The distribution of infection with <Emphasis Type="Italic">Propionibacterium acnes</Emphasis> is equal in patients with cervical and lumbar disc herniation

Background

Cervical and back pains are important clinical problems affecting human populations globally. It is suggested that Propionibacterium acnes (P. acnes) is associated with disc herniation. The aim of this study is to evaluate the distribution of P. acnes infection in the cervical and lumbar disc material obtained from patients with disc herniation.

Methods and material

A total of 145 patients with mean age of 45.21 ± 11.24 years who underwent micro-discectomy in cervical and lumbar regions were enrolled into the study. The samples were excited during the operation and then cultured in the anaerobic incubations. The cultured P. acnes were detected by 16S rRNA-based polymerase chain reaction.

Results

In this study, 145 patients including 25 cases with cervical and 120 cases with lumbar disc herniation were enrolled to the study. There was no significant difference in the age of male and female patients (p = 0.123). P. acnes infection was detected in nine patients (36%) with cervical disc herniation and 46 patients (38.3%) with lumbar disc herniation and no significant differences were reported in P. acnes presence according to the disc regions (p = 0.508.). Moreover, there was a significant difference in the presence of P. acnes infection according to the level of lumbar disc herniation (p = 0.028).

Conclusion

According to the results, the presence of P. acnes is equal in patients with cervical and lumbar disc herniation. There was a significant difference in the distribution of P. acnes infection according to level of lumbar disc herniation.

Level of Evidence

II

     

Arterial wall hypertrophy is ameliorated by α2-adrenergic receptor antagonist or aliskiren in kidneys of angiotensinogen-knockout mice

Background

Arterial hypertrophy and interstitial fibrosis are important characteristics in kidneys of angiotensinogen-knockout (Atg ^?/?) mice. In these mice, which exhibit polyuria and hypotension, sympathetic nerve signaling is estimated to be compensatorily hyperactive. Furthermore, transforming growth factor (TGF)-β1 is overexpressed in mice kidneys. To determine whether sympathetic nerve signaling and TGF-β1 exacerbate arterial hypertrophy and interstitial fibrosis, intervention studies of such signaling are required.

Methods

We performed renal denervation and administered the α2-adrenergic receptor (AR) antagonist, atipamezole, to Atg ^?/? mice. A renin inhibitor, aliskiren, which was preliminarily confirmed to reduce TGF-β1 gene expression in kidneys of the mice, was additionally administered to assess the effect on the arterial hypertrophy and interstitial fibrosis.

Results

Norepinephrine content in kidneys of Atg ^?/? mice was three times higher than in kidneys of wild-type mice. Interventions by renal denervation and atipamezole resulted in amelioration of the histological findings. Overexpression of TGF-β1 gene in kidneys of Atg ^?/? mice was altered in a manner linked to the histological findings. Surprisingly, aliskiren reduced α2-AR gene expression, interstitial fibrosis, and arterial hypertrophy in kidneys of Atg ^?/? mice, which lack renin substrate.

Conclusions

Alpha2-AR signaling is one of the causes of persistent renal arterial hypertrophy in Atg ^?/? mice. Aliskiren also angiotensinogen-independently reduces the extent of renal arterial hypertrophy, partly thorough downregulation of α2-ARs. Although renal arterial hypertrophy in Atg ^?/? mice appears to be of multifactorial origin, TGF-β1 may play a key role in the persistence of such hypertrophy.

     

A potentially crucial role of the <Emphasis Type="Italic">PKD1</Emphasis> C-terminal tail in renal prognosis

Background

Autosomal dominant polycystic disease (ADPKD) often results in renal failure. Recently, allelic influences of PKD1 mutation types on renal survival were extensively investigated. Here, we analyzed integrated influences of PKD1 mutation types and positions on renal survival.

Methods

We included 338 (82 pedigrees) and 72 (12 pedigrees) patients with PKD1 and PKD2 mutations, respectively, identified through comprehensive gene analysis of 101 probands with ADPKD. Genetic testing was performed using next-generation sequencing, long-range PCR, and multiplex ligation-dependent probe amplification. Pathogenic mutations were identified by a software package-integrated seven databases and provided access to five cloud-based computing systems.

