Tzu Chi Medical Journal - Articles in Press

Can a girl with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency live a normal life? - Corrected Proof

2012-05-17

3-Hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA lyase) deficiency (OMIM: 246450) is an extremely rare genetic metabolic autosomal recessive disorder. A higher incidence of the disorder is found in Saudi Arabia than in other countries. Fewer than 100 patients have been reported worldwide, with fewer than 10 in Taiwan. It is an enzymopathy of leucine metabolism that presents with metabolic decompensation because of accumulation of large amounts of organic acid metabolites in the serum and urine (). The clinical manifestations usually present before the first year of life. Patients may appear with episodic vomiting, diarrhea, poor activity, loss of consciousness, or a seizure disorder. Extreme tiredness, accompanied by hepatomegaly, liver dysfunction, or hyperammonemia, also occurs. These symptoms can be misdiagnosed as Reye syndrome. Metabolic decompensation, metabolic acidosis, ketoacidosis, and profound hypoglycemia are life-threatening situations and can lead to severe brain damage. Without appropriate management, the mortality rate is very high.

Postenzyme replacement therapy era for type 2 mucopolysaccharidosis - Corrected Proof

Wei-Chih Chou, Chun-Ying Weng, Shuan-Pei Lin, Shao-Yin Chu — 2012-05-14

Type 2 mucopolysaccharidosis (MPS), also calledHunter syndrome (MIM:309900), is a rare X-linked genetic disorder caused by mutation in the iduronate 2-sulfatase gene (IDS: 300823). The gene encodes for the lysosomal enzyme iduronate 2-sulfatase (I2S), which is responsible for degradation of the glycosaminoglycans (GAGs) heparin sulphate (HS) and dermatan sulphate (DS). Consequent accumulation of GAGs leads to pathologic changes in multiple organ systems.

Schizophrenia as a neuronal synaptic disorder related to multiple rare genetic mutations - Corrected Proof

Yu-Chih Shen, Chia-Hsiang Chen — 2012-05-07

Abstract: Schizophrenia is a highly heritable disorder, but many aspects of its etiology and pathophysiology remain poorly understood. Synaptic pathology has been reported as a feature of the brain in schizophrenia. Abnormal expression of some synaptic proteins (e.g., SYP, GAP-43, and NRGN) in different brain regions has been linked to this disorder in postmortem brain studies. In our series of genetic studies, we used a resequencing strategy to search for genetic variants in these candidate genes in a sample of patients with schizophrenia and nonpsychotic controls, all of whom were Han Chinese from Taiwan, and conducted further association and functional studies. After resequencing these candidate genes, no common polymorphisms appeared to play a major role in conferring susceptibility to schizophrenia in our population. In contrast, we identified some rare patient-specific variants. The results of the reporter gene assays and software analysis demonstrated the influence of reporter genes on the function of each studied gene, suggesting that they may contribute to the pathogenesis of schizophrenia. These data lend support to the hypothesis that multiple rare mutations are involved in the pathogenesis of schizophrenia, and provide genetic clues that indicate the involvement of synaptic pathology in this disorder.

An oriental understanding of health - Corrected Proof

Michael Cheng-Tek Tai — 2012-04-30

Abstract: Maintaining a balance between Yin and Yang within the macrocosm and microcosm is the key to a person's health according to Chinese traditional understanding. Hinduism's Ayurveda also shares this view regarding the balance of a person's mind, body, and spirit as the foundation of a good life. This article will examine the traditional Chinese understanding of health in comparison with Hindu thought. Both hold an integrated view of health.

Herpes zoster - Corrected Proof

Yung-Hsiang Hsu — 2012-04-19

A man 48 years of age presented with advanced gastric cancer. He had developed numerous hemorrhagic vesicles on his left thigh (A). He died of sepsis and an autopsy was performed. Histopathology showed intraepidermal hemorrhagic vesicles with basophilic herpes virus inclusion bodies that were diagnostic of herpes zoster (B). The first exposure to the varicella zoster virus produces chickenpox, an acute systemic illness that has a dominant feature of generalized vesicular skin eruption. The virus then becomes latent, and its reactivation in ganglion cells later in life, especially in conditions of immune suppression, causes herpes zoster. The virus travels down the sensory nerves of a single dermatome. It then infects the corresponding epidermis, producing a localized, painful eruption of vesicles.

