The association between BCG treatment in patients with bladder cancer and subsequent risk of developing Alzheimer and other dementia.-A Swedish nationwide cohort study from 1997 to 2019.

BACKGROUND: Alzheimer's disease (AD) affects 50 million people worldwide. The immune system plays a major role in the pathogenesis of AD. Several retrospective analyses have reported a decreased risk of AD and other dementias in bladder cancer patients treated with immunotherapy in the form of Bacillus Calmette-Guerin (BCG) bladder instillations. We tested this hypothesis in a Swedish population-based prospective cohort of patients with non-muscle invasive bladder cancer (NMIBC). METHODS AND FINDINGS: We utilized the BladderBaSe 2.0 database, which contains tumor-specific, health-related, and socio-demographic information for patients diagnosed with NMIBC between 1997 and 2019. The database also includes a matched comparison cohort sampled from the general population, consisting of individuals free from urinary tract cancer at the time of the index case's diagnosis. Five controls were randomly selected for each index case without replacement on the date of the index case's diagnosis. Our inclusion criteria identified participants diagnosed with NMIBC who had received BCG as primary treatment, along with their corresponding comparison cohort. We excluded those diagnosed with dementia before or within 6 months of NMIBC diagnosis. To compare the NMIBC cohort with their matched comparison cohort, we used a stratified Cox model, treating each case with its controls as a stratum. We identified 38,934 patients in the NMIBC cohort, with 6,496 receiving BCG after primary diagnosis (cases). AD/dementia was diagnosed during follow-up in 6.1% of cases and 7.4% of controls. Cases had a slightly lower risk of dementia than controls, with a hazard ratio (HR) of 0.88 (95% confidence interval [CI] 0.780-0.991), and a HR of 0.89 (CI 0.703-1.119) for AD. Subgroup analysis for dementia showed that age over 75 years had an HR of 0.73 (CI 0.616-0.863), and female gender had an HR of 0.73 (CI 0.552-0.971). The associations were similar for AD specifically, but not statistically significant. Similar to previous studies, we analyzed bladder cancer patients treated with and without BCG therapy. Multivariate Cox analysis indicated that those treated with BCG had a lower risk of dementia (HR 0.81, 95% CI 0.71-0.92), and an HR of 0.98 (95% CI 0.75-1.27) for AD specifically. High age was a significant risk modifier; the HR was 3.8 (CI 3.44-4.11) for dementia and 3.1 (CI 2.59-3.73) for AD. Even patients not receiving BCG had a significantly lower risk for AD than controls (HR 0.86, CI 0.77-0.96). CONCLUSIONS: This study observed a marginally decreased risk of developing AD/dementia associated with earlier intravesical BCG treatment in NMIBC patients. This small benefit was most pronounced in those with high age and female gender. The disparity from previous highly positive studies underscores the importance of using an appropriate control cohort.

Improved long-term outcome of patients with non-muscle invasive, low and intermediate risk bladder cancer between 1997 and 2014; a Swedish population-based study.

OBJECTIVE: The most common form of urinary bladder cancer is the low and intermediate risk categories of stage Ta. This patient group has a high recurrence rate, but progression is rare. The aim of this study was to investigate recurrence and survival in a large population-based setting, with respect to possible prognostic factors and during different time periods. PATIENTS AND METHODS: BladderBaSe is a database which links information from the Swedish National Register of Urinary Bladder Cancer with national healthcare and demographic registers. Between 1997 and 2014, 16,599 were diagnosed with low and intermediate risk of Ta cancer in Sweden. The times to recurrence and cancer-specific death were analysed concerning the differences in age, gender, grade, region and hospital type. For temporal analysis, we divided the material into 6-year periods. RESULTS: The mean age was 70 years and 75% were males. Low risk according to grade constituted 56%, whilst 44% had intermediate risk. With a median follow-up time of 63 months the recurrence rates were 47% and 59% for the respective categories and overall 52%. The rate was similar between the first two time periods, but became substantially lower in the most recent period. Five percent of patients died of the disease and risk category was the main prognostic variable. CONCLUSIONS: The risk of recurrence decreased in the last time period. Risk category based on grade was the most important prognostic indicator for outcome.

Radical cystectomy compared to intravesical BCG immunotherapy for high-risk non-muscle invasive bladder cancer - is there a long-term survival difference? A Swedish nationwide analysis.