Results

Mean renal survivals of carriers with PKD1 non-truncating-type mutations at positions upstream of G-protein-coupled receptor proteolytic site (GPS-upstream domain), transmembrane domain, or cytoplasmic C-terminal tail (CTT) domain were 70.2, 67.0, and 50.1 years, respectively (P < 0.0001); renal survival was shorter for mutation positions closer to CTT domain, suggesting its crucial role in renal prognosis. Furthermore, in truncating-type mutations, strong inactivation is anticipated on nucleotides downstream from the mutation site, implying CTT domain inactivation irrespective of mutation site. Shorter mean renal survival was found for PKD1 truncating-type than non-truncating-type mutation carriers (P = 0.0348); mean renal survival was not different between PKD1 3′- and 5′-region truncating-type mutation carriers (P = 0.4375), but was shorter in PKD1 3′-region than in 5′-region non-truncating-type mutation carriers (P = 0.0014). Variable strength of CTT domain inactivation might account for these results.

Conclusions

Aforementioned findings indicate that CTT domain’s crucial role in renal prognosis needs further investigation by larger studies (ClinicalTrials.gov; NCT02322385).

     

Urinary tract infection in infants caused by extended-spectrum beta-lactamase-producing <Emphasis Type="Italic">Escherichia coli</Emphasis>: comparison between urban and rural hospitals

Background

Community-acquired urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is an emerging problem. Compared with urban infants, rural infants may encounter different distributions of community-acquired resistant strains and various barriers to efficient management.

Methods

A retrospective survey and comparison was conducted for infants with UTI caused by ESBL-producing E. coli admitted to an urban hospital (n?=?111) and a rural hospital (n?=?48) in southern Taiwan from 2009 to 2012.

Results

Compared with 2009 and 2010, the total number of cases at both hospitals significantly increased in 2011 and 2012 (p?<?0.001). Compared with the rural patients, the urban patients were significantly younger, and they had fewer days of fever before and after admission, fewer presentations of poor activity and poor appetite, and a lower serum creatinine level. Most of the patients had no prior history of illness, and we could not identify any significant different risk factors for acquiring ESBL-producing E. coli, such as past antimicrobial use, hospitalization, UTI, and underlying renal diseases, between the urban and rural populations.

Conclusions

The increase in community-acquired UTI in infants caused by ESBL-producing E. coli was similar between the urban and rural populations. Our preliminary data suggest that the rural–urban disparities were probably related to easy access to health care by the urban population. ESBL complicates disease management, and the increase in the prevalence of ESBL producers is a major health concern and requires further healthy carrier and environmental surveillance.

     

Malaria und andere notfallmedizinische relevante Tropenerkrankungen mit dem Leitsymptom Fieber

Background

For people returning from the tropics, malaria is the most common cause of fever. Plasmodium falciparum causes the most common and most dangerous form of malaria, called malignant tertian malaria or falciparum malaria.

Method

Search and evaluation of the current literature.

Results and conclusion

Over 90?% of all malaria cases and malaria deaths occur in Africa, while the remaining cases are divided between India, Southeast Asia, Oceania, and Latin America. In Germany, between 513 and 613 cases of malaria have been reportet annually over the last 10 years according to the Robert Koch Institute, including 389–541 cases of potentially fatal falciparum malaria (Plasmodium falciparum). All fever patients who have been in to the tropics during the last 4 months must be tested for malaria. However, immigrants from tropical regions might develop malaria even years after their last trip to their former home country. Rapid diagnostic tests are now available—particularly for falciparum malaria. However, the occasional negative or false-positive results are possible. The treatment of malaria depends on the Plasmodium species, the clinical severity, and the region in which the infection was acquired.

     

Identification of 47 novel mutations in patients with Alport syndrome and thin basement membrane nephropathy

Background

Alport syndrome (ATS) is a progressive hereditary nephropathy characterized by hematuria and proteinuria. It can be associated with extrarenal manifestations. In contrast, thin basement membrane nephropathy (TBMN) is characterized by microscopic hematuria, is largely asymptomatic, and is rarely associated with proteinuria and end-stage renal disease. Mutations have been identified in the COL4A5 gene in ATS and in the COL4A3 and COL4A4 genes in ATS and TBMN. To date, more than 1000 different mutations in COL4A5, COL4A3, and COL4A4 are known.

