Chronic Toxoplasma gondii Infection Modulates Hearing Ability across the Adult Life Span.

While several studies have shown associations between hearing disorders and congenital toxoplasmosis, the present study investigated the impact of chronic, latent Toxoplasma gondii (T. gondii) infection on hearing loss. We used a regression analysis to explore whether latent T. gondii infection modulates changes in hearing thresholds over an age range from 20 to 70 years. We analyzed audiometric data of 162 T. gondii IgG-positive and 430 T. gondii-negative participants, collected in the Dortmund Vital Study (DVS, ClinicalTrials.gov Identifier: NCT05155397), a prospective study on healthy cognitive aging. The regression analysis indicated that latent toxoplasmosis was associated with an accelerated development in hearing loss over the observed age range. Hearing loss was less frequent in IgG-positive than in IgG-negative participants up to the age of about 40 for a low (0.125-1 kHz)-frequency range. For high (2-8 kHz) frequencies, this pattern reversed for ages above 65 years. We discuss these findings on hearing function in the context of a recently proposed model, suggesting that latent toxoplasmosis can differentially affect brain functions across a lifespan.

Bladder cancer course, four genetic high-risk variants, and histopathological findings.

Urinary bladder cancer, a smoking and occupation related disease, was subject of several genome-wide association studies (GWAS). However, studies on the course of the disease based on GWAS findings differentiating between muscle invasive bladder cancer (MIBC) and non-muscle invasive bladder cancer (NMIBC) are rare. Thus we investigated 4 single nucleotide polymorphisms (SNPs) detected in GWAS, related to the genes coding for TACC3 (transforming, acidic coiled-coil containing protein 3), for FGFR3 (fibroblast growth factor receptor 3), for PSCA (prostate stem cell antigen) and the genes coding for CBX6 (chromobox homolog 6) and APOBEC3A (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A). This study is based on 712 bladder cancer patients and 875 controls from 3 different case control studies in Germany. The 4 SNPs of interest (PSCA rs2294008 and rs2978974, FGFR3-TACC3 rs798766, and CBX6-APOBEC3A rs1014971) were determined by real-time polymerase chain reaction. The distribution of the 4 SNPs does not vary significantly between cases and controls in the entire study group and in the 3 local subgroups, including two former highly industrialized areas and a region without such history. Also, no significant differences in the bladder cancer subgroups of MIBC and NMIBC were observed. The 4 investigated SNPs do not noticeably contribute differently to the bladder cancer risk for the bladder cancer subgroups of MIBC and NMIBC.

Does physical fitness affect cognitive functions differently across adulthood? An advantage of being older.

Introduction: There is a large interindividual variability in cognitive functioning with increasing age due to biological and lifestyle factors. One of the most important lifestyle factors is the level of physical fitness (PF). The link between PF and brain activity is widely accepted but the specificity of cognitive functions affected by physical fitness across the adult lifespan is less understood. The present study aims to clarify whether PF is basically related to cognition and general intelligence in healthy adults, and whether higher levels of PF are associated with better performance in the same or different cognitive functions at different ages. Methods: A sample of 490 participants (20-70 years) was analyzed to examine this relationship. Later, the sample was split half into the young to middle-aged group (YM; 20-45 years; n = 254), and the middleaged to older group (MO; 46-70 years; n = 236). PF was measured by a quotient of maximum power in a bicycle ergometry test PWC-130 divided by body weight (W/kg), which was supported by a self-reported level of PF. Cognitive performance was evaluated by standardized neuropsychological test batteries. Results: Regression models showed a relationship between PF and general intelligence (g-factor) and its subcomponents extracted using structural equation modeling (SEM) in the entire sample. This association was moderated by age, which also moderated some specific cognitive domains such as attention, logical reasoning, and interference processing. After splitting the sample into two age groups, a significant relationship was found between cognitive status, as assessed by the Mini Mental State Examination (MMSE), and PF in both age groups. However, apart from cognitive failures in daily life (CFQ), no other association between PF and specific cognitive functions was found in the YM group. In contrast, several positive associations were observed in the MO group, such as with selective attention, verbal memory, working memory, logical reasoning, and interference processing. Discussion: These findings show that middle-aged to older adults benefit more from PF than younger to middle-aged adults. The results are discussed in terms of the neurobiological mechanisms underlying the cognitive effects of PF across the lifespan. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT05155397, identifier NCT05155397.

