Bilateral simultaneous laparoscopic adrenalectomy in Cushing's syndrome: safe, effective, and curative

INTRODUCTION: Surgical morbidity and mortality rates are high in patients with Cushing's syndrome. Nevertheless, simultaneous bilateral laparoscopic adrenalectomy (LA) is feasible in these patients with less morbidity and good long-term results. BACKGROUND AND RESULTS: Consecutive 22 patients who underwent LA for Cushing's syndrome between 2003 and 2010 in our institute were retrospectively studied. Ninteen patients underwent bilateral simultaneous and three underwent unilateral LA. Seven patients had Cushing's syndrome after failed pituitary surgery and five each had ectopic adrenocorticotrophic hormone dependent syndrome and bilateral macronodular hyperplasia respectively. LA was bilaterally done by lateral transabdominal adrenalectomy in 15 patients and retroperitoneal endoscopic adrenalectomy in 4 on the right side. Mean operative time for simultaneous bilateral cases was 199.45±72.43 minutes with mean blood loss of 72.72±48.6 mL. Patients were fit for discharge by the fifth postoperative day from the surgical aspect. Surgical complication rate was 26% that included wound infections in two, port site hernia, pleural effusion, and atelectasis in one each. One patient died of sepsis (5% mortality). Satisfactory metabolic control was achieved in all observable patients in the long term although Addisonian crisis and Nelson syndrome were seen in 26% and 15% respectively. CONCLUSION: LA has all advantages of minimal access surgery in patients with Cushing's syndrome who are immunocompromised and at high risk of delayed wound healing and infections. Magnification decreases the risk of retained adrenal remnants. Despite advances in minimal access surgery, perioperative morbidity continues to be significant for the procedure.     

Allograft transmission of hepatitis C virus infection from infected donors in cardiac transplantation

BACKGROUND: The frequency and outcome of hepatitis C virus (HCV) infection in recipients of hearts from HCV-infected donors remains poorly characterized. METHODS: Between 1991 and 1999, 10 anti-HCV-negative patients received hearts from donors who were anti-HCV and HCV RNA-positive. Each recipient was tested for anti-HCV and HCV RNA and serially evaluated for liver dysfunction. Recipient records were reviewed for cumulative steroid boluses in the first posttransplant year and other components of the immune suppression regimen. We analyzed recipient outcome in relation to the virologic status of the donor, including the level of HCV RNA and genotype and the type of antirejection therapy. RESULTS: All 10 recipients became HCV RNA positive. Donor-recipient pairs expressed identical genotypes in each instance. Six of nine evaluable recipients developed biochemical evidence of hepatitis. Recipients with genotype 1 (1a, 1b) accounted for five of the six cases, and all patients with genotype 1 developed hepatitis. Severe liver injury occurred in two patients. Two deaths occurred, both of which were genotype 1 patients who had been given multiple boluses of corticosteroids in the first posttransplant year. No definite relationship between viral load in the donor and recipient outcome was found. CONCLUSION: Transmission of HCV infection from cardiac donors who are viremic at the time of organ donation occurs with high frequency and can cause severe hepatitis. Hearts from infected patients should probably be restricted to those recipients who already have evidence for hepatitis C or are in need of emergent transplantation.     

Heart transplant for anomalous origin of left coronary artery from pulmonary artery

Anomalous origin of the left coronary artery from the pulmonary artery is a congenital coronary artery malformation most commonly present in infancy. A variety of surgical procedures have been described to achieve physiological correction of the coronary flow abnormalities. These techniques are effective as long as there is potential for myocardial recovery. However the sequelae of chronic myocardial ischemia that characterize this entity often irreversibly damage the heart and preclude correction and palliation of the native anomaly. In this type of setting, heart transplantation is a realistic option. Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) occasionally presents in adulthood. Anatomic repair with a two coronary artery system may not be optimal in patients presenting with ischemic cardiomyopathy. We report an adult patient with platelet factor 4 (PF4) antibodies who underwent orthotopic heart transplantation (OHT) for ALCAPA.     

