Transient liver injury and severe neonatal cholestasis in infant with glucose-6-phosphate dehydrogenase deficiency due to a new mutation.

We report the case of a neonate with a new, previously undescribed, glucose-6-phosphate dehydrogenase (G6PD) gene mutation, which was revealed by severe cholestasis, hyperbilirubinemia, and transient liver dysfunction. The severity of the clinical phenotype with ongoing chronic hemolytic anemia suggests that this mutation belongs to class 1 G6PD deficiency. The hemizygous mutation «c.675G>c; p.Trp225Cys¼ was detected by genomic sequencing. Since severe G6PD deficiency can be revealed by cholestasis, it is important to check G6PD enzyme activity when faced with a case of liver dysfunction in the neonatal period.

Neurofilament light chain levels in pregnant multiple sclerosis patients: a prospective cohort study.

BACKGROUND AND PURPOSE: Neurofilament light chain is a cytoskeletal protein of neurons. Its levels are increasingly recognized as measures of neuroaxonal damage. The aim of this study was to explore serum neurofilament light chain (sNfL) levels in multiple sclerosis (MS) patients and healthy controls during pregnancy and puerperium. METHODS: This was a prospective, longitudinal, single-center study. sNfL concentration was assessed using a highly sensitive single-molecule array during pregnancy and in puerperium, in a cohort of 39 pregnant patients with relapsing multiple sclerosis (P-MS). Twenty-one healthy pregnant women (HPW) served as a control group. Eight P-MS suffered relapses during pregnancy (P-MS-R) in the first or second trimesters. RESULTS: No differences in pregnancy and delivery data were observed between P-MS and HPW. P-MS showed higher sNfL values than HPW in the first trimester, independently of the presence (P = 0.002) or not (P = 0.02) of relapses during pregnancy. However, in the third trimester, only P-MS-R showed higher sNfL values than HPW (P = 0.001). These differences extended to the puerperium, where P-MS-R showed higher sNfL values than those with no relapses during gestation (P = 0.02). CONCLUSION: These data strongly suggest that sNfL levels reflect MS activity during pregnancy. Additionally, the absence of relapses during pregnancy may have a beneficial effect on neurodegeneration during puerperium.

Serum neurofilament light chain in patients with acute cerebrovascular events.

BACKGROUND AND PURPOSE: Serum neurofilaments are markers of axonal injury. We addressed their diagnostic and prognostic role in acute ischemic stroke (AIS) and transient ischemic attack (TIA). METHODS: Nested within a prospective cohort study, we compared levels of serum neurofilament light chain (sNfL) drawn within 24 h from symptom onset in patients with AIS or TIA. Patients without magnetic resonance imaging on admission were excluded. We assessed whether sNfL was associated with: (i) clinical severity on admission, (ii) diagnosis of AIS vs. TIA, (iii) infarct size on admission magnetic resonance diffusion-weighted imaging (MR-DWI) and (iv) functional outcome at 3 months. RESULTS: We analyzed 504 patients with AIS and 111 patients with TIA. On admission, higher National Institutes of Health Stroke Scale (NIHSS) scores were associated with higher sNfL: NIHSS score < 7, 13.1 pg/mL [interquartile range (IQR), 5.3-27.8]; NIHSS score 7-15, 16.7 pg/mL (IQR, 7.4-34.9); and NIHSS score > 15, 21.0 pg/mL (IQR, 9.3-40.4) (P = 0.01). Compared with AIS, patients with TIA had lower sNfL levels [9.0 pg/mL (95% confidence interval, 4.0-19.0) vs. 16.0 pg/mL (95% confidence interval, 7.3-34.4), P < 0.001], also after adjusting for age and NIHSS score (P = 0.006). Among patients with AIS, infarct size on admission MR-DWI was not associated with sNfL, either in univariate analysis (P = 0.15) or after adjusting for age and NIHSS score on admission (P = 0.56). Functional outcome 3 months after stroke was not associated with sNfL after adjusting for established predictors. CONCLUSIONS: In conclusion, among patients admitted within 24 h of AIS or TIA onset, admission sNfL levels were associated with clinical severity on admission and TIA diagnosis, but not with infarct size on MR-DWI acquired on admission or functional outcome at 3 months.

[Management of thrombotic thrombocytopenic purpura in two French centers: A series of 27 patients]. / Prise en charge du purpura thrombotique thrombopénique dans deux centres français : à partir de 27 patients.

INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy due to platelet microthrombosis involved in multiple systems associated with multiple organ dysfunctions and often severe disease course. METHODS: In order to enhance the understanding of TTP, the clinical features, laboratory characteristics, treatment and outcome of 27 patients with TTP were retrospectively analyzed and investigated in two centres (Annecy and Grenoble). RESULTS: All the 27 patients presented with haemolytic anemia and decreased platelet counts. Eight patients had fever. Thirteen patients had kidney involvement including proteinuria and renal function abnormalities. Eighteen patients had neurological manifestations. Association of the 5 characteristic features of TTP was rarely found (11%) which could lead to diagnosis delay. The von Willebrand factor-cleaving protease (ADAMTS13) activity was less than 10% in all patients. At the same time, plasma ADAMTS13 inhibitors were detected in 20 patients out of the 27. After treatment with plasma exchange, glucocorticoid and rituximab, 23 patients (85%) achieved complete remission. Four patients died, in which two cases were secondary to late diagnosis. CONCLUSION: TTP is a thrombotic microangiopathy often associated with multiple organ dysfunctions. Salvage therapy, based on some studies experiences and discussed with the Reference Center, could help getting answers in most severe cases. Awareness of physicians is an important step to further limit any delay in medical care, and to further improve the prognosis of patients with TTP.

The paradoxical association between inherited factor VII deficiency and venous thrombosis.

Inherited factor VII (FVII) deficiency is considered to be a haemorrhagic disease. Nonetheless, some patients paradoxically present with venous thrombosis. We assessed whether there was a link between phenotype and genotype in seven patients with inherited FVII deficiency and thrombosis (eleven venous thrombotic events). For each patient (FVII:C < 50%), clinical data were collected, aetiological assessment of risk factors for thrombosis was investigated, and direct sequencing of the nine exons and promoter of the FVII gene (F7) was performed. We present the second series ever published on FVII patients with thrombosis. In nine of the eleven thrombotic events, there was at least one classical triggering risk factor; clinical (n = 4), familial antecedent (n = 2), or biological, defined by phospholipid-binding antibodies or elevated FVIII:C levels (n = 7). In contrast to a previous series, only two events occurred after surgery, performed both with and without replacement therapy. The thrombotic event remained unexplained in one young patient, highlighting the lack of 'protection' against venous thrombosis by low FVII:C levels. Genetic mutations were found to be heterogeneous. Among the seven F7 sequence alterations identified in the present study, only two (p.Ala354Val and p.Arg364Gln) have previously been reported in FVII-deficient patients presenting with venous thrombosis. Our genetic analyses of the F7 mutations in these patients show the complexity of FVII deficiency associated with thrombosis. These data justify a holistic, clinical and biological approach for patients with these specific symptoms. This series also strongly suggest that mild FVII deficiency should not prevent physicians from using antithrombotic prophylaxis in FVII-deficient patients.

Phenotypic and genotypic risk factors for cardiovascular events in an incident dialysis cohort.

Cardiovascular disease (CVD) remains the major cause of death in patients with end-stage renal disease (ESRD). Traditional risk factors do not explain the high prevalence of CVD in this population, and other non-traditional cardiovascular (CV) risk markers have now been described. Therefore, the potential relationship between CVD and phenotypic and genotypic risk markers was investigated prospectively in incident dialysis patients cohort. The 279 patients (244 on hemodialysis, 35 on peritoneal dialysis) within the Diamant Alpin Dialysis Cohort Study were investigated. Phenotypic and genotypic parameters were determined at dialysis initiation, patients monitored over a 2-year period, and CV events (morbidity and mortality) recorded. Globally, 82 CV events occurred and 26 patients (9.3%) died from CVD, whereas 28 (10%) died from non-CV causes. Previous CV events were strongly predictive of CV events occurrence, whatever patients had had one (hazard ratio (HR) 2, 95% confidence intervals (CI) 1.1-3.5) or more (HR 3.9, 95% CI 2.1-7.1) CV accidents before starting dialysis. Both lipoprotein(a) (HR 1.67, 95% CI 1-2.5) and total plasma homocysteine at cutoff 30 micromol/l (HR 1.7, 95% CI 1.1-2.8) were independent predictors of CV events outcome. In the subgroup of patients with homocysteine < 30 micromol/l, methylenetetrahydrofolate reductase (MTHFR) TT was the sole biological parameter predictive of CV event outcome (HR 2.5, 95% CI 1.1-10, P = 0.03). ESRD patients who enter chronic dialysis with a previous CV event, high total homocysteinemia levels, or MTHFR 677TT genotype must be considered at high risk of incident CV events.

Quantitative high D-dimer value is predictive of pulmonary embolism occurrence independently of clinical score in a well-defined low risk factor population.

