Elevated hemoglobin A1c level and bariatric surgery complications.

INTRODUCTION: In cardiac and orthopedic surgery, elevated glycosylated hemoglobin (HbA1c) is a modifiable risk factor for postoperative complications. However, in bariatric surgery, there is insufficient evidence to assess the effectiveness of preoperative HbA1c assessment and its association with postoperative complications. The objective of this study was to assess the impact of HbA1c on early postoperative outcomes in bariatric surgery patients. METHODS: Patients who underwent laparoscopic sleeve gastrectomy and laparoscopic Roux-En-Y Gastric Bypass between 2017 and 2018 were selected for a retrospective review from the metabolic and bariatric surgery accreditation and quality improvement program (MBSAQIP) database. The study population of 118,742 patients was analyzed for our primary outcome which was defined as a composite of any postoperative complications occurring within 30 days. Two groups were defined by HbA1c cutoff: comparison point A (≤ 8% vs > 8%) and comparison point B (≤ 10% vs > 10%). Procedure-related complications were also examined on subgroup analysis. Propensity score matching (PSM) was used with one-to-one matching. The complication rates before and after PSM were calculated and assessed by Fisher's exact test and conditional logistic regression, respectively. RESULTS: After PSM, demographic and clinical characteristics were all balanced and elevated HbA1C was not associated with worse outcomes. After adjusting for underlying comorbidities, there was no statistically significant difference seen in the composite outcome for comparison point A HbA1C ≤ 8 and HbA1C > 8 (p = 0.22). For comparison point B, patients with HbA1C ≤ 10 had more composite complications compared to patients with HbA1C > 10 (p < 0.001). Also, on subgroup analysis after PSM for procedure-specific complications, patients above the cutoff threshold of 8 did not have worsened composite outcomes (p = 0.58 and 0.89 for sleeve and bypass, respectively). Again, at cutoff threshold of 10, patients in HbA1C ≤ 10 had more composite complications (p = 0.001 and 0.007 for sleeve and bypass, respectively). CONCLUSION: In this study of bariatric patients, elevated HbA1c > 8% or 10% was not associated with increased postoperative complications. HbA1c lower than 10% was associated with some types of adverse outcomes in this bariatric dataset. More studies are needed to investigate these findings further. A high HbA1c alone may not disqualify a patient from proceeding with bariatric surgery.

Diagnosis and operative management of a perforated de Garengeot hernia.

INTRODUCTION: A de Garengeot hernia, a femoral hernia containing the appendix, is a difficult diagnosis often made intra-operatively when the hernia sac is opened. It is a rare finding, and complications are more frequent with a de Garengeot hernia. PRESENTATION OF CASE: A 92 year-old female presented to the emergency department (ED) complaining of abdominal pain. A computed tomographic (CT) scan of the abdomen and pelvis demonstrated a hernia anterior to the inguinal ligament without strangulation. Two weeks later the patient returned to the ED with worsening abdominal pain in the right lower quadrant. Repeat CT scan demonstrated a 7×4cm complex fluid collection in the right inguinal region, and the patient was taken to the operating room for exploration. The hernia sac was entered and found to contain the appendix with evidence of distal perforation. The appendix was taken out, and the hernia defect was repaired. The patient tolerated the procedure well. DISCUSSION: Femoral hernias have a high risk of incarceration due to the tightness of the femoral canal (Talini et al. 2015 [4]). Due to anatomic location of the appendix, de Garengeot hernias are most often seen on the right. Incarceration of the appendix is a clear etiology for appendicitis secondary to ischemia. CONCLUSION: Full preoperative workup for a femoral hernia often fails to diagnose the presence of the appendix within the hernia. It is important to have a high clinical suspicion for a de Garengeot's hernia in patients with incarcerated or strangulated right femoral hernias.

Toward stratification of patients with pancreatic cancer: Past lessons from traditional approaches and future applications with physical biomarkers.

Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate and outcomes have not improved substantially for decades. Significant attention has focused on the biological drivers of the disease, and preclinical work has pointed to multiple biomarker candidates and therapeutic avenues. However, translation of these promising biomarkers and treatment strategies to patients has not been overwhelmingly successful. New strategies to account for the significant heterogeneity of the disease are needed so that rational treatments can be administered. Here, we focus on how physical sciences-based approaches may play a role in stratifying patients for clinical trials, and how this view of PDAC may reinvigorate treatment strategies that have been abandoned after "failing" to fulfill their potential in unselected patient populations. By complementing biological approaches, the development of physical biomarkers of PDAC may help deliver on the promise of personalized medicine for this devastating disease.

