The impact of postoperative infliximab maintenance therapy on preventing the surgical recurrence of Crohn’s disease: a single-center paired case–control study

Purpose

Preventing a recurrence of Crohn’s disease is a problem that remains to be solved. We evaluated the impact of using infliximab as a postoperative therapy on preventing the surgical recurrence of Crohn’s disease.

Methods

We performed a pair-matched study comparing 100 patients who had received postoperative infliximab maintenance therapy with those who had not between 1995 and 2010. The patients were matched by gender, Vienna classification and age at the time of the operation. Crohn’s disease-related reoperation was evaluated as surgical recurrence.

Results

In the postoperative infliximab maintenance therapy group, infliximab was administrated within 8 weeks after the operation. The median follow-up period was 36 months in the postoperative infliximab maintenance therapy group and 51 months in the control group. Surgical recurrences were recognized in 37 patients (three in the postoperative infliximab maintenance therapy group and 34 in the control group). A univariate analysis by the Kaplan–Meier method identified a body mass index >18 at the time of the operation (HR 0.19, p = 0.01) and postoperative infliximab maintenance therapy (HR 0.22, p = 0.0022) as factors related to the reduction of surgical recurrence. The multivariate analysis revealed that postoperative infliximab maintenance therapy was the only significant factor preventing surgical recurrence.

Conclusion

Postoperative infliximab maintenance therapy for Crohn’s disease prevents surgical recurrence, at least within 3 years after the operation.     

Current status of countermeasures for infectious diseases and resistant microbes in the field of urology

A worldwide increase in antimicrobial‐resistant microbes due to the improper use of antimicrobial agents, along with a lack of progress in developing new antimicrobials, is becoming a societal problem. Although carbapenem‐resistant Enterobacteriaceae, which are resistant to carbapenem antimicrobials, first appeared in 1993, treatment options remain limited. Mechanisms behind antimicrobial resistance involve changes to microbial outer membranes, drug efflux pump abnormalities, β‐lactamase production and the creation of biofilms around cell bodies. Genetic information related to these forms of antimicrobial resistance exists on chromosomes and plasmids, and when located on the latter can easily be transmitted to other strains, no matter the species, which creates a risk of antimicrobial resistance spreading exceptionally rapidly. To prevent the spread of antimicrobial resistance, the World Health Organization in 2015 published an action plan on antimicrobial resistance, based on which World Health Organization member countries have laid out specific policies and targets. Urinary tract infections are a type of healthcare‐associated infection, and the sexually transmitted disease pathogen, Neisseria gonorrhoeae, has been included in a list of microbes that pose a risk to human health published by the US Centers for Disease Control and Prevention. Urologists face numerous problems when attempting to use antimicrobials properly, which is one method of dealing with antimicrobial resistance. Therefore, this article describes the current state of resistant microbes associated with urinary tract infections and countermeasures for antimicrobial resistance, including new antimicrobials.     

Human parathyroid hormone (1-34) increases mass and structure of the cortical shell,with resultant increase in lumbar bone strength,in ovariectomized rats

Estrogen deficiency causes reduction of bone mass and abnormal bone microarchitecture, consequently reducing bone strength. Human parathyroid hormone (hPTH) (1-34) increases bone mass and strength. To clarify the factors that determine the recovery of bone strength in the lumbar vertebrae of ovariectomized rats by intermittent hPTH administration, we analyzed the relationship between skeletal measurements and bone strength. Human PTH (1-34) administration resulted in recovery of cortical bone mineral content (BMC) and cortical bone area to sham the levels, but in resulted in a less pronounced recovery of trabecular BMC and no increase in the total cross-sectional area of the vertebral body. Of the three-dimensional (3D) trabecular bone parameters, hPTH (1-34) increased trabecular thickness (Tb.Th). The cortical shell area of L4, determined by histomorphometry, was also increased. In hPTH-treated rats, the only determinant of the compressive load of L5 was the cortical shell BMC, in the early recovery period (days 42–84). Our data suggest that increased cortical bone mass contributes more than trabecular bone mass and structure to the recovery of bone strength in response to hPTH therapy in the rat lumbar vertebral body after ovariectomy.     

