Laparoscopy paediatric surgery offered advantages of fewer wound-associated complications, less incisional pain, a shorter recovery time, and improved cosmesis.

Isolated splenic abscess in children, role of splenic preservation.

PURPOSE: Splenic abscess (SA) is rare life threatening clinical condition in children. Diagnosis is delayed because of its non-specific clinical presentation. It has a high mortality rate even in the era of antibiotics. This study aim to determine the role of splenic preservation in the management of isolated splenic abscess in children, and to compare different treatment modalities for it. METHODS: A retrospective cross-sectional study of 20 years was conducted including all children <14 years of age with the principal diagnosis of "Splenic abscess". We have excluded all splenic abscesses occurring after penetrating or blunt abdominal trauma. RESULTS: Total of 17 children were managed during the study period. Most of our patients were older than 10 years of age. Majority of patients had a significant delay in presentation. Fever, abdominal pain, and vomiting were the main mode of presentation. Splenomegaly on abdominal examination was present in 12 patients. 15 (88 %) children were managed conservatively; however, 2 children required surgical intervention. CONCLUSION: Splenic abscess in children is a rare disease and its diagnosis is often delayed. Delay in diagnosis of SA in children can lead to life threatening complications. A high index of suspicion is needed to reduce delay in diagnosis. Children presenting with non-specific high grade fever vomiting and abdominal pain should be evaluated for SA. Timely ultrasound and CT scan will lead to earlier diagnosis. A conservative approach with intravenous antibiotics and early percutaneous drainage especially in immunocompetent children can preserve spleen to continue immune function.

Focused abdominal sonography for trauma (FAST) in blunt paediatric abdominal trauma.

OBJECTIVE: To evaluate the role of focussed abdominal sonography for trauma in blunt paediatric abdominal trauma patients, and to see if the role of computed tomography scan could be limited to only those cases in which sonography was positive. METHODS: The retrospective study covered 10 years, from January 1,2000 to December 31,2009, and was conducted at the Department of Radiology and Department of Emergency Medicine, Aga Khan University Hospital, Karachi. It comprised cases of 174 children from birth to 14 years who had presented with blunt abdominal trauma and had focussed abdominal sonography for trauma done at the hospital. The findings were correlated with computed tomography scan of the abdomen and clinical follow-up. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of focussed abdominal sonography for trauma were calculated for blunt abdominal trauma. SPSS 17 was used for statistical analysis. RESULTS: Of the total 174 cases, 31 (17.81%) were later confirmed by abdominal scan. Of these 31 children, sonography had been positive in 29 (93.54%) children. In 21 (67.74%) of the 31 children, sonograpy had been true positive; 8 (25%) (8/31) were false positive; and 2 (6%) (2/31) were false negative. There were 6 (19.3%) children in which sonography was positive and converted to laparotomy. There was no significant difference on account of gender (p>0.356). Focussed abdominal sonography for trauma in the study had sensitivity of 91%, specificity of 95%, positive predictive value of 73%, and negative predictive value of 73% with accuracy of 94%. All patients who had negative sonography were discharged later, and had no complication on clinical follow-up. CONCLUSIONS: Focussed abdominal sonography for trauma is a fairly reliable mode to assess blunt abdominal trauma in children. It is a useful tool to pick high-grade solid and hollow viscous injury. The results suggest that the role of computed tomography scan can be limited to those cases in which focussed sonography is positive.

Intussusception risk following oral monovalent rotavirus vaccination in 3 Asian countries: A self-control case series evaluation.

