Adaptation of a standardized lifestyle intervention to maximize health outcomes in adolescent metabolic and bariatric surgery patients.

BACKGROUND: Metabolic and bariatric surgery (MBS) is safe and efficacious in treating adolescents with severe obesity. Behavioral/lifestyle programs can support successful preparation for surgery and post-MBS weight loss, but no standardized lifestyle intervention exists for adolescents. Here we describe the process of developing and adapting the Diabetes Prevention Program Group Lifestyle Balance (DPP/GLB) curriculum to support adolescents pre- and post-MBS. METHODS: We collected both qualitative and quantitative data from a diverse group of adolescents (N = 19, mean age 15.2 years, range 13-17, 76% female, 42% non-Hispanic Black, 41% Hispanic, 17% other). Additionally, we included data from 13 parents, all of whom were mothers. These participants were recruited from an adolescent MBS program at Children's Health System of Texas. In an online survey, we asked participants to rank their preferences and interests in DPP/GLB content topics. We complemented these results with in-depth interviews from a subset of 10 participants. This qualitative data triangulation informed the development of the TeenLYFT lifestyle intervention program, designed to support adolescents who were completing MBS and described here. This program was adapted from adolescent and parent DPP/GLB content preferences, incorporating the social cognitive model (SCM) and the socioecological model (SEM) constructs to better cater to the needs of adolescent MBS patients. RESULTS: Adolescents' top 3 ranked areas of content were: (1) steps to adopt better eating habits and healthier foods; (2) healthy ways to cope with stress; and (3) steps to stay motivated and manage self-defeating thoughts. Nearly all adolescent participants preferred online delivery of content (versus in-person). Mothers chose similar topics with the addition of information on eating healthy outside the home. Key themes from the adolescent qualitative interviews included familial support, body image and self-confidence, and comorbidities as key motivating factors in moving forward with MBS. CONCLUSIONS: The feedback provided by both adolescents and parents informed the development of TeenLYFT, an online support intervention for adolescent MBS candidates. The adapted program may reinforce healthy behaviors and by involving parents, help create a supportive environment, increasing the likelihood of sustained behavior change. Understanding adolescent/parent needs to support weight management may also help healthcare providers improve long-term health outcomes for this patient population.

Disparity Between United States Adolescent Class II and III Obesity Trends and Bariatric Surgery Utilization, 2015-2018.

OBJECTIVES: Class II (120% > body mass index [BMI] < 140% of the 95th percentile for age and sex) and Class III (BMI >140% of the 95th percentile for age and sex) obesity are the fastest growing subcategories of obesity in the United States pediatric population. Metabolic and bariatric surgery (MBS) is a safe and effective treatment option for with class II/III obesity. The primary objectives of this analysis were to determine the (1) current US MBS utilization rates in those with class II/III obesity and (2) utilization rates and 30-day postoperative outcomes. BACKGROUND: The 2015 to 2018 National Health and Nutrition Examination Survey cross-sectional data (N = 19,225) generated US with class II/III obesity prevalence estimates. The 2015 to 2018 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) longitudinal (30 days) cohort data were used to compare adolescent and adult (N = 748,622) postoperative outcomes and to calculate utilization rates. METHODS: The 2015 to 2018 youth and adult MBS utilization rates were calculated using MBSAQIP data (numerator) and National Health and Nutrition Examination Survey data (denominator). Two-sample tests of proportions were performed to compare the MBS utilization rates by age, ethnicity, and sex and expressed per 1000. RESULTS: Mean age of the analytical MBSAQIP sample was 17.9 (1.15) years in youth (n = 3846) and 45.1 (11.5) in adults (N = 744,776), majority female (77.4%, 80.7%, respectively) and non-Hispanic White (68.5%, 59.4%, respectively). The overall 2015 to 2018 MBS utilization rate for youth was 1.81 per 1000 and 5.56 per 1000 for adults ( P < 0.001). Adult patients had slightly higher percentage (4.2%) of hospital readmissions compared to youth (3.4%, P = 0.01) but there were no other post-MBS complication differences. From 2015 to 2018 the US prevalence of youth with class II/III obesity increased in Hispanics and non-Hispanic Blacks (P trend < 0.001), but among youth who did complete MBS non-Hispanic Whites had higher rates of utilization (45.8%) compared to Hispanics (22.7%) and non-Hispanic blacks 14.2% (P = 0.006). CONCLUSIONS: MBS is an underutilized obesity treatment tool for both youth and adults, and among ethnic minority groups in particular.

