Utility of follow-up blood cultures for Gram-negative rod bacteremia in children

Persistent Gram-negative rod (GNR) bacteremia is uncommon under appropriate antibiotic therapy. A recent study showed that follow-up blood cultures (FUBCs) to confirm clearance 24–48 h after initiation of antibiotics, added little value in the management of GNR bacteremia in adults. However, the utility of FUBC in children is still unknown. We retrospectively reviewed the microbiology database to identify children aged <18 years with GNR bacteremia. Clinical information including gender, age, underlying diseases, presence of central venous line (CVC), source of bacteremia, and organisms was extracted from medical records. FUBCs for 99 episodes of GNR bacteremia in children became positive in 21%, which led to intervention in 57% of the episodes. In multivariate analysis between FUBC positive (n = 21) and negative (n = 78) groups, presence of CVC (n = 18, 86% vs n = 38, 49%, P = 0.001) and resistance to empirical antibiotics (n = 3, 14% vs n = 4, 5%, P = 0.04) were independently associated with positive FUBCs. Interestingly, no positive FUBC was observed in cases due to UTI (n = 13). Contrary to findings in adults, FUBC may still be useful in the management of GNR bacteremia in children.     

Alcohol consumption is associated with an increased risk of erosive esophagitis and Barrett's epithelium in Japanese men

Background

The precise role of capsule endoscopy in the diagnostic algorithm of obscure gastrointestinal bleeding has yet to be determined. Despite the higher diagnostic yield of capsule endoscopy, the actual impact on clinical outcome remains poorly defined. The aim of this study was to evaluate the follow-up results of patients with obscure gastrointestinal bleeding to determine which management strategies after capsule endoscopy reduced rebleeding.

Methods

All patients in whom the cause of obscure gastrointestinal bleeding was investigated between May 2004 and March 2007 were studied retrospectively. We evaluated the clinical outcome of patients with obscure gastrointestinal bleeding after capsule endoscopy using the rebleeding rate as the primary outcome.

Results

Seventy-seven patients with obscure gastrointestinal bleeding underwent capsule endoscopy. Capsule endoscopy identified clinically significant findings that were thought to be the sources of obscure gastrointestinal bleeding in 58.4% of the patients. The overall rebleeding rate was 36.4%. The rebleeding rate was significantly higher among patients with insignificant findings than among those with significant findings (p = 0.036). Among the patients in whom capsule endoscopy produced significant findings, the rebleeding rate of the patients who underwent therapeutic interventions was significantly lower than that in those who did not undergo intervention (9.5% vs 40.0%, p = 0.046).

Conclusion

Follow-up and further aggressive interventions are necessary for patients with obscure gastrointestinal bleeding and significant capsule endoscopy findings to reduce the chance of rebleeding.     

Observation of femtosecond X-ray interactions with matter using an X-ray–X-ray pump–probe scheme

