Community exercise programing and its potential influence on quality of life and functional reach for individuals with spinal cord injury*

Context/Objective: After an individual with a Spinal Cord Injury (SCI) participates in the initial rehabilitation process, they often experience limited access to physical therapy services and other fitness activities. The purpose of this study was to examine previously collected data for changes in quality of life (QoL) and functional reach in individuals with SCI following an 8-week community exercise program.

Design: Secondary analysis of previously collected data.

Setting: Community-based exercise program.

Participants: Twenty-two participants with an average of 9 years post-SCI, both complete and incomplete injuries, and injury levels ranging from C2 to L5.

Interventions: Participants completed an 8-week program, once per week for 4 hours that included a four-station circuit of resistance training, aerobic exercise, trunk stability, and education.

Outcome Measures: Physical function was measured using the modified Functional Reach Test (mFRT). QoL was measured with the Life Satisfaction Questionnaire-9 (LiSAT-9).

Results: The mFRT improved by 2 inches (±7.04) P?<?0.001 and QoL improved as well, P?<?0.001.

Conclusion: The findings of this study are consistent with the hypothesis that a supervised post-rehabilitation community exercise program, like Spinal Mobility, may positively impact the QoL and functional reach in individuals with SCI.     

A lymphoma patient with Cytomegalovirus retinitis and post‐autologous hematopoietic cell transplantation immune reconstitution uveitis: A case report and review of the literature

Cytomegalovirus (CMV) retinitis in hematologic malignancies in the absence of hematopoietic cell transplant (HCT) is uncommon. We report a case of a 54‐year‐old woman with peripheral T‐cell lymphoma who develops CMV retinitis and subsequently undergoes an autologous HCT, with eventual development of immune reconstitution uveitis. We further reviewed the PubMed literature on CMV retinitis in patients with lymphoma. We describe that CMV retinitis in patients with lymphoma has variable clinical presentations, may occur at any time during the course of the disease and chemotherapy, and is associated with significant morbidity.     

A Rare p.T599dup BRAF Mutant NSCLC in a Non-Smoker

V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) mutated non-small-cell lung cancer (NSCLC) is an exceptionally rare form of lung cancer, found only in one to two percent of patients with an NSCLC diagnosis. BRAF NSCLC traditionally affects former or active smokers. BRAF mutations have always been of special interest to the oncological community, as they offer potential for targeted therapies. BRAF mutation spectrum includes mutations that are of both V600 and non-V600 types. BRAF V600 is an activating mutation, which results in high kinase activity and overproduction of active oncoproteins such as rapidly accelerated fibrosarcoma (RAF). This makes them susceptible to targeted therapies with RAF inhibitors. There has been little evidence, however, regarding efficacy of RAF inhibitors towards non-activating mutations that have intermediate to low kinase activity, such as non-V600 BRAF mutations. While several approaches have been investigated to overcome the limitations of RAF inhibitors, such as use of mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK) inhibitors or combination of MEK and RAF inhibitors, none of them have been proven to have a superior efficacy for low kinase activity non-V600 BRAF tumors. We present a case of an extremely rare variant of NSCLC BRAF p.T599dup mutation in a non-smoker that responded to a targeted combination therapy with RAF and MEK inhibitors. The patient responded well to therapy that usually targets high kinase activity V600 mutations. Our hope is to bring more attention to non-V600 mutations and document their responses to existing and new therapies.     

Prostate‐specific membrane antigen expression in tumor‐associated vasculature of breast cancers