Safety and efficacy of Empagliflozin in Pakistani Muslim patients with type 2 diabetes (SAFE-PAK); a randomized clinical trial.

BACKGROUND: Sodium-Glucose-Co-Transporter 2 (SGLT2) inhibitor (Empagliflozin) is an effective drug in controlling blood glucose through predominantly glycosuria. Glycosuria increases the risk of genitourinary infections in diabetes. This study was aimed to establish the safety and efficacy of Empagliflozin (Group-A) versus standard care (Group-B) in Pakistani Muslim individuals with type 2 diabetes. METHODS: A multicenter, randomized clinical trial was conducted in five cities across Pakistan from July 2019 to August 2020. Patients of both genders aged 18-75 years, body mass index (BMI) ≤ 45 kg/m2, glycosylated hemoglobin (HbA1c) 7-10% (53 mmol/mol to 86 mmol/mol) and treatment-naive to Empagliflozin were included. Treatment was given for 24 weeks, and allocation was done through randomization. RESULTS: Out of 745 screened patients, 333 met the eligibility criteria, and a total of 244 (73.3%) patients were enrolled. More hypoglycemic events were reported in the standard care group, whereas positive urine culture, fungal infection, dehydration, and hypotension occurrence were comparable between the two groups. The 6 months mean HbA1c reduction was significant in both groups; (Group-A: 0.91 ± 0.15; p < 0.001 vs. Group-B2: 0.79 ± 0.14; p < 0.001). Efficacy comparison at 6 months revealed a significant reduction in weight and systolic blood pressure (SBP) in Group A only (Group-A: 1.4 ± 0.4 kg; p < 0.002 vs. Group-B: 0.01 ± 0.5 kg; p < 1.00), (Group-A: 5.1 ± 1.7 mmHg; p < 0.012 vs. Group-B: 2.3 ± 1.7 mmHg; p < 0.526). CONCLUSIONS: Empagliflozin was a safe drug compared to standard care in Pakistani Muslim patients with diabetes. It was as effective as standard care in the clinical setting but achieved glycemic control by reducing weight and SBP in type 2 diabetes patients. TRIAL REGISTRATION: This study was registered in the NIH US National Library of Medicine clinical trials registry at Clinicaltrials.gov with the registration number: NCT04665284 on 11/12/2020.

Is metformin use associated with a reduced risk of oesophageal cancer? A systematic review and meta-analysis.

OBJECTIVES: Studies on the association between metformin use and the risk of oesophageal cancer (OC) have generated controversial findings. This updated meta-analysis was conducted to reassess the effects of metformin on OC. METHODS: A comprehensive search strategy was conducted to select relevant studies from origination to February 2021. Heterogeneity was evaluated through the Q test and I2 statistics. HRs and 95% CIs were pooled through either random-effect or fixed-effect models. Meta-regression, subgroup analyses, sensitivity analysis and publication bias diagnosis were also performed. RESULTS: Seven studies with 5 426 343 subjects were included. Metformin use was associated with reduced risk of OC (HR=0.69, 95% CI 0.54 to 0.87, p<0.001). Sensitivity analysis suggested that the results were relatively stable. CONCLUSION: Metformin is associated with a reduced risk of OC. More well-designed studies are still needed to further elaborate on these associations. PROSPERO REGISTRATION NUMBER: CRD42021237127.

Postpartum Hypernatremia with Extrapontine Rhabdomyelinolysis: A Case Report.

