Postlaparotomy pain management: Comparison of patient-controlled analgesia pump alone, with subcutaneous bupivacaine infusion, or with injection of liposomal bupivacaine suspension.

OBJECTIVE: Efforts to achieve balance between effective pain management and opioid-related adverse events (ORAEs) have led to multimodal analgesia regimens. This study compared opioids delivered via patient-controlled analgesia (PCA) plus liposomal bupivacaine, a long-acting local anesthetic with potential to be an effective component of such regimens, to opioids delivered through PCA alone or PCA plus subcutaneous bupivacaine infusion (ONQ), following laparotomy. DESIGN: Prospective, randomized controlled trial. SETTING: Single, tertiary-care institution. PATIENTS: One hundred patients undergoing nonemergent laparotomy. INTERVENTIONS: Patients were randomly assigned to one of three study treatments: PCA only (PCAO), PCA with ONQ, or PCA with injectable liposomal bupivacaine suspension (EXP). MAIN OUTCOME MEASURES: Cumulative opioid use, daily mean patient-reported pain scores, and ORAEs through 72 hours postoperatively. RESULTS: On average, the EXP (n = 31) group exhibited less than 50 percent of the total opioid consumption of the PCAO (n = 36) group, and less than 60 percent of that for the ONQ (n = 33) group. Postoperative days 1 and 3 pain scores were significantly lower for the EXP group as compared to the ONQ and PCAO groups (p ≤ 0.005). Fewer patients in the EXP group (19.4 percent) experienced ORAEs compared to the PCAO (41.1 percent) and ONQ (45.5 percent) groups (p = 0.002). CONCLUSIONS: Laparotomy patients treated with liposomal bupivacaine as part of a multimodal regimen consumed less opioids, had lower pain scores, and had fewer ORAEs. The role of liposomal bupivacaine in the postoperative care of laparotomy patients merits further study.

RNP Assembly Defects in Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a motor neuron disease caused by mutations/deletions within the survival of motor neuron 1 (SMN1) gene that lead to a pathological reduction of SMN protein levels. SMN is part of a multiprotein complex, functioning as a molecular chaperone that facilitates the assembly of spliceosomal small nuclear ribonucleoproteins (snRNP). In addition to its role in spliceosome formation, SMN has also been found to interact with mRNA-binding proteins (mRBPs), and facilitate their assembly into mRNP transport granules. The association of protein and RNA in RNP complexes plays an important role in an extensive and diverse set of cellular processes that regulate neuronal growth, differentiation, and the maturation and plasticity of synapses. This review discusses the role of SMN in RNP assembly and localization, focusing on molecular defects that affect mRNA processing and may contribute to SMA pathology.

mRNP assembly, axonal transport, and local translation in neurodegenerative diseases.

The development, maturation, and maintenance of the mammalian nervous system rely on complex spatiotemporal patterns of gene expression. In neurons, this is achieved by the expression of differentially localized isoforms and specific sets of mRNA-binding proteins (mRBPs) that regulate RNA processing, mRNA trafficking, and local protein synthesis at remote sites within dendrites and axons. There is growing evidence that axons contain a specialized transcriptome and are endowed with the machinery that allows them to rapidly alter their local proteome via local translation and protein degradation. This enables axons to quickly respond to changes in their environment during development, and to facilitate axon regeneration and maintenance in adult organisms. Aside from providing autonomy to neuronal processes, local translation allows axons to send retrograde injury signals to the cell soma. In this review, we discuss evidence that disturbances in mRNP transport, granule assembly, axonal localization, and local translation contribute to pathology in various neurodegenerative diseases, including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD).

Intensity modulated radiation therapy with simultaneous integrated boost based dose escalation on neoadjuvant chemoradiation therapy for locally advanced distal esophageal adenocarcinoma.

