Citations

Obesity associated with metabolic derangements (ObM) worsens the prognosis of patients with coronary artery stenosis (CAS), but the underlying cardiac pathophysiologic mechanisms remain elusive. We tested the hypothesis that ObM exacerbates cardiomyocyte loss distal to moderate CAS. Obesity-prone pigs were randomized to four groups ( n = 6 each): lean-sham, ObM-sham, lean-CAS, and ObM-CAS. Lean and ObM pigs were maintained on a 12-wk standard or atherogenic diet, respectively, and left circumflex CAS was then induced by placing local-irritant coils. Cardiac structure, function, and myocardial oxygenation were assessed 4 wk later by computed-tomography and blood oxygenation level dependent (BOLD) MRI, the microcirculation with micro-computed-tomography, and injury mechanisms by immunoblotting and histology. ObM pigs showed obesity, dyslipidemia, and insulin resistance. The degree of CAS (range, 50–70%) was similar in lean and ObM pigs, and resting myocardial perfusion and global cardiac function remained unchanged. Increased angiogenesis distal to the moderate CAS observed in lean was attenuated in ObM pigs, which also showed microvascular dysfunction and increased inflammation (M1-macrophages, TNF-α expression), oxidative stress (gp91), hypoxia (BOLD-MRI), and fibrosis (Sirius-red and trichrome). Furthermore, lean-CAS showed increased myocardial autophagy, which was blunted in ObM pigs (downregulated expression of unc-51-like kinase-1 and autophagy-related gene-12; P < 0.05 vs. lean CAS) and associated with marked apoptosis. The interaction diet xstenosis synergistically inhibited angiogenic, autophagic, and fibrogenic activities. ObM exacerbates structural and functional myocardial injury distal to moderate CAS with preserved myocardial perfusion, possibly due to impaired cardiomyocyte turnover.

Pregnancy-associated plasma protein-A (PAPP-A) is a novel zinc metalloproteinase implicated in cardiovascular disease. The aim of this study was to determine whether a reduction in PAPP-A expression in the adult affects the progression of established atherosclerotic plaque. Apolipoprotein E-null mice were fed a high-fat diet for 5 weeks to initiate early-stage plaque development before tamoxifen-inducible, Cre recombinase–mediated excision of the floxed PAPP-A gene. High-fat feeding was continued, and after 10 weeks the aorta and brachiocephalic artery were harvested for atherosclerotic plaque analyses of overall burden and morphology, respectively. An inducible decrease in PAPP-A gene expression significantly inhibited atherosclerotic plaque progression as assessed by a 70% reduction in plaque burden in the aorta (P = .012) without an effect on the elevated circulating levels of cholesterol and triglycerides in this model. Furthermore, this reduction in PAPP-A prevented the development of advanced plaque with necrotic cores and buried fibrous caps in the brachiocephalic artery. These data indicate PAPP-A as a potential target to limit progression of established atherosclerotic plaque.

Lipomatosis of nerve (LN), or fibrolipomatous hamartoma, is a rare condition of fibrofatty enlargement of the peripheral nerves. It is associated with bony and soft tissue overgrowth in approximately one-third to two-thirds of cases. It most commonly affects the median nerve at the carpal tunnel or digital nerves in the hands and feet. The authors describe a patient with previously diagnosed hemihypertrophy of the trunk who had a history of large thoracic lipomas resected during infancy, a thoracic hump due to adipose proliferation within the thoracic paraspinal musculature, and scoliotic deformity. She had fatty infiltration in the thoracic spinal nerves on MRI, identical to findings pathognomonic of LN at better-known sites. Enlargement of the transverse processes at those levels and thickened ribs were also found. This case appears to be directly analogous to other instances of LN with overgrowth, except that this case involved axial nerves rather than the typical appendicular nerves.