Special surgical aspects of radical cystectomy in spinal cord injury patients with bladder cancer.

PURPOSE: Radical cystectomy in people with spinal cord injury (SCI) provides numerous additional difficulties, compared to able-bodied people. Therefore, it is important to obtain information from an experienced team about optimally managing these patients. METHODS: Surgical procedures, based on the experience of 12 radical cystectomies in SCI patients with bladder cancer between January 1st, 2001, and December 31st, 2020, were recorded and the operative and perioperative clinical data were evaluated. Surgery was performed in a high-volume center by the surgeon most experienced in radical cystectomies, assisted by the neuro-urologist, involved in the care of the patient from the spinal cord center. Furthermore, a checklist based on the experience of the surgeon and the assisting neuro-urologist was developed. RESULTS: SCI patients mostly suffered from an advanced disease and were always operated by the same team. The hospital stays ranged from 23 to 134 days (median 42 days). Four of the patients suffered from a postoperative paralytic ileus. Otherwise, both the operation time and the intraoperative blood loss as well as intraoperative and postoperative complications were basically comparable with those in able-bodied patients. The special features of radical cystectomy in SCI bladder cancer patients are described. Furthermore, a checklist addressing preoperative red flags, intra-operative challenges and post-operative challenges is presented. CONCLUSION: Radical cystectomy in SCI patients should be performed in a high-volume department by the most experienced surgical team. The inclusion of the urologist caring for the patient from the spinal cord injury center is highly recommended.

[Urinary Bladder Cancer as a Long-term Sequela of Spinal Cord Injury - Relevance to Practice]. / Harnblasentumoren als Langzeitfolge einer Querschnittlähmung ­ Bedeutung für die Praxis.

Urinary bladder cancer is the second most common tumour disease after lung cancer leading to death in people with a spinal cord injury. This paper provides a comprehensive overview of the differences relevant to urologists between urinary bladder tumours in this population compared with urinary bladder tumours in the general population.People with a spinal cord injury are 1 to 2 decades younger on average at the time of tumour diagnosis than patients without a spinal cord injury. Histopathologic findings at the initial diagnosis of urinary bladder cancer in people with a spinal cord injury are much less favourable than for urinary bladder cancers in the general population. Muscle-invasive tumours and tumours with poor differentiation are much more common, and the proportion of squamous cell carcinomas is significantly higher. The incidence rises after more than 10 years of paralysis. Urinary bladder cancer mortality is significantly elevated and increases with the duration of paralysis. In diagnostic procedures and, in particular, in radical cystectomy, clinically important features have to be considered. For example, urodynamic examinations or cystoscopy may trigger autonomic dysreflexia with hypertensive crises and the risk of life-threatening bradycardia.In the case of radical cystectomy, frequent adhesions and callosities of the urinary bladder, among other things, must be taken into account intraoperatively. Severe paralysis, prolonged intestinal atony and other conditions are frequently observed after the surgical procedure due to neurogenic bowel dysfunction. Correct positioning of the patient immediately after surgery to avoid decubitus and to support breathing, as well as bowel management specific to spinal cord injury, must be strictly observed.Other special features of paraplegic patients with urinary bladder cancer that should also be considered in clinical practice, as well as considerations for screening for urinary bladder tumors, are presented in the article.

Squamous cell carcinoma of the renal pelvis in a patient with long-term spinal cord injury-a case report.

