Clinical Evaluation of a Vancomycin Dosage Strategy Based on a Serum Trough Concentration Model in Elderly Patients with Severe Pneumonia.

Objective: This study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly patients. Methods: This prospective single-center, open-label, randomized controlled trial categorized 66 elderly patients with severe pneumonia into study and control groups. The control group received vancomycin using a regimen decided by the attending physician. Meanwhile, the study group received individualized vancomycin therapy with a dosing strategy based on a serum trough concentration model. The primary endpoint was the proportion of patients with serum trough concentrations reaching the target values. The secondary endpoints were clinical response, vancomycin treatment duration, and vancomycin-associated acute kidney injury (VA-AKI) occurrence. Results: All patients were at least 60 years old (median age = 81 years). The proportion of patients with target trough concentration achievement (≥ 15 mg/L) with the initial vancomycin regimen was significantly higher in the study group compared to the control group (75.8% vs. 42.4%, P = 0.006). Forty-five patients (68.2%) achieved clinical success, the median duration of vancomycin therapy was 10.0 days, and VA-AKI occurred in eight patients (12.1%). However, there were no significant differences in these parameters between the two groups. The model for predicting vancomycin trough concentrations was upgraded to: serum trough concentration (mg/L) = 17.194 - 0.104 × creatinine clearance rate (mL/min) + 0.313 × vancomycin daily dose [(mg/(kg∙d)]. Conclusion: A vancomycin dosage strategy based on a serum trough concentration model can improve the proportion of patients achieving target trough concentrations in elderly patients with severe pneumonia.

Influence of the Pre-shock State on the Prognosis of Medical Patients with Sepsis: A Retrospective Cohort Study.

Objective: To investigate the effects of the pre-shock state on the mortality of patients with sepsis. Methods: We enrolled patients with sepsis admitted to the medical intensive care unit of a tertiary care university hospital. These patients were then classified into three groups: sepsis, pre-shock state, and septic shock. The primary outcome was the 28-day mortality rate. The secondary outcomes were the 90-day, 180-day, and 1-year mortality rates. Results: A total of 303 patients (groups: sepsis 135 [44.6%]), pre-shock state (93 [30.7%]), and septic shock (75 [24.8%]) completed the 1-year follow-up. The mortality rates at 28 days, 90 days, and 180 days and 1 year were significantly higher in the pre-shock state group than those of the sepsis group, but significantly lower than those in the septic shock group, especially among older patients. When compared with the pre-shock state group, the sepsis group had significantly lower mortality risks at 28 days, 90 days, and 180 days and 1 year, whereas the sepsis shock group had higher mortality risks at these time points. Conclusion: The mortality rates of patients in the pre-shock state were notably different from those of patients with sepsis or septic shock. The introduction of a modified sepsis severity classification, which includes sepsis, pre-shock state, and septic shock, could offer valuable additional prognostic information.

Safe dose reduction of steroid pre-medication for docetaxel in head and neck neoplasm treatment.

CONCLUSION: The results suggest that the rate of severe hypersensitivity reactions did not increase when the dexamethasone pre-medication dose was reduced to 11 mg prior to docetaxel infusion. OBJECTIVES: Dexamethasone is commonly used to prevent the adverse effects of docetaxel in head and neck neoplasm treatment. The recommended dexamethasone dose is 8 mg orally twice daily for 3 days for each injection of docetaxel. This pre-medication reduces the incidence of adverse effects to 1-2% of treated patients. However, many adverse events have been observed with long-term steroid use. In an attempt to balance the benefits and harms of steroid prophylaxis without affecting the safety of docetaxel, this study tried to reduce the duration and dose of dexamethasone. METHODS: In this study, a total of 336 patients underwent docetaxel-containing protocols (TP or TPF regimens) to treat head and neck neoplasms. Docetaxel was given in doses of 70 mg/m(2) once every 3 weeks. Dexamethasone (0.75 mg/tablet) pre-medication was given in different doses (45, 24, 18, and 11 mg); the minimum dose included 6 mg orally in the morning and 5 mg intravenously immediately before docetaxel infusion. RESULTS: Severe hypersensitivity reactions were experienced by none of 30 patients who received 45 mg (7.5 mg orally twice for 3 days) dexamethasone pre-medication in 125 cycles, none of 20 patients who received 24 mg (6 mg orally twice for 2 days) dexamethasone in 77 cycles, and none of 20 patients who received 18 mg (4.5 mg orally twice for 2 days) dexamethasone in 79 cycles. Three of 266 patients who received 11 mg dexamethasone in 1054 applications developed a severe hypersensitivity reaction with bronchospasm and hypotension, two of the 266 patients developed a severe rash, and four developed severe oedema.

