High Incidence Of Premature Death Research Articles

A Practical Nomogram to Predict Early Death in Advanced Epithelial Ovarian Cancer.

Background: Ovarian cancer is a common gynecological malignancy, most of which is epithelial ovarian cancer (EOC). Advanced EOC is linked with a higher incidence of premature death. To date, no effective prognostic tools are available to evaluate the possibility of early death in patients with advanced EOC.Methods: Advanced (FIGO stage III and IV) EOC patients who were enrolled in the Surveillance, Epidemiology, and End Results database between 2004 and 2015 were regarded as subjects and studied. We aimed to construct a nomogram that can deliver early death prognosis in patients with advanced EOC by identifying crucial independent factors using univariate and multivariate logistic regression analyses to help deliver accurate prognoses.Results: In total, 13,403 patients with advanced EOC were included in this study. Three hundred ninety-seven out of a total of 9,379 FIGO stage III patients died early. There were 4,024 patients with FIGO stage IV, 414 of whom died early. Nomograms based on independent prognostic factors have the satisfactory predictive capability and clinical pragmatism. The internal validation feature of the nomogram demonstrated a high level of accuracy of the predicted death.Conclusions: By analyzing data from a large cohort, a clinically convenient nomogram was established to predict premature death in advanced EOC. This tool can aid clinicians in screening patients who are at higher risk for tailoring treatment plans.

Subclinical left ventricular dysfunction assessed by two-dimensional speckle tracking echocardiography in asymptomatic patients with carotid stenosis.

The relationship between subclinical left ventricular (LV) dysfunction and atherosclerosis may have been underestimated in the past, which might be responsible for the high incidence of premature death in individuals with carotid stenosis. We sought to evaluate the underlying myocardial dysfunction in asymptomatic carotid stenosis patients using speckle tracking echocardiography (STE). Fifty patients with carotid stenosis ≥ 50% and a preserved LV ejection fraction (LVEF), and 45 controls without carotid stenosis who were matched in terms of vascular comorbidities were enrolled. All participants underwent carotid ultrasound and echocardiographic examination. The global LV longitudinal strain (GLS) was measured using STE. Compared with the control group, the e' of the mitral annular velocity and GLS were decreased in asymptomatic carotid stenosis patients (p < 0.05), however, the LVEF was well preserved. Based on a predefined cutoff for subclinical LV systolic dysfunction that was defined at a GLS < - 18%, this dysfunction was detected in 22 patients with carotid stenosis (44%) and in 10 patients in the control group (22%) (p < 0.05). The GLS was negatively correlated with the levels of low-density lipoprotein cholesterol (r = - 0.356, p < 0.05) and triglyceride (r = - 0.396, p < 0.05). In conclusion,LV diastolic and systolic functioning were significantly decreased in patients with asymptomatic carotid stenosis, and dyslipidemia likely contributed to the subclinical LV dysfunction in these patients. Our findings indicated the importance of detecting LV subclinical dysfunction and early intervention in this patient population.

Coarctation of Aorta in a Child with Proteus Syndrome

Sir, Proteus syndrome is a rare, highly variable disorder with asymmetric and disproportionate overgrowth of body parts, connective tissue nevi, epidermal nevi, dysregulated adipose tissue, and vascular malformations [1]. The cause of this syndrome is unknown but it is thought to arise from a postzygotic mutation event resulting in mosaicism [2]. Due to several overlapping features with other syndromes and frequent misdiagnosis of the syndrome in the literature; detailed diagnostic criteria have been proposed [1, 3].We report a child with Proteus syndrome with coexistent coarctation of aorta. A 10-y-old boy was admitted with a history of severe, continous headache of 2 d duration. On examination, hemihypertrophy of upper limb and presence of a linear epidermal nevus were observed, which had been present at birth but gradually increased to the present size (Fig. 1). Child also had systemic hypertension with differential blood pressure in limbs, and fundal changes of hypertension. Echocardiography revealed coarctation of ascending aorta, which was confirmed on angiography (Fig. 2) and an aortoplasty was done. Further workup revealed presence of venous malformations in the left upper limb (ultrasound doppler), renomegaly, scoliosis, and bony cysts in limb bones (Fig. 3). The child’s development was normal and there was no history of similar illness in the family. Biochemical and hematological workup were normal. As per the standard criteria [1, 3], patient was diagnosed to have proteus syndrome (2 points in group B, 1 point in group C). Diagnosing Proteus syndrome is important as it has a high incidence of premature death and other complications (scoliosis, central nervous system abnormalities, tumors, otolaryngologic complications, pulmonary cystic malformations, dental and ophthalmic complications) [1]. Vascular malformations (one or more of capillary, lymphatic or venous malformations) is a low specificity finding in the syndrome, but malformation of major arteries has only once been reported before [4]. A boy who died at 16.5 mo with hemihypertrophy, eye abnormalities, macrodactyly, hamartomas, pigmented nevi, cerebral involvement, and other anomalies compatible with the Proteus syndrome also had complex congenital heart defects, including coarctation of aorta [4]. Although the occurrence of aortic coarctation may well be an