Melioidosis - Corrected Proof

Yung-Hsiang Hsu — 2012-04-19

A 42-year-old man with diabetes mellitus and hypertension, which were under medical control for 5 years, had right leg necrotizing fasciitis for months. He received debridement surgery several times. Wound culture grew Burkholderia pseudomallei. Abdominal computed tomography showed a splenic abscess, and a splenectomy was performed. Histopathology showed granulomatous inflammation, with caseous-like necrosis, consistent with melioidosis (). Melioidosis, caused by the Gram-negative bacilli B pseudomallei, is an important cause of septicemia in southeast Asia, including China, Taiwan and northern Australia. This chronic persistent infection has a high mortality rate. B pseudomallei is an environmental saprophyte found in wet soils. It mostly infects adults with an underlying predisposing background, mainly, as in this patient, diabetes mellitus. Melioidosis is histopathologically characterized by suppurative granulomas in the lungs, liver and spleen. The diagnosis relies on culture, as in our case. Even after extensive antibiotic therapy, the disease may relapse.

Cryptosporidiosis - Corrected Proof

Yung-Hsiang Hsu — 2012-04-19

A 44-year-old man with AIDS experienced watery diarrhea for 2 weeks. Examination of his stool using an acid-fast stain indicated Cryptosporidium (). Cryptosporidiosis is a recently recognized enteric infection caused by Cryptosporidium protozoa, which cause watery diarrhea. The infection varies from a self-limiting gastrointestinal infection in immunocompetent individuals to a potentially like-threatening illness in the immunocompromised. It is acquired by ingesting Cryptosporidium oocysts, which are shed in the feces of infected humans and animals. In immunologically competent individuals, diarrhea resolves spontaneously. In immunocompromised patients, diarrhea can persists indefinitely and may contribute to death.

Prevalence and factors associated with overactive bladder and urinary incontinence in community-dwelling Taiwanese - Corrected Proof

Aih-Fung Chiu, Mei-Huang Huang, Chung-Cheng Wang, Hann-Chorng Kuo — 2012-04-18

Abstract: Objective(s): To assess the prevalence of and factors associated with overactive bladder (OAB) and urinary incontinence (UI) in the Taiwanese community.Materials and Methods: A cross-sectional design with a participant-administered questionnaire was used in 1011 adults who voluntarily visited any of the four public health centers in Pingtung County, Taiwan, for physical examinations from March to July 2010. Participants who were 40 years of age or older, who agreed to participate, and who were free of severe disabilities related to hearing, vision, speaking, and walking were included in the study. OAB was defined as “urgency” at least once a week and a total overactive bladder symptom score of three or more, while UI was defined as involuntary urine leakage at least once a week. People with an active urinary tract infection (UTI) or had a new onset of UTI symptoms (dysuria, frequency, hesitancy, flank pain) within 4 weeks prior to the study, which could interfere with lower urinary tract function, were excluded from this study.Results: OAB was reported by 19.8% of participants (n=195; women, 18.7%; men, 19.9%), while UI was reported by 19.5% (n=197; women, 23.0%; men, 15.5%). OAB was significantly associated with heart disease, stroke, constipation, and UTI in the previous year. UI was significantly associated with constipation and UTI in the previous year.Conclusions: Several chronic illnesses coexisted with OAB and UI. Healthcare providers need to be aware of an increased risk of OAB or UI among people with certain chronic illnesses, and provide appropriate healthcare.

Scabies - Corrected Proof

Yung-Hsiang Hsu — 2012-04-17

A woman 25 years of age died of respiratory failure. On autopsy, generalized scaling of the skin was found. Histopathology showed scabies embedded in the keratin layer (). Scabies, an infection of the human itch mite Sarcoptes scabiei, remains a significant source of morbidity in residents of nursing homes because of its highly contagious nature. It is characterized by severe pruritus and papules, pustules, burrows, nodules, and occasionally urticarial lesions. Lesions are commonly found on the wrists, finger webs, antecubital region, fossa, axilla, areola, periumbilical region, lower abdomen, genitals, and the buttocks. The diagnosis is based on the history, physical examination, and demonstration of mites, eggs, or scybala (feces) on microscopic examination. Therapy for scabies requires the sequential use of scabicides, usually over a longer period than what is required to clear an ordinary case of scabies. Transmission in hospitals from an index patient with crusted scabies to other patients and healthcare workers is possible and should be avoided.

