Gastroschisis closure--does method really matter?

Background/Purpose

Management of gastroschisis varies. This study aims to determine which aspects of practice influence outcomes.

Methods

All cases of simple gastroschisis (N = 99) in the Canadian Pediatric Surgery Network database were analyzed looking at methods of preoperative bowel protection, timing of closure, and closure techniques; and outcome measures included time to onset of enteral feeds, duration of parenteral nutrition (PN), and length of stay (LOS).

Results

One third of infants had initial bowel protection using a spring-loaded silo, which was significantly associated with a delay (beyond 24 hours) in establishing primary closure. Neither preoperative bowel protection methods nor defect closure techniques conferred any significant effects on success at establishing primary closure or functional outcomes. After adjusting for all covariates, only failure to establish primary closure was associated with impaired outcomes with significantly delayed initiation of enteral feeds and prolonged LOS. Low birth weight (<2000 g) and younger gestational age (<36 weeks) were associated with a 3-fold increased risk of longer PN dependence and 5-fold risk of extended LOS, respectively. Babies undergoing the sutureless spontaneous closure technique had significant delays in initiating enteral feeds but no increased requirements for PN or LOS.

Conclusions

Modes of preoperative bowel protection and techniques of abdominal wall closure ultimately have no association with functional outcomes in infants with gastroschisis. Failure to establish primary closure, however, is significantly associated with delays in establishing intestinal function and subsequent time to discharge.     

Effects of the renal medullary pH and ionic environment on vasopressin binding and signaling

The kidney has a cortico-medullary interstitial gradient of decreasing pH and increasing concentrations of sodium chloride and urea, but the influence of these gradients on receptor signaling is largely unknown. Here, we measured G-protein coupled receptor function in LLC-PK1 cells acutely exposed to conditions mimicking different kidney regions. Signaling through the parathyroid hormone receptor, normally expressed in the cortex, was greatly reduced at an acidic pH similar to that of the inner medulla. Parathyroid hormone receptor, tagged with green fluorescent protein, showed no ligand-induced internalization. In contrast, under both acidic and hyperosmotic conditions, vasopressin increased intracellular cAMP, and upon binding to its type 2 receptor (V2R) was internalized and degraded. Dose-displacement binding assays with selective vasopressin/oxytocin receptor ligands under inner medullary conditions indicated a shift in the V2R pharmacological profile. Oxytocin did not bind to the V2R, as it does under normal conditions and the vasopressin type 1 receptor (V1R) had reduced affinity for vasopressin compared to the V2R in low pH and high osmolality. We suggest that the cortico-medullary gradient causes a receptor-specific selectivity in ligand binding that is of functional significance to the kidney. While the gradient is important for urinary concentration, it may also play a substantial role in fine-tuning of the vasopressin response through the V2R.     

Is there still a role for surgery in esophageal carcinoma in 2007?

Regarding curative treatment of oesophageal carcinoma, many therapeutic options could be planned. Surgery is traditionally considered as the most appropriate treatment for locoregional control and long-term survival. Because of the poor prognosis, muldisciplinary approach is necessary, including surgery, radiotherapy and chemotherapy, alone or in association. However, because of the small number of well randomised trials, the question of which treatment is the most appropriate is still under debate. In 2007, following therapeutic strategies could be drawn: surgery is the main treatment, used alone for stages I and IIa, in association with neoadjuvant chemotherapy (CT) or chemoradiation (CRT) for stages IIb. For locally advanced tumours (stage III), adenocarcinomas required neoadjuvant CT or CRT followed by surgery, whereas for squamous cell carcinomas exclusive CRT is the main treatment with following important conditions : (i) response to CRT, (ii) curative salvage surgery in case of non response after 2 cycles or persistent tumour after 4 cycles, (iii) long-term survival may be probably enhanced by adjuvant surgery in experienced centres for selected patients.     

Phase II study of low-dose decitabine in combination with imatinib mesylate in patients with accelerated or myeloid blastic phase of chronic myelogenous leukemia

BACKGROUND: Resistance to imatinib is a frequent clinical problem in advanced phase chronic myelogenous leukemia (CML). A Phase II study was performed on low-dose decitabine, a DNA methyltransferase inhibitor, in combination with imatinib in patients with CML in accelerated phase (AP) and myeloid blastic phase (BP). METHODS: Patients received decitabine 15 mg/m(2) intravenously daily, 5 days a week for 2 weeks, and imatinib 600 mg orally daily. Global DNA methylation was measured by long interspersed nucleotide element (LINE) bisulfite/pyrosequencing. RESULTS: Twenty-eight patients were enrolled (25 with imatinib resistance; 18 in AP, 10 in BP). A total of 91 cycles (median, 2.5 cycles per patient) was administered. Complete hematologic responses, partial hematologic responses, and hematologic improvement were observed in 9 (32%), 1 (4%), and 2 (7%) patients. Major and minor cytogenetic responses were observed in 5 (18%) and 3 (11%) patients. The hematologic response rate was higher in patients without BCR-ABL kinase mutations (10 of 19, 53%) than in those with mutations (1 of 7, 14%). Median duration of hematologic response was 18 (range, 4 to 107+) weeks. Myelosuppression was the major adverse effect, with neutropenic fever in 9 patients (32%). LINE methylation decreased from 71.6% +/- 0.9% (mean +/- standard error of the mean) to 60.4% +/- 2.0% on Day 5, 60.5% +/- 1.8% on Day 12, and returned to 68.8% +/- 1.4% at peripheral blood recovery. A decrease in LINE methylation tended to be greater in nonresponders than in responders on Days 5 and 12. CONCLUSIONS: Combination therapy with decitabine and imatinib is well tolerated and active in advanced phase CML without BCR-ABL kinase mutations.     