Frequency of Mitochondrial Defects in Patients With Chronic Intestinal Pseudo-Obstruction

Chronic intestinal pseudo-obstruction (CIPO) is a rare disorder caused by intestinal dysmotility and characterized by chronic symptoms suggesting bowel obstruction in the absence of fixed, occluding lesions. CIPO has been associated with primary defects of the mitochondrial oxidative phosphorylation pathway, although the frequency of mitochondrial disorders in patients with CIPO is unknown. This study evaluates mitochondrial function in patients with CIPO. A retrospective study was performed of data collected from 80 CIPO patients at a tertiary centre over a 25-year period. Mitochondrial disorders were detected by analysis of serum lactate and thymidine phosphorylase activities, brain magnetic resonance images, and muscle biopsies. Genes encoding thymidine phosphorylase, mitochondrial DNA tRNA(leu(UUR)) or tRNA(lys), and DNA polymerase-gamma were analyzed for mutations. Mitochondrial defects were identified in 15 patients (10 women; median age at diagnosis 32 years), representing 19% of the study cohort. All 15 patients had extra-digestive symptoms, 5 had mutations in the thymidine phosphorylase gene, 2 had mutations in tRNA(leu(UUR)), and 5 had mutations in the DNA polymerase-gamma gene. No genetic defect was detected in 3 of the patients with mitochondrial disorders. Patients with mitochondrial CIPO differed from patients without mitochondrial defects in their very severe nutritional status (frequent and long-term requirement for parenteral nutrition) and poor prognosis (frequent digestive and neurologic complications that led to a high incidence of premature death). Mitochondrial disorders seem to be an important cause of CIPO. Patients with CIPO, especially severe cases with associated neurologic symptoms, should be tested for mitochondrial defects.

A Contemporary Approach to Hypertrophic Cardiomyopathy

A previously healthy 32-year-old female undergoes evaluation after a syncopal episode. Physical examination reveals a systolic ejection murmur. Echocardiography demonstrates a vigorous LV with marked asymmetric septal hypertrophy, systolic anterior motion of the mitral valve, and a 50–mm Hg outflow tract gradient. Family history is notable for unexpected death in 4 paternal family members. She has 2 children (Figure 1A). Figure 1. A, HCM is a genetic cardiovascular disease. This family shows autosomal dominant inheritance with &50% of the family affected and equal numbers of affected male (▪) and female (•) family members. The case patient is indicated by an arrow. Deceased individuals are indicated by a diagonal slash (all died suddenly). B, DNA sequence analysis can identify sarcomere mutations that cause HCM. Top, The normal sequence of a portion of the cardiac troponin T gene is displayed with a triplet codon, TCC, encoding serine present. Bottom, DNA sequence obtained from a patient with HCM. The normal sequence is present on the allele inherited from the unaffected parent; the other allele shows a single base-pair substitution of a thymidine residue for the normal cytosine residue. This triplet codon, TTC, encodes phenylalanine and results in the substitution of a phenylalanine residue for the normal serine residue at amino acid position 179. The prevalence of unexplained left ventricular hypertrophy (LVH) in the general population is estimated to be 1 in 500.1,2 Hypertrophic cardiomyopathy (HCM) caused by sarcomere mutations may account for up to 60% of unexplained LVH, making HCM the most common genetic cardiovascular disorder.3–5 Accurate diagnosis of HCM is important for appropriate management of major HCM comorbidities, including atrial fibrillation, stroke, heart failure, and sudden cardiac death (SCD).6,7 HCM typically is diagnosed by unexplained LVH on echocardiography. Age of onset of LVH ranges from early childhood to …

Reassessment of the Proteus syndrome literature: application of diagnostic criteria to published cases.