Hypernatremia (serum sodium>160 meq/L) present with diverse neurological manifestations, ranging from flaccid paralysis to impaired cognition, encephalopathy, and even deep coma. Osmotic demyelination refers to changes in brain cells because of an acute change in plasma osmolality. It is further divided into two types, i.e., central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM). Patients with EPM, besides spasticity, may also present with other movement disorders such as catatonia, parkinsonism, and dystonia. We present a case of a postpartum woman bought to the emergency department by her relatives in an unconscious state. In view of poor sensorium (Glasgow coma scale < 7), she was intubated and received mechanical ventilatory support. On admission, computed tomography ofthebrain was normal, and the patient was transferred to the intensive care unit (ICU) for further management. The preliminary work-up in the ICU showed hypernatremia (serum sodium of 182 mEq/L) with hyper-osmolality (359 mOsm/kgH2O). She was managed as per the ICU protocol for hypernatremia. During her ICU stay, her sensorium improved, but she developed flaccid paralysis and was quadriplegic. Thus, a tracheostomy was performed, and she was weaned from the ventilator. After ventilator weaning, she was transferred to the ward for further rehabilitation. During rehabilitation, the patient was able to sit and takefoodorally.To date, only a few cases are reported in postpartum women with acute severe hypernatremia caused by high-grade fever and loss of body fluids leading to extra-pontine demyelination and flaccid paralysis. This case highlightsthat prompt recognition and appropriate intervention can improve the outcomes in these patients.

Asymptomatic urinary tract infections and associated risk factors in Pakistani Muslim type 2 diabetic patients.

BACKGROUND: One of the leading long-term complications of type 2 diabetes mellitus (T2DM) includes renal dysfunction and urinary tract infections (UTI) which are considered to be prevalent in uncontrolled diabetes. Moreover, physiological factors like age, gender, duration of diabetes, other diabetic complications like neuropathy, autonomic neuropathy and glycosuria are also considered as predisposing factors for increased prevalence of UTI in diabetes which can be symptomatic or asymptomatic. METHODS: This was a cross-sectional, multi-centre study including diabetic patients from 12 clinical sites spread across major cities of Pakistan. The inclusion criteria were adult Pakistani population of age between 18 to 75 years both genders and suffering from T2DM irrespective of duration. A detailed clinical history of the past 3 months was recorded and, biochemical investigations of blood samples were conducted. Urine culture analysis performed identified the type of pathogen present and was done only for asymptomatic patients. RESULTS: A total of 745 type 2 diabetic patients were initially screened, out of 545 patients considered for final analysis 501 (91.92%) were negative and the rest 44 (8.08%) had positive urine culture. Female gender had a significantly higher proportion of positive urine culture (77.27%, p-value< 0.001). Body mass index and mean age had insignificant distribution among the two groups of positive and negative urine culture, with age 40-59 years having higher proportion (70.45%) in the positive group. Escherichia coli was detected in most of the positive samples (52.3%). All bacterial samples were found resistant to Ciprofloxacin. CONCLUSION: Diabetic Pakistani muslim female patients are identified to be at high risk of suffering from asymptomatic UTI and age more than 40 years is an important risk factor. Escherichia coli was the most common causative organism among people living in this geographical area.

Longitudinal Outcomes in Adolescents After Referral for Metabolic and Bariatric Surgery.

BACKGROUND: Metabolic and bariatric surgery (MBS) can be a well tolerated and effective treatment option for severe obesity in adolescents. We compared outcomes for adolescents that did and did not proceed to surgery. METHODS: A single-center longitudinal study (2015-2020). Patients were identified as LSG if they completed laparoscopic sleeve gastrectomy within 6 months of initial visit and NoLSG if they did not. Chi-square, Fisher exact, nonparametric Kruskal-Wallis tests, and Linear Mixed Models (LMM) were used to compare outcomes over 2 years. RESULTS: Three hundred fifty-two adolescents were referred with a mean age of 15.6 ±â€Š1.4, 69% girls, 38% Hispanic, and 78% had noncommercial insurance. The median baseline weight was 135 kg and body mass index (BMI) was 48 kg/m2; 42% had a BMI >50. Seventy-nine (22%) underwent LSG whereas 273 (78%) did not complete MBS primarily because of lack of interest. LSG patients had 21% total weight loss and 22% total BMI loss at 24 months whereas NoLSG patients had 4% total weight gain and 3% BMI gain (P < 0.01). Obesity-associated conditions improved in the LSG group (P < 0.01). Follow-up in both groups was poor (≤30% at 24 months). Patients with public insurance and those with BMI from 50 to 59.9 kg/m2 were high performing LSG patients. CONCLUSIONS: A minority (22%) of adolescents referred for MBS proceeded to surgery, despite its demonstrated efficacy and safety in adolescence. Those that did not undergo surgery continued to gain weight. Further research is needed to understand patient preferences or concerns related to MBS utilization during adolescence.

