Predictors of 15-Day Survival for the Intensive Care Unit Patient on Continuous Renal Replacement Therapy: A Retrospective Analysis.

Purpose In the intensive care unit (ICU), acute renal failure is mostly part of multiple organ dysfunction syndromes with mortality ranging from 28%-90%, continuous renal replacement therapy (CRRT) is the predominant mode of RRT used in ICU. The main objective of the study was to evaluate the outcomes in patients with acute kidney injury (AKI) on CRRT in the ICU. Methods A retrospective chart review was conducted for all ICU patients with acute renal failure on CRRT in a tertiary care teaching hospital. A subgroup analysis was conducted between 15 days in hospital survivors and non-survivors to look for predictors of survival for patients on CRRT. Results Two-hundred twenty-six patients underwent CRRT from January 2007 to December 2013. The overall in-hospital mortality was 84.1%. Fifty-six patients (24.77%) survived to the 15-day post-CRRT mark. Acute respiratory failure requiring mechanical ventilation was associated with significantly increased mortality; 89.2% vs. 97.6% (P=0.008), ICU length of stay was significantly longer in the survivor group than the nonsurvivor group. Median±IQR; {20±24 vs 6±7(P: <0.0001)} and so were the ventilator-associated days {16±24 vs 4±6.5 (P: <0.0001)} and duration of CRRT {4.5±5.5 vs 2±2.0(P: <0.0001)}. Patients who survived had a lower incidence of metabolic acidosis {44.6% vs 62.9% (P: 0. 016)} and uremic encephalopathy {12.5% vs 26.5%; (P: 0.031)} but a greater incidence of volume overload {28.6% vs 15.9% (P: 0.031)} as compared to the non-survivor. Acute Physiology And Chronic Health Evaluation II (APACHE II) scores were significantly higher in the non-survivor group (mean SD) 26.9±28.0 vs. 23.9±25.8 (P: 0.0136). Conclusions This observational study in patients undergoing CRRT in an ICU setting revealed that the overall mortality was 84.1%. Fluid overload as an indication of CRRT was associated with improved 15 days' survival whereas higher APACHE II scores and the use of mechanical ventilation were associated with reduced 15 days' survival.

Dasatinib-induced pulmonary arterial hypertension - A rare late complication.

Dasatinib is a dual Src/Abl tyrosine kinase inhibitor approved for frontline and second line treatment of chronic phase chronic myelogenous leukemia. Pulmonary arterial hypertension is defined by an increase in mean pulmonary arterial pressure >25 mmHg at rest. Dasatinib-induced pulmonary hypertension has been reported in less than 1% of patients on chronic dasatinib treatment for chronic myelogenous leukemia. The pulmonary arterial hypertension from dasatinib may be categorized as either group 1 (drug-induced) or group 5 based on various mechanisms that may be involved including the pathogenesis of the disease process of chronic myelogenous leukemia. There have been reports of dasatinib-induced pulmonary arterial hypertension being reversible. We report a case of pulmonary arterial hypertension in a 46-year-old female patient with chronic phase chronic myelogenous leukemia on dasatinib treatment for over 10 years. She had significant improvement in symptoms after discontinuation of dasatinib and initiation of vasodilators. Several clinical questions arise once patients experience significant adverse effects as discussed in our case.

An unusual complication of pigtail catheter insertion.

Thoracostomy tubes are indicated for management of air or fluid in the pleural cavity. Pigtail catheters have emerged as an effective and less morbid alternative to traditional large bore chest tubes for evacuation of pleural air or fluid. However, they do not come without complications which commonly include pneumothorax and hemothorax. Rare complications in the literature such as left ventricular penetration, subclavian artery laceration and cerebral air embolism have been reported. We report a case of a 72-year-old male who presented with dyspnea and was found to have a right-sided pleural effusion requiring thoracentesis and subsequent pigtail catheter placement because of re-accumulation of the fluid. After accidental dislodgement of the catheter, it was replaced and the following day a chest X-ray (CXR) demonstrated diffuse subcutaneous emphysema. Computed tomography (CT) scan of the chest demonstrated the pigtail catheter tracking through the right middle and lower lobes reaching the posterior pleural space. We discuss the implications of this occurrence and recommended management based on our experience.

