Neurohormonal response to left ventricular reconstruction surgery in ischemic cardiomyopathy

OBJECTIVES: Activation of the neuroendocrine axis in congestive heart failure is of prognostic significance, and neurohumoral blocking therapy prolongs survival. The hypothesis that surgical reduction of left ventricular size and function decreases neuroendocrine activation is less established. We evaluated the neurohormonal response to left ventricular reconstruction surgery in ischemic cardiomyopathy. METHODS: Norepinephrine, plasma renin activity, and angiotensin II were measured in 10 patients before and 12 months after left ventricular reconstruction. In an additional 5 patients, brain natriuretric peptide was measured before and 3 months postoperatively. Three-dimensional cardiovascular imaging was used to assess ejection fraction and left ventricular end-diastolic volume index. RESULTS: Concurrent with improvements of New York Heart Association functional class (2.9 +/- 0.5 preoperatively vs 2.0 +/- 0.4 postoperatively, P <.001), ejection fraction (23.9% +/- 6.6% vs 36.2% +/- 6.2%, P <.01), and left ventricular end-diastolic volume index (140.8 +/- 33.8 mL/m(2) vs 90.6 +/- 18.3 mL/m(2), P <.01), considerable reductions were observed for median plasma profiles of norepinephrine (562.0 pg/mL vs 319.0 pg/mL, P <.05), plasma renin activity (5.75 microg/L/h vs 3.45 microg/L/h, P <.05), angiotensin II (41.0 ng/mL vs 23.0 ng/mL, P =.051), and brain natriuretric peptide (771.0 pg/mL vs 266.0 pg/mL, P <.05). The more plasma renin activity or angiotensin II decreased after left ventricular reconstruction, the higher was the increase in ejection fraction (R = -.745, P <.05 [plasma renin activity]; R = -.808, P <.05 [angiotensin II]). CONCLUSIONS: Surgical improvements of ejection fraction and left ventricular end-diastolic volume index by left ventricular reconstruction were accompanied by improvement of both the neuroendocrine activity and the functional status in patients with congestive heart failure. Whether this favorable neurohormonal response is predictive of an improved survival requires further evaluation.     

Exome Sequence Data From Multigenerational Families Implicate AMPA Receptor Trafficking in Neurocognitive Impairment and Schizophrenia Risk

Schizophrenia is a mental disorder characterized by impairments in behavior, thought, and neurocognitive performance. We searched for susceptibility loci at a quantitative trait locus (QTL) previously reported for abstraction and mental flexibility (ABF), a cognitive function often compromised in schizophrenia patients and their unaffected relatives. Exome sequences were determined for 134 samples in 8 European American families from the original linkage study, including 25 individuals with schizophrenia or schizoaffective disorder. At chromosome 5q32–35.3, we analyzed 407 protein-altering variants for association with ABF and schizophrenia status. For replication, significant, Bonferroni-corrected findings were tested against cognitive traits in Mexican American families (n = 959), as well as interrogated for schizophrenia risk using GWAS results from the Psychiatric Genomics Consortium (PGC). From the gene SYNPO, rs6579797 (MAF = 0.032) shows significant associations with ABF (P = .015) and schizophrenia (P = .040), as well as jointly (P = .0027). In the Mexican American pedigrees, rs6579797 exhibits significant associations with IQ (P = .011), indicating more global effects on neurocognition. From the PGC results, other SYNPO variants were identified with near significant effects on schizophrenia risk, with a local linkage disequilibrium block displaying signatures of positive selection. A second missense variant within the QTL, rs17551608 (MAF = 0.19) in the gene WWC1, also displays a significant effect on schizophrenia in our exome sequences (P = .038). Remarkably, the protein products of SYNPO and WWC1 are interaction partners involved in AMPA receptor trafficking, a brain process implicated in synaptic plasticity. Our study reveals variants in these genes with significant effects on neurocognition and schizophrenia risk, identifying a potential pathogenic mechanism for schizophrenia spectrum disorders.Key words: schizophrenia, cognition, SYNPO, WWC1, synaptic plasticity     