AIM: To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost (IMRT-SIB). METHODS: We retrospectively reviewed the patients who underwent four-dimensional-based IMRT-SIB-based neoadjuvant chemoradiation protocol. During the concurrent chemoradiation therapy, radiation therapy was through IMRT-SIB delivered in 28 consecutive daily fractions with total radiation doses of 56 Gy to tumor and 5040 Gy dose-painted to clinical tumor volume, with a regimen at the discretion of the treating medical oncologist. This was followed by surgical tumor resection. We analyzed pathological completion response (pCR) rates its relationship with overall survival and event-free survival. RESULTS: Seventeen patients underwent dose escalation with the IMRT-SIB protocol between 2007 and 2014 and their records were available for analysis. Among the IMRT-SIB-treated patients, the toxicity appeared mild, the most common side effects were grade 1-3 esophagitis (46%) and pneumonitis (11.7%). There were no cardiac events. The Ro resection rate was 94% (n = 16), the pCR rate was 47% (n = 8), and the postoperative morbidity was zero. There was one mediastinal failure found, one patient had local failure at the anastomosis site, and the majority of failures were distant in the lung or bone. The 3-year disease-free survival and overall survival rates were 41% (n = 7) and 53% (n = 9), respectively. CONCLUSION: The dose escalation through IMRT-SIB in the chemoradiation regimen seems responsible for down-staging the distal esophageal with well-tolerated complications.

A method to estimate the chronic health impact of air pollutants in U.S. residences.

BACKGROUND: Indoor air pollutants (IAPs) cause multiple health impacts. Prioritizing mitigation options that differentially affect individual pollutants and comparing IAPs with other environmental health hazards require a common metric of harm. OBJECTIVES: Our objective was to demonstrate a methodology to quantify and compare health impacts from IAPs. The methodology is needed to assess population health impacts of large-scale initiatives-including energy efficiency upgrades and ventilation standards-that affect indoor air quality (IAQ). METHODS: Available disease incidence and disease impact models for specific pollutant-disease combinations were synthesized with data on measured concentrations to estimate the chronic heath impact, in disability-adjusted life-years (DALYs) lost, due to inhalation of a subset of IAPs in U.S. residences. Model results were compared with independent estimates of DALYs lost due to disease. RESULTS: Particulate matter ≤ 2.5 µm in aerodynamic diameter (PM2.5), acrolein, and formaldehyde accounted for the vast majority of DALY losses caused by IAPs considered in this analysis, with impacts on par or greater than estimates for secondhand tobacco smoke and radon. Confidence intervals of DALYs lost derived from epidemiology-based response functions are tighter than those derived from toxicology-based, interspecies extrapolations. Statistics on disease incidence in the United States indicate that the upper-bound confidence interval for aggregate IAP harm is implausibly high. CONCLUSIONS: The approach demonstrated in this study may be used to assess regional and national initiatives that affect IAQ at the population level. Cumulative health impacts from inhalation in U.S. residences of the IAPs assessed in this study are estimated at 400-1,100 DALYs lost annually per 100,000 persons.

Laparoscopic transhiatal esophagectomy at a low-volume center.

BACKGROUND AND OBJECTIVES: Surgical treatment of esophageal cancer is associated with a high rate of morbidity, even in specialized centers. Minimally invasive esophageal resection has become increasingly feasible and is gaining popularity in some high-volume institutions. This study assesses the short-term outcomes of laparoscopic transhiatal esophagectomy performed by a single surgeon at a single low-volume institution over a 20-month period. METHODS: Over the study period, 16 patients underwent laparoscopic transhiatal esophagectomy. All patients were men with an average age of 70 years (range, 50 to 81). RESULTS: Two patients required intraoperative conversion to alternative surgical techniques, 1 to an Ivor-Lewis esophagectomy and 1 to an open transhiatal approach. Average operative time was 198 minutes (range, 147 to 303). Mean hospital stay was 16.7 days (range, 9 to 30). The average number of resected lymph nodes was 11.7, and 2 patients had benign pathology. No deaths occurred in the 30-day postoperative period. CONCLUSION: Laparoscopic transhiatal esophagectomy is an advanced laparoscopic procedure that can be performed with equivalent morbidity and mortality by a low-volume surgeon in a low-volume center with results comparable to those of high-volume centers. While several authors have demonstrated a correlation between lower mortality rates and high-volume esophagectomy hospitals, our results support surgeon experience as more important than the absolute number of procedures performed each year.

Laparoscopic repair of chronic traumatic diaphragmatic hernia using biologic mesh with cholecystectomy for intrathoracic gallbladder.