Methods

In this study mutational analysis by exon sequencing and multiplex ligation-dependent probe amplification was performed in a large European cohort of families with ATS and TBMN.

Results

Molecular diagnostic testing of 216 individuals led to the detection of 47 novel mutations, thereby expanding the spectrum of known mutations causing ATS and TBMN by up to 10 and 6 %, respectively, depending on the database. Remarkably, a high number of ATS patients with only single mutations in COL4A3 and COL4A4 were identified. Additionally, three ATS patients presented with synonymous sequence variants that possible affect correct mRNA splicing, as suggested by in silico analysis.

Conclusions

The results of this study clearly broaden the genotypic spectrum of known mutations for ATS and TBMN, which will in turn now facilitate future studies into genotype–phenotype correlations. Further studies should also examine the significance of single heterozygous mutations in COL4A3 and COL4A4 and of synonymous sequence variants associated with ATS.

     

Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis

Background

Periprosthetic osteolysis is a major cause of aseptic loosening in joint arthroplasty. This study investigates the impact of CT (calcitonin) deficiency and CT substitution under in-vivo circumstances on particle-induced osteolysis in Calca -/- mice.

Methods

We used the murine calvarial osteolysis model based on ultra-high molecular weight polyethylene (UHMWPE) particles in 10 C57BL/6J wild-type (WT) mice and twenty Calca -/- mice. The mice were divided into six groups: WT without UHMWPE particles (Group 1), WT with UHMWPE particles (Group 2), Calca -/- mice without UHMWPE particles (Group 3), Calca -/- mice with UHMWPE particles (Group 4), Calca -/- mice without UHMWPE particles and calcitonin substitution (Group 5), and Calca -/- mice with UHMWPE particle implantation and calcitonin substitution (Group 6). Analytes were extracted from serum and urine. Bone resorption was measured by bone histomorphometry. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase (TRACP) + cells.

Results

Bone resorption was significantly increased in Calca -/- mice compared with their corresponding WT. The eroded surface in Calca -/- mice with particle implantation was reduced by 20.6% after CT substitution. Osteoclast numbers were significantly increased in Calca -/- mice after particle implantation. Serum OPG (osteoprotegerin) increased significantly after CT substitution.

Conclusions

As anticipated, Calca -/- mice show extensive osteolysis compared with wild-type mice, and CT substitution reduces particle-induced osteolysis.

     

Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice

Summary

Mice with osteogenesis imperfecta (+/oim), a disorder of bone fragility, were bred to mice with muscle over growth to test whether increasing muscle mass genetically would improve bone quality and strength. The results demonstrate that femora from mice carrying both mutations have greater mechanical integrity than their +/oim littermates.

Introduction

Osteogenesis imperfecta is a heritable connective tissue disorder due primarily to mutations in the type I collagen genes resulting in skeletal deformity and fragility. Currently, there is no cure, and therapeutic strategies encompass the use of antiresorptive pharmaceuticals and surgical bracing, with limited success and significant potential for adverse effects. Bone, a mechanosensing organ, can respond to high mechanical loads by increasing new bone formation and altering bone geometry to withstand increased forces. Skeletal muscle is a major source of physiological loading on bone, and bone strength is proportional to muscle mass.

Methods

To test the hypothesis that congenic increases in muscle mass in the osteogenesis imperfecta murine model mouse (oim) will improve their compromised bone quality and strength, heterozygous (+/oim) mice were bred to mice deficient in myostatin (+/mstn), a negative regulator of muscle growth. The resulting adult offspring were evaluated for hindlimb muscle mass, and bone microarchitecture, physiochemistry, and biomechanical integrity.

Results

+/oim mice deficient in myostatin (+/mstn +/oim) were generated and demonstrated that myostatin deficiency increased body weight, muscle mass, and biomechanical strength in +/mstn +/oim mice as compared to +/oim mice. Additionally, myostatin deficiency altered the physiochemical properties of the +/oim bone but did not alter bone remodeling.

Conclusions

Myostatin deficiency partially improved the reduced femoral bone biomechanical strength of adult +/oim mice by increasing muscle mass with concomitant improvements in bone microarchitecture and physiochemical properties.