Correlation analysis of genotypes, auditory function, and vestibular size in Chinese children with enlarged vestibular aqueduct syndrome.

CONCLUSION: In children with enlarged vestibular aqueduct syndrome (EVAS), their hearing was more related to genotype than VA size, and VA size was related to genotype. OBJECTIVE: To study genotypes of the SLC26A4 gene, types and levels of hearing loss, and vestibular aqueduct (VA) size in children with EVAS. METHODS: A total of 271 children with nonsyndromic sensorineural hearing loss and EVA underwent SLC26A4 gene screening. According to genotype typing, the phenotypes including pure tone average (PTA), distribution of subjects, and diameters of the external aperture and middle portion of the VA, were compared by t test or Pearson's χ(2) tests. Further, divided by the dilated level of the VA, subject distribution in different hearing loss levels was compared by Pearson's χ(2) test. RESULTS: In all, 66 types of mutations were identified and 2 were novel (c.665G >T and c.1639G >A). Biallelic genotype was found in 207 subjects, monoallelic in 56, and no mutation in 8. The hearing loss was more stable in the subjects with monoallelic mutation than in other genotype groups. An air-bone gap was more frequently found in subjects with biallelic missense mutations than in other groups. The patients with no mutation had the most slightly enlarged VA. There was no dominant correlation between hearing loss level and VA size, and between VA size and different genotypes.

[Clinical analysis of sudden sensorineural hearing loss in patients with different ages].

OBJECTIVE: To investigate the clinical materials of sudden sensorineural hearing loss (SSNHL) in different ages of patients, and explore their clinical characteristics and prognosis. METHODS: A retrospective review was conducted by the clinical symptoms, predisposing factors and prognosis in SSNHL patients with different ages in the past two years (from 2008 to 2010). All patients were divided into three groups according to age, including Group 1 (0-18 years old), Group 2 (19-59 years old), and Group 3 (over 60 years old). RESULTS: Part of patients (28.1%) had a clear history of virus infection in Group 1. Some patients (18.7%) had obvious history of emotional fluctuations or fatigue before the onset of SSNHL. Three groups of patients with "aural fullness" symptom accounted for 3.1%, 41.3% and 29.4% respectively. The proportions of patients with profound hearing loss in three groups were 62.5%, 40.0% and 33.3% respectively. Most patients improved hearing level during systemic internal medicine treatment. However, many patients (68.8%) in Group 1 showed poor therapeutic effect. CONCLUSIONS: SSNHL in different age stages has different clinical features. We can improve the personalized treatment program to this disease through the classification and grading treatment.

[Clinical and prognostic analyses of juvenile sudden sensorineural hearing loss].

OBJECTIVE: To explore the clinical profiles of juvenile sudden sensorineural hearing loss (JSSNHL) and examine its clinical characteristics and prognosis. METHODS: A retrospective review was conducted for the clinical symptoms, audiological characteristics, hematological indices and prognosis in JSSNHL during the past 2 years (from June 2008 to November 2010). All patients were divided into 2 groups according to age, that is group childhood (A, 0-12 years old) and group adolescence (B, 13-18 years old). RESULTS: JSSNHL patients were rarely associated with "aural fullness" symptoms. Two groups of patients with "tinnitus" symptom accounted for 88.2% and 89.5%. Those with "vertigo" symptom accounted for 47.1% and 44.4% respectively. Most patients (81.6%) showed severe and profound hearing loss. The most common types of audiometric curve were flat and total deafness. Some obvious differences existed between two groups in hematological indices, such as platelet count, concentrations of electrolyte ions, mean corpuscular volume and mean corpuscular hemoglobin. Almost half of them (42.1%) improved hearing level during systemic medical treatment. The patients of two groups showed no significant difference in efficacies. And the hearing enhancement degree of patients in group B was more apparent than that of group A. CONCLUSIONS: JSSNHL has different clinical features in different age groups. And the outcomes of personalized treatment regimens may be further improved through classification and grading.

Four systems involved with congenital abnormalities: a new type of syndromic hearing loss - ADOC Wang's syndrome?