Chronic Inflammatory Placental Lesions Correlate With Bronchopulmonary Dysplasia Severity in Extremely Preterm Infants.

OBJECTIVE: Correlation of BPD with placental pathology is important for clarification of the multifactorial pathogenesis of BPD; however, previous reports have yielded varying results. We report placental findings in no/mild BPD compared to moderate/severe BPD, and with and without pulmonary hypertension (PH). METHODS: Eligible infants were 230/7-276/7 weeks gestational age. BPD was defined by the need for oxygen at ≥28 days with severity based on need for respiratory support at ≥36 weeks. Acute and chronic inflammatory placental lesions and lesions of maternal and fetal vascular malperfusion were examined. RESULTS: Of 246 eligible infants, 146 (59%) developed moderate/severe BPD. Thirty-four (23%) infants developed PH, all but 1 being in the moderate/severe BPD group. Chronic deciduitis (32% vs 16%, P = .003), chronic chorioamnionitis (23% vs 12%, P = .014), and ≥ 2 chronic inflammatory lesions (13% vs 3%, P = .007) were more frequent in the moderate/severe BPD group. Development of PH was associated with placental villous lesions of maternal vascular malperfusion (30% vs 15%, P = .047). CONCLUSIONS: The association of chronic inflammatory placental lesions with BPD severity has not been previously reported. This supports the injury responsible for BPD as beginning before birth in some neonates, possibly related to cytokines associated with these chronic inflammatory lesions.

Disorders of placental villous maturation are present in one-third of cases with spontaneous preterm labor.

OBJECTIVES: Spontaneous preterm labor is an obstetrical syndrome accounting for approximately 65-70% of preterm births, the latter being the most frequent cause of neonatal death and the second most frequent cause of death in children less than five years of age worldwide. The purpose of this study was to determine and compare to uncomplicated pregnancies (1) the frequency of placental disorders of villous maturation in spontaneous preterm labor; (2) the frequency of other placental morphologic characteristics associated with the preterm labor syndrome; and (3) the distribution of these lesions according to gestational age at delivery and their severity. METHODS: A case-control study of singleton pregnant women was conducted that included (1) uncomplicated pregnancies (controls, n=944) and (2) pregnancies with spontaneous preterm labor (cases, n=438). All placentas underwent histopathologic examination. Patients with chronic maternal diseases (e.g., chronic hypertension, diabetes mellitus, renal disease, thyroid disease, asthma, autoimmune disease, and coagulopathies), fetal malformations, chromosomal abnormalities, multifetal gestation, preeclampsia, eclampsia, preterm prelabor rupture of the fetal membranes, gestational hypertension, gestational diabetes mellitus, and HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome were excluded from the study. RESULTS: Compared to the controls, the most prevalent placental lesions among the cases were the disorders of villous maturation (31.8% [106/333] including delayed villous maturation 18.6% [62/333] vs. 1.4% [6/442], q<0.0001, prevalence ratio 13.7; and accelerated villous maturation 13.2% [44/333] vs. 0% [0/442], q<0.001). Other lesions in decreasing order of prevalence included hypercapillarized villi (15.6% [68/435] vs. 3.5% [33/938], q<0.001, prevalence ratio 4.4); nucleated red blood cells (1.1% [5/437] vs. 0% [0/938], q<0.01); chronic inflammatory lesions (47.9% [210/438] vs. 29.9% [282/944], q<0.0001, prevalence ratio 1.6); fetal inflammatory response (30.1% [132/438] vs. 23.2% [219/944], q<0.05, prevalence ratio 1.3); maternal inflammatory response (45.5% [195/438] vs. 36.1% [341/944], q<0.01, prevalence ratio 1.2); and maternal vascular malperfusion (44.5% [195/438] vs. 35.7% [337/944], q<0.01, prevalence ratio 1.2). Accelerated villous maturation did not show gestational age-dependent association with any other placental lesion while delayed villous maturation showed a gestational age-dependent association with acute placental inflammation (q-value=0.005). CONCLUSIONS: Disorders of villous maturation are present in nearly one-third of the cases of spontaneous preterm labor.