     

Oxidative stress markers in type 2 diabetes patients with diabetic nephropathy

Background

Epidemiological studies show that 5–40 % of type 2 diabetes (T2DM) patients have diabetic nephropathy, and oxidative stress is one of several underlying mechanisms. We investigated associations between oxidative stress markers and severity of diabetic nephropathy.

Methods

Fifty-nine T2DM patients from the endocrinology outpatient department were included, and their levels of oxidative stress markers were measured. Three groups were determined by their urine albumin-to-creatinine ratio (UACR): group A (UACR < 30 mg/g, n = 22); group B (30 ≤ UACR < 300 mg/g, n = 22); and group C (UACR ≥ 300 mg/g, n = 15).

Results

Vitamin C levels correlated negatively and moderately with serum creatinine (γ = ?0.459, p < 0.001), urine albumin (γ _s = ?0.458, p = 0.001) and UACR (γ _s = ?0.408, p = 0.001), but only weakly with hydroxy-2-deoxyguanosine (8-OHdG) and estimated glomerular filtration rate (eGFR). Vitamin C levels decreased as 8-OHdG, serum creatinine, albumin and UACR increased. T2DM patients with more severe diabetic nephropathy had lower vitamin C levels.

Conclusion

Our results identified several oxidative stress markers that may be clinically important in diabetic nephropathy. Studies with larger sample sizes should be undertaken to confirm these findings.

     

Analysis of <Emphasis Type="Italic">PLA2R1</Emphasis> and <Emphasis Type="Italic">HLA</Emphasis>-<Emphasis Type="Italic">DQA1</Emphasis> sequence variants in Japanese patients with idiopathic and secondary membranous nephropathy

Background

Several recent studies in patients with idiopathic membranous nephropathy (iMN) from Western and Asian counties showed that some single nucleotide polymorphisms (SNPs) within the PLA2R1 and HLA-DQA1 genes are significantly associated with iMN. However, there is only 1 report on analysis of PLA2R1 and HLA regions in Japanese patients with iMN.

Methods

A total of 58 patients with iMN, 26 patients with secondary MN (sMN), and 50 patients with other diseases were enrolled. All patients were Japanese. We selected 6 SNPs within PLA2R1 and 1 SNP within HLA-DQA1, which were significantly associated with iMN in reported white European cohorts, and sequenced these exons using genomic DNA prepared from peripheral mononuclear cells from each patient. We then analyzed differences in PLA2R1 and HLA-DQA1 sequence variants among the 3 groups.

Results

Genotypic and allelic frequency distributions for 3 out of 6 SNPs within PLA2R1, rs3749117, rs35771982, and rs2715918 were significantly different between the iMN and control groups. Allelic frequency distributions for SNP rs2187668 within HLA-DQA1 were significantly different between the iMN and control groups. There were no correlations between PLA2R1 and HLA-DQA1 sequence variants and clinical parameters in patients with iMN. There were no significant differences in genotypic or allelic frequency distributions for examined SNPs between the sMN and control groups.

Conclusions

There are some differences in PLA2R1 SNP distributions between previously reported cohorts from other countries and our Japanese cohort of patients with iMN, while there is a significant association between SNP rs35771982 and iMN in most of reported cohorts.

     

Implementing a Program of <Emphasis Type="Italic">Talimogene laherparepvec</Emphasis>

Background

Oncolytic viruses are genetically engineered or naturally occurring viruses that selectively replicate in cancer cells without harming normal cells. Talimogene laherparepvec (Imlygic^®), the first oncolytic viral therapy approved for treatment of cancer, was approved for treatment of locally advanced melanoma in October 2015.

Purpose

As a biologic product, use of T. laherparepvec in the clinical setting requires pretreatment planning and a unique systematic approach to deliver the therapy. The processes we describe herein could be adopted by other centers that choose to prescribe T. laherparepvec.

Methods

We studied our clinical trial experience with T. laherparepvec before we embarked on using commercially available T. laherparepvec. We created a standard operating procedure (SOP) with multidisciplinary buy-in and oversight from leadership in Infection Control at our institution. We reflected on clinical cases and the actual procedures of administering T. laherparepvec to create the SOP.

Results

The preimplementation planning, patient selection, identification of lesions to treat, the actual procedure, and ongoing assessment of patients are described. Tumoral-related factors that lead to unique challenges are described.

