Changes in Neuron-Specific Enolase are More Suitable Than Its Absolute Serum Levels for the Prediction of Neurologic Outcome in Hypothermia-Treated Patients with Out-of-Hospital Cardiac Arrest

Background

To determine neurologic outcome in patients with out-of-hospital cardiac arrest (OHCA) and treatment with mild therapeutic hypothermia (MTH).

Methods

Seventy-three consecutive OHCA patients treated with MTH were retrospectively analyzed. Serum neuron-specific enolase (NSE) was measured 24, 48, and 72 h after admission. In patients with no motor response 48 h after termination of analgosedation (n = 40), clinical neurological examination and evoked potentials (EPs) were determined. Neurological outcome was assessed after 2 months based on the cerebral performance categories (CPC), and categorized as good (CPC 1–3) or poor (CPC 4 and 5).

Results

Forty-three patients had a CPC score of 1–3 and 30 patients had a CPC 4–5. The best predictive value for poor neurologic outcome was an increase of NSE by ≥4.3 ng/mL between day 1 and day 2 (sensitivity 80 %, specificity 100 %, positive predictive value (PPV) 100 %, negative predictive value 86 %). Absolute NSE values were less reliable in the prediction of poor outcome with the highest sensitivity (88 %) and specificity (95 %) if values reached ≥36.3 ng/mL on day 3. Somatosensory EPs (SSEPs) showed a specificity of 100 % and PPV of 100 %; however, sensitivity for evoked potentials was low (29 %). Intriguingly, two initially comatose patients with excessive NSE values (24 h NSE: 101 and 256 ng/mL, and 48 h NSE: 93 and 110 ng/mL, respectively) had physiological SSEPs and regained a CPC score of 1.

Conclusion

In patients treated with MTH after OHCA changes in NSE are more suitable than its absolute serum levels for the prediction of poor neurologic outcome. Since unequivocal prediction of poor neurologic outcome is of utmost importance in these patients the decision to limit therapy must be based on several prediction tools with the highest PPV and specificity including SSEPs.     

Prenatal molecular diagnosis of X‐linked hydrocephalus via a silent C924T mutation in the L1CAM gene

We present a case of a patient whose L1CAM gene in X‐chromosome has a C924T transition. Her first son's ventriculomegaly was prenatally detected. A mature infant was born, his head circumference was large, and thumbs were bilaterally adducted. X‐linked hydrocephalus (XLH) was suspected. The DNA examination revealed that both her and boy's LICAM gene had a C924T transition. She became pregnant 5 years later and amniocentesis was performed. The results of cytogenetic analysis revealed that the fetus was female. She continued her pregnancy and delivered a healthy girl. She again became pregnant 3 years later. The chromosomal analysis revealed that the fetus was male. Fetal DNA analysis determined that the fetus had the inherited mutation. She chose to terminate the pregnancy. A C924T mutation can be disease causing for XLH, and the detection of this mutation would aid in genetic counseling for the prenatal diagnosis of XLH.     

Cost of illness study for adult atopic dermatitis in Japan: A cross-sectional Web-based survey

Atopic dermatitis is a pruritic, eczematous dermatitis, the symptoms of which chronically fluctuate with remissions and relapses. Although a high psychosomatic and economic burden caused by atopic dermatitis is expected, few studies have been conducted estimating the cost of illness, including the self-medication costs and productivity loss due to atopic dermatitis. The aim of this study was to conduct a cross-sectional, Web-based survey of the direct medical costs, self-medication costs and productivity loss for adult atopic dermatitis patients, and estimate the burden of Japanese adult atopic dermatitis patients by disease severity. In a physician survey, the medical resource consumption related to medical treatments was surveyed by disease severity. The direct medical costs were calculated by multiplying the medical resource consumption and medical fee corresponding to each treatment. Based on the results of a patient survey, the self-medication costs and productivity loss were estimated by sex and disease severity. Atopic dermatitis-related productivity loss was calculated based on absenteeism, presenteeism, overall work impairment for employed workers and activity impairment for housewives. The nationwide estimations were calculated based on the estimated number of atopic dermatitis patients, employed workers with atopic dermatitis, and housewives with atopic dermatitis in their 20s–50s in Japan. Based on the surveys, all costs per patient and the scores increased with disease severity. The cost of illness for adult atopic dermatitis patients in Japan was estimated to be approximately JPY 3 trillion/year. Considering the physical and mental burdens, the burden of illness for adult atopic dermatitis was demonstrated to be vast.     

Prognostic factors in the treatment of non-small-cell lung carcinoma (NSCLC)

From 1980 to 1990 we treated 107 non-small-cell lung carcinomas (NSCLC) with radiotherapy alone. The study was done to evaluate the prognostic factors in an absolutely negative selected group of patients with regard to the International Union Against Cancer (UICC) classification published in 1987. Patients who had a prior response to neo-adjuvant chemotherapy were excluded from the analysis. Therefore, a negative selection of 98 males and 9 females were treated. All patients were classified retrospectively according to UICC 1987. Nine males and 7 females were stages I and II, respectively. In stage IIIa there were 41 patients, and in stage IIIb 42. A total of 18 patients were staged IV. Results: 5-year overall actuarial survival was approximately 1 %. As main prognostic factor we found the stage of disease. Two-year survival rates in stages I and II were 25 %, in stage IIIa 20 %, in stage IIIb 12 % and in stage IV 0%. The Karnowsky Index (KI) was an important second factor: Patients with a good KI (90–100 %) had a 2-year survival rate of 27 %, and patients with a KI of 70–80 % had a 6.5 % 2-year survival rate. Other prognostic factors were: (1) given total radiation dose, (2) actual response to radiation therapy and (3) normal white blood cell (WBC) count. Leukocytosis is a negative factor for prognosis. We conclude that the stage and, among other factors, the general condition (KI, WBC), are relevant for the prognosis of patients with NSCLC. Correspondence to: M. Busch     