Comparison of Maryland hospital discharge and trauma registry data

BACKGROUND: This study aimed to examine the validity of using Maryland hospital discharge data to characterize injuries sustained by trauma patients. METHODS: Maryland hospital discharge and Maryland trauma registry data for 1999 were merged, and the extent of agreement regarding the presence and severity of injuries sustained was evaluated. RESULTS: The mean Injury Severity Score was 8.4 according to the Maryland hospital discharge data and 10 according to the Maryland trauma registry data (p < 0.0001). The Maryland hospital discharge data identified 95% or more of all moderate to severe injuries (Abbreviated Injury Score, > or =2) for all body regions except the head. There was substantial agreement between the two data sets for mechanism of injury (weighted kappa, 0.62), the number of preexisting conditions present (weighted kappa, 0.45) and final disposition (weighted kappa, 0.78). CONCLUSIONS: The Maryland hospital discharge data are a valid source for documenting the nature and severity of injuries sustained by trauma patients, except for those with a relatively minor head injury.     

Operative differences for posterior spinal fusion after vertebral body tethering: Are we fusing more levels in the end?

Purpose

Little is known about the perioperative characteristics associated with a posterior spinal fusion (PSF) in adolescent idiopathic scoliosis patients previously treated with vertebral body tethering (VBT). We aimed to determine if operative time, estimated blood loss, postoperative length of stay, instrumentation type, and implant density differed in patients that received a PSF (i.e., PSF-Only) or a PSF following a failed VBT (i.e., PSF–VBT).

Methods

We retrospectively assessed matched cohort data (PSF–VBT = 22; PSF-Only = 22) from two multi-center registries. We obtained: (1) operative time, (2) estimated blood loss, (3) postoperative length of stay, (4) instrumentation type, and (5) implant density. Theoretical fusion levels prior to the index procedure were obtained for PSF–VBT and compared to the actual levels fused.

Results

We observed no difference in operative time, estimated blood loss, or postoperative length of stay. Instrumentation type was all-screw in PSF-Only and varied in PSF–VBT with nearly 25% of patients exhibiting a hybrid construct. There was no added benefit to removing anterior instrumentation prior to fusion; however, implant density was higher in PSF-Only (1.9 ± 0.2) than when compared to PSF–VBT (1.7 ± 0.3). An additional two levels were fused in 50% of PSF–VBT patients, most of which were added to the distal end of the construct.

Conclusions

We found that operative time, estimated blood loss, and postoperative length of stay were similar in both cohorts; however, the length of the fusion construct in PSF–VBT is likely to be two levels longer when a failed VBT is converted to a PSF.

     

Posttraumatic stress disorder and functional impairment among World Trade Center Health Registry enrollees 14–15 years after the September 11, 2001, terrorist attacks

The September 11, 2001, terrorist attacks on the World Trade Center (WTC) in New York City (9/11) had health-related consequences, including posttraumatic stress disorder (PTSD). PTSD is associated with functional impairment, which varies by symptom severity and other factors. This study aimed to identify predictors of functional impairment in individuals with low versus high PTSD symptom severity levels. WTC Health Registry enrollees exposed to 9/11 were surveyed four times between 2003 and 2015; cumulated data for individuals who endorsed at least one symptom on the PTSD Checklist–Civilian Version (PCL-C) at Wave 4 (2015–2016) were included (N = 30,287) and examined cross-sectionally. Individuals were classified based on PCL-C scores as having low/no (2–29) or high levels of PTSD symptom severity (≥ 44). Functional impairment was defined as subsequent difficulties in daily living. Among low/no PTSD severity participants, adjusted odds ratios (aORs) for the associations between functional impairment and poor self-rated health (vs. good), low social support (vs. high), and no physical activity (vs. active) were 1.23–1.92. In the same group, low versus high household income was associated with more functional impairment, aOR = 1.34, 95% CI [1.13, 1.59]. Among participants with high-level PTSD symptoms, women, aOR = 1.70, 95% CI [1.31, 2.20], and Hispanic enrollees, aOR = 1.76, 95% CI [1.31, 2.36], were more likely to report an absence of impairment. Self-rated health, social support, and physical activity emerged as important predictors of PTSD-related functional impairment across PTSD symptom severity levels, supporting clinical interventions targeting these factors.     