Conclusions

A process to ensure safe and responsible implementation of a program to administer T. laherparepvec for treatment of melanoma may improve the quality of treatment for patients who suffer from advanced melanoma.

     

Which method is the most effective for preventing postoperative infection in spinal surgery?

Background

Several methods have been used to reduce the infection rate in spinal surgeries with instrumentation.

Purpose

Which method is the most effective for preventing postoperative infection?

Study design

Basic science, animal model.

Objective

In the present study, the efficiency of antibiotic prophylaxis, silver-plated screws, and local rifamycin application to the surgical site was investigated in an experimental animal model. Staphylococcus aureus was used as the pathogen.

Methods

Fifty 6-month-old female Wistar albino rats were used. The animals were randomly numbered and divided into five groups of ten rats each (Group 1, control group; Group 2, titanium screw and S. aureus inoculation; Group 3, titanium screw, 0.1 ml rifamycin application to the surgical area, and bacterial inoculation; Group 4, titanium screw, single preoperative dose of IM cefazolin, and bacterial inoculation; Group 5, silver-plated screw and bacterial inoculation). Titanium micro-screws were placed into the pedicles. The control group received a sterile isotonic solution, and the other four groups received bacterial suspensions containing S. aureus. The animals were killed 15 days later.

Results

Intensive S. aureus growth was observed in all tissue and screw samples from Group 2. The results for Group 3 were similar to those for Group 1, no growth was observed in the screw cultures. Intensive growth was observed in the five screw samples in Group 4 and in the eight samples in Group 5.

Conclusion

Our study suggests that rifamycin application to the surgical area in spinal operations with instrumentation is an effective method to prevent S. aureus infections.

     

Modic changes in the adjacent vertebrae due to disc material infection with <Emphasis Type="Italic">Propionibacterium acnes</Emphasis> in patients with lumbar disc herniation

Introduction

Modic changes (MCs) in vertebral bones are induced by two mechanisms of mechanical factors and infection. As Propionibacterium acnes (P. acnes) have been reported to be associated with LBP. The aim of this study is to evaluate the MCs in patients with disc herniation and positive for P. acnes.

Methods and material

A total of 120 patients with disc herniation surgery were enrolled into the study. The samples were excised during discectomy and then cultured in both anaerobic and aerobic incubations. Gram staining was employed for investigation of all colonies. The cultured P. acnes were detected by 16S rRNA-based polymerase chain reaction (PCR). MCs of baseline MRI were evaluated.

Results

In this study, 120 subjects (69 male and 51 female) with mean age of 43.15 ± 12.62 years were investigated. Sixty disc samples and eight muscle samples were positive for microorganisms. Moreover, 16S rDNA gene was identified in 46 (38.3%) disc samples. Moreover, 36/46 patients with P. acnes in their sample had MCs.

Conclusion

According to the results and presence of 36/46 MCs in patients with lumbar disc herniation, positive for P. acnes suggests that P. acnes can lead to edema on the vertebrae endplates near to infected area.

     

Long-term treatment with EGFR inhibitor erlotinib attenuates renal inflammatory cytokines but not nephropathy in Alport syndrome mouse model

Background

Alport syndrome (AS) is a hereditary kidney disease caused by mutation of type IV collagen. Loss of collagen network induces collapse of glomerular basement membrane (GBM) structure. The previous studies showed that upregulation of some tyrosine kinase receptors signaling accompanied GBM disorder in AS mouse model. EGFR signaling is one of the well-known receptor kinase signaling that is involved in glomerular diseases. However, whether EGFR signaling is relevant to AS progression is still uninvestigated. Here, we determined the involvement of EGFR in AS and the effect of suppressing EGFR signaling by erlotinib treatment on AS progression.

Methods

Phosphorylated EGFR expression was investigated by Western blotting analysis and immunostaining of kidney tissues of Col4a5 mutant mice (a mouse model of X-linked AS). To check the effect of blocking EGFR signaling in AS, we administered erlotinib to AS mice once a day (10 mg/kg/day) orally for 18 weeks. Renal function parameters (proteinuria, serum creatinine, and BUN) and renal histology were assessed, and the gene expressions of inflammatory cytokines were analyzed in renal tissues.