Interaction between valproic acid and carbapenems: Case series and literature review - Corrected Proof

Ming-Chia Lee, Yi-Hsuan Sun, Chih-Hsin Lee, An-Jan Wu, Ta-Wei Wu — 2012-04-16

Abstract: Several case reports and retrospective studies have indicated that carbapenems decrease the serum concentration of valproic acid (VPA), thus decreasing its therapeutic activity. This study evaluates a potential drug interaction between VPA and carbapenems in a regional hospital. This retrospective observational study was performed over a 14-month period from January 2010 to February 2011. Patients concurrently receiving VPA and carbapenems who had at least two serially measured concentrations of serum VPA prior to, during, or after this combined treatment were included. Patients whose serum samples for VPA were drawn within 2 hours after VPA administration who had severe liver impairment or who received other drugs that could potentially interact with VPA were excluded from the study. The serum levels and therapeutic activities of VPA during coadministration of carbapenems were recorded and evaluated. Nine VPA-treated patients were identified who concomitantly received meropenem (n = 5), ertapenem (n = 3), or imipenem (n = 1). Mean serum VPA trough levels during combined treatment decreased by 76.3% (from 55.6 ± 22.9 μg/mL to 13.2 ± 6.1 μg/mL) from values before carbapenem treatment. However, only one patient experienced seizures after a combination of VPA and carbapenems. The coadministration of VPA and carbapenems resulted in decreased trough concentrations of VPA. Clinicians should be aware of this potential interaction and closely monitor serum VPA levels and possible failure to control seizures with the concomitant use of carbapenems.

Selective surgical shunts for treating complications of portal hypertension: 10-year experience in a single institution in eastern Taiwan - Corrected Proof

Yen-Cheng Chen, Guan-Jin Ho, Ying-Chin Yang, Ming-Che Lee — 2012-04-09

Abstract: Objective: Surgical portosystemic shunts are safe and effective for treating rebleeding gastric varices (GV) in portal hypertensive patients with well-preserved liver function. The aim of this study is to investigate the clinical outcomes of using selected surgical shunts for managing rebleeding GV at a single institution in eastern Taiwan.Materials and Methods: We retrospectively recruited 12 patients who received distal splenorenal shunts (DSRS) following the indication of rebleeding GV or hypersplenism from January 2001 through December 2010. Their demographic data, etiology of portal hypertension, associated treatments, perioperative complications and clinical outcomes were reviewed.Results: All patients received DSRS, including 10 adults and two children, and were examined for a median follow-up period of 53 months. No postoperative encephalopathy, major complications, or surgical mortality occurred. Two of the patients were waiting for liver transplants. Late rebleeding in esophageal varices developed in two patients who were successfully managed using endoscopic treatment. The etiology of portal hypertension had no significant impact on the postoperative complications.Conclusion: Although there were a limited number of cases in this series, our results indicate that the DSRS is an effective treatment for rebleeding GV, especially for patients with well-preserved liver function and taking into account the realities of organ shortages.

Validation of the laboratory risk indicator for necrotizing fasciitis (LRINEC) score for early diagnosis of necrotizing fasciitis - Corrected Proof

Chun-I Liao, Yi-Kung Lee, Yung-Cheng Su, Chin-Hsiang Chuang, Chun-Hing Wong — 2012-04-09

