Genetic and biochemical analysis of severe hypertriglyceridemia complicated with acute pancreatitis or with low post-heparin lipoprotein lipase mass.

Severe hypertriglyceridemia is a pathological condition caused by genetic factors alone or in combination with environmental factors, sometimes leading to acute pancreatitis (AP). In this study, exome sequencing and biochemical analyses were performed in 4 patients with hypertriglyceridemia complicated by obesity or diabetes with a history of AP or decreased post-heparin LPL mass. In a patient with a history of AP, SNP rs199953320 resulting in LMF1 nonsense mutation and APOE rs7412 causing apolipoprotein E2 were both found in heterozygous form. Three patients were homozygous for APOA5 rs2075291, and one was heterozygous. ELISA and Western blot analysis of the serum revealed the existence of apolipoprotein A-V in the lipoprotein-free fraction regardless of the presence or absence of rs2075291; furthermore, the molecular weight of apolipoprotein A-V was different depending on the class of lipoprotein or lipoprotein-free fraction. Lipidomics analysis showed increased serum levels of sphingomyelin and many classes of glycerophospholipid; however, when individual patients were compared, the degree of increase in each class of phospholipid among cases did not coincide with the increases seen in total cholesterol and triglycerides. Moreover, phosphatidylcholine, lysophosphatidylinositol, and sphingomyelin levels tended to be higher in patients who experienced AP than those who did not, suggesting that these phospholipids may contribute to the onset of AP. In summary, this study revealed a new disease-causing gene mutation in LMF1, confirmed an association between overlapping of multiple gene mutations and severe hypertriglyceridemia, and suggested that some classes of phospholipid may be involved in the pathogenesis of AP.

Risk of severe COVID-19 in unvaccinated patients during the period from wild-type to Omicron variant: real-world evidence from Japan.

BACKGROUND: Many studies have reported that the Omicron variant is less pathogenic than the Delta variant and the wild-type. Epidemiological evidence regarding the risk of severe COVID-19 from the wild-type to the Omicron variant has been lacking. METHODS: Study participants were COVID-19 patients aged 18 and older without previous COVID-19 infection who were notified to the Nara Prefecture Chuwa Public Health Center from January 2020 to March 2023, during the periods from the wild-type to the Omicron variant. The outcome variable was severe COVID-19 (i.e., ICU admission or COVID-19-related death). The explanatory variable was SARS-CoV-2 variant type or the number of COVID-19 vaccinations. Covariates included gender, age, risk factors for aggravation, and the number of general hospital beds per population. The generalized estimating equations of negative binomial regression models were used to estimate the adjusted incidence proportion (AIP) with 95% confidence interval (CI) for severe COVID-19. RESULTS: Among 77,044 patients included in the analysis, 14,556 (18.9%) were unvaccinated and 520 (0.7%) developed severe COVID-19. Among unvaccinated patients, the risk of severe COVID-19 increased in the Alpha/Delta variants and decreased in the Omicron variant compared to the wild-type (AIP [95% CI] was 1.55 [1.06-2.27] in Alpha/Delta and 0.25 [0.15-0.40] in Omicron), but differed by age. Especially in patients aged ≥80, there was no significant difference in the risk of severe COVID-19 between the wild-type and the Omicron variant (AIP [95% CI] = 0.59 [0.27-1.29]). Regarding the preventive effect of vaccines, among all study participants, the number of vaccinations was significantly associated with the prevention of severe COVID-19, regardless of variant type. After stratified analyses by age, patients aged ≥80 remained a significant association for all variant types. On the other hand, the number of vaccinations had no association in Omicron BA.5 of patients aged 18-64. CONCLUSIONS: Patients aged ≥80 had less reduction in risk of severe COVID-19 during the Omicron variant period, and a greater preventive effect of vaccines against severe COVID-19, compared to younger people. Our findings suggest that booster vaccination is effective and necessary for older people, especially aged ≥80.

