Coagulopathy in the absence of overt DIC in postoperative neurosurgical patients is a strong predictor of poor outcome.

OBJECTIVES: To assess the prevalence of coagulopathy in postoperative neurosurgical patients and correlate it with the outcome. MATERIALS AND METHOD: This longitudinal study was conducted in a tertiary care hospital in the Department of Pathology and Neurosurgery. Ethical approval was taken from the Institutional Ethical Committee - Human Research. Seventy-two (72) participants were recruited within 48 hours of surgery after obtaining consent. Complete clinical and surgical details were recorded. A 6.5 mL venous sample was collected and dispensed in two separate vials. The EDTA sample was run within 2 hours of collection on an automated hematology analyzer to obtain complete blood counts, including platelet count. The citrated sample was run on a fully automated coagulometer to determine PT, APTT, plasma fibrinogen, FVIII assay, and D-dimer levels. Subjects with a DIC-ISTH score of 5 or more were excluded. Coagulopathy was defined as three or more coagulation parameters deranged in a patient. All patients were followed up for the outcome. The outcome was correlated with coagulopathy, and a p-value less than 0.05 was considered statistically significant. RESULTS: The study found that the number of hemostatic parameters deranged correlated with outcome (P < 0.001). The proportion of patients with coagulopathy was 32/72 (44.4%), while those without coagulopathy were 40/72 (55.6%). Of patients with coagulopathy, 87.5% (28/32) had an adverse outcome, while 12.5% (4/32) had a favorable outcome. The difference was found to be statistically significant (P < 0.001). CONCLUSIONS: Coagulopathy, defined as the derangement of three or more parameters, is a predictor of poor outcomes in postoperative neurosurgical patients. This timely recognition of coagulopathy can help triage patients requiring appropriate blood products, significantly reducing morbidity and mortality associated with postoperative neurosurgical patients.

Monocyte CD36 expression associates with atherosclerotic burden in diabetes mellitus.

BACKGROUND: By virtue of its role in oxidized low-density lipoprotein uptake and foam cell transformation, monocyte CD36 (mCD36) is a potential non-invasive tool to detect atherosclerosis (ATH) in patients of type 2 diabetes mellitus (DM). METHODS: Flowcytometric expression of mCD36 was evaluated with reference to ankle brachial index (ABI) in 70 patients of type 2 DM [40 with and 30 without coronary artery disease (CAD) respectively] and 30 age and gender matched normoglycemic controls (NGCs). RESULTS: DM patients had significantly higher mCD36 indices than NGCs (p < 0.001). The mCD36 expression was significantly higher in DM persons with CAD and those with poor glycemia control (glycosylated haemoglobin, HbA1c ≥ 7%) than their respective counterparts (p < 0.001 for both). Thirty subjects had compromised ABI (≤0.9); all were DM persons with CAD. ABI compromised subjects had consistently higher mCD36 indices than all other sub-groups (p < 0.001 for all comparisons). Notably, within the ABI-uncompromised group, mCD36 indices differed significantly and showed progressive increase from NGCs to diabetics without and with CAD respectively. CONCLUSIONS: mCD36 plays an important role in atherogenesis. With reference to ABI, mCD36 performed robustly as a marker of ATH. Furthermore, it could stratify subjects within the 'ABI-uncompromised group' commensurate with their conventional clinico-pathological ATH risk predisposition.

Plasma Fibrinogen and D-dimer in Children With Sepsis: A Single-Center Experience.

