Long-Term Results of Seton Placement for Fistula-in-ano in Infants

Background

The present study aimed to assess the long-term results of seton placement for fistula-in-ano (FIA) in infants.

Methods

Data of patients aged <1 year who presented to our department with perianal abscess (PA) between January 2006 and February 2010 were retrospectively reviewed. Our standard initial treatment for PA was incision and drainage. Patients with systemic diseases and inflammatory bowel diseases were excluded.

Results

Ninety-five patients were treated for PA and/or FIA during the 5-year period, and follow-up data were available for 90 patients. The mean follow-up duration in these patients was 49.8?±?11.4 months, and mean age at presentation was 3.1?±?2.7 months. Of the 90 patients, 36 (40 %) developed FIA (39 lesions) and underwent seton placement. The condition healed in a mean period of 6.3?±?4.0 weeks after the placement of a cutting seton. Healing of the fistula was achieved in 35 (97.2 %) of 36 patients after the initial seton procedure, and one patient who showed recurrence underwent a second seton placement, resulting in successful healing of the FIA after 5 weeks.

Conclusions

The long-term success of seton placement indicates that this procedure should be a treatment option for FIA in infants.     

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.     

Prediction of the prognosis of liver cirrhosis in Japanese using Cox's proportional hazard model

Data on 155 patients with liver cirrhosis were analyzed, using Cox's proportional hazard model. Twenty variables were screened, using a multiple linear regression analysis in a stepwise manner and 6 were considered to reflect the prognosis of cirrhotics. Three of the 6 variables were significantly prognostic, i.e. ascites, atrophy of the right lobe of the liver seen on liver scintigram and the concentration of serum albumin. The prognostic index (PI) for each patient was calculated by adding all the products of scores of these three variables with the corresponding coefficient: PI = 0.895 X ascites (absent = 0, present = 1) + 0.983 X atrophy of right lobe of the liver on the liver scintigram (absent = 0, present = 1) + (-0.561) X serum albumin (g/dl). According to the PI, the subjects were separated into three groups; group 1: PI less than -1.9, group 2: -1.9 less than or equal to PI less than -0.6, group 3: PI greater than or equal to -0.6. The global 5- and 10-year survival rates of each group were 80% and 65% in group 1, 50% and 30% in group 2 and 12% and 0% in group 3, respectively. Four of the 14 deaths in group 1, 8 of 47 in groups 2 and 10 of 24 in group 3 were caused by hepatocellular carcinoma. Our observations suggest that advanced stage cases of cirrhosis are at a high risk concerning development of hepatocellular carcinoma.     

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.     

The effect of docosahexaenoic acid on bone microstructure in young mice and bone fracture in neonates

Background

As low bone mineral density is a risk factor for fracture in childhood, optimizing age appropriate bone mass is recommended and might lower the impact of bone loss related to age. Consumption of omega-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic and docosahexaenoic (DHA) acids have been shown to beneficially modulate bone metabolism. The objective of this study was to determine the incidence of fracture in neonates receiving a fish compared with soybean oil–based intravenous lipid emulsion and evaluate the effect of varying dietary omega-3 PUFA consumption on growing bone in young mice.

Materials and methods

Eligibility criteria for the clinical study included gestational age ≤37 wk and parenteral nutrition–dependence for ≥4 wk. Radiographs were reviewed after lipid initiation to identify radiologic bone fracture. The animal study evaluated female C57/Bl6 mice randomized into one of five groups from age 3–12 wk, at which time femurs were harvested for micro–computed tomography and light microscopy analysis.

Results

A lower incidence of bone fracture was found in neonates maintained on fish compared with soybean oil. In the animal study, findings suggest the DHA diet provides the best protection against trabecular bone loss as evidenced by increased bone volume fraction, increased trabecular number, and decreased trabecular separation on micro–computed tomography. These protective effects appeared to affect the bone microstructure alone.

Conclusions

The lower fracture risk observed in fish oil fed neonates in combination with the protective effects of DHA observed in the femurs of young C57/BL6 mice suggest an important role for omega-3 PUFAs on bone growth.     

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.     

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.