Abstract: Objective: Necrotizing fasciitis is a surgical emergency. It has a poor outcome after late operative intervention but the clinical diagnosis is difficult. The laboratory risk indicator for necrotizing fasciitis (LRINEC) score was first introduced in 2004 and several clinicians have suggested it is useful for early recognition of necrotizing fasciitis but its validation still needs to be examined. We collected our hospital data from May 2003 to September 2010 to validate whether the LRINEC score can aid in early recognition of necrotizing fasciitis.Materials and Methods: This is a validation cohort study. We reviewed all necrotizing fasciitis patients admitted from the emergency department at Buddhist Tzu Chi Dalin General Hospital in Taiwan from May 2003 to September 2010. All patients had pathological diagnoses. We used multiple imputations for missing patient data. We analyzed these data and examined whether the LRINEC score had a higher diagnostic value than the clinical diagnosis before admission. We also examined the LRINEC score in patients with severe cellulitis to determine its usefulness in excluding necrotizing fasciitis.Results: A total of 233 patients with necrotizing fasciitis and 3155 with severe cellulitis were included in our study. A LRINEC score ≥6 had a sensitivity of 59.2% (CI 52.9–65.6%), specificity of 83.8% (CI 81.9–85.7%), likelihood ratio of 3.89, positive predictive ratio of 37.9% (95% CI 32.9–42.9%), and negative predictive ratio of 92.5% (95% CI 91.0–94.0%). The rate of clinical diagnosis of necrotizing fasciitis by emergency physicians before admission was 58.4% (95% CI 52.0–64.8%). Of the 97 patients with necrotizing fasciitis who were not clinically diagnosed before admission, 43.3% (95% CI 36.9–49.7%) had a LRINEC score <6.Conclusion: The LRINEC score is an impressive diagnostic tool to distinguish necrotizing fasciitis from other severe soft tissue infections, but it is not useful for early recognition of necrotizing fasciitis.

Long-term comparison of subthalamic nucleus stimulation between patients with young-onset and late-onset Parkinson’s disease - Corrected Proof

2012-04-05

Abstract: Objectives: The aim of this study was to compare the long-term effectiveness of subthalamic nucleus deep brain stimulation (STN-DBS) between patients with young-onset Parkinson’s disease (YOPD) and late-onset Parkinson’s disease (LOPD).Materials and Methods: Twenty-one YOPD patients with a mean age at onset of 32.8 ± 6.9 years and another 69 LOPD patients with a mean age at onset of 53.2 ± 6.9 years undergoing STN-DBS were followed. The mean durations of follow-up for those who were followed for more than 3 years were 57.22 ± 14.54 months in the YOPD group and 46.77 ± 13.84 months in the late onset group.Results: Motor disabilities and activities of daily living in patients with LOPD and YOPD significantly improved after the operation. However, YOPD patients showed significantly less improvement in Unified Parkinson’s Disease Rating Scale Part II (p = 0.001) and Part III (p = 0.031), rigidity (p = 0.033), and axial (p = 0.046) scores than late onset patients more than 3 years after surgery. YOPD patients had higher scores for rigidity (p = 0.007) and bradykinesia (p = 0.044) than LOPD patients at the final post-surgery follow-up. Late onset PD patients had more postoperative hypophonia, whereas EOPD patients displayed more stimulation dyskinesia. The effects of STN-DBS on psychiatric complications and cerebral bleeding were similar in both groups.Conclusion: YOPD patients and LOPD patients had similar benefits and risks from medication-related complications with STN-DBS. The YOPD group had relatively less improvement from acute deep brain stimulation than the LOPD group during long-term follow-up, which could possibly be explained by different disease evolutions and underlying pathophysiology in these two groups.

Clinical encounter with a woman with Costello syndrome - Corrected Proof

Chun-Ying Weng, Yung-Hsiang Hsu, Jia-Woei Hou, Shao-Yin Chu — 2012-03-14

Costello syndrome (MIM number 218040) is a rare genetic disorder caused by mutation in the v-Ha-ras Harvey rat sarcoma viral oncogene homolog (HRAS) gene. Clinically, patients present with distinctive facial features, cutaneous manifestations and skeletal abnormalities. This syndrome is also called facio-cutaneous-skeletal syndrome.

Effectiveness of rater consensus training in objective structured clinical examination using Kolb’s experiential learning - Corrected Proof

Shao-Yin Chu, Yu-Ling Lan, Sheng-Po Kao, Tsung-Ying Chen, Ming-Chen Hsieh — 2012-03-14

A successful, valid, reliable, and defensible high-stakes objective structured clinical examination (OSCE) depends on many factors, such as the test contents, the quality of the performance of standardized patients (SPs), and the consensus of judgments by raters on student OSCE performance. Higher inter-rater reliability of clinician examiners is demonstrated when assessments are recorded on structured forms and examiners participate in station construction . The consistency among raters’ judgments was affected by the level of rater training . The literature shows few rater training methods or models . This article describes the effectiveness of rater consensus training in high-stakes OSCE using Kolb’s cycle of experiential learning . According to Kolb , learning is the process whereby knowledge is created through the transformation of experience.

