Hsueh-Wen Chang

Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma

Inactivation of the tumor suppressor gene PTEN/MMAC1/TEP1, located on chromosome 10q23, is a common event in advanced stages of diverse human malignancies. However, the prognostic role of PTEN expression in patients with hepatocellular carcinoma (HCC) has not been characterized.

Adult spinal epidural abscess: clinical features and prognostic factors.

Twenty-nine adult patients with spinal epidural abscess (SEA), aged 31-73 years, have been identified over a period of 8 years. The 29 SEA patients included 21 men and eight women with a mean age of 54 years. Initial diagnosis of SEA was made in only 17% of our patients and another 48% of patients were initially suggested of having infection or mass of the spine. Spinal pain and fever were the two most common clinical features shared among our patients. The two most common pathogens were Staphylococcus aureus and Mycobacterium tuberculosis, which were found in 62% of patients. Twenty-seven patients received surgical intervention and antibiotic treatment for SEAs, one of which succumbed to meningitis. Two patients without neurological abnormalities received conservative treatment alone and survived. The number of patients, which showed improvement of symptoms, included all seven patients with neck/back pain without neurologic deficits, all 15 patients with paraparesis, 10 of 13 patients with bladder/bowel dysfunction with or without motor deficits, and none of the five with plegia. Preoperative plegia was identified as a poor prognostic factor, and patients with SEA continue to show high rates of morbidity and mortality. Thus, in order to improve the therapeutic outcome of patients with SEA, early diagnosis and management are mandatory to treat the patients before the deterioration of neurologic deficit occurs.

Community-acquired bacterial meningitis in adults: the epidemiology, timing of appropriate antimicrobial therapy, and prognostic factors

Between January 1986 and December 1999, 109 adult patients with culture-proven community-acquired bacterial meningitis were identified at Kaohsiung Chang Gung Memorial Hospital. To compare changes over time, the appearance of disease among our patients was divided into two equal time periods: an earlier time period (1986-1992) and a later time period (1993-1999). In this study, there was a decreasing proportion of community-acquired bacterial meningitis compared with nosocomial bacterial meningitis in adult patients in recent years. Its proportion declined dramatically from 81% in the earlier 7 years to 37% in the later 7 years. Of the pathogens, Klebsiella (K.) pneumoniae was the most frequently implicated pathogen, followed by Viridans (V.) streptococci, Streptococcus pneumoniae, and Staphylococcus aureus. Other rare organisms including Acinetobacter baumannii, Salmonella Group B and D, Proteus mirabilis, Group B, D, and non-A, non-B and non-D streptococci, and coagulase-negative staphylococci emerged during the second period. There was a decrease in the mortality rate from 44% in the first to 34% in the second time period, but the overall mortality rate remained high. Of the implicated pathogens, patients infected with V. streptococci had a consistently favorable prognosis, while a dramatic decrease in the mortality rate of those infected with K. pneumoniae was seen in recent years. In the multiple logistic regression analysis, only the presence of septic shock and seizures was independently associated with mortality. The timing of appropriate antimicrobial therapy, as defined by consciousness level, was a major determinant of survival and neurological outcomes for patients with community-acquired bacterial meningitis, and the first dose of an appropriate antibiotic should be administrated before a patients consciousness deteriorates to a Glasgow coma scale score lower than 10.

Gram-negative bacillary meningitis in adult post-neurosurgical patients

BACKGROUNDnTo assess the clinical features and therapeutic outcomes of gram-negative bacillary meningitis (GNBM) in adult postneurosurgical patients.nnnMETHODSnThirty adult patients with GNBM were included in this study. Their clinical features, laboratory data, prognostic factors, and therapeutic outcome were analyzed. The patients were 22 males and 8 females, aged 17-72 years. Seven had community-acquired infections and 23 had nosocomial infections. Two patients were associated with brain abscess.nnnRESULTSnThe pathogens found in the 30 GNBM patients were Pseudomonas aeruginosa, Klebsiella species, Escherichia coli, Acinetobacter baumannii, and some rare pathogens including Citrobacter freundii, Serratia marcescens, Enterobacter cloacae, and Proteus mirabilis. Among these 30 patients, 8 patients with third-generation cephalosporin-resistant GNBM were identified since 1994; all infections were nosocomially acquired. Appropriate antibiotics were given to 22 patients. Eight patients did not receive appropriate antibiotic therapy. All eight died. The mortality rate in those treated with appropriate antibiotics was 14%.nnnCONCLUSIONSnThere has been an increase of GNBM in postneurosurgical patients in recent years. In addition, the emergence of strains resistant to third-generation cephalosporins in this specific group of patients has also been noted in recent years, and has become a great therapeutic challenge. We noted many prognostic factors in postneurosurgical patients in this study; however, appropriate antibiotic therapy and initial consciousness level are the most significant ones. Therefore, in cases of postneurosurgical patients with nosocomially acquired GNBM, the possibility of third-generation cephalosporin resistance should be strongly suspected. Early initiation of appropriate antibiotic therapy is needed in this potentially fatal disease.