We performed a prospective study to assess whether positive quantitative D-dimer (DD) levels could be integrated for a selected population in a defined strategy to accurately diagnose pulmonary embolism (PE). For this purpose, 1528 in- or outpatients with clinically suspected PE were investigated according to our prescription rules. Clinical probability was defined as low, intermediate or high. Patients in whom DD levels were measured met criteria defined by our previously described decision-making algorithm: in- and outpatients, < 80 years, without surgery in the previous 30 days or active cancer. Nine hundred and twenty-three patients (60.4%) had quantitative DD measurement using automated latex DD assay (STA-Liatest D-Di). According to our decision-making algorithm, DD measurement was applied to 70.5% of out-, and 55.7% of inpatients, and PE diagnosis was ruled out in 49.5% of the 923 patients. This allowed us to confirm prospectively that our specific rules greatly improve the DD testing efficiency. PE was diagnosed in 115 (12.5%) patients. For a 0.5 mg L(-1) cut-off, the test sensitivity was 97.4%, but its specificity was only 56.7%. However, PE prevalence increased gradually with DD levels. The true observed PE prevalence, according to the quantitative assessment of DD levels, differed from that predicted with pretest clinical probability only. Moreover, in this well-defined patient group, a quantitative DD level > 2 mg L(-1) was predictive of PE occurrence independently of the clinical score (odds ratio 6.9, 95% confidence interval 3.7, 12.8). As part of a defined strategy, knowledge of positive DD quantitative value, together with the clinical probability score, improves the PE predictive model. A clinical validation of these results in a follow-up study would now be necessary before considering the implementation of this strategy into clinical practice.

Successful use of recombinant factor VIIa for severe surgical liver bleeding in a 5 month-old baby.

A 5 month-old baby developed non-ceasing intra-peritoneal bleeding after extensive surgical biopsy for an hepatoblastoma. A single recombinant activated factor VII injection following enlarged hepatectomy helped to resolve quickly this life-threatening haemorrhagic syndrome.

[Routine preoperative evaluation of hemostasis]. / Exploration pratique pré-opératoire de l'hémostase.

Preoperative evaluation of hemostasis is mainly based on the clinical investigation. Clinical symptoms and history taking help target the most at risk patients. Clinical assessment is also helpful in defining the acquired or constitutional nature of any hemostatic disorder and the type of anomaly involved, e.g. primary hemostatic disorder or coagulation defect. Proper evaluation also helps detect the potential risk of bleeding independently of biological defects detectable with routine tests. Applied in an informative population, clinical evaluation enables optimal utilization of laboratory results.

Surgery in severe factor XIII deficiency: report of a case of epilepsy neurosurgery and review.

Factor XIII (FXIII) deficiency is a rare autosomal recessive congenital disorder of haemostasis, associated with a high risk of intracranial haemorrhage. Intracranial haemorrhage can result in neurological sequelae including seizure disorders. In some cases, medically intractable epilepsy led to epilepsy surgery. Little has been reported on the management of FXIII deficiency during surgery, and there is only a few data on the management, safety and efficacy of epilepsy surgery in the patients with haemostatic disorder. We report here an epilepsy neurosurgery in a case of severe FXIII deficiency.

[Factors affecting local and regional control and survival of carcinomas of the tongue and floor of mouth]. / Factores que afectan el control local, regional y supervivencia en carcinomas de lengua móvil y suelo de boca.

A retrospective study of 142 patients that had previous surgery for carcinoma of the tongue or floor of mouth looking into the factors that affect significantly the evolution of our patients and in which circumstances we could benefit from new therapeutic techniques. Cause specific survival at 3 and 5 years was 63.4% and 56.9% respectively. Recurrences were found locally in 32 patients (22.5%), regional in 32 (22.5%) and metastasis in 11 (7.4%). T staging had no did impact on local recurrence, but the presence of positive margins (p = 0.0323). Regional control for N0/N1 was 85% (90/106) versus 55.5% (20/36) for N2/N3 (p = 0.001). Regional control by N staging was 84.5% (73/86) for N0, 85% (17/20) for N1, 57% (30/35) for N2 and 0% for N3 (0/1). Both, N staging and number of positive nodes had a significant impact in specific survival. Positive margins and the presence of positive nodes have the greatest impact on survival and regional control. Adjuvant postoperative radiotherapy did not increase survival, but not prospective random selection was performed. To evaluate this.

Factores que afectan el control local, regional y supervivencia en carcinomas de lengua móvil y suelo de boca / Factors affecting local and regional control and survival of carcinomas of the tongue and floor of mouth

