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.     

Effect of Staphylococcus aureus extracellular proteinaceous fraction in an isolated osteoclastic resorption assay

Staphylococcus aureus infection of bone causes severe bone damage but the mechanisms responsible remain to be established. We used the protein-rich fraction released by saline extraction of Staphylococcus aureus (SAM) to test the hypothesis that the surface-associated proteins promote bone breakdown by directly activating osteoclasts. Isolated chick osteoclasts were incubated on dentine slices with or without the surface protein fraction from S. aureus. The resulting osteoclastic excavations were measured using confocal reflection microscopic surface mapping. SAM both stimulated the formation of resorption pits and induced the production of pits with larger volume : area ratios.. Received: Jan. 5, 1998 / Accepted: March 18, 1998     

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.     

Jejunoileal bypass reversal: effect on renal function, metabolic parameters and stone formation

PURPOSE: While the effect of jejunoileal bypass (JIB) reversal has been well studied regarding hepatic function, there is little information regarding the effect of reversal on renal function and even less data regarding the metabolic urinary stone environment. We evaluated the results of JIB reversal on renal function, the urinary stone milieu and the clinical development of recurrent calculi in affected patients. MATERIALS AND METHODS: From 1995 to 2003, 4 female patients with a mean age of 48.2 years underwent JIB reversal primarily for refractory stone disease. The clinical and metabolic courses prior to and following bypass reversal were reviewed specifically to evaluate renal function, serum and urinary metabolic stone profiles, and clinical stone formation. RESULTS: At initial presentation following JIB all 4 patients had significantly increased 24-hour urinary oxalate (range 80 to 160 mg, mean 112.5, normal less than 50) and significantly low 24-hour urinary citrate (range 5 to 62 mg, mean 21.5, normal greater than 320). Following reversal 24-hour urinary oxalate normalized to between 31 and 36 mg (mean 33.75). However, 24-hour urinary citrate continued to be low (range 215 to 248 mg, mean 226.5). After JIB reversal all 4 patients continued to have new stones until the commencement of urinary alkalization, following which only 1 had 1 calculus, which occurred 47 months after reversal. After JIB mean serum creatinine was 1.48 mg/dl (range 0.8 to 1.9) and mean urinary creatinine excretion was 0.91 mg per hour (range 0.69 to 1.15). After JIB reversal mean serum creatinine was 1.28 mg/dl (range 0.6 to 2.0) and mean urinary creatinine excretion was 1.0 mg per hour (range 0.85 to 1.10). CONCLUSIONS: JIB reversal normalizes 24-hour urinary oxalate. While urinary citrate improves, it continues to be low and such patients are at high risk for recurrent stone formation. However, in this setting appropriate replacement therapy has a significant and positive impact on that propensity.     

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.     

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.     

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.     

Soleus H-reflex modulation after motor incomplete spinal cord injury: effects of body position and walking speed

Objective:

To examine position-dependent (semireclined to standing) and walking speed–dependent soleus H-reflex modulation after motor incomplete spinal cord injury (SCI).

Participants:

Twenty-six patients with motor incomplete SCI (mean: 45 ± 15 years) and 16 noninjured people (mean: 38 ± 14 years).

Methods:

Soleus H-reflexes were evoked by tibial nerve stimulation. Patients were tested in semireclined and standing positions (experiment 1) and in midstance and midswing positions (experiment 2).

Results:

H-reflexes were significantly greater after SCI in all positions compared with noninjured people (P < 0.05). Position-dependent modulation from semireclined to standing (normally observed in noninjured people) was absent after SCI. In SCI patients, H-reflex modulation was not significantly different at 1.2 m/s compared with 0.6 m/s treadmill walking speed; in noninjured people, H-reflex modulation was significantly greater at 1.2 m/s compared with 0.6 m/s treadmill walking speed. There was a significant positive correlation between modified Ashworth scores, a clinical measure of spasticity and soleus H-reflex amplitudes tested in all positions. A significant negative correlation was also found between H-reflexes in standing and midstance positions and the amount of assistance patients required to walk.

Conclusions:

An improvement in position-dependent and walking speed–dependent reflex modulation after SCI may indicate functional recovery. Future studies will use H-reflex testing to track changes as a result of therapeutic interventions.