Association between vaccination status and COVID-19-related health outcomes among community-dwelling COVID-19 patients in Nara, Japan.

BACKGROUND: Many previous studies have reported COVID-19 vaccine effectiveness, but there are few studies in Japan. This community-based, retrospective observational study investigated the association between vaccination status and COVID-19-related health outcomes in COVID-19 patients by SARS-CoV-2 variant type. METHODS: The study participants were 24,314 COVID-19 patients aged 12 or older whose diagnoses were reported to the Nara Prefecture Chuwa Public Health Center from April 2021 to March 2022, during periods when the alpha, delta, and omicron variants of COVID-19 were predominant. The outcome variables were severe health consequences (SHC) (i.e., ICU admission and COVID-19-related death), hospitalization, and extension of recovery period. The explanatory variable was vaccination status at least 14 days prior to infection. Covariates included gender, age, population size, the number of risk factors for aggravation, and the number of symptoms at diagnosis. The generalized estimating equations of the multivariable Poisson regression models were used to estimate the adjusted incidence proportion (AIP) and 95% confidence interval (CI) for each health outcome. We performed stratified analyses by SARS-CoV-2 variant type, but the association between vaccination status and COVID-19-related health outcomes was stratified only for the delta and omicron variants due to the small number of vaccinated patients during the alpha variant. RESULTS: Of the 24,314 participants, 255 (1.0%) had SHC; of the 24,059 participants without SHC, 2,102 (8.7%) were hospitalized; and of the 19,603 participants without SHC, hospitalization, and missing data on recovery period, 2,960 (15.1%) had extension of recovery period. Multivariable Poisson regression models showed that regardless of SARS-CoV-2 variant type or health outcome, those who received two or more vaccine doses had significantly lower risk of health outcomes than those who did not receive the vaccine, and there was a dose-response relationship in which the AIP for health outcomes decreased with an increased number of vaccinations. CONCLUSION: A higher number of vaccinations were associated with lower risk of COVID-19-related health outcomes, not only in the delta variant but also in the omicron variant. Our findings suggest that increasing the number of COVID-19 vaccine doses can prevent severe disease and lead to early recovery of patients not requiring hospitalization.

Association between vaccination status and severe health consequences among community-dwelling COVID-19 patients during Omicron BA.1/BA.2 and BA.5-predominant periods in Japan.

BACKGROUND: Many previous studies have reported that COVID-19 vaccine effectiveness decreased over time and declined with newly emerging variants. However, there are few such studies in Japan. Using data from a community-based retrospective study, we aimed to assess the association between vaccination status and severe COVID-19 outcomes caused by the Omicron variant, considering the length of time since the last vaccination dose. METHODS: We included all persons aged ≥12 diagnosed with COVID-19 by a doctor and notified to the Chuwa Public Health Center of Nara Prefectural Government during the Omicron BA.1/BA.2 and BA.5-predominant periods in Japan (January 1 to September 25, 2022). The outcome variable was severe health consequences (SHC) (i.e., COVID-19-related hospitalization or death). The explanatory variable was vaccination status of the individuals (i.e., the number of vaccinations and length of time since last dose). Covariates included gender, age, risk factors for aggravation, and the number of hospital beds per population. Using the generalized estimating equations of the multivariable Poisson regression models, we estimated the cumulative incidence ratio (CIR) and 95% confidence interval (CI) for SHC, with stratified analyses by period (BA.1/BA.2 or BA.5) and age (65 and older or 12-64 years). RESULTS: Of the 69,827 participants, 2,224 (3.2%) had SHC, 12,154 (17.4%) were unvaccinated, and 29,032 (41.6%) received ≥3 vaccine doses. Regardless of period or age, there was a significant dose-response relationship in which adjusted CIR for SHC decreased with an increased number of vaccinations and a longer time since the last vaccination. On the one hand, in the BA.5 period, those with ≥175 days after the third dose had no significant difference in people aged 65 and older (CIR 0.77; 95% CI, 0.53-1.12), but significantly lower CIR for SHC in people aged 12-64 (CIR 0.47; 95% CI, 0.26-0.84), compared with those with ≥14 days after the second dose. CONCLUSION: A higher number of vaccinations were associated with lower risk of SHC against both BA.1/BA.2 and BA.5 sublineages. Our findings suggest that increasing the number of doses of COVID-19 vaccine can prevent severe COVID-19 outcomes, and that a biannual vaccination is recommended for older people.