Intra-tumoral heterogeneity of gemcitabine delivery and mass transport in human pancreatic cancer.

There is substantial heterogeneity in the clinical behavior of pancreatic cancer and in its response to therapy. Some of this variation may be due to differences in delivery of cytotoxic therapies between patients and within individual tumors. Indeed, in 12 patients with resectable pancreatic cancer, we previously demonstrated wide inter-patient variability in the delivery of gemcitabine as well as in the mass transport properties of tumors as measured by computed tomography (CT) scans. However, the variability of drug delivery and transport properties within pancreatic tumors is currently unknown. Here, we analyzed regional measurements of gemcitabine DNA incorporation in the tumors of the same 12 patients to understand the degree of intra-tumoral heterogeneity of drug delivery. We also developed a volumetric segmentation approach to measure mass transport properties from the CT scans of these patients and tested inter-observer agreement with this new methodology. Our results demonstrate significant heterogeneity of gemcitabine delivery within individual pancreatic tumors and across the patient cohort, with gemcitabine DNA incorporation in the inner portion of the tumors ranging from 38 to 74% of the total. Similarly, the CT-derived mass transport properties of the tumors had a high degree of heterogeneity, ranging from minimal difference to almost 200% difference between inner and outer portions of the tumor. Our quantitative method to derive transport properties from CT scans demonstrated less than 5% difference in gemcitabine prediction at the average CT-derived transport value across observers. These data illustrate significant inter-patient and intra-tumoral heterogeneity in the delivery of gemcitabine, and highlight how this variability can be reproducibly accounted for using principles of mass transport. With further validation as a biophysical marker, transport properties of tumors may be useful in patient selection for therapy and prediction of therapeutic outcome.

Towards an off-the-shelf vaccine therapy targeting shared B-cell tumor idiotypes.

The ideal tumor antigen is one expressed selectively by the tumor, present in all cancer patients, essential for tumor survival and nonetheless able to induce both humoral and cellular immune response. The personalized idiotype (Id) of the surface immunoglobulin is a tumor specific antigen in that it is expressed on clonal B-cell tumors, mediates B-cell survival, and induces tumor specific immunity in both human and animal models. With the availability of monoclonal antibodies against B cells, such as rituximab, the cellular immune response mediated by specific T cells has gained more importance as a combination therapy for the complete elimination of residual tumor cells in lymphoma and myeloma.

Nonstereotyped lymphoma B cell receptors recognize vimentin as a shared autoantigen.

Ag activation of the BCR may play a role in the pathogenesis of human follicular lymphoma (FL) and other B cell malignancies. However, the nature of the Ag(s) recognized by tumor BCRs has not been well studied. In this study, we used unbiased approaches to demonstrate that 42 (19.35%) of 217 tested FL Igs recognized vimentin as a shared autoantigen. The epitope was localized to the N-terminal region of vimentin for all vimentin-reactive tumor Igs. We confirmed specific binding to vimentin by using recombinant vimentin and by performing competitive inhibition studies. Furthermore, using indirect immunofluorescence staining, we showed that the vimentin-reactive tumor Igs colocalized with an anti-vimentin mAb in HEp-2 cells. The reactivity to N-terminal vimentin of IgG FL Igs was significantly higher than that of IgM FL Igs (30.4 versus 10%; p = 0.0022). However, vimentin-reactive FL Igs did not share CDR3 motifs and were not homologous. Vimentin was expressed in the T cell-rich regions of FL, suggesting that vimentin is available for binding with tumor BCRs within the tumor microenvironment. Vimentin was also frequently recognized by mantle cell lymphoma and multiple myeloma Igs. Our results demonstrate that vimentin is a shared autoantigen recognized by nonstereotyped FL BCRs and by the Igs of mantle cell lymphoma and multiple myeloma and suggest that vimentin may play a role in the pathogenesis of multiple B cell malignancies. These findings may lead to a better understanding of the biology and natural history of FL and other B cell malignancies.