We report a case of acute-onset type 1 diabetes due to combined application of nivolumab and intravesical Bacillus Calmette-Guérin (BCG). An 84-year-old woman underwent lung resection for pulmonary ...squamous cell carcinoma. She had been treated for type 2 diabetes and later experienced lung cancer recurrence. She was started on nivolumab treatment, and complete response was achieved for one year. However, during this time, she was diagnosed with superficial bladder cancer and underwent surgery but experienced recurrence. After one month of intravesical BCG instillation, the patient developed acute-onset type 1 diabetes. Thus, we recommend that combined application of nivolumab and intravesical BCG be avoided.
Attribute-based medicine is essential for patient-centered medicine. To date, the groups of patients with chronic kidney disease (CKD) requiring urate-lowering therapy are clinically unknown. Herein, ...we evaluated the efficacy of febuxostat using a cross-classification, attribute-based research approach. We performed post hoc analysis of multicenter, randomized, double-blind, placebo-controlled trial data for 395 patients with stage 3 CKD and asymptomatic hyperuricemia. Participants were divided into febuxostat or placebo groups and subcohorts stratified and cross-classified by proteinuria and serum creatinine concentrations. In patients stratified based on proteinuria, the mean eGFR slopes were significantly higher in the febuxostat group than in the placebo group (P = 0.007) in the subcohort without proteinuria. The interaction between febuxostat treatment and presence of proteinuria in terms of eGFR slope was significant (P for interaction = 0.019). When cross-classified by the presence of proteinuria and serum creatinine level, the mean eGFR slopes significantly differed between the febuxostat and placebo groups (P = 0.040) in cross-classified subcohorts without proteinuria and with serum creatinine level ≥ median, but not in the cross-classified subcohorts with proteinuria and serum creatinine level < median. Febuxostat mitigated the decline in kidney function among stage 3 CKD patients with asymptomatic hyperuricemia without proteinuria.
Abstract Background Difelikefalin, a potent and highly selective agonist of kappa opioid receptors, is used to treat moderate-to-severe pruritus in hemodialysis patients. Methods This was a 52-week, ...open-label phase 3 trial following a 6-week randomized double-blind placebo-controlled treatment period to investigate the efficacy and safety of difelikefalin in Japanese hemodialysis patients. Having completed the 6-week double-blind period, patients received difelikefalin 0.5 μg/kg three times per week intravenously for 52 weeks. Efficacies were assessed using numerical rating scale (NRS) scores, proportion of patients whose NRS score improved by ≥ 3 points and ≥ 4 points, Shiratori severity score, proportion of patients with a nighttime Shiratori severity score of ≤ 2, the Skindex-16 score, 5-D itch scale score, and patient global impression of change (PGIC). Safety was assessed on the basis of adverse events, clinical laboratory tests, vital signs, body weight, 12-lead electrocardiography, and dependency. Results The number of patients who entered the extension treatment period from the difelikefalin (MR–MR) and placebo (P-MR) groups was 85 and 83, respectively. The weekly mean NRS scores (mean ± SD) in the MR–MR group at baseline, week 6, and week 58 were 6.57 ± 1.32, 4.04 ± 2.24, and 2.36 ± 1.86, respectively. The weekly mean scores in the P-MR group, at baseline, week 6, and week 58 were 6.42 ± 1.29, 4.85 ± 1.90, and 2.73 ± 2.14, respectively. In patients receiving difelikefalin, there was a decline in the score from treatment initiation, and this decline continued until week 58. Similarly, improvements were seen until week 58 in the proportion of responders, Shiratori severity score, proportion of responders based on the Shiratori severity score, the Skindex-16 score, 5-D itch scale score, and PGIC. A correlation was seen between the change in NRS and itch-related quality of life (QOL), including the Shiratori severity score, Skindex-16 score, 5-D itch scale score, and PGIC. Difelikefalin was well tolerated and safe even when used long term. Conclusions Difelikefalin improved itching and itch-related quality of life during long-term treatment in hemodialysis patients with moderate-to-severe pruritus whose response to conventional medications had been inadequate. It also demonstrated excellent safety and tolerability. Trial registration : ClinicalTrials.gov; NCT04711603. Registered 15 January 2021, https://www.clinicaltrials.gov/study/NCT04711603?term=NCT04711603&rank=1 .
Background: Naloxone enhances bladder activity in patients with chronic spinal cord injury. However, there are few reports on naloxone for bladder morbidity in acute spinal cord injury.
Methods: We ...performed a prospective, controlled study of the effects of naloxone on bladder function in rabbits with and without surgical transection of the spinal cord at the 10th thoracic vertebra. Acute and chronic stages of injury were defined according to bladder function. Naloxone was given intravenously at both stages, and intrathecally at the acute stage. Bladder activity was monitored by cystometry. Blood concentrations of methionine‐enkephalin were measured by radioimmunoassay.
Results: Spinal cord injuries were acute 1 or 2 days after surgery, and chronic after 1 or 2 weeks. Bladder capacity significantly decreased after 0.01 mg of intravenous naloxone in uninjured control rabbits, and after 0.03 mg of intravenous naloxone in rabbits with chronic‐phase injuries. During the acute‐injury phase, 0.3 mg of intravenous naloxone, or 0.02 mg of intrathecal naloxone, was necessary to evoke the micturition reflex. No significant changes in blood enkephalin levels were seen before or after spinal cord injury.
Conclusion: In rabbits with acute spinal cord injury, intrathecal naloxone evoked the micturition reflex at a much lower dose than did intravenous naloxone. Intrathecal naloxone promises to become a new therapy for the acute stage of spinal cord injury for active recovery of bladder function, and could replace current therapy.
Of several reflexes operating between bladder and urethra, the urethrodetrusor facilitative reflex (UDFR) originates in the urethra and is activated by intraurethral urinary flow, resulting in ...maintenance of detrusor contraction during micturition. This paper deals with the characteristics of bladder contractions induced by urethral perfusion, passive distention of urethra and active contraction of urethral muscle in female mongrel dogs anesthetized with α-choralose. Contractile response of the bladder was recorded simultaneously with urethral pressure using a special preparation in which the urethra was isolated from the bladder. Of 35 dogs studied, 32(91.4%) showed a marked bladder contraction when the urethra was antegradely perfused with warm saline at the const ant urethral perfusion pressure of 100cm H2O. The mean values±SD of contractile pressure and latency were 56.3±24.3cm H2O and 0.80±0.08 second, respectively. The bladder contraction continued as long as the urethra was perf used with saline. In order to distend the whole urethra passively, the urethral meatus was closed and saline was slowly infused from the bladder neck into the urethral lumen. The result showed that passive distention of urethra also caused bladder contraction with approximately the same magnitude as that in urethral perfusion. Spontaneous, rhythmic urethral contractions were observed in 4 dogs. Immediately after each urethral contraction, the bladder contraction occurred with a constant latency, demonstrating that active contraction of urethra also induced a bladder contraction. These results indicated that the neuroreceptors which primarily activated UDFR were stretch receptors in the urethral wall, and thus a contribution of friction receptors to this reflex was doubtful. It was also suggested that these stretch receptors were in series with the muscle fibers because passive distention and active contraction of the urethra could evoke detrusor contraction.
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