Indwelling pleural catheters: complications and management strategies.

Indwelling pleural catheters (IPCs) are increasingly being used for patients with recurrent malignant pleural effusions. They are simple to place and can be done on an outpatient basis under local anesthesia. IPCs uniformly relieve dyspnea and improve quality of life of patients with malignant pleural effusions. In some patients with recurrent non-malignant pleural effusions, IPCs proved to be effective as well. With increasing use of IPCs, physicians and patients are faced with complications related to the presence of an indwelling catheter for extended periods of time. The purpose of this review is to describe the various complications of IPCs and to present the available data on how to best treat and potentially prevent these complications.

ALK-Negative Anaplastic Large Cell Lymphoma Presenting as Disseminated Intravascular Coagulation and Hemophagocytic Lymphohistiocytosis: A Potentially Fatal Presentation.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder that can be familial in etiology or a result of infections, malignancy, and autoimmune or inflammatory disorders. Disseminated intravascular coagulation (DIC) is common in patients admitted to intensive care units and can confound and delay the diagnosis of HLH. We present a case of a 69-year-old female who presented with dyspnea and malaise. Her condition declined rapidly with laboratory parameters consistent with DIC. In addition, she had a ferritin of 32,522 ng/mL, low haptoglobin, and elevated LDH, and bone marrow biopsy showed hemophagocytic lymphohistiocytes. She was started on HLH-directed therapy, and later, a diagnosis of ALK-negative anaplastic large cell lymphoma was made on an excisional inguinal lymph node biopsy specimen. Our case emphasizes the importance of prompt recognition, diagnosis, and treatment of HLH while workup for a primary disorder is still being pursued.

Synchronous Pulmonary Neoplasms: A Chance Occurrence or is There More Than Meets the Eye?

Primary bronchus-associated lymphoid tissue (BALT) lymphoma comprises 5% of non-Hodgkin's lymphoma (NHL) and usually has an indolent course. Synchronous primary lung cancers with BALT lymphoma are seldom seen in patients with adenocarcinoma of the lung. Synchronous squamous cell carcinoma (SCC) and BALT lymphoma is an extremely rare occurrence. We report an unusual case of stage 4 BALT lymphoma requiring treatment that revealed an underlying ipsilateral mass causing a diagnostic dilemma. An 84-year-old female with a history of systemic lupus erythematosus, deep vein thrombosis, and thrombotic microangiopathy presented to the hospital with cough and dyspnea on exertion. A chest X-ray revealed right hemi-thorax opacification and computed tomography (CT) of the chest showed a large right effusion and a soft tissue density extending into the proximal right bronchus. She required repeated thoracentesis until the pleural fluid analysis showed the presence of small lymphocytes and bronchial washings revealed an abnormal B cell population consistent with extranodal marginal zone lymphoma. The patient received four cycles of bendamustine and rituximab resulting in near-complete resolution of the effusion. Four months from diagnosis, imaging showed an increase in the size of the soft tissue density with pathologic fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET). A CT-guided biopsy was consistent with squamous cell lung cancer (SCLC) and radiotherapy was started for clinical stage 2 disease since the patient was not a surgical candidate. BALT lymphoma is a low-grade malignancy classified as extranodal marginal zone lymphoma with a five-year survival rate of over 80%. Several cases of synchronous lung adenocarcinoma and BALT lymphoma have been described. However, our case is among the rare few cases of synchronous occurrence of SCLC with BALT lymphoma. This report highlights the challenges associated with establishing an accurate and timely diagnosis.

Rasburicase-induced methemoglobinemia: The eyes do not see what the mind does not know.

Rasburicase is indicated for the prevention and treatment of tumor lysis syndrome which can be a potentially life-threatening emergency. The drug has oxidizing potential and as an adverse effect, it can convert the ferrous form of iron in erythrocytes to its ferric form resulting in the formation of methemoglobin which makes the heme component incapable of carrying oxygen. Patients with glucose-6-phosphate dehydrogenase enzyme deficiency are at high risk of methemoglobinemia from oxidizing agents. Symptoms of methemoglobinemia range from none to life-threatening hypoxemia, cyanosis and respiratory compromise. Treatment is indicated at levels above 20% and at lower levels if the patient is significantly anemic. We present a case of a 60-year-old male with diffuse large B cell lymphoma at high risk of tumor lysis syndrome. Rasburicase was administered to prevent renal failure and further rise in uric acid. Twenty-four hours later, a bedside pulse oximetry showed an oxygen saturation ranging from 60 to 65% with minimal cyanosis. Co-oximetry revealed a methemoglobin level of 9.8%. Methylene blue was administered and the methemoglobin level decreased to 2.6%. However, the patient developed hemolysis several hours later, likely secondary to rasburicase and methylene blue, requiring transfusion support. We discuss this potentially fatal and initially asymptomatic adverse effect of rasburicase along with diagnostic and treatment considerations, and review the cases described in the current literature.