Long-term follow-up and the role of surgery in adolescents with morbid obesity

PURPOSE: Obesity has become a health-care crisis in the United States. Adolescent obesity is now one of the most common childhood disorders, with 4.7 million American adolescents having a body mass index (BMI) greater than the 95th percentile. Most patients do not respond to diet modification or exercise programs and attention is now turning toward surgery as a source of weight loss in adolescents. Few studies have looked at the overall morbidity and mortality of weight loss surgery in this patient population. METHODS: This is a retrospective study of medical charts of 15 bariatric surgical procedures performed on 14 adolescents without known genetic syndromes associated with severe childhood obesity from 1971 to 2001 at the University of Minnesota. Procedures performed on these patients included vertical banded gastroplasty (n = 7), Roux-en-Y gastric bypass (n = 5), and jejunoileal bypass (n = 3). Jejunoileal bypass procedures were performed from 1971 to 1977, after which time this procedure was abandoned. Patient age ranged from 13 to 17 years (mean, 15.7 years). Mean follow-up time was 6 years, with 9 patients available for long-term follow-up. RESULTS: All procedures were performed using an open technique by 1 surgeon. There were no perioperative deaths; complications included 1 case of wound infection, 2 episodes of dumping syndrome that resolved without revision, 1 episode of hypoglycemia, and 1 case of short-term electrolyte imbalance in a patient who underwent jejunoileal bypass. The average BMI dropped from 58.5 +/- 13.7 to 32.1 +/- 9.7 kg/m(2) (P < .01)--a 45% reduction. CONCLUSIONS: Surgery for morbid obesity is safe and results in significant weight loss in adolescents who fail medical therapy.     

Bone Disease in Thalassemia: A Frequent and Still Unresolved Problem

Adults with β thalassemia major frequently have low BMD, fractures, and bone pain. The purpose of this study was to determine the prevalence of low BMD, fractures, and bone pain in all thalassemia syndromes in childhood, adolescence, and adulthood, associations of BMD with fractures and bone pain, and etiology of bone disease in thalassemia. Patients of all thalassemia syndromes in the Thalassemia Clinical Research Network, ≥6 yr of age, with no preexisting medical condition affecting bone mass or requiring steroids, participated. We measured spine and femur BMD and whole body BMC by DXA and assessed vertebral abnormalities by morphometric X‐ray absorptiometry (MXA). Medical history by interview and review of medical records, physical examinations, and blood and urine collections were performed. Three hundred sixty‐one subjects, 49% male, with a mean age of 23.2 yr (range, 6.1–75 yr), were studied. Spine and femur BMD Z‐scores < ?2 occurred in 46% and 25% of participants, respectively. Greater age, lower weight, hypogonadism, and increased bone turnover were strong independent predictors of low bone mass regardless of thalassemia syndrome. Peak bone mass was suboptimal. Thirty‐six percent of patients had a history of fractures, and 34% reported bone pain. BMD was negatively associated with fractures but not with bone pain. Nine percent of participants had uniformly decreased height of several vertebrae by MXA, which was associated with the use of iron chelator deferoxamine before 6 yr of age. In patients with thalassemia, low BMD and fractures occur frequently and independently of the particular syndrome. Peak bone mass is suboptimal. Low BMD is associated with hypogonadism, increased bone turnover, and an increased risk for fractures.     

Magnetic resonance imaging as a diagnostic tool for breast cancer in premenopausal women

BACKGROUND: Screening mammography has led to earlier diagnosis of breast cancer; however, the increased tissue density of young women can complicate mammographic interpretation. We hypothesized that magnetic resonance imaging (MRI) has value in detection of mammographically occult breast cancers, particularly in premenopausal women for whom the sensitivity of mammography is compromised. METHODS: Data were available for 89 women with biopsy-proven breast cancer who had undergone both mammography and breast MRI. Variables evaluated included menopausal status and radiographic findings. Data were analyzed using Fisher's Exact test; P < .05 was considered significant. RESULTS: Of the 89 women in our study, 69 were perimenopausal or postmenopausal and 20 were premenopausal at the time of diagnosis. The malignant lesion was identified on mammography and MRI for a majority of patients. One third of premenopausal women had negative mammography but positive MRI findings. CONCLUSIONS: Our findings support a role for breast MRI in supplementing conventional mammography for early detection of breast cancer in premenopausal women.     

