Jennifer Q. Zhang

Differential response of the plant Medicago truncatula to its symbiont Sinorhizobium meliloti or an exopolysaccharide-deficient mutant

Sinorhizobium meliloti forms symbiotic, nitrogen-fixing nodules on the roots of Medicago truncatula. The bacteria invade and colonize the roots through structures called infection threads. S. meliloti unable to produce the exopolysaccharide succinoglycan are unable to establish a symbiosis because they are defective in initiating the production of infection threads and in invading the plant. Here, we use microarrays representing 16,000 M. truncatula genes to compare the differential transcriptional responses of this host plant to wild-type and succinoglycan-deficient S. meliloti at the early time point of 3 days postinoculation. This report describes an early divergence in global plant gene expression responses caused by a rhizobial defect in succinoglycan production, rather than in Nod factor production. The microarray data show that M. truncatula inoculated with wild-type, succinoglycan-producing S. meliloti more strongly express genes encoding translation components, protein degradation machinery, and some nodulins than plants inoculated with succinoglycan-deficient bacteria. This finding is consistent with wild-type-inoculated plants having received a signal, distinct from the well characterized Nod factor, to alter their metabolic activity and prepare for invasion. In contrast, M. truncatula inoculated with succinoglycan-deficient S. meliloti more strongly express an unexpectedly large number of genes in two categories: plant defense responses and unknown functions. One model consistent with our results is that appropriate symbiotically active exopolysaccharides act as signals to plant hosts to initiate infection thread formation and that, in the absence of this signal, plants terminate the infection process, perhaps via a defense response.

Risk factors for readmission after lower extremity bypass in the American College of Surgeons National Surgery Quality Improvement Program

OBJECTIVE Readmission is associated with high mortality, morbidity, and cost. We used the American College of Surgeons National Surgery Quality Improvement Program (ACS-NSQIP) to determine risk factors for readmission after lower extremity bypass (LEB). METHODS We identified all patients who received LEB in the 2011 ACS-NSQIP database. Multivariable logistic regression was used to assess independent predictors of 30-day readmission. We also identified our institutional contribution of LEB patients to the ACS-NSQIP from 2005 to 2011 to determine our institutions rate of readmission and readmission indications. RESULTS Among 5018 patients undergoing LEB, ACS-NSQIP readmission analysis was performed on 4512, excluding those whose readmission data were unavailable, who suffered a death on index admission, or who remained in the hospital at 30 days. Overall readmission rate was 18%, and readmission rate of those with NSQIP-captured complications was 8%. Multivariable predictors of readmission were dependent functional status (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.08-1.79), dyspnea (OR, 1.28; 95% CI, 1.02-1.60), cardiac comorbidity (OR, 1.46; 95% CI, 1.16-1.84), dialysis dependence (OR, 1.44; 95% CI, 1.05-1.97), obesity (OR, 1.28; 95% CI, 1.07-1.53), malnutrition (OR, 1.42; 95% CI, 1.12-1.79), critical limb ischemia operative indication (OR, 1.40; 95% CI, 1.10-1.79), and return to the operating room on index admission (OR, 8.0; 95% CI, 6.68-9.60). The most common postdischarge complications occurring in readmitted patients included wound complications (55%), multiple complications (22%), and graft failure (5%). Our institutional data contributed 465 LEB patients to the ACS-NSQIP from 2005 to 2012, with an overall readmission rate of 14%. Unplanned readmissions related to the original LEB (related unplanned) made up 75% of cases. The remainder 25% included readmissions that were planned staged procedures related to the original LEB (related planned, 11%) and admissions for a completely unrelated reason (unrelated unplanned, 14%). The most common readmission indications included wound infection (37%) and graft failure (10%). Readmissions were attributable to NSQIP-captured postdischarge complications in 44% of cases, an additional 44% had a non-NSQIP-defined reason for readmission, and the remainder (12%) included patients admitted for complications described in NSQIP but not meeting strict NSQIP criteria. CONCLUSIONS Readmissions are common after LEB. Optimization of select chronic conditions, closer follow-up of patients in poor health and those who required return to the operating room, and early detection of surgical site infections may improve readmission rates. Our finding that 25% of readmissions after LEB are not procedure related informs the broader discussion of how a readmission penalty affects vascular surgery in particular.

Neoadjuvant chemoradiation therapy is beneficial for clinical stage T2 N0 esophageal cancer patients due to inaccurate preoperative staging.