BACKGROUND AND OBJECTIVES: Diaphragmatic rupture is a serious complication of both blunt and penetrating abdominal trauma. In the acute setting, delay in diagnosis can lead to severe cardiovascular and respiratory compromise. Chronic cases can present years later with a plethora of clinical symptoms. Laparoscopic techniques are being increasingly utilized in the diagnosis and treatment of traumatic diaphragmatic hernias. METHOD: We describe a case of a 70-year-old female who presented with signs and symptoms of a small bowel obstruction. She was ultimately found to have an obstruction secondary to a chronic traumatic diaphragmatic hernia with an intrathoracic gallbladder and incarcerated small intestine. A cholecystectomy and diaphragmatic hernia repair were both performed laparoscopically. This case report presents an atypical cause of bowel obstruction and reviews the current literature on laparoscopic management of traumatic diaphragmatic hernias. RESULTS AND CONCLUSION: Laparoscopy is increasingly used in the diagnosis and treatment of traumatic diaphragmatic hernias with good results.

Postcolonoscopy appendicitis.

Outpatient colonoscopy has been proven safe but can rarely be associated with serious complications. The addition of polypectomy to the procedure increases the incidence of all complications with hemorrhage accounting for approximately half. The use of electrocautery for hot biopsy or polyp removal can result in a full-thickness burn without perforation in approximately 1 per cent of cases and typically presents as focal peritonitis without pneumoperitoneum. This so-called "postpolypectomy syndrome" or "serositis" is often successfully managed medically with resolution of symptoms in 24 to 48 hours. Bowel perforation occurs in less than 1 per cent of patients but requires emergent laparotomy. Appendicitis, both acute and perforated, has been reported as a rare complication of colonoscopy.

Framework for evaluating anthrax risk in buildings.

If Bacillus anthracis (BA), the organism that causes anthrax, is known or suspected to have contaminated a building, a critical decision is what level of contamination is unacceptable. This decision has two components: (1) what is the relationship between the degree of contamination and the risk to occupants, (2) and what is an acceptable risk to occupants? These lead to a further decision: (3) how many samples must be taken to determine whether a building is unacceptably contaminated? We discuss existing data that bear on these questions, and introduce a nomogram that can be used to investigate the relationship between risk of contracting anthrax, the surface concentration of BA, the probability of detection, and the number of samples needed to ensure detection with a given degree of certainty. The same approach could be used for other agents that are dangerous due to resuspension of deposited particles.

Mortality rate associated with 56 consecutive esophagectomies performed at a "low-volume" hospital: is procedure volume as important as we are trying to make it?

BACKGROUND: Esophagectomy procedures have been associated with high morbidity and mortality rates. Recent articles in the literature have focused on the relationship between operative volume and the rates of mortality and morbidity in association with esophagectomy. The common theme among these publications is the statistically significant correlation between high-volume centers (typically defined as at least 10 esophagectomies per year) and lower mortality rates. The authors hypothesized that an individual surgeon's expertise with the various esophagectomy procedures would better correlate to mortality rates than the absolute number performed in an institution per year. STUDY DESIGN: The study involved a retrospective cohort of a single surgeon over a 7-year period (August 17, 1999-December 23, 2006). Selection criteria included all patients who had undergone a transhiatal esophagectomy, transabdominal with diaphragmatic split esophagectomy, or Ivor-Lewis esophagectomy procedure by a single surgeon (PP) during the specified time period. The main outcome measures were 30-day mortality and postoperative complications. RESULTS: Over the 7-year study period, 56 esophagectomies were performed (average, eight per year). The 30-day morbidity and mortality rates were 48% (27/56) and 3.57% (2/56), respectively. CONCLUSIONS: If low-volume esophagectomy centers are to be defined in the literature as completing <10 procedures per year, then these data represent such an institution. While several authors have demonstrated a correlation between lower mortality rates and high-volume esophagectomy hospitals, our results support surgeon experience as potentially being more significant than absolute number of procedures performed in an institution per year.

Comorbidity among the morbidly obese: a comparative study of 2002 U.S. hospital patient discharges.

