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Cleveland, OH, United States

DeBrosse S.D.,1100 Euclid Avenue | Okajima K.,1100 Euclid Avenue | Okajima K.,Case Western Reserve University | Okajima K.,Asahikawa University | And 8 more authors.
Molecular Genetics and Metabolism | Year: 2012

Pyruvate dehydrogenase complex (PDC) deficiency is a relatively common mitochondrial disorder that primarily presents with neurological manifestations and lactic acidemia. We analyzed the clinical outcomes and neurological features of 59 consented symptomatic subjects (27 M, 32 F), who were confirmed to have PDC deficiency with defined mutations in one of the genes of PDC (PDHA1, n = 53; PDHB, n = 4; DLAT, n = 2), including 47 different mutations, of which 22 were novel, and for whom clinical records and/or structured interviews were obtained.39% of these subjects (23/59) have died. Of these, 91% (21/23) died before age 4. years, 61% (14/23) before 1. year, and 43% (10/23) before 3. months. 56% of males died compared with 25% of females. Causes of death included severe lactic acidosis, respiratory failure, and infection. In subjects surviving past 6. months, a broad range of intellectual outcomes was observed. Of 42 subjects whose intellectual abilities were professionally evaluated, 19% had normal or borderline intellectual ability (CQ/IQ ≥ 70), 10% had mild intellectual disability (ID) (CQ/IQ 55-69), 17% had moderate ID (CQ/IQ 40-54), 24% had severe ID (CQ/IQ 25-39) and 33% had profound ID (CQ/IQ < 25). Assessment by parents was comparable. Of 10 subjects who reached age 12. years, 9 had had professional IQ assessments, and only 4 had IQs ≥ 70 (only 2 of these 4 had assessments after age 12. years). The average outcome for females was severe-to-profound ID, whereas that of males was mild-to-moderate ID.Of subjects for whom specific neurological data were available, the majority had hypotonia (89%), and hypertonia or mixed hyper-/hypotonia (49%) were common. Seizures (57%), microcephaly (49%), and structural brain abnormalities including ventriculomegaly (67%) and agenesis, dysgenesis, or hypoplasia of the corpus callosum (55%) were common. Leigh syndrome was found in only 35%. Structural brain abnormalities were more common in females, and Leigh syndrome was more common in males. In a subgroup of 16 ambulatory subjects > 3.5. years in whom balance was evaluated, ataxia was found in 13. Peripheral neuropathy was documented in 2 cases but not objectively evaluated in most subjects.Outcomes of this population with genetically confirmed PDC deficiency are heterogeneous and not distinctive. Correlations between specific genotypes and outcomes were not established. Although more females survive, related to the prevalence of X-linked PDHA1 mutations, symptomatic surviving females are generally more severely impaired cognitively and have a different pattern of neurological impairment compared to males. Neonatal or infant onset of symptoms was associated with poor outcomes. Males with PDHA1 mutations and low fibroblast PDC activity were less likely to survive beyond infancy. Recurrence rate in siblings of subjects with PDHA1 mutation was less than 5%. Paradoxically, in this retrospective review, potential factors considered possibly relevant to development, such as in vitro PDC activity, specific mutations, use of ketogenic diets, supplements, or medications, were generally not confirmed to be significantly correlated with objective outcomes of survival or neuro-cognitive function. Therefore, the basis of variability of these outcomes remains largely undetermined. © 2012 Elsevier Inc.

Petro C.C.,1100 Euclid Avenue | Petro C.C.,University Hospitals Case Medical Center | Raigani S.,1100 Euclid Avenue | Raigani S.,University Hospitals Case Medical Center | And 12 more authors.
Plastic and Reconstructive Surgery | Year: 2015

Background: Repair of hernias with loss of domain can lead to elevated intraabdominal pressure. The authors aimed to characterize the effects of elective hernia repair on intraabdominal pressure, as well as its predictors and association with negative outcomes. Methods: Patients undergoing elective hernia repair requiring myofascial release had intraabdominal and pulmonary plateau pressures measured preoperatively, postoperatively, and on the morning of the first postoperative day. Loss of domain was measured by preoperative computed tomography. Outcome measures included predictors of an increase in plateau pressure, respiratory complications, and acute kidney injury. Results: Following 50 consecutive cases, diagnoses of intraabdominal hypertension (92 percent), abdominal compartment syndrome (16 percent), and abdominal perfusion pressure less than 60 mmHg (24 percent) were determined. Changes in intraabdominal pressure (preoperative, 12.7 ± 4.0 mmHg; postoperative, 18.2 ± 5.4 mmHg; postoperative day 1, 12.9 ± 5.2 mmHg) and abdominal perfusion pressure (preoperative, 74.7 ± 15.7; postoperative, 70.0 ± 14.4; postoperative day 1, 74.9 ± 11.6 mmHg) consistently resolved by postoperative day 1, and were not associated with respiratory complications or acute kidney injury. Patients who remained intubated postoperatively for an elevation in pulmonary plateau pressure (≥6 mmHg) all demonstrated an improvement in plateau pressure by postoperative day 1 (preoperative, 18.9 ± 4.5 mmHg; postoperative, 27.4 ± 4.0 mmHg; postoperative day 1, 20.1 ± 3.7 mmHg), and could be identified preoperatively as having a hernia volume of greater than 20 percent of the abdominal cavity (p < 0.001), but were still more likely to have postoperative respiratory events (p = 0.01). Conclusions: Elevated intraabdominal pressure following elective hernia repair requiring myofascial releases is common but transient. Change in plateau pressure by 6 mmHg or more following repair can be expected with a loss of domain greater than 20 percent and is a more useful surrogate than intraabdominal pressure measurements with regard to predicting postoperative pulmonary complications. The perception and management of elevated intraabdominal pressure should be considered distinct and "permissible" in this context. Copyright © 2015 by the American Society of Plastic Surgeons.

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