Adhesive small bowel obstruction after appendectomy in children: comparison between the laparoscopic and open approach

Introduction

Adhesive small bowel obstruction (SBO) is a common postoperative complication. Published data in the pediatric literature characterizing SBO are scant. Furthermore, the relationship between the risk of SBO for a given procedure is not well described. To evaluate these parameters, we reviewed the incidence of SBO after laparoscopic appendectomy (LA) and open appendectomy (OA) performed at our institution.

Methods

With institutional review board approval, all patients that developed SBO after appendectomy for appendicitis from January 1998 to June 2005 were investigated. Hospital records were reviewed to identify the details of their postappendectomy SBO. The incidences of SBO after LA and OA were compared with χ² analysis using Yates correction.

Results

During the study period, 1105 appendectomies were performed: 477 OAs (8 converted to OA during laparoscopy) and 628 LAs. After OA, 7 (6 perforated appendicitis) patients later developed SBO of which 6 required adhesiolysis. In contrast, a patient with perforated appendicitis developed SBO after LA requiring adhesiolysis (P = .01). The mean time from appendectomy to the development of intestinal obstruction for the entire group was 46 ± 32 days.

Conclusions

The overall risk of SBO after appendectomy in children is low (0.7%) and is significantly related to perforated appendicitis. Small bowel obstruction after LA appears statistically less common than OA. Laparoscopic appendectomy remains our preferred approach for both perforated and nonperforated appendectomy.     

N-Phenylethyl Amitriptyline in Rat Sciatic Nerve Blockade

Background: The antidepressant amitriptyline is commonly used orally for the treatment of chronic pain, particularly neuropathic pain, which is thought to be caused by high-frequency ectopic discharge. Among its many properties, amitriptyline is a potent Na+ channel blocker in vitro, has local anesthetic properties in vivo, and confers additional blockade at high stimulus-discharge rates (use-dependent blockade). As with other drug modifications, adding a phenylethyl group to obtain a permanently charged quaternary ammonium derivative may improve these advantageous properties.

Methods: The electrophysiologic properties of N-phenylethyl amitriptyline were assessed in cultured neuronal GH3 cells with the whole cell mode of the patch clamp technique, and the therapeutic range and toxicity were evaluated in the rat sciatic nerve model.

Results: In vitro, N-phenylethyl amitriptyline at 10 [mu]m elicits a greater block of Na+ channels than amitriptyline (resting block of approximately 90%vs. approximately 15%). This derivative also retains the attribute of amitriptyline in evoking high-degree use-dependent blockade during repetitive pulses. In vivo, duration to full recovery of nociception in the sciatic nerve model was 1,932 +/- 72 min for N-phenylethyl amitriptyline at 2.5 mm (n = 7) versus 72 +/- 3 min for lidocaine at 37 mm (n = 4; mean +/- SEM). However, there was evidence of neurotoxicity at 5 mm.     

Peripheral administration of the melanocortin-4 receptor antagonist NBI-12i ameliorates uremia-associated cachexia in mice

We have recently shown that genetic or pharmacological blockade of the melanocortin-4 receptor (MC4-R) attenuates uremia-associated cachexia. However, the potential clinical utility of this approach has been limited by the need to deliver a peptide MC4-R antagonist into the ventricles of the brain. NBI-12i is a recently developed small molecule MC4-R antagonist, with high affinity and selectivity that penetrates the central nervous system after peripheral administration. We tested whether NBI-12i would also be effective in attenuating uremia-associated cachexia in a mouse model. Intraperitoneal administration of NBI-12i stimulated food intake and weight gain in uremic mice. Furthermore, NBI-12i-treated uremic mice gained lean body mass, fat mass, and had a lower basal metabolic rate compared to vehicle-treated and diet-supplemented uremic mice, which lost both lean body mass and fat mass and had an increase in basal metabolic rate. We found that NBI-12i normalizes the expression of uncoupling protein, which is normally upregulated in uremic mice, and we speculate that this may contribute to the drug's protective effect. These data underscore the importance of melanocortin signaling in the pathogenesis of uremia-associated cachexia and demonstrate the potential of peripheral administration of MC4-R antagonists as a novel therapeutic approach.     