Adult bacterial meningitis in southern Taiwan: epidemiologic trend and prognostic factors

In two investigative phases over a 13.5-year study period (January 1986-June 1999), 202 adult patients with culture-proven bacterial meningitis were enrolled in this study. In order to determine the epidemiologic trend, prognostic factors and therapeutic results for this disease. Klebsiella pneumoniae (K. pneumoniae), Pseudomonas aeruginosa, and Streptococcus pneumoniae were the three most commonly revealed pathogens, accounting for about 48% of the episodes. Although there was a change in relative frequency for the pathogens, K. pneumoniae remained the most prevalent during the two periods studied (January 1986-December 1992 and January 1993-June 1999). Multiantibiotic resistant strains have been in evidence since their appearance in 1994, with most of our patients acquiring their infection nosocomially. The overall mortality rates during the two periods were 40% and 34%, respectively. In stepwise logistic regression analysis, only initial conscious level, appropriate antibiotic therapy and septic shock were independently associated with mortality, after adjustment for other potentially confounding factors. Initial empirical antibiotics with both third-generation cephalosporin and penicillin G, should be considered for the majority of meningitis cases resulting from infection with Gram-negative bacilli and streptococcal species. Besides the evolution of newer pathogens, there has been increasing incidence for nosocomially acquired bacterial meningitis for patients postneurosurgery, with the emergence of resistant strains presenting a therapeutic challenge in recent years. Vancomycin and imipenem/cilastatin should be considered as the initial empirical antibiotics of choice for the treatment of this special group of patients.

Bacterial meningitis in infants: the epidemiology, clinical features, and prognostic factors.

This 16-year (1986-2001) retrospective study enrolled 80 infantile patients (aged, 30-365 days old) with culture-proven bacterial meningitis. The most prevalent pathogens were Salmonellaspecies, Streptococcus (S.) agalactiae, Escherichia (E.) coli, and Haemophilus (H.) influenzae, accounting for about 59% of the episodes. Meningitis caused by Salmonella species, E. coli and H. influenzae occurs more often in the older infants, while that caused by S. agalactiae occurs more often in young infants. Our study revealed a decrease in the proportion of Salmonella meningitis from 27% in the first 8 years to 9% in the second 8 years with E. coli replacing Salmonella species as the leading pathogen of this disease during the second period. Overall mortality rate for both periods of time was 11%. However, if we take those with undesirable poor outcomes into account, 43% of patients could be considered treatment failures. The study also reveals a high prevalence of neurological complications when this disease is caused by H. influenzae, S. pneumoniae, and Salmonella species. Stepwise logistic regression analysis revealed that only initial changing levels of consciousness (P = 0.006) were independently associated with treatment failure. The most frequent neurological complications associated with this disease included subdural empyema, hydrocephalus, cerebral infarctions, and seizures. Because therapeutic regimens may require attention to the eradication of bacterial pathogen but also the neurological complications, early diagnosis and choice of appropriate antibiotics are essential to increasing the possibility of survival.

Klebsiella meningitis in adults: clinical features, prognostic factors and therapeutic outcomes.

Sixty adult Klebsiella meningitis patients have been identified at Kaohsiung Chang Gung Memorial Hospital in a period of 13 years. Most cases were associated with debilitating diseases, and devastating metastatic septic abscesses are common in diabetic patients with K. pneumoniae meningitis. Although the mortality rate has been significantly reduced in recent years, there has been an increase in nosocomial infections and the emergence of multi-antibiotic resistant strains. Significant prognostic factors include appropriate antibiotic therapy, the presence of septic shock, disseminated intravascular coagulation, and high cerebrospinal fluid protein levels and white blood cell counts. Initial empiric therapy with a third generation cephalosporin should be considered for community-acquired meningitis while antibiotics such as carbapenems should be considered as initial empiric therapy for patients with postneurosurgical meningitis. Early diagnosis and the use of appropriate antibiotics are of crucial importance.