BACKGROUND & OBJECTIVE: In sepsis, enhanced fibrin formation, impaired fibrin degradation, and intravascular fibrin deposition lead to a prothrombotic state. The current study aimed at measuring various coagulation parameters to predict an early marker for disseminated intravascular coagulation(DIC). METHODS: The current prospective study was conducted from January 2012 to April 2013 on 50 children aged 1-10 years with clinically suspected sepsis referred to the Department of Pediatrics of a tertiary care center in New Delhi, India. Patients were evaluated in accordance with criteria for acute infection (ie, symptoms less than seven days) confirmed in all patients in the laboratory. Patients receiving antibiotics 24-48 hours preceding admission were excluded from the study. Prothrombin time, activated partial thromboplastin time, plasma fibrinogen, and D-dimer were measured at the time of admission in 50 patients and 50 controls. RESULTS & CONCLUSION: D-dimer was positive in 36 (72%) patients and negative in all controls. The difference was statistically significant (P<0.01). Plasma fibrinogen was significantly (P<0.01) higher in patients compared with the controls. It was decreased in 6% and increased in 8% of the patients, and normal in all controls.PT and APTT were significantly (P<0.01) higher in patients compared with the controls.Though none of the current study patients developed overt disseminated intravascular coagulation, the high positivity for D-dimer suggested that it should be measured in children with sepsis for early identification of DIC. This can aid better management as additional coagulation based therapy such as recombinant anti-thrombin and thrombomodulin may help to improve prognosis.

Diagnostic utility of Wilms' tumour-1 protein (WT-1) immunostaining in paediatric renal tumours.

BACKGROUND & OBJECTIVES: Renal tumours constitute about 7 per cent of all neoplasms in children. It is important to differentiate Wilms' tumour (commonest tumour) from non-Wilms' tumours. The aim of this study was to evaluate the immunoexpression and diagnostic role of Wilms' tumour-1 protein (WT1) in paediatric renal tumours. METHODS: A total of 53 cases of renal tumours in children (below 18 yr) who underwent total nephrectomy were included in this retrospective study. WT1 immunostaining was done using mouse monoclonal WT1 antibody (clone: 6F-H2). RESULTS: Of the 53 cases, 38 (72%) were of Wilms' tumour. Non-Wilms' group (15) included six cases of mesoblastic nephroma (MN), two each of clear cell sarcoma (CCSK), renal cell carcinoma (RCC) and peripheral neuroectodermal tumour (PNET) and one each of angiomyolipoma (AML), rhabdomyosarcoma (RMS) and malignant rhabdoid tumour (MRT). Proportion of WT1 positivity in Wilms' tumour was 100 per cent in contrast to 26.7 per cent in non-Wilms' tumours ( P<0.001). Epithelial and blastemal components of Wilms' tumour showed moderate (2+) nuclear and cytoplasmic staining in 80 (24/30) and 75 per cent (24/32) cases, respectively. MN, PNET, CCSK and AML were negative for WT1. RMS, RCC and MRT showed cytoplasmic staining, strongest in RMS. No significant association was seen between WT1 expression and NWTSG (National Wilms' Tumor Study Group) stage. INTERPRETATION & CONCLUSIONS: WT1 helps to differentiate Wilms' tumour from other paediatric renal tumours. It may help in differentiating the two subgroups of Wilms' tumour which have distinct molecular pathogenesis and biological behaviour, however, further prospective studies are required for validation of this hypothesis.

Evaluation of apoptosis in skin biopsies of patients of borderline leprosy and lepra type 1 reaction.

BACKGROUND: The role of apoptosis is not clear in leprosy and lepra reactions. OBJECTIVES: To evaluate frequency of apoptosis in skin lesions of borderline leprosy and Type 1 lepra reaction. METHODS: Sixty patients with borderline leprosy (30 with clinically diagnosed Type 1 reaction (T1R) (Group I) and 30 without clinical evidence of reaction (Group II)) were analyzed in this prospective study. Apoptosis was detected by two different methods for comparison, that is, histopathologic examination (HPE) and deoxyribonucleic acid (DNA) fragmentation and electrophoresis. Quantification of apoptotic bodies/10 high power fields (HPF) was also done. RESULTS: Out of 30 cases, apoptosis was detected in 29 cases in Group I and 24 cases in Group II by HPE (P = 0.103), whereas, with the use of DNA electrophoresis it was detected in 24 cases in Group I and 18 cases in Group II (P = 0.091). On quantitative estimation it was found that number of apoptotic bodies are higher in Group I in comparison to Group II (2.77 vs 1.99), which is statistically significant. CONCLUSIONS: There was moderate agreement (κ = 0.47) between the two methods of apoptosis detection. Apoptosis was seen more in patients with T1R both qualitatively (statistically nonsignificant) and quantitatively (statistically significant). Clinical significance of this novel finding is that apoptosis can be used as one of the variables for diagnosis of T1R to increase detection rate.