Resolution in the X-ray structure determination of noncrystalline samples has been limited to several tens of nanometers, because deep X-ray irradiation required for enhanced resolution causes radiation damage to samples. However, theoretical studies predict that the femtosecond (fs) durations of X-ray free-electron laser (XFEL) pulses make it possible to record scattering signals before the initiation of X-ray damage processes; thus, an ultraintense X-ray beam can be used beyond the conventional limit of radiation dose. Here, we verify this scenario by directly observing femtosecond X-ray damage processes in diamond irradiated with extraordinarily intense (∼10¹⁹ W/cm²) XFEL pulses. An X-ray pump–probe diffraction scheme was developed in this study; tightly focused double–5-fs XFEL pulses with time separations ranging from sub-fs to 80 fs were used to excite (i.e., pump) the diamond and characterize (i.e., probe) the temporal changes of the crystalline structures through Bragg reflection. It was found that the pump and probe diffraction intensities remain almost constant for shorter time separations of the double pulse, whereas the probe diffraction intensities decreased after 20 fs following pump pulse irradiation due to the X-ray–induced atomic displacement. This result indicates that sub-10-fs XFEL pulses enable conductions of damageless structural determinations and supports the validity of the theoretical predictions of ultraintense X-ray–matter interactions. The X-ray pump–probe scheme demonstrated here would be effective for understanding ultraintense X-ray–matter interactions, which will greatly stimulate advanced XFEL applications, such as atomic structure determination of a single molecule and generation of exotic matters with high energy densities.Since W. C. Röntgen discovered X-rays emitted from vacuum tube equipment in 1895, scientists have continuously endeavored to develop brighter X-ray sources throughout the 20th century. One of the most remarkable breakthroughs was the emergence of synchrotron light sources, which were much more brilliant than the early lab-based X-ray sources. Such dramatic increase in X-ray brilliance provided a pathway to obtain high-quality X-ray scattering data. This, in turn, enabled one to solve the structures of complex systems such as proteins, functional units of living organisms, and viruses. However, the increase in the brilliance is also accompanied by a severe problem of X-ray radiation damage to the samples being examined (1). X-rays ionize atoms and generate highly activated radicals that break chemical bonds and cause changes in the structures of the samples. To achieve structure determination precisely, a sufficient scattering signal should be recorded before the samples are severely damaged. Radiation damage was considered to be an intrinsic problem associated with X-ray scattering experiments, which imposed a fundamental limit on the resolution in X-ray structure determination (2).The recent advent of X-ray free-electron lasers (XFELs) (3–5), which emit ultraintense X-ray pulses with durations of several femtoseconds, may totally avoid the problem of radiation damage. The irradiation of intense XFEL pulses generates highly ionized atoms, and the strong Coulomb repulsive force leads to evaporation of the samples. Meanwhile, it has been predicted theoretically (6) that atoms do not change their positions before the termination of the femtosecond X-ray pulse owing to inertia, thus enabling the use of X-ray radiations beyond the conventional X-ray dose limit. This innovative concept, called a “diffraction-before-destruction” scheme (6, 7), has paved a clear way to high-resolution structure determinations of weak scattering objects, including nanometer-sized protein crystals (8), noncrystalline biological particles (9), and damage-sensitive protein crystals (10).Despite the potential impact of XFELs, detailed understanding of the ultrafast XFEL damage processes has been missing. As a pioneering work, Barty et al. (11) measured the diffraction intensities of protein nanocrystals by changing the XFEL pulse durations from 70 to 300 fs at intensities of ∼10¹⁷ W/cm². They found that the diffraction intensities greatly decrease for longer durations, clearly indicating sign of structural damage, i.e., X-ray–induced atomic displacements within the XFEL pulse durations. For further understanding of ultraintense X-ray interactions with matter, we need to directly measure the temporal changes of the structural damage. In particular, measuring the ignition time of the atomic displacements is crucial for realizing advanced applications with greatly intense XFELs. Although improving our knowledge of the X-ray damage processes is essential for all aspects of XFEL science, the experimental verifications have been missing because of the extreme difficulty in observation with ultrahigh resolutions in space (ångstrom) and time (femtosecond).As a new approach to investigate the femtosecond X-ray damage processes, we here propose an X-ray–X-ray pump–probe experiment using double X-ray pulses; a pump X-ray pulse excites a sample and a probe X-ray pulse with a well-controlled time delay characterizes the change in the sample. In this approach, it is highly useful to exploit two-color double pulses with tunable temporal separations (12–15), which have been developed at SPring-8 Angstrom Compact free-electron LAser (SACLA) (4) and Linac Coherent Light Source (3). In this article, we measured the X-ray damage processes of diamond by using an X-ray–X-ray pump–probe diffraction experiment at SACLA. As the carbon–carbon bond is one of the most fundamental bonds in biomolecules, our results should provide a benchmark for XFEL-induced damage to practical samples.     

Allogeneic hematopoietic stem cell transplantation for aplastic anemia with pre-transplant conditioning using fludarabine,reduced-dose cyclophosphamide,and low-dose thymoglobulin: A KSGCT prospective study

The optimal pre-transplant conditioning for aplastic anemia (AA) remains unclear. We performed a prospective study on allogeneic transplantation from a related or unrelated donor for adult patients with AA. We assessed whether reduced-dose cyclophosphamide (CY) could decrease toxicity while maintaining engraftment, and low-dose thymoglobulin could safely prevent graft-vs-host disease (GVHD). The pre-transplant conditioning regimen consisted of fludarabine 120 mg/m², CY 100 mg/kg, and thymoglobulin 2.5 mg/kg with or without 2 Gy of total body irradiation. Twenty-seven patients with a median age of 36 years were analyzed. Sixteen patients received graft from related donors. The stem cell source was bone marrow in 26 patients. All of the patients but one, who died early, achieved neutrophil engraftment at a median of 19 days. Mixed chimerism was observed in six and five patients at days 30 and 90, respectively. Only one patient experienced secondary engraftment failure with complete donor-type chimerism. None of the patients developed severe acute GVHD. The cumulative incidence of chronic GVHD was 37.7% at 1 year. The overall survival rate was 96.3% at 1 year and 3 years. A high EB virus-DNA load was detected in one patient at days 60. No one developed EBV-lymphoproliferative disorder within a year. The results suggest that the conditioning regimen in this study was safe and effective. However, relatively high incidence of chronic GVHD needs further improvement.     