Survival advantage with decitabine versus intensive chemotherapy in patients with higher risk myelodysplastic syndrome: comparison with historical experience

BACKGROUND: Decitabine, a hypomethylating agent, is active and has been approved for the treatment of myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia. Intensive chemotherapy is an accepted form of therapy for patients with higher risk MDS. The comparative efficacy of these 2 forms of treatment in MDS is unknown. The objective of the current study was to compare the efficacy and toxicity profiles of decitabine and intensive chemotherapy in MDS. METHODS: The authors compared lower intensity decitabine therapy (n = 115 patients) with intensive chemotherapy (as it is used in acute myeloid leukemia [AML]) in patients with higher risk MDS. Two comparisons were made with a cohort of 376 historic patients (from 1995 to 2005): The first comparison included a subcohort of 115 patients (Group A) who matched the 115 decitabine study patients according to age, International Prognostic Scoring System, and cytogenetics; and the second comparison included the whole cohort of 376 patients without matching (Group B). A multivariate analysis was performed for outcome. RESULTS: The complete remission (CR) rate according to AML criteria was 43% with decitabine, 46% with intensive chemotherapy in Group A, and 52% with intensive chemotherapy in Group B. Compared with Group A, mortality at 6 weeks was 3% with decitabine versus 13% with intensive chemotherapy (P = .006) and, at 3 months, 7% with decitabine versus 23% with intensive chemotherapy (P = .001). Survival was better with decitabine versus intensive chemotherapy in Group A (median survival: 22 months vs 12 months; P < .001). A multivariate analysis of survival in all 491 patients who received decitabine or intensive chemotherapy (Group B) selected decitabine as an independent, favorable prognostic factor for survival (P = .006; hazard ratio, 0.74) after accounting for the independent prognostic effect of pretreatment factors. CONCLUSIONS: In this analysis, decitabine was associated with a survival advantage compared with intensive chemotherapy in patients with higher risk MDS. Future studies should evaluate prospectively the results of decitabine versus intensive chemotherapy in this setting.     

Accuracy of the screening physical examination to identify subclinical atherosclerosis and peripheral arterial disease in asymptomatic subjects

OBJECTIVES: This study assessed the accuracy of the screening vascular physical examination for predicting asymptomatic peripheral arterial disease (PAD) or subclinical atherosclerosis in asymptomatic and apparently healthy subjects. METHODS: A standardized physical examination and a carotid and femoral ultrasonography were administered to 2736 men and women aged 20 to 90 years old, with no personal history of cardiovascular disease (CVD) and no complaint of neurologic, coronary, or lower limb symptom. We assessed the accuracy of auscultation for bruits and pulse palpation for identifying the presence of significant carotid stenosis, carotid plaque, femoral plaque, and ankle-brachial index (ABI) <0.9 at ultrasonography. RESULTS: The presence of a femoral bruit provided information on the presence of both an ABI <0.9 (positive likelihood ratio [+LR], 2.90; 95% confidence interval [CI], 1.63 to 5.16) and a femoral plaque (+LR, 3.23; 95% CI, 2.22 to 4.71), and this information was independent from the cardiovascular risk factors. The absence of both pedal pulses also provided additional information, beyond risk factors, on the presence of an ABI <0.9 (+LR, 3.57; 95% CI, 1.93 to 6.60). The presence of a carotid bruit did not affect the likelihood of carotid stenosis, plaque, or intima-media thickness above the median. CONCLUSION: Unlike carotid auscultation, pulse palpation and auscultation for femoral bruits provided valuable information on the presence of asymptomatic PAD and underlying atherosclerosis in apparently healthy subjects.     

Ventilator-associated pneumonia: follow the guidelines!

Objectives

To compare the clinical outcomes and the causative pathogens of early-onset and late-onset ventilator-associated pneumonia (VAP) diagnosed by bronchoalveolar lavage (BAL).

Study design

Prospective, observational, epidemiological study.

Patients and methods

During a 7-years period, all first episodes of VAP were prospectively included. Diagnosis was confirmed by a BAL with a threshold of 10⁴ cfu/ml. Late-onset pneumonia was defined if occurred after the seventh day after mechanical ventilation.

Results

One hundred and thirteen VAP were studied. Fifty were early-onsets and 63 late-onsets. Thirty-four per cent of early-onset VAP and 73% of late-onset VAP were due to potential multiresistants pathogens. Pseudomonas aeruginosa was the most commonly isolated bacteria both in early-onset and late-onset VAP (16 and 39% respectively). Morbidity and mortality (29 vs 29%, ns) were not statically different between the two groups (early-onset and late-onset VAP).

Conclusion

In our study, both early-onset and late-onset VAP were mainly caused by potentially multiresistants bacteria, most commonly Gram negative bacilli. Even for early VAP, clinicians should be aware about all risk factors for potentially multiresistants pathogens and not only the delay of onset of the VAP episode.