Cytotoxic lesions of the corpus callosum after COVID-19 vaccination.

A 23-year-old previously healthy man (Patient 1) and a 33-year-old woman with a past history of depression (Patient 2) developed neurological symptoms approximately 1 week after receipt of the first COVID-19 mRNA vaccination and deteriorated over the next week. Patient 1 reported nausea, headache, a high fever, and retrograde amnesia. Patient 2 reported visual disturbance, headache, dysarthria, a left forearm tremor, dysesthesia of the mouth and distal limbs, and visual agnosia. PCR test results for SARS-CoV-2 were negative. Complete blood cell count, biochemistry, and antibody test and cerebrospinal fluid test findings were unremarkable. Diffusion-weighted and fluid-attenuated inversion recovery MRI of the brain showed a high signal intensity lesion at the midline of the splenium of the corpus callosum compatible with cytotoxic lesions of the corpus callosum (CLOCCs). High-dose intravenous methylprednisolone improved their symptoms and imaging findings. CLOCCs should be considered in patients with neurological manifestation after COVID-19 vaccination.

Three-dimensional measurement for spherical and nonspherical shapes of contact lenses.

In recent years, with the development of precise lathe-cutting equipment, special shaped contact lenses (CL) have been crafted. However, while it is possible to manufacture such a lens, its shape evaluation has not been well-established. We conducted a basic optical experiment using special lenses to measure a spherical lens and nonspherical mold. As the measurement sample, a metal ball, special CL, and a toric-shaped mold were adopted. In order to accurately measure those real shapes, we proposed an algorithm in which the probe light is vertically incident to the sample surface within a numerical aperture of the optical probe. For this algorithm, we developed the specialized time-domain optical coherence tomography (TD-OCT), which was designed to conduct circular scanning while maintaining vertical incidence by driving a two-axis (vertical and horizontal) micro-electromechanical system mirror with a phase difference of 90°. The shape, thickness distribution, and curvature radii of both front and back surfaces of a CL were estimated with this OCT signal analysis and sphere fitting. The shape and curvature radius were evaluated by using the simulated data under the same experimental conditions. They were sufficiently accurate based on the resolution of this OCT. Also, a toric-shaped mold was evaluated by comparing the relationship between each coordinate and intensity of the interference signal. As a result, it is confirmed that the experimental result and the simulated matched well.

Diagnostic value of standard deviation score of log-transformed serum dehydroepiandrosterone sulfate in patients with hypothalamic-pituitary-adrenal axis insufficiency.

Serum dehydroepiandrosterone sulfate (DHEA-S) levels reflect the state of adrenocorticotropic hormone (ACTH) secretion. However, it is difficult to use serum DHEA-S to diagnose hypothalamic-pituitary-adrenal (HPA) axis insufficiency due to its non-normal and highly skewed distribution. In this study, we focused on HPA insufficiency caused by hypothalamic and/or pituitary dysfunction and evaluated the usefulness of the standard deviation score of log-transformed DHEA-S (ln DHEA-S SD score), which was calculated from the established age- and sex-specific reference values. We retrospectively reviewed the medical records of 94 patients suspected of having HPA insufficiency, in whom serum DHEA-S measurement and the rapid ACTH stimulation test were performed, and included 65 patients who met our criteria in this study. The ln DHEA-S SD scores were distributed more normally than measured DHEA-S levels and were significantly higher in patients with a peak cortisol level ≥18 µg/dL than in those below this value, suggesting that this score is a legitimate and strong indicator of adrenocortical function. The optimal cut-off value for impaired HPA function was -0.853, with a sensitivity of 70.3% and a specificity of 100%. Among the 37 patients whose peak cortisol levels were below 18 µg/dL, 11 patients with ln DHEA-S scores ≥-0.853 exhibited significantly higher basal ACTH and basal and peak cortisol levels than the 26 patients with scores <-0.853. Thus, this score plays a supportive role in evaluating HPA axis function, particularly in patients with borderline cortisol responses to ACTH.