Rotavirus vaccines have substantially decreased rotavirus hospitalizations in countries where they have been implemented. In some high- and middle-income countries, a low-level of increased risk of intussusception, a type of acute bowel obstruction, has been detected following rotavirus vaccination. However, no increased risk of intussusception was found in India, South Africa, or a network of 7 other African countries. We assessed the association between a 2-dose monovalent rotavirus vaccine (Rotarix) and intussusception in 3 early-adopter low-income Asian countries -- Afghanistan, Myanmar, and Pakistan. Children <12 months of age admitted to a sentinel surveillance hospital with Brighton level 1 intussusception were eligible for enrollment. We collected information about each child's vaccination status and used the self-controlled case series method to calculate the relative incidence of intussusception 1-7 days, 8-21 days, and 1-21 days following each dose of vaccine and derived confidence intervals with bootstrapping. Of the 585 children meeting the analytic criteria, the median age at intussusception symptom onset was 24 weeks (IQR: 19-29). Overall, 494 (84 %) children received the first Rotarix dose and 398 (68 %) received the second dose. There was no increased intussusception risk during any of the risk periods following the first (1-7 days: 1.01 (95 %CI: 0.39, 2.60); 8-21 days: 1.37 (95 %CI: 0.81, 2.32); 1-21 days: 1.28 (95 %CI: 0.78, 2.11)) or second (1-7 days: 0.81 (95 %CI: 0.42, 1.54); 8-21 days: 0.77 (95 %CI: 0.53, 1.16); 1-21 days: 0.78 (95 %CI: 0.53, 1.16)) rotavirus vaccine dose. Our findings are consistent with other data showing no increased intussusception risk with rotavirus vaccination in low-income countries and add to the growing body of evidence demonstrating safety of rotavirus vaccines.

Assessment of pediatric surgical needs, health-seeking behaviors, and health systems in a rural district of Pakistan.

Surgical conditions are responsible for up to 15% of total Disability-Adjusted Life Years (DALY) lost globally. Approximately 4.8 billion people have no access to surgical care and this studies aim is to assess the surgical disease burden in children under the age of five years. We used Surgeons OverSeas Assessment of Surgical Need (SOSAS) and Pediatric Personnel, Infrastructure, Procedures, Equipment, and Supplies (PediPIPES) survey tools in Tando Mohammad Khan (TMK). A set of photographs of lesions were also taken for review by experts. All the data was recorded electronically via an android application. The current surgical need was defined as the caregiver's reported surgical problems in their children and the unmet surgical need was defined as a surgical problem for which the respondent did not access care. Descriptive analysis was performed. Information of 6,371 children was collected. The study identified 1,794 children with 3,072 surgical lesions. Categorization of the lesions by the six body regions suggested that head and neck accounted for the greatest number of lesions (55.2%) and the most significant unmet surgical need (16.6%). The chest region had the least unmet surgical need of 5.9%. A large percentage of the lesions were managed at a health care facility, but the treatment essentially consisted of mainly medical management (87%), and surgical treatment was provided for only 11% of lesions. The health facility assessment suggested that trained personnel including surgeons, anesthetic, or trained nurses were only available at one hospital. Basic procedures such as suturing and wound debridement were only performed frequently. This study suggests a high rate of unmet surgical need and a paucity of trained health staff and resources in this rural setting of Pakistan. The government needs to make policies and ensure funding so that proper trained staff and supplies can be ensured at district level.

Incidence of typhoid and paratyphoid fever in Bangladesh, Nepal, and Pakistan: results of the Surveillance for Enteric Fever in Asia Project.