Results

Phosphorylated EGFR expression was upregulated in AS mice kidney tissues. Erlotinib slightly reduced the urinary protein and suppressed the expression of renal injury markers (Lcn2, Lysozyme) and inflammatory cytokines (Il-6, Il-1β and KC). Erlotinib did not improve renal pathology, such as glomerular sclerosis and fibrosis.

Conclusion

These findings suggest that EGFR signaling is upregulated in kidney, but although inhibiting this signaling pathway suppressed renal inflammatory cytokines, it did not ameliorate renal dysfunction in AS mouse model.

     

Impact of high mortality in incident dialysis patients due to hypertensive nephrosclerosis: a multicenter prospective cohort study in Aichi,Japan

Introduction

An increasing number of patients worldwide require dialysis as a result of hypertensive nephrosclerosis (HTN). However, in Japan, mortality in patients with end-stage renal disease (ESRD) has not been well by primary kidney disease including HTN and diabetic nephropathy (DN). Hence, we examined the differences in mortality among the primary kidney diseases of incident dialysis patients.

Methods

The study was a multicenter prospective cohort analysis including 1520 incident dialysis patients in Aichi prefecture, Japan. We classified patients into three groups according to the primary kidney disease [i.e., a HTN group, n?=?384, a DN group n?=?658, and a chronic glomerulonephritis (CGN) group, n?=?224]. In addition, we classified patients into the HTN group and the DN group using propensity score matching. We compared outcomes including all-cause and infection-related mortality.

Results

The mortality rates of the HTN, the DN, and the CGN group, were 135.9, 64.2, and 34.8 per 1000 patient years, respectively. All-cause mortality and infection-related mortality rates in the HTN group were as high as those in the DN group after adjustment for age, gender, history of cardiovascular disease, and estimated glomerular filtration rate. No significant difference of all-cause mortality was observed after propensity score matching between the two groups (Logrank test: p?=?0.523).

Conclusions

The present study was Japan’s first large-scale prospective cohort to demonstrate that HTN is the second most common cause of ESRD. In addition, the prognosis of patients with HTN was as poor as that of patients with DN.

     

<Emphasis Type="Italic">Ureaplasma urealyticum</Emphasis> and <Emphasis Type="Italic">Mycoplasma hominis</Emphasis> infections and semen quality in 19,098 infertile men in China

Objective

This study aimed to determine the incidence of Ureaplasma urealyticum and Mycoplasma hominis infections in infertile and fertile men and to investigate their effects on the semen quality. The study also aimed to analyze the drug susceptibility of UU and MH to provide guidance for reasonable antibiotic use.

Methods

A total of 19,098 semen specimens were obtained from infertile men at our hospital from January to December 2014. In addition to these specimens, 3368 semen specimens of sperm were obtained from donors at the sperm bank of our hospital from January 2011 to December 2014. Semen analysis was performed using the methods outlined by the World Health Organization.

Results

The prevalence of UU and MH significantly differed between infertile and fertile men. The mean progressive motility, total motility, and normal forms in the semen samples of infertile males positive for UU significantly differed from the corresponding values of uninfected men. However, the semen parameters did not differ between MH-infected and uninfected men. In the antibiotic sensitivity test, UU, MH, and UU mixed with MH were all found susceptible to doxycycline and josamycin with drug resistance rates below 6 %, but both species were highly resistant to ciprofloxacin.

Conclusions

Clinical assessment revealed a significant relationship between UU and MH infections and male infertility. UU was found to significantly affect sperm quality, but this was not the case with MH. Doxycycline and josamycin should be preferred for clinically treating UU and MH infections.

     

ISSLS PRIZE IN CLINICAL SCIENCE 2017: Is infection the possible initiator of disc disease? An insight from proteomic analysis

Study design

Proteomic and 16S rDNA analysis of disc tissues obtained in vivo.

Objective

To address the controversy of infection as an aetiology for disc disorders through protein profiling.

Summary of background data

There is raging controversy over the presence of bacteria in human lumbar discs in vivo, and if they represent contamination or infection. Proteomics can provide valuable insight by identifying proteins signifying bacterial presence and, also host defence response proteins (HDRPs), which will confirm infection.