The medical care of patients affected by rare disorders depends heavily on experiences garnered from prior cases, including those patients evaluated by the treating physician and those published in the medical literature. The utility of published cases is wholly dependent upon accurate diagnosis of those patients. In our experience, the rate of misdiagnosis in Proteus syndrome (PS) is high. Diagnostic criteria have been published, but these criteria have not been applied consistently and were published after many case reports appeared in the literature. We reviewed 205 cases of individuals reported to have PS in the literature and three of us independently applied the diagnostic criteria to these case reports. Our initial diagnostic congruence was 97.1% (199/205); the discrepancies in six cases were easily resolved. Only 97 (47.3%) of reported cases met the diagnostic criteria for PS; 80 cases (39%) clearly did not meet the criteria; and although 28 cases (13.7%) had features suggestive of PS, there were insufficient clinical data to make a diagnosis. Reported cases that met the PS criteria had a higher incidence of premature death, and other complications (scoliosis, megaspondyly, central nervous system abnormalities, tumors, otolaryngologic complications, pulmonary cystic malformations, dental and ophthalmogic complications) compared to those in the non-Proteus group. The cases that met the criteria were more often male, which has implications for hypotheses regarding the etiology and pathophysiology of PS. We also studied the attributes that led authors to conclude the reported patients had PS when we concluded they did not. We found that two of the diagnostic criteria (disproportionate overgrowth and connective tissue nevi) were often misinterpreted. In PS, the abnormal growth is asymmetric, distorting, relentless, and occurred at a faster rate compared to the rest of the body. Furthermore, PS was associated with irregular and disorganized bone, including hyperostoses, hyperproliferation of osteoid with variable calcification, calcified connective tissue, and elongation of long bones with abnormal thinning. In contrast, non-Proteus cases displayed overgrowth that was asymmetric but grew at a rate similar to the growth found in unaffected areas of the body. Also, the overgrowth in non-Proteus cases was associated with normal or enlarged bones together with ballooning of the overlying soft tissues. Taken together, these data show that (1) PS diagnostic criteria sort individuals with asymmetric overgrowth into distinct groups; (2) individuals with PS were more likely to have serious complications; (3) PS affects more males than females; and 4) the published diagnostic criteria are useful for clinical care and research. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299/suppmat/index.html.

Genotype-phenotype relationships in Berardinelli-Seip congenital lipodystrophy

Generalised lipodystrophy of the Berardinelli-Seip type (BSCL) is a rare autosomal recessive human disorder with severe adverse metabolic consequences. A gene on chromosome 9 (BSCL1) has recently been identified, predominantly...

Systemic and neurologic abnormalities distinguish the lysosomal disorders sialidosis and galactosialidosis in mice

Neuraminidase initiates the hydrolysis of sialo-glycoconjugates by removing their terminal sialic acid residues. In humans, primary or secondary deficiency of this enzyme leads to two clinically similar neurodegenerative lysosomal storage disorders: sialidosis and galactosialidosis (GS). Mice nullizygous at the Neu1 locus develop clinical abnormalities reminiscent of early-onset sialidosis in children, including severe nephropathy, progressive edema, splenomegaly, kyphosis and urinary excretion of sialylated oligosaccharides. Although the sialidosis mouse model shares clinical and histopathological features with GS mice and GS patients, we have identified phenotypic abnormalities that seem specific for sialidosis mice. These include progressive deformity of the spine, high incidence of premature death, age-related extramedullary hematopoiesis, and lack of early degeneration of cerebellar Purkinje cells. The differences and similarities identified in these sialidosis and GS mice may help to better understand the pathophysiology of these diseases in children and to identify more targeted therapies for each of these diseases.

Prognostic implications of novel beta cardiac myosin heavy chain gene mutations that cause familial hypertrophic cardiomyopathy.

Three novel beta cardiac myosin heavy chain (MHC) gene missense mutations, Phe513Cys, Gly716Arg, and Arg719Trp, which cause familial hypertrophic cardiomyopathy (FHC) are described. One mutation in exon 15 (Phe513Cys) does not alter the charge of the encoded amino acid, and affected family members have a near normal life expectancy. The Gly716Arg mutation (exon 19; charge change of +1) causes FHC in three family members, one of whom underwent transplantation for heart failure. The Arg719Trp mutation (exon 19; charge change of -1) was found in four unrelated FHC families with a high incidence of premature death and an average life expectancy in affected individuals of 38 yr. A comparable high frequency of disease-related deaths in four families with the Arg719Trp mutation suggests that this specific gene defect directly accounts for the observed malignant phenotype. Further, the significantly different life expectancies associated with the Arg719Trp vs. Phe513Cys mutation (P < 0.001) support the hypothesis that mutations which alter the charge of the encoded amino acid affect survival more significantly than those that produce a conservative amino acid change.