BACKGROUND: Precise enteric fever disease burden data are needed to inform prevention and control measures, including the use of newly available typhoid vaccines. We established the Surveillance for Enteric Fever in Asia Project (SEAP) to inform these strategies. METHODS: From September, 2016, to September, 2019, we conducted prospective clinical surveillance for Salmonella enterica serotype Typhi (S Typhi) and Paratyphi (S Paratyphi) A, B, and C at health facilities in predetermined catchment areas in Dhaka, Bangladesh; Kathmandu and Kavrepalanchok, Nepal; and Karachi, Pakistan. Patients eligible for inclusion were outpatients with 3 or more consecutive days of fever in the last 7 days; inpatients with suspected or confirmed enteric fever; patients with blood culture-confirmed enteric fever from the hospital laboratories not captured by inpatient or outpatient enrolment and cases from the laboratory network; and patients with non-traumatic ileal perforation under surgical care. We used a hybrid surveillance model, pairing facility-based blood culture surveillance with community surveys of health-care use. Blood cultures were performed for enrolled patients. We calculated overall and age-specific typhoid and paratyphoid incidence estimates for each study site. Adjusted estimates accounted for the sensitivity of blood culture, the proportion of eligible individuals who consented and provided blood, the probability of care-seeking at a study facility, and the influence of wealth and education on care-seeking. We additionally calculated incidence of hospitalisation due to typhoid and paratyphoid. FINDINGS: A total of 34 747 patients were enrolled across 23 facilitates (six tertiary hospitals, surgical wards of two additional hospitals, and 15 laboratory network sites) during the study period. Of the 34 303 blood cultures performed on enrolled patients, 8705 (26%) were positive for typhoidal Salmonella. Adjusted incidence rates of enteric fever considered patients in the six tertiary hospitals. Adjusted incidence of S Typhi, expressed per 100 000 person-years, was 913 (95% CI 765-1095) in Dhaka. In Nepal, the adjusted typhoid incidence rates were 330 (230-480) in Kathmandu and 268 (202-362) in Kavrepalanchok. In Pakistan, the adjusted incidence rates per hospital site were 176 (144-216) and 103 (85-126). The adjusted incidence rates of paratyphoid (of which all included cases were due to S Paratyphi A) were 128 (107-154) in Bangladesh, 46 (34-62) and 81 (56-118) in the Nepal sites, and 23 (19-29) and 1 (1-1) in the Pakistan sites. Adjusted incidence of hospitalisation was high across sites, and overall, 2804 (32%) of 8705 patients with blood culture-confirmed enteric fever were hospitalised. INTERPRETATION: Across diverse communities in three south Asian countries, adjusted incidence exceeded the threshold for "high burden" of enteric fever (100 per 100 000 person-years). Incidence was highest among children, although age patterns differed across sites. The substantial disease burden identified highlights the need for control measures, including improvements to water and sanitation infrastructure and the implementation of typhoid vaccines. FUNDING: Bill & Melinda Gates Foundation.

Determination of reference interval (RI) of spot urinary oxalate to creatinine ratio in children of pakistani origin under six years of age: A cross-sectional study.

BACKGROUND: The gold standard screening method of hyperoxaluria in children is using 24-hour urine collection. Urine collection may be cumbersome and challenging for children. Reference intervals (RI) of oxalate for the Pakistani population are not readily available. Therefore we aimed to determine the oxalate to creatinine ratio (Ox: Cr) for Pakistani children <6 years of age. MATERIALS AND METHODS: A cross-sectional study was conducted at Aga Khan University from June 2018 to October 2019. Random urine samples from apparently healthy children < 6 years were collected and stored at -30°C until analysis after adding 6M HCl. Oxalate was measured on Micro lab 300 using a kit based on oxalate oxidase principle, while creatinine was measured by kinetic Jaffe reaction. Data was analyzed by EP evaluator and SPSS 23. Ox: Cr ratio was calculated and reported with 90% confidence interval (CI) and interquartile range (IQR). RESULTS: The mean age of study subjects (n=120) was 29 ±22.3 months with an M: F ratio of 1:1. Children of various ethnicities were included from all over Karachi. The majority of the subjects were Urdu speaking (37.5%). Median Ox: Cr was 0.13(0.10). No significant difference was noted in the median Ox: Cr ratio between various ethnicities (p>0.05). It was significantly different in group I to V which was 0.25 (IQR: 0.06), 0.19 (IQR: 0.11), 0.15 (IQR: 0.04), 0.11 (IQR: 0.06) and 0.08 (IQR: 0.04) respectively (pvalue <0.001). CONCLUSION: The established RIs of Ox: Cr ratio was 0.05-0.34 (90% CI). Ox: Cr ratio showed a declining trend with age. Large scale reference interval studies are encouraged, taking diet and age into consideration.