Intensive care management of a patient with necrotizing fasciitis due to non-O1/O139 Vibrio cholerae after traveling to Taiwan: a case report.

BACKGROUND: Vibrio cholerae are oxidase-positive bacteria that are classified into various serotypes based on the O surface antigen. V. cholerae serotypes are divided into two main groups: the O1 and O139 group and the non-O1/non-O139 group. O1 and O139 V. cholerae are related to cholera infection, whereas non-O1/non-O139 V. cholerae (NOVC) can cause cholera-like diarrhea. A PubMed search revealed that only 16 cases of necrotizing fasciitis caused by NOVC have been recorded in the scientific literature to date. We report the case of a Japanese woman who developed necrotizing fasciitis caused by NOVC after traveling to Taiwan and returning to Japan. CASE PRESENTATION: A 63-year-old woman visited our hospital because she had experienced left knee pain for the past 3 days. She had a history of colon cancer (Stage IV: T3N3 M1a) and had received chemotherapy. She had visited Taiwan 5 days previously, where she had received a massage. She was diagnosed with septic shock owing to necrotizing fasciitis. She underwent fasciotomy and received intensive care. She recovered from the septic shock; however, after 3 weeks, she required an above-knee amputation for necrosis and infection. Her condition improved, and she was discharged after 22 weeks in the hospital. CONCLUSIONS: With the increase in tourism, it is important for clinicians to check patients' travel history. Clinicians should be alert to the possibility of necrotizing fasciitis in patients with risk factors. Necrotizing fasciitis caused by NOVC is severe and requires early fasciotomy and debridement followed by intensive postoperative care.

Measurement algorithm for real front and back curved surfaces of contact lenses.

The optical measurement algorithm for the real front and back surfaces of contact lenses from their center to periphery accurately and simultaneously is proposed. It is an algorithm that makes light incident vertically along the curved surfaces of contact lenses under the condition that the difference of curvature radii between the front and back surfaces is small enough within the NA of the optical probe. For this purpose, we adopted time-domain optical coherence tomography (OCT) with translation and rotation mechanisms. The shape, thickness distribution, and curvature radii of both surfaces were estimated with OCT signal analysis and circular approximation. The measured results were compared with the designed values and the measured data from a conventional shape measurement device. The curved shape of both surfaces and thickness were well matched with the designed values from lens center to periphery. In a curvature radius of the front surface, there was a proportional bias with a limit of agreement of -0.77% to -2.09%, and the correlation coefficient was 0.57. On the back surface, there was no systematic bias, and minimal detectable change was 0.178 mm, in a range of 95% confidential interval. The proposed algorithm well visualized the real shape and optical characteristics of the contact lens with enough accuracy to the design.

Filifactor alocis brain abscess identified by 16S ribosomal RNA gene sequencing: A case report.

We report a clinical case of Filifactor alocis brain abscess in an 85-year-old man who had decayed teeth 1 week prior. In this case, the abscess was surgically drained after empirical antibiotics had been initiated. Although the causative organism could not be identified by culture, F. alocis was detected via 16S ribosomal RNA (16S rRNA) gene sequencing of the pus isolated from the abscess. The patient recovered without serious sequelae after surgical drainage and prolonged antibiotic treatment, including metronidazole, ceftriaxone and meropenem for 8 weeks. The findings in this case emphasize that 16S rRNA gene sequencing allows bacterial diagnosis of brain abscess when phenotypic identification fails, such as in cases where patients are undergoing antimicrobial treatment at the time of sampling or where patients are infected with fastidious organisms.