Evaluation of key histologic variables in skin biopsies of patients of borderline leprosy with type 1 lepra reaction.

BACKGROUND: Leprosy remains an important health problem mainly in the African and South-East Asia regions. Type 1 reaction is an immune-mediated phenomenon known to complicate at least 30% of patients of leprosy. Diagnosing type 1 reaction correctly is important for timely institution of therapy to prevent and treat neuropathy-associated disability and morbidity. There is paucity of literature on definitive criteria for histologic diagnosis of type 1 reaction. This study was conducted to determine the key histologic variables for diagnosing type 1 reaction. METHODS: This was a prospective study recruiting 104 patients with borderline leprosy. Three pathologists blinded to the clinical diagnosis independently assessed the cases. The agreement between each histological variable and clinical diagnosis was then calculated by using Cohen's kappa (Κ) coefficient. RESULTS: Histological diagnosis of type 1 reaction was given to 27 (67.5%) of 40 clinically diagnosed cases of type 1 reaction cases. Histological variables chosen as key variables for histological diagnosis of type 1 reaction were presence of giant cells, dermal edema, intragranuloma edema, granuloma fraction 31-50%, and presence of medium to large giant cells. CONCLUSION: This study has shown that T1R are still underdiagnosed histologically in comparison with clinical assessments. The key variables for diagnosing type 1 reaction were proposed.

Evaluation of CD64 expression on neutrophils as an early indicator of neonatal sepsis.

BACKGROUND: Enhanced neutrophil CD64 (nCD64) expression is likely to be useful in diagnosis of neonatal sepsis. This study evaluated the diagnostic efficacy of nCD64 expression as an early indicator of neonatal sepsis. METHODS: Sixty neonates (culture positive, 24; negative, 36) with suspected sepsis and 30 controls were studied prospectively. CD64 expression was evaluated flow cytometrically on neutrophils and monocytes. Mean and median nCD64 expression, mean and median monocyte CD64/nCD64 (M/N CD64) ratios were computed. Results were correlated with blood culture and other conventional indices of sepsis. RESULTS: The sick neonates had significantly higher mean and median nCD64 expression compared with controls. Monocyte CD64 values did not differ significantly among the groups. Both mean and median M/N CD64 ratios were significantly lower in the former group. Culture-positive neonates had significantly higher mean and median nCD64 values and significantly lower mean and median M/N CD64 ratios than clinically indistinguishable but culture-negative neonates. Both groups were significantly different with respect to these indices from normal controls. Median M/N CD64 ratio was the best discriminant by virtue of highest area under the receiver operator characteristic curve (0.903), with sensitivity and specificity of 91.7% and 88.9%, respectively. Conventional indices were inferior, both singly and in combination. CONCLUSIONS: Enhanced nCD64 reported as median M/N CD64 ratio is a highly sensitive marker of culture-positive neonatal sepsis. It additionally identifies a separate group among culture-negative sick neonates and may be useful to guide antibiotic administration especially in these neonates.

Thrombophilic molecular markers in young patients (<40 years) with coronary artery disease.

BACKGROUND: There has been an alarming rise in the incidence of coronary artery disease (CAD) in India especially involving the age group of less than 45 years. In recent past, various studies focused on hemostatic aspects of CAD, but could not determine the significance of thrombophilic molecular marker in combination. The study was undertaken to investigate the association of thrombophilia related molecular markers in young patients with CAD. MATERIALS AND METHODS: Thirty diagnosed patients with CAD of either sex under 40 years were included. Thirty healthy age and sex matched control subjects without evidence of CAD formed the control group. Detailed history and clinical examination findings were recorded. In addition to routine investigations, polymerase chain reaction (PCR) based molecular analysis for Factor V Leiden (FVL), methyltetrahydrofolate reductase (MTHFR) gene, tumor necrosis factor receptor 2 (TNFR2) gene, and prothrombin gene mutation were carried out. RESULTS: The mean age (± SD) was 36.86 ± 3.90 years in the patients. Smoking was the most prevalent risk factor. FVL, MTHFR and TNFR2 gene mutation were seen in nine (30%) patient. Three patients had presence of more than one mutation. FVL, MTHFR and TNFR2 gene mutation was found in 4 (13.3%), 3 (10%), and 5 (16.6%) patients respectively. Prothrombin gene mutation was not seen in any of the subjects. There was no significant difference in lipid profile, fibrinogen levels and CRP among the patients with mutation and patients without mutation. CONCLUSION: Almost one-third of the cases were positive for the various mutations in the study and the presence of at-least one or the other risk factor adds on to the risk of future thrombosis. There is a need to demonstrate or document these mutations in a larger group further based upon ethnicity and geographic distribution.