Elective Tracheostomy in Critically Ill Children: A 10-Year Single-Center Experience From a Lower-Middle Income Country.

Objective Tracheostomy is a commonly performed procedure amongst critically ill patients, especially in cases of prolonged mechanical ventilation (PMV). This study aimed to describe the indications, clinical characteristics, and outcomes of elective pediatric tracheostomies in critically ill children at our center. Methods A retrospective review of medical records of children who underwent elective tracheostomies in our pediatric intensive care unit (PICU) was conducted from January 2009 to June 2018. Data were extracted based on demographics, indications of tracheostomy, and patient outcomes. Results were reported as mean with standard deviation and as frequencies with percentage. Results Of the 3,200 patients admitted to the PICU during the study period, 1,130 were intubated. A total of 48 (4.2% of 1,130) children underwent an elective tracheostomy. 30/48 (62.5%) children had an early tracheostomy. 34/48 (71%) patients were males. Approximately 25% of our patients undergoing a tracheostomy had an underlying neurological condition as the primary diagnosis, followed by respiratory conditions (23%). The most common indications for elective tracheostomy were PMV (>7 days) (n=24, 50%) and extubation failure (n=9, 18.7%). Early tracheostomy (<14 days) had better patient outcomes in terms of ventilator-free days (8.57±4.64 in early tracheostomy vs. 6.38±6.17 days in late tracheostomy, P=0.04). The sedation-free days and ICU-free days were also significantly increased in the early tracheostomy group than in the late tracheostomy group. The successful weaning and ICU discharge rate were significantly higher in the early tracheostomy group than in the late tracheostomy group (78.1% vs. 59.7%, P<0.05; and 69.2% vs. 49.5%, P<0.05, respectively). Ventilator-associated pneumonia was more common in the late tracheostomy group (n= 14, 77%), compared to early tracheostomy group (n=12, 40%) (P=0.03). Two patients expired from tracheostomy-related complications. Conclusion PMV was the most common indication for an elective tracheostomy. Early tracheostomy is associated with improved patient outcomes; therefore, a standardized approach toward mechanically ventilated children is recommended.

Approaches to the management of pediatric ovarian masses in the 21st century: Systematic review and meta-analysis.

BACKGROUND: Laparoscopy is increasingly being adopted for the treatment of ovarian pathologies in adults. However, its implementation for the management of pediatric ovarian masses varies and the evidence, to date, has not been comprehensively analyzed. This review aims to compare laparoscopic and open surgical management of pediatric ovarian masses. METHODS: We searched PubMed, Cochrane Library and Google Scholar from the year 2000 till April 2017. Studies selected for this included those on epidemiological trends of pediatric ovarian lesions, assessing outcomes of laparoscopic management and comparison of laparoscopic and open surgical techniques for pediatric ovarian masses. A meta-analysis comparing outcomes of both modalities was performed using standard methodology. RESULTS: A total of 44 studies met the inclusion criteria of which 15 were on histological types of ovarian lesions, 24 assessed laparoscopic management only and five compared laparoscopy with open surgery for pediatric ovarian masses. Nonneoplastic lesions were the most common ranging from 36.5% to 73.7%, with cystic lesions being the most prevalent. Neoplastic lesions ranged between 26.3% and 63.5%, with germ cell tumors being the most common, while malignancy ranged between 3.5% and 10.8%. Laparoscopic management was generally advocated for managing benign lesions with a cautious approach for suspicion of malignant lesions. In comparison to open surgery, laparoscopic surgery had shorter operating time (MD = -33.24 min, 95% CI = -34.29 to -32.19, p < 0.0001), less intraop bleeding (MD = - 61.46 ml, 95% CI = -62.69 to -60.24, p < 0.0001), and reduced length of hospital stay (MD = -2.78 days, 95% CI= -2.82 to -2.74, p<0.0001). Complication rates were equivocal between the two approaches. Spillage rates could not be assessed. CONCLUSION: Limited evidence suggests that laparoscopic approach to presumptively benign ovarian masses have better outcomes when compared to open surgery with regards to operating time, blood loss and hospital stay. However, complication rates were similar between the two approaches. Studies with rigorous scientific methods are needed for a definitive recommendation, especially in resource limiting settings. However malignant lesions should still be managed with an open surgical approach to avoid upstaging of disease status. LEVEL OF EVIDENCE: II.