INTRODUCTION: For individuals with spinal cord injury/disease (SCI/D) the risk of developing a stone in the upper urinary tract is up to six times higher than in the able-bodied population. Upper urinary tract carcinomas, in general, are rare and account for only 5-10% of all urinary tract carcinomas. It is believed that chronic upper urinary tract irritation caused by e.g., kidney stones or recurrent upper urinary tract infections may be associated with an increased risk of renal squamous cell carcinoma (RSCC). CASE PRESENTATION: We report on a 64-year-old male who suffered a spinal cord injury in 1981 resulting in a complete sensory and motor impairment below T6, AIS A. Recurrent left-sided kidney stone disease had to be treated repeatedly from 1984 onwards. Despite repeated surgical attempts, it was ultimately not possible to achieve stone clearance in the long term. Within the concept of life-long surveillance of SCI/D, the patient was examined regularly, including ultrasound examinations of the kidneys. Six months after the last control examination, the patient was admitted to our hospital with a locally advanced tumor of the left kidney, so that only the option of palliative treatment remained. Histologically an RSCC was found. DISCUSSION: As people with SCI/D have a higher risk of developing kidney stones, it is of utmost importance to check regularly for stone disease and, if necessary, treat with the aim of long-term stone clearance in order to protect renal function and to avert potentially malignant changes at an early stage.

Bladder management, severity of injury and period of latency: a descriptive study on 135 patients with spinal cord injury and bladder cancer.

STUDY DESIGN: Longitudinal study. OBJECTIVES: To describe the severity of spinal cord injury/disease (SCI/D), type and management of neurogenic lower urinary tract dysfunction, tumor characteristics, and bladder cancer latency period in SCI/D patients. SETTING: Spinal cord injury centers in Germany, Austria, and Switzerland. METHODS: Data of SCI/D patients diagnosed with bladder cancer were collected between Jan 2012-Dec 2019 in the course of annual surveys in the neuro-urological departments of all 28 centers. Demographic and paralysis-specific data, data on the type and management of neurogenic lower urinary tract dysfunction, and histopathological tumor characteristics were collected. RESULTS: Regarding histopathological tumor characteristics, no significant differences were found in 135 individuals with SCI/D when stratified for bladder management without chronic catheterization, SCI/D severity, and ASIA classification. The mean latency period between the onset of SCI/D and the diagnosis of bladder cancer was significantly longer in patients with catheter-free emptying methods compared to patients with intermittent catheterization, and in patients with LMNL (Lower Motor Neuron Lesion) compared to patients with UMNL (Upper Motor Neuron Lesion). CONCLUSIONS: Urinary bladder carcinomas are late events in the long-term course of SCI/D. Follow-up and approaches to screening must therefore be intensified with increasing duration of long-term SCI.

Urinary bladder cancer as a late sequela of traumatic spinal cord injury.

BACKGROUND: Traumatic spinal cord injury (SCI) is also a combat-related injury that is increasing in modern warfare. The aim of this work is to inform medical experts regarding the different course of bladder cancer in able-bodied patients compared with SCI patients based on the latest medical scientific knowledge, and to present decision-making aids for the assessment of bladder cancer as a late sequela of traumatic SCI. METHODS: A study conducted between January 1998 and December 2019 in the BG Trauma Hospital Hamburg formed the basis for the decision-making aids. Urinary bladder cancer was diagnosed in 40 out of 7396 treated outpatient and inpatient SCI patients. General patient information, latency period, age at initial diagnosis, type of bladder management and survival of SCI patients with bladder cancer were collected and analysed. T category, grading and tumour entity in these patients were compared with those in the general population. Relevant bladder cancer risk factors in SCI patients were analysed. Furthermore, relevant published literature was taken into consideration. RESULTS: Initial diagnosis of urinary bladder cancer in SCI patients occurs at a mean age of 56.4 years (SD ± 10.7 years), i.e., approximately 20 years earlier as compared with the general population. These bladder cancers are significantly more frequently muscle invasive (i.e., T category ≥ T2) and present a higher grade at initial diagnosis. Furthermore, SCI patients show a significantly higher proportion of the more aggressive squamous cell carcinoma than that of the general population in areas not endemic for the tropical disease schistosomiasis. Consequently, the survival time is extremely unfavourable. A very important finding, for practical reasons is that, in the Hamburg study as well as in the literature, urinary bladder cancer is more frequently observed after 10 years or more of SCI. Based on these findings, a matrix was compiled where the various influencing factors, either for or against the recognition of an association between SCI and urinary bladder cancer, were weighted according to their relevance. CONCLUSIONS: The results showed that urinary bladder cancer in SCI patients differs considerably from that in able-bodied patients. The presented algorithm is an important aid in everyday clinical practice for assessing the correlation between SCI and bladder cancer.