OBJECTIVES: High-risk non-muscle invasive urinary bladder cancer (NMIBC) presents an increased risk of progression and cancer death. To reduce these risks, two different treatments are recommended - BCG or radical cystectomy (RC). The purpose of this study is to analyze cancer-specific survival of these two initial treatments. MATERIALS AND METHODS: BladderBaSe links information from the SNRUBC from 1997 to 2014, with a number of national healthcare and demographic registers. BCG was used for 3,862 patients (399 had delayed RC), while 687 had initial RC. Propensity scores were used to match the patients treated with RC and with relevant variables such as age, gender, and tumor stage with the same number treated with BCG (673 each arm). In a further comparison, an instrumental variable analysis using hospital strategy as the instrument was used. RESULTS: The 5-year cancer-specific survival chance was higher for the BCG group than it was for the initial RC group, 87 vs 71%, respectively. In the population with propensity score matching, 78 died from cancer in the BCG group during follow-up and 162 in the RC group. In the instrumental variable analysis, the multivariate adjusted risk difference of cancer-specific death 2 years after diagnosis was 32 per 100 treated patients, in favor of the BCG group. CONCLUSIONS: BCG therapy had better cancer-specific survival than RC also when two different statistic methods were used to try to control for confounding. A prospective randomized trial will be necessary to rule out that selection is a major factor for the outcome.

A small difference in recovery between total knee arthroplasty with and without tourniquet use the first 3 months after surgery: a randomized controlled study.

PURPOSE: When a tourniquet is used during surgery on the extremities, the pressure applied to the muscles, nerves and blood vessels can cause neuromuscular damage that contributes to postoperative weakness. The hypothesis was that the rehabilitation-related results would be improved if total knee arthroplasty (TKA) is performed without the use of a tourniquet. METHODS: 81 patients with osteoarthritis of the knee who underwent TKA surgery were randomized to surgery with or without tourniquet. Active flexion and extension of the knee, pain by visual analog scale (VAS), swelling by knee circumference, quadriceps function by straight leg raise, and timed up and go (TUG) test results were measured before and up to 3 months after surgery. RESULTS: ANCOVA revealed no between-groups effect for flexion of the knee at day 3 postsurgery. Compared with the tourniquet group, the nontourniquet group experienced elevated pain at 24 h, with a mean difference of 16.6 mm, p = 0.005. The effect on mobility (TUG test) at 3 months was better in the nontourniquet group, with a mean difference of -1.1 s, p = 0.029. CONCLUSIONS: The hypothesis that the rehabilitation-related results would be improved without a tourniquet is not supported by the results. When the results in this study for surgery performed with and without tourniquet are compared, no clear benefit for either procedure was observed, as the more pain exhibited by the nontourniquet group was only evident for a short period and the improved mobility in this group was not at a clinically relevant level. LEVEL OF EVIDENCE: Inconsistent results, Level II.

Quality of life and functional outcomes 10 years after laparoscopic radical prostatectomy.

BACKGROUND: Minimally invasive laparoscopic radical prostatectomy (LRP) has proven equally effective as open surgery in terms of cancer control and peroperative complication rate with less bleeding and postoperative pain. However, long-term follow-up data after LRP are scarce, especially as related to quality of life (QoL). AIM: To compare QoL and functional outcomes at least 10 years after LRP with a population-based control group matched for age and region. METHODS: Follow-up data were obtained by mailed questionnaires from patients who responded anonymously to five international questionnaires (EQ-5D, QLQ-C30, QLQ-PR25, IPSS, and IIEF). We collected self-reported outcome data directly from 49 patients who underwent LRP more than 10 years ago in our centre. The results of the patients' overall QoL and urinary continence rates were compared with 918 controls matched for region and age. RESULTS: Forty-two patients (86%) and 808 (88%) controls reported having no urinary leakage. Only 11 patients (24%) still had sexual activities 10 years after LRP, and three were without erectile dysfunction. There was no difference in four of five statements of the self-assessed QoL questionnaires between the LRP and control group. Anxiety level was higher in the LRP group (44%) than in the control group (23%). CONCLUSION: Patients reported high self-assessed QoL, although they also reported low sexual activity 10 years after LRP. Prevalence of urinary leakage was similar in both groups. However, anxiety was more common in LRP patients.