Hemos realizado un estudio retrospectivo de 142 pacientes intervenidos de carcinoma de lengua móvil o suelo de boca buscando qué factores afectan de forma significativa la evolución de nuestros pacientes y en qué circunstancias podríamos beneficiarnos de nuevas modalidades terapéuticas. La supervivencia causa específica a 3 y 5 años fue de 63,4 por ciento y 56,9 por ciento respectivamente. Se detectó una recidiva local en 32 pacientes (22,5 por ciento), regional en 32 (22,5 por ciento) y a distancia en 11 (7,4 por ciento). No se ha encontrado influencia del T en la incidencia de recidiva local pero sí lo tiene la presencia de márgenes positivos (p=0,0323). El control regional en N0/N1 fue de un 85 por ciento (90/106) frente a un 55,5 por ciento (20/36) en los N2/N3 (p=0,001). El control regional, especificado por estadio N fue de 84,5 por ciento (73/86) en los N0, 85 por ciento (17/20) en los N1, 57 por ciento (30/35) para los N2 y 0 por ciento para los N3 (0/1). Tanto el estadio N como el número de ganglios mostró una significativa repercusión en la supervivencia específica. En nuestra experiencia los factores que mayor impacto tienen en el control del cáncer de cavidad oral y suelo de boca son la presencia de bordes quirúrgicos infiltrados y el estado del cuello. El empleo de radioterapia adyuvante no implicó un incremento en la supervivencia, si bien no se hicieron grupos aleatorios para su valoración (AU)

A retrospective study of 142 patients that had previous surgery for carcinoma of the tongue or floor of mouth looking into the factors that affect significantly the evolution of our patients and in which circumstances we could benefit from new therapeutic techniques. Cause specific survival at 3 and 5 years was 63.4% and 56.9% respectively. Recurrences were found locally in 32 patients (22.5%), regional in 32 (22.5%) and metastasis in 11 (7.4%). T staging had no did impact on local recurrence, but the presence of positive margins (p = 0.0323). Regional control for N0/N1 was 85% (90/106) versus 55.5% (20/36) for N2/N3 (p = 0.001). Regional control by N staging was 84.5% (73/86) for N0, 85% (17/20) for N1, 57% (30/35) for N2 and 0% for N3 (0/1). Both, N staging and number of positive nodes had a significant impact in specific survival. Positive margins and the presence of positive nodes have the greatest impact on survival and regional control. Adjuvant postoperative radiotherapy did not increase survival, but not prospective random selection was performed. To evaluate this (AU)

Dehydrated hereditary stomatocytosis: a cause of prenatal ascites.

Dehydrated hereditary stomatocytosis (DHS) is a rare congenital hemolytic anemia. We observed that some patients had presented with different prenatal or perinatal forms of edema in some kindreds. Within weeks or months after birth, these exhibited a spontaneous, complete and definitive resorption. We assumed that some DHS patients, who were born without edema before ultrasound was available, might nonetheless have exhibited this during the prenatal period. The present report follows up the first pregnancy in a woman with overt DHS, but not herself having a known history of perinatal effusions. Ultrasound revealed that the fetus displayed ascites that disappeared prior to birth. The neonate had DHS. Prenatal edema must therefore be more frequent in DHS than known until now. DHS is another cause of prenatal edema to be considered in the differential diagnosis.

Complications after total laryngectomy in nonradiated laryngeal and hypopharyngeal carcinomas.

To study the complications of total laryngectomy, we evaluated 471 previously untreated patients who underwent total laryngectomy between 1980 and 1997. This series consisted of 358 patients with primary carcinoma of the larynx and 113 with carcinoma of the hypopharynx. Concurrent neck dissection was performed in 85% of patients. Complications were studied in relation to age, T and N stage, previous tracheostomy, neck dissection, margins, reconstruction, tracheoesophageal puncture, and surgeon. Complication treatment and hospitalization were also evaluated. The overall complication rate was 30.7%, with 29.2% major and 6.5% minor complications. The mortality rate was 0.6% (3/471). Pharyngocutaneous fistula was the most frequent wound complication (21%), followed by wound infection (4.2%) and hemorrhage (2.3%). Pneumonia (1.4%) and embolism (0.4%) were the most frequent medical complications. Hypopharyngeal tumors, neck dissection, and extended procedures had a significantly higher rate of complications. Complication causes, prevention, and treatment are discussed.

[Radiotherapy in glottic T1 carcinoma. Local control and survival]. / Radioterapia en el carcinoma T1 glótico. Control local y supervivencia.

Between January 1980 and April 1995, 57 treatment-naive patients diagnosed as glottic epidermoid T1 carcinoma were treated in the ear, nose and throat department of Juan Canalejo Hospital of La Coruña, Spain. Seventy-nine percent (79%) (45/57) had T1a lesions and 21% (12/57) had T1b. All patients were treated by the radiotherapy department of the Regional Oncological Center with Co60 at doses ranging from 50 Gy to 70 Gy. Local control was achieved in 74.5% (43/57). Cause-specific survival was 96% at 3, 5, and 10 years. The larynx was preserved in 96.5% (55/57). The local recurrence rate was significantly lower for T1a (16.8%) than for T1b (57.8%) (p < 0.05). No significant differences were found in local control or survival with different dosing regimens.