PGL-III, a Rare Intermediate of <i>Mycobacterium leprae</i> Phenolic Glycolipid Biosynthesis, Is a Potent Mincle Ligand

Although leprosy (Hansen's disease) is one of the oldest known diseases, the pathogenicity of Mycobacterium leprae (M. leprae) remains enigmatic. Indeed, the cell wall components responsible for the immune response against M. leprae are as yet largely unidentified. We reveal here phenolic glycolipid-III (PGL-III) as an M. leprae-specific ligand for the immune receptor Mincle. PGL-III is a scarcely present trisaccharide intermediate in the biosynthetic pathway to PGL-I, an abundant and characteristic M. leprae glycolipid. Using activity-based purification, we identified PGL-III as a Mincle ligand that is more potent than the well-known M. tuberculosis trehalose dimycolate. The cocrystal structure of Mincle and a synthetic PGL-III analogue revealed a unique recognition mode, implying that it can engage multiple Mincle molecules. In Mincle-deficient mice infected with M. leprae, increased bacterial burden with gross pathologies were observed. These results show that PGL-III is a noncanonical ligand recognized by Mincle, triggering protective immunity. </p

Role of voiding and storage symptoms for the quality of life before and after treatment in men with voiding dysfunction

Previous studies on associations between voiding dysfunction and quality of life (QoL) have largely been limited to baseline data. Therefore, we have explored associations between Q (max) and voiding and storage sub-scores of the International Prostate Symptom Score (IPSS) before and after treatment with QoL. Analysis of a single-center database of 2,316 men with voiding dysfunction attributed to benign prostatic hyperplasia undergoing various medical and surgical treatment forms. Q (max) exhibited little correlation with QoL before or after treatment. IPSS inversely correlated with QoL at baseline and after treatment, and IPSS improvements correlated with those of QoL. The associations applied to both the voiding and storage sub-score of the IPSS, with the latter consistently exhibiting somewhat tighter associations. Our post-treatment data support the idea of a cause-effect relationship between voiding symptoms and QoL irrespective of treatment form. While both voiding and storage symptoms contribute to this relationship, storage symptoms play a somewhat greater rol

The effect of a temporary prostatic stent on sexual function

Introduction. This study was conducted to explore the effects of the bell-shaped Horizon prostatic stent on sexual function in the treatment of patients with LUTS/ BPH. Materials and methods. 108 Patients with LUTS/BPH were prospectively enrolled in the study. All stents were inserted in an outpatient setting under local anesthesia. To assess sexual function, the 15 item International Index of Erectile Function (IIEF) questionnaire was used. A comparison was made between the total score of the IIEF and the different domains (erectile function (EF), orgasmic function (OF), sexual desire (SD), intercourse satisfaction (IS), and overall satisfaction (OS)) at baseline, one month, and three months after placement of stents. In addition, patients were given the general assessment question "have you experienced any retrograde or painful ejaculations?". Results. At baseline, one patient complained of painful ejaculations (1%). After one month, four (4%) patients complained of painful and two (2%) complained of retrograde ejaculations. A statistically significant decline in the mean OF and IS scores was found. After three months, the IS score significantly improved and the decrease in the OF was smaller than after one month. However, the number of patients reporting painful and retrograde ejaculation was again higher than at baseline (three (4%) and five (7%) percent respectively). There was no change in the total IIEF score or the other subscores of the IIEF at one and three month(s). Conclusion. The bell-shaped Horizon prostatic stent had a negative influence on OF, which did not improve with time. The first month after stent placement, IS was lower than at baseline. After three months however, IS significantly improved compared to baseline. The stent did not negatively affect the total IIEF score or the other domains of the IIEF.</p

The effect of a temporary prostatic stent on sexual function

Introduction. This study was conducted to explore the effects of the bell-shaped Horizon prostatic stent on sexual function in the treatment of patients with LUTS/ BPH. Materials and methods. 108 Patients with LUTS/BPH were prospectively enrolled in the study. All stents were inserted in an outpatient setting under local anesthesia. To assess sexual function, the 15 item International Index of Erectile Function (IIEF) questionnaire was used. A comparison was made between the total score of the IIEF and the different domains (erectile function (EF), orgasmic function (OF), sexual desire (SD), intercourse satisfaction (IS), and overall satisfaction (OS)) at baseline, one month, and three months after placement of stents. In addition, patients were given the general assessment question "have you experienced any retrograde or painful ejaculations?". Results. At baseline, one patient complained of painful ejaculations (1%). After one month, four (4%) patients complained of painful and two (2%) complained of retrograde ejaculations. A statistically significant decline in the mean OF and IS scores was found. After three months, the IS score significantly improved and the decrease in the OF was smaller than after one month. However, the number of patients reporting painful and retrograde ejaculation was again higher than at baseline (three (4%) and five (7%) percent respectively). There was no change in the total IIEF score or the other subscores of the IIEF at one and three month(s). Conclusion. The bell-shaped Horizon prostatic stent had a negative influence on OF, which did not improve with time. The first month after stent placement, IS was lower than at baseline. After three months however, IS significantly improved compared to baseline. The stent did not negatively affect the total IIEF score or the other domains of the IIEF.</p

Hourglass-shaped nitinol prostatic stent in treatment of patients with lower urinary tract symptoms due to bladder outlet obstruction

