Unraveling the complexity of bladder-centric chronic pain by intravesical contrast enhanced MRI

SWOT and Root Cause Analyses of Antimicrobial Resistance to Oral Antimicrobial Treatment of Cystitis

“…The bladder participates in homeostasis via endocrine and stretch-mediated urine reabsorption [9,51,52,54,55] to match with the constant-but-slow rate of urine production during sleep [56]. The multicellular layer of the urothelium [57] lining the bladder is a highly metabolically active [12] multifunctional tissue for monitoring bladder distension [58] and signaling constitutional changes in urine [53,59,60] to the detrusor, micturition centers, and the immune system [61]. The top layer of the urothelium relies on the restricted transcellular permeability [62] of the umbrella cells endowed with the asymmetric membrane on the apical side to survive the low pH and three-fold-higher osmotic pressure of urine [9,63] than the serum (Figure 1).…”

“…The top layer of the urothelium relies on the restricted transcellular permeability [62] of the umbrella cells endowed with the asymmetric membrane on the apical side to survive the low pH and three-fold-higher osmotic pressure of urine [9,63] than the serum (Figure 1). The intermediate cells replacing the infected superficial urothelial cells are smaller in size than the mature umbrella cells [64], which leads to a greater passive paracellular diffusion of urine constituents during cystitis [65][66][67], which may account for a lower abdominal discomfort and dysuria, prominent symptoms of cystitis [12]. The highest prevalence of UPEC in human cystitis informed its selection for the inoculation of pig bladders to model human cystitis, where the ingress of UPEC into umbrella cells was noted near tight junctions (Figure 1) [68].…”

“…A history of two or more episodes of bacterial cystitis is an independent risk factor [15,79] for recurrent cystitis, defined as ≥2 episodes in 6 months or ≥3 in a year. Compared to men, the higher incidence of cystitis in women is generally linked to their shorter urethra and infrequent voiding [69] that thins the urothelial barrier [12,62,80] for the proximal seeding of uropathogens from the adjacent cavities of the vagina and anus [81]. It is also likely that the periodic shedding of the urothelium, observed exclusively in the females of mammals [82][83][84] may increase the inherent predisposition to cystitis [12] but frequent shedding of urothelium may be lowering the incidence of urothelial carcinoma in women [85,86].…”

“…Furthermore, cystitis can dilate the tight junctions of the inflamed urothelium [12,65,82] to reportedly cause a four-fold rise in creatinine reabsorption [55,67] via passive paracellular diffusion, and the resulting decline in the urine creatinine levels can potentially introduce errors in the estimation of the renal function status of cystitis patients, leading to their under-and overdosing of OAT [25,113]. Given that every dose of an OAT regimen produces an initial subtherapeutic concentration in urine [122] during the intended build-up to the MIC, which is itself indeterminable, there is an inevitable period of potential AMR risk with the initiation of OAT, even with AMS [40,41,[137][138][139].…”

“…In contrast, complicated cystitis generally refers to the infection of the urothelium in males or infection together with obstruction, hydronephrosis, renal tract calculi, colovesical fistula, or a compromised immune system. While described by the symptoms of frequency, urgency, and/or dysuria [11], the overlap of these symptoms with interstitial cystitis symptoms and other urological diseases complicates the diagnosis of uncomplicated bacterial cystitis [12], hereafter referred to as cystitis in this paper.…”