Case of endobronchial metastasis from breast cancer accompanied with Cunninghamella bertholletiae tracheobronchial mycetoma.

Cunninghamella is a member of the class Zygomycetes. Cunninghamella species include ubiquitous filamentous fungi; infections caused by Cunninghamella species are less frequent but have higher mortality rates than infections caused by Mucorales group members such as Rhizopus and Mucor. Herein, we reported a rare fatal case of endobronchial metastasis from breast cancer accompanied with Cunninghamella bertholletiae tracheobronchial mycetoma. A 73-year-old female with a history of right-sided breast cancer who had undergone mastectomy 11 years previously and had no recurrence presented to our emergency department with a 1-week history of left-sided back pain. Chest X-ray revealed left lung atelectasis; bronchoscopy revealed an endobronchial mass lesion in the left main bronchus. Pathological examination revealed fungal mycetoma but malignant lesions were not detected. Endobronchial and lung mycetoma caused by Cunninghamella bertholletiae were initially diagnosed; liposomal amphotericin B was administered, but her condition deteriorated. Rigid endoscopy showed growth of hemorrhagic tissue occupying the left main bronchus just under the carina. Pathological examination of the shaved lesion revealed metastasis from breast cancer covered with abundant necrotic tissue. No mold was observed in the necrotic tissue; this was probably due to liposomal amphotericin B treatment. To our knowledge, this is the first case of endobronchial metastasis from breast cancer accompanied with Cunninghamella bertholletiae mycetoma. Distinguishing endobronchial metastases from breast cancer and atypical presentations of Cunninghamella endobronchial mycetomas can be very difficult. Repeated bronchoscopies maybe helpful in establishing an accurate diagnosis when clinical prognosis does not match the initial diagnosis.

Activation of the Hypoxia Inducible Factor 1α Subunit Pathway in Steatotic Liver Contributes to Formation of Cholesterol Gallstones.

BACKGROUND & AIMS: Hypoxia-inducible factor 1α subunit (HIF1A) is a transcription factor that controls the cellular response to hypoxia and is activated in hepatocytes of patients with nonalcoholic fatty liver disease (NAFLD). NAFLD increases the risk for cholesterol gallstone disease by unclear mechanisms. We studied the relationship between HIF1A and gallstone formation associated with liver steatosis. METHODS: We performed studies with mice with inducible disruption of Hif1a in hepatocytes via a Cre adenoviral vector (inducible hepatocyte-selective HIF1A knockout [iH-HIFKO] mice), and mice without disruption of Hif1a (control mice). Mice were fed a diet rich in cholesterol and cholate for 1 or 2 weeks; gallbladders were collected and the number of gallstones was determined. Livers and biliary tissues were analyzed by histology, quantitative reverse-transcription polymerase chain reaction, immunohistochemistry, and immunoblots. We measured concentrations of bile acid, cholesterol, and phospholipid in bile and rates of bile flow. Primary hepatocytes and cholangiocytes were isolated and analyzed. HIF1A was knocked down in Hepa1-6 cells with small interfering RNAs. Liver biopsy samples from patients with NAFLD, with or without gallstones, were analyzed by quantitative reverse-transcription polymerase chain reaction. RESULTS: Control mice fed a diet rich in cholesterol and cholate developed liver steatosis with hypoxia; levels of HIF1A protein were increased in hepatocytes around central veins and 90% of mice developed cholesterol gallstones. Only 20% of the iH-HIFKO mice developed cholesterol gallstones. In iH-HIFKO mice, the biliary lipid concentration was reduced by 36%, compared with control mice, and bile flow was increased by 35%. We observed increased water secretion from hepatocytes into bile canaliculi to mediate these effects, resulting in suppression of cholelithogenesis. Hepatic expression of aquaporin 8 (AQP8) protein was 1.5-fold higher in iH-HIFKO mice than in control mice. Under hypoxic conditions, cultured hepatocytes increased expression of Hif1a, Hmox1, and Vegfa messenger RNAs (mRNAs), and down-regulated expression of AQP8 mRNA and protein; AQP8 down-regulation was not observed in cells with knockdown of HIF1A. iH-HIFKO mice had reduced inflammation and mucin deposition in the gallbladder compared with control mice. Liver tissues from patients with NAFLD with gallstones had increased levels of HIF1A, HMOX1, and VEGFA mRNAs, compared with livers from patients with NAFLD without gallstones. CONCLUSIONS: In steatotic livers of mice, hypoxia up-regulates expression of HIF1A, which reduces expression of AQP8 and concentrates biliary lipids via suppression of water secretion from hepatocytes. This promotes cholesterol gallstone formation. Livers from patients with NAFLD and gallstones express higher levels of HIF1A than livers from patients with NAFLD without gallstones.