Magnetic resonance imaging for preoperative evaluation of breast cancer: a comparative study with mammography and ultrasonography

BACKGROUND: The widespread use of mammographic screening has led to increased detection of small tumors that are often difficult to diagnose with conventional imaging modalities such as mammography and ultrasonography. Intraductal spread of breast cancer, a principle risk factor for local recurrence, is also difficult to diagnose with mammography and ultrasonography. We investigated the clinical usefulness of magnetic resonance imaging of the breast in the therapy of breast cancer and we compared it with mammography and ultrasonography. STUDY DESIGN: A total of 183 patients with primary breast cancer underwent surgery at our institute between September 1, 1999, and November 30, 2002. They were examined preoperatively with magnetic resonance imaging, mammography, and ultrasonography. Magnetic resonance imaging evaluation included contrast-enhanced dynamic studies using IV injection of gadolinium-diethylenetriamine pentaacetic acid. RESULTS: Detection rates of breast cancers by magnetic resonance imaging, mammography, and ultrasonography were 93.7%, 84.6%, and 97.3%, respectively (magnetic resonance imaging versus mammography, p < 0.05). Patterns of time-intensity curves in dynamic magnetic resonance imaging differed with histologic types. Sensitivity, specificity, and accuracy of detection of intraductal spread were 66.7%, 64.2%, and 65.6% with MRI; 22.2%, 85.7%, and 50% with mammography; and 20.6%, 85.2%, and 50% with ultrasonography, respectively (sensitivity, specificity, and accuracy; p < 0.05, respectively). CONCLUSIONS: Magnetic resonance imaging can diagnose breast cancer as accurately as ultrasonography and more accurately than mammography. Patterns of time-intensity curves correlated with tumor histology. In addition, magnetic resonance imaging can detect intraductal spread more accurately than the other two methods. Magnetic resonance imaging appears to be indispensable in breast-conserving surgery to minimize local recurrence.     

A case of superior mesenteric artery syndrome after left nephrectomy

Postoperative superior mesenteric artery syndrome is a rare complication of left nephrectomy. We treated a case of superior mesenteric artery syndrome that occurred 7 days after radical left nephrectomy for renal cell carcinoma. The patient was a 54-year-old Japanese man who presented with gross hematuria. Abdominal computed tomography showed a 3.8 x 3.8 x 5 cm heterogeneous cystic mass in the left kidney. Transperitoneal left radical nephrectomy was performed because renal cell carcinoma was suspected. The patient resumed oral intake 3 days after surgery, but he began vomiting repeatedly from the 7th day after surgery. Gastroduodenography showed an abrupt vertical linear obstruction of the third portion of the duodenum. Superior mesenteric artery syndrome was diagnosed. Conservative therapy (indwelling nasogastric tube, intravenous hyperalimentation and postural changes) was effective.     

Functional brain mapping of the macaque related to spatial working memory as revealed by PET

To define the cortical areas that subserve spatial working memory in a nonhuman primate, we measured regional cerebral blood flow (rCBF) with [(15)O]H(2)O and positron emission tomography while monkeys performed a visually guided saccade (VGS) task and an oculomotor delayed-response (ODR) task. Both Statistical Parametric Mapping and regions of interest-based analyses revealed an increase of rCBF in the area surrounding the principal sulcus (PS), the superior convexity, the anterior bank of the arcuate sulcus (AS), the lateral orbitofrontal cortex (lOFC), the frontal pole (FP), the anterior cingulate cortex (ACC), the lateral bank of the intraparietal sulcus (lIPS) and the prestriate cortex. In the prefrontal cortex (PS, superior convexity, AS, lOFC and FP), rCBF values correlated positively with ODR task performance scores. From the hippocampus, rCBF values correlated negatively with ODR task performance. From the AS, superior convexity, lOFC, FP, ACC and lIPS, rCBF values of the PS correlated positively with rCBF values and negatively with hippocampus rCBF values. These results suggest that neural circuitry in the prefrontal cortex directly contributes the spatial working memory processes and that, in spatial working memory processes, the posterior parietal cortex and hippocampus have a different role to the prefrontal cortex.     

Important role for macrophages in induction of crescentic anti-GBM glomerulonephritis in WKY rats.