T Cell Histiocyte Rich Large B Cell Lymphoma Presenting as Hemophagocytic Lymphohistiocytosis: An Uncommon Presentation of a Rare Disease.

T cell histiocyte rich large B cell lymphoma (THRLBCL) is a rare subtype of non-Hodgkin's lymphoma characterized by malignant B cells with reactive T lymphocytes. The pathophysiology is thought to involve cytokine-mediated evasion of T cell immune response by malignant B cells. It usually presents at an advanced stage with extranodal involvement. An extremely unusual manifestation of the disease is hemophagocytic lymphohistiocytosis (HLH) which is a hyperinflammatory disorder. We present a case of a 43-year-old male who presented with recurrent fever and recent radiologic imaging showing splenomegaly and right inguinal lymphadenopathy. On presentation, he had a fever of 105°F. Laboratory work-up was consistent with pancytopenia, elevated lactate dehydrogenase, elevated D-dimer, and a ferritin of 24,247 ng/mL. The patient was started on steroid therapy. An excisional biopsy of the right inguinal lymph node was consistent with a diagnosis of THRLBCL and the patient subsequently received six cycles of chemotherapy with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) after which a PET-CT scan showed no evidence of biologically active disease and ferritin was down to 822 ng/mL. We discuss the clinical manifestations and diagnostic and therapeutic considerations of this rare disease along with a review of reported cases in the literature.

EGFR exon 18 delE709_T710insD mutated stage IV lung adenocarcinoma with response to afatinib.

Epidermal Growth Factor Receptor (EGFR) targetable mutations have changed the landscape for treatment of advanced stage non-small cell lung cancer in recent years. Three generations of tyrosine kinase inhibitors are now available to target cancers harboring these mutations. The most common EGFR mutations occur in Exons 19 and 21. Exon 18 mutations are extremely rare comprising of 4.1% of all EGFR mutations and the delE709_T710insD mutation accounts for only 0.16% of mutations when occurring as a sole mutation, however, the frequency can vary with the kit utilized for testing. The rarity makes the clinical relevance of these mutations largely unknown. We report a case of a 52year old female with bilateral advanced adenocarcinoma of the lung harboring the delE709_T710insD mutation with significant clinical and radiographic response to treatment with afatinib. We discuss the reported cases of delE709_T710insD mutated non-small cell lung cancer variably treated with geftinib, erlotinib or afatinib. This particular exon 18 mutation seems to preferentially respond to afatinib as reported in two cases including the current case, and in an in vitro experimental model. These reports have implications in guiding decisions for treatment of patients harboring rare EGFR mutations.

IgG4-related Disease Presenting as a Pancreatic Mass and Bilateral Lacrimal Gland Swelling.

IgG4-related disease is characterized by multi-system inflammation and possible elevation in serum immunoglobulin-G4 level. Treatment regimens include glucocorticoids, disease-modifying anti-rheumatic agents and recently, rituximab infusions have been reported to be effective in treatment-refractory disease. We present a case of a 64-year-old male presenting with acute abdominal pain and scleral icterus. An abdominal ultrasound demonstrated extensive biliary ductal dilatation. A computed tomography (CT) scan and a magnetic resonance cholangiopancreatography (MRCP) revealed a 4.8 cm pancreatic head mass. He underwent an exploratory laparotomy, and a pathologic examination of the mass revealed a dense lymphoplasmacytic infiltrate. The patient's IgG subclass 2 level was elevated. A review of the patient's medical records revealed that, in 1992, he presented with bilateral periorbital discomfort not severe enough to require intervention. In 2006, he presented with bilateral periorbital swelling and discomfort. A magnetic resonance imaging (MRI) scan showed gross enlargement of the lacrimal glands, and a biopsy revealed a dense lymphoplasmacytic infiltrate. He was treated with corticosteroids, cyclosporine and methotrexate. The regimen was repeated in 2009 for recurrent symptoms. Hence, on our encounter, a diagnosis of IgG4-related disease was made and he was treated with rituximab that resulted in complete remission.

