Hybrid repair of type II thoracoabdominal aortic aneurysm using modified branch-first technique.

The hybrid modified branch-first technique has extended the feasibility of open thoracoabdominal aortic aneurysm (TAAA) repair in otherwise hostile aortic anatomy that is not entirely amenable for extent II open TAAA conventional repair or total endovascular repair. The modified branch-first open TAAA technique has been developed successfully at our center and has been used to treat extent III TAAAs with successful outcomes. By combining the modified technique with endovascular thoracic aortic repair, we have been able to successfully extend its use to more extensive extent II TAAAs. This could prove to be a useful technique in the armamentarium of aortic surgeons.

COVID-19 Related Arterial Coagulopathy.

Coronavirus disease of 2019 (COVID-19) is a disease caused by the novel coronavirus SARS-CoV-2, which is characterized by a multitude of clinical abnormalities, including hypercoagulability. Although thrombosis is commonly observed in sepsis, the hypercoagulable state associated with COVID-19 is much more dramatic and may not be related to either the severity of the disease or the D-dimer levels. It may be due to a prothrombotic state induced by the disease itself. We report three cases of arterial thrombosis with a significant clot burden requiring urgent medical and surgical intervention. It is now a common practice to initiate anticoagulation for deep venous thrombosis (DVT) prophylaxis based on the D-dimer level in hospitalized patients with COVID-19. However, in our clinical experience, D-dimer levels did not correlate well with the clot burden or the risk for future thrombosis.

Preclinical molecular imaging of the translocator protein (TSPO) in a metastases model based on breast cancer xenografts propagated in the murine brain.

Previous studies have demonstrated the feasibility of translocator protein (TSPO) imaging to visualize and quantify human breast adenocarcinoma (MDA-MB-231) cells in vivo using a TSPO-targeted near-infrared (NIR) probe (NIR-conPK11195). This study aimed to extend the use of the TSPO-targeted probe to a more biologically relevant and clinically important tumor microenvironment as well as to assess our ability to longitudinally detect the presence and progression of breast cancer cells in the brain. The in vivo biodistribution and accumulation of NIR-conPK11195 and free (unconjugated) NIR dye were quantitatively evaluated in intracranial MDA-MB-231-bearing mice and non-tumor-bearing control mice longitudinally once a week from two to five weeks post-inoculation. The in vivo time-activity curves illustrate distinct clearance profiles for NIR-conPK11195 and free NIR dye, resulting in preferential accumulation of the TSPO-targeted probe in the intracranial tumor bearing hemisphere (TBH) with significant tumor contrast over normal muscle tissue (p < 0.005 at five weeks; p < 0.01 at four weeks). In addition, the TSPO-labeled TBHs demonstrated significant contrast over the TBHs of mice injected with free NIR dye (p < 0.001 at four and five weeks) as well as over the TSPO-labeled non-tumor-bearing hemispheres (NTBHs) of control mice (p < 0.005 at four and five weeks). Overall, TSPO-targeted molecular imaging appears useful for visualizing and quantifying breast cancer xenografts propagated in the murine brain and may assist in preclinical detection, diagnosis and monitoring of metastatic disease as well as drug discovery. Furthermore, these results indicate it should be possible to perform TSPO-imaging of breast cancer cells in the brain using radiolabeled TSPO-targeted agents, particularly in light of the fact that [11C]-labeled TSPO probes such as [11C]-PK 11195 have been successfully used to image gliomas in the clinic.

Community acquired pneumonia: risk factors associated with mortality in a tertiary care hospitalized patients.

OBJECTIVE: To evaluate risk factors associated with mortality in patients hospitalized with CommunityAcquired Pneumonia (CAP) from a developing country. METHODS: An observational study was conducted on adult patients admitted with a diagnosis of CAP from January 2002 to August 2003 at Aga Khan University hospital, Karachi, Pakistan. Clinical records were reviewed for demographic characteristics, clinical and laboratory features, hospital course, and risk factors associated with mortality. RESULTS: A total of 329 patients (187 males) were admitted with CAP. Two-third of patients had underlying co-morbid medical illnesses. Complications developed in 15.7% cases and the overall mortality rate was 11%. Risk factors were identified on initial clinical assessment, laboratory and radiological features and during hospital course. On admission elevated blood urea, new onset of confusion, abnormal liver function test, low serum albumin, cardiomegaly and presence of underlying malignancy were strongly associated with increased mortality. Failure to respond to therapy was associated with a high risk of mortality as depicted by complication during hospital stay (Odds Ratio = 23.3, 95% Confidence Interval = 10.3-52.8), need for mechanical ventilation (OR = 17.1, 95% CI = 7.4-39.8) and need for intensive care unit (OR = 9, 95% CI = 4.2-19.3). CONCLUSIONS: Abnormal liver function test, low albumin and presence of cardiomegaly were more significant mortality risk factors than age, respiratory rate and blood pressure. Elevated blood urea and confusion remain strong risk factors on admission. Failure of response to therapy and onset of complications heralded a high risk of death.