BACKGROUND: A crucial role for CD8(+) cells in induction of crescentic anti-glomerular basement membrane (GBM) glomerulonephritis (GN) in WKY rats was demonstrated in studies showing that depletion of CD8(+) cells completely suppressed glomerular accumulation of monocytes/macrophages (Mo/Mphi), crescent formation and proteinuria. Because these studies did not definitively identify CD8(+) cells as the cause of tissue injury, we examined the roles of Mo/Mphi in the development of anti-GBM GN. METHODS: We examined correlations between the amount of urinary protein and the numbers of glomerular CD8(+) cells or Mo/Mphi in rats after administrating different doses of anti-GBM antibody (5.0, 7.5, 10.0 and 25.0 microl/100 g body weight). The roles of Mo/Mphi in induction of GN were examined in animals by depleting Mo/Mphi in the glomerulus. To do this, rats were injected intravenously with liposome-encapsulated dichloromethylene diphosphonate (liposome-MDP) from day 3 to day 7 after anti-GBM antibody injection and they were then sacrificed at day 8. RESULTS: Liposome-MDP treatment significantly reduced the number of ED-1(+) Mo/Mphi accumulated in glomeruli from 32.1 +/- 1.2 to 1.4 +/- 0.3/glomerular cross-section (mean +/- SD, P < 0.01), and the amount of urinary protein from 103.8 +/- 19.8 to 31.8 +/- 15.9 mg/day (P < 0.01), as well as the incidence of crescentic glomeruli from 91.3 +/- 2.7 to 23.3 +/- 7.6% (P < 0.01) at day 8. This treatment also reduced the number of CD8(+) cells accumulating in the glomeruli from 5.4 +/- 0.7 to 0.5 +/- 0.1/glomerular cross-section (P < 0.01). Upregulation of glomerular intercellular adhesion molecule 1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1) mRNA expression was suppressed by Mo/Mphi depletion. CONCLUSION: These results indicate that Mo/Mphi play an important role in the induction of crescentic anti-GBM GN and glomerular injury.     

A novel Na+‐Independent alanine‐serine‐cysteine transporter 1 inhibitor inhibits both influx and efflux of D‐Serine

NMDA receptor dysfunctions are hypothesized to underlie the pathophysiology of schizophrenia, and treatment with D‐serine (D‐Ser), an NMDA receptor coagonist, may improve the clinical symptoms of schizophrenia. Thus, upregulating the synaptic D‐Ser level is a novel strategy for schizophrenia treatment. Na⁺‐independent alanine‐serine‐cysteine transporter 1 (asc‐1) is a transporter responsible for regulating the extracellular D‐Ser levels in the brain. In this study, we discovered a novel asc‐1 inhibitor, (+)‐amino(1‐(3,5‐dichlorophenyl)‐3,5‐dimethyl‐1H‐pyrazol‐4‐yl)acetic acid (ACPP), and assessed its pharmacological profile. ACPP inhibited the D‐[³H]Ser uptake in human asc‐1‐expressing CHO cells and rat primary neurons with IC₅₀ values of 0.72 ± 0.13 and 0.89 ± 0.30 μM, respectively. In accordance with the lower asc‐1 expression levels in astrocytes, ACPP did not inhibit D‐Ser uptake in rat primary astrocytes. In a microdialysis study, ACPP dose dependently decreased the extracellular D‐Ser levels in the rat hippocampus under the same conditions in which the asc‐1 inhibitor S‐methyl‐L‐cysteine (SMLC) increased it. To obtain insights into this difference, we conducted a D‐[³H]Ser efflux assay using asc‐1‐expressing CHO cells. ACPP inhibited D‐[³H]Ser efflux, whereas SMLC increased it. These results suggest that ACPP is a novel inhibitor of asc‐1. © 2016 Wiley Periodicals, Inc.     

Cerebellar Contribution to Pattern Separation of Human Hippocampal Memory Circuits

The cerebellum is a crucial structure for cognitive function as well as motor control. Benign brain tumors such as schwannomas, meningiomas, and epidermoids tend to occur in the cerebellopontine angle cisterns and may cause compression of the posterior lateral cerebellum near the superior posterior fissure, where the eloquent area for cognitive function was recently identified. The present study examined cognitive impairment in patients with benign cerebellar tumors before and after surgical intervention in order to clarify the functional implications of this region in humans. Patients with cerebellar tumors showed deficits in psychomotor speed and working memory compared with healthy controls. Moreover, these impairments were more pronounced in patients with right cerebellar tumors. Functional magnetic resonance imaging during performance of a lure task also demonstrated that cerebellar tumors affected pattern separation or the ability to distinguish similar experiences of episodic memory or events with discrete, non-overlapping representations, which is one of the important cognitive functions related to the hippocampus. The present findings indicate that compression of the human posterior lateral cerebellum affects hippocampal memory function.