Standardization of Intraoperative Neuromonitoring of Recurrent Laryngeal Nerve in Thyroid Operation

Background  

The lack of standardized procedures of intraoperative neuromonitoring (IONM) during thyroid operations may lead to highly variable results, and many of these results can cause misleading information and, conversely, increase the risk of recurrent laryngeal nerve (RLN) injury. Therefore, standardization of IONM procedures is necessary.     

Platelets in Early Antibody-Mediated Rejection of Renal Transplants

Antibody-mediated rejection is a major complication in renal transplantation. The pathologic manifestations of acute antibody-mediated rejection that has progressed to functional impairment of a renal transplant have been defined in clinical biopsy specimens. However, the initial stages of the process are difficult to resolve with the unavoidable variables of clinical studies. We devised a model of renal transplantation to elucidate the initial stages of humoral rejection. Kidneys were orthotopically allografted to immunodeficient mice. After perioperative inflammation subsided, donor-specific alloantibodies were passively transferred to the recipient. Within 1 hour after a single transfer of antibodies, C4d was deposited diffusely on capillaries, and von Willebrand factor released from endothelial cells coated intravascular platelet aggregates. Platelet-transported inflammatory mediators platelet factor 4 and serotonin accumulated in the graft at 100- to 1000-fold higher concentrations compared with other platelet-transported chemokines. Activated platelets that expressed P-selectin attached to vascular endothelium and macrophages. These intragraft inflammatory changes were accompanied by evidence of acute endothelial injury. Repeated transfers of alloantibodies over 1 week sustained high levels of platelet factor 4 and serotonin. Platelet depletion decreased platelet mediators and altered the accumulation of macrophages. These data indicate that platelets augment early inflammation in response to donor-specific antibodies and that platelet-derived mediators may be markers of evolving alloantibody responses.     

Can Machine Learning Methods Produce Accurate and Easy-to-Use Preoperative Prediction Models of One-Year Improvements in Pain and Functioning After Knee Arthroplasty?

BackgroundApproximately 15%-20% of total knee arthroplasty (TKA) patients do not experience clinically meaningful improvements. We sought to compare the accuracy and parsimony of several machine learning strategies for developing predictive models of failing to experience minimal clinically important differences in patient-reported outcome measures (PROMs) 1 year after TKA.MethodsPatients (N = 587) in 3 large Veteran Health Administration facilities completed PROMs before and 1 year after TKA (92% follow-up). Preoperative PROMs and electronic health record data were used to develop and validate models to predict failing to experience at least a minimal clinically important difference in Knee Injury and Osteoarthritis Outcome Score (KOOS) Total, KOOS JR, and KOOS subscales (Pain, Symptoms, Activities of Daily Living, Quality of Life, and recreation). Several machine learning strategies were used for model development. Ten-fold cross-validation and bootstrapping were used to produce measures of overall accuracy (C-statistic, Brier Score). The sensitivity and specificity of various predicted probability cut-points were examined.ResultsThe most accurate models produced were for the Activities of Daily Living, Pain, Symptoms, and Quality of Life subscales of the KOOS (C-statistics 0.76, 0.72, 0.72, and 0.71, respectively). Strategies varied substantially in terms of the numbers of inputs required to achieve similar accuracy, with none being superior for all outcomes.ConclusionModels produced in this project provide estimates of patient-specific improvements in major outcomes 1 year after TKA. Integrating these models into clinical decision support, informed consent and shared decision making could improve patient selection, education, and satisfaction.Level of EvidenceLevel III, diagnostic study.     

Osteopontin inhibits macrophage nitric oxide synthesis to enhance tumor proliferation

BACKGROUND: Interactions between tumor cells and their host environment can play a major role in regulating survival programs required for tumor progression. Osteopontin (OPN) is a glycophosphoprotein overexpressed by tumors, and is a key molecule for tumor progression and metastasis. OPN also inhibits expression of autocrine and paracrine inducible nitric oxide synthase (iNOS). Given the cytotoxic effects of macrophage NO expression, we hypothesized that tumor-derived OPN inhibits expression of local macrophage iNOS to potentiate tumor survival. METHODS: We used a coculture system of murine CT26 colorectal cancer cells with RAW264.7 murine macrophage cells. CT26 expresses OPN at high levels. RNA interference was utilized to produce long-term specific silencing of OPN in CT26. RESULTS: Inhibition of constitutive OPN synthesis in CT26 upregulates local NO production with inhibition of CT26 proliferation and promotion of CT26 apoptosis. Macrophage iNOS expression is accompanied by increased binding activity of nuclear factor-kappaB DNA. When the CT26 culture media were examined for a panel of proinflammatory cytokines, elevated concentrations of granulocyte colony-stimulating factor (G-CSF) were found. Subsequently, in CT26 cells treated with antisense-G-CSF, NO levels in CT26-RAW cocultures were significantly decreased. CONCLUSION: In our system of CT26-RAW264.7 coculture, we conclude that inhibition of OPN synthesis in CT26 results in G-CSF-mediated induction of macrophage iNOS expression with resultant inhibition of CT26 proliferation via increased apoptosis. Our results suggest that tumor-derived OPN may enhance tumor survival by down regulating expression of NO in the local microenvironment. This is one mechanism by which OPN may potentiate cancer survival and progression.     