Activated protein C and septic shock: a propensity-matched cohort study*.

BACKGROUND: Septic shock is a highly inflammatory and procoagulant state associated with significant mortality. In a single randomized controlled trial, recombinant human activated protein C (drotrecogin alfa) reduced mortality in patients with severe sepsis at high risk of death. Further clinical trials, including a recently completed trial in patients with septic shock, failed to reproduce these results. OBJECTIVE: To evaluate the effectiveness of recombinant human activated protein C on mortality in a cohort of patients with septic shock and to explore possible reasons for inconsistent results in previous studies. DESIGN: Retrospective, 2:1 propensity-matched, multicenter cohort study. SETTING: Twenty-nine academic and community intensive care units in three countries. PATIENTS: Seven thousand three hundred ninety-two adult patients diagnosed with septic shock, of which 349 received recombinant human activated protein C within 48 hrs of intensive care unit admission between 1997 and 2007. MEASUREMENTS AND MAIN RESULTS: Our primary outcomes were mortality over 30 days and mortality stratified by Acute Physiology and Chronic Health Evaluation II quartile. Using a propensity-matched Cox proportional hazard model, we observed a 6.1% absolute reduction in 30-day mortality associated with the use of recombinant human activated protein C (108/311 [34.7%] vs. 254/622 [40.8%], hazard ratio 0.72, 95% confidence interval 0.52-1.00, p = .05) and noted consistent reductions in mortality among Acute Physiology and Chronic Health Evaluation II quartiles. A time to event analysis showed that the time to appropriate antimicrobials after documented hypotension decreased for each year of study (p = .003), a finding that was congruent with a decrease in annual mortality over the study period (odds ratio 0.96 per year [95% confidence interval 0.93-0.99], p = .003). CONCLUSIONS: In this retrospective, propensity-matched, multicenter cohort study of patients with septic shock, early use of recombinant human activated protein C was associated with reduced mortality. Improvements in general quality of care such as speed of antimicrobial delivery leading to decreasing mortality of patients with septic shock may have contributed to the null results of the recently completed trial of recombinant human activated protein C in patients with septic shock.

Developmental and neurophysiologic deficits in iron deficiency in children.

INTRODUCTION: Several studies in animals and humans have clearly demonstrated the effect of ID on development, cognition, behavior and neurophysiology. The effect of ID have been shown: on brain metabolism, neurotransmitter function, and myelination. Changes in brain iron content caused by early ID in animals are not reversible by iron therapy, inspite of correction of anemia and other tissue deficits and result in changes in behavior which continue into adulthood. ID has repercussions in the perinatal period, infancy and childhood. Some effects are irreversible while other defects may be corrected: timing of ID in a child may be critical. DEVELOPMENTAL DEFICITS: Children (6-23 months) with moderate to severe anemia (ID) or chronic anemia (>3 months) had lower mental and psychomotor development scores than the nonanemic, and except for some continued to have lower scores in spite of iron therapy for 3 months although anemia was corrected. The deficits persisted on re-evaluation at 5, 11-14, and at 19 years. SCHOLASTIC ACHIEVEMENT: Scholastic achievement is lower and ID children are twice more likely to have problems with mathematics. Ten year follow-up indicated special educational assistance was required for initially anemic children. ID affects WICS items of information, comprehension and verbal performance and full scale IQ. EEG power spectrum had a slower activity suggesting developmental lag compared to iron sufficient children. Treatment with iron improved IQ scores significantly; other studies found differential effects: improvement in cognition and mental scores in older but not in younger children. IQ levels are affected by ID: IQ at 4 years may be predicted by hemoglobin at 5 and 36 months. NEUROPHYSIOLOGICAL DEFICITS: Abnormal Evoked Response Potentials (ERPs):ABRs and VEPs are seen in ID, which persist in children who were anemic in infancy on retesting at 4 years. Differences have been consistently found in ID infants and in older children. Iron supplementation may significantly reduce latencies of some ERPs. ID affects newborn temperament, ERPs and recognition memory. Iron supplementation in infants (<1,301 g) improved neurocognitive and psychomotor development by 5.3 years (median age). Preventive iron supplementation in well nourished infants also show a positive effect on motor development. The changes are usually subtle, however, with prevalence of anemia of 79.2% in children 6-35 months and 57.9% in pregnant women (NFHS-3, 2005-06), the adverse effects of cognitive, development and behavioral defects should not be underestimated.