BACKGROUND It remains unclear if patients with clinical stage T2 N0 (cT2 N0) esophageal cancer should be offered induction therapy vs surgical intervention alone. METHODS This was a retrospective cohort study of cT2 N0 patients undergoing induction therapy, followed by surgical resection, or resection alone, at the Johns Hopkins Hospital from 1989 to 2009. Kaplan-Meier analysis was used to compare all-cause mortality in cT2 N0 patients who had resection alone vs those who had induction chemoradiation therapy, followed by resection. RESULTS A study cohort of 69 patients was identified and divided into two groups: 55 patients (79.7%) received induction therapy and 14 (20.3%) did not. No statistically significant difference in 5-year survival rate was observed for the two groups: 49.5% for the resection-only group and 53.8% for the induction group. More than 50% of cT2 N0 patients were understaged. CONCLUSIONS For cT2 N0 esophageal cancer patients, the benefit of neoadjuvant therapy is still unclear. Induction therapy for cT2 N0 did not translate into a statistically significant improvement in survival. However, due to the significant understaging of T2 N0 patients, we recommend neoadjuvant therapy to all cT2N0 patients before operation.

Long-term Survival Outcomes by Smoking Status in Surgical and Nonsurgical Patients With Non-small Cell Lung Cancer: Comparing Never Smokers and Current Smokers

BACKGROUND Survival outcomes of never smokers with non-small cell lung cancer (NSCLC) who undergo surgery are poorly characterized. This investigation compared surgical outcomes of never and current smokers with NSCLC. METHODS This investigation was a single-institution retrospective study of never and current smokers with NSCLC from 1975 to 2004. From an analytic cohort of 4,546 patients with NSCLC, we identified 724 never smokers and 3,822 current smokers. Overall, 1,142 patients underwent surgery with curative intent. For survival analysis by smoking status, hazard ratios (HRs) were estimated using Cox proportional hazard modeling and then further adjusted by other covariates. RESULTS Never smokers were significantly more likely than current smokers to be women (P < .01), older (P < .01), and to have adenocarcinoma (P < .01) and bronchioloalveolar carcinoma (P < .01). No statistically significant differences existed in stage distribution at presentation for the analytic cohort (P = .35) or for the subgroup undergoing surgery (P = .24). The strongest risk factors of mortality among patients with NSCLC who underwent surgery were advanced stage (adjusted hazard ratio, 3.43; 95% CI, 2.32-5.07; P < .01) and elevated American Society of Anesthesiologists classification (adjusted hazard ratio, 2.18; 95% CI, 1.40-3.40; P < .01). The minor trend toward an elevated risk of death on univariate analysis for current vs never smokers in the surgically treated group (hazard ratio, 1.20; 95% CI, 0.98-1.46; P = .07) was completely eliminated when the model was adjusted for covariates (P = .97). CONCLUSIONS Our findings suggest that smoking status at time of lung cancer diagnosis has little impact on the long-term survival of patients with NSCLC, especially after curative surgery. Despite different etiologies between lung cancer in never and current smokers the prognosis is equally dismal.

Banff study of pathologic changes in lung allograft biopsy specimens with donor-specific antibodies

BACKGROUND The diagnosis of antibody-mediated rejection (AMR) in the lung transplant is still an area under investigation. We performed a blinded multicenter study to determine if any statistically significant histologic findings in transbronchial biopsy specimens from lung transplant patients correlate with the presence of donor-specific antibodies (DSAs). METHODS We asked 9 pathologists with experience in lung transplantation to evaluate 161 lung transplant biopsy specimens for various histologic parameters. The findings were correlated with antibody status positive for DSAs, positive for non-DSAs, and no antibodies (NABs) present. The significance of each histologic variable was reviewed. RESULTS We found no statistically significant association with acute cellular rejection, airway inflammation, or bronchiolitis obliterans and the presence or absence of antibodies. However, biopsy specimens with DSAs had a statistically significant difference vs NABs in the setting of acute lung injury, with or without diffuse alveolar damage (p = 0.0008), in the presence of capillary neutrophilic inflammation (p = 0.0014), and in samples with endotheliitis (p = 0.0155). In samples with complement 4d staining, there was a trend but no statistically significant difference between specimens associated with DSAs and specimens with NABs. CONCLUSIONS Capillary inflammation, acute lung injury, and endotheliitis significantly correlated with DSAs. The infrequently observed diffuse staining for complement 4d limits the usefulness of this stain.