Grade progression and regression in recurrent urothelial cancer

PURPOSE: Recurrent urothelial cancers are reported to have characteristics similar to those of the primary tumor, with 10% to 25% of low grade tumors recurring as high grade disease. We determined how often grade progression and regression occur and whether abnormalities in p53 protein expression in original tumors are preserved in recurrences. MATERIALS AND METHODS: Two groups of patients treated for recurrent stages Ta/T1 urothelial bladder cancers with at least 1 tumor-free examination between the index and recurrent tumors were reviewed. Group 1 included 115 patients in whom the first available tumor was compared with the last recurrence and group 2 included 42 in whom the initial tumor was compared with the first recurrence. Immunohistochemical analysis of p53 expression was performed on a subset of 34 tumor pairs. RESULTS: In group 1, 33 grade 3 tumors (45%) recurred as grade 1 or 2 tumors, while 9 of 82 grades 1 and 2 tumors (11%) recurred as grade 3 tumors. Five of 7 group 2 grade 3 tumors (71%) recurred as grade 1 or 2 disease, while 1 of 35 grades 1 and 2 tumors (3%) recurred as grade 3 disease. In the 34 pairs studied immunohistochemically 6 of 14 grade 3 tumors recurred at lower grades. Nuclear p53 over expression occurred in 21 index tumors (12 of 14 grade 3, 8 of 17 grade 2 and 1 of 3 grade 1) and in 9 recurrences (6 of 10 grade 3, 2 of 17 grade 2 and 1 of 7 grade 1). Only 7 of 21 p53 positive and 2 of 12 p53 negative index tumors were p53 positive on recurrence. CONCLUSIONS: While progression from low to high grade occurred in less than 15% of patients, grade regression was observed in almost 50%. The loss of p53 positivity in regressing tumors indicates that these recurrences are molecularly distinct from the corresponding initial tumor.     

First demonstration of leukemia imaging with the proliferation marker 18F-fluorodeoxythymidine

Acute myeloid leukemia (AML) is a neoplasm of hematopoietic stem cells with partial or complete loss of the ability to differentiate but with preserved proliferation capacity. The aim of our study was to evaluate if the in vivo proliferation marker 3'-deoxy-3'-18F-fluorothymidine (FLT) is suitable for visualizing leukemia manifestation sites and if 18F-FLT is a surrogate marker for disease activity. METHODS: In this pilot study, 10 patients with AML underwent pretherapeutic imaging with 18F-FLT PET or 18F-FLT PET/CT. The biodistribution of 18F-FLT was assessed 60 min after intravenous injection of the radiotracer. Standardized uptake values were calculated for reference segments of bone marrow, spleen, and normal organs. 18F-FLT PET in 10 patients with benign pulmonary nodules and the absence of malignant or inflammatory disease served as controls. RESULTS: Retention of 18F-FLT was observed predominantly in bone marrow and spleen and was significantly higher in AML patients than in controls (mean 18F-FLT SUV in bone marrow, 11.5 and 6.6, P < 0.05; mean 18F-FLT SUV in spleen, 6.1 and 1.8, P < 0.05). Outside bone marrow, focal 18F-FLT uptake showed extramedullary manifestation sites of leukemia in 4 patients (meningeal disease, pericardial, abdominal, testicular, and lymph node), proven by other diagnostic procedures. CONCLUSION: This pilot study indicated that PET using 18F-FLT is able to visualize extramedullary manifestation sites of AML and reflects disease activity. Because 18F-FLT uptake in bone marrow is caused by a combination of both neoplastic and normal hematopoietic cells, the correlation of 18F-FLT uptake in bone marrow and leukemic blast infiltration did not reach statistical significance.