Syndromic hearing impairment encompasses hundreds of phenotypes. We identified a young female patient affected by the unique combination of dysplasia of the auricular system, patent ductus arteriosus (PDA), choroideremia, and enamel hypoplasia. The patient was treated with PDA ligature and left exploratory tympanotomy. Impairment in all four systems suggests a correlation with the neural crest. It is presumed that all of the features result from the same origin, probably through autosomal recessive inheritance or a novel mutation during the embryonic period. When audio-dento-oculo-cardio systems are involved, we suggest that this new syndrome can be named 'ADOC Wang's syndrome', summarizing the disorders of the four systems and indicative of the founding person (Dr Wang, the first and corresponding author of the paper).

Phenotype-genotype correlation in 295 Chinese deaf subjects with biallelic causative mutations in the GJB2 gene.

AIMS: The connexin 26 coding gene (GJB2) is the primary causative gene for nonsyndromic sensorineural hearing impairment (NSSHI). More than 100 mutations in this gene have been reported to be linked to hearing impairment (HI), from mild to profound hearing loss. To precisely estimate the impact of GJB2 mutations in the Chinese population, a cross-sectional study was performed to analyze the auditory data of Chinese patients with NSSHI. RESULTS: Two hundred ninety-five unrelated patients with NSSHI with biallelic mutations in GJB2 were recruited from seven provinces in Northern China from 2004 to 2008. The levels of HI and average pure tone audiometry were compared across different genotypes by χ(2) testing. The subjects with the genotypes of combined truncating mutations had more cases of severe HI than the subjects with a genotype of several nontruncating mutations. It was also revealed that subjects carrying either c.[79G>A; 341A>G]+[79G>A; 341A>G] or c.[109G>A]+[79G>A; 341A>G] had significantly fewer cases of severe HI than the reference group of homozygous c.235delC, whereas the subjects carrying c.[235delC]+[176_191del16] had more cases of severe HI than the homozygous c.235delC group. CONCLUSIONS: This is the first study to clarify the correlations between different GJB2 biallelic genotypes and NSSHI phenotype in the Chinese population. The Chinese subjects with two truncating mutations in GJB2 were shown to correlate with more severe HI.

Molecular epidemiological analysis of mitochondrial DNA12SrRNA A1555G, GJB2, and SLC26A4 mutations in sporadic outpatients with nonsyndromic sensorineural hearing loss in China.

CONCLUSION: GJB2 mutation was frequent in sporadic outpatients and its mutation frequency was significant higher in the prelingual group than in the postlingual group, whereas the mutation of mtDNA A1555G and SLC26A4 was very rare in Chinese sporadic outpatients with nonsyndromic sensorineural hearing loss (NSHL). Standard and comprehensive inclusion and grouping criteria are necessary for epidemiological studies of deafness-related gene mutations. OBJECTIVES: This study aimed to examine the mutations of the three common deafness genes GJB2, SLC26A4, and mtDNA A1555G in Chinese sporadic outpatients with NSHL and to discuss the factors that influence the detection accuracy of mutation frequencies. METHODS: A total of 473 sporadic NSHL patients without any type of inner ear malformation, including both prelingual and postlingual groups were enrolled in this study. Three genes of mtDNA A1555G, GJB2, and SLC26A4 were screened for mutation in our study cohort. A chi-square test was performed to compare mutation frequencies between prelingual and postlingual groups. RESULTS: The mutation frequencies of MtDNA A1555G, GJB2, and SLC26A4 were 1.63%, 13.63%, and 0%, respectively, in our study cohort. The mutational hot spot of GJB2 was c.235delC, whose allele frequency was 12.68% in sporadic outpatients. Mutation frequency of GJB2 in the prelingual group was significantly higher than in the postlingual group (p < 0.05).

Analysis of a large-scale screening of mitochondrial DNA m.1555A>G mutation in 2417 deaf-mute students in northwest of China.