Facial Paralysis and Hearing Loss: A Rare Manifestation of Prostate Cancer Metastases.

Dural prostate metastases (DPM) are a rare manifestation of metastatic prostate cancer seen in approximately one to six percent of cases. Presenting symptoms may include signs of elevated intracranial pressure, headache, altered mental status, or cranial nerve palsies. Hearing loss, sensory changes, dysarthria, and dysphagia are rare symptoms in DPM that were present in our patient. We present a case of a 58-year-old male with a known diagnosis of adenocarcinoma of the prostate presenting with symptoms of acute exacerbation of chronic obstructive pulmonary disease (COPD), sub-acute right-sided hearing loss, and right-sided facial paralysis. Over the course of hospitalization, his neurological symptoms worsened and he developed dysarthria, dysphagia, facial numbness, and worsening back pain. He also appeared more withdrawn and lethargic. The symptoms prompted a neurological evaluation and a magnetic resonance imaging (MRI) revealed multiple areas of bone marrow signal abnormality compatible with osseous metastatic disease. There was extensive smooth dural thickening as well as focal nodular thickening, both consistent with dural metastases. The patient was treated with corticosteroids and external beam radiation therapy (EBRT) with improvement in his back pain and facial paralysis. He died two weeks after completing EBRT. Although rare, DPM should be suspected in males over 50 years of age presenting with neurological symptoms. An MRI with gadolinium is most helpful in delineating the presence and extent of dural and calvarial involvement. Corticosteroids and EBRT have been shown to improve neurological function in up to 67% of patients. However, median survival post-radiation remains approximately three months.

Mortality among high-risk patients admitted with septic shock to U.S. teaching hospitals in July: Does the 'July Effect' exist?

BACKGROUND: The 'July effect' is a phenomenon of inferior delivery of care at teaching hospitals during July because of relative inexperience of new physicians. OBJECTIVE: To study the difference in mortality among septic shock patients during July and another month. METHODS: Using the U.S. Nationwide Inpatient Sample, we estimated the difference in mortality among septic shock patients admitted during May and July from 2003 to 2011. RESULTS: 117,593 and 121,004 patients with septic shock were admitted to non-teaching and teaching hospitals, respectively, in May and July. High-risk patients had similar mortality rates in non-teaching hospitals and teaching hospitals. Mortality rates were higher in teaching versus non-teaching hospitals in high-risk patients both in May and July. Overall, mortality rates were higher in teaching versus non-teaching hospitals both in May and July. CONCLUSION: Similar trends in mortality are observed in both settings in May and July and no "July effect" was observed.

KSHV-associated extracavitary primary effusion lymphoma in an HIV seronegative patient: a case report and review of the literature.

Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin's lymphoma presenting as a lymphomatous effusion and absence of a solid tumor mass. Extracavitary PEL (EC-PEL) is a subtype of PEL with the absence of an effusion but presence of solid tumor. PEL and EC-PEL share the same histopathologic and immunophenotypic features. Kaposi sarcoma-associated herpesvirus (KSHV) positivity is seen universally in these malignancies and is a requisite for diagnosis. Most cases are seen to occur in HIV positive individuals. We present a unique case of a 21-year-old male who presented with ongoing chest pain and right hip pain found to have an extensive lytic lesion of the right iliac bone, a paratracheal mass and a large pelvic mass. All the involved sites were FDG (F-18 fluorodeoxyglucose)-avid on PET-CT scan. The patient was seronegative for HIV with no risk factors for immunosuppression. A biopsy of the pelvic mass and bone marrow showed large atypical cells with irregular multi-lobulated nuclei, prominent nucleoli, and abundant amphophilic cytoplasm. The cells were positive for MUM1, in situ hybridization for EBV-encoded RNA (EBER), and KSHV, while negative for B-cell and T-cell markers. The patient was treated with six cycles of DA-EPOCH with a follow up PET scan showing a decrease in size of the masses and bone lesion and conversion to non-FDG-avid status. To the best of our knowledge, our case is the first in published English literature with bone involvement with EC-PEL regardless of HIV status. We review the reported cases of EC-PEL including their presentation, diagnostic features, treatment and outcomes.