AbstractPurposeTo develop and test a decision support tool that identifies patients who would benefit from early consult with discharge planners.Design and MethodsA predictive, correlational design was used with parents/guardians of children (1 month to 18 years; N = 197). Data were collected by interviews and record reviews. Expert consensus determined referral to discharge planning.ResultsMean age was 8.7 years; mean length of stay was 7.5 days. Forty percent (n = 79) were identified for early referral. The variable “substantial post‐acute care needs” had the strongest association with expert consensus (internally validated AUC = 0.79).Practice ImplicationsFindings from this study provide preliminary evidence for a decision support tool to improve the discharge planning process by reducing individual decision‐making variability through systematic matching of patient needs to service delivery.

The earliest recorded application of therapeutic hypothermia in medicine spans about 5000 years; however, its use has become widespread since 2002, following the demonstration of both safety and efficacy of regimens requiring only a mild (32°C-35°C) degree of cooling after cardiac arrest. We review the mechanisms by which hypothermia confers neuroprotection as well as its physiological effects by body system and its associated risks. With regard to clinical applications, we present evidence on the role of hypothermia in traumatic brain injury, intracranial pressure elevation, stroke, subarachnoid hemorrhage, spinal cord injury, hepatic encephalopathy, and neonatal peripartum encephalopathy. Based on the current knowledge and areas undergoing or in need of further exploration, we feel that therapeutic hypothermia holds promise in the treatment of patients with various forms of neurologic injury; however, additional quality studies are needed before its true role is fully known.

ObjectivesTo evaluate the oncologic safety of the submental flap regarding potential transposition of involved nodes to the reconstruction site and recognize the submental flap as an excellent option for oral cavity reconstruction.Study DesignCase series with chart review.SettingTertiary academic referral center.Subjects and MethodsAll patients undergoing reconstruction with submental flaps following the resection of primary and recurrent malignancies of the oral cavity between 2002 and 2012 were reviewed. Analysis included tumor location, staging, reconstructive details, postoperative course, and outcomes.ResultsFifty patients were identified having undergone submental flap reconstruction of defects following resection for oral cavity malignancies. No patient had identifiable clinical or radiographic level I nodal involvement preoperatively. Patients’ ages ranged from 35 to 88 years (mean, 70 years). American Joint Committee on Cancer staging of patients included stage II (n = 16, 32%), stage III (n = 10, 20%), and stage IVa disease (n = 28, 48%). All patients underwent a level 1A and 1B dissection with removal of the nodal basin and submandibular gland. The prevalence of occult lymph node metastasis involving level 1 was 10%. On follow‐up, there were no local recurrences associated with submental flap transposition to the oral cavity. One patient with multifocal oral disease had a tongue recurrence geographically separate from the submental flap reconstruction. There was 100% flap survival.ConclusionsThe submental flap provides a rapid and reliable option for oral cavity defect reconstruction. With appropriate management of the level 1 nodal compartment, oncologic outcomes are not compromised.

AbstractImmunoglobulin light chain (AL) Amyloidosis is a condition whereby misfolded proteins generated by plasma cells deposit in tissues causing organ dysfunction. Chemotherapy and autologous stem cell transplant when eligible are standard treatment options. Several studies report long‐term outcomes of patients post‐transplant. However, there is a paucity of literature describing outcomes of relapsed patients post‐transplant. We performed a retrospective study to assess outcomes and therapies employed upon relapse after transplant. Between 1996 and 2009, 410 patients received transplant at the Mayo Clinic as first‐line therapy. Of those patients, 42 (10%) died within 3 months of transplant, 64 (16%) died without documented relapse, 158 (38%) were alive without documented progression, and 146 (36%) had documented progression. Those 146 patients are the subject of our study, and their median time to hematologic relapse/progression was 23.6 months (95%CI 18.3, 26.3 months). Their median overall survival and 5‐yrs overall survival from post‐transplant relapse/progression was 51.7 months (95%CI 34.1–62.3) and 39%, respectively. The most common first regimen for treatment after relapse was lenalidomide or thalidomide. In conclusion, our study indicates that patients with AL amyloidosis fare well post‐transplant relapse/progression. Additionally, it provides a yardstick to design clinical trials to determine best treatment options.