Abdominal lean muscle is associated with lower mortality among kidney waitlist candidates

Morphometric assessments, such as muscle density and body fat distribution, have emerged as strong predictors of cardiovascular risk and postoperative morbidity and mortality. To date, no study has examined morphometric mortality risk prediction among kidney transplant (KT) candidates. KT candidates, waitlisted 2008‐2009, were identified (n=96) and followed to the earliest of transplant, death, or administrative end of study. Morphometric measures, including abdominal adipose tissue, paraspinous and psoas muscle composition, and aortic calcification, were measured from CTs. Risk of waitlist mortality was examined using Cox proportional hazard regression. On adjusted analyses, radiologic measures remained independently and significantly associated with lower waitlist mortality; the addition of radiologic measures significantly improved model predictive ability over models containing traditional risk factors alone (net reclassification index: 0.56, 95% CI: 0.31‐0.75). Higher psoas muscle attenuation (indicative of leaner muscle) was associated with decreased risk of death (aHR: 0.93, 95% CI: 0.91‐0.96, P<.001), and for each unit increase in lean paraspinous volume, there was an associated 2% decreased risk for death (aHR: 0.98, 95% CI: 0.96‐0.99, P=.03). Radiologic measures of lean muscle mass, such as psoas muscle attenuation and paraspinous lean volume, may improve waitlist mortality risk prediction and candidate selection.     

The neoadjuvant rectal score and a novel magnetic resonance imaging based neoadjuvant rectal score are stage independent predictors of long-term outcome in locally advanced rectal cancer

Aim

Neoadjuvant rectal (NAR) score is an early surrogate for longer-term outcomes in rectal cancer undergoing radiotherapy and resection. In an era of increasing organ preservation, resection specimens are not always available to calculate the NAR score. Post-treatment magnetic resonance imaging (MRI) re-staging of regression is subjective, limiting reproducibility. We explored the potential for a novel MRI-based NAR score (mrNAR) adapted from the NAR formula.

Methods

Locally advanced rectal cancer patients undergoing neoadjuvant therapy (nCRT) and surgery were retrospectively identified between 2008 and 2020 in a single cancer network. mrNAR was calculated by adapting the NAR formula, replacing pathological (p) stages with post-nCRT MR stages (ymr). Cox regression assessed relationships between clinicopathological characteristics, NAR and mrNAR with overall survival (OS) and recurrence-free survival (RFS).

Results

In total, 381 NAR and 177 mrNAR scores were calculated. On univariate analysis NAR related to OS (hazard ratio [HR] 2.05, 95% confidence interval [CI] 1.33–3.14, p = 0.001) and RFS (HR 2.52, 95% CI 1.77–3.59, p = 0.001). NAR 3-year OS <8 was 95.3%, 8–16 was 88.6% and >16 was 80%. mrNAR related to OS (HR 2.96, 95% CI 1.38–6.34, p = 0.005) and RFS (HR 2.99, 95% CI 1.49–6.00, p = 0.002). 3-year OS for mrNAR <8 was 96.2%, 8–16 was 92.4% and >16 was 78%. On multivariate analysis, mrNAR was a stage-independent predictor of OS and RFS. mrNAR corresponded to NAR score category in only 15% (positive predictive value 0.23) and 47.5% (positive predictive value 0.48) of cases for categories <8 and >16, respectively.

Conclusions

Neoadjuvant rectal score is validated as a surrogate end-point for long-term outcomes. mrNAR categories do not correlate with NAR but have stage-independent prognostic value. mrNAR may represent a novel surrogate end-point for future neoadjuvant treatments that focus on organ preservation.     

Lessons learned: optimization of a murine small bowel resection model

Purpose

Central to the use of murine models of disease is the ability to derive reproducible data. The purpose of this study was to determine factors contributing to variability in our murine model of small bowel resection (SBR).

Methods

Male C57Bl/6 mice were randomized to sham or 50% SBR. The effect of housing type (pathogen-free vs standard housing), nutrition (reconstituted powder vs tube feeding formulation), and correlates of intestinal morphology with gene expression changes were investigated. Multiple linear regression modeling or 1-way analysis of variance was used for data analysis.

Results

Pathogen-free mice had significantly shorter ileal villi at baseline and demonstrated greater villus growth after SBR compared to mice housed in standard rooms. Food type did not affect adaptation. Gene expression changes were more consistent and significant in isolated crypt cells that demonstrated adaptive growth when compared with crypts that did not deepen after SBR.

Conclusion

Maintenance of mice in pathogen-free conditions and restricting gene expression analysis to individual animals exhibiting morphologic adaptation enhances sensitivity and specificity of data derived from this model. These refinements will minimize experimental variability and lead to improved understanding of the complex process of intestinal adaptation.     