Embryonal Rhabdomyosarcoma of the Cervix: A Rare Disease at an Uncommon Age.

Embryonal rhabdomyosarcoma (RMS) is a rare type of sarcoma, primarily seen in the pediatric and adolescent population. Three subtypes of embryonal RMS are described, with the botryoid type being the most common. The incidence of this disease in adult females is 0.4% to 1% with the affected age group being patients in the third to fourth decade of life. It is exceedingly rare in patients above 40 years of age. We describe the case of a 48-year-old female, gravida 9 para 5, who presented with abnormal vaginal bleeding and an exophytic mass on examination. Given her lack of requirement of maintaining parity, she underwent radical surgery. The tumor was 8 cm in the largest dimension with a high histologic grade and some cartilaginous differentiation. Immunohistochemical stains were positive for vimentin, CD99, myogenin, and MyoD1 consistent with a diagnosis of embryonal rhabdomyosarcoma, botryoid subtype. Based on high survival rates when treated with aggressive adjuvant chemotherapy, a decision was made to treat the patient with the ARST0331 regimen. We discuss the diagnostic pathologic features of the disease, the epidemiology, and the most common presentation along with prognostic factors, treatment strategies, and outcomes.

Eosinophilia as the presenting sign in pancreatic cancer: an extremely rare occurrence.

A case of pancreatic adenocarcinoma diagnosed following work up for eosinophilia is reported. A 68-year-old female was referred to our Hematology clinic for an absolute eosinophil count of 1869 per microliter. No allergic signs or symptoms were reported. Laboratory studies for parasitic infestations autoimmune disease and collagen vascular disease were negative. Computed tomography of the abdomen revealed a mass in the neck of the pancreas with fine needle aspiration biopsy consistent with adenocarcinoma. The patient received one cycle of modified FOLFIRINOX with complete resolution of the eosinophilia. There are rare case reports of tumor-associated blood eosinophilia in solid malignancies. The finding may be indicative of rapid disease progression and poor prognosis. Our case is the third in published English literature with eosinophilia being the initial finding in pancreatic cancer.

An Unusual Presentation of Nocardiosis in an Allogeneic Transplant Recipient.

Nocardiosis is a rare cause of opportunistic infection post hematopoietic stem cell transplant (HSCT) occurring in about 0.3% of patients. The risk factors include delayed immune reconstitution, prolonged neutropenia, and graft-versus-host disease. The most common site of infection is the lung, followed by the brain and the skin. Concomitant pulmonary and central nervous system (CNS) nocardiosis is an extremely rare entity as presented in our case. We present the case of a 72-year-old male at 137 days post transplant presenting with complaints of headache and slurred speech. A magnetic resonance imaging (MRI) brain scan revealed two ring-enhancing lesions: 1.6 cm in the right frontal lobe and 1 cm in the left parietal lobe. The patient had an outpatient computed tomography (CT) chest scan a month prior showing a 1.4 cm solid right upper lobe nodule prompting bronchoalveolar lavage (BAL) that was nondiagnostic. On repeat inpatient CT chest scan, the nodule had increased in size to 3.3 x 2.5 x 2.1 cm, prompting a percutaneous fine-needle aspiration biopsy. He was started on empiric trimethoprim-sulfamethoxazole (TMP-SMX) and liposomal amphotericin B. The tissue mycology and acid-fast cultures were reported positive for nocardia species. The patient was discharged on intravenous TMP-SMX. A follow-up CT chest scan and MRI brain scan four months later showed resolution of the right upper lobe nodule and significant decrease in size of the brain lesions. The patient will continue TMP-SMX for a total of nine to 12 months. Given the increase in transplant recipients and the ongoing risk of developing nocardiosis several months post transplant, there is a need for standardized diagnostic and treatment guidelines. Meanwhile, our case highlights the importance of aggressiveness in pursuing a prompt diagnosis including invasive procedures, if required, in order to begin specific treatment.

A Case of an Enigmatic Pulmonary Infiltrate.