Incidental bladder cancer at initial urological workup of spinal cord injury patients.

STUDY DESIGN: Retrospective descriptive study. OBJECTIVES: To compare histopathological findings and the long-term course of SCI patients with bladder cancer found incidentally at the initial urological workup to those diagnosed with bladder cancer many years after the onset of SCI. SETTING: Spinal cord injury center in Germany. METHODS: Data and follow-up of consecutive in- and out-patients with SCI admitted at a tertiary spinal cord injury center between January 1, 1998 and December 31, 2018 were screened retrospectively. All patients with acquired SCI were evaluated for pathological findings in the urinary bladder present at the time of SCI on the initial urological workup. Data of 37 long-term SCI patients from the same center with diagnosed bladder cancer and data of the general German population served as reference groups. Descriptive statistics were applied. RESULTS: In total, four patients with bladder cancer at initial urological workup were assessed. They all had non-muscle invasive bladder cancer. Two of the patients were cystectomized 34 and 106 months after first bladder cancer diagnosis, due to relapsing tumor and progressive renal failure, respectively. In both cases no tumor was found in the resected bladder. All four patients are currently alive with no tumor and a mean follow-up of 105 months. CONCLUSIONS: In incidental bladder cancer observed at the initial urological workup after acquired SCI, the duration of SCI, at least in the first 5 years, does not noticeably contribute to a poor prognosis, i.e., progression to muscle invasive bladder cancer (≥T2) or a higher grading (G3).

Traumatic spinal cord injury confers bladder cancer risk to patients managed without permanent urinary catheterization: lessons from a comparison of clinical data with the national database.

PURPOSE: Life expectancy for people with traumatic spinal cord injury (SCI) is increasing due to advances in treatment methods and in neuro-urology. Thus, developing urinary bladder cancer (UBC) is gaining importance. METHODS: Single-centre retrospective evaluation of consecutive in- and out-patient data with spinal cord injury between January 1st, 1998 and December 31st, 2018 was carried out and data were compared with UBC data of the German population from the German Centre for Cancer Registry Data at Robert Koch Institute. RESULTS: A total of 37 (4 female, 33 male) out of 7004 patients with SCI were diagnosed with histologically proven UBC (median follow-up 85 months). Median age at UBC diagnosis was 54.0 years (general population: 74 years). The SCI patients had significantly (p < 0.0001, each) more frequent muscle-invasive tumors (81% ≥ T2) and unfavorable grading (76% G3), compared to the general population. Median survival was 13 months for transitional cell carcinoma (n = 31) and 4 months for squamous cell carcinoma (n = 5) (p = 0.0039), resp. The median survival of the 24 cystectomized patients was 15.0 months. Long-term suprapubic or indwelling catheterization was found in only eight patients for a total of only 5.09% (median 15.5 months) of the latency of all patients. No significant differences for T category and grading were observed between the bladder emptying methods intermittent catheterisation and catheter-free voiding. CONCLUSION: The results indicate that in patients with SCI bladder management even without permanent catheterization represents a considerable risk for the development of UBC.

[Spinal cord injury with neurogenic lower urinary tract dysfunction as a potential risk factor for bladder carcinoma]. / Querschnittlähmung mit neurogener Harnblasenfunktionsstörung als möglicher Risikofaktor für Harnblasen-Karzinome.