Frequency of ß-thalassemia trait and other hemoglobinopathies in northern and western India.

INTRODUCTION: India is an ethnically diverse country with an approximate population of 1.2 billion. The frequency of beta-thalassemia trait (ßTT) has variously been reported from <1% to 17% and an average of 3.3%. Most of these studies have been carried out on small population groups and some have been based on hospital-based patients. There is also a variation in the prevalence of hemoglobinopathies in different regions and population groups in the country. A high frequency of Hb D has been reported from the North in the Punjabi population, Hb E in the eastern region of India and Hb S is mainly reported from populations of tribal origin from different parts of the country. OBJECTIVES: To study the gene frequency of ßTT and other hemoglobinopathies in three regions East (Kolkata), West (Mumbai) and North (Delhi) in larghe population group (schoolchildren) for a more accurate assessment of gene frequency for planning of control programmes for haemoglobinopathies. MATERIALS AND METHODS: This study included 5408 children from 11 schools in Delhi, 5682 from 75 schools in Mumbai and 957 schoolchildren from Kolkata who were screened for ßTT and haemoglobinopathies. These included 5684 children from 75 schools in Mumbai and 5408 children from 11 schools in Delhi. Children were 11-18 years of age of both sexes. The final report is, however, only on 11090 schoolchildren from Mumbai and Delhi as data from Kolkata was restricted both in numbers and objectives and could not be included for comparison. RESULTS: The overall gene frequency of ßTT in Mumbai and Delhi was 4.05% being 2.68% and 5.47% in children of the two cities respectively. In Mumbai, the gene frequency was evenly distributed. Majority of the children with ßTT from Mumbai were from Marathi (38.9%) and Gujarati (25%) speaking groups. Gene frequency was >5% in Bhatias, Khatris, Lohanas and Schedule Castes. In Delhi, a higher incidence was observed in schoolchildren of North and West Delhi (5.8-9.2%). The schoolchildren of North and West Delhi comprised predominantly of Punjabi origin compared to children in the South of the city (2.2%, 2.3%). When analyzed state-wise, the highest incidence was observed in children of Punjabi origin (7.6%) and was >4% from several other states. Majority of the traits from Mumbai were anemic (95.1% male and 85.6% in female). The prevalence of anemia was lower (62.7% male and 58.4% female) children with ßTT from Delhi. This was a reflection of the higher prevalence of anemia in children without hemoglobinopathy in Mumbai than in Delhi. Nutritional deficiency was probably more severe and rampant in children Mumbai. Gene frequency of Hb D was greater in schoolchildren from Delhi (1.1%) than in Mumbai (0.7%). Hb S trait (0.2%) was observed exclusively in children from Mumbai. A low incidence of Hb E trait (0.04%) was seen in children in Mumbai. A higher incidence is reported from the East. The number of cases studied from the eastern region was small as the data from the East (Kolkata) could not be included in the analysis. CONCLUSION: This study comprises a larger number of children studied for the gene frequency of ßTT and other hemoglobinopathies from India. Population groups with higher gene frequencies require screening programmes and facilities for antenatal diagnosis as well as increased awareness and educational programmes to control the birth of thalassemic homozygotes. The overall carrier frequency of ßTT was 4.05% and reinforces the differential frequency of ß-thalassemia trait in schoolchildren from Delhi and Mumbai and the higher incidence of hemoglobin D in Punjabis as reported previously. The birth incidence calculated thereof for homozygous thalassemics would be 11,316 per year which are added each year to the existing load of homozygous thalassemics. This is much higher than the previously reported number of births annually. Hence suitable control measures need to be undertaken urgently in India.