Selective insulin resistance with differential expressions of IRS-1 and IRS-2 in human NAFLD livers.

BACKGROUND/OBJECTIVE: Insulin signals, via the regulation of key enzyme expression, both suppress gluconeogenesis and enhance lipid synthesis in the liver. Animal studies have revealed insulin signaling favoring gluconeogenesis suppression to be selectively impaired in steatotic livers. However, whether, and if so how, such selective insulin resistance occurs in human steatotic livers remains unknown. Our aim was to investigate selective insulin resistance in human livers with non-alcoholic fatty liver disease (NAFLD). SUBJECTS/METHODS: We examined mRNA expressions of key molecules for insulin signaling, gluconeogenesis and lipogenesis in human liver biopsy samples obtained from 51 non-diabetic subjects: 9 healthy controls and 42 NAFLD patients, and analyzed associations of these molecules with each other and with detailed pathological and clinical biochemistry data. RESULTS: In NAFLD patients, insulin receptor substrate (IRS)-2 expression was decreased, while those of key enzymes for gluconeogenesis were increased. These alterations of IRS-2 and gluconeogenesis enzymes were induced both in simple steatosis (SS) and non-alcoholic steatohepatitis (NASH), while these expression levels did not differ between SS and NASH. Furthermore, alterations in the expressions of IRS-2 and gluconeogenesis enzymes showed strong negative correlations and were concurrently induced in the early histological stage of NAFLD. In contrast, fatty acid synthase (FAS) expression was not decreased in NAFLD, despite IRS-2 downregulation, but correlated strongly with IRS-1 expression. Furthermore, no histological scores were associated with these molecules. Thus, IRS-1 signaling, which is not impaired in NAFLD, appears to modulate FAS expression. CONCLUSION: These analyses revealed that selective insulin resistance is present in human NAFLD livers and occurs in its early phases. The effect of insulin, during the IRS step, on gene expressions for lipogenesis and gluconeogenesis are apparently distinct and preferential downregulation of IRS-2 may contribute to selective resistance to the suppressive effects of insulin on gluconeogenesis.

Characteristics of health problems in returned overseas travelers at a tertiary teaching hospital in a suburban area in Japan.

Few studies have analyzed the characteristics of patients who develop physical disorders after overseas travel. We retrospectively reviewed the medical records of 183 patients who visited Nara Medical University Hospital from 2008 to 2016 because of physical problems after traveling abroad. The main travel destinations were Southeast Asia (n = 100), Africa (n = 27), and South Asia (n = 23). The main reasons for the travel were leisure (n = 96), business (n = 51), and volunteer work (n = 19). The most common final diagnosis was gastrointestinal disease (n = 72), followed by febrile disease (n = 59) and respiratory disease (n = 19). There were eight malaria cases, including one patient who was infected after <14 days of overseas travel. Additionally, 61 of 71 cases of travelers' diarrhea and 15 of 21 cases of dengue fever occurred after <14 days travel. 26 cases of vaccine preventable diseases, such as hepatitis A, typhoid fever, and influenza, were observed. Consequently, healthcare providers should notify Japanese overseas travelers that there is a non-negligible health risk inherent to short-term travel, while stressing on the importance of pre-travel medical consultation.