Methods

22 discs (15-disc herniations (DH), 5-degenerate (DD), 2-normal in MRI (NM) were harvested intraoperatively and immediately snap frozen. Samples were pooled into three groups and proteins extracted were analysed with liquid chromatography-tandem mass spectrometry (LC–MS/MS). Post identification, data analysis was performed using Uniprotdb, Pantherdb, Proteome discoverer and STRING network. Authentication for bacterial presence was performed by PCR amplification of 16S rDNA.

Results

LC–MS/MS analysis using Orbitrap showed 1103 proteins in DH group, compared to 394 in NM and 564 in DD. 73 bacterial specific proteins were identified (56 specific for Propionibacterium acnes; 17 for Staphylococcus epidermidis). In addition, 67 infection-specific HDRPs, unique or upregulated, such as Defensin, Lysozyme, Dermcidin, Cathepsin-G, Prolactin-Induced Protein, and Phospholipase-A2, were identified confirming presence of infection. Species-specific primers for P. acnes exhibited amplicons at 946 bp (16S rDNA) and 515 bp (Lipase) confirming presence of P. acnes in both NM discs, 11 of 15 DH discs, and all five DD discs. Bioinformatic search for protein–protein interactions (STRING) documented 169 proteins with close interactions (protein clustering co-efficient 0.7) between host response and degenerative proteins implying that infection may initiate degradation through Ubiquitin C.

Conclusion

Our study demonstrates bacterial specific proteins and host defence proteins to infection which strengthen the hypothesis of infection as a possible initiator of disc disease. These results can lead to a paradigm shift in our understanding and management of disc disorders.

     

Clinical and genetic characteristics of Japanese nephronophthisis patients

Background

Nephronophthisis (NPH) accounts for 4–5 % of end-stage renal disease occurring in childhood.

Method

We investigated the clinical context and characteristics of renal and extrarenal symptoms, as well as the NPHP genes, in 35 Japanese patients with clinical and histologic features suggesting NPH.

Results

NPH occurred fairly uniformly throughout Japan irrespective of region or gender. In three families, NPH affected siblings. The median age of patients was 12.5 years. Renal abnormalities attributable to NPH discovered through mass screening, such as urine tests in school. However, NPH accounted for less than 50 % of children with abnormal findings, including incidentally discovered renal dysfunction during evaluation of extrarenal symptoms or during routine check-ups. Typical extrarenal manifestations leaded to discovery including anemia and delayed physical development. The urine often showed low gravity specific density and low molecular weight proteinuria. Frequent renal histologic findings included cystic dilation of tubules, mainly in the medulla, and irregularity of tubular basement membranes. Genetically abnormalities of NPHP1 were not common, with large deletions frequently noted. Compound heterozygotes showing single abnormalities in each of NPHP1, NPHP3, and NPHP4 were observed.

Conclusions

Our findings resemble those reported in Western populations.

     

Suburethral sling procedures in the United States: complications,readmission, and reoperation

Introduction and hypothesis

Hospital readmission is increasingly used as a measure of quality care. Our objective was to evaluate the rate of readmission and associated factors in women undergoing suburethral sling placement in the USA.

Methods

This is a cohort study of suburethral sling procedures performed in the USA from 2012 to 2014 using the American College of Surgeons’ National Surgical Quality Improvement Program database. The database was queried for suburethral sling procedures. Records were excluded if concomitant surgery had been performed. Patient and surgical characteristics were evaluated for association with readmission using Chi-squared test for categorical variables and Student’s t test for continuous variables. All results yielding p?<?0.05 were deemed statistically significant.

Results

A total of 7,117 suburethral sling procedures were identified. There were 83 (1.16%) hospital readmissions. Those who were readmitted tended to be older (p?=?0.011), non-Hispanic (p?=?0.04), smokers (p?<?0.001), and have an American Society of Anesthesiologists Physical Status Classification System score of 3 or 4 (p?=?0.001). A history of bleeding disorder (p?<?0.001), congestive heart failure (p?<?0.001), or chronic obstructive pulmonary disease (p?<?0.001) was associated with readmission. Fifty-four (0.75%) patients underwent reoperation within 30 days of suburethral sling placement. The most common reoperation procedure was sling excision (20 patients). The most common complication was urinary tract infection, which occurred in 189 patients (2.7%).

Conclusions

Suburethral sling placement is a safe procedure with a low rate of readmissions, reoperations, and complications. Consistent with other types of surgery, infection is the most common post-operative complication.