INTRODUCTION AND OBJECTIVES: Life expectancy for people with spinal cord injury/disease (SCI/D) is increasing, due to modern advances in treatment methods and in neuro-urology. However, with the increased life expectancy the risk of developing urinary bladder cancer is gaining importance. How is this patient group different from the general population? METHODS: Single-centre retrospective evaluation of consecutive patient data with spinal cord injury and proven urinary bladder cancer. RESULTS: Between January 1st 1998 and March 31st 2017, 32 (3 female, 29 male) out of a total of 6432 patients with SCI/D were diagnosed with bladder cancer.The average age at bladder cancer diagnosis was 54.5 years, which is well below the average for bladder cancer cases in the general population (male: 74, female: 75).Twenty-seven patients suffered from urodynamically confirmed neurogenic detrusor overactivity, while five patients (all male) had detrusor acontractility.The median latency period between the onset of SCI/D and tumor diagnosis was 29.5 years. Temporary indwelling catheterisation was found in four patients for only 1.61 % of the overall latency period of all patients.The majority of the patients (n = 27) had transitional cell carcinoma, while five had squamous cell carcinoma. Of the 32 patients, 25 (78 %) had muscle invasive bladder cancer at ≥ T2 at the time of diagnosis. Regarding tumour grading, 23 out of 32 patients showed a histologically poorly differentiated G3 carcinoma; two patients each had G2 and G1 tumours repectively (no information on tumour grading was available in five patients).The median survival for all patients was 11.5 months. The prognosis of patients with squamous cell carcinoma was even worse; 4 out of 5 died within 7 months (median 4 months). CONCLUSIONS: The significantly younger age at onset and the frequency of invasive, poorly differentiated tumour at diagnosis indicate that SCI/D influences both bladder cancer risk and prognosis significantly. The latency period between paralysis and tumour disease seems to be a decisive risk parameter.The type of neurogenic bladder dysfunction and the form of bladder drainage do not appear to influence the risk. Long-term indwelling catheter drainage played only a minor role in the investigated patients.Early detection of bladder cancer in patients with spinal cord injury remains a challenge.

Urinary bladder cancer risk factors in an area of former coal, iron, and steel industries in Germany.

This study was performed to investigate the frequency of bladder cancer in patients with an occupational history such as underground hard coal mining and/or painting after the structural change in the local industry. A total of 206 patients with bladder cancer and 207 controls were enlisted regarding occupational and nonoccupational bladder cancer risk factors by questionnaire. The phase II enzymes N-acetyltransferase 2 (NAT2), glutathione S-transferases M1 (GSTM1), and T1 (GSTT1) and the single nucleotide polymorphism (SNP) rs11892031[A/C] reported to be associated with bladder cancer in genome-wide association studies were genotyped. The bladder cancer risk in varnishers and underground hard coal miners was increased as previously shown in a study in this area performed in the 1980s. The occupation of a car mechanic was associated with a significantly elevated bladder cancer risk and higher in the case of underground hard coal miners even though the mine was closed in 1987. The frequency of GSTM1 negative genotype was comparable in cases and controls (53% versus 54%). In the case of NAT2, the slow NAT2 genotype was more frequent (62% versus 58%) and ultra-slow NAT2 genotype (NAT2*6A and/or *7B alleles only) was 23% versus 15%. An occupational history of a varnisher or an underground hard coal miner remains a risk factor for bladder cancer occurrence. Data indicate that in the case of bladder cancer, GSTM1 is a susceptibility factor related to environmental and/or occupational exposure.

Clinical characteristics of bladder cancer in patients with spinal cord injury: the experience from a single centre.

INTRODUCTION: Life expectancy for people with spinal cord injury has shown a marked increase due to modern advances in treatment methods and in neuro-urology. However, since life expectancy of people with paralysis increases, the risk of developing of urinary bladder cancer is gaining importance. MATERIALS AND METHODS: Single-centre retrospective evaluation of patient data with spinal cord injuries and proven urinary bladder cancer and summary of the literature. RESULTS: Between 1998 and 2014, 24 (3 female, 21 male) out of a total of 6599 patients with spinal cord injury were diagnosed with bladder cancer. The average age at bladder cancer diagnosis was 57.67 years, which is well below the average for bladder cancer cases in the general population (male: 73, female: 77). All but one patient had a latency period between the onset of the spinal paralysis and tumour diagnosis of more than 10 years. The median latency was 29.83 years. The median survival for these patients was 11.5 months. Of the 24 patients, 19 (79%) had muscle invasive bladder cancer at ≥T2 at the time of diagnosis. The type of neurogenic bladder (neurogenic detrusor overactivity or acontractility) and the form of bladder drainage do not appear to influence the risk. Long-term indwelling catheter drainage played only a minor role in the investigated patients. CONCLUSIONS: The significantly younger age at onset and the frequency of invasive tumours at diagnosis indicate that spinal cord injury influences bladder cancer risk and prognosis as well. Early detection of bladder cancer in patients with spinal cord injury remains a challenge.