Delayed Diagnosis of Injury in Pediatric Trauma Patients at a Level I Trauma Center.

BACKGROUND: Trauma care per Advanced Trauma Life Support addresses immediate threats to life. Occasionally, delays in injury diagnosis occur. Delayed diagnosis of injury (DDI) is a common quality indicator in trauma care, and pediatric DDI data are sparse. OBJECTIVE: Our aim was to describe the DDI rate in a severely injured pediatric trauma population and identify any factors associated with DDI in the pediatric population. METHODS: A prospective cohort of trauma activations in 0- to 16-year-old patients admitted to a pediatric level I trauma center over 12 months with injuries prospectively recorded were followed during admission to identify DDI. RESULTS: A total of 170 trauma activations were enrolled. Twelve patients had type I DDI (7.1%), 15 patients had type II DDI (8.8%), and 5 patients had both type I and type II DDI (2.9%). DDI patients had twice as many injuries and higher Injury Severity Scores (ISS) as non-DDI patients. DDI patients were more likely to require intensive care unit (ICU) admission, longer hospital stay, and ventilator support. Controlling for age and ISS in multivariate analysis, the number of injuries found and requiring a ventilator were significantly associated with DDI. CONCLUSIONS: This prospective study found a type I DDI rate of 7.1% and a type II DDI rate of 8.8% in the pediatric population. DDI patients had a greater number of injuries, higher ISS, higher rate of ICU admission, and were more likely to require mechanical ventilation. This study adds prospective data to the pediatric DDI literature, increases provider awareness of pediatric DDI, and lays the foundation for future study and quality improvement.

Classification and reporting guidelines for the pathology diagnosis of placenta accreta spectrum (PAS) disorders: recommendations from an expert panel.

The terminology and diagnostic criteria presently used by pathologists to report invasive placentation is inconsistent and does not reflect current knowledge of the pathogenesis of the disease or the needs of the clinical care team. A consensus panel was convened to recommend terminology and reporting elements unified across the spectrum of PAS specimens (i.e., delivered placenta, total or partial hysterectomy with or without extrauterine tissues, curetting for retained products of conception). The proposed nomenclature under the umbrella diagnosis of placenta accreta spectrum (PAS) replaces the traditional categorical terminology (placenta accreta, increta, percreta) with a descriptive grading system that parallels the guidelines endorsed by the International Federation of Gynaecology and Obstetrics (FIGO). In addition, the nomenclature for hysterectomy specimens is separated from that for delivered placentas. The goal for each element in the system of nomenclature was to provide diagnostic criteria and guidelines for expected use in clinical practice.

Physician-Estimated Depth as a Screening Tool for Computed Tomography Evaluation of Pectus Excavatum.

BACKGROUND: Pectus excavatum (PE) is the most common congenital chest wall anomaly with a reported incidence of 1/300 to 1/400 live births and a male predominance. Preoperative evaluation of defect severity typically requires a calculation of the Haller index (HI) and/or correction index (CI) using computed tomography (CT) or x-rays. The purpose of this study was to determine whether physician-estimated depth (PED), a bedside screening tool, could be used to identify a subset of pediatric patients in whom CT was unnecessary. METHODS: After institutional review board approval (IRB #032018-091), we retrospectively reviewed all patients with a diagnosis of PE between 2009 and 2018 at our academic pediatric center. Demographic information including age, sex, and body mass index were abstracted. Imaging was reviewed to obtain HI and CI and to retrospectively calculate PED. The PED is calculated at the bedside by measuring the depth of the pectus at the site of greatest depression relative to a horizontal surface laid across the deformity. For this retrospective study, we calculated the CT-derived PED by measuring the depth from the horizontal on the respective CT images. Patients without imaging studies and patients with pectus carinatum, arcuatum, or mixed deformities were excluded from this study. RESULTS: A total of 94 patients met inclusion criteria. Of these, 82% were male, with a median age of 15 y. Patients were further subdivided by BMI, with 46% of patients having a BMI of <18.5 kg/m2 (i.e., underweight), whereas 54% of patients had a BMI of ≥18.5 kg/m2. Using a threshold PED of 2 cm, patients with a BMI of <18.5 kg/m2 had correct classification rates of 93% and 95% using PED relative to HI and CI, respectively. Patients with a BMI of ≥18.5 kg/m2 had correct classification rates of 80% and 88% using PED relative to HI and CI, respectively, at the same 2 cm threshold. CONCLUSIONS: PED is a viable screening tool for the preoperative evaluation of PE with a 2 cm threshold providing the combination of high sensitivity, specificity, and correct classification rates especially in underweight patients.

