An Intensive Multidisciplinary Approach in Management of Extensive Nonuremic Calciphylaxis of the Bilateral Lower Extremities with Angioinvasive Fungus and Mold.

Management of infected wounds related to calciphylaxis poses a significant clinical challenge with high morbidity and mortality. Given no definitive management guidelines exist specific to nonuremic calciphylaxis, multiple modalities including sodium thiosulfate, antibiotics, hyperbaric oxygen therapy, and surgical debridement with wound care must be considered. When occurring over a large surface area, standard daily dressing changes are especially labor intensive, inefficient, and ineffective. Negative pressure wound therapy with instillation and dwell time offers broad wound coverage with ongoing therapeutic benefit. We present the case of a previously healthy 19-year-old woman who was transferred for tertiary level care of extensive nonuremic calciphylaxis wounds of the bilateral lower extremities complicated by angioinvasive coinfection with fungus and mold that was managed with a multidisciplinary approach of intensive medical management, aggressive surgical debridement, and negative pressure wound therapy with instillation of hypochlorous acid solution. Ultimately, she achieved full granulation and wound coverage with skin grafting. Large area, infected wounds related to nonuremic calciphylaxis can be successfully managed with multidisciplinary medical management, aggressive surgical debridement, and negative pressure wound therapy that can instill and dwell hypochlorous acid solution.

A Rabbit Model for Optimization of Amniotic Fluid Components in the EXTrauterine Environment for Newborn Development (EXTEND) System.

In this model article, we present a protocol for continuous amniotic fluid exchange in rabbits using a novel system to test the effects of growth factor-deficient, artificial amniotic fluid on bowel development. BACKGROUND: Ideally, the EXTrauterine Environment for Neonatal Development (EXTEND) will provide physiologic support to the extreme premature infant. An important component of that environment is the amniotic fluid. Thus, we developed an animal model to study the growth factors found within amniotic fluid and inform design of a synthetic fluid to optimize fetal development. METHODS: We designed a model of amniotic fluid exchange within the pregnant rabbit, continuously removing the natural fluid from around 2 fetuses per doe and replacing it with a physiologic electrolyte solution during the final 100 h of gestation. Two fetuses from the contralateral uterine horn were used as sham-operated controls. Thirty-eight fetuses were analyzed, 19 in each group. We analyzed the fetal growth and bowel development. RESULTS: Ultrasound after 100 h of exchange showed equivalent fluid volumes, p = 0.63. Cultures were negative for bacterial colonization. Final fluid protein concentrations were 11.6% that of control fluid (mean 1,451 ± 224.2 vs. 12,491 ± 849.2 µg/mL). There was no significant difference in fetal growth, with experimental weights 91.4% of control weights, p = 0.07. Fetal bowel weights (90.1%, p = 0.16) and lengths (94.2%, p = 0.49) were also not significantly less compared to controls. There was no significant difference in villous height or crypt depth measurements between the groups, and absorptive capacity of the bowel was not different between groups, p = 0.44. CONCLUSION: This animal model allows for manipulation of the components of amniotic fluid. Marked reduction of natural amniotic fluid proteins during gestation does not appear to significantly impair fetal growth or bowel development. Further work with this model will assess the importance of amniotic fluid components for normal development to inform design of a synthetic fluid for use during EXTEND.

The EXTrauterine Environment for Neonatal Development Supports Normal Intestinal Maturation and Development.

BACKGROUND AND AIMS: The Extra-Uterine Environment for Neonatal Development (EXTEND) aims to avoid the complications of prematurity, such as NEC. Our goal was to determine if bowel development occurs normally in EXTEND-supported lambs, with specific emphasis on markers of immaturity associated with NEC. METHODS: We compared terminal ileum from 17 pre-term lambs supported on EXTEND for 2- 4 weeks to bowel from age-matched fetal lambs that developed in utero. We evaluated morphology, markers of epithelial integrity and maturation, enteric nervous system structure, and bowel motility. RESULTS: EXTEND-supported lamb ileum had normal villus height, crypt depth, density of mucin-containing goblet cells, and enteric neuron density. Expression patterns for I-FABP, activated caspase-3 and EGFR were normal in bowel epithelium. Transmural resistance assessed in Ussing chambers was normal. Bowel motility was also normal as assessed by ex vivo organ bath and video imaging. However, Peyer's patch organization did not occur normally in EXTEND ileum, resulting in fewer circulating B cells in experimental animals. CONCLUSION: EXTEND supports normal ileal epithelial and enteric nervous system maturation in pre-term lambs. The classic morphologic changes and cellular expression profiles associated with NEC are not seen. However, immune development within the EXTEND supported lamb bowel does not progress normally.

Defining the Burden of Emergency General Surgery in Transplant Patients: A Nationwide Examination.