Spontaneous disappearance of an acute epidural hematoma with emergence of a contralateral subdural hematoma after traumatic brain injury - Corrected Proof

Sheng-Wen Wu, Tsung-Lang Chiu, Shin-Yuan Chen, Chain-Fa Su, Sheng-Tzung Tsai — 2012-03-14

Abstract: Epidural hematoma (EDH) is a common sequela of traumatic brain injury (TBI) and usually results in life-threatening brain compression, which warrants emergency surgical evacuation. Here we present an 85-year-old man who had a traumatic brain injury with an EDH in the right frontoparietal area. He was transferred to our hospital with deep coma status and follow-up computed tomography (CT) showed the EDH had spontaneously disappeared within 2 hours. Furthermore, a contralateral subdural hematoma had developed, which caused a midline shift. Rare cases of rapid spontaneous resolution of an EDH have been reported in the literature. In our patient, the EDH seemed to have been pushed out from the fractured skull because the hematoma would not coagulate due to an underlying coagulopathy. Repeat CT is imperative before surgery for acute TBI and for unconscious patients whose initial CT was performed within 3 hours of injury.

Do baseline urodynamic parameters affect the treatment outcome after intravesical 100 U onabotulinumtoxinA injection in patients with idiopathic detrusor overactivity? - Corrected Proof

Qian-Shen Ke, Yih-Chou Chen, Hann-Chorng Kuo — 2012-03-05

Abstract: Objectives: Intravesical injection of onabotulinumtoxinA (BoNT-A) provides effective treatment for idiopathic detrusor overactivity (IDO). However, not all patients have successful long-term therapeutic effects. This study investigated the effects of baseline urodynamic parameters on the therapeutic outcome, after injecting 100 U BoNT-A in patients with IDO.Materials and Methods: A total of 174 patients who received a first single intravesical BoNT-A 100 U injection for refractory IDO were included. A successful outcome was defined as an improvement of at least two points on a patient perception of bladder condition scale, which was scored from 0 to 6. The short-term (3 months) and long-term (up to 24 months) success rates were analyzed according to baseline urodynamic parameters, including cystometric bladder capacity, maximum flow rate, postvoid residual, voiding efficiency, and detrusor overactivity (DO) subtypes. BoNT-A- related adverse events were also reported.Results: A successful outcome was reported by 138 (79.3%) patients at 3 months. The baseline urodynamic parameters did not affect the success rates, except that patients with phasic DO had a significantly higher success rate at 3 months than patients with terminal DO. Patients with a baseline postvoid residual (PVR) > 100mL, had higher rates of acute urinary retention and need to strain to void. However, long-term success rates up to 24 months showed no significant differences between patients with different urodynamic parameters.Conclusions: Except for patients with phasic DO, the baseline urodynamic parameters did not affect the treatment outcome of intravesical injection of 100 U BoNT-A for IDO. However, acute urinary retention and difficult urination occurred more often in patients with a baseline PVR of > 100mL.

Pneumocystis jirovecii pneumonia manifesting as a lung abscess in a woman with systemic lupus erythematosus - Corrected Proof

Hsiao-Hui Chia, Ming-Chia Lee, Chih-Hsin Lee, Shiu-Feng Huang, Yao-Kuang Wu — 2012-02-27

Pneumocystis jirovecii pneumonia (PCP) is a potentially life-threatening infection encountered in immunocompromised individuals . The radiographic appearance of a cavity in Pneumocystis jirovecii pneumonia is unusual . Delayed diagnosis and treatment could result in a poor outcome . We report a patient with systemic lupus erythematosus (SLE) who developed a cavitating pneumonia in the presence of PCP.

Dup(3) (p23p25) syndrome and array-based comparative genomic hybridization - Corrected Proof

2012-01-24

A high resolution peripheral blood G-banded chromosome study was arranged for a 3-month-old female infant due to the presence of multiple congenital anomalies (MCA), including: flat face, flat occiput, flat nasal bridge, retrognathia, fish mouth, low set and dysplastic ears, temporal narrowing, short neck and prominent nuchal fold, and clinodactyly and hypoplastic toe nails (). Soon after birth, the infant was found to have mild whole body edema with hypoalbuminemia of an unknown cause and congenital heart disease, which included patent ductus arteriosus (PDA) and tricuspid regurgitation. No evidence of congestive heart failure or PDA persisted after two doses of oral indomethacin. Preterm labor had not occurred and the infant’s birth weight was 3.2kg. During follow-up at an outpatient clinic, weak crying, extended daytime sleeping, and delayed developmental milestones were noted by the early infant developmental screening program.