Predicting Morbidity and Mortality in Neonates Born With Gastroschisis.

BACKGROUND: Gastroschisis is an increasingly common congenital abdominal wall defect. Due to advances in neonatal critical care and early surgical management, mortality from gastroschisis and associated complications has decreased to less than 10% in most series. However, it has been recognized that the outcome of gastroschisis has a spectrum and that the disorder affects a heterogeneous cohort of neonates. The goal of this study is to predict morbidity and mortality in neonates with gastroschisis using clinically relevant variables. METHODS: A multicenter, retrospective observational study of neonates born with gastroschisis was conducted. Neonatal characteristics and outcomes were collected and compared. Prediction of morbidity and mortality was performed using multivariate clinical models. RESULTS: Five hundred and sixty-six neonates with gastroschisis were identified. Overall survival was 95%. Median hospital length of stay was 37 d. Sepsis was diagnosed in 107 neonates. Days on parenteral nutrition and mechanical ventilation were considerable with a median of 27 and 5 d, respectively. Complex gastroschisis (atresia, perforation, volvulus), preterm delivery (<37 wk), and very low birth weight (<1500 g) were associated with worse clinical outcomes including increased sepsis, short bowel syndrome, parenteral nutrition days, and length of stay. The composite metric of birth weight, Apgar score at 5 min, and complex gastroschisis was able to successfully predict mortality (area under the curve, 0.81). CONCLUSIONS: Clinical variables can be used in gastroschisis to distinguish those who will survive from nonsurvivors. Although these findings need to be validated in other large multicenter data sets, this prognostic score may aid practitioners in the identification and management of at-risk neonates.

Do Increased Intra-alveolar Squamous Cells at Autopsy Correlate With Acute Fetal Asphyxia?

It is a generally held concept that finding increased aspirated amniotic fluid squames at autopsy supports a diagnosis of acute fetal asphyxia, the massive aspiration of squames being an indicator of terminal gasping. To evaluate this concept, we identified autopsies on 15 third-trimester stillborns with clinical acute placental abruption (acute asphyxia); 13 also had thymic petechiae and none had severe acute thymic involution, findings also supporting acute asphyxia. Thirty third-trimester stillborns with findings supporting a subacute or chronic mode of death, including severe thymic involution and absence of thymic petechiae, comprised the comparison group. Intra-alveolar squames were scored as 0, no squames; 1+, scattered squames singly or in small groups; and 2+, squames in many alveoli, at least focally in compacted clusters. In all cases, the squames were patchily distributed, and none received a score of 0. In the abruption group, the intra-alveolar squames were scored as 1+ in 12 (80%) and as 2+ in 3 (20%) cases, while in the comparison group, the squames were scored as 1+ in 20 (67%) and 2+ in 10 (33%) cases (P = NS). There was also no difference in the quantification of intra-alveolar squames in term compared to preterm stillborns. In conclusion, quantification of intra-alveolar squames did not aid in separating an acute mode of death (acute asphyxia) from subacute or chronic modes of death.

Disorders of placental villous maturation in fetal death.