Intussusception among children less than 2years of age: Findings from pre-vaccine introduction surveillance in Pakistan.

BACKGROUND: Rotavirus vaccination introduction in routine immunization is under consideration in Pakistan. Data on the baseline epidemiology of intussusception will inform surveillance strategies for intussusception after rotavirus vaccine introduction in Pakistan. We describe the epidemiology of intussusception-associated hospitalizations among children <2years of age in Karachi, Pakistan. METHODS: We conducted a retrospective chart review for July 01, 2012 through June 30, 2015 at the National Institute of Child Health (NICH) and Aga Khan University Hospital (AKUH) Karachi. At AKUH, the International Classification of Disease, ninth revision, code 560.0 for intussusception was used to retrieve intussusception case records. At NICH, daily Operation Theater, Emergency Room, and surgical daycare log sheets and surgical ward census sheets were used to identify cases. Records of children who fulfilled eligibility criteria and the Brighton Collaboration level one case definition of intussusception were selected for data analysis. We used structured case report forms to extract data for the descriptive analysis. RESULTS: We identified 158 cases of confirmed intussusception; 30 cases (19%) were from AKUH. More than half (53%) of the cases occurred in children aged 6-12months, followed by 35% among those aged <6months. Two-thirds (106/158) of the cases were male. The most common presenting complaints were vomiting and bloody stool. At NICH, almost all (93%) were managed surgically, while at AKUH, ∼57% of the cases were managed with enemas. Three deaths occurred, all from NICH. Cases occurred without any seasonality. At NICH, 4% (128/3618) of surgical admissions among children aged <2years were attributed to intussusception, while that for AKUH was 2% (30/1702). CONCLUSION: In this chart review, intussusception predominantly affected children 0-6months of age and occurred more commonly in males. This information on the baseline epidemiology of intussusception will inform post-vaccine introduction adverse event monitoring related to intussusception in Pakistan.

Primary hyperoxaluria in populations of Pakistan origin: results from a literature review and two major registries.

Primary hyperoxalurias (PH) are devastating, autosomal recessive diseases causing renal stones. Undifferentiated hyperoxaluria is seen in up to 43% of Pakistani paediatric stone patients. High rates of consanguinity in Pakistan suggest significant local prevalence. There is no detailed information regarding number of cases, clinical features, and genetics in Pakistan-origin (P-o) patients. We reviewed available information on P-o PH patients recorded in the literature as well as from two major PH registries (the Rare Kidney Stone Consortium PH Registry (RKSCPHR) and the OxalEurope PH Registry (OxER); and the Aga Khan University Hospital in Pakistan. After excluding overlaps, we noted 217 P-o PH subjects (42 in OxER and 4 in RKSCPHR). Presentations were protean. Details of mutations were available for 94 patients of 201 who had genetic analyses. Unique mutations were noted. Mutation [c.508G>A (p. Gly170Arg)] (present in up to 25% in the West) was reported in only one case. In one series, only 30% had mutations on exons 1,4,7 of AGXT. Of 42 P-o patients in OxER, 52.4% were PH1, 45.2% PH2, and 2.4% PH3. Of concern is that diagnosis was made after renal transplant rejection (four cases) and on bone-marrow aspiration (in five). Lack of consideration of PH as a diagnosis, late diagnosis, and loss of transplanted kidneys mandates that PH be searched for diligently. Mutation analysis will need to extend to all exons and include PH 1,2,3. There is a need to spread awareness and identify patients through a scoring or screening system that alerts physicians to consider a diagnosis of PH.