The differential diagnosis of a pulmonary mass in an immunosuppressed host with a history of cancer is broad and includes malignant, infectious and inflammatory etiologies. Mycobacterium avium complex (MAC) is a rare cause of opportunistic infection in susceptible individuals that can present as either localized or disseminated disease. On radiologic studies, the pulmonary disease can manifest as heterogeneous linear or nodular densities, a mass-like lesion, or thin-walled cavitary lesions. We present the case of pulmonary MAC in a patient with a history of lung cancer requiring lobectomy, and splenic lymphoma being treated with chemotherapy, presenting with extreme fatigue and a fludeoxyglucose (FDG)-avid mass on positron emission tomography-computed tomography (PET-CT). The patient had a CT-guided biopsy of the mass that demonstrated non-caseating granulomas followed by a right middle lobe transbronchial biopsy that upon histologic examination revealed mild acute and chronic inflammation, and necrotizing caseating granulomas. The acid-fast culture of bronchoalveolar lavage showed the growth of acid-fast bacilli that were identified by deoxyribonucleic acid (DNA) probe as Mycobacterium avium complex. We discuss the typical radiological manifestations of MAC as well as the role of immunosuppression and B cell-depleting therapy from the predisposition to infection.

Primary Pulmonary Lymphoma and Synchronous Cecal Adenocarcinoma: A Rare Occurrence.

In the era of extensive imaging and increasing indications for performing PET-CT scans, the recognition of synchronous tumors may be greater than before. However, the majority of these tumors are seen to occur in the same organ system, likely because of sharing similar pathogenic mechanisms. Synchronous lung cancers of similar or differing histologies have been reported. Primary pulmonary lymphoma, which is a rare form of non-Hodgkin's lymphoma, has also been seen with a synchronous primary lung cancer. However, we report a case of a 56-year-old male diagnosed with primary pulmonary lymphoma and on PET-CT imaging, found to have a cecal lesion, the biopsy of which showed adenocarcinoma. We discuss the incidence of the co-existence of multiple tumors, the pathogenic mechanisms involved, and approaches to the management of these rare clinical scenarios.

Adeno-associated virus serotype 9-mediated overexpression of extracellular superoxide dismutase improves recovery from surgical hind-limb ischemia in BALB/c mice.

OBJECTIVE: Neovascularization is a physiologic repair process that partly depends on nitric oxide. Extracellular superoxide dismutase (EcSOD) is the major scavenger of superoxide. It is an important regulator of nitric oxide bioavailability and thus protects against vascular dysfunction. We hypothesized that overexpression of EcSOD in skeletal muscle would improve recovery from hind-limb ischemia. METHODS: Adeno-associated virus serotype 9 (AAV9) vectors expressing EcSOD or luciferase (control) from the cytomegalovirus promoter were cross-packaged into AAV9 capsids and injected intramuscularly into the hind-limb muscles (1 × 10(11) viral genomes/limb) of 12-week-old mice. Ischemia was induced after intramuscular injections. Laser Doppler was used to measure limb perfusion on days 0, 7, and 14 after injection. Values were expressed as a ratio relative to the nonischemic limb. EcSOD expression was measured by Western blotting. Capillary density was documented by immunohistochemical staining for platelet endothelial cell adhesion molecule. Apoptosis was assessed by terminal deoxynucleotide transferase-mediated biotin-deoxy uridine triphosphate nick-end labeling and necrosis was visually evaluated daily. RESULTS: EcSOD expression was twofold upregulated in EcSOD treated vs control ischemic muscles at day 14. Capillary density (capillaries/fiber) was 1.9-fold higher in treated (1.65 ± 0.02) vs control muscle (0.78 ± 0.17, P < .05). Recovery of perfusion ratio at day 14 after ischemia was 1.5-fold greater in EcSOD vs control mice (P < .05). The percentage of apoptotic nuclei was 1.3% ± 0.4% in EcSOD-treated mice compared with 4.2% ± 0.2% in controls (P < .001). Limb necrosis was also significantly lower in EcSOD vs control mice. CONCLUSION: AAV9-mediated overexpression of EcSOD in skeletal muscle significantly improves recovery from hind-limb ischemia in mice, consistent with improved capillary density and perfusion ratios in treated mice.