A clinical and electrophysiologic survey of childhood Guillain-Barré syndrome

In this 16-year (1986-2001) retrospective study, 23 childhood patients were identified with Guillain-Barré syndrome. According to clinical and electrophysiologic findings, 18 patients manifested acute inflammatory demyelinating polyradiculoneuropathy, 2 had Miller Fisher syndrome, 1 had axonal forms, and 2 were unclassified. Seasonal preponderance was evident in 39% of patients with Guillain-Barré syndrome, developing the disease in the winter (November to January) with upper respiratory infection the most frequent preceding event. The most common manifestation was limb weakness, with various degrees of motor weakness in 22 patients. Bulbar involvement was the most common cranial palsy, and it was evident in 30% of the episodes. Only one of these progressed to mechanical ventilation during hospitalization. Altogether, approximately 61% of the episodes exhibited sensory symptoms. At a follow-up of 1 year or more, 20 patients recovered and 3 had residua. Furthermore, no fatality occurred in our study. Our study also demonstrates that the clinical course of childhood Guillain-Barré syndrome has a shorter recovery time as compared with an adult patient group. Therapeutic outcome is favorable for patients who receive prompt treatment.

Adult Acinetobacter Meningitis and Its Comparison with Non-acinetobacter Gram-negative Bacterial Meningitis

Between January 1999 and December 2003, 81 cases of single pathogen-related culture-proven Gram-negative adult bacterial meningitis were identified at Chang Gung Memorial Hospital-Kaohsiung. Of these 81 cases, Acinetobacter infection was found in 13 cases. Clinical and laboratory data of these Acinetobacter meningitis patients were studied and were compared with those of other 68 non-Acinetobacter Gram-negative bacterial meningitis (GNBM) patients. Of the 13 implicated Acinetobacter strains, A. baumannii was the most common (12), and the other was A. lwoffii (1). Eleven of these 13 cases were due to a post-neurosurgical infection. The results of the antibiotic susceptibility test of the 13 Acinetobacter strains from cerebrospinal fluid included ceftriaxone, (1/13, 8%), ciprofloaxin (6/13, 46%), ceftazidime (6/13, 46%), cefepime (7/13, 54%), ampicillin-subtactam (7/13, 54%), imipenem (12/13, 92%) and meropenem (12/13, 92%). One strain with pan-drug resistant A. baumannii (PDRAB) emerged in 2003. A statistically significant difference between Acinetobacter meningitis and non-Acinetobacter GNBM included hydrocephalus and ceftazidime-resistance. A mortality rate was 30% (4/13), and 7 of the other 9 survivals had severe neurologic deficits. The emergence of Acinetobacter infections in adult post-neurosurgical infections, multiple antibiotic resistant characteristics, and the emergence of PDRAB strain remained a challenge of the initial management of this specific meningitis. Use of carbapenem, especially meropenem, could be considered as one of the initial empiric antibiotics chosen for the management of adult post-neurosurgical meningitis.

Neonatal bacterial meningitis in southern Taiwan.

To determine the epidemiologic trends, prognostic factors, and therapeutic results of neonatal bacterial meningitis, 60 neonatal patients with culture-proven neonatal bacterial meningitis were enrolled in this study. To compare changes over time, the appearance of disease among the patients was divided into two equal periods (1986-1993 and 1994-2001). Group B streptococci were the most common causative pathogens, accounting for approximately 32% of the episodes. Escherichia coli, the next most common pathogen, was more frequently observed in the second period. Seventy-seven percent of gram-negative bacilli isolates were resistant to ampicillin. Moreover, oxacillin-resistant Staphylococcus and ampicillin-resistant group B streptococci strains occurred in the second periods as late-onset neonatal bacterial meningitis. The overall mortality rates for the first and second study period were 17% and 8%, respectively. However, if individuals with poor outcomes were taken into account, 38% of patients were considered treatment failures. Significant prognostic factors included the presence of seizures, thrombocytopenia, and high cerebrospinal fluid protein and low cerebrospinal fluid glucose concentration. Although the mortality rate was significantly reduced in the second period, there has been increasing incidence of the emergence of resistant strains presenting a therapeutic challenge. The presentation in neonatal bacterial meningitis might be nonspecific, and blood culture results were negative in 45% of the episodes. Early diagnosis, choice of appropriate antibiotics, and correction of metabolic derangement are essential to improving outcomes.