Chronic invasive sinus and intracerebral aspergillosis controlled by combination therapy with micafungin and a daily dose of 400 mg itraconazole oral solution.

Chronic invasive aspergillosis of the sinus is frequently fatal in the absence of early surgical and chemotherapeutic intervention because of its invasion of vascular tissue. We attempted to control a case of inoperable invasive aspergillosis of the sinus with micafungin and itraconazole oral solution. We prescribed a daily oral dose of 400 mg of itraconazole, which is twice the usual dose, and monitored the serum concentration of the drug. Finally, we were able to control the spread of the lesion. This case indicates that combination therapy with micafungin and a daily dose of 400 mg itraconazole oral solution is an alternative treatment strategy for inoperable invasive aspergillosis of the sinus.

[A Case of Disseminated Cutaneous Mycobacterium chelonae Infection Successfully Improved with Thermal Therapy].

A 54-year-old female with dermatomyositis treated with cyclosporine and methylprednisolone presented with multiple subcutaneous nodules on her upper and lower extremities on December 2011. The number of lesions gradually increased. She had a history of surgical intervention such as debridement, skin graft of right lower leg due to trauma and subsequent bacterial infection on August 2011. Culture from a skin lesion on June 2012 confirmed Mycobacterium chelonae, which was susceptible to clarithromycin (CAM). We started treatment with CAM, imipenem/cilastatin (IPM/CS) and tobramycin (TOB) for 2 weeks. Then CAM monotherapy was continued, however CAM was discontinued because of liver dysfunction. In September 2012 new nodular lesions were observed on the left arm and right leg. We administrated azithromycin, IPM/CS and TOB. Subcutaneous nodules were partially improved, but new lesions appeared on her right leg. A culture of skin lesion yielded M. chelonae, which was highly resistant to CAM and IPM/CS. Based on the sensitivity test, moxifloxacin was used. However, there was no significant improvement in her skin lesions, so we started thermal therapy on day 57 after admission. She showed an excellent response to thermal therapy, and there has been no recurrence.

Continuous ampicillin infusion as an alternative to intermittent infusion for adult inpatients: a case series.

Intravenous ampicillin has been extensively used for various kinds of infections for more than fifty years. This drug is administered intermittently, which can result in missed or delayed drug administration and sleep interruption that can have a negative impact on the quality of life during hospitalization. Continuous infusion may solve these concerns. We reviewed the cases of five patients who were treated with continuous ampicillin infusions in our hospital. The ampicillin serum concentrations were from 11.3 to 32.8 µg/mL, which was above the ampicillin MICs of the causative organisms, ≤0.06 to 4 µg/mL. Although the dosages given of ampicillin varied in each case, the serum concentrations showed a strong correlation with creatinine clearance (r(2) = 0.91). All the patients improved at the time of discharge, or transfer to another hospital, with no significant complications during the continuous infusion. Continuous ampicillin infusion could be a better alternative for frequent intermittent infusion for adult inpatients with infections due to ampicillin-susceptible organisms.

Infective endocarditis and meningitis due to Scedosporium prolificans in a renal transplant recipient.

Scedosporium prolificans is a ubiquitous filamentous fungi that may cause disseminated diseases in neutropenic patients with hematological malignancies. We report a fatal case of renal transplant recipient who developed both infective endocarditis and meningitis due to S. prolificans during treatment with micafungin and itraconazole for chronic necrotizing aspergillosis. Breakthrough Scedosporium infection should be considered among differential diagnosis of invasive fungal diseases in patients with renal transplant recipients receiving antifungal agents.