BACKGROUND: Increased morbidity is associated with increasing severity of obesity. However, among morbidly obese patients, comorbid prevalence has been reported primarily in the bariatric surgical literature. This study compares demographic characteristics and selected comorbid conditions of morbidly obese patients discharged after surgical obesity procedures and morbidly obese patients discharged after all other hospital procedures. METHODS: The 2002 National Hospital Discharge Survey (a nationally representative sample of hospital discharge records) and the International Classification of Diseases, 9th Revision, Clinical Modification were used to identify and describe all morbidly obese patient discharges (n = 3,473) and to quantify the prevalence of selected obesity-related comorbid conditions. RESULTS: Compared with all other morbidly obese patients, the obesity surgery patients (n = 833) were younger (median, 42 vs 48 years; range, 17 to 67) and more female (82.3% vs. 63.7%), with higher rates of sleep apnea (24.0% vs. 11.8%), osteoarthritis (22.9% vs. 11.8%), and gastroesophageal reflux disease (27.7% vs. 11.7%) (all P < .001). The prevalence of type 2 diabetes mellitus was lower in the obesity surgery patients (16.1% vs. 24.3%; P = .003), whereas the rates of hypertension (45.9% vs. 41.0%; P = .13) and asthma (9.6% vs. 12.0%; P = .26) were similar in the two groups. CONCLUSIONS: Demographic characteristics and comorbid prevalence of morbidly obese patients discharged after obesity surgery are consistent with reports in the bariatric surgical literature. Obesity surgery patients had a higher prevalence of some comorbid conditions. Possible explanations for this include preferential diagnosis, differential diagnostic coding, or increased severity of morbid obesity. Advancing surgical and insurance guidelines for bariatric surgery will require clinical data that accurately describe and quantify the demographic distribution of obesity and the associated burden of disease.

Using image and curve registration for measuring the goodness of fit of spatial and temporal predictions.

Conventional measures of model fit for indexed data (e.g., time series or spatial data) summarize errors in y, for instance by integrating (or summing) the squared difference between predicted and measured values over a range of x. We propose an approach which recognizes that errors can occur in the x-direction as well. Instead of just measuring the difference between the predictions and observations at each site (or time), we first "deform" the predictions, stretching or compressing along the x-direction or directions, so as to improve the agreement between the observations and the deformed predictions. Error is then summarized by (a) the amount of deformation in x, and (b) the remaining difference in y between the data and the deformed predictions (i.e., the residual error in y after the deformation). A parameter, lambda, controls the tradeoff between (a) and (b), so that as lambda-->infinity no deformation is allowed, whereas for lambda=0 the deformation minimizes the errors in y. In some applications, the deformation itself is of interest because it characterizes the (temporal or spatial) structure of the errors. The optimal deformation can be computed by solving a system of nonlinear partial differential equations, or, for a unidimensional index, by using a dynamic programming algorithm. We illustrate the procedure with examples from nonlinear time series and fluid dynamics.

Migrating mesh plug: complication of a well-established hernia repair technique.

The mesh plug technique for repair of inguinal hernia has become one of the standard procedures in general surgery. The evolution of the technique of occluding the fascial defect with a foreign body has extensively been described in the surgical literature. The associated complications are also well described. We find only two published reports describing complications related to migration of a mesh plug. We present a case of a 50-year-old man with vague left lower quadrant pain approximately 18 months after left indirect inguinal hernia repair with the PerFix plug (Bard, Murray Hill, NJ) and overlay patch method. Laparoscopic exploration determined that the plug had migrated away from the left internal ring in the preperitoneal space and was involved with significant adhesions. The plug was removed, and his hernia was repaired laparoscopically with GORE-TEX mesh (W.L. Gore, Tempe, AZ). The patient's symptoms were relieved, and he remained pain free through follow-up at 6 months.

Laparoscopic Heller myotomy with epiphrenic diverticulectomy.

BACKGROUND AND OBJECTIVES: To describe the technique and results of laparoscopic Heller myotomy and Toupet fundoplication combined with epiphrenic diverticulectomy. CASE REPORT: A 75-year-old man presented to our institution complaining of dysphagia to solid foods and liquids. The preoperative preparation included a barium swallow, esophagoscopy, and esophageal manometry. Three months earlier, the patient had a botulinum toxin injection, which provided temporary relief. Ten months later, the patient underwent a laparoscopic Heller myotomy and Toupet fundoplication combined with an epiphrenic diverticulectomy. RESULTS: No complications occurred. The patient tolerated clear liquids on postoperative day 1; on postoperative day 2, he was discharged tolerating full liquids. He returned to full activity in 1 week. CONCLUSIONS: Epiphrenic diverticulectomy combined with treatment for the underlying motor disorder and gastroesophageal reflux prevention is an accepted practice. We demonstrate that this rare problem can be approached with the laparoscopic technique. Given this favorable result, we plan to continue this technique and establish a longer follow-up and wider series.