Early intravenous unfractionated heparin and mortality in septic shock.

BACKGROUND: Sepsis and septic shock represent a systemic inflammatory state with substantial pro-coagulant elements. Unfractionated heparin is a known anticoagulant, which also possesses anti-inflammatory properties. Unfractionated heparin has been shown to increase survival in experimental models of septic shock. OBJECTIVE: To evaluate the impact of intravenous therapeutic dose unfractionated heparin in a cohort of patients diagnosed with septic shock. DESIGN: Retrospective, propensity matched, multicenter, cohort study. SETTING: Regional intensive care units in Winnipeg, Canada between 1989 and 2005. PATIENTS: Two thousand three hundred fifty-six patients diagnosed with septic shock, of which 722 received intravenous therapeutic dose heparin. MEASUREMENTS AND MAIN RESULTS: The primary outcome of study was 28-day mortality, and mortality stratified by severity of illness (Acute Physiologic and Chronic Health Evaluation II quartile). Safety was assessed by comparing rates of gastrointestinal hemorrhage, intracranial hemorrhage, and the need for transfusion. By using a Cox proportional hazards model, systemic heparin therapy was associated with decreased 28-day mortality (307 of 695 [44.2%] vs. 279 of 695 [40.1%]; hazard ratio 0.85 [confidence interval (CI) 95% 0.73-1.00]; p = 0.05). In the highest quartile of severity of illness (Acute Physiologic and Chronic Health Evaluation II score 29-53), heparin administration was associated with a clinically and statistically significant reduction in 28-day mortality [127 of 184 (69.0%) vs. 94 of 168 (56.0%); hazard ratio 0.70 (CI 95% 0.54-0.92); p = 0.01]. The use of intravenous unfractionated heparin was associated with successful liberation from mechanical ventilation [odds ratio of 1.42 (CI 95% 1.13-1.80); p = 0.003], and successful discontinuation of vasopressor/inotropic support [odds ratio of 1.34 (CI 95% 1.06-1.71); p = 0.01]. No significant differences in the rates of major hemorrhage or need for transfusion were identified. CONCLUSION: Early administration of intravenous therapeutic dose unfractionated heparin may be associated with decreased mortality when administered to patients diagnosed with septic shock, especially in patients with higher severity of illness. Prospective randomized trials are needed to further define the role of this agent in sepsis and septic shock.

Congenital duodenal obstruction with situs inversus totalis: Report of a rare association and discussion.

This report is to present and discuss an extremely rare association of situs inversus with duodenal atresia in an 11-day-old male neonate born full term and weighing 1.9 kg. The baby presented with recurrent bilious vomiting. Babygram revealed situs inversus and duodenal obstruction. Echocardiography showed dextrocardia with a small ASD. Exploration confirmed a duodenal diaphragm with a central perforation between the third and fourth part of the duodenum and situs inversus. The literature search revealed 20 cases reported so far.

Esophageal atresia: Factors influencing survival - Experience at an Indian tertiary centre.