Objective The aims of this study were to ascertain the frequency of disorders of villous maturation in fetal death and to also delineate other placental histopathologic lesions in fetal death. Methods This was a retrospective observational cohort study of fetal deaths occurring among women between January 2004 and January 2016 at Hutzel Women's Hospital, Detroit, MI, USA. Cases comprised fetuses with death beyond 20 weeks' gestation. Fetal deaths with congenital anomalies and multiple gestations were excluded. Controls included pregnant women without medical/obstetrical complications and delivered singleton, term (37-42 weeks) neonate with 5-min Apgar score ≥7 and birthweight between the 10th and 90th percentiles. Results Ninety-two percent (132/143) of placentas with fetal death showed placental histologic lesions. Fetal deaths were associated with (1) higher frequency of disorders of villous maturation [44.0% (64/143) vs. 1.0% (4/405), P < 0.0001, prevalence ratio, 44.6; delayed villous maturation, 22% (31/143); accelerated villous maturation, 20% (28/143); and maturation arrest, 4% (5/143)]; (2) higher frequency of maternal vascular malperfusion lesions [75.5% (108/143) vs. 35.7% (337/944), P < 0.0001, prevalence ratio, 2.1] and fetal vascular malperfusion lesions [88.1% (126/143) vs. 19.7% (186/944), P < 0.0001, prevalence ratio, 4.5]; (3) higher frequency of placental histologic patterns suggestive of hypoxia [59.0% (85/143) vs. 9.3% (82/942), P < 0.0001, prevalence ratio, 6.8]; and (4) higher frequency of chronic inflammatory lesions [53.1% (76/143) vs. 29.9% (282/944), P < 0.001, prevalence ratio 1.8]. Conclusion This study demonstrates that placentas of women with fetal death were 44 times more likely to present disorders of villous maturation compared to placentas of those with normal pregnancy. This suggests that the burden of placental disorders of villous maturation lesions is substantial.

Diagnosis of Invasive Fungal Infection Among Pediatric Oncology Patients.

INTRODUCTION: The diagnosis of pulmonary invasive fungal infection (IFI) in the pediatric oncology patient is challenging. Consensus criteria developed in 2008 state that bronchioalveolar lavage (BAL) results cannot confirm this diagnosis. A video-assisted thoracoscopic biopsy (VATS-biopsy) of lungs has been increasingly used to assist in evaluating these children for IFI. Our goal was to evaluate the impact of BAL and VATS-biopsy results on the management of IFI among pediatric oncology patients. METHODS: A retrospective review of all oncology patients evaluated for IFI with VATS-biopsy and/or BAL over 9 years was carried out at a single free-standing children's hospital. The primary outcome was management changes in the use of antifungal therapy on the basis of diagnostic procedure, fungal culture results, lung imaging, and serological markers. RESULTS: A total of 102 patients underwent 122 diagnostic evaluations for IFI. Ninety-one workups included only BAL, 17 evaluations involved only VATS-biopsy, and 14 cases involved both BAL and VATS-biopsy. The diagnostic yield of VATS-biopsy (38.7%) was superior to that of BAL (27.6%). There was poor concordance between VATS-biopsy and BAL results in the 14 cases where both were performed. Upon workup completion, IFI was proven in 12 children, probable in 29, and possible in 52. The odds of continuing antifungals increased 3-fold for patients with probable IFI and 12.7 times for those with the proven disease. DISCUSSION: On the basis of the inferior diagnostic yield of BAL, we believe that VATS-biopsy may be a more useful diagnostic adjuvant in the diagnosis of IFI in the immunocompromised pediatric oncologic patient population.

Expert Opinion: Use of sodium glucose co-transporter type-2 inhibitors in South Asian population -The Pakistan perspective.

Sodium-glucose co-transporter type 2 inhibitors (SGLT 2- i)are increasingly being used in the management of type 2 diabetes mellitus (T2DM). With the novel insulinindependent glycosuric action, these agents help to attain glycaemic goals by lowering HbA1c and fasting blood glucose. In addition, these agents improve metabolic control in diabetes and ameliorate comorbidities like obesity and hyper tension. Beneficial effec ts on cardiovascular outcomes have been a key attraction for physicians. These agents are used alone or in combination with oral antidiabetic agents and insulin to attain glycaemic and metabolic targets. A major disadvantagewith these agents is the increased risk for genital andurinary infections. When used in appropriate settings, there is no additional increased risk of hypoglycaemia or volume depletion with these agents. Available evidence suggests good efficacy and safety of these agents in diabetes management. The easy and convenient oncedaily dosing should be customized according to patient needs and glycaemic profiles.

Cardiovascular disease risk factors in Pakistani population with newly diagnosed Type 2 diabetes mellitus: A cross-sectional study of selected family practitioner clinics in four provinces of Pakistan (CardiP Study).