Photodynamic inactivation of <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> biofilms and planktonic cells by 5-aminolevulinic acid and 5-aminolevulinic acid methyl ester

The treatment of Klebsiella pneumoniae, particularly extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae, is currently a great challenge. Photodynamic antimicrobial chemotherapy is a promising approach for killing antibiotic-resistant bacteria. The aim of this study was to evaluate the capacity of 5-aminolevulinic acid (5-ALA) and its derivative 5-ALA methyl ester (MAL) in the presence of white light to cause photodynamic inactivation (PDI) of K. pneumoniae planktonic and biofilm cells. In the presence of white light, 5-ALA and MAL inactivated planktonic cells in a concentration-dependent manner. Biofilms were also sensitive to 5-ALA and MAL-mediated PDI. The mechanisms by which 5-ALA and MAL caused PDI of ESBL-producing K. pneumonia were also investigated. Exposure of K. pneumonia to light in the presence of either 5-ALA or MAL induced cleavage of genomic DNA and the rapid release of intracellular biopolymers. Intensely denatured cytoplasmic contents and aggregated ribosomes were also detected by transmission electron microscopy. Scanning electron microscopy showed that PDI of biofilms caused aggregated bacteria to detach and that the bacterial cell envelope was damaged. This study provides insights into 5-ALA and MAL-mediated PDI of ESBL-producing K. pneumoniae.     

Differential responses of visceral and subcutaneous fat depots to nutrients

Increased visceral adiposity is a pivotal component of the metabolic syndrome. Differential gene expression patterns of fat-derived peptides (FDPs) in visceral fat and subcutaneous fat have been characterized in the fasting state. Here we examined whether delivery of nutrients differentially affects the expression of FDPs in visceral fat versus subcutaneous fat (in the fed state). We increased the rate of glucose flux into adipose tissue of normal rats (n = 16) by hyperglycemia or hyperinsulinemia using the clamp technique. Glucose uptake was associated with increased expression of FDPs, including resistin ( approximately 5-fold), adiponectin ( approximately 2-fold), leptin ( approximately 15-fold), plasminogen activating inhibitor-1 ( approximately 10-fold), and angiotensinogen ( approximately 4-fold) in visceral fat, but markedly less in subcutaneous fat. Cytokine expression derived mainly from vascular/stromal/macrophage components of adipose tissue was less dramatically increased. Infusion of glucosamine amplified the results obtained by increasing glucose uptake into adipose tissue, suggesting that flux through the hexosamine biosynthetic pathway may serve as a mechanism for "nutrient sensing." Nutrient-dependent expression of FDPs in visceral fat was also associated with increased plasma levels of several FDPs. Because a biologic sensing pathway can dynamically couple daily food intake to abnormal plasma levels of important FDPs, we challenge the practice of obtaining plasma levels after fasting to assess risk factors for metabolic syndrome.     

Heavy metal accumulation in medicinal plants collected from environmentally different sites

Objective To estimate the heavy metal content in soil and selected medicinal plants procured from environmentally different sites of the same city. Methods Soil and plant samples of Abutilon indicum, Calotropis procera, Euphorbia hirta, Peristrophe bycaliculata, and Tinospora cordifolia were collected from 3 environmentally different sites of the city： heavy traffic area （HTA）, industrial area （IA）, and residential area （RA）. Pb by inductively coupled plasma emission spectrometry and compared Cd, Cr, and Ni were estimated in soil and plant samples Results The level of heavy metal was higher in soil than in plant parts studied. Accumulation of heavy metals varied from plant to plant. Pb was the highest in Calotropis procera root from HTA site and the lowest in Peristrophe bycaliculata whole plant from IA site. It was also lower in residential area than in heavy traffic area. Conclusion The level of heavy metal content differed in the same medicinal plant collected from environmentally different sites of the same city. Thus, it reiterates our belief that every medicinal plant sample should be tested for contaminant load before processing it further for medication.     

Myotonic dystrophy with pregnancy

Myotonic dystrophy is a rare heredodegenerative muscular disorder in which pregnancy is unusual. Because of the autosomal dominant inheritance of the disease, 50% of children of an affected parent may have the disease; 20% of them are asymptomatic at birth. Foetal involvement may be manifested by polyhydramnios, arthrogryposis multiplex in utero, respiratory difficulties, and floppiness at birth. A case of myotonic dystrophy with pregnancy is presented here.