CXCR4 mediates the proliferation of glioblastoma progenitor cells.

Increasing evidence points to a fundamental role for cancer stem cells (CSC) in the initiation and propagation of many tumors. As such, in the context of glioblastoma multiforme (GBM), the development of treatment strategies specifically targeted towards CSC-like populations may hold significant therapeutic promise. To this end, we now report that the cell surface chemokine receptor, CXCR4, a known mediator of cancer cell proliferation and invasion, is overexpressed in primary glioblastoma progenitor cells versus corresponding differentiated tumor cells. Furthermore, administration of CXCL12, the only known ligand for CXCR4, stimulates a specific and significant proliferative response in progenitors but not differentiated tumor cells. Taken together, these results implicate an important role for the CXCR4 signaling mechanism in glioma CSC biology and point to the therapeutic potential of targeting this pathway in patients with GBM.

CXCR4 expression is elevated in glioblastoma multiforme and correlates with an increase in intensity and extent of peritumoral T2-weighted magnetic resonance imaging signal abnormalities.

OBJECTIVE: With the objective of investigating the utility of CXCR4, a chemokine receptor known to mediate glioma cell invasiveness, as a molecular marker for peritumoral disease extent in high-grade gliomas, we sought to characterize the expression profile of CXCR4 in a large panel of tumor samples and determine whether CXCR4 expression levels within glioblastoma multiforme might correlate with radiological evidence of a more extensive disease process. METHODS: Freshly resected tumor tissue samples were processed for immunohistochemical and quantitative polymerase chain reaction analyses to identify and quantify expression levels of CXCR4 and its corresponding ligand CXCL12. T1 postcontrast and T2-weighted magnetic resonance imaging brain scans were used to generate voxel signal intensity histograms that were quantitatively analyzed to determine the extent and intensity of peritumoral signal abnormality as a marker of disseminated disease in the brain. RESULTS: CXCR4 expression was markedly elevated in Grade III and IV tumors compared with Grade II gliomas. Significantly, when patients with glioblastoma multiforme were segregated into two groups based on CXCR4 expression level, we observed a statistically significant increase in the intensity and extent of peritumoral magnetic resonance imaging signal abnormalities associated with CXCR4 high-expressing gliomas. CONCLUSION: Our data confirm that high-grade gliomas robustly express CXCR4 and demonstrate a correlative relationship between expression levels of the CXCR4 receptor and the magnetic resonance imaging-based finding of a diffuse and more extensive disease process in the brain. CXCR4 expression status may, therefore, prove useful as a marker of disseminated disease in patients with glioblastoma multiforme.

Integrating spatially resolved three-dimensional MALDI IMS with in vivo magnetic resonance imaging.

We have developed a method for integrating three dimensional-volume reconstructions of spatially resolved matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) ion images of whole mouse heads with high-resolution images from other modalities in an animal-specific manner. This approach enabled us to analyze proteomic profiles from MALDI IMS data with corresponding in vivo data provided by magnetic resonance imaging.

Stem cells as vehicles for the treatment of brain cancer.

Stem cell therapy represents a promising new therapeutic modality for infiltrative gliomas. The promise of this emerging technology centers on the potent migratory tropism exhibited by stem cells for disseminated foci of intracranial pathologic findings. This important characteristic, which has been validated in a wide set of preclinical studies, forms a foundation for the use of transplanted stem cell populations as vehicles for the delivery of tumor-toxic molecules to sites of intracranial tumor. Nevertheless, although experimental models using this technique to target brain tumors have shown encouraging results, many concerns and questions remain to be addressed before realistic clinical implementation of this strategy can begin. Key among these are an inadequate understanding of the specific tropic mechanisms that govern stem cell migration toward invasive tumors and the need to identify appropriate tissue sources and culture processes for the generation of adequate therapeutic stem cell populations. Despite these limitations, the use of stem cells as vectors for the treatment of brain tumors holds significant promise and may prove to be an important therapeutic modality for patients with malignant glioma.