OBJECTIVE: To explore cardiovascular risk factors in people with newly-diagnosed type 2 diabetes mellitus. METHODS: The cross-sectional, prospective, multicentre, study was conducted from June 2014 till July 2015 at family practice clinics in 27 cities across Pakistan, and comprised individuals aged 30-50 years diagnosed with type 2 diabetes mellitus within the preceding six months. Laboratory investigations were conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, and Aga Khan University Hospital, Karachi. The 10-year absolute risk of fatal or non-fatal coronary heart disease and stroke was calculated using the United Kingdom Prospective Diabetes Study Risk Engine version 2.0. Data were analysed using SPSS 19. RESULTS: Out of 888 subjects, 362(40.8%) were women and 526(59.2%) were men. The overall mean presenting age was 42.4}5.8 years. After stratification by age, those ≥40 years were significantly associated with higher glycated haemoglobin (p=0.02) and those ≤39 years were associated with higher levels of very low density lipoprotein (p=0.001) and triglyceride (p=0.006). The mean risk estimate for CHD was 9.7% (95% Confidence Interval (CI) 9.0- 10.1)), for fatal CHD 4.4% (95% CI 4.0-4.6), for stroke 1.5% (95% CI 1.2-1.7), and for fatal stroke 0.25% (95% CI 0.24- 0.26). CONCLUSIONS: There is a need for screening cardiovascular risk factors even in younger age groups of newlydiagnosed diabetes.

Hypoglycemia Prevention by Algorithm Design During Intravenous Insulin Infusion.

PURPOSE OF REVIEW: This review examines algorithm design features that may reduce risk for hypoglycemia while preserving glycemic control during intravenous insulin infusion. We focus principally upon algorithms in which the assignment of the insulin infusion rate (IR) depends upon maintenance rate of insulin infusion (MR) or a multiplier. RECENT FINDINGS: Design features that may mitigate risk for hypoglycemia include use of a mid-protocol bolus feature and establishment of a low BG threshold for temporary interruption of infusion. Computer-guided dosing may improve target attainment without exacerbating risk for hypoglycemia. Column assignment (MR) within a tabular user-interpreted algorithm or multiplier may be specified initially according to patient characteristics and medical condition with revision during treatment based on patient response. We hypothesize that a strictly increasing sigmoidal relationship between MR-dependent IR and BG may reduce risk for hypoglycemia, in comparison to a linear relationship between multiplier-dependent IR and BG. Guidelines are needed that curb excessive up-titration of MR and recommend periodic pre-emptive trials of MR reduction. Future research should foster development of recommendations for "protocol maxima" of IR appropriate to patient condition.

Management of nonparasitic splenic cysts in children.

BACKGROUND: The management of nonparasitic splenic cysts in children is unclear. Options include observation, cystectomy, partial or total splenectomy and percutaneous aspiration with and without sclerotherapy. The aim of this study is to assess the outcomes of these interventions at a children's hospital. MATERIALS AND METHODS: A retrospective review of patients aged <18 y with splenic cysts over 7 y was performed. Demographics, mode of intervention, and outcome data were collected. RESULTS: Forty-two patients were identified and their initial management was as follows: 32 patients were observed and 10 underwent intervention (four aspiration and sclerotherapy and six resection). Age (y) was higher for intervention patients than observation patients (P = 0.004), as was the cyst size (P < 0.001). Incidental finding was the most common presentation in observation patients (n = 30; 94%) and abdominal pain for intervention groups: aspiration and sclerotherapy (n = 3; 75%) and resection (n = 5; 83%). Two patients failed observation and required aspiration and sclerotherapy due to persistence of symptoms or size increase. Median number of aspiration with and without sclerotherapy interventions was three (range 1-5). All six patients had persistence, with two requiring surgical resection due to symptomatic persistence. Surgical procedures included laparoscopic cystectomy (n = 3), laparoscopic partial (n = 2) or complete splenectomy (n = 1), and/or open splenectomy (n = 2). One laparoscopic cystectomy patient had persistence but the other two had no follow-up imaging. Partial and total splenectomy patients had no recurrence and/or persistence. CONCLUSIONS: Observation is an appropriate management strategy for small asymptomatic splenic cysts. Aspiration with and without sclerotherapy and laparoscopic cystectomy are associated with higher rates of recurrence; thus, partial splenectomy may provide the best balance of recurrence and spleen preservation.