Objectives. To assess the efficacy and safety of the thermoexpandable hourglass-shaped nitinol prostatic stent in the treatment of patients with lower urinary tract symptoms due to bladder outlet obstruction. Methods. The stents were inserted in an outpatient setting under local anesthesia and direct vision. Five different stent lengths (2.0 to 4.0 cm) were used, depending on the length of the prostatic urethra. Assessment of voiding function and symptom scores was performed at baseline, directly after stent insertion, at 14 days, and 1, 3, 6, and 12 months after stent placement. Results. We enrolled 35 men in the trial. In 5 patients, insertion of the stent failed, mainly because of anatomical limitations. After all placement procedures, minimal temporary hematuria was observed. Spontaneous voiding was achieved in all patients, with immediate significant improvements in voiding parameters and symptom scores. The median indwelling time of the stent was 70 days. Kaplan-Meier survival analysis showed that at 14 days and at 3, 6, and 12 months, the stent was still in situ in 73%, 40%, 33%, and 23% of the patients, respectively. The main reason for removal of the stent was migration (93%), in most cases toward the bladder. Removal was uneventful in all but 1 case. Conclusions. The placement of the thermoexpandable hourglass-shaped nitinol stent results in relief of outflow obstruction and improvement of symptom scores. Because of the high migration rate, however, this stent design needs further improvement to be suitable for clinical practic

The role of nocturia in the quality of life of men with lower urinary tract symptoms

To determine the role of treatment-associated improvement in nocturia in health-related quality of life (HRQL) in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia, and secondarily to confirm the role of nocturia in HRQL at baseline and to compare the effects of watchful waiting, transurethral microwave treatment (TUMT) and transurethral resection of the prostate (TURP) to those of α1-adrenoceptor antagonists (α-blockers) on nocturia. We retrospectively analysed using multiple regression a large single-centre database of patients receiving routine care for treatment-associated alterations of symptoms and HRQL (assessed at baseline, 2611 men) and 6-12 months after initiation of treatment (1258 men). Among the symptoms assessed using the International Prostate Symptom Score, nocturia (together with urgency and weak stream) had the strongest correlation with HRQL at baseline and after treatment. Watchful waiting, α-blockers, TUMT and TURP reduced nocturia episodes by a mean (sd) of 7 (53)%, 17 (40)%, 32 (47)% and 75 (23)%, respectively. The treatment-associated improvements in nocturia (together with those of weak stream) had the strongest association with those of HRQL. We conclude that among all LUTS assessed in the IPSS, nocturia has one of the strongest associations with HRQL, and that treatment-associated improvements in nocturia contribute considerably to overall improvements in HRQ

Transplantation outcomes in patients with primary hyperoxaluria: a systematic review

Background: Primary hyperoxaluria type 1 (PH1) is characterized by hepatic overproduction of oxalate and often results in kidney failure. Liver-kidney transplantation is recommended, either combined (CLKT) or sequentially performed (SLKT). The merits of SLKT and the place of an isolated kidney transplant (KT) in selected patients are unsettled. We systematically reviewed the literature focusing on patient and graft survival rates in relation to the chosen transplant strategy. Methods: We searched MEDLINE and Embase using a broad search string, consisting of the terms ‘transplantation’ and ‘hyperoxaluria’. Studies reporting on at least four transplanted patients were selected for quality assessment and data extraction. Results: We found 51 observational studies from 1975 to 2020, covering 756 CLKT, 405 KT and 89 SLKT, and 51 pre-emptive liver transplantations (PLT). Meta-analysis was impossible due to reported survival probabilities with varying follow-up. Two individual high-quality studies showed an evident kidney graft survival advantage for CLKT versus KT (87% vs. 14% at 15 years, p<0.05) with adjusted HR for graft failure of 0.14 (95% confidence interval: 0.05–0.41), while patient survival was similar. Three other high-quality studies reported 5-year kidney graft survival rates of 48–89% for CLKT and 14–45% for KT. PLT and SLKT yielded 1-year patient and graft survival rates up to 100% in small cohorts. Conclusions: Our study suggests that CLKT leads to superior kidney graft survival compared to KT. However, evidence for merits of SLKT or for KT in pyridoxine-responsive patients was scarce, which warrants further studies, ideally using data from a large international registry

Nephron-sparing surgery and percutaneous biopsies in renal-cell carcinoma: a global impression among endourologists

BACKGROUND AND PURPOSE: On the one hand, nephron-sparing surgery (NSS) in small renal tumors is a safe and effective alternative to radical nephrectomy. On the other hand, the role of preoperative percutaneous needle biopsies (PNB) remains controversial. The purpose of this study was to evaluate the global current use of NSS in the treatment of renal-cell carcinoma (RCC) and the use of PNB among endourologists. MATERIALS AND METHODS: One thousand questionnaires were distributed during the 23rd World Congress of Endourology and SWL. Six questions regarding NSS and two questions regarding PNB were presented. Two hundred twenty-two questionnaires were returned. RESULTS: Of the respondents, 86.6% perform NSS for small renal tumors, whereas 13.4% perform only radical nephrectomies; 7.5% will consider NSS only in patients with a solitary kidney, and 0.5% will never consider NSS. The techniques for NSS, in descending order of preference, are partial nephrectomy, enucleation, cryoablation, radiofrequency ablation, and high-intensity focused ultrasound. The mean and maximum diameter of the tumor in patients with a normal contralateral kidney for which the urologists perform NSS is 4.0 cm. For a centrally located tumor, NSS is an option for 27.2% of the respondents. Regarding PNB in patients with suspicion of RCC, 55.9% of respondents never obtain renal biopsies in the preoperative assessment and 41.8% obtain them only in rare cases. The majority (90%) prefer histologic over cytologic biopsies. CONCLUSIONS: Nephron-sparing surgery is evolving to a global worldwide standard treatment for small renal tumors. Percutaneous needle biopsy remains a highly debated procedur