Feasibility of genetic testing for tuberous sclerosis in a 13-year-old boy - Corrected Proof

2012-01-24

A 13-year-old boy was brought to a genetic counseling clinic for a tuberous sclerosis complex (TSC) gene test by his mother who was affected by TSC. The boy’s mother had facial angiofibromas, multiple periungual fibromas, shagreen patches over her lower back, and hypomelanotic macules (ash leaf) over the left side of her waist (). The boy’s family history revealed that his 17-year-old brother was also affected by TSC with facial angiofibromas, a left index finger periungual fibroma, shagreen patches over the right lower abdomen, and de-pigmented lesions over the left lower back. Both the mother and the elder brother had their tuberous sclerosis 1 (TSC1) gene sequenced directly from peripheral blood leukocyte DNA. Sequencing revealed a T to C point mutation over the TSC1 gene at exon 6, codon 482, causing an amino acid change from leucine to proline (TSC1 c.482 T>C CTG>CCG Leu>Pro) (). High resolution melting (HRM) curve analysis of the TSC1 gene also revealed a nucleotide T to C mutation in codon 482 () from the mother and elder brother’s peripheral blood leukocyte DNA. This mutated single nucleotide substitution has not been previously reported.

Extrapulmonary tuberculosis in the wrist presenting as a ganglion cyst-like mass: A case report - Corrected Proof

Kun-Chi Wu, Huan-Ming Tang, Kuang-Ting Yeh, Dah-Ching Ding — 2012-01-16

Abstract: There has been recent interest in tuberculosis of the hand because of its rising incidence. Musculoskeletal tuberculosis accounts for only 20% of cases of tuberculosis. The most common musculoskeletal sites are the spine, hip and knee. Hand involvement is seen in 10% of patients with musculoskeletal tuberculosis. This study reports an unusual case of extrapulmonary tuberculosis in the soft tissues of the wrist, presenting as a ganglion cyst-like lesion with concurrent lung cancer. The condition occurred in a 55-year-old woman with underlying rheumatoid arthritis that had been diagnosed 3 years previously and was under control with regular medication. For several months the patient had noted a metapharyngeal joint mass in her right wrist and hand. The unmovable soft mass was approximately 2cm×2cm in the metapharyngeal joint and 4.5cm×4.5cm in the wrist, and displayed local tenderness and limited range of motion. Under the impression of a ganglion cyst-like soft tissue mass, the patient underwent marginal excision. However, the pathological report indicated tuberculosis. Antituberculosis treatment was prescribed. Simultaneously, lung cancer was also diagnosed. The patient then received chemotherapy and regular follow-up. Although the case described here is rare, preoperative evaluation can help considerably in early detection of cancer. Additionally, postoperative pathology can help define tuberculosis. Medical treatment plays a major role in tuberculosis.

Nocardiosis of the lung - Corrected Proof

Yung-Hsiang Hsu — 2011-09-07

A 43-year-old man with acute myelogenous leukemia (M4) received peripheral blood stem cell transplantation in April 2010.He had fever and chills for one week. Posteroanterior radiography of the chest showed a 2.0 cm patch nodule in the right upper lobe. A computed tomography-guided biopsy was performed. Histopathology showed numerous neutrophils admixed with necrotic debris in the alveolar spaces (A). A Gomori methenamine silver stain demonstrated numerous blackish filamentous bacteria diagnostic of nocardiosis (B). The nocardia belong to aerobic actinomyces, and contain 9 species. In humans, nocardia asteroides accounts for 86% of infections caused by this organism. They are important parts of normal soil microflora worldwide and cause a variety of diseases in both healthy and immunocompromised humans. Inhalation of airborne fragments or spores is the usual route of lung infection. Nocardiosis is both a primary and an opportunistic infection process with compromised hosts, and there is extensive organ involvement, including the lungs, skin, central nervous system, kidneys, liver, and heart. The mortality is high (overall 50%, brain abscess 78%, lung <10%) and the causes of death include sepsis, brain abscess, and overwhelming pneumonia.