Cerebral Infarction with Pulmonary Thromboembolism Due to Immobilization

Arterial and venous thrombi can coexist without preexisting conditions, such as malignant disease, thrombotic predisposition, or arteriovenous shunt. We herein report a case of acute cerebral infarction and pulmonary thromboembolism in the absence of underlying disease. A 71-year-old woman presented with left hemiplegia. On an examination, her oxygen saturation was 91% on ambient air despite the absence of chest symptoms and clear lung fields on a chest radiograph. The patient was finally diagnosed with acute cerebral infarction caused by large artery atherosclerosis and acute pulmonary thromboembolism due to deep vein thrombosis, consequent to immobilization for three days after the onset of cerebral infarction.     

Case report: The operation for the lumbar disk herniation just after cesarean delivery in the third trimester of pregnancy

INTRODUCTION

Low back pain is common during pregnancy. However, the incidence of symptomatic lumbar disc herniation during pregnancy is very rare. We report a case of lumbar disc herniation underwent discectomy just after cesarean delivery in the third trimester of pregnancy.

PRESENTATION OF CASE

A 33-year-old woman presented at 32 weeks gestation. She had a low back pain and the left-sided leg pain below the knee. At 34 weeks gestation, she had severe weakness of the left extension halluces longus, left ankle dorsiflexion. MRI showed a large disc herniation at L4/5 expanded to the spinal canal more. The cesarean delivery was performed in the supine position. The patient was then turned to a prone position, and a left L4/5 discectomy was performed. But the day after surgery, she had a severe low back pain and the right leg pain below the knee. MRI showed a disc herniation at L4/5 on the right side of the spinal canal. At 6 days after the first surgery, a right L4/5 discectomy was performed. In the immediate postoperative period, the patient experienced complete relief of the right leg pain.

DISCUSSION

It is necessary to cooperate with a pediatrician, an obstetrician, and an anethesiologists. For obtaining the best outcome on mother and child, it is important to discuss in advance to be able to respond quickly for changeable situation.

CONCLUSION

It is necessary to conduct the operation under pregnancy in consideration of the great influence on mother and child.     

Oral vaccination against HPV E7 for treatment of cervical intraepithelial neoplasia grade 3 (CIN3) elicits E7-specific mucosal immunity in the cervix of CIN3 patients

Background

Cervical intraepithelial neoplasia grade 3 (CIN3) is a mucosal precancerous lesion caused by high-risk human papillomavirus (HPV). Induction of immunological clearance of CIN3 by targeting HPV antigens is a promising strategy for CIN3 therapy. No successful HPV therapeutic vaccine has been developed.

Methods

We evaluated the safety and clinical efficacy of an attenuated Lactobacillus casei expressing modified full-length HPV16 E7 protein in patients with HPV16-associated CIN3. Ten patients were vaccinated orally during dose optimization studies (1, 2, 4, or 6 capsules/day) at weeks 1, 2, 4, and 8 (Step 1). Seven additional participants were only tested using the optimized vaccine formulation (Step 2), giving a total of 10 patients who received optimized vaccination. Cervical lymphocytes (CxLs) and peripheral blood mononuclear cells (PBMCs) were collected and E7 specific interferon-γ-producing cells were counted (E7 cell-mediated immune responses: E7-CMI) by ELISPOT assay. All patients were re-evaluated 9 weeks after initial vaccine exposure using cytology and biopsy to assess pathological efficacy.

Results

No patient experienced an adverse event. E7-CMI in both CxLs and PBMCs was negligible at baseline. All patients using 4–6 capsules/day showed increased E7-CMI in CxLs, whereas patients using 1–2 capsules/day did not. No patient demonstrated an increase in E7-CMI in their PBMCs. In comparison between patients of cohorts, E7-CMI at week 9 (9 wk) in patients on 4 capsules/day was significantly higher than those in patients on 1, 2, or 6 capsules/day. Most patients (70%) taking the optimized dose experienced a pathological down-grade to CIN2 at week 9 of treatment. E7-CMI in CxLs correlated directly with the pathological down-grade.

Conclusions

Oral administration of an E7-expressing Lactobacillus-based vaccine can elicit E7-specific mucosal immunity in the uterine cervical lesions. We are the first to report a correlation between mucosal E7-CMI in the cervix and clinical response after immunotherapy in human mucosal neoplasia.