OBJECTIVE: To study the clinical profile of the cases of esophageal atresia (EA) and/or tracheoesophageal fistula (TEF) and various factors affecting the surgical and early postoperative management and their outcome. MATERIALS AND METHODS: A prospective analysis of 127 cases of EA from February 2004 to May 2006 was performed. Waterston prognostic criteria were used for grading. RESULTS: EA with TEF was the commonest type in 117 cases (92%). Associated congenital anomalies were present in 52 (41%) patients, the commonest being the cardiac anomalies, which was followed by the gastrointestinal anomalies. VACTERL was found in 6 (5%) cases. Prematurity, associated congenital anomalies, gap between esophageal ends and preoperative respiratory status were the significant factors affecting the survival (P = < 0.001). Primary extrapleural repair was the surgical approach in most of the patients. Azygos vein was preserved in 46 cases and no retropleural drainage was used in 27 cases. Staged procedures were performed in 19 cases, including 6 cases of isolated esophageal atresia. Pneumonitis and sepsis were the most common early postoperative complications (42%). Hypoxia and cardiorespiratory arrest were the most common causes of mortality (11 cases). Anastomotic leak complicated 13 cases, including 9 major and 4 minor leaks. Major leak followed by sepsis caused 7 deaths. Survival as per Waterston criteria was 100% in group A, 83% in group B and 22% in group C. CONCLUSION: Factors affecting the survival are major or life-threatening associated anomalies, long gap, pneumonia and sepsis at presentation or that acquired during hospitalization and major leaks. The high incidence of low birth weight, delayed diagnosis, poor referral, low-socio economic status and lack of advanced neonatological back up are important contributory factors to poor outcome.

Azygos vein preservation in primary repair of esophageal atresia with tracheoesophageal fistula.

The aim of this study is to report a series of patients with the Azygos vein preserved during the surgery for esophageal atresia with tracheoesophageal fistula (EA&TEF), highlighting the advantages in terms of survival and prevention of anastomotic leak. Ninety-six neonates with EA&TEF, admitted to the Department of Pediatric Surgery, King George Medical University between 2004 and 2006, were reviewed prospectively; the babies were randomly allocated to two groups: Group A (n = 46) in which the Azygos vein was preserved and Group B (n = 50), wherein it was ligated. The two groups were comparable in respect to sex, weight, prematurity, associated anomalies, Waterston classification, Spitz classification and distance between the pouches after mobilization. Anastomotic leak occurred in three cases (6%) in Group A and ten cases (20%) in Group B and was responsible for mortality in one (2%) case in Group A and six cases (12%) in Group B. Preservation of Azygos vein resulted in significant reduction in the number of anastomotic leaks. We propose that preservation of the Azygos vein prevents early postoperative edema of the esophageal anastomosis by maintaining the venous drainage and thus may form an additional protective factor against anastomotic leaks.

Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock.

OBJECTIVE: To determine the prevalence and impact on mortality of delays in initiation of effective antimicrobial therapy from initial onset of recurrent/persistent hypotension of septic shock. DESIGN: A retrospective cohort study performed between July 1989 and June 2004. SETTING: Fourteen intensive care units (four medical, four surgical, six mixed medical/surgical) and ten hospitals (four academic, six community) in Canada and the United States. PATIENTS: Medical records of 2,731 adult patients with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome measure was survival to hospital discharge. Among the 2,154 septic shock patients (78.9% total) who received effective antimicrobial therapy only after the onset of recurrent or persistent hypotension, a strong relationship between the delay in effective antimicrobial initiation and in-hospital mortality was noted (adjusted odds ratio 1.119 [per hour delay], 95% confidence interval 1.103-1.136, p<.0001). Administration of an antimicrobial effective for isolated or suspected pathogens within the first hour of documented hypotension was associated with a survival rate of 79.9%. Each hour of delay in antimicrobial administration over the ensuing 6 hrs was associated with an average decrease in survival of 7.6%. By the second hour after onset of persistent/recurrent hypotension, in-hospital mortality rate was significantly increased relative to receiving therapy within the first hour (odds ratio 1.67; 95% confidence interval, 1.12-2.48). In multivariate analysis (including Acute Physiology and Chronic Health Evaluation II score and therapeutic variables), time to initiation of effective antimicrobial therapy was the single strongest predictor of outcome. Median time to effective antimicrobial therapy was 6 hrs (25-75th percentile, 2.0-15.0 hrs). CONCLUSIONS: Effective antimicrobial administration within the first hour of documented hypotension was associated with increased survival to hospital discharge in adult patients with septic shock. Despite a progressive increase in mortality rate with increasing delays, only 50% of septic shock patients received effective antimicrobial therapy within 6 hrs of documented hypotension.