Biofilm Producing Staphylococcus epidermidis (RP62A Strain) Inhibits Osseous Integration Without Osteolysis and Histopathology in a Murine Septic Implant Model

Despite its presence in orthopaedic infections, Staphylococcus epidermidis's ability to directly induce inflammation and bone destruction is unknown. Thus, we compared a clinical strain of methicillin-resistant biofilm-producing S. epidermidis (RP62A) to a highly virulent and osteolytic strain of methicillin-resistant Staphylococcus aureus (USA300) in an established murine implant-associated osteomyelitis model. Bacterial burden was assessed by colony forming units (CFUs), tissue damage was assessed by histology and micro-computed tomography, biofilm was assessed by scanning electron microscopy (SEM), host gene expression was assessed by quantitative polymerase chain reaction, and osseous integration was assessed via biomechanical push-out test. While CFUs were recovered from RP62A-contaminated implants and surrounding tissues after 14 days, the bacterial burden was significantly less than USA300-infected tibiae (p < 0.001). In addition, RP62A failed to produce any of the gross pathologies induced by USA300 (osteolysis, reactive bone formation, Staphylococcus abscess communities, marrow necrosis, and biofilm). However, fibrous tissue was present at the implant-host interface, and rigorous SEM confirmed the rare presence of cocci on RP62A-contaminated implants. Gene expression studies revealed that IL-1β, IL-6, RANKL, and TLR-2 mRNA levels in RP62A-infected bone were increased versus Sterile controls. Ex vivo push-out testing showed that RP62A-infected implants required significantly less force compared with the Sterile group (7.5 ± 3.4 vs. 17.3 ± 4.1 N; p < 0.001), but required 10-fold greater force than USA300-infected implants (0.7 ± 0.3 N; p < 0.001). Taken together, these findings demonstrate that S. epidermidis is a commensal pathogen whose mechanisms to inhibit osseous integration are limited to minimal biofilm formation on the implant, and low-grade inflammation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:852-860, 2020     

Nationwide survey of Arima syndrome: Revised diagnostic criteria from epidemiological analysis

Aim: We have never known any epidemiological study of Arima syndrome since it was first described in 1971. To investigate the number of Arima syndrome patients and clarify the clinical differences between Arima syndrome and Joubert syndrome, we performed the first nationwide survey of Arima syndrome, and herein report its results. Furthermore, we revised the diagnostic criteria for Arima syndrome. Methods: As a primary survey, we sent out self-administered questionnaires to most of the Japanese hospitals with a pediatric clinic, and facilities for persons with severe motor and intellectual disabilities, inquiring as to the number of patients having symptoms of Arima syndrome, including severe psychomotor delay, agenesis or hypoplasia of cerebellar vermis, renal dysfunction, visual dysfunction and with or without ptosis-like appearance. Next, as the second survey, we sent out detailed clinical questionnaires to the institutes having patients with two or more typical symptoms. Results: The response rate of the primary survey was 72.7% of hospitals with pediatric clinic, 63.5% of national hospitals and 66.7% of municipal and private facilities. The number of patients with 5 typical symptoms was 13 and that with 2–4 symptoms was 32. The response rate of the secondary survey was 52% (23 patients). After reviewing clinical features of 23 patients, we identified 7 Arima syndrome patients and 16 Joubert syndrome patients. Progressive renal dysfunction was noticed in all Arima syndrome patients, but in 33% of those with Joubert syndrome. Conclusion: It is sometimes difficult to distinguish Arima syndrome from Joubert syndrome. Some clinicians described a patient with Joubert syndrome and its complications of visual dysfunction and renal dysfunction, whose current diagnosis was Arima syndrome. Thus, the diagnosis of the two syndromes may be confused. Here, we revised the diagnostic criteria for Arima syndrome.     

Clinico-radiological spectrum of reversible splenial lesions in children

Recently, many cases of children presenting reversible splenial lesions during febrile illness (RESLEF) have been reported; however, their overall clinico-radiological features are unclear.     

Cryptococcal meningitis following umbilical cord blood transplantation,association between the occurrence of cryptococcal infection and tacrolimus discontinuation among allogeneic hematopoietic stem cell recipients

Few cases of cryptococcal infection following umbilical cord blood transplantation (UCBT) have been reported. We report a case, where cryptococcal infection occurred soon after rapidly reducing the dose of tacrolimus in a UCBT recipient who received micafungin prophylaxis during the early phase of transplantation. The etiology of cryptococcal infection following allogeneic hematopoietic stem cell transplantation (allo-HSCT), including UCBT, might be associated with rapid dose-reduction of calcineurin inhibitors, such as tacrolimus during early phase of allo-HSCT. To our knowledge, this is the first English-language report to describe in detail a case of cryptococcal meningitis with fungemia during early phase of UCBT.     

New protocol to detect coronary spastic angina without fixed stenosis

A new combined test, accelerated exercise following mild hyperventilation (HV), was examined to determine whether it is effective at detecting a positive response in patients with pharmacologically-induced coronary vasospasm and near normal coronary arteries. Fifty-eight consecutive patients who underwent both triple non-invasive spasm provocation tests and diagnostic coronary angiography were enrolled. They all had pharmacologically-induced coronary vasospasms and no significant organic stenosis. In these patients, an HV test was performed first, followed by a treadmill exercise test (TET), and finally the new combined test under no medication within 3 days. Of the 58 patients, positive responses were observed in 9 patients to the HV, in 15 to the TET, and in 35 to the newly combined test. The remaining 21 patients had negative responses although the triple sequential tests were perfomed. Thus, the sensitivities of the HV test, TET, and newly combined test were 16% (9/58), 26% (15/58), and 63% (35/56), respectively. Forty-six subjects with near normal coronary arteries and no ACh-provoked spasm served as controls. None of these subjects had positive responses to any of these three tests, and thus their specificity was all 100%. No serious or irreversible complications were seen in this study. We recommend this newly-combined protocol for the induction of coronary artery spasm in patients with vasospastic angina pectoris and without significant stenosis as a diagnostic tool.     

The tight junction of pancreatic exocrine cells is a morphometrically dynamic structure altered by intraductal hypertension

The tight junction of pancreatic exocrine cells is thought to regulate paracellular permeability, and is a possible reflux route of pancreatic juice into the blood flow. Morphological changes in the tight junction of canine pancreatic acinar cells following intraductal hypertension and secretin stimulation were morphometrically analyzed to obtain evidence of the control of the paracellular reflux. Pancreatic tissues obtained from 25 dogs after intraductal hypertension, 3 dogs after secretin stimulation, and 5 control dogs were studied. Intraductal pressure was either 20 cmH2O, 30 cmH2O, or 40 cmH2O. Freeze fracture replicas of these pancreatic tissues were observed by electron microscopy. Tight junctions were classified into six morphometric types. Reticular type, parallel type, and mixed type comprised the common types predominantly found in all groups, and three special types were found, infrequently, only after intraductal hypertension. The percentages of the common types were significantly different between the groups. The areas of the tight junctions, and other morphometric parameters, were significantly less after 20 cmH2O intraductal hypertension and secretin stimulation than in the controls. However, these findings after 30 cmH2O or 40 cmH2O intraductal hypertension did not differ from those in the controls. The areas of the three special types of tight junctions were larger than those of the common types. These results suggest that the tight junction of pancreatic exocrine cells is a morphologically dynamic structure that is altered by the extent of intraductal hypertension, and support the hypothesis that paracellular permeability is the mechanism of the reflux of pancreatic juice. Received: November 10, 1999 / Accepted: April 28, 2000