Prostate‐specific membrane antigen (PSMA) has been found to be expressed in the tumor‐associated neovasculature of multiple solid tumor types including breast cancers. However, thus far, the number of cases studied from some tumor types has been limited. In this study, we set out to assess PSMA expression in the tumor‐associated vasculature associated with invasive breast carcinomas in a sizable cohort of patients. One hundred and six patients with AJCC stage 0‐IV breast cancer were identified. Ninety‐two of these patients had primary breast cancer [invasive breast carcinoma with or without co‐existing ductal carcinoma in situ (DCIS) (74) or DCIS alone (18)]. In addition, 14 patients with breast cancer metastases to the brain were identified. Immunohistochemical staining for PSMA and CD31 was performed on parallel representative tumor sections in each case. Tumor‐associated vascular endothelial cell PSMA immunoreactivity was semi‐quantitatively assessed based on two parameters: overall percent of endothelial positivity and staining intensity. PSMA expression for tumor‐associated vascular endothelial cells was scored 0 if there was no detectable PSMA expression, 1 if PSMA staining was detectable in 5–50%, and 2 if PSMA expression was positive in >50% of microvessels. CD 31 staining was concurrently reviewed to confirm the presence of vasculature in each case. Tumor‐associated vasculature was PSMA‐positive in 68/92 (74%) of primary breast cancers and in 14/14 (100%) of breast cancers metastatic to brain. PSMA was not detected in normal breast tissue or carcinoma cells. All but 2 cases (98%) showed absence of PSMA expression in normal breast tissue‐associated vasculature. The 10‐year overall survival was 88.7% (95% CI = 80.0%, 93.8%) in patients without brain metastases. When overall survival (OS) was stratified based on PSMA score group, patients with PSMA scores of 0, 1, and 2 had 10‐year OS of 95.8%, 96.0%, and 79.7%, respectively (p = 0.12). When PSMA scores of 0 and 1 were compared with 2, there was a statistically significant difference in OS (96.0% vs 79.7%, respectively, p = 0.05). Patients with a PSMA score of 2 had a significantly higher median tumor size compared with patients in the lower PSMA score groups (p = 0.04). Patients with higher nuclear grade were more likely to have a PSMA score of 2 compared with patients with lower nuclear grade (p < 0.0001). Patients with a PSMA score of 2 had a significantly higher median Ki‐67 proliferation index compared with patients in the lower PSMA score groups (p < 0.0001). Patients with estrogen receptor (ER)‐negative tumors were more likely to have a PSMA score of 2 compared with patients with ER‐positive tumors (p < 0.0001). Patients with progesterone receptor (PR)‐negative tumors were more likely to have a PSMA score of 2 compared with patients with PR‐positive tumors (p = 0.03). No significant association was observed between PSMA score group status and lymph node involvement (p = 0.95). Too little variability was present in Human epidermal growth factor receptor‐2 (Her2/neu) amplified tumors to correlate with PSMA score group status. To date, this is the first detailed assessment of PSMA expression in the tumor‐associated vasculature of primary and metastatic breast carcinomas. Further studies are needed to evaluate whether PSMA has diagnostic and/or potential therapeutic value.     

Sphingomyelinase-Like Phosphodiesterase 3b Expression Levels Determine Podocyte Injury Phenotypes in Glomerular Disease

Diabetic kidney disease (DKD) is the most common cause of ESRD in the United States. Podocyte injury is an important feature of DKD that is likely to be caused by circulating factors other than glucose. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating factor found to be elevated in the serum of patients with FSGS and causes podocyte αVβ₃ integrin-dependent migration in vitro. Furthermore, αVβ₃ integrin activation occurs in association with decreased podocyte-specific expression of acid sphingomyelinase-like phosphodiesterase 3b (SMPDL3b) in kidney biopsy specimens from patients with FSGS. However, whether suPAR-dependent αVβ₃ integrin activation occurs in diseases other than FSGS and whether there is a direct link between circulating suPAR levels and SMPDL3b expression in podocytes remain to be established. Our data indicate that serum suPAR levels are also elevated in patients with DKD. However, unlike in FSGS, SMPDL3b expression was increased in glomeruli from patients with DKD and DKD sera-treated human podocytes, where it prevented αVβ₃ integrin activation by its interaction with suPAR and led to increased RhoA activity, rendering podocytes more susceptible to apoptosis. In vivo, inhibition of acid sphingomyelinase reduced proteinuria in experimental DKD but not FSGS, indicating that SMPDL3b expression levels determined the podocyte injury phenotype. These observations suggest that SMPDL3b may be an important modulator of podocyte function by shifting suPAR-mediated podocyte injury from a migratory phenotype to an apoptotic phenotype and that it represents a novel therapeutic glomerular disease target.     

Multipoint dilution hemofiltration: A new technology for maximum convective clearance

Convection-based renal replacement therapies (RRTs) have the potential to improve patient outcomes when compared to diffusion-based RRT such as hemodialysis (HD), but have limited clearance rates. We propose and characterize multipoint dilution hemofiltration (MPD-HF), a purely convective blood purification technology which removes the fundamental filtration limit associated with convective RRT resulting in clearance rates on par with HD. In MPD-HF, filtration of liquid and solutes occurs along the length of the hollow fibers that convey the blood, and substitution fluid is pushed into the fibers at multiple points along their length. Since multiple filtration and dilution steps are contained within one pass of the blood through the hollow fiber, the fraction of fluid that can be filtered may be increased to allow a high clearance rate that removes a wide range of toxins. In vitro tests yielded an average steady-state filtrate fraction of 68%, exceeding commercial HDF cartridge filtrate fractions by a factor of approximately 3. The molecular weights of molecules cleared spans up to the cutoff of 66 kDa for albumin.