Alpha‐actinin‐4 (ACTN4) gene amplification is a predictive biomarker for adjuvant chemotherapy with tegafur/uracil in stage I lung adenocarcinomas

Although adjuvant tegafur/uracil (UFT) is recommended for patients with completely resected stage I non‐small‐cell lung cancer (NSCLC) in Japan, only one‐third of cases has received adjuvant chemotherapy (ADJ) according to real‐world data. Therefore, robust predictive biomarkers for selecting ADJ or observation (OBS) without ADJ are needed. Patients who underwent complete resection of stage I lung adenocarcinoma with or without adjuvant UFT were enrolled. The status of ACTN4 gene amplification was analyzed by FISH. Statistical analyses to determine whether the status of ACTN4 gene amplification affected recurrence‐free survival (RFS) were carried out. Formalin‐fixed, paraffin‐embedded samples from 1136 lung adenocarcinomas were submitted for analysis of ACTN4 gene amplification. Ninety‐nine (8.9%) of 1114 cases were positive for ACTN4 gene amplification. In the subgroup analysis of patients aged 65 years or older, the ADJ group had better RFS than the OBS group in the ACTN4‐positive cohort (hazard ratio [HR], 0.084, 95% confidence interval [CI], 0.009‐0.806; P = .032). The difference in RFS between the ADJ group and the OBS group was not significant in ACTN4‐negative cases (all ages: HR, 1.214; 95% CI, 0.848‐1.738; P = .289). Analyses of ACTN4 gene amplification contributed to the decision regarding postoperative ADJ for stage I lung adenocarcinomas, preventing recurrence, improving the quality of medical care, preventing the unnecessary side‐effects of ADJ, and saving medical costs.     

The efficacy of herbal medicine (kampo) in reducing the adverse effects of IFN-beta in chronic hepatitis C

The purpose of this study was to determine if the adverse effects of interferon (IFN) in hepatitis C patients could be reduced by treatment with Japanese Oriental (Kampo) medicine. Twelve patients with chronic hepatitis C were treated with a combination of IFN-beta and either Mao-to or Dai-seiryu-to (groups A and B), and 16 patients were treated with IFN-beta alone (group C). Mao-to was administered to eight patients and Dai-seiryu-to was administered to four in groups A and B, respectively. Adverse effects were evaluated by clinical and laboratory examinations. The severity of symptoms was daily self-classified into four categories (1: none, 2: very slight, 3: moderate, and 4: serious), using a questionnaire consisting of 29 items. Scores of symptom such as discomfort and fever in group A, and discomfort, general malaise, paresthesia and arthralgia in group B were significantly lower than those in group C (p < 0.05). In all patients, HCV-RNA was negative at the end of the treatment, and serum alanine aminotransferase (ALT) levels had normalized transiently in all group A and B patients with genotype 1b by 2 weeks after cessation of IFN treatment. This study indicates that Kampo medicines are useful for reducing the adverse effects accompanying IFN treatment in patients with chronic hepatitis C without reducing the antiviral effects.     

Anesthetic management of a patient with hereditary spastic paraplegia

We experienced the anesthetic management of a 39 year-old-male with hereditary spastic paraplegia (HSP) associated with pain due to pes cavus. He underwent orthomorphia ostectomy and tenodesis. Preoperative neurological examination revealed that he had slight dementia, symptoms of the pyramidal tract, lower limb bathyhypesthesia, and neurogenic bladder in addition to spastic paraplegia, and he was diagnosed as having combined type of HSP. Spinocerebellar degeneration is often accompanied with this type of HSP. To avoid the use of muscle relaxants and narcotics, we tried to induce anesthesia with inhalation of nitrous oxide (N2O), oxygen and sevoflurane (sevo). A laryngeal mask (LM) was inserted at the expiratory concentration of sevo 3.5%. Anesthesia was maintained by N2O, oxygen and sevo (2-3%) under spontaneous respiration. The patient recovered from anesthesia after the end of surgery, and the LM was removed smoothly. The patient's respiratory condition was stable, and no problems were found in the postoperative period.     

Anesthetic management of four cases of craniotomy with alternate monitoring of motor and somatosensory evoked potentials

We experienced four cases of craniotomy in which motor evoked potential (MEP) and somatosensory evoked potential (SEP) were monitored alternately. Anesthesia was induced with propofol and fentanyl, and it was maintained with continuous infusion of propofol. Intermittently, propofol and fentanyl were administered as needed. Inhalation of 66% nitrous oxide did not prolong latency, but significantly reduced the amplitude of MEP. We could obtain the largest amplitude of MEP using five consecutive stimuli of which duration and frequency were 0.5 milliseconds and 500 Hz, respectively. Anesthetic management using propofol and fentanyl is useful for craniotomy with monitoring of MEP and SEP.