The ancient Silk Road (also called "Northwest Silk Road") in Northwest China, starting from Xi'an, passes through Gansu, Xinjiang, Central Asia, West Asia, and the land passage connecting the Mediterranean countries. The aim of the present study was to determine the frequency of mitochondrial DNA12SrRNA m.1555A>G mutation in a total of 2417 cases of nonsyndromic deaf-mute patients representative of the general population of Shaanxi, Gansu, Qinghai, Ningxia, and Xinjiang along the Silk Road. Enzyme digestion and direct sequencing were applied to identify sequence variations. The carrier frequency of mitochondrial DNA12S rRNA m.1555A>G mutation was estimated to be 5.21% (126/2417) in the studied population. In detail, the carrier frequency of Uighur and Hui was 1.62% (3/185) and 3.29% (10/304), respectively, compared with 6.09% (113/1856) that of Han. There was a statistically significant difference between Uighur and Han (chi-square test, chi(2) = 6.437, p = 0.011 and p < 0.05), whereas no significant difference in m.1555A>G mutation spectrum or prevalence of mitochondrial DNA12SrRNA was found between Uighur and Hui or Hui and Han. In the 126 m.1555A>G mutation carriers, 52 cases were found to have a clear history of using aminoglycoside antibiotics. Results suggested that the application of aminoglycoside antibiotics in this region is an important reason for higher incidence of m.1555A>G mutation in the deaf-mute population.

Identification of two novel mutations, c.232T>C and c.2006A>T, in SLC26A4 in a Chinese family associated with enlarged vestibular aqueduct.

It is known that enlarged vestibular aqueduct syndrome is closely related to the SLC26A4 mutation. Up to date, more than 200 of SLC26A4 mutations have been described, and novel mutations are being continually identified in different countries and ethnic groups. In this study, two novel variations were identified in a Chinese family associated with enlarged vestibular aqueduct. The two novel substitutions, c.232T>C and c.2006A>T, were detected in exon 3 and exon 17 of the pendrin encoding gene, respectively. The T/C transversion at 232 nucleotide caused p.Y78H mutation while the A/T transversion at 2006 nucleotide caused p.D669V mutation.

[Clinical analysis of adenoid cystic carcinoma of external auditory canal].

OBJECTIVE: To explore methods of treatment for adenoid cystic carcinoma of external auditory canal, and discuss the correlating factors that effect prognosis. METHODS: A retrospective analysis of 19 cases of adenoid cystic carcinoma of external auditory canal treated from 1988 to 2004 was carried out. Based on University of Pittsburgh TNM staging system of external auditory canal carcinoma, 19 cases were classified into groups as 5 cases in T1, 2 in T2, 6 in T3, and 6 in T4. Local resection was performed in cases in stage T1 and T2, while radical mastoidectomy or temporal bone resection was performed in stage T3 and T4. Radiotherapy was applied after operation. Relapsed cases with isolated metastasis were treated by surgery. Multiple metastasis were treated with radiotherapy. RESULTS: The follow-up time is from 6 months to 19 years, and the median is 44 months. There're 8 cases with more than 5 years' follow-up. Twelve patients relapsed and 7 had metastasis but 4 died. The cases with positive incisal edge after first operation relapsed even treated with radiotherapy. In recurrent cases, 9 cases received more than 2 operations, 8 more than 3, and 4 received 4 operations. CONCLUSIONS: The adenoid cystic carcinoma of external auditory canal grows insidiously, and relapses frequently. But the patients can live long with neoplasm implanted. A wide surgical excision combined with post operative radiotherapy was proposed, and negative incision edge should be confirmed. Recurrent cases can be treated with several operations to elongate survival. Multiple relapses will cause metastasis more frequently. Metastasis is the main reason to cause death.

[Study on trans-differentiation of adult human myoblasts into neural precursor cells and its implantation in rats].

OBJECTIVE: To investigate the feasibility of inducing adult human myoblasts into neural precursor cells. METHODS: The myoblasts were isolated with mixed digestive enzyme from minced human temporal muscle samples, cultured and purified clonally. The 3rd passage cells were incubated with serum free medium including basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and leukemia inhibitory factor (LIF). Morphological change was investigated during incubation period. Immunofluorescence cytochemistry and RT-PCR analysis were used to assess cell differentiation and trans differentiation. RESULTS: After the induction, cells became non-adherent aggregates as neurospheres. The myoblast-derived neurospheres was immuno-positive for nestin. In differentiation condition, they looked like neurons and glial cells and expressed neuronal (microtubule associated protein 2, MAP-2), astrocytic (Glial fibrillary acidic protein, GFAP) and oligodendrocytic (Galactocerebroside, Galc) markers by immunocytochemistry. The result by RT-PCR was coincident with immunocytochemistry. The myoblast-derived neurospheres expressed MAP-2 and GFAP after they were transplanted into the brain of rats with cerebral ischemia. CONCLUSION: Adult human myoblasts can be inducted to trans-differentiate into neural precursor cells.