BACKGROUND: Transplant patients are at the risk of serious sequelae from medical and surgical intervention. The incidence and burden of emergency general surgery (EGS) in transplant patients are scarcely known. This study aims to identify predictors of outcomes in transplant patients with EGS needs. METHODS: The Nationwide Inpatient Sample (2007-2011) was queried for adult patients (aged ≥16 y) who underwent abdominal visceral transplantation. These were further queried for a secondary diagnosis of an American Association for the Surgery of Trauma-defined EGS condition. Outcome measures included mortality, complications, length of stay, and cost of care. Propensity scores were used to match patients across baseline characteristics. Multivariate analysis was used to further adjust propensity score quintiles and hospital-level characteristics. RESULTS: A total of 35,573 transplant patients were identified. Of these, 30% (n = 10,676) developed an EGS condition. Most common EGS conditions were resuscitation (7.7%), intestinal obstruction (7.3%), biliary conditions (3.9%), and hernias (3.2%). Patients with public insurance, those in the highest income quartile, and those treated at larger hospitals had a lower likelihood of developing an EGS condition (P < 0.05). Patients with an EGS condition had a ninefold higher likelihood of mortality and a threefold higher likelihood of developing complications (odds ratio [95% confidence interval (CI)]: 9.21 [1.80-10.89] and 3.17 [3.02-3.34], respectively). Transplant patients after EGS had a longer risk-adjusted length of stay and cost of index hospitalization (Absolute difference [95% CI]: 12.70 [12.14-13.26] and $57,797 [55,415-60,179], respectively]). CONCLUSIONS: Transplant patients fare poorly after developing an EGS condition. The results of this study will help in identifying at-risk patients and determining outcomes.

Impressions and attitudes of adult residents of Karachi towards a possible public health insurance scheme.

OBJECTIVE: To gauge the general population's knowledge and attitude towards a possible public health insurance scheme. METHODS: This descriptive, cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, from April to May 2015, and comprised permanent residents of the city. Convenience sampling was used. Data was collected via questionnaires. SPSS 22 was used for data analysis. RESULTS: There were 340 participants in the study with an overall mean age of 32.9±12.4 years. Besides, 159(46.8%) participants were aware of the concept of medical insurance while the correct definition was identified by 160(50.5%) respondents. Overall, 256(75.3%) participants were willing to join a theoretical public health insurance scheme. Of all the respondents, 107(31.5%) had faced a catastrophic event in the past and consequently were more willing to join. Of those unsure or not willing to join, 33(37.9%) respondents identified lack of trust in government programmes as the main reason for their choice. CONCLUSIONS: A large majority of adults had a favourable attitude towards the implementation of a possible public health insurance scheme.

Screening of subclinical hypothyroidism during gestational diabetes in Pakistani population.

OBJECTIVE: The increased prevalence of adverse effects of altered thyroid functions in pregnancy inspired us to study the frequency of subclinical hypothyroidism (SCH) and the relationship with glycaemic control and foetal weight in pregnant females with and without gestational diabetes mellitus (GDM) in Pakistani population. PATIENTS AND METHODS: Five hundred and eight pregnant females were enrolled and grouped as per the International Diabetes Association criteria into GDM (n = 208) and healthy control (n = 300). Random blood glucose (RBG), thyroid function tests, anthropometric analysis and foetal ultra sound scans were performed on all study subjects. Data were analysed using Mann-Whitney U test and Chi-square test wherever applicable. Spearman correlation and multiple regression analysis were performed. p values of <0.05 was considered significant. RESULTS: A total of 61.5% GDM subjects depicted SCH with normal circulating T4 and T3 versus 6.0% healthy controls (p-value < 0.001). Moreover, TSH remained independently associated with RBG (r = 0.109; p < 0.05), poor glycaemic control (r = 0.227; p < 0.001) and negatively associated with foetal growth (r = -0.206; p < 0.001). CONCLUSION: The detection of high TSH with normal T3 and T4 in females with GDM strongly emphasises the need of thyroid screening as a routine in all antenatal clinics.

Role of multifunctional Chemerin in obesity and preclinical diabetes.

BACKGROUND: "Chemerin" is a multifuntional peptide involved in lipid and glucose metabolism. Elevated levels of this peptide have been associated with insulin resistance and systemic inflammation. This study aims to identify whether Chemerin along with other inflammatory markers (TNFα and hsCRP) can discriminate subjects with subclinical diabetes. METHODOLOGY/FINDINGS: Fifty-two asymptomatic healthy volunteers and 22 chronic diabetics (T2DM) were enrolled in a cross sectional study design. They were subjected to a 75 g oral glucose tolerance test [OGTT (2-h glucose>200 mg/dL)] and were then classified as either newly diagnosed diabetics (NDM) (n=23) or healthy controls (n=29). Our results showed a higher Chemerin level in NDM (p<0.01; MWU) compared to controls and previously diagnosed DM. Using ROC analysis, Chemerin level in NDM and T2DM had AUC of 0.963 and 0.764 respectively, compared to healthy controls. We suggest that the cut off of 13.7 ng/ml of Chemerin can discriminate 73% of NDM subjects with impaired glucose level with 91% and 96% of sensitivity and specificity respectively. Elevated serum Chemerin in NDM group is a surrogate of impairment in glucose metabolism in obese individual. CONCLUSIONS: Chemerin along with other inflammatory biomarkers suggest an ongoing inflammatory process in a high risk obese group that indicates a pre-diabetic state.