Evaluation of mandibular block using a standardized method.

The purpose of this prospective randomized study was to investigate the manifestations and efficiency of mandibular block (MB) using a standardized method. In this study, 123 patients requiring MB were randomly assigned to receive MB using a repeated measures design. Mandibular block was administered in each patient by using 2.1 mL of 2% lidocaine with 1:100 000 epinephrine for the inferior alveolar nerve, lingual nerve, and/or buccal nerve. Clinical parameters including the electric pulp test and test for soft tissue sensation using a sharp dental explorer were assessed on both the operated side and contralateral side before and 5, 10, and 15 minutes after injection, and at the end of surgical procedure. Results of the test of the contralateral tooth served as the control group. No response to the electric pulp test at a maximum output (80 readings) was used as the criterion for pulpal anesthesia. Results obtained with electric pulp test and sharp explorer test were not significantly different during various intervals on the contralateral side, indicating the reliability of this standardized method for assessing MB. The MB technique achieved a high rate of subjective numbness (100%) according to the perception of the patients of overall numbness and lip numbness. Overall anesthetic success rates of pulpal anesthesia were 5.7% for the central incisor, 38.2% for the canine, 55.3% for the first premolar, and 90.2% for the first molar. No significant difference was found in the efficiency of anesthesia related to sex or age of the patients. A slower onset of pulpal anesthesia after MB was found for the anterior teeth than for the posterior teeth. This study suggests that the use of a standardized method might produce a clearer and more comprehensive evaluation of the efficiency and manifestations of MB.     

Urinary nerve growth factor but not prostaglandin E2 increases in patients with interstitial cystitis/bladder pain syndrome and detrusor overactivity

Study Type – Aetiology (case series)
Level of Evidence 4

OBJECTIVE

To compare urinary nerve growth factor (NGF) and prostaglandin E2 (PGE2) levels among patients with detrusor overactivity (DO), increased bladder sensation (ISB), interstitial cystitis/bladder pain syndrome(IC/BPS) and controls.

PATIENTS, SUBJECTS AND METHODS

Urine samples were collected from 40 women with IC/BPS, 54 with overactive bladder (OAB) and 27 normal women as controls, all with a full bladder. Patients with OAB were further classified into subgroups of DO or IBS by urodynamic results. Urinary NGF and PGE2 levels were measured using an enzyme‐linked immunosorbent assay. Urinary NGF and PGE2 levels were normalized by urinary creatinine (Cr) levels and compared among all subgroups.

RESULTS

Urinary NGF levels were increased in the 40 women with IC/BPS and 23 with DO but not in 31 with IBS and the 27 controls. Mean (sd ) urinary NGF/Cr levels were not significantly different between patients with IC/BPS, at 1.35 (0.36), and DO, at 1.93 (0.77). Urinary NGF/Cr levels were significantly higher in women with IC/BPS than in women with IBS, at 0.25 (0.10) (P = 0.01). Using receiver operating characteristic curves for assessing urinary NGF/Cr levels in patients with IC/BPS and IBS, IC/BPS was diagnosed with a sensitivity and specificity of 75% and 65.5%, respectively, based on a urinary NGF/Cr threshold of 0.015. However, urinary PGE2/Cr levels were not significantly different among all subgroups.

CONCLUSIONS

Urinary NGF/Cr levels are elevated in women with IC/BPS or DO, but not in those with IBS. The differential diagnosis of women with IC/BPS from those with frequency‐urgency syndrome is possible based on urinary NGF/Cr levels but not urinary PGE2/Cr level.